Over-the-Counter (OTC) Medications and Devices Released within the Last Three Years

After completing this application-based continuing education activity, pharmacists will be able to

· Describe the significance of the availability of each recently released over-the-counter medication or device

· List the common uses or indications for each over-the-counter medication or device

· Explain the directions for use for each over-the-counter medication or device

After completing this application-based continuing education activity, pharmacy technicians will be able to:

· Describe the significance of the availability of each recently released over-the-counter medication or device

· List the common uses or indications for each over-the-counter medication or device

· Explain the directions for use for each over-the-counter medication or device

The material presented here does not necessarily reflect the views of The University of Connecticut School of Pharmacy or its co-sponsor affiliates. These materials may discuss uses and dosages for therapeutic products, processes, procedures and inferred diagnoses that have not been approved by the United States Food and Drug Administration. A qualified health care professional should be consulted before using any therapeutic product discussed. All readers and continuing education participants should verify all information and data before treating patients or employing any therapies described in this continuing education activity.

Demands on pharmacists have continued to increase over the past few years. Pharmacists feel confident about dispensing medications, but some do not feel equally as confident when recommending over-the-counter medications. It is important for pharmacists to stay informed about new over-the-counter medications and be able to counsel patients on the selection and use of these products. New over-the-counter medications released in the past few years include birth control, devices that detect heart arrhythmias, allergy remedies, and products to treat opioid overdoses.

Content

INTRODUCTION

Self-care involves patients' ability to diagnose and treat their own illness without the help of a health care practitioner. Ninety-six percent of patients believe that over-the-counter (OTC) medications make it easy to care for these self-care conditions.¹Patients save $56.8 billion annually when they use OTC/nonprescription medications instead of prescription medications.² Pharmacists and pharmacy technicians are frequently consulted about different self-care conditions and the appropriate choice of OTC medications and devices.

PAUSE AND PONDER: Would you be able to recognize the symptoms of an overdose?

Naloxone Nasal Spray

The Center for Disease Control and Prevention (CDC) reported that there were 106,363 opioid-related deaths during a 12-month period ending in July 2023.³ The Food and Drug Administration (FDA) originally approved Naloxone to reverse an opioid overdose in 2015 as prescription only.⁴ It moved to OTC/nonprescription status in March 2023 through the FDA’s Rx-to-OTC switch process.^5,6 The manufacturer drove this change to nonprescription status by providing data showing that the drug is safe and effective and that consumers could understand how to use the product based on the proposed labeling.⁵

Naloxone (Narcan, Emergent BioSolutions) was the first OTC medication approved to reverse opioid overdose in community settings. Patients (who use prescription or illegal opioids), caregivers, family members, or friends can now purchase naloxone in community pharmacies, grocery stores, and online without a prescription.^5,7Based on Federal law, people of any age can purchase naloxone, but state laws may differ.⁷ Table 1 describes symptoms of an opioid overdose. The overdose can result from use of fentanyl, heroin, morphine, oxycodone, and other opioids. Naloxone works by blocking the opiate receptors in the brain so that the opiate cannot exert its effects. If it is not an overdose situation, patients will experience no effect.⁵

Table 1. Opioid Overdose Symptoms⁵

· Body aches

· Diarrhea

· Fever

· Goose bumps

· Increased blood pressure

· Increased heart rate

· Nausea or vomiting

· Restlessness or irritability

· Sweating

Naloxone nasal spray contains only one dose and is not reusable. It is available in a 4 mg dose. Observers or caregivers should administer naloxone as soon as possible when they suspect an overdose. The observer/caregiver should lay the patient down on his or her back with their neck supported and the head tilted back. The caregiver should remove the tab from the nasal spray. It does not need to be primed. Caregivers place their thumb on the bottom of the red plunger and the first and middle fingers around the nozzle. The caregiver then places the tip of the nasal spray inside the patient’s nose. They should press the red plunger to administer the medication. They can give additional doses every two to three minutes if needed. They should also call emergency services immediately.

During an overdose situation, the patient could experience withdrawal effects such as nausea, vomiting, sweating, tremors, shivering, or irritability.⁸ The cost is approximately $45 for two single doses.⁹

A Naloxone Nasal Spray Training Device is available for anyone that wants to learn how to administer the nasal spray. The kit contains instructions and two training devices. It does not contain active medication.¹⁰

In July 2023, the FDA approved a second OTC naloxone product. RiVive (Harm Reduction Therapeutics) contains 3 mg naloxone. This is also a Rx-to-OTC change supported by evidence demonstrating that the naloxone levels that reach the blood stream are similar in the prescription and nonprescription product.¹¹ The approximate cost is $36 for a twin pack.

PAUSE AND PONDER: How would you respond if a 13-year-old girl approached you and began asking questions about the norgestrel birth control? What questions would you ask?

Norgestrel 0.075 mg Tablets

In 2019, the CDC reported that 35.7% of pregnancies were unintended in women aged 15 to 44.¹²Unintended pregnancies may result in negative consequences due to a lack of early prenatal care and increased risk of preterm delivery.¹³Having norgestrel available without a prescription may help to reduce unintended pregnancies.¹⁴

Opill (Perrigo) is the first nonprescription oral contraceptive. Opill tablets contain norgestrel 0.075 mg, which is a progestin, or a form of progesterone. It is only used to prevent pregnancy; it does not protect against sexually transmitted diseases such as HIV. The American College and Obstetricians and Gynecologists and the American Medical Medication Association have endorsed this product. Women of any age can purchase Opill in community pharmacies, grocery stores, and online.^14,15

Norgestrel thickens the mucus in the cervix, preventing sperm from reaching the egg. The progestin may also inhibit ovulation, but not in all cases. Each pack contains 28 tablets, 24 active tablets that contain progestin and four inactive tablets that do not contain progestin. Norgestrel will begin working two days after the patient starts a pack and patients must take one tablet at the same time daily to be effective.

Missing tablets or not taking the tablets at the same time every day may reduce the birth control’s effectiveness and increase the chance of pregnancy. If a patient fails to take the tablet by three hours or more of her scheduled time, she should take the next tablet as soon as possible. In this case, she and her partner should also use condoms (or another backup method of birth control) or avoid sex (vaginal) for the next two days.¹⁵ Once a pack is completed, patients should start the next pack without any break in between.¹⁶ With typical use, the pregnancy rate is 9 in 100 during the first year of progestin-only tablets and for perfect use (never forgetting to take a tablet and taking the same time every day), the pregnancy rate is 1 in 100 women.¹⁵

Patients may experience side effects such as headache, dizziness, nausea, fatigue, cramps, or bloating.¹⁶ Progestin-only medications are contraindicated in women who have a history of lupus or breast cancer. Opill will be available on store shelves in March 2024. The suggested cost is $19.99 for a one month supply.¹⁷

OTC Hearing Aids

Approximately 30 million adults in the United States have some type of hearing loss.¹⁸ OTC hearing aids are credited for improving the quality of life in patients, according to a study in the Journal of the American Medication Association.¹⁹ The study used a previously validated model (Decision model of the Burden of Hearing Loss Across the Lifespan: DeciBHAL-US) and simulated the projected probability of hearing loss and the use of traditional and OTC hearing aids in 40- and 50-year old males and females. Use of OTC hearing aids resulted in a $70 to $200 savings over a lifetime. Patients also began using OTC hearing aids earlier in life compared to traditional hearing aids (77.6 versus 78.9 years respectively).¹⁹ The OTC Hearing Aid Act provided the opportunity for patients to purchase OTC hearing aid devices without a medical examination or the necessity of being fitted by a hearing aid specialist.

OTC hearing aids are approved for adults 18 years of age and older and can be purchased online or in stores.¹⁸OTC hearing aids are appropriate for patients with mild or moderate hearing loss. They are not appropriate for severe or profound hearing loss. OTC hearing devices have limits on the maximum output and would not treat severe hearing loss appropriately. Table 2 provides questions that a pharmacist might ask a patient regarding use of OTC hearing aids.

Table 2. Questions Pharmacists Should Ask Patient about OTC Hearing Aids²⁰

· Are you 18 years or older?

· Why do you think you need a hearing aid?

· Have you had your hearing tested either by a professional or by using an online tool?

· Do sounds appear muffled?

· Do you have trouble hearing in a group or a noisy area?

· Do you turn the television up to an excessively high level?

Patients wear OTC hearing aids behind or in the ear canal; implantation is not required. Sound is amplified in the ear canal and moved to the inner ear, where processing and transmission to the brain occurs.¹⁸

Patients should first test their hearing by using an online resource that is provided on the product’s website. Once the results are provided, patients can select the best product for their needs using online product selection tools, based on their brand name choice. Table 3 lists features of some OTC hearing devices.²¹

Table 3. Features of some OTC Hearing Devices²¹

· Advanced acoustics

· Bluetooth streaming

· Hands-free phone calling

· Rechargeable

· Water resistant

Brands include Jabra Enhance, Audicus, and MDHearing. Costs range from $200 to $1000 per pair.²² Some health insurance companies may provide coverage for OTC hearing devices based on specific brands.²³

Lidocaine 4% Patch

Lidocaine is a topical anesthetic and works by inhibiting nerve impulse conduction. It provides a numbing sensation and is used to treat minor pain. Areas that can be treated include the back, neck, shoulders, and knees/elbows.²⁴Lidocaine patches are not appropriate for areas of inflammation.²⁵

Lidocaine patches can be used on patients 12 years of age and older. Patients apply the patch to the affected area of the skin every six to eight hours and should not exceed three applications per day.¹The patch may fall off if exposed to water, so waiting until the patch is off is the best time to shower or swim. Patches should not be applied to damaged or broken skin.The patch should not be covered with a bandage or a heating pad because too much lidocaine may be absorbed through the skin.²⁵

After the patch is removed, it can be discarded in the trash after it’s folded in half (adhesive side in).²⁵ Common side effects include warmth or stinging.²⁶ This product should not be used longer than seven days.

Brand names include Salonpas (lidocaine 4%) Pain Relieving Gel Patch (approximate cost is $11 for 6 patches) and Aspercreme(lidocaine 4%) Lidocaine Pain Relief Patch (approximate cost is $10 for 3 patches).²⁴ Pharmacists and technicians should pay careful attention to brand name products with different ingredients. Salonpas Pain Relieving Patch contains camphor, methyl salicylate, and menthol.

Diclofenac Sodium 1% Gel

Diclofenac topical gel was also changed to nonprescription through the Rx-to-OTC switch process. The FDA approved it as a prescription in 2007 and approved the move to nonprescription status in 2020.²⁷

Voltaren (Haleon) is a nonsteroidal anti-inflammatory (NSAID) gel, which means that it reduces prostaglandins, which are often responsible for inflammation. It is approved for the treatment of arthritis pain in the hand, wrist, elbow, foot, ankle, or knee in adults older than 18 years. It is not approved for sprains, strains, or sport injuries.²⁷

Diclofenac relieves joint pain and stiffness.¹ Dosing is based on the area of application. Patients apply 2.25 inches to the upper body (hand, wrist, elbow) and apply 4.5 inches to the lower body (foot, ankle, knee). The dose is measured using an enclosed dosing card.

Diclofenac comes with an easy twist cap, which is helpful for patients with arthritis. The gel should be rubbed into the affected area up to four times a day for up to 21 days.²⁸ Voltaren does not feel greasy and has a clean scent, compared to other topical preparations used to treat joint pain and stiffness. Common side effects include mild skin irritation. Patients who are allergic to aspirin should not use diclofenac topical gel.²⁷Diclofenac has limited systemic absorption and provides pain relief at the site of application.²⁹Diclofenac topical gel does not work immediately. Patients may not notice relief for one week.²⁷

The cost is approximately $19 for a 3.5 oz tube.³⁰

PAUSE AND PONDER: What symptoms would patients experience if they thought they have atrial fibrillation?

KardiaMobile

KardiaMobile (Alivecor) is used as a personal electrocardiogram (ECG), which measures the electrical activity in the heart. It is FDA-cleared. KardiaMobile is a single-lead ECG used to detect common arrhythmias such as atrial fibrillation, bradycardia, and tachycardia in 30 seconds.³¹ More than 454,000 hospitalizations occur each year in the United States due to atrial fibrillation.³²

The KardiaMobile device is the size of a credit card and pairs or communicates with a smartphone. Patients open the Kardia app on their smartphone and press “Record now.” The patient should place the KardiaMobile device near the smartphone so that the two can connect. The patient places two fingers on each of the pads on the KardiaMobile device. After a few seconds, the results appear in the Kardia app. Patients can save the results or email them to a health care practitioner.³¹ Patients also have access for one year to KardiaCare, which is a service that includes ECG evaluations by cardiologists and monthly reports.³³

The sensitivity and specificity for atrial fibrillation are 92% and 95%, respectively, and 85% and 83% for normal sinus rhythm.³⁴

The Apple Watch also provides a similar service for the detection of heart arrhythmias. According to a study conducted in 2022, the Apple Watch and KardiaMobile can both detect rhythm and heart rate issues but the KardiaMobile had a nonsignificant trend toward better accuracy and rhythm detection.³²

The approximate cost for the KardiaMobile device is $79.³¹

Azelastine HCl 0.15% Nasal Spray

Azelastine (Astepro, Bayer) is approved for the temporary relief of nasal congestion, runny nose, and sneezing due to indoor and outdoor allergies. This is the first available OTC antihistamine nasal spray. It is steroid free and approved for adults and children 6 years of age and older.³⁵About 25.7% of adults and 18.9% of children have seasonal allergies.³⁶

Azelastine is an H₁-receptor antagonist that prevents histamine from activating the histamine receptor and producing symptoms such as nasal congestion, runny nose, and sneezing. Patients should prime the spray before using it by pumping the spray until a fine mist comes out.³⁷ Before using the spray, they must blow their nose to clear the nostrils. The patient may then tilt their head downward and insert the tip ¼” to ½” into the nostril. Patients then press the pump once and sniff gently.³⁸

Children 6 to 11 years of age should use one spray in each nostril twice daily. Children 12 years of age and older and adults should use one or two sprays in each nostril once or twice daily.Common adverse effects include runny nose, headache, and bitter taste. If patients experience drowsiness, they can use the spray at bedtime (and this is a good counseling point). The labeling recommends avoiding azelastine with alcohol or sedatives. Patients should experience relief within the first three hours of the dose.¹

If the nozzle is clogged, the patient should unscrew the spray pump unit. The patient should fill a bowl or container with warm water, soak the nozzle, and pump the nozzle several times under water to clear the clog. Finally, the patient should let the nozzle dry before putting it back on the bottle. The product will need to be primed again before the next use.³⁸

The cost is approximately $24 for 120 metered sprays.³⁹

Olopatadine Hydrochloride 0.1%

Olopatadine (Pataday, Alcon) is used to treat itchy, red eyes caused by ragweed, grass, animal hair, and pollen allergies.⁴⁰ Forty percent of the population has experienced itchy, red eyes due to allergies.⁴¹ Olopatadine is a mast cell stabilizer, which prevents histamine from forming during the allergic cascade.²⁷ Patients 2 years of age and older can use this product. The dose is one drop in the affected eye twice daily every six to eight hours. Reminding patients to remove contacts before use and wait 10 minutes after using the drops before reinserting them is a key counseling point.⁴²

Patients should stop using the product if they experience changes in vision, increased eye redness, or eye pain.²⁷The cost is approximately $20 for a 5 mL bottle.⁴²

Pataday (olopatadine 0.2%) Once Daily Relief and Pataday(olopatadine 0.7%) Once Daily Relief Extra Strength are also available as nonprescription products.⁴³

Mometasone Furoate 50 mcg Nasal Spray

Mometasone furoate (Nasonex, Perrigo) is used to treat allergies, such as hay fever, that produces symptoms such as nasal congestion, runny and itchy nose, and sneezing.⁴⁴ Mometasone is a corticosteroid.⁴⁰ It blocks the release of substances that produce inflammation in the body. Nasonex can be used in patients 2 years of age and older. It is the first nonprescription nasal steroid and is full prescription strength.⁴⁰

As with many other nasal products, the steps for administration start with shaking mometasone furoate before each use and executing a priming spray before the first use. The patient should

insert the tip of the bottle in the nostril using a finger to hold the other nostril closed
breathe in and spray at the same time
repeat the process in the other nostril
avoid blowing their nose right after using the nasal spray.⁴⁴

Patients 2 to 11 years of age should use one spray in each nostril once daily and patients 2 years of age and older should use two sprays in each nostril once daily. Stinging of the nasal passages is a common side effect. The product must be discarded after 75 days from the first use, even if product remains in the bottle.⁴⁴Pharmacists and pharmacy technicians can remind patients to note the day they start using the product and/or the day when it needs to be discarded on the label. The cost is approximately $15 for 60 sprays.⁴⁵

Ivermectin 0.5% Lotion

Approximately 6 to 12 million cases of head lice occur each year. Children between the ages of 3 and 11 years are most commonly affected.⁴⁶ Ivermectin was originally available by prescription only. In 2020, the manufacturer started the process to change the classification to nonprescription. Ivermectin lotion is no longer available as a prescription.⁴⁷

Head lice are parasites that survive by feeding on human blood. Lice are spread by person-to-person contact in close environments. Adult head lice are between 2 to 3 mm in length and move by crawling; they cannot hop or fly.⁴⁶Commons symptoms of head lice include itching on the head and scratching behind the ears.⁴⁸

Ivermectin 0.5% lotion (Sklice, Azurity Pharmaceuticals) is used to treat head lice and nits and is approved for children 6 months of age and older. Sklice is applied to dry hair and the scalp. The entire scalp and the hair nearest the scalp should be completely covered before the person applying the lotion pulls it through to the end of the hair. Patients may require the entire tube of product. Sklice is left on the hair for 10 minutes and then rinsed with water only. Patients should wait 24 hours before applying shampoo. Side effects include ocular irritation and a feeling of burning skin. These effects are rare.

Lice eradication is possible with one treatment. Treatment is effective for 94.9% of patients.⁴⁹ The approximate cost is $293 for 177 grams, which is a single treatment.⁵⁰ Generic alternatives are also available. Other therapies for head lice include permethrin (approximate cost is $39)⁵¹ and pyrethrin/piperonyl butoxide (approximate cost is $14)⁵².

CONCLUSION

More than 700 products have been changed to OTC status through the Rx-to-OTC switch process.⁵³ More are sure to come. It is very important that pharmacists and pharmacy technicians stay up-to-date with not only products on the market from the Rx-to-OTC switch process but also with entirely new product entities. Continuing education programs, product websites, and package information are an appropriate way to become familiar with all new product releases.

Pharmacist Post Test (for viewing only)

1. What is TRUE with regard to opioid overdose and the use of naloxone spray?
A. The person observing the possible overdose should place the patient on their side before administering the naloxone spray.
B. If an additional dose is needed, the caregiver should wait 2 or 3 minutes before administering the next dose.
C. The person observing the possible overdose will only ever need to give one spray to treat an opioid overdose.

2. A patient calls you on the phone and says that she is six hours late in taking her next dose of the norgestrel tablet pack. What do you tell her?
A. She should throw away the pack immediately and start a new pack.
B. She should just skip the dose and start again the next day at the usual time.
C. She should take the tablet and use a backup method of birth control.

3. What symptom does azelastine (Astepro) treat?
A. Cough
B. Headache
C. Runny nose

4. KardiaMobile is available for over-the-counter use. Why is this device important?
A. It allows patients to detect heart rhythm abnormalities that they may not know that they have.
B. Patients need fewer visits to healthcare providers and can self-monitor arrhythmias without follow-up.
C. Athletes can monitor their heart rates during workouts so they can maximize the benefit of exercise.

5. What is a TRUE statement relating to lice and its treatment?
A. Patients should apply Sklice (ivermectin) lotion to freshly shampooed wet hair.
B. Patients should always apply a second treatment within 24 to 48 hours.
C. Patients should leave Sklice on the hair for 10 minutes then rinse with water.

Pharmacy Technician Post Test (for viewing only)

3. What symptom does azelastine (Astepro) treat?
A. Cough
B. Headache
C. Runny nose

Full List of References

References

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Accessed December 28, 2023. https://www.pharmacytimes.com/view/clinical-overview-opill-as-first-otc-contraception-in-united-states
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23. Does Medicare or insurance cover hearing aids in 2023? November 2023. Accessed January 1, 2024. https://www.ncoa.org/adviser/hearing-aids/hearing-aids-insurance-coverage/#:~:text=While%20most%20insurance%20plans%20don,a%20few%20plans%20that%20do.
24. Salonpas. Accessed December 28, 2023. https://www.amazon.com/Salonpas-Lidocaine-Gel-Patch-Strength-Available/dp/B01MF68INT/ref=sr_1_4?crid=V9IZ016RWHLK&keywords=salonpas&qid=1703780356&rdc=1&sprefix=salonpa%2Caps%2C86&sr=8-4
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28, 2023. https://www.webmd.com/drugs/2/drug-16986/salonpas-hot-topical/details
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28. Voltaren Arthritis Pain Relief Gel. Accessed December 28, 2023. https://www.voltarengel.com/arthritis-pain-gel/
29. Topical NSAID therapy for musculoskeletal pain. March 2010. Accessed January 1, 2024. https://academic.oup.com/painmedicine/article/11/4/535/1893796
30. Voltaren Arthritis Pain Gel. Accessed December 28, 2023. https://www.walmart.com/ip/Voltaren-Topical-Arthritis-Medicine-Gel-Pain-Reliever-for-Arthritis-3-5-Oz/556463039?athbdg=L1103&adsRedirect=true
31. Kardia. Accessed December 28, 2023. https://store.kardia.com/products/kardiamobile
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33. FDA clears world’s first credit-card-sized personal ECG. February 2022. Accessed January 1, 2024. https://www.prnewswire.com/news-releases/fda-clears-worlds-first-credit-card-sized-personal-ecg-301472260.html
34. KardiaMobile for ECG monitoring and arrythmia diagnosis. November 2020. Accessed January 1, 2024.
https://www.aafp.org/pubs/afp/issues/2020/1101/p562.html#:~:text=The%20sensitivity%20and%20specificity%20of,premature%20atrial%20or%20ventricular%20contractions
35. FDA approves Astepro Allergy Nasal Spray for over-the-counter use in the United States. June 2021. Accessed December 28, 2023. https://www.businesswire.com/news/home/20210617005872/en/FDA-Approves-Astepro%C2%AE-Allergy-Nasal-Spray-for-Over-the-Counter-Use-in-the-United-States
36. More than a quarter of U.S. adults and children have at least one allergy. January 2023. Accessed January 1, 2024. https://www.cdc.gov/nchs/pressroom/nchs_press_releases/2022/20220126.htm#:~:text=For%20Immediate%20Release%3A%20January%2026%2C%202023&text=Findings%20from%20the%20adults'%20report,6.2%25%20have%20a%20food%20allergy.
37. How to use nasal sprays correctly. December 30, 2022. Accessed March 16, 2024. https://www.news-medical.net/health/How-to-Use-Nasal-Sprays-Correctly.aspx#:~:text=If%20the%20patient%20is%20using,mist%20comes%20out%20when%20pumped.
38. Astepro Allergy. Accessed January 1, 2024. https://www.asteproallergy.com/products/astepro-allergy-nasal-spray
39. Astepro Allergy. Accessed December 28, 2023. https://www.walmart.com/ip/Astepro-Allergy-Medicine-Steroid-Free-Antihistamine-Nasal-Spray-120-Metered-Sprays/900785735?from=/search
40. FDA approves Rx-to-OTC switch for nasal allergy spray. March 2022. Accessed January 1, 2024. https://www.empr.com/home/news/fda-approves-rx-to-otc-switch-for-nasal-allergy-spray/
41. Allergic conjunctivitis. May 2022. Accessed January 1, 2024. https://www.ncbi.nlm.nih.gov/books/NBK448118/
42. Pataday. Accessed December 28, 2023. https://www.walgreens.com/store/c/pataday-eye-itch-relief/ID=300399614-product
43. Pataday. Accessed January 1, 2024. https://www.myalcon.com/professional/ocular-health/allergy-drops/pataday/#:~:text=Pataday%C2%AE%20Once%20Daily%20Relief,Available%20Without%20a%20Prescription.&text=The%20highest%20concentration%20of%20olopatadine,your%20patients%20without%20a%20prescription
44. Nasonex 24HR Allergy. Accessed December 28, 2023. https://www.drugs.com/nasonex.html
45. Nasonex. Accessed December 28, 2023. https://www.target.com/p/nasonex-24hr-non-drowsy-mometasone-furoate-allergy-medicine-nasal-spray-60-sprays/-/A-86065697?ref=tgt_adv_xsp&AFID=google&fndsrc=tgtao&DFA=71700000049427614&CPNG=PLA_Health_Priority%2BShopping_Local%7CHealth_Ecomm_Essentials&adgroup=Health_Priority+TCINs&LID=700000001170770pgs&LNM=PRODUCT_GROUP&network=g&device=c&location=9005861&targetid=pla-323070238464&gad_source=1&gclid=Cj0KCQiA1rSsBhDHARIsANB4EJbiey-yBHLXAeMjOJoCM5FdUr0QBYiy9gRQjLS2mNX3pvHhtZaCvd8aAhtYEALw_wcB&gclsrc=aw.ds
46. Epidemiology & risk factors. October 2019. Accessed January 1, 2024. https://www.cdc.gov/parasites/lice/index.html
47. FDA approves lotion for nonprescription use to treat head lice. October 27, 2020. Accessed March 16, 2024. https://www.fda.gov/news-events/press-announcements/fda-approves-lotion-nonprescription-use-treat-head-lice#:~:text=Sklice%20is%20for%20external%20use,available%20as%20a%20prescription%20drug
48. Sklice lotion. Accessed January 1, 2024. https://www.sklice.com/images/1.0-home/sklice-lotion-cil.pdf
49. Ivermectin lotion (Sklice) for head lice. June 2014. Accessed January 1, 2024. https://www.aafp.org/pubs/afp/issues/2014/0615/p984.html#:~:text=EFFECTIVENESS,31.3%25%20for%20placebo).
50. Sklice prices, coupons and patient assistance programs. Accessed December 28, 2023. https://www.drugs.com/price-guide/sklice
51. Nix Complete Treatment Kit. Accessed January 12, 2024. https://www.walmart.com/ip/Nix-Complete-Treatment-Kit-Permethrin-Cream-Rinse-1-for-Lice-Eggs-5-oz/772728163?from=/search
52. RID. Accessed January 12, 2024. https://www.walmart.com/ip/RID-Lice-Killing-Shampoo-2-oz/226676020?from=/search
53. FAQs about Rx-to-OTC switch. Accessed January 12, 2024. https://www.chpa.org/about-consumer-healthcare/faqs/faqs-about-rx-otc-switch#:~:text=106%20ingredients%2C%20indications%2C%20or%20dosage,been%20newly%20approved%20since%201976

Dealing with Difficult Students: Simple(ish) Solutions to Common Problems

Every student is different. Preceptors may encounter a student who has habits or behaviors that need adjustment. Often, these habits or behaviors are reflective of a lack of professionalism. Preceptors who anticipate certain behaviors and develop strategies to deal with them can usually help students navigate the rotation successfully. It's critical to address poor behaviors the first time they happen, document carefully if the behaviors persist, and involve the school of pharmacy if the behaviors continue. This continuing education activity will describe common challenges and propose effective solutions for dealing with difficult students. It will also discuss student centered learning and present case studies.

Content

INTRODUCTION

Pharmacist preceptors shape the future of pharmacy by mentoring students during their experiential learning experiences. It is not uncommon for preceptors to encounter challenging situations and difficult student behaviors that can ultimately test a preceptor’s skills and patience. A faculty preceptor once said, “Students don’t usually fail rotations because they don’t know brand and generic drug names; they fail because of behaviors incompatible with the pharmacist’s professional identity. No one becomes a preceptor to hunt for students and force them to go to rounds!”

By addressing diverse behaviors and challenges that preceptors commonly encounter, this activity will empower preceptors to address troublesome behaviors effectively.

PAUSE AND PONDER: What types of difficult behavior have you encountered in the students you precept in the past?

TYPES OF DIFFICULT BEHAVIOR

Preceptors report a variety of challenging student behaviors during introductory pharmacy practice experiences (IPPE) or advanced pharmacy practice experiences (APPE) rotations. This continuing education activity explores the following behaviors as they relate to experiential education; failure to answer introductory emails, dressing inappropriately, cursing, poor language choices, disrespectful oral or written language, tardiness, and making excuses for unacceptable behaviors.

Failure to Send Introductory E-mail

Schools of pharmacy typically notify students about their IPPE or APPE rotations several months in advance, often in April for the latter. The timing for reaching out to preceptors may differ for IPPE and APPE students. For example, some schools require IPPE students to contact their preceptors shortly after receiving their site match notification. They may also expect APPE students to introduce themselves and address any site requirements approximately two weeks in advance of the first scheduled day unless the preceptor contacts them sooner. Students should take the initiative and reach out to their preceptors first. This communication serves multiple purposes, including introducing themselves, demonstrating awareness of the start date, confirming the student’s ability to fulfill the expected hourly commitment of the rotation, and addressing any scheduling adjustments. Students spend 120 to 160 valuable hours under the preceptor’s guidance. A student’s failure to initiate or answer introductory emails can significantly impact the student-preceptor relationship and hinder early establishment of effective communication channels.

When students fail to communicate, it opens the door to discuss the importance of good communication in the workplace. Preceptors can use a few techniques to encourage better communication from students^1,2:

Create an electronic reminder on your calendar that will notify you one week before a student is expected. If you haven’t heard from the student, use the contact information the school provided for the student and send a brief message. Something like, “My calendar indicates you are scheduled for your rotation at (INSERT LOCATION) starting Monday. I haven’t heard from you. Are you still scheduled or has your situation changed?”
Consider copying the school’s Office of Experiential Education (OEE) and asking if the preferred contact method has changed.
Know that 47% of e-mail is opened or deleted based on the subject line. Be sure to use a specific subject line, like “IMMEDIATE RESPONSE NEEDED: Your April 2024 rotation.” Experts recommend starting with a command and using seven or few words so the subject line will be visible on a phone. Using four or fewer words increases the likelihood e-mail will be opened, so a subject line of “TIME SENSITIVE: IPPE Rotation” might be even better.
When the student responds, reply promptly (modeling good communication), providing information like start time, hours, dress code, and other essential information as you would with any student. Ask for a reply confirming the student received the information.
If the student does not reply, resend the communication, and copy the OEE. Add a sentence at the start of the communication (and consider highlighting it) that says, “I haven’t heard from you. Is this your preferred method of communication?”
When the student reports, discuss the need for prompt responses, underscoring that preceptors are busy and do not have time to track students down.

Inappropriate Dress and Hygiene

Schools of pharmacy and preceptors expect students to adhere to professional dress standards during their experiential rotations. Dressing appropriately can improve the student’s self-perception and confidence and also improves the public’s confidence and perceptions of a pharmacist’s abilities.³ Preceptors can explain to students that dressing professionally also reflects the workplace institutional culture. Dressing appropriately can improve the likelihood of career advancement.^4,5 Table 1 lists examples of appropriate and inappropriate attire for pharmacy students.

Table 1. Professional Attire^3,6

Appropriate Attire

Inappropriate Attire

· A clean, ironed white lab coat with name tag

· Full length slacks with a collared dress shirts or skirts with blouses or dress shirts, or dresses

· Maintains good hygiene

· Blue jeans, shorts, overalls, sorority or fraternity jerseys, t-shirts, halter tops, tank tops

· Hats, caps

· Tennis shoes, sandals, bare feet

· Excessive jewelry

· May also include revealing clothing, unkept appearance, or lack of attention to personal hygiene

Consider the case of Ally, a P2 pharmacy student on her first IPPE rotation at a large, well-recognized health system. Ally always reported for her shifts wearing dress pants and a turtleneck of sorts under her white coat. One day, Ally joined her preceptor for a meeting with the organization’s medical directors and the room was quite warm. Ally removed her white coat, which revealed the fact that her top was a crop-top and exposed her torso. Ally had always appeared to dress professionally before but always kept her white coat on.

While conversations about dress are sensitive and may be uncomfortable, it’s important to address issues early when appropriate. Experiential rotations may be the first time a student has ever needed to dress professionally. It may take some students time to assimilate to professional dress standards.^4,5 Providing feedback supports the students ability to make a positive first impression and aids in overall career readiness.

After the meeting ended, the preceptor (who was also female) privately addressed Ally’s attire. She suggested that Ally dress professionally daily for any occasion with or without her white coat. If the preceptor had been male, he could ask another female pharmacist to speak with Ally. The key is to address these issues in private and with discretion.

Hygiene is often closely related to attire. Students who have poor hygiene and noticeable body odor often fail to launder, repair, or replace their clothes when they should. Talking with students about hygiene problems is embarrassing for everyone involved. Here, too, it’s often less embarrassing for the student if the person who addresses the issue is of the same gender. The discussion also needs to be conducted in private and with absolute discretion. Some students may have underlying medical conditions that contribute to the problem, like lack of smell or difficulty with executive functioning or organization.⁷ Preceptors can point out that a lack of proper hygiene can lead to social problems with peers and patients and sometimes increases the likelihood of illness. Clothing like white coats that aren’t washed often harbor bacteria and accumulate odors.⁸ Students may need very specific direction. For example, the preceptor may need to tell the student that white coats must be washed every week, or that showering and washing hair at least every other day is the expectation. They can also suggest that students establish routines and incorporate hygiene activities into their routines, like showering every evening if students tend to run late in the morning.⁷

A growing concern in workplaces is the use of fragrance.⁹ More than one-third of Americans report scent sensitivity.¹⁰The reason: artificial fragrances can be irritating to individuals who have allergies and asthma. Colognes and perfumes are not the only problem. Products like lotions, soaps, hairsprays, laundry detergent, and dryer sheets designed to reduce static can also trigger allergies and asthma. For individuals who have sensitivities to fragrances, exposure can lead to headache, respiratory distress, itching/burning eyes, runny nose or congestion, and nausea. The end result is presenteeism, meaning they are present in the workplace but unable to perform as well as they might.⁹ For this reason, some workplaces have policies indicating that employees may not wear any fragrances while on duty.

Here, too, the best intervention is to discuss the problem directly with the student as soon as it's noticed. Since about one-third of workplaces include individuals who have scent sensitivities, establishing a fragrance-free policy is prudent. Consistency is important. Site supervisors who ask one employee or student to stop wearing fragrance should make sure that the rule applies to everyone. Again, it’s often more comfortable for students if the person who approaches them is of the same gender.

PAUSE AND PONDER: What types of difficult behavior might stem from little exposure to professional environments and lack of experience?

Profane or Poor Language Choices

Patients often complain about profanity in healthcare, as they expect professionals to remove these words from professional discussions. But it’s a fact that people—all kinds of people—curse. Experts indicate that people use profane words in two ways: (1) in casual conversation, and (2) in anger.¹¹ Students sometimes use profanity or inappropriate language, and in some cases, they are unaware that the words or phrases they choose are offensive, unprofessional, or incomprehensible. Some students simply use words that they grew up hearing and using, and they believe the words are acceptable. These words usually refer to biologic functions. One pharmacist was surprised when she heard her technician talking to a patient about diarrhea using the *s*-word to describe feces. When she approached the technician, the technician said with all sincerity, “That’s what it is! (The *s*-word)!” And while the *s*-word is unprofessional, students will need to know patient-friendly terms because “feces” is too high level for many patients. (Suggest bowel movement, stool, or even poop.) Students may also be accustomed to using curse words in casual conversation and simply swear habitually. Unfortunately, others may overhear even casual conversations between coworkers and be offended, so using profanities at work (even in casual conversation) should be avoided.¹¹

Using profanity in anger is a different issue.¹¹Employees and students usually curse in angerwhen they are frustrated or arguing with someone. Usually, the person is in a heightened emotional state and the conversation is loud. The cursing affects everyone who hears the profanity, and patients are especially likely to be affected. Humans translate loud conflict as a survival threat and it activates the fight or flight response, raising others’ emotional states, too. Such a change can affect the performance of those involved in or witnessing the conflict for the next few hours. It’s possible that the incident could affect patient outcomes.¹¹

Preceptors should consider a “No Swearing Policy.” Such policies should be enforced with a well-defined managerial plan for disciplinary action or possible termination for employees and specific repercussions for students (discussed below). While swearing, in and of itself, may not constitute serious misconduct, understanding its context and the potential harm it can cause is crucial.

When preceptors observe a student breaching a no swearing policy, they should consider several factors¹²:

Intention: Determine whether the student accidentally used profanity as an outlet for frustration or used swear words to voice abuse or threats.
Delivery: Assess the specific words being used, the volume, and the student’s tone when swearing.
Context: Examine the circumstances in which an individual swore and the motivations behind it.
Workplace Environment: Consider the nature of your workplace, including the type of work being performed and the overall atmosphere.

With employees, the recourse is corrective or disciplinary action. With students, the recourse is documentation in the next evaluation and if the event is serious enough, failing the student in the professionalism section of the evaluation (which in some schools precipitates a failing grade for the entire rotation).

It's important for preceptors to recognize when a student’s behavior may be considered unsafe or harmful to themselves, to patients, or other health care personnel. In cases when a student displays behavior that endangers others, preceptors should

Involve the student’s school immediately.
Provide timely, constructive, and actionable feedback. Identifying and sharing concerns as soon as they arise offers students the opportunity to correct the behavior promptly. Students may not receive a tremendous amount of feedback on their professionalism. It’s important to be transparent about a student’s progress or standing in a rotation.
Inform students that they are breaching workplace policies and the types of disciplinary action that may follow.
Document the date, time, and specific details of any concerning behavior. For situations in which students are at risk of a low to failing grades, documenting behaviors with dates can help justify grading decisions and address concerns with the OEE.

Similar steps can be taken when students violate other polices like dress code, attendance, workplace harassment, cell phone use, etc.^13,14

Disrespectful Language

Another type of inappropriate communication is biased language. Clearly, abusive language, hate speech, and racist or sexist remarks are never appropriate, but biased language may occur without the student being cognizant of it.¹⁵ Preceptors should address the student immediately and explain why what the student said or how the student said it is inappropriate. Some students may come from environments at home or socially where inappropriate language is normalized. These students may voice opinions that reflect their cultural biases, political persuasion, or religious beliefs, or demean others who believe differently. They may also use language that has been common and accepted by society but has now fallen from favor.¹⁵ For example, referring to the technicians as “the girls who run the register,” needs gentle correction. Similarly, labeling patients crazy, drug addict, and senile should prompt preceptors to suggest kinder, gentler terms. These terms have been replaced by mentally ill, person who uses drugs, and person with dementia, respectively. Explaining why negative words may be hurtful can help students develop empathy. It’s also an opportunity to explain how these conditions, like all medical diagnoses, are not the patient’s fault.^16,17

Finally, elderspeak is something pharmacy staff often use unintentionally to demonstrate support for the elderly patient.¹⁸ Elderspeak may become obvious as students encounter older adults. It’s a kind of speech adjustment—often called “baby talk” or “pet talk”—that young people may use when talking with an elder. Table 2 provides some examples of elderspeak.¹⁸

Table 2. Examples of Elderspeak¹⁸

Changing the delivery of verbal information to
- Raise the pitch and tone
- Speak in a singsong tempo
- Exaggerate words
- Speak more slowly
Shortening sentence length
Simplifying sentence complexity by using limited (and sometimes condescending) vocabulary
Repeating or paraphrasing what the elder just said
Using terms like "dear," "honey," “old buddy,” or “young lady”
Using statements that sound like questions
- Ending sentences with a negative question (e.g., You want to take this medicine as directed, don’t you?”)

In short, elders often find elderspeak condescending and patronizing.¹⁸Elderspeak can have a significant impact on specific patient populations. For example, patients with dementia or Alzheimer’s may experience progressive symptoms of aphasia as they age. Many caretakers and healthcare providers resort to language that is simple and limited to alpha commands, or language that is concise, straightforward, and direct. While elderspeak may help compensate for natural changes in older adults’ cognitive abilities, it may consequently cause older people to question their abilities and reinforce negative stereotypes about aging. Because opportunities for communication using elderspeak are constrained (often can be answered with yes or no or the communication invites a “correct” answer or no answer at all), older adults may perceive elderspeak negatively. It may cause reduced self-esteem, depression, and withdrawal from social interactions.Pointing out the problem when students use elderspeak is often enough to correct the behavior. Some students, however, will need coaching. Some strategies to minimize elderspeak include repeating and paraphrasing what you are saying, simplifying phrases, actively listening, and asking appropriate questions.^18,19

It’s essential for students to communicate effectively, maintaining a professional and positive demeanor at all times. Rotations with patient interaction are excellent opportunities to help students communicate their thoughts and feelings effectively. Poor language choices reflect poorly on the student, the school of pharmacy, and the pharmaceutical profession.

Other Specific Behaviors

While the list of challenging student behaviors may be endless, this section touches on some of the other most common difficult behaviors preceptors encounter. This includes tardiness, boundary violations like practicing beyond one’s scope, inappropriate cell phone use, lacking accountability, lacking initiative and motivation, sloppy work practices, and gossiping. Employing effective strategies to manage these behaviors foster a more professional and productive educational experience.

Last to Arrive, First to Leave

Students are expected to be punctual and arrive at their rotations 15 minutes early. These standards are in place to replicate the pharmacist’s obligations and duties. While students aren’t responsible for opening a pharmacy at 8:00 AM, students must demonstrate their ability to be held accountable to such standards in the future. Students must adhere to their agreed scheduling commitments and communicate any delays or absences promptly. Tardiness creates lost productivity. Being 10 minutes late each day is equal to a week's paid vacation by year’s end! It can also inconvenience others if they need to delay meetings or events.

Students who have chronic tardiness problems usually have time management issues. It’s a habit that's difficult to defeat. Preceptors can use a number of interventions, described in Table 3.²⁰

Table 3. Dealing with Tardiness^20,21

Encourage punctuality with a clear policy. Communicate the policy to students when they arrive (and consider putting it in your introductory email) and enforce it consistently.
Send reminders of early meetings or events. Send an e-mail reminder the evening before or 30 minutes before every meeting. Remind participants to be on time. Do not backtrack to fill them in on missed discussions if they are late.
Deal with tardy individuals privately. Meet with the student, revisit company policies, and ask about extenuating circumstances or logistics problems. Clarify the consequences for being late, which may include asking the school to reassign the student.
Describe punctuality as a choice. Convey to students that attendance is not an option, but a critical component of their professional training. They have a choice: To be punctual or the school will have to be notified immediately.
Document, Document, Document. Keep written documentation of all incidents of tardiness, detailing the date and time. This will provide an accurate report to the OEE regarding the student’s behavior.
Keep the pharmacy school involved and aware.

Tardiness doesn’t just affect the student but the entire workplace dynamic. As one professor commented, “When you are late, it makes us ALL late. This is because, even if you think you’re just a student, you have a job here. When you don’t show up on time, you can’t do all the things we count on you.” This statement emphasizes the cascading effects of lateness and the importance of punctuality as just one way to demonstrate professionalism and teamwork.

Addressing Boundary Issues and Protocol Deviation

Students may fail to adhere to established procedures when the pharmacist is not present. For instance, students may provide patient counseling without the pharmacist present or verify medications without the pharmacist’s supervision to speed up workflow. This is called performing outside the scope of training or practice.²²

Some pharmacy employees are tempted to perform outside the scope of training or practice. Sometimes students feel pressured or justified to perform beyond their scope, but doing so violates professional guidelines, risks patient safety, and may violate state or national laws and regulations.²² Pharmacists might also choose to overlook or fail to confront boundary crossing. However, if allowed once, it sets a precedent for the future. Preceptors need to be clear that emergencies and staffing shortages happen, but all employees including students need to work within their scope of practice. Preceptors need to address mismatched expectations (i.e., that a student thinks it’s OK to counsel if the preceptor is busy) and ensure that the workplace has adequate supervision.²²

Preceptors can coach students that while they are on rotation and after they are licensed, they need to be aware of exactly what they can and can’t do. Students should watch for key phrases that signal danger which include

I’ll just do this first and then (show the pharmacist, call the doctor, convince the patient) later, I’m sure he won’t mind…
We do this all the time…
I know how to do this, it’s no big deal.

When they start thinking like that, they need to stop and make sure they are practicing within their scope of practice.

Practicing outside the scope aligns with another ethical concept known as incrementalism. Incrementalism suggests that as individuals repeatedly observe unethical behavior, they perceive it as less wrong, eventually normalizing it or deeming it acceptable. As the mind struggles to detect subtle changes over time, people may engage in unethical behavior more readily through a gradual process of minor infractions, ultimately escalating unethical behaviors. Unethical or challenging behavior typically doesn’t arise as a conscious decision to violate ethical standards; instead, it often occurs incrementally along a slippery slope, in tandem with peer interactions.

Using cell phones at inappropriate times

Cellphones, tablets, and other electronic devices can help students access pertinent information to better support their pharmacy practice experience. However, engaging with these devices in ways not related to their practice, such as unnecessary texting or browsing on social media, is inappropriate.

Social media encompasses Internet-based tools that facilitate networking and collaboration, and real-time sharing of information, photos, videos, and more. Social media can be referred to as “social networking” or “Web 2.0.”²³ These platforms can have positive and negative consequences on a student’s performance. While cell phones can be an indispensable tool for communicating and information access, misuse, or excessive use, can also be a source of distraction. When social media is excessive, it can lead to social media addiction (which is not yet a recognized medical condition). As with substance use, social media addiction can negatively impair physical and psychological health and cause behavioral disorders such as depression, anxiety, and mania. Researchers have not identified a threshold that would suggest what levels of social media use is considered to have poor outcomes. It’s clear poor management of social media use presents many concerning consequences on students’ academic performance and interpersonal relations ^24-26

As the technology landscape is always changing, consequences are unpredictable. Some practical solutions to supporting a student’s management of social media use can include:

Set clear expectations: Early on, practice settings need to communicate and enforce guidelines about cell phone use. A simple approach is to set parameters in the syllabus.
Suggest time management tools: Encourage students to use timers to manage their engagement with social media effectively. In the settings app on most phones, students can set a time limit that alerts the user when the time has been met.
Be informative: Preceptors can encourage students to join online medical communities to access news articles, expert insights, and stay up to date on research and trends. Some students may simply have never thought to do so. Examples of social networking sites available for pharmacists include the following:

ASHP Connect (connect.ashp.org )
APhA (www.pharmacist.com)
The Pharmacist Society (www.pharmacistsociety.com)
LinkedIn

Connect with students: Preceptors might also share readings, blogs, or podcasts that relate to the experiential rotation with students. As a supplement, following up on these materials can also exercise a student’s communication skills and their proficiency in relaying medical information.

Lack of accountability and dishonesty

At times, it may be necessary to address a student’s challenging behavior by discussing it privately. Many reactions can emerge from such conversations. Honesty and accountability should be prioritized – students should openly acknowledge their actions or lack thereof. As aspiring licensed pharmacists, they must uphold principles of integrity and accountability from the early stages of their advanced pharmacy practice experiences. Lack of accountability and dishonesty are character flaws that preceptors should consider quite serious.

Let's talk about a student, Jeff, who started his IPPE rotation in a chain pharmacy location. Jeff's school of pharmacy has experienced recurring issues with him. He often fails to respond to emails in a timely manner if at all. Staff in the experiential education office has to nag at him constantly to update records about vaccinations, license renewals, and similar necessary documentation. He is often flippant about why OEE needs any of this information. On the first day of his rotation, his preceptor asked if he was up to date with all of his vaccinations and licensure renewals, to which he responded, “Of course. I wouldn't be here if I wasn't!” Over the first few days that Jeff worked at the store, the preceptor noticed some incongruities in several of Jeff’s explanations. He had unusual explanations for tardiness, was very defensive when he didn't know the answer to a question, and he was caught using the photocopier for personal purposes even after he had been told not to.

Several days later, the person who was responsible for tracking documentation in the OEE called and asked to speak with Jeff. She had heard that Jeff reported to this site even though the school had told him not to until his vaccinations were current. Jeff took the phone off to a corner of the pharmacy and spoke in hushed tones. When he was done, he told the preceptor that unfortunately he had an emergency and had to leave, and he would let him know when he would return. When the preceptor expressed concern, Jeff said that he had not submitted his vaccination documentation. When pressed further, Jeff confessed that he actually had failed to receive his vaccinations.

Dishonesty is unacceptable in a professional setting. When encountering similar situations, the preceptor should consider the following:

Preceptors should report dishonesty to the OEE as soon as they notice it. Often, preceptors think that this may be a one-off instance of a student’s bad judgement, or preceptors think they may not understand something. Usually, however, this is a behavior that the school of pharmacy has been tracking and other people have noticed also.
Documentation is critical. It needs to be thorough and clear. Preceptors should document what they saw or heard, how they disproved or came to realize that the information was dishonest, and when exactly it happened. They should not wait till the final evaluation to make note of the problems. It should occur in the very first evaluation and it's acceptable to do an immediate interim evaluation.
If the preceptor decides to pass a student who showcased moments of dishonesty on a rotation, they should document in writing that they are passing the student, but they experienced professionalism problems during the rotation.
At some schools that use a pass-fail system, professionalism violations are an immediate “fail.” We don't want people who have this magnitude of dishonesty entering the profession.

PAUSE AND PONDER: What kinds of behaviors would improve with discussion and direction, and what kind of behaviors would improve with more practice?

Inability to take initiative and unwillingness to participate in activities

Some students may appear frustrated, bored, underprepared, and distracted. This lack of engagement may manifest in communication styles aimed at minimizing interactions or diverting attention away from meaningful conversations. An essential component of professional development is the student’s capacity to engage proactively in various learning activities.

A particularly concerning sign is a student’s lack of motivation, which may be evident in their reluctance to engage in self-directed learning or displaying disinterest in the rotation site, assigned activities, or patient care. To address this issue, Table 4 outlines several coaching strategies designed to re-engage students lacking motivation.

Table 4. Strategies to Engage Students Lacking Motivation^27,28

Discuss your observations regarding their disinterest and lack of motivation with the student.
Encourage the student to create a personal success plan, including:
Self-assessment of performance areas needing improvement, as identified by the preceptor
Development of a concrete, actionable plan for improvement
Engagement in critical reflection
Revisit the learner’s professional and rotational goals to realign the students focus
Consider setting mutual goals with the student, focusing on how to use discretionary time during the rotation to meet their unique needs and interests.

Students may distance themselves for several reasons. This could be due to finding a topic uninteresting, lacking understanding of situational expectations, or facing difficulties engaging with an interprofessional team or among cross-generational groups. By allowing students the opportunity to receive feedback and create their own success plan, they can incorporate a self-directed learning process. This approach provides a scaffold in developing essential self-awareness skills.

Consider Sally, who was two weeks in her rotation at Rosemary Hospital. Her preceptor, Dr. Unconfrontational (“Dr. U”), observed that Sally was unengaged, asked no questions, and kept disappearing in the break room for long stretches of time. Five days into the rotation, Dr. U asked Sally if she had read the assigned chapter the evening before. She said she did. When he asked questions about its content, she couldn’t answer. He needed to take a phone call, and she slipped away. He found her in the break room with the book open to the chapter (but she seemed to just stare at the pages). Dr. U was disappointed that Sally wasn’t interested in what he considered the most fascinating—but not the most difficult—part of his specialty. He decided that it was easier to stop assigning reading to Sally because she seemed uninterested. At the rotation’s end, he passed her with a C.

Cases like this demonstrate that precepting can be difficult and students can be puzzling. Although it’s hard to tell if Sally read the chapter, her behavior suggests she did not. The way that Dr. U interacted with Sally provides little information about the root of the problem. Dr. U could have done a number of things when he noticed Sally’s lack of enthusiasm^29-31:

He could have educated himself about disengagement. It’s usually not directed at the preceptor. It could be poor self-esteem, difficult home situations, or the need to work after hours to support oneself. It may be that the student doesn’t see the assignment as challenging. Or, the student may be bored and need more—rather than less—work.
He could have spent time asking Sally about her interests and what she hoped to learn in his rotation. While getting to know her, he could have asked if she had concerns or obligations outside of the rotation that he should know about. Ice-breaking activities are critical with students and should reveal students’ talents, passions, questions, and challenges. Asking questions like, “How do you learn best?” or “Would you rather read about a topic, watch a video, or do both?” can also provide good information.
He could have examined his own expectations to make sure they were SMART (specific, measurable, achievable, realistic, and time-tagged). Was he asking too much?
He could have asked her what she learned in pharmacy school related to his specialty, and what she liked and disliked about it.
He could provide “hooks” to start her thinking about what’s coming next. This is the practice of providing just a little bit of attention-grabbing information about a topic. Preceptors can make a controversial statement (“Some people believe that gargling with bleach kills COVID. We’ll talk about how to respond to that kind of talk next week.”), asking a provocative question (“Why do you think that more than half of patients don’t take their medication? Do you think that statistic is accurate?”), or telling a good story (“I keep this x-ray on the bulletin board because it reminds me of a child who had nausea, vomiting, diarrhea, and low copper levels. It all came down to those things you see in his gut! Anyway…think about that and we’ll talk about it next week)
He could have asked her to develop three goals for the rotation, and three sub-goals for each of the main goals so she could plan her own learning. If she couldn’t do this activity (which would explain much about why she is disengaged), he could work with her to develop goals.
He could have asked her to create a deliverable as she read the chapter. Asking her to write down 10 interesting facts or use sticky notes to mark the pages she found most interesting and least comprehensible would have added an interactive element to the assignment.
He could have asked her if she has had any experience with patients or family members who have diagnoses related to his field. This often provides some real-world relevance to learning.

Sloppiness

Health professionals including pharmacy students are held to rigorous standards of cleanliness, organization, and adherence to site-specific protocols. These protocols are not merely procedural formalities but are fundamental to maintaining quality standards and preventing pharmacy errors.

Pharmacy students, through their education and practical experiences, should be well-versed in these high standards. In compounding labs, for instance, faculty emphasize meticulous attention to detail and stringent adherence to procedures. As future pharmacists, they will prepare or verify medications that are often ingested orally, where the risk of contamination carries potentially severe consequences. Table 5 shares examples of how a student may exhibit sloppy behavior.

Table 5. Examples of the Sloppy, Disorganized, and Nonadherent Student

Poor medication management: This can include incorrect labeling, improper storage of drugs, or disorganized inventory management. These practices can lead to medication errors, altered drug metabolism, or even possible harm to patients.
Lack of attention to detail: This can manifest in several ways such as making calculation errors, misinterpreting prescriptions, or failing to recognize important patient information. Again, this is a patient safety issue.
Failure to clean up: Leaving behind clutter and the detritus of pharmacy work for others to clean not only disrupts workflow but also reflects a lack of professionalism and responsibility.
Improper waste disposal: Disregarding proper guidelines for drug disposal of expired or unused medications, sharps, and other waste can pose environmental and safety repercussions.
Improper recycling practices: In hospital and community pharmacy settings, waste bins are often color-sorted for proper disposal. For example, disposing patient information in a regular trash bin instead of its designated bin violates HIPAA regulations.

Addressing these issues in educational settings is imperative for students to be aware of their habits and actions. This involves reinforcing the importance of these standards early, modeling these behaviors, and holding students accountable when necessary.

Gossiping

During rotations, some students may seamlessly connect with other staff members. In some cases, students may observe instances when coworkers engage in gossip and complaints about the workplace and colleagues. While it might be tempting to indulge in such discussion, setting boundaries is crucial when displaying leadership. This includes no gossiping or destructive criticism, and showing empathy when other coworkers present difficult behaviors. Students should be embedded in the healthcare team with a healthy sense of belonging. As students practice mirroring the pharmacist’s actions, they learn to act as mediators in workplace conflict.

One way to discuss gossip with students is to ask them if they know what Socrates said about repeating information.³² This Greek philosopher said that before speaking, people need to ask themselves three questions about the information they plan to convey: Is it true, is it kind, and is it necessary? These questions are filters. Asking these questions guides the honest person to engage in ethical thinking and decision-making. Taking a few minutes to shift the discussion from the juicy tidbit of gossip to the related and more important topic of truth, kindness, and necessity can (but doesn’t always) help people who gossip develop some insight into their behavior. Emphasizing that these questions help individuals develop nurturing, trusting, empathetic relationships is key. This technique is useful with students and coworkers and can often start the process of reducing gossiping.³²

LEARNING THEORY TO ENHANCE ROTATIONS

Canadian psychologist Albert Bandura is widely recognized for introducing the concept of social cognitive theory.³³ He postulated that learning of any type occurs through observation, imitation, and modeling with influence from the learner’s attention, motivation, attitudes, and emotions. It means that the environment interacts with the individual’s cognitive makeup as learning occurs. Preceptors can use his tenets to help students engage and learn. Bandura’s observational learning theory moves through four key cognitive processes^33,34:

Attention: Learning starts with an individual’s engagement and focus on a particular behavior or task. The ability to imitate a behavior hinge on the accessibility of role models, behavior complexity, and perceived value of behavior. Ultimately, students need to perceive a model, or their preceptor, as someone worth imitating.
Retention: Students should register and retain information that they observe from their model preceptor. Learners retain information in a symbolic form of imagery and verbal elements. When preceptors perform actions repeatedly, they enhance the student’s retention.
Motor reproduction: As students are assigned to new tasks or behaviors associated with being a pharmacist, they will use clues from imagery and verbal elements to guide their actions. Frequent motor reproduction exposes students to new situational contexts and empowers them to adapt and refine their behaviors in future interactions. Role models who demonstrate positive behaviors subtly influence others’ actions and responses.
Motivation, reinforcement and punishment: Attention, retention, and motor reproduction all contribute to the ability to imitate a behavior. To stimulate positive reinforcement of behavior, the motivation and will to perform is often based on the rewards and punishment that result from modeling those actions.

Preceptors who understand another theory—that of unconscious learning—will also be able to assess students based on their past experiences and present materials appropriately. It describes the acquisition, access, and application of knowledge without deliberate and controlled attention. It’s the opposite of studying for an exam. It’s basically the “learn by doing” model, students are unaware it’s happening, and it, too, has four stages.^35,36

In the first stage, unconscious incompetence, students are unaware of how little they know about a subject. These are entry level students who have little experience. They may think they know more than they actually do.
In the second stage—conscious incompetence—students are able to recognize knowledge deficits. Preceptors can think of this as the point where students experience that AH-HA! moment of enlightenment.
Learning begins to accelerate and coalesce in the third stage—conscious competence. Students will begin to see patterns and store that information. An example would be learning the top 200 drugs after processing prescriptions or orders, rather than just memorizing them.
In the fourth stage, students develop unconscious competence. A task or process becomes second nature. Preceptors will not need to remind students to complete steps. Students will simply do the right thing.

Learning barriers can contribute to student difficulties, so understanding learning theory can assist preceptors to support students and reduce difficult behaviors. Exposure to a variety of situations in the workplace will help students learn unconsciously.³⁶ Fear and anxiety are barriers to unconscious learning (and contributors to difficult behaviors), so creating a learning environment that is comfortable (and maybe even fun) can speed the process. So can asking students to take a few moments and visualize processes and procedures before starting.³⁶

In the unconscious incompetence stage, preceptors will need to look for signs that students are recognizing they don’t know what they don’t know.³⁷ Having students repeat processes until they can do them without error is essential. Asking students how they think they are doing may stimulate some self-awareness. Encouraging them to periodically question what they think they know is also good.³⁷ These steps break down learning barriers gradually.

When students reach conscious incompetence, preceptors need to be observant. It’s the step where students, frustrated with their deficits, may want to give up. Preceptors who provide encouragement and additional practice can help them move on. Students need positive feedback to progress to the last step of unconscious competence, or mastery.

PAUSE AND PONDER: Think about a student whose behavior was difficult to address in the past. After taking this continuing education activity, how would you have addressed the issues differently?

CONCLUSION

When students are on rotations, they are in certain respects on their own and need oversight from preceptors and the preceptors’ team. Students benefit from preceptors who engage with their students. Oversight and feedback are needed consistently during this crucial time because preceptors want their students to succeed in the profession and the workplace. Pharmacy preceptors who explore the effectiveness of managing tardiness and use strategies to reinforce accountability and motivation will find the precepting experience more fulfilling. A thorough understanding and application of social cognitive theory and stages of learning will enhance a preceptors response to difficult student behaviors. They can use the interventions they develop to build better pharmacy student experiences. Before giving up on the student, they should ask for help from the pharmacy school’s OEE and reach out to people with good supervisory skills.

Why does early intervention on the preceptor’s part to correct difficult student behaviors matter? Developing good workplace behaviors is critical to prepare students for the rigors and responsibilities of the pharmacy workplace. Precepting students is a phenomenal opportunity to practice life-long learning and working mantras.

Pharmacist Post Test (for viewing only)

POST TEST QUESTIONS

Dealing with Difficult Students: Simple(ish) Solutions to Common Problems

Educational Objectives
1. DEFINE types of student behaviors and common challenges preceptor’s encounter
2. EXPLAIN the underlying factors and learning needs that contribute to difficult student behaviors
3. APPLY the principles of student-centered learning to develop appropriate responses to difficult students
4. ANALYZE case studies and develop strategies for difficult student behaviors

1. Why is dressing appropriately important for students on rotation in a community pharmacy setting?
A. Community pharmacies usually enforce dress codes strictly.
B. It can improve the student’s self-perception and confidence.
C. It ensures that students bathe and groom regularly.

2. Why should a preceptor intervene when a student addresses an older patient as “honey” or “sweetie”?
A. Elderspeak usually signals conflict and activates the fight or flight response, creating fear and anxiety among people who are nearby.
B. Elderspeak is demeaning to older people and may cause them to question their abilities and reinforce negative stereotypes about aging.
C. Elderspeak is usually reserved for speaking to children as it describes using endearments, so children feel more relaxed.

3. Why might a student use poor word choices that may be considered profane for biologic functions?
A. They may have grown up in a home where those words were used exclusively and not realize that most people consider the words profane.
B. The problem isn't the student; The problem is that the preceptor doesn't understand that English is changing and some words are more acceptable now.
C. The student probably perceives that the patient will be more comfortable with common slang and needs to be corrected.

4. A student is on his first rotation in a hospital setting. He has no experience other than a few weeks working in a chain pharmacy. The preceptor observes the student using a procedure that may be acceptable in a chain pharmacy but it's not acceptable in a hospital pharmacy. What step of unconscious learning does this reflect?
A. unconscious incompetence
B. conscious incompetence
C. conscious competence

5. A student reports for her rotation wearing a white coat that is clean and pressed but smells like a popular laundry additive that adds a strong scent to the fabric. Two employees at this location are extremely allergic to strong scents. Select the statement that is TRUE.
A. All health care facilities have policies that prohibit the use of scents.
B. The preceptor’s introductory e-mail should have said not to use fragrance.
C. More than one-third of Americans report scent sensitivity.

6. Why might a student be tempted to perform outside the scope of work appropriate for an intern?
A. The student might feel pressured to do more than she should.
B. The pharmacy school might not have explained scope of work.
C. State law might be vague about an intern’s scope of work.

7. A student has prepared inadequately on several occasions and presented work that is sloppy and incomplete. The preceptor asks the student to create a personal success plan. What is one possible component to such a plan?
A. A face-to-face discussion with the preceptor
B. Engagement in critical reflection about motivation
C. A letter to the pharmacy school documenting deficits

8. You overhear a student discussing information about one employee with one of your other employees. You know that the information is untrue and mean-spirited. You pull the student aside and counsel him about gossip. What question would help the student develop insight?
A. Is it true, is it kind, and is it necessary?
B. Where did you get that information?
C. Why would say something like that?

9. Which of the following is an example of a “hook” to increase student engagement?
A. Ensuring you make only uncontroversial statements
B. Asking questions that student will surely be able to answer
C. Telling a story about materials to be covered next week***

10. Your current APPE student tends to arrive 15 minutes late every day and seems to disappear about 10 minutes before the close of business. Which of the following is the BEST approach?
A. Clarify the store's hours and that the student needs to arrive and leave on time, explain why it's necessary to be on time, and document if the problem persists
B. Document the problem on the first offense, explain why it's necessary to be on time, clarify the store's hours and that only paid employees can arrive late
C. Notify the school of pharmacy immediately that the student is a problem and needs to be reassigned to a different rotation site because she is too difficult

11. Which of the following statements is the best strategy for dealing with difficult students?
A. Preceptors should address problems only if they reoccur since most times, students simply are ignorant of certain rules.
B. Preceptors should address problems as soon as they see them using kind corrective action and positive reinforcement.
C. Preceptors should realize that when they have difficult students, the problem is usually a mismatch with the rotation site.

Full List of References

REFERENCES
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2. Zucker R. How to Follow Up with Someone Who’s Not Getting Back to You. Harvard Business Review. January 13, 2021. Accessed March 19, 2024. https://hbr.org/2021/01/how-to-follow-up-with-someone-whos-not-getting-back-to-you
3. Naughton CA, Schweiger TA, Angelo LB, Lea Bonner C, Dhing CW, Farley JF. Expanding Dress Code Requirements in the Doctor of Pharmacy Program. Am J Pharm Educ. 2016;80(5):74. doi:10.5688/ajpe80574
4. Cardon PW, Okoro EA. Professional characteristics communicated by formal versus casual workplace attire. Bus Comm Q. 2009;72(3): 355–360. doi: 10.1177/1080569909340682
5. Furnham A, Chan PS, Wilson E. What to wear? The influence of attire on the perceived professionalism of dentists and lawyers. J Appl Soc Psychol. 2013;43(9):1838-1850. doi:10.1111/jasp.12136
6. Rickles NM. UConn School of Pharmacy Student Handbook. University of Connecticut School of Pharmacy
7. McClure C. Autism and Poor Hygiene: The Smelly Truth to Overcome. My Autism Mind. July 13, 2023. Accesse March 19, 2024. https://myautismmind.com/poor-hygiene/
8. Chan CK, Lam TY, Mohanavel L, et al. Knowledge, attitude, and practice of white coat use among medical students during clinical practice (LAUNDERKAP): A cross-sectional study. Am J Infect Control. 2024;52(1):35-40. doi:10.1016/j.ajic.2023.06.022
9. Rádis-Baptista G. Do Synthetic Fragrances in Personal Care and Household Products Impact Indoor Air Quality and Pose Health Risks?. J Xenobiot. 2023;13(1):121-131. Published 2023 Mar 1. doi:10.3390/jox13010010
10. Steinemann A. International prevalence of fragrance sensitivity. Air Qual Atmos Health. 2019;12(8):891–897. doi: 10.1007/s11869-019-00699-4.
11. Thompson R. The Profanity Problem. January 24, 2022. Accessed August 27, 2023. https://www.workingnurse.com/articles/the-profanity-problem/
12. Raptis G. My Employee is Swearing in the Workplace. What can I do?. Updated April 11, 2022. Accessed February 15, 2024. https://legalvision.com.au/my-employee-is-swearing-in-the-workplace-what-can-i-do/
13. Chunta KS, Custer NR. Addressing unsafe student behavior. AJN, American Journal of Nursing. 2018;118(11):57-61. doi:10.1097/01.naj.0000547667.08087.51
14. Raptis G. My employee is swearing in the workplace. what can I do? LegalVision. April 11, 2022. Accessed September 9, 2023. https://legalvision.com.au/my-employee-is-swearing-in-the-workplace-what-can-i-do/.
15. Morgan K. Why swearing could have a place in the office. May 16, 2021. Accessed August 27, 2023. https://www.bbc.com/worklife/article/20210514-why-swearing-could-have-a-place-in-the-office
16. Szalavitz M. Why We Should Say Someone Is A 'Person With An Addiction,' Not An Addict. NPR. June 11, 2017. https://www.npr.org/sections/health-shots/2017/06/11/531931490/change-from-addict-to-person-with-an-addiction-is-long-overdue
17. Senile: Why Not to Use the Term and How You Can Age Well. Healthline. Accessed August 27, 2023. https://www.healthline.com/health/senior-health/senile
18. Simpson J. Elderspeak – Is it helpful or just baby talk? Merril Center. Accessed September 1, 2023.https://merrill.ku.edu/elderspeak-it-helpful-or-just-baby-talk
19. Torres-Soto K. The Effects of Elderspeak on the Mood of Older Adults with Dementia: A Preliminary Report. Order No. 13885707 ed. Minnesota State University, Mankato; 2019. Assessed August 31, 2023. https://www.proquest.com/dissertations-theses/effects-elderspeak-on-mood-older-adults-with/docview/2247140946/se-2
20. DeLonzor D. Taming Tardiness. SHRM. August 18, 2020. Accessed October 1, 2023. https://www.shrm.org/resourcesandtools/hr-topics/people-managers/pages/taming-tardiness.aspx
21. Edwards P. HR in Practice: Addressing Employee Tardiness. MedEsthetics. August 25, 2016. Accessed October 1, 2023. https://scholar.google.com/scholar?as_ylo=2019&q=tardiness+healthcare+worker+punctuality&hl=en&as_sdt=0,7
22. Doobay-Persaud A, Evert J, DeCamp M, et al. Extent, nature and consequences of performing outside scope of training in global health. Global Health. 2019;15(1):60. Published 2019 Nov 1. doi:10.1186/s12992-019-0506-6
23. Ventola CL. Social media and health care professionals: benefits, risks, and best practices. P T. 2014;39(7):491-520.
24. Azizi, S.M., Soroush, A. & Khatony, A. The relationship between social networking addiction and academic performance in Iranian students of medical sciences: a cross-sectional study. BMC Psychol 7, 28 (2019). https://doi.org/10.1186/s40359-019-0305-0
25. Bhandarkar AM, Pandey AK, Nayak R, Pujary K, Kumar A. Impact of social media on the academic performance of undergraduate medical students. Med J Armed Forces India. 2021;77(Suppl 1):S37-S41. doi:10.1016/j.mjafi.2020.10.021
26. Lahiry S, Choudhury S, Chatterjee S, Hazra A. Impact of social media on academic performance and interpersonal relation: A cross-sectional study among students at a tertiary medical center in East India. J Educ Health Promot. 2019;8:73. Published 2019 Apr 24. doi:10.4103/jehp.jehp_365_18
27.Davis LE, Miller ML, Raub JN, Gortney JS. Constructive ways to prevent, identify, and remediate deficiencies of "challenging trainees" in experiential education. Am J Health Syst Pharm. 2016;73(13):996-1009. doi:10.2146/ajhp150330
28. Briceland LL, Caimano RC, Rosa SQ, et al. Exlporing the impact of engaging student pharmacists in developing individualized experiential success plans
29. Barkley EF. 7 Ways to Use “The Hook” to Grab Students’ Attention. Wiley Network. Accessed January 16, 2024. https://www.wiley.com/en-us/network/education/instructors/teaching-strategies/7-ways-to-use-the-hook-to-grab-students-attention
30. Chipchase L, Davidson M, Blackstock F, et al. Conceptualising and measuring student disengagement in higher education: A synthesis of the literature. Int J Higher Ed. 2017;6(2):31-42.
31. [No author.] A Gentle Nudge: How Teachers Can Address Disinterested Students. Accessed January 15, 2024. https://blog.planbook.com/disinterested-students/
32. Is it True, Is It Kind, or Is It Necessary Quote: Origin and Explanation. QUOTELYFE. Accessed January 16, 2024. https://quotelyfe.com/is-it-true-is-it-kind-or-is-it-necessary-quote-origin-and-explanation/
33. Fuente J de la, Kauffman DF, Boruchovitch E. Editorial: Past, present and future contributions from the social cognitive theory (Albert Bandura). Frontiers in Psychology. Published online August 7, 2023. Accessed September 8, 2023.
34. Incrementalism. Ethics Unwrapped. November 5, 2022. Accessed September 7, 2023. https://ethicsunwrapped.utexas.edu/glossary/incrementalism.
35. Kuldas S, Ismail HN, Hashim S, Bakar ZA. Unconscious learning processes: mental integration of verbal and pictorial instructional materials. Springerplus. 2013;2(1):105. doi: 10.1186/2193-1801-2-105.
36. Griffen M. Unconscious Incompetence and the Four Stages of Learning. Medium. January 13, 2014. Accessed January 31, 2023. https://mattangriffel.medium.com/unconscious-incompetence-ad5583abf646
37. Cherry K. What Is the Dunning-Kruger Effect? A cognitive bias that causes an overestimation of capability. verywellMind. November 5, 2022. Accessed January 31, 2023. https://www.verywellmind.com/an-overview-of-the-dunning-kruger-effect-4160740

ACUTE AND CHRONIC HYPERKALEMIA: TREATMENT OPTIONS, POTASSIUM BINDERS, AND CLINICAL CASES

After completing this application-based continuing education activity, pharmacists will be able to

· Identify foods that cause hyperkalemia

· List medications that cause hyperkalemia

· Compare and contrast medications that manage acute and chronic hyperkalemia

· Determine the best agent to manage hyperkalemia in each case study

After completing this application-based continuing education activity, pharmacy technicians will be able to:

· Identify foods that cause hyperkalemia

· List medications that cause hyperkalemia

· Describe the dosing and storage information of patiromer and SZC

· Describe the steps of the drug prior authorization process

Hyperkalemia—high potassium levels—is a serious disorder that warrants appropriate treatment. Defined as a serum potassium level greater than 5.5 mEq (mmol/L), hyperkalemia can be asymptomatic or symptomatic. Severe hyperkalemia can cause irregular heart rhythms. Both drugs and foods can cause hyperkalemia. Medications for the management of acute and chronic hyperkalemia include calcium, insulin, beta-agonists, sodium bicarbonate, loop diuretics, and potassium binders. Sodium polystyrene sulfonate (SPS) has been a gold standard for chronic hyperkalemia for several decades. However, sodium overload can be a concern with SPS. Newer drugs such as patiromer and sodium zirconium cyclosilicate offer both safety and effectiveness, but they are costly alternatives. Pharmacists and pharmacy technicians must be prepared to navigate the prior authorization process to seek coverage for these costly alternatives.

Content

INTRODUCTION

Did you know that all living cells need potassium to maintain cellular fluid balance? Potassium has many benefits. First, it helps muscles to contract. Second, it helps maintain blood pressure. Third, it helps regulate bodily fluids inside cells (intracellular). However, having too much potassium (hyperkalemia) may have a negative impact. Hyperkalemia may cause arrhythmia (irregular heart rhythm), which could be life-threatening. Hyperkalemia can be categorized into two main types: acute and chronic. Patients with chronic kidney disease are especially prone to elevated potassium levels.¹

Consider these situations:

Gonzalez comes to your pharmacy with a prescription for patiromer. The pharmacy technician attempted to bill her insurance, but the drug required prior authorization. What do you do next? What are the elements of a prior authorization process?
Williams comes to your pharmacy complaining about edema (swelling due to excess fluid). He has been taking sodium polystyrene sulfonate (SPS). His doctor asks you, the pharmacist, to recommend an alternative to SPS because of the sodium load concern. What would your response be? What would you recommend to replace SPS?

Acute and chronic hyperkalemia continue to present as major medical dilemmas for healthcare professionals. There is no universally accepted guideline to treat them, and there is no universally accepted classification and monitoring frequency for hyperkalemia. Newer potassium binders, such as patiromer and sodium zirconium cyclosilicate (SZC), may allow optimal use of renin-angiotensin-aldosterone system inhibitor (RAASi) therapy in patients with hyperkalemia. However, these newer therapies are costly alternatives to traditional treatment.

Helping patients navigate the health insurance prior authorization process to seek coverage is a challenging task for pharmacists and pharmacy technicians. If a patient comes to your pharmacy with a prescription for a potassium binder, are you fully equipped to provide the patient with information regarding dosing, storage, and insurance authorization?

Simply put, hyperkalemia is a general medical term that describes a higher-than-normal potassium level in the blood. Normally, a person’s extracellular (outside the cells/in the blood) potassium concentration falls between 3.5 to 5 mmol/L. Mild, moderate, and marked hyperkalemia are defined as potassium levels between 5 to 5.9 mmol/L, 6 to 7 mmol/L, and exceeding 7.0 mmol/L, respectively. While mild hyperkalemia requires monitoring and diet restriction, moderate and severe hyperkalemia may cause cardiac complications.²

Epidemiology of Hyperkalemia

Hyperkalemia is a common occurrence. A 2016 American study of 194,456 outpatients found that over a 3-year period, 10.8% of patients had potassium levels greater than 5 mEq/L and 2.3% of the patients had potassium levels greater than 5.5 mEq/L.³ A 2017 study conducted in a large Swedish healthcare system followed 364,955 participants over three years.⁴ The researchers defined hyperkalemia as potassium exceeding 5 mmol/L and moderate/severe hyperkalemia as potassium exceeding 5.5 mmol/L. Hyperkalemia occurred in 25,461 individuals (7%), and 9,059 individuals (2.5%) had moderate/severe hyperkalemia.⁴

Elevated potassium levels are more common in patients with chronic kidney disease (CKD) than in patients without CKD. One study involving four clinical centers and 820 patients in the United States (U.S.) found that 8% of patients with CKD had hyperkalemia.⁵ A study involving 55,266 patients with glomerular filtration rate (GFR) less than 60 (an indicator of kidney dysfunction) enrolled in a managed care organization in the U.S. found that 5% of patients had potassium levels at or exceeding 5.5 mEq/L and 20% experienced potassium levels at or exceeding 5 mEq/L.⁵ A French study involving 1,038 patients found that 17% of those with stage 2 through 5 CKD had potassium levels at or exceeding 5 mEq/L.⁵ An additional study that enrolled 36,359 patients with stage 3 or 4 CKD found that 3% had potassium levels at or exceeding 5 mEq/L.⁵

Hyperkalemia’s History

Sir Humphry Davy at the Royal Institution in London first isolated potassium in 1807 using electrolysis of dry molten caustic potash (KOH, potassium hydroxide). Potassium is an alkali metal and silvery-white in color. It consists of 19 electrons and 19 protons. At 20°C, it has a density of 0.862 g/cm. Potassium is present in all meats, plants, and dairy products and is abundant in fruits and vegetables.⁶

Potassium is important for maintaining cellular function. All cells have a sodium-potassium ATPase (Na+ -K+ ATPase) exchanger, which is partially responsible for maintaining the membrane potential. This serves as a basis for conduction of nerve impulse and stabilization of blood pressure.⁷A diet rich in potassium has been associated with reducing blood pressure, lowering the risk of stroke and nephrolithiasis (kidney stones), and improving bone health.

The body maintains potassium homeostasis through various means. Total body potassium content is achieved by alterations in renal (kidney) excretion of potassium in response to potassium intake. Insulin and beta-adrenergic tone (responsiveness of the autonomic nervous system) help regulate extracellular and intracellular content of potassium.⁷ In short, extreme low and high potassium levels are not compatible with life.

PAUSE and PONDER: Did you know that a higher-than-normal potassium level (hyperkalemia) can cause neuromuscular symptoms such as muscle cramps and cardiovascular symptoms such as irregular heartbeat? What causes hyperkalemia?

Causes and Clinical Manifestations

Hyperkalemia has many causes, including but not limited to, tissue injury, insulin deficiency, exercise, medications, and excess dietary potassium intake^8,9:

Trauma, massive hemolysis (destruction of red blood cells), and tumor lysis (rapid breakdown of cancer cells) may cause tissue injury, which in turn may cause hyperkalemia.
Insulin deficiency may cause hyperkalemia. Insulin regulates glucose concentration in the plasma and also causes potassium to move into cells until the kidneys have sufficient time to excrete the dietary potassium load and re-establish total-body potassium content.
During exercise, potassium is released from skeletal muscle cells and accumulates in the interstitial compartment (a small space in a tissue or between parts of the body), where it exerts a vasodilatory effect (widening of blood vessels).
Medications may cause hyperkalemia by interfering with the renin-angiotensin-aldosterone system (RAAS). RAAS is a normal cascade that functions in the homeostatic control of arterial pressure, tissue perfusion, and extracellular volume. While many medications may offer cardiovascular benefits by deregulating the RAAS, they can cause concurrent hyperkalemia because the RAAS facilitates potassium excretion in the kidneys.
Medications such as nonsteroidal anti-inflammatory drugs (NSAIDs), beta-blockers (e.g., atenolol, metoprolol, propranolol), cyclosporine, and tacrolimus may cause hyperkalemia by impairing the release of renin.
Angiotensin-converting-enzyme inhibitors (ACEi) such as benazepril, captopril, enalapril, lisinopril, perindopril, and quinapril block the formation of angiotensin II. Angiotensin-receptor blockers (ARBs) such as azilsartan, candesartan, irbesartan, losartan, olmesartan, telmisartan, and valsartan prevent angiotensin II from binding to its adrenal receptor. Both mechanisms contribute to the development of hyperkalemia.
Heparin causes hyperkalemia by interfering with aldosterone biosynthesis in the adrenal gland.
Amiloride, pentamidine, triamterene, and trimethoprim block sodium reabsorption in the collecting tubule and reduce the negative potential of the lumen. By doing so, they reduce potassium secretion from the kidneys.
Spironolactone and eplerenone prevent aldosterone from binding with its receptor and increase the likelihood of hyperkalemia.

Excess potassium intake contributes the development of hyperkalemia. Table 1 lists foods and their elemental potassium contents. Patients with CKD should adhere to a low potassium diet, but patients often find this difficult in real-world scenarios.¹⁰ In addition, potassium-rich diets (foods with more than 200 mg per serving are considered potassium-rich) have numerous health benefits including blood pressure reduction, reduction in risk of CKD progression, and cardiovascular disease and stroke prevention. A low potassium diet may present a treatment dilemma because it may prevent patients from receiving these benefits.¹⁰

To prevent hyperkalemia, limited dietary potassium intake is necessary. Patients who are diagnosed with hyperkalemia or at risk of developing hyperkalemia should limit potassium intake from all sources including food, salt substitutes, and supplements to about 40 to 60 mEq (mmol) per day.¹¹

Table 1. Potassium Content of Selected Common Food and Salt Substitutes¹²

Food	Elemental Potassium Content
	Milligrams (mg)	Milliequivalents (mEq)*
Milk	350	9
Apricot (5)	480	12
Avocado	300	7-10
Banana	451	12
Cantaloupe (1/4)	412	11
Kiwi	252	6
Nectarine	288	7
Orange	300	7
Papaya (1/4)	390	10
Peach	305	8
Prunes, 5 dried	365	9
Raisins (1/2 cup)	553	14
Watermelon (1/16)	560	14
Juices (serving size 4oz = 1/2 cup = 120ml)
Apple juice	148	4
Grapefruit juice	210	6
Orange juice, frozen	252	7
Pineapple juice	148	4
Prune juice	301	8
Tomato juice	225	6
Nuts (serving size 1oz = 30 g)
Almonds, dry roasted	210	5
Cashews	187	4
Salt substitutes (serving size ¼ cup)
Examples: NoSalt, Nu-Salt	610-795	15-20
Vegetables (Serving size 8 oz = 1 cup = 240ml)
Acorn squash, cooked	896	23
Beets	530	13
Broccoli, frozen, cooked	332	9
Brussel sprouts, cooked	494	13
Butternut squash, cooked	583	15
Collards, frozen, cooked	427	11
Kidney beans, cooked	713	18
Lentil, cooked	731	19
Lettuce, 1 head Boston	419	10
Mushrooms	550	14
Pinto beans, cooked	800	20
Potato, baked with skin	844	21
Potato without skin	600	15
Pumpkin, canned	506	12
Soybeans, cooked	972	24
Spinach, raw or cooked	838	21
Split peas, cooked	710	18
Sweet potato, baked with skin	350	9
Tomato	251-273	7
White navy beans, cooked	669	18
Zucchini, cooked, sliced	456	12

*Also equivalent to millimoles (mmol)

PAUSE AND PONDER: In a reported case, an individual chewed and ingested burnt match heads in a condition called cautopyreiophagia. This activity resulted in a plasma potassium concentration of 8 mmol/L and contributed 80 mmol of daily potassium intake. What signs of hyperkalemia did he probably experience?

Hyperkalemia is usually asymptomatic. However, neuromuscular and cardiac abnormalities may develop as hyperkalemia worsens. Neuromuscular manifestations of hyperkalemia can include paresthesia (tingling or prickling) and fasciculations (muscle twitching) in the arms and legs.⁸ Severe hyperkalemia can cause paralysis that leads to flaccid quadriplegia (paralysis of all four limbs).⁸ In addition to neuromuscular abnormalities, hyperkalemia may lead to electrocardiogram (ECG) changes. Hyperkalemia causes ECG changes in a dose-dependent manner¹³:

Potassium levels between 5.5 to 6.5 mEq/L: ECG will show tall, peaked T waves
Potassium levels between 6.5 to 7.5 mEq/L: ECG will show loss of P waves
Potassium levels between 7 to 8 mEq/L: ECG will show widening of the QRS complex
Potassium levels between 8 to 10 mEq/L: ECG will produce cardiac arrhythmias, sine wave pattern, and asystole

These cardiac abnormalities can lead to dysrhythmias and death.¹³

TREATING HYPERKALEMIA

In acute hyperkalemia, patients with potassium levels exceeding 6 mmol/L or patients have who hyperkalemia with any new ECG changes should be referred to a healthcare facility with cardiac monitoring. Kidney Disease: Improving Global Outcomes (KDIGO) recommends monitoring vital signs and cardiac changes.¹⁴ In hyperkalemic patients with ECG changes, KDIGO recommends treatment with calcium chloride, insulin, and beta-agonists. In patients with concomitant metabolic acidemia (lower blood pH), KDIGO recommends sodium bicarbonate. Subsequently, KDIGO considers the use of potassium-binding drugs and loop diuretics. KDIGO suggests dialysis in cases of persistently elevated potassium concentrations exceeding 6 mmol/L or ECG changes that are unresponsive to medical management.¹⁴

Treatment of Acute Hyperkalemia

Acute hyperkalemia is generally defined as a serum potassium concentration exceeding the upper limit of normal that is not known to be chronic.¹⁴ Currently, clinicians use no universal classification or monitoring for hyperkalemia. Similarly, no universally accepted treatment guidelines for acute and chronic hyperkalemia exist. Clinicians should not initiate treatment of acute hyperkalemia solely based on serum level of hyperkalemia; they should also consider patients’ clinical manifestations (e.g., ECG changes). Treatment options for acute hyperkalemia may include intravenous calcium gluconate, insulin, inhaled beta-agonists, intravenous sodium bicarbonate, and dialysis. Table 2 expounds on these treatment options.¹¹

Table 2. A Summary of Treatment Options for Acute Hyperkalemia¹¹

Treatment Option	Dosage	Advantage(s)	Disadvantage(s)
Intravenous calcium gluconate	1 gram via IV piggyback (small bag of solution attached to primary infusion line). Repeat in 5 minutes if needed	Fast onset	Dose not lower potassium level, only normalizes ECG changes
Intravenous insulin	5–10 units or 0.1 units/kg, maximum 10 units	Fast onset, most reliable treatment	Usually given with dextrose to minimize hypoglycemia
Inhaled beta-agonists (e.g., albuterol)	10–20 mg via nebulizer	Fast onset	Inconsistent effect, nonselective beta-blockers such as propranolol and sotalol may be less effective
Intravenous sodium bicarbonate	50 mEq, which is equivalent to 50 ml of 8.4 % sodium bicarbonate over 5 minutes. Repeat in 30 minutes as needed	Work best with acidosis (pH < 7.2)	Variable onset of action
Dialysis	Treatment given daily or a few days a week	Reliable treatment to remove waste, effective method to attain norkalemia	Extensive equipment and knowledge required to conduct treatment

ECG, electrocardiogram; IV, intravenous.

Intravenous calcium gluconate for acute hyperkalemia works by stabilizing membrane potential and normalizing ECG changes to prevents irregular heart rhythm. However, it does not lower serum potassium levels. It’s duration of effect ranges from 15 minutes to one hour. It may cause adverse effects such as local irritation, hypercalcemia (elevated calcium levels), hypotension (low blood pressure), and bradycardia (slowed heart rate). If no effect is observed in five minutes, another dose may be given.¹⁰

Intravenous insulin works by shifting potassium from extracellular to intracellular space. It has an onset of 15 to 30 minutes and a duration of four to six hours. It may cause hypoglycemia (low blood sugar) and hypokalemia (low potassium levels). Clinicians typically give intravenous insulin with glucose to prevent hypoglycemia during acute hyperkalemia treatment.¹⁰

Inhaled beta-agonists act within 30 minutes to redistribute potassium from the extracellular to intracellular space. It has an onset of 30 to 60 minutes and duration of effect from two to four hours. Adverse effects include tachycardia (elevated heart rate), tremor, vasoconstriction (narrowing of blood vessels), and hyperglycemia.¹⁰

Intravenous sodium bicarbonate is another option to treat acute hyperkalemia. It lowers serum potassium levels by increasing potassium elimination through the urine. It has an onset of action of 30 minutes to four hours and a duration of effect of approximately two hours. Possible adverse events include hypocalcemia, metabolic alkalosis (elevated blood pH), hypernatremia (elevated sodium), fluid overload, worsening hypertension, and heart failure.¹⁰

Patients may receive one of two types of dialysis: peritoneal dialysis or hemodialysis. Peritoneal dialysis uses the lining of the abdominal cavity to filter body waste. A surgeon places a catheter in the abdominal cavity. The dialysis solution enters the abdominal cavity through the catheter and will drain out of the abdominal cavity. Hemodialysis, uses a machine to remove excess water and waste products. A machine removes blood from the body and infuses it through a filter. A dialysate solution flows on the other side of the membrane and draws impurities from the blood. Dialysis is an effective treatment for hyperkalemia.¹⁵

Pause and Ponder: SPS used to be the “gold standard” in treating chronic hyperkalemia. What are the newer potassium binders? Are they safe and effective?

Treatment of Chronic Hyperkalemia

Chronic hyperkalemia is defined as recurrent episodes of elevated serum potassium concentrations.¹⁰ Treatment options include loop diuretics, RAASi dose modification, identification and removal of hyperkalemia-causing medications, and potassium binders.¹⁰

Loop diuretics—often used for other indications, such as hypertension and heart failure—increase urinary potassium excretion at the collecting duct of the kidney. Providers commonly use furosemide, a loop diuretic, in chronic hyperkalemia. They often prescribe them with thiazides, ACEIs, and ARBs. However, loop diuretics have their limitations. They may cause volume depletion (reduced blood volume) and their effectiveness declines as renal function declines.¹¹

Another treatment option for chronic hyperkalemia is the modification of dosage or interruption of RAASi therapy. No generally accepted guidelines regarding this strategy in patients who experience hyperkalemia exist. However, the European Society of Cardiology recommends patients continue or titrate RAASi treatment to optimal doses in the event of mild hyperkalemia levels between 5.1 and 5.5 mEq/L and moderate hyperkalemia levels between 5.6 and 6 mEq/L.¹⁶

Potassium binders—including SPS, SZC, and patiromer—are one of the most promising treatments for chronic hyperkalemia. In general terms, a patient will consume fluids with potassium binders. Potassium binders bind to potassium in the bowel and exchange with calcium, sodium and/or hydrogen, usually at the colon. The body will then excrete the potassium in the feces.¹⁷ Table 3 displays onset of action, mechanism of action, and common adverse effects of potassium binders.¹⁰ Note that all potassium binders have a relatively slow onset of action, making them inadequate therapies for acute hyperkalemia.

Table 3. Selected Characteristics of Available Potassium Binders^{10, 20, 18, 19}

Drug	Onset of Action	Mechanism of Action	Adverse Effects	Usual adult starting dose
Patiromer	7 hours	Potassium binding in exchange for calcium in GI tract	Abdominal discomfort, constipation, diarrhea, nausea, flatulence, hypomagnesemia	8.4 grams orally once daily
Sodium zirconium cyclosilicate (SZC)	1–6 hours	Potassium binding in exchange for hydrogen and sodium in GI tract	Constipation, diarrhea, nausea, vomiting, mild-to-moderate edema	5 grams orally once daily
Sodium polystyrene sulfonate (SPS)	2-6 hours	Potassium binding in exchange for sodium in GI tract	constipation, diarrhea, nausea, vomiting, gastric irritation, hypomagnesemia, hypocalcemia, edema, hypokalemia, systemic alkalosis, intestinal necrosis	15 to 60 grams orally daily

GI, gastrointestinal.

SPS, approved by the Food and Drug Administration (FDA) in 1958, has been the “gold standard” and the lone potassium binder for several decades. Its mechanism of action is potassium binding in exchange for sodium in the gastrointestinal (GI) tract. However, its adverse effect profile is unfavorable and erratic. In fact, the FDA issued a warning for SPS regarding the risk of colonic necrosis (tissue death) and other GI adverse effects when used with sorbitol in 2009.¹⁰

Patiromer is a potassium binder approved by the FDA in 2015. It works by binding potassium in exchange for calcium in the GI tract. To date, it has not caused serious adverse effects. Most of the adverse effects are GI disorders (e.g., constipation).¹⁰ Approved in 2018 by the FDA, SZC is the newest potassium binder. Its mechanism of action differs from patiromer. It binds potassium in exchange for hydrogen and sodium in the GI tract and its main site of action is in the small and large intestines. No serious adverse effects have been reported. Adverse effects are mild and usually GI disorders such as constipation.¹⁰Veltassa (patiromer) comes in single-use packets containing 1 gram, 8.4 grams, 16.8 grams, or 25.2 grams. User should store Veltassa in the refrigerator at 2°C to 8°C (36°F to 46°F).²⁰

Lokelma (SZC) comes in packets containing 5 grams or 10 grams. User should store Lokelma at 15°C to 30°C (59°F to 86°F).¹⁸

COMPARING PATIROMER AND SZC

Patiromer and SZC are safe and effective treatments for chronic hyperkalemia. They allow for continuance and optimal doses of RAASi in patients who develop hyperkalemia secondary to RAASi use. They also enable patients to experience optimal hemodialysis outcomes and can ease the dietary potassium restriction. Providers select a potassium binder based on safety and efficacy, cost, insurance coverage, and roles in the treatment of chronic hyperkalemia, which are discussed in detail below.

Cost and Insurance Coverage

Newer potassium binders are costly alternatives to traditional drugs for hyperkalemia. Table 4 lists their estimated out-of-pocket costs as of December, 25, 2023 according to GoodRx. The cost difference between patiromer and SZC is relatively small.²¹

Table 4. Estimated Out-of-Pocket Costs of Patiromer and SZC²²

Drug	Units	Cost
Patiromer	8.4 g x 4 Packs	$ 181.53
	8.4 g x 30 Packs	$ 940.61 – 989.34
	16.8 g x 30 Packs	$ 940.61 – 989.34
	25.2 g x 30 Packs	$ 940.61 – 989.34
Sodium zirconium cyclosilicate (SZC)	10 g x 11	$ 289.27 – 324.67
	10 g x 30	$ 782.16 – 871.05
	5 g x 11	$ 289.40 – 324.67
	5 g x 30	$ 781.61 – 782.16

Typical monthly costs associated with patiromer and SZC might be unaffordable for many Americans. However, the vast majority of patients have health plan coverage. (Note that the insurance discussions below are current as of January 2023.)

The Humana website reveals that some Humana Medicare plans cover all doses of patiromer at tier 3 (i.e., they are covered with a prior authorization), while some plans cover only select doses of SZC. These Humana plans include, but are not limited to, Humana Gold Plus HMO H5619-150, Humana Community H7621-002, Humana Gold Plus HMO H5619-148, Humana Walmart Value Rx Plan PDP, Humana Basic Rx Plan PDP, and Humana Premier Rx Plan PDP.²³ (Note that an HMO is a type of insurance with a network of contracted physicians and a PDP is a Medicare Part D prescription drug plan.)

A cursory check on Scan Health Plans website reveals that Scan Medicare plans appear to cover all doses of patiromer at tier 3, while SZC is not on formulary. These Scan health plans include but are not limited to, Village Health, Scan Classic, and Scan Venture. These plans require a prior authorization on patiromer.²⁴

The Wellcare website indicates that Wellcare Medicare plans cover patiromer at tier 3 without a prior authorization. These plans include but are not limited to Wellcare Classic PDP, Wellcare Value Script PDP, and Wellcare Medicare RX Value Plus PDP. Interestingly, the Wellcare Dual Align 129 plan covers SZC at tier 1 and it requires no prior authorization. It’s important to remember that a covered drug does not mean free. Patiromer’s yearly copay costs (what a patient is required to pay) may exceed $2000, and SZC can cost patients more than $1000 annually.²⁵

Manufacturers of both SZC and patiromer offer $0 per month copay savings cards. To use these cards, patients must have commercial insurance that does not cover the full prescription cost or be uninsured and responsible for the full prescription cost. Patients who are ineligible for these savings cards include those who are^26,27

enrolled in Medicare Part D, Medicaid, Medigap, Veterans Affairs, Department of Defense programs, or TriCare
Medicare eligible and enrolled in an employer-sponsored group waiver health plan or government-subsidized prescription drug benefit program for retirees

Pharmacy staff can assist cash-paying patients without insurance contact drug manufacturers to inquire about their patient assistance programs.

Breaking Down the Prior Authorization Process

As noted, some health insurance plans require a prior authorization to cover the newer potassium binders such as patiromer and SZC. This means the insurance company requires extra steps to determine whether a specific medical treatment, procedure, medication, or service is medically necessary and covered under a patient's health insurance plan. Pharmacists and pharmacy technicians can initiate the prior authorization process. Familiarity with the prior authorization process for various insurance plans is imperative for pharmacy staff. Although insurance plans have different forms and requirements within the prior authorization process, the basic steps are the same.

The major steps of the prior authorization process are as follows:

Download prior authorization forms from the insurance company website to determine what they require
Collect laboratory values, medical history, diagnosis, medical justification, drug history, rationale for request, and other pertinent patient information
Complete the prior authorization forms
Fax completed prior authorization forms to the insurance company or upload them via online platforms
Start the appeal process if denied

Pharmacists can enlist pharmacy technicians’ help to perform most or all of these steps.

The prior authorization process can take up anywhere from one day to more than a week. It is important to explain to patients that a prior authorization requirement does not mean a medication is not covered. It simply means that the insurance company might need more information before it covers the medication.

Pharmacy staff can sometimes initiate an appeal process if the insurer denies the medication. The most common reason for rejection/denial is insufficient supporting information. The other common reason for rejection/denial is drug class exclusion. For example, some Medicare part D plans do not cover certain drug classes. Once the provider or pharmacy submits an appeal, the insurance company usually takes one to two days to respond. Remember that manufacturer sponsored patient assistance programs can help patients who cannot afford the copay and patients who do not have insurance, and pharmacy staff can help patients with enrollment.

Table 5 lists the contact information for selected insurance plans. However, most tasks or inquiries can be handled online.

Table 5. Contact Information on Selected Insurance Plans^28,23,24,25

Plan	Department	Phone number
Humana	Humana Clinical Pharmacy Review Department	800-555-2546
Express Scripts	Express Scripts Coverage Review Department	800- 753-2851
Scan	Medical Reviews Department	844-424-8886
WellCare	Pharmacy Appeals Department	855-538-0453

Safety and Efficacy of Patiromer

The phase 2, multicenter, open-label, randomized AMETHSYT-DN trial determined patiromer starting doses for a phase 3 study and evaluated the long-term safety and efficacy of patiromer in 306 outpatients with hyperkalemia. The mean reduction from baseline in serum potassium level at week 4 or time of first dose titration in patients with mild hyperkalemia was 0.35, 0.51, and 0.55 mEq/L for groups starting at 4.2 g twice daily, 8.4 g twice daily, and 12.6 g twice daily, respectively.²⁹ For patients with moderate hyperkalemia, the reduction was 0.87, 0.97, and 0.92 mEq/L for patients starting at 8.4 g twice daily, 12.6 g twice daily, and 16.8 g twice daily, respectively.²⁹

From week four through week 52, AMETHYST-DN researchers observed statistically significant mean decreases in serum potassium levels. Over the 52-week-long trial, hypomagnesemia (7.2%) was the most common treatment-related adverse event and mild to moderate constipation (6.3%) was the most common GI adverse event. The researchers concluded that patiromer starting doses of 4.2 to 16.8 g twice daily resulted in statistically significant decreases in serum potassium levels after four weeks of treatment, lasting through 52 weeks.²⁹

The OPAL-HK clinical trial assessed the safety and efficacy of patiromer with an initial treatment phase and a withdrawal phase.³⁰ Among 237 patients in the initial treatment phase, the mean change in serum potassium level was -1.01 mmol per liter. Among 107 patients in the randomized withdrawal phase, the median increase in potassium levels from baseline of that phase was greater with placebo than with patiromer. The most common adverse effect in the initial treatment phase was constipation (11%), followed by diarrhea (3%), hypomagnesemia (3%), and nausea (3%). The most common adverse effects of the randomized withdrawal phase in the patiromer group were headache, supraventricular extra systoles (heart rhythm irregularities), constipation, diarrhea, and nausea; all occurred in 4% of all patients.³⁰

Safety and Efficacy of SZC

The phase 3, multicenter, randomized, double-blind, placebo-controlled HARMONIZE clinical trial evaluated SZC’s efficacy and safety for 28 days in outpatients with hyperkalemia at 44 sites in the U.S., Australia, and South Africa over six months.³¹ Patients received 10 g of SZC three times daily in the initial 48-hour open-label phase. Of the 258 patients, 237 patients achieved normokalaemia (normal potassium levels) with levels between 3.5 and 5 mEq/L and were randomized to receive SZC 5 g, 10 g, or 15 g or placebo daily for 28 days. In the open-label phase, serum potassium levels declined from 5.6 mEq/L at baseline to 4.5 mEq/L at 48 hours. In the randomized phase, serum potassium was significantly lower during days 8 through 29 with all SZC doses compared to placebo. Adverse events were comparable between SZC and placebo. Edema occurred more often in the 15 g group. Compared with placebo, all three doses of SZC resulted in lower potassium levels and a higher proportion of patients with normal potassium levels for up to 28 days.³¹

The double-blind, placebo-controlled, phase 3b multicenter DIALIZE study evaluated SZC for the management of hyperkalemia in patients undergoing hemodialysis.³² The researchers randomized adults with end-stage renal disease (ESRD) who were managed with hemodialysis three times weekly to SZC or placebo. These patients had pre-dialysis hyperkalemia and received SZC 5 g once daily on non-dialysis days. The researchers titrated doses to maintain normokalaemia over four weeks in 5 g increments to a maximum of 15 g. About 41.2% of patients in the SZC group responded to treatment compared with 1% of the 99 patients receiving placebo. Serious adverse events occurred in 7.3% of patients in the SZC group and 8.1 % of patients in the placebo group.³²

CASE STUDIES

Hyperkalemia usually occurs as a result of other illnesses. Certain medical conditions such as advanced stages of CKD, heart failure, hypertension, diabetes, myocardial infarction, and/or any combinations of these conditions increase the risk of hyperkalemia.¹⁰Treating the underlying diseases may alleviate the severity of hyperkalemia. While it’s critical to treat the whole patient, certain comorbidities are of utmost importance, including those imposing the greatest risks of morbidity and mortality. The key is to prioritize treatments according to the risks. Heart diseases, stroke, diabetes, and kidney diseases ranked first, fifth, eighth, and tenth, respectively, in the top 10 leading causes of death in the U.S. in 2021.³³

Case Study #1

Joan Smith is a female patient born on June 18, 1956. She has been diagnosed with type 2 diabetes, ESRD, osteoarthritis, hypertension, atrial fibrillation, and hyperkalemia. Dr. Bach contacted the pharmacist to conduct a comprehensive medication therapy management (MTM) and suggest an alternative to replace SPS.

Below is a list of selected recent lab values for Joan:

Item	Result	Units	Interval
A₁C	9.6 (H)	N/A	< 6.5
BUN	28 (H)	mg/dL	8 – 27
Creatinine	2.3 (H)	mg/dL	0.76 – 1.27
Potassium	5.3 (H)	mmol/L	3.5 – 5.2
Sodium	145 (H)	mmol/L	134 – 144
Chloride	99	mmol/L	96 – 106
Carbon dioxide	26	mmol/L	20 – 29
Calcium	9.1	mg/dL	8.6 – 10.2
Protein, total	8.2 (H)	g/dL	6.8 – 8.0
Albumin (A)	5.0 (H)	g/dL	3.8 – 4.8
Globulin (G), total	3.3	g/dL	1.5 – 4.5
A/G ratio	1.6	N/A	1.2 – 2.2
Bilirubin, total	0.4	mg/dL	< 1.2

A₁C, hemoglobin A1C; BUN, blood urea nitrogen.

Joan is taking the following medications:

NPH/regular human insulin 70/30 50 units subcutaneously twice daily
Lisinopril 20 mg orally once daily
SPS 60 mL orally as needed
Nephro-Vite 1 tablet orally once daily
Apixaban 5 mg orally twice daily
Aspirin 81 mg orally once daily
Ibuprofen 600 mg orally three times daily

Joan’s A₁C is out of range, so she would benefit from tighter blood sugar control. The pharmacist recommended changing NPH/regular human insulin (70/30) to lispro 16 units subcutaneously three times daily before meals and glargine 50 units subcutaneously once daily at bedtime. For Joan’s osteoarthritis, changing ibuprofen to acetaminophen 650 mg by mouth every eight hours is prudent because ibuprofen, an NSAID, may precipitate the development of hyperkalemia. While NSAIDs are not contraindicated in patients with kidney disease, clinicians should use the lowest dose possible for the shortest duration and avoid using NSAIDs at all in patients with severe kidney disease. Clinicians can consider a topical NSAID for mild osteoarthritis pain in smaller joints.³⁴Joan had mild hyperkalemia as indicated by her laboratory result. Her elevated BUN and creatinine values indicate that her renal function is insufficient. Joan’s sodium level is also elevated at 145 mmol/L. Both SPS and SZC can cause sodium overload, so they might not be the most appropriate choice for Joan. It may not be prudent to discontinue or reduce Joan’s lisinopril dose (RAASi therapy). Joan was advised to follow up with Dr. Bach at the next office visit.

After a thorough teleconference with Dr. Bach, the pharmacist recommends starting patiromer with an initial dose of 8.4 g once daily after discontinuing the SPS. Upon consultation with the patient and her caregiver, the technician reminds them to store patiromer in the refrigerator at 2°C to 8°C (36°F to 46°F). If stored at room temperature (25°C ± 2C° [77°F ± 4°F]), they must use the patiromer within three months. For either storage condition, they must not use patiromer after the expiration date printed on the packet and avoid exposing it to excessive heat greater than 40°C (104°F).²⁰

In addition, the pharmacist inquired about Joan’s use of over-the-counter herbal medications. The pharmacist informed Joan that certain herbal medications or supplements such as noni juice may cause or exacerbate hyperkalemia.³⁵Unconventional over-the-counter traditional Chinese medicines such as dried skin of toads (Chinese name: Chan Su) may cause poisoning and result in hyperkalemia.³⁶

Case study #2

John Williams is a male patient born on August 29, 1965. He has been diagnosed with hyperkalemia, ESRD, hyperlipidemia, type 2 diabetes, erectile dysfunction, hypertension, and heart failure. His most recent lab values are presented below.

Item	Result	Units	Interval
A₁C	11.1 (H)	N/A	< 6.5
BUN	29 (H)	mg/dL	8 – 27
Creatinine	2.45 (H)	mg/dL	0.76 – 1.27
Potassium	4.8	mmol/L	3.5 – 5.2
Sodium	135	mmol/L	134 – 144
Chloride	98	mmol/L	96 – 106
Carbon dioxide	27	mmol/L	20 – 29
Calcium	11.0 (H)	mg/dL	8.6 – 10.2
Protein, total	8.2 (H)	g/dL	6.8 – 8.0
Albumin (A)	5.1 (H)	g/dL	3.8 – 4.8
Globulin (G), total	3.4	g/dL	1.5 – 4.5
A/G ratio	1.5	N/A	1.2 – 2.2
Bilirubin, total	0.5	mg/dL	< 1.2

A₁C, hemoglobin A1C; BUN, blood urea nitrogen.

John is taking the following medications:

Patiromer 16.8 mg orally once daily
Metoprolol succinate ER 100 mg orally once daily
Simvastatin 40 mg orally once daily
Sildenafil 50 mg orally as needed for sexual activity
Sacubitril-valsartan 97-103 mg orally twice daily
Spironolactone 100 mg orally once daily
Insulin glargine 40 units subcutaneously at bedtime
Insulin lispro 14 units subcutaneously 15 minutes before each meal
Semaglutide 2 mg subcutaneously once weekly
Empagliflozin 25 mg orally once daily
Calcifediol 30 mg orally once daily

John first experienced high sodium levels while on SPS due to the sodium load per dose. Subsequently, John was prescribed patiromer and experienced stomach upset. Dr. Kidd contacts the pharmacist to conduct a comprehensive MTM and suggest an alternative to replace patiromer.

John’s potassium level was within range and his condition has been stable. However, the calcium level (11.0 mg/dL) is elevated. Patiromer might not be the most appropriate choice. The pharmacist recommended considering SZC. John can start on an initial dose of 10 g orally 3 times daily for 48 hours, followed by 10 g once daily thereafter. Sacubitril-valsartan (RAASi therapy) reduces the risk of hospitalization and spironolactone substantially lowers the risk of both morbidity and death among patients with severe heart failure.³⁷As a result, the pharmacist recommended that John remain on sacubitril-valsartan and spironolactone as prescribed.

John’s glucose level (A₁C) was out of range at 11.1. He would benefit from continuous glucose monitoring (CGM). The pharmacist introduced a commercially available CGM device to John and encouraged him to monitor his glucose level after meals, at bedtime, and at any time John feels there is a need to monitor. To reach A₁C target, John should titrate his basal insulin (glargine) by increasing 2 units every three days and prandial insulin (lispro) by 1 to 2 units twice weekly without hypoglycemia.

The pharmacist asked John about the use of salt substitutes and advised him that some salt substitutes may cause hyperkalemia. Regarding erectile dysfunction, John stated that sildenafil was, “…working somewhat but I need a bit more help. My sex life is not what it used to be. Maybe I can purchase something over-the-counter to spice it up!” The pharmacist discouraged the use of commercially available over-the-counter aphrodisiacs containing digoxin-like substances. Atrial fibrillation, ventricular fibrillation, and death have been reported with their use.³⁸

CONCLUSION

No universally accepted guidelines exist for monitoring and classification of hyperkalemia. Similarly, no universally accepted guidelines exist for dosage modification of RAASi therapy. When selecting drugs to treat hyperkalemia, healthcare professionals should consider factors such as co-existing diseases, duration of action, onset of action, cost, drug interactions, food interactions, cardiovascular benefits, and renal benefits. Newer potassium binders may help optimize RAASi therapy and provide a safe and reliable chronic hyperkalemia treatment option. The use of these newer potassium binders and the optimal use of RAASi therapy may improve cardiovascular outcomes.

Pharmacist Post Test (for viewing only)

ACUTE AND CHRONIC HYPERKALEMIA: TREATMENT OPTIONS, POTASSIUM BINDERS, AND CLINICAL CASES
Pharmacist Post-test

Learning Objectives
After taking the continuing education activity, pharmacists will be able to
• Identify foods that cause hyperkalemia
• List medications that cause hyperkalemia
• Compare and contrast medications that manage acute and chronic hyperkalemia
• Determine the best agent to manage hyperkalemia in each case study

1. Which of the following juices (serving size = 120 ml) contains the MOST potassium?
A. Apple juice
B. Pineapple juice
C. Prune juice

2. Which of the following medications is known to cause hyperkalemia?
A. Acetaminophen
B. Losartan
C. Amlodipine

3. Jerry Smith is a 55-year-old male patient with a potassium level of 5.5 mEq/L. He is on hydralazine 100 mg three times daily for heart failure. Jerry has occasional episodes of edema in his lower extremities. Dr. Gore, Jerry’s cardiologist, asks you, the pharmacist, to recommend a potassium binder. Which of the following potassium binders is the most appropriate treatment?
A. Sodium polystyrene sulfonate
B. Sodium zirconium cyclosilicate
C. Patiromer

4. Which of the following adverse effects is the most concerning regarding sodium polystyrene sulfonate when used with sorbitol?
A. Constipation
B. Edema
C. Colonic necrosis

5. Which of the following foods contains the MOST potassium?
A. One whole orange
B. One whole peach
C. One whole nectarine

6. Which one of the following medications can cause hyperkalemia?
A. IV calcium gluconate
B. Insulin glargine
C. Beta-blockers

7. Melissa Kennedy is a 60-year-old female patient with acute hyperkalemia (potassium level > 6.5 mEq/L). Her ECG shows loss of P waves. Dr. Patel would like to start treatment. However, Dr. Patel is concerned with the accompanying metabolic acidosis. Which of the following acute hyperkalemia treatments is the MOST appropriate?
A. Intravenous sodium bicarbonate
B. Inhaled beta-agonist
C. Intravenous calcium gluconate

8. Which of the following treatments is BEST for acute hyperkalemia?
A. Potassium binders
B. Sodium zirconium cyclosilicate (SZC)
C. Intravenous insulin

9. Which of the following potassium binders exchanges potassium for calcium in the GI tract?
A. Sodium polystyrene sulfonate
B. Sodium zirconium cyclosilicate
C. Patiromer

10. Sophia Raya Corona is a 65-year-old patient with underlying renal dysfunction. Sophia has been on losartan 50 mg once daily and spironolactone 25 mg once daily for 5 years. Her hypertension is well-controlled at 120/80 mmHg. Her most recent potassium level is 5.4 mEq/L. Which one of the following actions is MOST appropriate?
A. Reduce losartan and spironolactone doses by 50%
B. Initiate patiromer therapy
C. Initiate sodium polystyrene sulfonate therapy

Pharmacy Technician Post Test (for viewing only)

ACUTE AND CHRONIC HYPERKALEMIA: TREATMENT OPTIONS, POTASSIUM BINDERS, AND CLINICAL CASES
Pharmacy Technician Post-test

Learning Objectives
After taking the continuing education activity, pharmacy technicians will be able to
• Identify foods that cause hyperkalemia
• List medications that cause hyperkalemia
• Describe the dosing and storage information of patiromer and SZC
• Describe the steps of the drug prior authorization process

1. Which one of the following doses of patiromer is commercially available?
A. 8.5 g
B. 15.8 g
C. 25.2 g

2. Which of the following medications is known to cause hyperkalemia?
A. Acetaminophen
B. Losartan
C. Amlodipine

3. Which of the following statements is TRUE regarding storage of patiromer?
A. If stored at room temperature, patiromer must be used within six months
B. Patient may expose patiromer to excess heat greater than 30°C (86°F) but less than 35°C (95°F)
C. Patiromer should be stored in the refrigerator at 2°C to 8°C (36°F to 46°F)

4. A patient is picking up a prescription for a potassium lowering medication. You note that he has a piece of fruit in his hand and he seems to be preparing to eat it. Which of the following fruits contains the most potassium and might prompt you to warn him to avoid eating that fruit?
A. One whole orange
B. One whole peach
C. One whole nectarine

5. Which one of the following is the first step of the prior authorization process?
A. Collecting necessary patient information
B. Downloading prior authorization forms
C. Completing the prior authorization forms

6. Which one of the following is the last step of prior authorization process?
A. Starting appeal process if denied
B. Downloading prior authorization forms
C. Collecting patient information

7. Which one of the following medications can cause hyperkalemia?
A. IV calcium gluconate
B. Insulin glargine
C. Beta-blockers

8. Which of the following foods contains the MOST potassium?
A. Five apricots
B. One kiwi
C. One banana

9. Which of the following statements is TRUE regarding storage requirement of SZC?
A. SZC should be stored at room temperature
B. SZC should be stored frozen until opened
C. SZC should be refrigerated until opened

10. Which one of the following medications causes hyperkalemia?
A. Ibuprofen
B. Acetaminophen
C. Patiromer

Full List of References

References

1. Potassium. MedlinePlus. Accessed December 25, 2023. https://medlineplus.gov/potassium.html
2. Stöppler MC. High potassium (hyperkalemia). MedicineNet. Updated May 16, 2022. Accessed December 15, 2023. https://www.medicinenet.com/hyperkalemia/article.htm
3. Chang AR, Sang Y, Leddy J, Yahya T, Kirchner HL, Inker LA, Matsushita K, Ballew SH, Coresh J, Grams ME. Antihypertensive Medications and the Prevalence of Hyperkalemia in a Large Health System. Hypertension. 2016;67(6):1181-8. doi:10.1161/HYPERTENSIONAHA.116.07363.
4. Nilsson E, Gasparini A, Ärnlöv J, Xu H, Henriksson KM, Coresh J, Grams ME, Carrero JJ. Incidence and determinants of hyperkalemia and hypokalemia in a large healthcare system. Int J Cardiol. 2017;245:277-284. doi:10.1016/j.ijcard.2017.07.035.
5. Gilligan S, Raphael KL. Hyperkalemia and Hypokalemia in CKD: Prevalence, Risk Factors, and Clinical Outcomes. Adv Chronic Kidney Dis. 2017;24(5):315-318. doi:10.1053/j.ackd.2017.06.00.
6. Kidadl. Accessed October 15,2023. https://kidadl.com/facts/interesting-facts-about-potassium-you-should-know-about.
7. Palmer BF, Clegg DJ. Physiology and pathophysiology of potassium homeostasis. Adv Physiol Educ. 2016;40(4):480-490. doi:10.1152/advan.00121.2016.
8. Palmer BF, Clegg DJ. Diagnosis and treatment of hyperkalemia. Cleve Clin J Med. 2017;84(12):934-942. doi:10.3949/ccjm.84a.17056.
9. Palmer BF. Managing hyperkalemia caused by inhibitors of the renin-angiotensin-aldosterone system. N Engl J Med. 2004;351(6):585-92. doi:10.1056/NEJMra035279.
10. Palmer BF, Carrero JJ, Clegg DJ, et al. Clinical Management of Hyperkalemia. Mayo Clin Proc. 2021;96(3):744-762. doi:10.1016/j.mayocp.2020.06.014
11. Clinical Resource. Management of acute and chronic hyperkalemia. Pharmacist’s Letter. Nov 2019 (351115). Accessed February 10, 2024. https://pharmacist.therapeuticresearch.com/Content/Segments/PRL/2016/Feb/Management-of-Acute-and-Chronic-Hyperkalemia-9412
12. Clinical Resource. Potassium Content of foods and salt substitutes. Pharmacist’s Letter. Feb 2021 (370227). Accessed February 10, 2024. https://pharmacist.therapeuticresearch.com/Content/Segments/PRL/2008/Sep/Potassium-Content-of-Foods-and-Salt-Substitutes-1122
13. Simon LV, Hashimi M, Farrell MW. Hyperkalemia. Treasure Island: StatPearls Publishing; 2023. Accessed Sep 1, 2023. https://hyperkalemia - StatPearls - NCBI Bookshelf (nih.gov)
14. Clase CM, Carrero JJ, Ellison DH, et al. Potassium homeostasis and management of dyskalemia in kidney diseases: conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference. Kidney Int. 2020;97(1):42-61. doi:10.1016/j.kint.2019.09.018
15. Reddenna L, Basha S, Kumar K. Dialysis Treatment: A Comprehensive Description. Int. J. of Pharm. 2014;3(1)1-13.
16. Butler J, Khan MS, Anker SD. Novel potassium binders as enabling therapy in heart failure. Eur J Heart Fail. 2019;21(5):550-552. doi:10.1002/ejhf.1474
17. Rxlist.com. Accessed February 10, 2024. https://www.rxlist.com/how_do_potassium_binders_work/drug-class.htm#:~:text=They%20bind%20to%20the%20excess,thereby%20lowering%20blood%20potassium%20levels.
18. Lokelma [package insert}. AstraZeneca Pharmaceuticals LP; 2023.
19. Drugs.com. Accessed December 25, 2023. Sodium Polystyrene Sulfonate: Package Insert - Drugs.com
20. Veltassa [package insert]. Vifor Pharma, Inc; 2023.
21. Huda AB, Langford C, Lake J, Langford N. Hyperkalaemia and potassium binders: Retrospective observational analysis looking at the efficacy and cost effectiveness of calcium polystyrene sulfonate and sodium zirconium cyclosilicate. J Clin Pharm Ther. 2022;47(12):2170-2175. doi:10.1111/jcpt.13766
22. GoodRx. Lokelma: Prices. Accessed December 15, 2023. https://www.goodrx.com/lokelma
23. Humana. Let us help you choose a plan. Accessed December 15,2023. https://plans.humana.com/plans
24. Scan: Plans and Benefits. Accessed December 15, 2023. https://www.scanhealthplan.com/plans-and-benefits
25. Wellcare. Explore Plans. Accessed December 15, 2023. https://wellcare.isf.io/2024/g/b0003db0c5534c0aaa58d48d58be37c5/AssistedShopping
26. Veltassa savings and affordability. Veltassa. Accessed December 15, 2023. https://veltassa.com/patient/savings-affordability
27. Lokelma Support Program. Accessed December 15, 2023. https://www.lokelma.com/support-program.html
28. Express Scripts. Electronic prior authorization. Accessed October 15, 2023. https://www.express-scripts.com/corporate/prior-authorization-resources
29. Bakris GL, Pitt B, Weir MR, et al. Effect of Patiromer on Serum Potassium Level in Patients With Hyperkalemia and Diabetic Kidney Disease: The AMETHYST-DN Randomized Clinical Trial [published correction appears in JAMA. 2015 Aug 18;314(7):731. Dosage error in article text]. JAMA. 2015;314(2):151-161. doi:10.1001/jama.2015.7446
30. Weir MR, Bakris GL, Bushinsky DA, et al. Patiromer in patients with kidney disease and hyperkalemia receiving RAAS inhibitors. N Engl J Med. 2015;372(3):211-221. doi:10.1056/NEJMoa1410853
31. Kosiborod M, Rasmussen HS, Lavin P, et al. Effect of sodium zirconium cyclosilicate on potassium lowering for 28 days among outpatients with hyperkalemia: the HARMONIZE randomized clinical trial [published correction appears in JAMA. 2015 Feb 3;313(5):526. Dosage error in text]. JAMA. 2014;312(21):2223-2233. doi:10.1001/jama.2014.15688
32. Fishbane S, Ford M, Fukagawa M, et al. A Phase 3b, Randomized, Double-Blind, Placebo-Controlled Study of Sodium Zirconium Cyclosilicate for Reducing the Incidence of Predialysis Hyperkalemia. J Am Soc Nephrol. 2019;30(9):1723-1733. doi:10.1681/ASN.2019050450
33 Xu J, Murphy SL, Kochanek KD, Arias E. Mortality in the United States, 2021. NCHS Data Brief. 2022;(456):1-8.
34. Consider Kidney Risk Before Suggesting an NSAID, Pharmacist’s Letter, October 2022. https://pharmacist.therapeuticresearch.com/Content/Articles/PL/2022/Oct/Consider-Kidney-Risks-Before-Suggesting-an-NSAID
35. Mueller BA, Scott MK, Sowinski KM, Prag KA. Noni juice (Morinda citrifolia): hidden potential for hyperkalemia?. Am J Kidney Dis. 2000;35(2):310-312. doi:10.1016/s0272-6386(00)70342-8
36. Pantanowitz, L. To the editor, Drug-induced hyerkalemia, Amjmed. 2002 March. Pantanowitz L. Accessed February 10, 2024. http://Drug-induced hyperkalemia. Am J Med. 2002;112(4):334-335. doi:10.1016/s0002-9343(01)00688-x
37. Pitt B, Zannad F, Remme WJ, et al. The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators. N Engl J Med. 1999;341(10):709-717. doi:10.1056/NEJM199909023411001
38. Centers for Disease Control and Prevention (CDC). Deaths associated with a purported aphrodisiac--New York City, February 1993-May 1995. MMWR Morb Mortal Wkly Rep. 1995;44(46):853-861.

Getting a Slice of the (AD)PIE: The Pharmacy Team’s Guide to Collaborating with the RN for Pain Management

After completing this application-based continuing education activity, pharmacists will be able to

Recognize how the registered nurse’s scope of practice supports the pharmacist

Identify appropriate nonpharmacologic and pharmacologic pain management practices

Describe how the registered nurse and pharmacist can collaborate to improve patient outcomes

Use the ADPIE framework to write a pain management care plan

After completing this application-based continuing education activity, pharmacy technicians will be able to:

Recognize how the registered nurse’s scope of practice supports the pharmacy technician

Identify appropriate nonpharmacologic and pharmacologic pain management practices

Describe how the registered nurse and pharmacy technician can collaborate to improve patient outcomes

Use the ADPIE framework to review a pain management care plan

Healthcare educators and researchers frequently proclaim that teamwork improves patient outcomes, yet some collaboration opportunities are left unseized. In parallel, pain management is integral to a great proportion of conditions, yet discussion of analgesic therapies is generally narrow in scope. Specifically, pharmacologic strategies tend to take precedence over non-pharmacologic modalities. These overarching topics unite when healthcare professionals regard collaboration between the pharmacy team and nurse team as a means to ameliorate pain and minimize pharmacologic analgesics. Coordination between the pharmacy and nurse teams is a natural component of the nursing process, which culminates in the nurse’s development of a care plan. Pharmacy teams that are well-versed in the nursing process can capitalize on opportunities to apply non-pharmacologic pain control methodologies and seek interprofessional collaboration to improve patient outcomes.

Content

INTRODUCTION

Interprofessional collaboration crops up as a topic in many healthcare facility staff meetings. However, team members often don’t know how to collaborate effectively, so the conversation quickly trails off. Before you know it, everyone’s talking about the new espresso machine in the break room, and attendees are leaving the meeting without practicable advice.

Insufficient guidance on how to work together results in lost opportunities to improve patient outcomes. Consider the heart failure medication titration clinic that tested a pharmacist-driven titration protocol. Pharmacists collected data from vital signs and patient interviews to optimize drug dosages in heart failure, with statistically significant improvements in dosages.¹ There was a key opportunity to collaborate here. The job description of someone on your team includes taking vitals and interviewing patients: the registered nurse (RN)!

Step one of effective teamwork is recognizing opportunities to put your heads together. Pain management took center stage when the multi-wave opioid overdose epidemic began in the 1990s.² Plus, pain is an intrinsic characteristic of nearly all physical afflictions. What do you get when you combine these facts? An issue that’s causing significant problems and is ubiquitous— it’s ripe for collaboration.

What do RNs do? How can you partner with them? And what is this about pie?! This continuing education activity will guide you through those questions and provide an overview of trends in pharmacologic pain management. You’ll also learn several nonpharmacologic pain management strategies.

Note: “RN” and “nurse” are used interchangeably in this activity. Many of an RN’s responsibilities (comprehensive assessment and care plan creation in particular) are outside the scope of practice of, for example, a Licensed Practical Nurse (LPN).^3,4,5

Furthermore, RNs are as ubiquitous as pharmacy professionals. Pieces of this activity apply mostly to RNs in specific settings such as hospitals. However, it’s helpful to keep in mind that RNs work in skilled nursing facilities, telehealth, schools, home healthcare, correctional facilities, and more. Considering these different areas can keep your gears turning when deducing how to crack the nut of collaboration.

THE NURSE’S ROLE

Working with every member of the healthcare team necessitates understanding everyone’s role. Ask five people what an RN does, and you’ll probably hear five different answers. One misconception is that the nurse is an extension of the doctor. On the contrary, nurses have their own chain of command and overarching objectives in patient care. The doctor’s focus centers around an injury's or illness’ physiological implications, whereas the nurse manages how the condition affects the patient.^6,7,8 The SIDEBAR about nursing diagnoses later in the activity differentiates these concepts.

What nurses do is part of the picture—the other part is how they do it. RNs use communication and four of their five senses (hopefully they’re not tasting anything, anyway…) to establish and continually revise a care plan.The framework for a care plan is known as ADPIE.^4,8

We’ll circle back to RNs, care plans, and that pie you were promised. Let’s look at pharmacologic and nonpharmacologic pain management methods first, and we’ll connect the dots later.

PAIN MANAGEMENT

At its most fundamental level, every pain treatment is pharmacologic or nonpharmacologic. Both have the power to help the patient, but any number of minutiae about the patient and condition dictates which therapy or combination of therapies is best.

Pharmacologic Pain Management

Numerous factors including etiology, coexisting conditions (e.g., pregnancy, disease), and pain type (e.g., neuropathic, pleuritic, visceral) steer analgesic selection. This activity primarily categorizes pharmacologic therapies by classifying pain as acute or chronic. You will understand the reason for this delineation when you read about nursing diagnoses.

Considerations for cancer pain and the geriatric and pediatric populations close the section.

Acute Pain

The Centers for Disease Control and Prevention (CDC) classifies pain lasting three months or less as acute.⁹Today’s analgesic guidance for acute pain centers around multimodal strategies, due in part to the opioid crisis. These strategies’ end goal is effective pain relief with minimal adverse effects.^9,10 “Balanced analgesia” is the term for this concept. Its underlying principle is to reduce opioid and non-opioid dosages by attacking pain from multiple angles.¹⁰

One such approach is channels-enzymes-receptors targeted analgesia, or CERTA. This approach boils down to pathways and progression. Namely, practitioners can achieve balanced regimens by deploying interventions that act on different pathways and progressing to more potent therapies as needed.¹⁰

A balanced and stepwise approach to acute pain therapies comes to life in Table 1. As with all matters in healthcare, patient-specific care is paramount. For instance, although opioids are not necessarily first-line therapies, a non-opioid trial is not required before initiating opioid therapy.⁹

Table 1. Pharmacologic Medications for Acute Pain^10,11

Topical
· Diclofenac or ibuprofen for musculoskeletal injuries · Camphor, menthol, and clove oil for headache or muscle pain

Mild to moderate acute pain
Medication	Example indications	What to know
Acetaminophen	Headache, sprain	· Combine with NSAIDs for postoperative pain · Limit 75 mg/kg/day or 4,000 mg/day (2,000 mg/day in hepatic disease and alcohol use disorder)
NSAIDs (ibuprofen, naproxen, diclofenac, ketorolac, meloxicam, celecoxib)	Migraine, postoperative pain, low back pain	· Patient might need a PPI · Combinations with acetaminophen improve analgesia

Moderate to severe acute pain
Medication	Example indications	What to know
[Opioid] + [acetaminophen or NSAID] (HYDROcodone/acetaminophen, HYDROcodone/ibuprofen, oxyCODONE/acetaminophen)	Fracture, postoperative pain	Combinations reduce the opioid dosage needed
Dual-action opioids (traMADol, tapentadol)	Therapeutic failure of other agents	· Risk for opioid use disorder and serotonin syndrome · TraMADol reduces seizure threshold
Full-agonist opioids (oxyCODONE, morphine, HYDROmorphone, fentanyl)	Therapeutic failure of other agents	· Risk for sedation, respiratory depression, and opioid use disorder · 3-day limit

NSAID = nonsteroidal anti-inflammatory drug

PPI = proton pump inhibitor

Nonsteroidal anti-inflammatory drugs (NSAIDs) enter virtually every discussion about acute pain. Note that this drug class may cause complications in patients with cardiovascular or renal impairment or a history of gastrointestinal (GI) bleed.^9,12

Adverse GI effects of NSAIDs are less likely to occur with a selective COX-2 inhibitor such as celecoxib. In turn, the patient is less likely to need a PPI (proton pump inhibitor) than with other NSAIDs. Eliminating a PPI lowers costs and helps inhibit polypharmacy’s adverse effects.¹¹

Is the first column of Table 1 reminiscent of alphabet soup? Drug names that resemble one another—aptly named “look-alike and sound-alike” (LASA) drugs—present an opportunity for unfortunate drug mix-ups. The LASA Drugs SIDEBAR has more information about these drug name pairings.

SIDEBAR

LASA Drugs^13,14

Nurses learn about and watch out for look-alike and sound-alike (LASA) drugs. However, the pharmacy team—the pharmacy technician, in particular—is the first line of defense in preventing related errors.

Mix-ups between HYDROmorphone and morphine constitute an example of a common and serious LASA-related problem. Some ways to help prevent med errors involving these two drugs include

Placing each agent and strength in its own bin or drawer.
Looking for tall man lettering: HYDROmorphone.
Stating the name of the drug before providing it to a patient for confirmation.
Using brand names for additional confirmation.

The LASA list is a living document. How can you keep up to date on changes and additions? The ISMP (Institute for Safe Medication Practices) maintains this table—find it here.

Drug name	Confused drug name
acetaminophen	acetaZOLAMIDE
buprenorphine	HYDROmorphone
carBAMazepine	OXcarbazepine
codeine	Lodine
DULoxetine	Dexilant, FLUoxetine, PARoxetine
EPINEPHrine	ePHEDrine
fentaNYL	ALfentanil, SUFentanil
gabapentin	gemfibrozil
HYDROcodone	oxyCODONE
HYDROmorphone	buprenorphine, hydrALAZINE, hydrOXYzine, morphine, oxyMORphone
ketamine	ketorolac
ketorolac	Ketalar, ketamine, methadone
methadone	dexmethylphenidate, ketorolac, memantine, Mephyton, Metadate, Metadate ER, methylphenidate, metOLazone
morphine*	HYDROmorphone
oxyCODONE	HYDROcodone, oxybutynin, OxyCONTIN, oxyMORphone
traMADol	traZODone

*Morphine has a non-concentrated oral liquid form and a concentrated oral liquid form.

Note: Names with first letter capital letters indicate trade names.

PAUSE AND PONDER: Where can you refer patients if you suspect drug abuse, or if a patient requests such a resource for himself or a loved one?

Chronic Pain

Per the CDC, pain lasting longer than three months is chronic. Following are select chronic pain management recommendations from the CDC Clinical Practice Guideline for Prescribing Opioids for Pain.⁹ Practitioners who prescribe opioids should read this comprehensive guideline in full—click here to access this free document.

Use nonopioid therapies to the greatest extent possible.
Discuss the risks and benefits of opioids with the patient.
Prescribe immediate-release formulations at the start of opioid therapy.
Start with the lowest dosage possible for opioid-naïve patients.
Evaluate the risk/benefit balance before increasing dosages.
Do not discontinue or rapidly decrease dosages in the absence of a life-threatening condition.
Evaluate risks and benefits 1-4 weeks after starting therapy and periodically thereafter.
Use a prescription drug monitoring program to help evaluate the risk of overdose.
Evaluate the risk/benefit balance of concurrent benzodiazepines.

Extensive news coverage of the opioid crisis means that even individuals far removed from healthcare are wary of opioids. Serious adverse effects and associations include respiratory depression, overdose, opioid use disorder, falls, and death from all causes. All healthcare providers must inform patients that benzodiazepines, alcohol, and some illicit drugs increase the risk for respiratory depression.^9,15

Common adverse effects of opioids include constipation, nausea/vomiting, and drowsiness. These effects might cause patients to discontinue therapy. Practitioners should warn against abrupt opioid discontinuation, explaining that withdrawal syndrome could result. They should inform patients that certain behaviors can mitigate adverse effects, such as hydration, fiber intake, and exercise for constipation.^9,15

What alternatives to opioids exist? Other drug classes for chronic pain include NSAIDs, anticonvulsants (pregabalin, gabapentin), and serotonin and norepinephrine reuptake inhibitors (SNRIs; DULoxetine, milnacipran).⁹ These are associated with their own risks to consider when planning a patient’s drug regimen.

Cancer Pain: The WHO Analgesic Ladder

The World Health Organization (WHO) released an algorithm in the mid-1980s to steer pain management planning in cancer, as this condition warrants unique considerations.¹⁶

The WHO analgesic ladder, replicated in Figure 1, is a major element of the algorithm. It provides visual guidance for prescribing and deprescribing adjuvant, non-opioid, and opioid analgesics for varying pain severities. Following are select examples^16,17:

Adjuvants: antidepressants (amitriptyline, DULoxetine), anticonvulsants (gabapentin, carBAMazepine), corticosteroids, cannabinoids
Non-opioid analgesics: NSAIDs (ibuprofen, ketorolac), acetaminophen
Weak opioids: HYDROcodone, codeine, traMADol
Potent opioids: morphine, HYDROmorphone, methadone, fentaNYL, oxyCODONE, buprenorphine

Figure 1. WHO Analgesic Ladder¹⁷

Reproduced from WHO Guidelines for the Pharmacological and Radiotherapeutic Management of Cancer Pain in Adults and Adolescents, World Health Organization, Annex 1: Evaluation of Pain, P. 70, 2018.

Note that the model has criticisms. For instance, it can lead to the erroneous inference that NSAIDs are safe since they are the ladder’s entry point. Furthermore, the WHO designed the ladder for simplicity, causing clinicians to reference it outside the bounds of cancer pain. However, research findings point to abandoning the algorithm in chronic non-cancer pain (CNCP). Pharmacologic and nonpharmacologic strategies that better control CNCP while limiting opioid usage exist.^16,18,19

The WHO analgesic ladder is just one constituent of the extensive WHO Guidelines for the Pharmacological and Radiotherapeutic Management of Cancer Pain in Adults and Adolescents (click here to access). Reference this manual for further guidance in cancer pain management, such as the following principles that should accompany the ladder¹⁷:

By mouth: Use the oral route of administration when possible.
By the clock: Administer pain medication at set intervals rather than pro re nata (PRN).
For the individual: Tailor pain management to the individual; the ladder is only a guideline.
With attention to detail: Base first and last doses on sleep/wake times. Write down drug and administration regimen information for caretakers. Inform patients of potential side and adverse effects.

Geriatric Considerations

Common origins of pain in the geriatric population are arthritis, postherpetic neuralgia, and cancer. And although more common as we age, pain is not a normal element of the aging process.²⁰ However, practitioners must consider certain essential physiological changes when prescribing for older patients. These include increased body fat and decreased rates of GI absorption and renal and hepatic clearance.²¹

Also notable is that older adults often experience insufficient pain relief, such as when they cannot communicate the presence or degree of pain.²¹

Drugs from several classes indicated for pain appear in the AGS Beers Criteria for Potentially Inappropriate Medication Use in Older Adults (AGS: American Geriatric Society). These classes include benzodiazepines, certain antidepressants, skeletal muscle relaxants, and NSAIDs.²² Healthcare providers should check this publicly accessible document (click here to access) when prescribing or reviewing an older adult’s medications.

Consider acetaminophen to be the first-line analgesic for pain in the older adult. Hospitalized older patients with oral intake restrictions might require intravenous (IV) acetaminophen. If acetaminophen is insufficient, NSAIDs follow. They are relatively safe for short-term use such as during an emergency room visit, although the provider should consider including a PPI. In terms of safety and timelines, NSAID use increases the risk for cardiac events after just one week of regular use. Topical formulations can be an effective alternative in the face of GI or cardiovascular contraindications to NSAIDs.^21,23

Prescribers should also start opioids at a lower dosage in geriatric patients. Morphine and HYDROmorphone can be initial analgesics, but note that their metabolites are excreted by the kidneys. Therefore, fentaNYL might be a better option for the older patient with renal impairment.^21,24

Pediatric Considerations

Pain control is especially important for pediatric patients since unmanaged pain can develop into hyperalgesia (excessive response to pain).^25,26

Unlike with other populations, the first-line pain therapy for pediatric patients isn’t part of the formulary—it’s nonpharmacologic intervention. Methods range from breastfeeding for the youngest to distraction with video games for the teens.²⁷

If nonpharmacologic techniques are insufficient, the clinical team needs to make route of administration a top consideration in drug therapy. They should start with the least invasive route, considering non-parenteral routes first (inhaled, intranasal, oral, rectal, topical).²⁷ Table 2 lists common medications by route.

Table 2. Pharmacologic Medications for Pediatric Patients²⁷

Route of administration	Common medications
Topical	· Lidocaine · Lidocaine and prilocaine · Lidocaine, EPINEPHrine, and tetracaine · Ethyl chloride · Pentafluoropropane and tetrafluoroethane
Oral	Acetaminophen, ibuprofen, naproxen, sucrose (infants)
Intranasal	Ketamine, fentaNYL, HYDROmorphone
Inhaled	Ketamine, nitrous oxide
Intravenous	Ketorolac, acetaminophen, ketamine, morphine, HYDROmorphone, fentaNYL

Here’s a PRO TIP: Children are not simply “small humans.” They are physiologically different from adults, necessitating special considerations in pharmacology even within sub-stages of the broad category of pediatrics. In other words, treatment for a 4-year-old cannot be the same as for her 15-year-old sister.^27,28

Moreover, when prescribing for the pediatric population—which often involves weight-based dosing—clinicians must consult prescribing guidelines specific to the pediatric population. Calculating the pediatric dosage by extrapolating the adult dosage-to-weight ratio could yield a subtherapeutic or supratherapeutic dosage.^27,28

PAUSE AND PONDER: Patients with painful conditions generally fear or dread this aspect of their affliction. What are some ways you can respond when patients communicate these feelings, such as when expressing worry that their analgesic prescriptions will be insufficient?

Nonpharmacologic Pain Management

Nonpharmacologic pain control is so important that the Joint Commission stipulates its availability in hospitals.²⁹ Supplementing drug therapy with nonpharmacologic interventions further reduces pain and does not present significant risk.⁹

Inpatient nurses are generally with patients for a short period (average length of acute care stay is approximately 6.5 days), so they might use the same techniques for acute and chronic pain.³⁰ Hence, this section doesn’t focus on such a distinction, but Table 3 lists statistics-based guidance regarding nonpharmacologic therapy specifically for chronic pain.

Table 3. Nonpharmacologic Strategies for Chronic Pain³¹

Pain type	Term	Successful modality(ies)
Chronic low back pain	Short	Psychological therapy, massage, stress reduction, acupuncture
	Intermediate	Psychological therapy, spinal manipulation, yoga
	Long	Psychological therapy
Chronic neck pain	Short	Low-level laser therapy
Osteoarthritis pain	Short	Exercise
Fibromyalgia	Short	Exercise
Fibromyalgia	Intermediate	Exercise

Short term: 1 to < 6 months

Intermediate term: ≥ 6 to < 12 months

Long term: ≥ 12 months

Note 1: “Term” is the length of time between intervention and assessment.

Note 2: This table only includes data with moderate strength of evidence.

Note 3: The research did not find high-quality evidence for nonpharmacologic pain relief for chronic tension headaches.

Because this continuing education activity centers around collaborating with the RN, the nonpharmacologic techniques detailed omit those outside the RN’s scope of practice. Interested learners can seek other literature for information about the following examples of such modalities^32,33:

Ablation
Acupuncture
Cognitive behavioral therapy
Counseling
Electrical nerve stimulation
Physical and occupational therapy

The coming subsections cover some techniques the RN can apply. But any healthcare provider can employ these strategies, wherever the patient is, and without preparation. Plus, you can suggest these ideas to the RN during rounds or team meetings.

Journaling

Patients can journal about their pain to reduce its intensity and its interference in their daily life. Researchers who conducted a study in CNCP had 72 patients journal quantitative information each day. Included were a body pain map, pain intensity, and ratings for disturbance to activities and quality of life. Patients recorded qualitative data at the end of each week, including pain management methods and communication with others about pain.³⁴

How did journaling help?

Patients understood their pain better.
Providers supported and communicated with patients more effectively.
Journals served as an outlet for negative emotions.

Here’s another PRO TIP: The study found that journaling was effective only in patients with adaptive coping mechanisms—healthy stress management techniques, such as exercise or religious practices. Consider other nonpharmacologic modalities for patients who use avoidance or other maladaptive strategies.³⁴

Mind-Body Interventions

When advising patients, it is as important to know what works as it is to know what doesn’t work. Claims regarding mind-body techniques for pain relief abound, but are any effective?

A study on mind-body interventions divided 244 participants into three parallel arms. Of 159 participants undergoing a mind-body intervention, researchers led 86 in mindfulness training and 73 in hypnotic suggestion. The control group of 85 received training regarding pain management strategies.

The mind-body interventions provided significantly more pain relief than the education session. Specifically, 15-minute sessions of the following techniques reduced pain immediately³⁵:

Mindfulness training (23% pain reduction): patients listened to a script guiding them to focus on sensations and breathing and to accept pain and negative thoughts
Hypnotic suggestion (29% pain reduction): patients listened to a script guiding them to visualize floating in a peaceful location and to manifest temperature or tingling in place of pain

The control group experienced a pain reduction of just 9%.

These methods do not require specially credentialed personnel—study interventionists received training from a professional certified in clinical hypnosis. Hence, the healthcare team does not need to consult a hypnotherapist to apply the hypnotic suggestion technique with each patient.³⁵

Mind-body exercise is on the table, too. Osteoarthritis Research Society International guidelines (OARSI) now name tai chi and yoga as Core Treatments for knee osteoarthritis.¹²

Distraction

Ever plop down in front of the TV to take your mind off a troubling issue? There’s science behind that! Multiple hypotheses attempt to pin down the psychology and physiology behind distraction and pain relief. Many postulate that the mind has the capacity to focus on or process only so much at a time. When people make their brains focus on something else, suddenly the pain can’t demand so much attention.^36,37,38

Unfortunately, many studies evaluating these hypotheses and methodologies are inconclusive or poorly designed. Nevertheless, one can accept several useful findings relatively confidently, summarized next.³⁶

Pain perception occurs differently in chronic pain than in acute pain. Research findings do not support distraction as an effective pain management strategy in chronic pain.³⁶

Conversely, distraction can mitigate acute pain. For instance, visual distraction—particularly if the medium is interactive—is effective in children and adults. Participants in various studies reported improved pain characteristics during activities such as playing simplistic computer games or using a virtual reality (VR) headset.^36,39,40

One study measured how long 79 children could keep a hand submerged in cold water (painful stimulus) while playing a VR video game. Each child underwent the test while watching a recording of that same game and, as a control, while simply wearing the headset. Urn randomization counterbalanced the order of the two distraction conditions. Passive visual distraction (watching the game) increased pain tolerance significantly, and active distraction (playing the game) increased it further.³⁹

In a similar study (N = 107), adults played a simple, slow computer game while a heating pad provided a painful stimulus. Participants’ pain perception variables improved during gameplay (higher pain threshold and tolerance, lower intensity).⁴⁰

Some research reveals no correlation between pain and auditory stimuli such as a recorded description of a scene or audible tones study participants were to react to.³⁶ But what happens with auditory input the listener actually enjoys? Investigating the relationship between music and pain in adults corroborates its analgesic effect, particularly when the patient chooses or approves the genre.^41,42 In fact, some investigations found pain relief to be so significant that patients required less opioids and other analgesics.^42,43,44

One such study evaluated the pain levels and morphine requirements of patients undergoing the same procedure by the same surgeon and analgesic protocol. The researchers randomized 75 patients into blocks of 25. All patients wore headphones connected to a CD player intraoperatively and postoperatively. One block’s headphones were connected to CD players playing soft music intraoperatively and sham CD players postoperatively. Sham CD players displayed track numbers on their indicators but played no audio. The second block received sham CD players intraoperatively and heard music postoperatively. The control group had sham CD players during both phases.⁴⁴

Both blocks receiving the intervention reported lower pain ratings in the post-anesthesia care unit (PACU) compared with the control group. Furthermore, total morphine required in the PACU was lower for the intervention blocks—1.2 mg for postoperative listeners, 2.3 mg for intraoperative listeners, 3.6 mg for the control group.⁴⁴

Research does not support sweeping generalizations regarding music for pain management in pediatrics. A substantial proportion of pertinent studies report inconclusive results or have insufficient sample sizes. However, two meta-analyses (429 and 5601 participants) found music therapy to reduce pain in pediatric cancer and in needlestick, procedural, and postoperative pain.^45,46

Additional methods

The nurse’s toolbelt contains an array of nonpharmacologic pain control tools, all appropriate in different contexts. A 9-year-old might enjoy a large-piece puzzle, which is unlikely to satisfy a teen. A patient with mild to moderate pain who has been resting in bed for several days might like to attempt guided imagery or meditation. That’s probably not the case for a patient wheeled into the ER following traumatic amputation of a limb.

Hot and cold therapy are yet another option, but they require training. Practitioners must know when heat versus ice is appropriate, how to apply different equipment and media, and how to assess for effectiveness and warning signs. As such, facility policy may stipulate provider prescription before applying heating pads, ice packs, and other such therapies.

THE ADPIE FRAMEWORK

Take a slow, deep breath. Smell that blueberry filling inside its flaky, buttery home? Or that warm layer of pecans awaiting a cool scoop of vanilla? It’s time for pie…

Overarching Concept

ADPIE is an acronym describing the five elements of the nursing process: assess, diagnose, plan, implement, evaluate. It’s the framework that shapes everything the RN does.^4,8

PAUSE AND PONDER: The Joint Commission once endorsed pain as the fifth vital sign. The organization rescinded the statement following substantial backlash.⁴⁷ Does pain’s inclusion as a fundamental component of assessment increase the likelihood of treatment or result in overzealous prescribing of analgesics?

ADPIE Letter by Letter

A: Assess

Assessment is the core of nursing and the foundation of the nursing process. It involves collecting objective and subjective data about a patient’s physical and non-physical status (emotional, spiritual, economic, etc.).^8,48,49Lab values, comorbidities, the patient’s and family’s statements, diagnostic imaging results, past medical history, physical assessment findings, and much more all coalesce into a comprehensive assessment.

Assessment sometimes lacks sharp boundaries. Take this example: A nurse passes an LPN pushing a newly admitted patient onto the unit in a wheelchair. The patient has a furrowed brow and is clutching her hip. The patient is not yet under the nurse’s care, nor did the nurse step in front of the wheelchair and proclaim, “I am now assessing you.” Yet the nurse has already assessed through passing observation that this patient might have pain in her hip, which requires further investigation.

Put simply, the adept nurse is constantly observing for key insights into the patient’s overall condition!

D: Diagnose

Recall that the nurse’s role is not to resolve an affliction, but rather to manage how it affects the patient. Just like the pharmacy team, nurses cannot diagnose medical conditions. ADPIE diagnoses are nursing diagnoses, not medical diagnoses. Entire books are dedicated to nursing diagnoses, and while in-depth coverage is outside the scope of this continuing education activity, the Nursing Diagnoses SIDEBAR contains more information.

NANDA International, Inc. is an industry-standard organization that defines nursing diagnoses.* Their taxonomy is called “NANDA-I”; however, this is not the only taxonomy, and many healthcare facilities develop their own. When it comes to pain as a nursing diagnosis, these taxonomies often list acute pain and chronic pain as the primary pain-related categories.^8,50,51

*Before 2002, “NANDA” stood for “North American Nursing Diagnosis Association.” It is no longer an acronym.⁵²

SIDEBAR

Nursing Diagnoses^4,8,48,53

Nursing diagnoses have multiple components, starting with the diagnosis itself. This can come from taxonomies such as NANDA International, Inc., the ICNP (International Classification for Nursing Practice), or the facility where the RN practices.

Take pneumonia as an example to illustrate nursing diagnoses and how they differ from medical diagnoses. The medical diagnosis is simply “pneumonia,” potentially with a qualifier such as “bacterial.” This is what the provider treats.

When selecting diagnoses, the RN considers how the illness affects the specific patient. Virtually all patients with pneumonia will have a nursing diagnosis of ineffective airway clearance.

This is a valid nursing diagnosis because the nurse can “do something for it” (and it’s in the NANDA-I taxonomy). The nurse can teach the patient turn, cough, and deep breath (TCDB) exercises to alleviate this. If the patient has impaired mobility (another nursing diagnosis), the RN can also turn the patient in bed periodically to help different areas of the lung inflate.

Say the patient is a star athlete and single father of three. The RN has additional diagnoses to consider now: anxiety, caregiver role strain, and insomnia. These issues reflect how pneumonia affects this patient, and the RN can take several steps to alleviate the problems. Potential steps include teaching anxiety management techniques, helping source childcare resources, and collaborating with the provider and pharmacist for pharmacologic sleep aids.

The other parts of a nursing diagnosis’ anatomy vary based on complex considerations, but they generally include

Related factors, or etiology—in the case of pneumonia, the offending species
Defining characteristics—objective and subjective data collected upon assessment that supports the nursing diagnosis

Having a strong handle on nursing diagnoses is a fundamental skill for an RN, as these short statements guide the outcomes and interventions.

Back to our new arrival on the unit, who the RN has learned is an 85-year-old woman named Sheila. Upon further assessment, Sheila shows signs of infection at the incision of her recent total hip replacement (THR). Sheila reports a pain level of 5 on a scale of 1 to 10 as part of the admission assessment. Multiple nursing diagnoses apply (to these and any number of other assessment findings), but the nurse notes acute pain in particular.

P: Plan

Now that the nurse has assessed the patient and made the relevant diagnoses, planning begins. Nurses plan outcomes, or goals, that are SMART: specific, measurable, achievable, realistic, and timed. They also plan interventions—ways to accomplish each outcome—that are evidence based wherever possible.^4,8,48

A simple way to look at these two components of the Plan stage is that the outcomes are what the patient will do, and the interventions are what the nurse will do.

Let’s zoom in on outcomes first. Every nursing diagnosis needs one outcome statement. Relevant data from the entire picture—Sheila’s comprehensive assessment findings—feeds into each goal.⁴⁸ We’ll define Sheila’s outcome statement for the diagnosis of acute pain as follows: Report pain of 0 to 3 on a 10-point scale by discharge. Where does the “realistic” criterion fit? Sheila’s condition is acute, and her reported pain level was 5. A rating of 0 to 3 is probably realistic for her, although it likely wouldn’t be for a patient with stage IV bone cancer.

Now for those interventions. What can or should the nurse do? Well, she must perform at least one action that supports meeting the outcome. And she’ll need to assess metrics relevant to the outcome (in this case, pain level).

All other interventions come from a complex web influenced by the nurse’s training and clinical experience. Patient teaching, collaborating, recommending and evaluating labs, and supporting nutrition and hydration are other facets of virtually all care plans. In any case, every intervention should support achievement of the respective outcome statement.

Here’s a small sample of what the RN might plan as the actions she will take (i.e., interventions) for Sheila:

Administer pain medication as prescribed; collaborate with provider and pharmacist to determine appropriate therapy.
Encourage distraction as nonpharmacologic pain management.
Perform wound care.
Teach hand and wound hygiene techniques.
Assess pain every four hours.

Science drives the nursing process. Each intervention supports achievement of the outcome. The outcome represents a resolution to the nursing diagnosis. The diagnosis comes from assessment data. Here’s how it all comes together: Every step of the nursing process flows into the next.⁸ The nurse’s actions are not haphazard.

I: Implement

The implementation stage involves conducting the plan: doing, delegating, and documenting.⁸ The RN acts independently for certain actions, such as performing wound care and administering medications.⁴⁸

However, no one in healthcare acts alone. The implementation stage is where collaboration happens!⁴ That’s right, this is when the RN is thinking about you, the pharmacy team. Does the RN need the pharmacist’s help teaching a patient about self-administration of a new prescription? Maybe she needs some help from the pharmacy technician for a patient who needs a special drawer in the drug dispensing cabinet. In Sheila’s case, the RN collaborates with the provider and pharmacist to discuss pharmacologic analgesia.

E: Evaluate

How do we know we’ve made a positive difference for the patient? We go back and evaluate. The RN reassesses Sheila to determine whether her situation improved. If Sheila rates her pain as 3 or lower, the goal was met, and the RN can focus on other diagnoses. If Sheila says her pain is 4 or higher, the goal is unmet, and the RN must modify the care plan.⁸ Maybe she could try another nonpharmacologic strategy. Perhaps the pharmacist and provider need to increase dosages, consider a drug with a different method of action, or change the route of administration.

NOTES ABOUT ADPIE

Like the Song that Doesn’t End

The nursing process is an endless loop. After classifying each goal as met or unmet, the RN may continue, modify, or discontinue that part of the care plan.^4,8

If a goal is unmet, the RN must revise something. Often, he must add or modify an intervention. Perhaps, though, the goal was unrealistic. Or could the assessment have been incorrect? If a patient was admitted while comatose, certain assessment data could be erroneous if his next of kin provided an inaccurate past medical history.

IE-PIE-PIE

You were promised PIE, yet collaboration with the pharmacy team wasn’t mentioned until implementation (I). What gives?

The RN is headed your way during the first round of implementation, but once you’re roped in, you can be involved in each iterative loop, particularly in the P-I-E.

Remember that assessment (A) is a key function of the nurse. Pharmacists should certainly feel free to assess patients, but for the purpose of effective collaboration, they need to recognize that a team member is performing continuous assessment. Diagnosis (D) is solely the responsibility of the nurse. Therefore, each round of PIE is when other members of the healthcare team should proactively check in. The nurse has to deal with the ads, and you just get the pie!

Too Cool for Nursing School

The acronym ADPIE is seldom mentioned outside the context of nursing school. If after this continuing education activity, you ask a nurse to collaborate on ADPIE, you might receive a less-than-friendly response. Nurses in the wild rarely plan care by literally defining each element of ADPIE. Rather, ADPIE is a cognitive process in the background of the nurse’s mind. As such, many nurses believe ADPIE to be the busy work of nursing school and inapplicable to nursing practice.

However, while some nurses assert that ADPIE is not used in the profession, it is. In fact, these elements are part of the American Nurses Association’s Scope of Nursing Practice. Even if a nurse doesn’t conscientiously analyze each letter of the formula when providing patient care, the principles remain the framework of nursing practice.^4,8

THE PHARMACY TEAM’S SLICE OF PIE: HOW TO COLLABORATE

RNs are trained to view patients holistically, connecting the dots between multiple aspects of a patient’s status and medical history.^4,8 Every dot is an input to the care plan and a piece of the puzzle the pharmacy team might need to know.

Furthermore, RNs work to establish an environment where patients feel open to sharing.⁴ Hence, the RN might have information that’s valuable to the rest of the team.

A patient who reveals he is unhoused might not have a safe place to store prescribed narcotics. If a patient shares that she suffers from bulimia nervosa, the provider and pharmacist will need to reconsider certain therapies. These include QT-prolonging tricyclic antidepressants, drugs that increase weight or appetite (some antidepressants), and bupropion, which lowers the seizure threshold.⁵⁴

What a nurse can learn from assessment that might be valuable to the pharmacy team is practically limitless. Following are some examples:

Comorbidities—gastroesophageal reflux disease is a contraindication for many drugs.
Dietary habits—if the patient practices fasting, this affects drugs he must take with food.
Acute changes—the sudden onset of severe nausea calls for a change in route of administration for oral prescriptions.
Sleep cycles—some therapies affect or are administered based on sleep/wake cycles, which the RN observes.
Adverse effects and side effects—the nurse can keep an eye open for signs and a listening ear open for symptoms.

This list paints the picture that the RN has loads of useful information. Consider this PRO TIP: Talk to the nurses! They are the constant set of eyes on the patient. They are the patient’s interviewer, day and night.

If you know of a common issue with a drug, such as its tendency to affect appetite, ask the RN if the patient’s eating habits have changed. Maybe you attended a seminar and learned about a potential drug-drug interaction recently uncovered. If this is relevant to your patient, share this information with the nurse, and ask him to observe for the interaction. Attend the nurse’s rounds if you can. ADPIE presents multiple ways to get involved!

If you’re not sure where to start or aren’t comfortable bringing up ADPIE as a springboard, there’s a simpler way in. Introduce yourself to the RN (in person if possible) and state your objective plainly: “I’d like to collaborate!” This fulfills multiple purposes:

The RN receives the clear message that you want to collaborate—she won’t need to infer your objective from your actions.
The RN understands your goal as intended. Otherwise, the RN might mistake your sudden interest for mistrust in his competence.
Owing to the previous point, an RN who understands your wish to collaborate will realize that you welcome her data and opinions.

If you’re stuck on starting this conversation, be even more direct: “I did a continuing education activity last week that was all about collaborating with RNs. I want to give it a try. Can we discuss what you and I can learn from each other about our patients and how to incorporate that in our day to day?”

Still looking for another nudge? Consider setting yourself a SMART goal! Example: Introduce myself to the day-shift RNs and explain my intention to collaborate by the end of next week.

By the way, if you work with facilities with multiple shifts, make sure to visit each shift if possible. Evening and night shift personnel frequently feel neglected and forgotten, so meeting them personally shows that you acknowledge and value their work. And if you really want to win the nurse team over, maybe even show up with pie!

Further Opportunities for Collaboration

The previous section focuses on partnering with the RN organically within ADPIE, but you’re not limited to this sphere. Keep your antenna up for situations pointing to more complex issues that warrant combining forces.

Community pharmacists can detect misuse by monitoring prescription activity. Teamwork is in order if the nature of the facility where a given patient receives care involves repeated or long-term visits. In other words, if the RN will see the patient again—such as at a family physician’s office—he will establish a database of assessment data over time on this patient.

Subsequent communication with the RN is a two-way street. The pharmacist can advise the RN to be cognizant of potential misuse, or she can ask the RN about assessment findings. For instance, the pharmacist could learn through the RN that a family member might be stealing the patient’s prescriptions.

Pharmacy technicians can capture medication history when patients transfer facilities. A geriatric patient transferring between long-term care and critical care, for example, is likely to have an abundant list of prescriptions at both facilities. This implicates a high likelihood of polypharmacy, interactions, and toxic levels of components such as aspirin and acetaminophen. Plus, polypharmacy is a nursing diagnosis, which means by definition that the nurse can intervene.⁵¹ It’s a multidisciplinary problem—time to collaborate!

Does your patient need assistance communicating due to factors such as age, sensory deficit, or cognitive impairment? Work with the nurse to ensure the right pain scale is being used and that the patient has a means of communicating adverse effects.

CONCLUSION

Every member of the healthcare team has a distinct role. Nurses are no exception—they continuously assess patients by physical and verbal means and establish and continually revise care plans accordingly. Knowing each team member’s function is crucial to maximally effective collaboration. In the face of the opioid crisis, healthcare providers should capture every opportunity for better patient care, particularly in pain management. This includes incorporating nonpharmacologic pain control strategies and intelligently selecting pharmacologic methods. Regardless of the modalities chosen, abundant opportunity for coordination between the nurse and pharmacy teams exists. This is especially true when the pharmacist and pharmacy technician understand the principles behind the nursing practice and care planning, summarized by the acronym ADPIE. Marrying the concepts of pharmacologic and nonpharmacologic pain control therapies with nursing care plans enables the pharmacy team to collaborate effectively for patients’ pain relief.

Pharmacist Post Test (for viewing only)

Getting a Slice of the (AD)PIE: The Pharmacy Team’s Guide to Collaborating with the RN for Pain Management

Pharmacist post-test

After completing this continuing education activity, pharmacists will be able to

1. Recognize how the registered nurse’s scope of practice supports the pharmacist
2. Identify appropriate nonpharmacologic and pharmacologic pain management practices
3. Describe how the registered nurse and pharmacist can collaborate to improve patient outcomes
4. Use the ADPIE framework to write a pain management care plan

1. Max is a 56-year-old being treated for cancer. His health care team has struggled to keep his pain controlled and recently increased his HYDROmorphone dosage. Which of the following reflects smart collaboration when the pharmacist wishes to evaluate effectiveness of the new prescription?

A. Meet with the LPN to discuss detailed assessment data and modify the care plan.
B. Ask the RN for Max’s phone number to interview him about his pain characteristics.
C. Ask the RN about Max’s recent assessment data and his pain-related interview data.

2. A patient says he will no longer be taking his fentaNYL because it causes constipation. Which of the following is an appropriate response?

A. This could cause you to go through withdrawal, which is dangerous. Do not discontinue the fentaNYL. Constipation is a side effect that you unfortunately cannot mitigate.
B. Constipation is a sign of impending gastrointestinal system shutdown. Discontinue the fentaNYL as planned and seek emergency care.
C. This could cause you to go through withdrawal, which is dangerous. Do not discontinue the fentaNYL. Exercise daily and increase your water and fiber intake.

3. Which list below contains effective nonpharmacologic pain methods virtually any health care team member can administer?

A. Pain journal, hypnotic suggestion, guided imagery
B. Cognitive behavioral therapy, computer games, cold packs
C. Puzzles, music, recordings of scenery descriptions

4. Which of the following is true regarding music for nonpharmacologic pain management?

A. Study findings are inconclusive regarding its effectiveness for adults.
B. Pain relief can be so effective that the patient requires less opioids.
C. The type of music is irrelevant – even simple tones provide pain relief.

5. Which statement below is true regarding pediatric pharmacologic pain management?

A. You must account for physiological differences even between subdivisions of the pediatric age range.
B. It should precede nonpharmacologic intervention to achieve immediate and effective pain relief.
C. The ratio of an adult dosage to average weight can be used to determine the pediatric weight-based dosage ratio.

6. What makes pain management unique for the geriatric population?

A. Older patients frequently exaggerate their pain, contributing to polypharmacy and toxicities.
B. Changes influencing pharmacokinetics occur in the digestive, hepatic, and renal systems.
C. Older patients are less likely to be opioid naïve, so they should be started on higher dosages.

7. Assuming all options below are indicated, which is the best initial therapy to attempt for a pediatric patient?

A. Inhaled ketamine
B. Intravenous acetaminophen
C. Topical lidocaine

8. The nurse evaluates a patient’s pain management goal as unmet. Which of the following could the pharmacist anticipate as an upcoming action the nurse will take?

A. They will evaluate the care plan as ineffective, discontinue it, and complete a Care Plan Discontinuation form.
B. They will notify the pharmacist and provider of the result and request to collaborate regarding the analgesic prescription.
C. They will initiate a new ADPIE cycle without collaborating with other health care team members so as not to skew data.

9. Which assessment finding by the nurse supports the pharmacist by serving as information that could improve the patient’s outcome?

A. A patient cannot effectively complete physical therapy because he is excessively tired and dizzy since starting morphine.
B. A patient recently started amitriptyline as an adjuvant pain therapy. Her daily weights are 181.6 kg, 180.0 kg, and 182.2 kg.
C. A patient prescribed HYDROcodone/ibuprofen status post femoral fracture reports discontinuing the over-the-counter ibuprofen they were taking.

10. Read the case study below and select the option that represents a valid care plan.

Case study:

Alex is a 36-year-old male who has reported to the walk-in clinic where Darius, the RN, works. Alex started working at a warehouse a year ago. He’s had low back pain for about eight months but hasn’t sought care for it because he doesn’t have insurance. He says the pain is sharp, occurs during work and upon waking in the morning, and radiates into both legs. He rates it a 7 out of 10. Between answering questions, Alex groans, massages his back with one hand, grips the treatment table with the other, and clenches his teeth. Alex says he takes “two big tablets” of acetaminophen every morning and night and uses an ice pack for four consecutive hours a night.

Darius discusses the relevant assessment data to the provider. The provider sees Alex and prescribes oxyCODONE/acetaminophen (Percocet). Darius calls Alex to follow up four days later. Alex says his pain is a bit better but is still a 4 out of 10.

A. ASSESS: The patient’s self-rated pain level is 7/10, duration eight months. Pain occurs while working and upon waking.
DIAGNOSE: Acute pain.
PLAN – OUTCOME: The patient will report a pain level of 3/10 or lower within four days.
PLAN – INTERVENTIONS: Reassess pain in four days, collaborate with the provider and pharmacist to ensure appropriate analgesic prescription, and teach how to complete a pain journal.
IMPLEMENT: All actions above were implemented.
EVALUATE: Based on the reassessment, the goal was met – discontinue the care plan.
B. ASSESS: The patient’s self-rated pain level is 7/10, duration eight months.
DIAGNOSE: Chronic pain.
PLAN – OUTCOME: The patient will report a pain level of 3/10 or lower within four days.
PLAN – INTERVENTIONS: Reassess pain in four days, collaborate with the provider and pharmacist to ensure appropriate analgesic prescription, and teach how to complete a pain journal.
IMPLEMENT: All actions above were implemented.
EVALUATE: Based on the reassessment, the goal is unmet – modify the care plan.
C. ASSESS: The patient’s self-rated pain level is 7/10, duration eight months.
DIAGNOSE: Chronic pain.
PLAN – OUTCOME: The patient will report a pain level of 3/10 or lower.
PLAN – INTERVENTIONS: Reassess pain via follow-up interview, teach lifting techniques, and teach how to complete a pain journal.
IMPLEMENT: All actions above were implemented.
EVALUATE: Based on the reassessment, the goal is unmet – modify the care plan.

Pharmacy Technician Post Test (for viewing only)

Getting a Slice of the (AD)PIE: The Pharmacy Team’s Guide to Collaborating with the RN for Pain Management

Pharmacy technician post-test

After completing this continuing education activity, pharmacy technicians will be able to

1. Recognize how the registered nurse’s scope of practice supports the pharmacy technician
2. Identify appropriate nonpharmacologic and pharmacologic pain management practices
3. Describe how the registered nurse and pharmacy technician can collaborate to improve patient outcomes
4. Use the ADPIE framework to review a pain management care plan

1. According to the Institute for Safe Medication Practices, when filling a prescription for buprenorphine, you should be especially sure you are not handling which drug?

A. Norepinephrine
B. HYDROmorphone
C. Morphine

2. Which of the following is an effective method to help ensure patients receive the correct drug?

A. State only the generic name for confirmation, as trade names can change.
B. Combine all strengths of a given agent in the same drawer.
C. Use tall man lettering to differentiate drugs from others with similar spellings.

3. While working at a long-term care facility, you notice a resident (a patient at the nursing home) getting settled back in her room after a hospital visit. This is a great opportunity to collaborate with the RN by taking which of the following actions?

A. Telling the resident she’s just missed med rounds but will receive her meds ASAP.
B. Checking for tall man lettering on each of the resident’s prescriptions.
C. Ensuring the medication history is conducted in a timely manner.

4. While stocking the medication room, you observe an RN retrieving an acetaminophen suppository for a patient. You pass that patient’s room on your way back to the pharmacy and overhear the patient talking to a friend. You must notify the pharmacist and nurse if you overhear which statement?

A. “I have got to get my Tylenol out of my purse. This headache is killing me!”
B. “That nurse needs to hurry back with the water I asked for. I am so dehydrated.”
C. “They’ve had to increase my insulin dose a lot since I was admitted.”

5. Which nonpharmacologic pain strategy below is effective for children and adults?

A. Topical lidocaine
B. Visual distraction
C. Audible tones

6. A patient picking up his prescriptions says he will no longer be taking his fentaNYL because it causes constipation. Which of the following is an appropriate response?

A. This could cause you to go through withdrawal, which is dangerous. Do not discontinue the fentaNYL. Constipation is a side effect that you unfortunately cannot mitigate.
B. Constipation is a sign of impending gastrointestinal system shutdown. Discontinue the fentaNYL as planned and seek emergency care.
C. This could cause you to go through withdrawal, which is dangerous. Let me have the pharmacist talk to you about some ways to limit constipation.

7. Which list below contains effective nonpharmacologic pain methods virtually any health care team member can administer?

A. Pain journal, hypnotic suggestion, guided imagery
B. Cognitive behavioral therapy, computer games, heat therapy
C. Puzzles, music, recordings of scenery descriptions

8. For collaboration to be effective, every health care team member must understand what their counterparts’ roles are. What is the nurse’s role in patient care?

A. They manage how an illness, injury, or condition affects a patient.
B. Their entire scope of practice comprises procedural, hands-on patient care.
C. They practice under a physician, executing his or her orders.

9. During which step of the nursing process might the nurse seek assistance from the pharmacy team?

A. Assessment
B. Diagnosis
C. Planning

10. Read the case study below and select the option that represents a valid care plan.

Case study:

Full List of References

References

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34. Charoenpol F, Tontisirin N, Leerapan B, Seangrung R, Finlayson RJ. Pain experiences and intrapersonal change among patients with chronic non-cancer pain after using a pain diary: a mixed-methods study. J Pain Res. 2019;12:477-487. https://doi.org/10.2147/JPR.S186105
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36. Bascour-Sandoval C, Salgado-Salgado S, Gómez-Milán E, Fernández-Gómez J, Michael GA, Gálvez-García G. Pain and distraction according to sensory modalities: current findings and future directions. Pain Pract. 2019;19(7):686-702. doi:10.1111/papr.12799
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Exploring Implicit Bias and Its Impact in Pharmacy

After completing this application-based continuing education activity, pharmacists will be able to

· DEFINE different types of bias and how they are formed

· RECOGNIZE what bias may look like in the pharmacy setting

· IDENTIFY how bias can impact patient care

· APPLY methods to address and mitigate bias in the workplace

After completing this application-based continuing education activity, pharmacy technicians will be able to:

· DEFINE different types of bias and how they are formed

· RECOGNIZE what bias may look like in the pharmacy setting

· IDENTIFY how bias can impact patient care

· ILLUSTRATE methods to address and mitigate bias in the workplace

Implicit bias is an important buzzword in healthcare. It has received much attention in the past few years because many researchers have documented its pervasive existence among healthcare providers. Implicit bias involves consciously or unconsciously thinking of some patient groups (or some coworkers) as less important than others, less deserving of care, or simply “less than.” Related concepts include second victim phenomena and imposter syndrome. Good research documents that many people from disenfranchised groups experience implicit or explicit bias when they visit pharmacies. Educational institutions have started to develop programs to educate pharmacists about potential implicit bias before they graduate. Yet most pharmacy personnel who work in clinical contexts have not had such education and need to understand the basic concepts of implicit bias. Pharmacy staff who take time to examine their own attitudes can improve care in influential ways and become significantly more enlightened. This continuing education activity provides basic education on implicit bias and refers readers to evaluation tools.

Content

INTRODUCTION

Can you solve this riddle?

A father and son are involved in a car crash. The son is rushed to the hospital. As the son is about to enter surgery the surgeon says, “I can’t operate—that boy is my son!”

People answer this question in a variety of ways, revealing different implicit biases. Some answers include 1) the boy has two fathers or 2) the father was actually a priest or 3) the whole thing was a dream. Researchers asked this question to two focus groups, one consisting of 197 college students from Boston University and the other, 103 children from Brookline Summer camps.¹ Only 14% of college students and 15% of children answered correctly with the “mom’s the surgeon."¹ A majority of people didn’t guess that the surgeon was the boy’s mother until a few tries, revealing the implicit bias that females are not meant to be doctors or surgeons.

TYPES OF BIAS

Implicit biases are unconscious mental processes that create unintentional automatic associations and reactions.²Implicit bias is more than a stereotype, which is a fixed set of characteristics associated with a particular social group. Implicit bias occurs when people harbor biases unconsciously. A person can develop negative feelings or attitudes towards another person by failing to connect to another person’s identities. The other person may then become part of an “out-group.”²This is not to say that those with shared identities hold no bias towards each other; some women think that women cannot be surgeons, for example. It’s important to look at other factors that cause implicit bias. Besides obvious differences in identities, social norms can influence biases and media outlets, public policy, and even education may magnify bias.² People may not often express implicit biases out loud because of their hidden, unconscious nature. Implicit biases contribute to a person’s explicit biases.

Explicit biases include peoples’ conscious preferences, beliefs, and attitudes, and people may communicate them outright.²For example, people may express explicit biases verbally and expose their prejudicial opinions. Prejudice—a biased response towards a social group and its members based on preconceptions³—may lead to irrational hostility directed towards an individual or group.

In-Group vs Out-Group

Social psychologists have long known that people define themselves in terms of social groups and often malign or disparage others who don't fit into their social groups. People who are part of the “in-group” feel they belong to that group because of social perceptions. People part of the in-group generally have positive views of each other and perceive that the group is composed of individual people.⁴In direct comparison, in-group members view people in the “out-group” negatively because they do not belong to the in-group. People in the in-group characterize the out-group as a homogeneous collective rather than individuals. Thus, it becomes easy for members of the in-group to label the out-group as “all the same” rather than treat them like individuals.⁴

Simply put, in-vs-out group labeling becomes a case of “us-vs-them" with those in the in-group being “us” and those in the out-group being “them.”⁴This tendency explains why hostility can exist between certain groups based on factors like political parties, race, or sexual orientation. This concept of “othering” people is fundamental to understanding how bias can influence personal opinions. Healthcare workers must be mindful of their opinions to ensure biases do not interfere with patient care.

Differentiating Stereotypes, Microaggressions, and Discrimination

Stereotypes are a fixed set of attributes associated with a particular group.²Stereotypes are often untrue or unfair generalizations about people who may appear or identify a certain way. Stereotypical beliefs can lead to displays of microaggression, discrimination, and harmful judgment. Some common examples of stereotypes include

People who wear glasses are smart
Boys are stronger than girls
People with tattoos are dangerous
Men are better drivers than women

Microaggressions are physical or verbal acts that subtly express stereotypical thoughts. A 2010 study tracked high school students (N = 342) over their four-year progression and found that students had experienced 21 different types of microaggressions at least once.⁵ Some examples of reported microaggressions included⁵

Teachers assuming a Black student was poor or illiterate
Hispanic and Asian students were asked to teach “native words” even if they only spoke English
Students of color being called on to speak on behalf of their race

Discrimination is the result of implicit or explicit biases. It causes unfair treatment of individuals and communities based on general policies, practices, or norms.²

PAUSE AND PONDER: What kinds of implicit bias have you observed in your workplace?

Consider this example: Kate was shopping at the rear of a beauty store when suddenly, someone robbed the cashier located at the front of the store. She rushed home and immediately called her friends Mark and Sylvia to share what she had experienced. Mark asked what the robber looked like. Sylvia says, “I didn’t see him. He was probably Black. They usually are.” This demonstrates a stereotype about Black people. Her comments are the microaggressions in this case. Sylvia’s racial bias is what contributed to this reaction.

BIAS SUBGROUPS

Bias comes in many forms and is not limited to particular set of individuals. It can affect any group. Common biases are based on⁶

Beauty
Educational background
Gender
Race/Ethnicity
Religion
Sexual orientation
Socioeconomic background

Unconscious biases are more difficult to identify given that people rarely verbalize them, but they still play crucial roles in affecting behavior and judgment. Bias is a large umbrella term that can further be broken down into subgroups and sub-definitions. Table 1 lists some common categories of unconscious or implicit bias. The SIDEBAR discusses recency bias, a type of bias that can have significant influence on providers’ and patients’ healthcare decisions.

Table 1. Major Biases Present in Everyday Life⁶

Affinity bias	Unconscious preference for people with whom you share qualities or interests
Ageism	Negative feelings towards others based on their age
Attribution bias	Related to how you infer the reasons that others act as they do and misunderstand motivations; individuals may attribute their own accomplishments to skill, but assign no fault to their failures; they may be less generous in their thinking when examining others’ behaviors
Beauty bias	Belief that attractive people are more successful, competent, and qualified than unattractive people; physical appearance is used to judge competency
Confirmation bias	Searching for information that backs the opinion an individual holds and rejecting information that contradicts that opinion
Conformity bias	Others’ views influence an individual’s views; this concept is related to peer pressure and acceptance seeking

SIDEBAR: RECENCY BIAS^7,8

Recency bias affects cognitive decision-making by favoring recent events over historic events to estimate future events. Recency bias is also defined as the tendency to base thinking on what comes easily to mind based on recent events.

For example, an employer is conducting employee evaluations and greets an employee who consistently meets performance goals and expectations. However, the employer chooses to deny the employee a promotion based on a recent mistake. Despite consistent success, a recent error influenced the employer’s decision.

In healthcare settings, some examples of recency bias include

Rejecting older evidence that disproves new (mis)information
Emphasizing recent information and failing to consider the entire evidence set
Seeking new information rather than older, more voluminous, and more consistent facts

ETIOLOGY OF BIAS

Science offers some explanation as to how and why biases form in the human mind. The amygdala and the prefrontal cortex (PFC) are most involved in forming bias.⁹The amygdala, a small structure located in the temporal lobe of the brain, is responsible for receiving direct information from all the body’s sensory organs.³It is the part of the brain that generates responses to stimuli, whether that be arousal, attention, or fear.³The amygdala controls the body’s fight-or-flight response, which is activated in situations that are frightening like walking down a dark alleyway, hearing unfamiliar sounds, or seeing unfamiliar people.^3,10

Several neuroimaging studies have shown that activity in the amygdala heightens when people view pictures that trigger biases. For instance, when people see facial images of those from a different ethnic background than that of their own, the amygdala is activated more so than seeing people who look similar to them.^3,10

The PFC processes cues and is involved with contingency-based learning, decision-making, and evaluation.³Essentially, the PFC communicates with the amygdala to signal that visual or auditory cues may not be a danger at all; it effectively regulates or “calms” immediate amygdala activation based on situational surroundings.^9,10The PFC functions to help the brain adjust to fit the environment’s social norms.

Influences of Bias

Social attitudes and expectations that reinforce stereotypes and microaggressions change the way the brain processes behavior. That said, implicit bias is not intrinsic (or hard-wired), meaning although it may exist in the unconscious parts of the brain, it can be “un-wired.”¹⁰Experiments involving children who had diverse friend groups show less reactive amygdala activation, meaning their brains did not automatically associate negative reactions based on skin color.⁹

What does this have to do with bias? It suggests that bias is not inherently present in children from birth and develops in adolescence.⁹ The social, physical, and economic environment in which people are raised affects brain development and ultimately alters individual implicit biases.

Identity, Individuality, and Intersectionality

People use their social identity to compartmentalize themselves into specific groups or categories. In 1974, sociologist Henri Tajfel first proposed the social identity theory that suggested social identity derives from the “knowledge of membership” in a group (or groups), and that membership in those groups creates individual significance and value.¹¹Social identity defines how individuals characterize their own traits. Common identities include things like¹²

Disability
Ethnicity
Gender or sex
Nationality
Political party
Race
Religion
Economic status

Personal identities are adjectives used to describe oneself, like smart, tall, or funny.¹²

Social identity is dynamic in that it can develop in various ways.¹⁰ For example, society classifies people born in the early 1980s to mid-1990s as being part of the millennial generation. Although membership requires nothing other than birth at a specific time, others group millennials into a category (their generation) that has over time acquired certain characteristics typical of group members. Individuals can also develop identity through conscious choices, like choosing to go into a healthcare profession or going to school to be a writer.¹⁰People are not usually limited to one identity, but rather possess multiple social identities that work to influence a person’s experiences in life.¹² For example, a White man fits into categorical groups of (1) White person and (2) male sex, yet his life experience may differ depending on if he is born into higher socioeconomic class, identifies as heterosexual, or has a disability.

Society’s cultural norms shape identities.¹³ As attitudes towards cultures (or groups) change over time, societal standards change as well. Certain identities may have more value and importance than others because society emphasizes those differences. Identities may also shift importance based on the context in which a person lives. A White American living in North America might think about national identity only infrequently. However, if that person takes a job in China, national identity might suddenly feel like a significant part of individual identity, because it will likely impact how others see the person and how the person interprets experiences.¹²

Social identity overlaps strongly with intersectionality, or the multifaceted interplay of social identities, systems of power, and oppression of certain groups.¹³As mentioned above, social identities exist in various combinations that make individuals unique. Intersectionality allows us to see how different identities may affect one another, and how that in turn relates back to concepts of bias, discrimination, and stereotypes.¹³

Bias within groups can affect intersectionality. For example, studies show that people of color who also identify as part of a sexuality minority experience internalized stigma related to gender and/or sexual orientation within their racial groups; these people experience what is called intersectional minority stress.¹⁴Individuals experiencing discrimination in both racial and gender or sexuality identities are more vulnerable to poor health outcomes given the increased bias and discrimination they face.¹⁴

A public health researcher from the University of Michigan introduced the “weathering” hypothesis, which suggests that Blacks experience health deterioration as a result of chronic social and economic stressors or political marginalization.¹⁵ Some studies have explored and validated this hypothesis. A recent study found that the COVID-19 mortality rate was 2.1 times higher for Black Americans than that of White Americans.¹⁶ The researchers indicate that weathering from chronic and toxic stress magnified COVID-19’s effects in people of color.People of color are more likely to suffer job loss as a result of the COVID-19 outbreak, which in turn affects health insurance coverage and thus contributes to poorer health outcomes. Regardless, even those who possess employment and health insurance are more likely to receive inferior care due to the implicit biases present in healthcare. This study emphasizes the concept of “weathering” in a way that is relevant in our world today.¹⁶

PAUSE AND PONDER: How might implicit biases in your workplace affect patient care and outcomes?

Bias and social identity are entwined. Social identities stem from a person belonging to a group, whether that be an “in-group” or “out-group.” Figure 1 provides examples of the groups, such as middle class or documented citizens. A person can belong to more than one group. Society tends to label certain groups as more valuable than others, which leads to re-enforcement of certain biases. People tend to conform to societal standards, and placing oneself into these groups creates the foundation for bias, stereotypes, and prejudice to occur. It is still important to recognize that while our personal and social identities place us into groups with shared attributes, we are still unique individuals.

SOURCE: Adapted from James R Vanderwoerd ("Web of Oppression"), and Sylvia Duckworth ("Wheel of Power/Privilege")

Institutional Bias

“Power tends to corrupt, and absolute power corrupts absolutely.”

– Lord Acton, British Historian

All people have unconscious or conscious biases. Ultimately, biases result from social identities’ influence on the brain and our environment. But what happens when a collection of individuals with a shared bias comes together? Biases can become discrimination. While prejudice is the pre-conceived notion about someone based on bias, discrimination is conscious, intentionally disparate treatment.¹⁷

Institutional bias, known also as structural bias, ties many issues that arise from discrimination together. Institutional bias—the established laws, customs and practices that methodically reflect and produce group-based inequities in any society—involves policies and practices that are discriminatory beyond that of the individual level.¹⁸ Even in an ideal situation wherein individuals do not possess a certain bias or prejudice towards a group of people, discrimination may still occur because the institutions in which they are involved may have biased practices in place.¹⁸

Nearly every type of social institution exhibits some form of bias against groups of people. Examples of institutions include¹⁸

Education
Environmental management
Healthcare
Law/Criminal justice
Military
Politics
Politics
Retail and housing market
Workforce

Some people allege that individual and institutional bias may not co-exist, but that belief is a bit contradictory. Since the civil rights movement, individual expression of stereotypes and prejudice against Black people in the United States has declined. However, racial discrimination is still widespread and may be as prevalent as it was before the civil right movement in some areas. In 2007, the legal system incarcerated Black people at a rate four times higher than White people in the U.S.¹⁸ Although other factors may contribute to this disparity, institutional racism is still prevalent regardless of individuals’ attitudes or bias towards Black people.¹⁸

Power and legitimacy also influence institutional biases.¹⁸Groups in power are more likely to control institutional bias since they are most likely to control the institutions and create policy.¹⁸Legitimacy is a word used to describe the perception that a policy that is detrimental to the oppressed group is fair or somehow justified.¹⁸

For example, the housing market enables implicit associations between minorities and the risk they present to the value of the neighborhood in which they live or seek to live. As a result, the perception influences certain housing and lending practices for minority applicants.¹⁹Another example is more nuanced. Adults younger than 21 cannot purchase or drink alcohol in the United States; one may argue that this is a form of bias against this age group. However, given the shared societal attitude that teens and young adults should not drink alcohol due to its potential to cause impairment, few people fight against this bias.¹⁸

While some biases are widely accepted, others are clearly not. For example, some immigrants don’t qualify for high level positions within companies. Members of immigrant groups are more likely to take low-level, undesirable positions. As a result, they tend not to stay at that company for long, increasing turnover and decreasing ambition within their fields.¹⁸A similar predicament is the standardized college admission tests; depending on their exam score, students may not qualify for admission to certain schools, perpetuating the idea that they are not smart enough to be admitted.¹⁸Standardized tests fail to take into account students’ different backgrounds; some students benefit from simply being in a higher socioeconomic status with resources available to ensure success.

IMPLICATIONS OF BIAS

Negative attitudes have the potential to affect decision making and health outcomes across various healthcare settings. In 2021, the three largest motivations for hate crimes in the U.S. were race, sexual orientation, and religion.²⁰Maternal mortality rates in the U.S. by race are disproportionate. Black women die during childbirth nearly three times more often than White or Hispanic women.²¹These discrepancies are due to institutional biases and existing racism toward Black women in healthcare. The Centers for Disease Prevention and Control adds that implicit bias prevents people of color from having fair opportunities for economic, physical, and emotional health.²²As part of the healthcare workforce, pharmacists and pharmacy technicians should be able to identify how implicit biases can adversely impact relationships with patients and customers.

PAUSE AND PONDER: Which interventions described in this CE might help you and your coworkers
have frank discussion about bias and discrimination?

Recent research shows people have self-reported experiences of discrimination in healthcare. These instances frequently occur in the following groups of people²³:

LGBTQ (lesbian, gay, bisexual, transgender, queer)
Low socioeconomic status
Older adults

Overweight or obese
Poor health
Racial/ethnic minorities
Uninsured
Women

Patterns of bias and discrimination towards marginalized groups becomes evident. As a result, these individuals can feel perceived discrimination, which is anticipation of unfair treatment they may receive due to their characteristics.²³These groups are more likely to have high stress and mental health disorders such as anxiety, depression, and substance abuse.²³Table 2 lists examples of studies that highlight implicit biases related to healthcare.

Table 2. Studies that Highlight Implicit Biases Related to Healthcare^24-28

A study (N = 142) of emergency response situations showed that White bystanders were slower to provide help to Black victims than the speed at which White bystanders helped White victims. White participants helped 88% of White victims compared to 58% of Black victims. “Help Time” was ~120 sec for Black victims compared to ~40 sec for White victims.

A review (N = 7070) found Black and Latino patients are less likely to receive medication, especially opioids, to alleviate acute pain in the emergency department than White patients (OR 0.60 [95%-CI], 0.43-0.83).

Asian Americans (N = 521) reported feeling like their doctors do not involve them in shared decision making, do not listen to their concerns, and spend less time with them. They were also less likely to receive counseling on mental health or lifestyle issues compared to White patients (N = 3205) in the survey.

An analysis found doctors perceived Black patients (N = 618) to be less educated, less likable, less intelligent, and nonadherent to medical advice and medication therapy. Physicians were less likely to agree that Black patients vs. White patients are `the kind of person they could be friends with’ (34% of White vs. 27% of Black patients).

A survey (N = 316) showed transgender or gender nonconforming people worry about discrimination when they use pharmacy services; 41.6% reported discrimination associated with such services, and 52.5% reported pharmacists as having very little or no competency in providing gender-affirming care.

Gender-Diverse Care and Ageism

An emerging topic is gender-diverse care. The Human Rights Campaign Foundation and the American Pharmacist Association (APhA) released a joint pharmacy resource guide for gender diverse care. The guide includes key terms, inclusive communication, staff training and other essential points of patient centered care for gender diverse patients.²⁹It is accessible for free at https://www.thehrcfoundation.org/professional-resources/transgender-pharmacy-guide

Nicole Avant, PharmD, BCACP, founder, owner, and consultant at Avant Consulting Group, presented key studies on implicit bias during a session at the 2022 National Community Pharmacy Association Annual Convention. They include³⁰

Black women are more likely to die after being diagnosed with breast cancer.
Patients of color (POC) receive fewer cardiovascular interventions and fewer renal transplants than White patients.
POC who have diabetes are more likely to undergo leg amputation.

Poor provider-based interactions negatively impact the quality of care and the desire to seek medical help. This fosters mistrust of healthcare and healthcare workers, like pharmacists and pharmacy technicians. Poor interactions can significantly delay treatment-seeking, which worsens health complications by creating avoidable increases in emergency healthcare use and increasing health disparities. The SIDEBAR provides an example of poor care.

SIDEBAR: A Health Professional’s Observation³¹

Joanne Whitney is a retired pharmacy professor who has shared her experiences when interacting with healthcare providers.

She went to the emergency room for a urinary tract infection (UTI) and severe pain. She asked for hydromorphone (Dilaudid) since it had helped her before, but a young physician told her that they don’t prescribe opioids to “those who seek them.”
Her pain continued for eight hours. She states, “When older people come in like that, they don’t get the same level of commitment to do something to rectify the situation. It’s like ‘Oh, here’s an old person with pain. Well, that happens a lot to older people.’”
She also told the physician the prescribed antibiotic was incorrect for her UTI, but the provider disregarded her concern despite her pharmacy background.

The prejudice in this case is the notion that older people are unpleasant and difficult to treat. Discrimination occurs when healthcare providers do not manage older adults’ needs appropriately or treat them less favorably than younger patients.

Her experience emphasizes ageism in healthcare settings. More than half a million Americans aged 65 and up encountered ageism during the COVID-19 pandemic.

Ageism can be explicit in some healthcare settings. In 2021, an advocacy group for older adults filed a lawsuit in Idaho over the state’s crisis guidelines for hospitals that were overwhelmed with COVID-19 patients. The protocol stated staff should triage and treat younger patients before older adults because “they have more years left” to live.³²

Other examples of ageism prevalent in healthcare today include

Assuming older patients who talk slowly are cognitively compromised
Rushing patients, not listening to their concerns
Only speaking to the patient’s family member
Ignoring or minimizing pain complaints

Racism in Pharmacies

A 2021 U.S. Qualtrics Survey found that nearly 20% of people perceived racial discrimination in community pharmacy settings.²³Of those people, one-third of them felt they had to be particularly careful about their appearance to receive “good service” and avoid harassment.²³On average, people visit doctors and specialists a handful of times but can visit their community pharmacies up to 35 times a year.The study showed that perceived discrimination significantly affects healthcare. One third of respondents stated they tried to avoid certain pharmacies, and 17% reported switching pharmacies.Switching pharmacies may seem like an adequate temporary solution, but in actuality fragments medical records, increases the likelihood that pharmacists will miss potential drug interactions, and compounds adherence issues.²³

Thus, healthcare providers must be cognizant of their biases and avoid acting on them when interacting with patients in pharmacy settings. Pharmacy workers should strive to be fair and aware of their personal implicit biases. They should also be conscientious and deliberate when interacting with patients. Management must ensure adequate training is in place for pharmacists and technicians to create a welcoming, inclusive atmosphere. If it is not, pharmacy employees should suggest it is needed.

Becoming conscious about implicit biases should begin during the education of future pharmacists. Six PharmD programs surveyed students (N = 357) using the Harvard Race Implication Test.³³The test determines implicit associations by measuring the time it takes a person to connect two concepts, i.e. (Black/White to good/bad). The survey found that pharmacy students exhibited preference for White patients and moderately negative implicit and explicit bias towards Black patients.³³Although many pharmacy schools have already incorporated the concepts of cultural competence, increasing awareness of how implicit biases negatively affect patient interactions should be a focus area.

Bias Affecting Decision-Making Processes 

Implicit bias has been associated with several downstream effects. Consider “second victim” effect. The term “second victim” describes healthcare professionals and the unanticipated emotional impact they feel after making a medical or clinical error.³⁴Medical errors are one of the top leading causes of death in the U.S.³⁵The first victim is the patient who experiences the medical error. The second victim—the person who made the errors—feels distress and personal responsibility after an unexpected adverse patient outcome or error. This directly impacts the healthcare professional’s career and life.³⁴ In many cases, implicit bias is not a factor in second victim effect, but sometimes it is. For example, consider a provider who has an implicit bias towards Black women. The provider fails to intervene aggressively when a patient, a Black woman, is experiencing pain and hemorrhaging due to complications during childbirth. The patient soon becomes unconscious from blood loss. The patient unfortunately dies. The patient’s family files a complaint with the hospital regarding the provider’s lack of standard care during her birthing process. The provider is then afflicted by second-victim effect.

Many second victims suffer from job-related emotional and physical stress, and their additional feelings of powerlessness and insecurity can prompt them to leave the profession.³⁴Lack of support for coworkers and management contributes to the second victim phenomenon, and coworkers and managers may be less likely to support the second victim if they have biases against that person for some reason.³⁴The second victim’s self-blaming negative feelings could influence future decision making.

Nearly half of healthcare professionals experience second victim effect at least once in their careers.³⁴This effect may lead to changes in clinical judgment and inadvertently affect patient care. It is important to recognize when it occurs. To combat second victim phenomenon’s negative effects, mindfulness-based interventions have shown efficacy in reducing stress and burnout.³⁴Also, psychological first aid fosters resilience in healthcare professionals by establishing formal support teams within health institutions.³⁶This includes education about normal responses to traumatic events, active listening skills, understanding the importance of nutrition and rest, and clarifying when to seek help.³⁶

Interprofessional Bias

Interprofessional collaboration is an important part of managing and delivering quality patient care. Biases about other professions can create conflict within the team, which has negative consequences for communication, decision-making, and trust.³⁷Implicit biases influence a person’s actions unconsciously and can intrude in various cultural and structural settings. For example, individuals may have preferences for certain specialties or simply certain people over others. Their implicit biases can influence decisions, like who rounds on an inpatient hospital team.The traditional hierarchy of physicians as team “leaders” can create tension within a group that must work with (as equals), but not for (as subordinates), that physician.³⁷

Research shows that biases adversely affect the quality of healthcare delivered to patients. A systematic review on implicit biases in interprofessional collaboration found that biases between professions were predominately negative.³⁷The review mentioned the concept of internalization, which describes how people internalize biases towards their profession towards their own self and behaviors.³⁷For example, physicians mostly saw themselves as leaders while nurses consistently perceived themselves as powerless and lacking authority. As such, physicians exhibit behaviors such as authoritatively shutting down communication in case conferences, whereas non-physician professionals tended to be silent, less engaged, or chose to skip team meetings. Bias internalization influenced which professions voiced their opinions and inhibited the team’s overall growth.³⁷Consequently, these healthcare teams developed feelings of disrespect and mistrust, which impedes patient care. Another study found that when team members perceived they were not consulted about a decision, they exhibited defensive posturing and frustration in meetings.³⁸

Imposter Syndrome

Imposter syndrome is defined as self-doubt about intellect, skills or accomplishments among high achieving individuals.³⁹Imposter syndrome and disorders such as depression and anxiety are often comorbid.³⁹Many healthcare professionals strive for perfection, but those with imposter syndrome tend to associate their success with random chance as opposed to their own intelligence.³⁹Imposter syndrome tends to be more common in marginalized groups (e.g., minority races) in high pressure settings due to underrepresentation in the field; poor representation and pressure exacerbate imposter syndrome.³⁹ It may also be a result of lifelong bias and discrimination, which can affect professionals in their clinical roles as well.

Interestingly, a study of pharmacy residents (N = 720) found higher Clance Imposter Scale scores correlated with the number of hours worked per week and prior mental health treatment, factors associated with high stakes learning environments.⁴⁰This study validates other studies done with various medical professionals and demonstrates the connection between highly focused academic and healthcare areas and the increased likelihood of imposter syndrome.⁴⁰

Imposter syndrome, like the second victim effect, can affect clinical judgement in healthcare professions. It may promote certain biases when they normally would not be due to those feelings of inadequacy, and thus mistakes occur.

Bias in the Pharmacy

Pharmacists hold crucial positions in healthcare, especially since they engage with diverse groups of patients regardless of the setting in which they work. Pharmacists can stimulate broader efforts to address health disparities, especially as their scope of practice widens.⁴¹Social determinants of health (SDOH) are the social and structural conditions in which people are born, live, and work.⁴²Figure 2 shows the key SDOH.

Source: Healthy People 2030, U.S. Department of Health and Human Services, Office of Disease Prevention and Health Promotion. Retrieved July 28, 2023, from https://health.gov/healthypeople/objectives-and-data/social-determinants-health

A 2016 review of pharmacy literature highlighted issues stemming from SDOH affecting pharmacies. These factors are known to influence health outcomes, and pharmacy workers need to be aware when SDH may affect the population they serve. The study showed the following knowledge gaps among pharmacists⁴¹:

Mental illness
Substance/drug abuse with prescription and illicit drugs
Those at risk for HIV/AIDS or hepatitis C infection

Although pharmacists provide care to groups that suffer from effects of SDH, they may not understand entirely or have access to information that could expose SDH. More education on cultural competency is needed within pharmacy.⁴¹

Bias can influence the pharmacy workforce. Perhaps one of the most relevant examples of bias in pharmacy workers concerns opioid use disorder (OUD). The U.S. has battled the opioid crisis for more than two decades.⁴³Those who suffer with OUD are often stigmatized. Pharmacists and pharmacy technicians frequently interact with patients who are diagnosed with such disorders. The lack of knowledge and understanding surrounding OUD underscores biases that exist towards people with OUD.

A small study that examined pharmacy technicians’ attitudes (N = 46) using focus groups found that participants had negative perceptions of patients using opioids. Pharmacy technicians reported “ever-present” negative feelings (meaning they persisted over time) toward patients with OUD, even if they did not know opioid’s indication for a particular person.⁴³The researchers asked pharmacy technicians to recount their experiences with patients who recieved opioids. Figure 3 highlights their perceptions.⁴³

Figure 3. Comments from Pharmacy Staff about Patients with OUD⁴³

A multitude of reasons may explain why participants felt this way. Their experiences may be tied to aggressive encounters between healthcare professionals and patients who use opioids and negative media portrayals of opioid use.⁴³The study went into further detail on early refills, a situation where patients want to fill a prescription when their fill histories indicate it’s too early. Most technicians stated they tried to be compassionate and non-judgmental in these situations to overcome the stigmas associated with opioid prescriptions.⁴³

The discussion further explained that the negative perception of patients who take opioids compromises quality of care because it is difficult to reverse formed opinions. The National Institute on Drug Abuse stresses the importance of accurate, complete medication histories and reporting to prescription drug monitoring programs to create healthier patient-provider relationships in the pharmacy.⁴³

Another study focused on pharmacy personnel responses to expedited partner therapy (EPT) in the management of sexually transmitted infections. EPT effectively prevents chlamydia and gonorrhea infections for partners of patients already infected.⁴⁴Providers can give patients diagnosed with chlamydia or gonorrhea prescriptions for the partner without having to name the partner. EPT is protected by law in 41 states and supported by numerous organizations including⁴⁴

American Academy of Pediatrics

American Academy of Family Physicians
American Congress of Obstetricians and Gynecologists
Society of Adolescent Health and Medicine

The study (N = 50) found pharmacists refused to fill 58% of EPT prescriptions, and suburban pharmacists were more likely to refuse than city pharmacists.⁴⁴Refusal was more likely if the pharmacists were older than the patient and if patients were White.Pharmacists most commonly cited lack of name on the prescription as the reason for refusal, even if the law does not require a partner name. This indicates a general lack of knowledge about EPT among study participants, which may have contributed to their decisions.⁴⁴

A literature review on weight management programs found implicit and explicit weight bias exists within the pharmacy profession. Weight management programs can vary, and pharmacies offer some in conjunction with prescription medications and nonpharmacologic lifestyle interventions.⁴⁵The review found stigmatizing language in the screening processes for weight management programs. It is unclear to what extent weight biased communication exists between pharmacists to patients.⁴⁵ The stigma that surrounds obesity affects other related health problems, like diabetes or cardiovascular concerns, and can weaken the pharmacist-patient relationship.⁴⁵

ADDRESSING BIAS

Implicit biases are present in all people, but the importance lies not in the existence of bias, but how to overcome it. Several strategies address biases, the most important being education in pharmacy school curriculums. Many studies use the IAT to measure implicit bias. The test is free to the public and can be found here: https://implicit.harvard.edu/implicit/

Learners should note that this is not just one test, but a series of different tests.

The IAT measures the time it takes for the individual to match concepts in categories to descriptive words, like race, skin tone, and weight to good, bad, or other stereotypical language.^46,47An individual’s underlying beliefs drive responses time, thus measuring the strength of the association between concepts (a person, image, etc.) and evaluations (good, bad). Researchers recommend incorporating the IAT in curriculums prior to before direct patient exposure.⁴⁶

Other interventions that may be helpful in pharmacy education and other pharmacy settings include⁴⁴

Practicing mindfulness (directing active, open attention to the present to examine one’s thoughts and feelings without judging them). Mindfulness reduces the likelihood of activating implicit biases and enhances the ability to control biases in patient care situations.
Self-awareness/self-reflection training: After completing the IAT, individuals can reflect on identified biases.

Activating goals: Healthcare workers can identify goals that promote fairness and equality for patients and coworkers.
Stereotype replacement: Individuals who collect information that is opposite of cultural stereotypes can replace stereotypical thoughts with non-biased thoughts.
Case studies observing implicit bias: Analyzing case studies where implicit bias was involved helps people recognize how to approach situations differently.
Individuating: This action challenges people to see others for their individual traits as opposing to grouping them by their stereotypical components.
Perspective-taking: This “walk a mile in their shoes” activity asks individuals to assume the perspective of a stigmatized or marginalized member to build empathy.

The University of Utah Pharmacy Residency program implemented an implicit bias awareness and action seminar with four training modules and a pre- and post-test survey. After training, pharmacy residents indicated higher comfort and confidence addressing personal biases and were better able to identify biases of others.⁴⁷While not accessible to the public, this shows that implementing training programs makes a difference in future of pharmacy delivered care.

Conclusion

Implicit biases have overall negative effects on patient care, which is detrimental to patients and those that harbor the implicit biases. Pharmacists and pharmacy technicians who are aware of and take steps to address their implicit biases will improve the way they treat patients and each other as colleagues.

Pharmacist Post Test (for viewing only)

Exploring Implicit Bias and Its Impact in Pharmacy
POST-TEST Pharmacists
Learning Objectives
After completing the continuing education activity, pharmacists will be able to
• DEFINE different types of bias and how they are formed
• RECOGNIZE what bias may look like in the pharmacy setting
• IDENTIFY how bias can impact patient care
• APPLY methods to address and mitigate bias in the workplace

1. You are a 52-year-old clinical pharmacist who works with an interprofessional team. The doctor is a 33-year-old resident who has just started working at the hospital. He does not ask for your input, yet you have caught several prescribing errors he made. He also ignores your questions. He has openly stated that he thinks pharmacists “don’t know what they are talking about.” What potential bias may be occurring?
a. Age bias
b. Interprofessional bias
c. Confirmation bias

2. Which strategy could potentially help mitigate implicit biases in pharmacy education or clinical settings?
a. Behavioral therapy
b. Anonymous reporting
c. Self-awareness training

3. Which of the following statements best describes an explicit bias?
a. “Women who have children are not serious about professional careers.”
b. “Pharmacists and doctors have more clinical education than nurses do.”
c. “Patients of color receive fewer primary care interventions than White patients.”

4. Which of the following statements is CORRECT regarding the etiology of bias?
a. The amygdala processes cues and “calms” the PFC to adjust to social norms.
b. Neuroimaging studies do not associate amygdala activity and bias.
c. Bias triggers amygdala activity and affects decision-making processes.

5. How does bias negatively impact marginalized pharmacy customers?
a. Patients struggle to fill medications due to shortages.
b. Patients feel they have to be careful of their appearance.
c. There is not really bias towards patients in pharmacy.

6. A new pharmacy resident was paged to attend a stroke code and unfortunately, the patient died because the resident did not know which medication to give at the moment. This was the fifth unsuccessful stroke code this month, and the resident is troubled. He starts drinking more after his work shift to help cope with the feelings of loss. After several months, he is diagnosed with depression. He is often late to work and his supervisors counsel him several times. What is the resident experiencing?
a. The resident is experiencing second victim syndrome.
b. The resident does not like his job or his bosses.
c. The resident is experiencing imposter syndrome.

7. Which choice correctly defines social identity and intersectionality?
a. Social identity is the relationship between intersectionality and systems of power; intersectionality is the process of being placed into a group
b. Social identity and intersectionality are different terms for the same concept, and researcher tend to use the two interchangeably in studies and review articles
c. Social identity relates to being placed in an “out-group” or “in-group”; intersectionality is the relationship between social identities and power systems

8. How does the Implicit Association Test (IAT) work?
a. It measures how fast White responders help Black victims in emergencies.
b. It measures the strength of participants’ personal beliefs towards minorities.
c. It measures how quickly participants associate concepts to categories.

9. Which of the following statements about bias internalization is TRUE?
a. Internalized bias has no impact on teamwork, and affects only the individual.
b. Internalized bias has no impact on individual, and affects only the whole team.
c. A bias toward a group of people can be internalized and applied to one’s self.

10. A recently pharmacy graduated has been hired to work on your team. You notice that the new pharmacist tends to hand off minority patients who need a language interpreter to other coworkers. You bring this up to your supervisor, who asks for your suggestions. Which statement is the best intervention?
a. The supervisor should call a team meeting and directly address the new pharmacist in front of everyone to hold that person accountable.
b. The team should review case studies similar to the minority patients so the new pharmacist can feel more comfortable working on those cases.
c. The manager should fire the new pharmacist because recent graduates should know how to manage all cases, even when an interpreter is needed.

Pharmacy Technician Post Test (for viewing only)

Pharmacy technician post-test

After completing the continuing education activity, the pharmacy technician will be able to:
• define different types of bias and how they are formed
• recognize what bias may look like in the pharmacy setting
• identify how bias can impact patient care
• illustrate understanding of strategies that mitigate bias

1. A female technician has worked in a retail pharmacy for several years. She notices the pharmacist always asks for the male technicians to help her put away the order, despite her being there much longer than they have. When she asks the pharmacist why she doesn’t ask for her help, the pharmacist says, “Oh, I just thought it was too heavy for you.” Which statement best describes this case?
a. Male technicians are better and more efficient workers than female technicians.
b. The pharmacist does not like working with the female technician.
c. The pharmacist’s thinking that females are not as strong as males is gender bias.

2. Which statement correctly identifies the differences between explicit and implicit bias?
a. Implicit biases are unconscious; explicit biases are conscious.
b. Explicit biases are harsher than implicit biases.
c. Implicit biases do not have anything to do with explicit biases.

3. You work in a retail pharmacy and a patient drops off a new prescription for Suboxone. When the patient comes to pick up the medication, you notice he is defensive when you ask to see an ID for verification purposes. What is one possible reason for their reaction?
a. The patient feels you may be judging him for his prescription.
b. The patient is offended and thinks you are calling him old.
c. The patient does not have his ID with him at the moment.

4. A female inpatient pharmacy technician is working with a male pharmacy resident to perform a medication history review. The tech notices the resident tends to rush through the interactions with older patients and will only speak to the family if they are present in the room. The tech has overheard this resident state he thinks the nurses should take medication histories since residents have “more important jobs than nurses.” With regard to the pharmacy resident, which bias may negatively affect patient care the most?
a. Affinity bias
b. Interprofessional bias
c. Age bias

5. Which statement is a microaggression?
a. A doctor says “Black women are at higher risks for maternal mortality.”
b. A faculty member says, “Most Black students are poor or illiterate”
c. A patient says, “I want to speak with to the doctor I saw last month.”

6. An APRN is concerned with a medication dose and asks to speak to the pharmacist. When finished with the call, the pharmacist turns to you and says, “APRNs are so incompetent. They never know how to send things over the right way.” Which statement describes the bias the pharmacist is displaying?
a. The pharmacist shows interprofessional bias towards the APRN.
b. The pharmacist in this example is not showing any explicit bias.
c. The pharmacist shows unprofessional bias towards the APRN.

7. How can practicing mindfulness help reduce biases in healthcare settings?
a. It reduces the likelihood of activating implicit biases and enhances the ability to control biases in patient care.
b. It helps healthcare providers take on the perspective of stigmatized or marginalized group members to build empathy.
c. It is designed to let healthcare providers develop goals that promote fairness and equality among coworkers.

8. Over the course of your career in pharmacy, you come to realize that your initial belief that patients who are prescribed multiple refills of opioids are abusing them is wrong. What is this an example of?
a. Stereotype
b. Interprofessional Bias
c. Ageism

9. Which statement describes how the brain plays a role in forming bias?
a. The amygdala and PFC both process social cues that turn to bias most of the time.
b. The PFC is triggered by sensory information while the amygdala processes cues.
c. The amygdala is triggered by sensory information while the PFC processes cues.

10. Which is an example of how implicit biases can influence institutional bias?
a. A Black male is unable to cast his vote at the ballots because he forgot his ID at home
b. A young Hispanic female is denied pain medication because the doctor thinks she’s exaggerating her pain
c. A disabled male athlete does not qualify for a sporting event because he places last in the competition

Full List of References

References

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13. Kearney, DB. Universal Design for Learning (UDL) for Inclusion, Diversity, Equity, and Accessibility (IDEA). Module 4.2 Positionality and Intersectionality. eCampus Ontario; 2022. Accessed April 10, 2023. https://ecampusontario.pressbooks.pub/universaldesign/
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15. Geronimus AT, Hicken M, Keene D, Bound J. "Weathering" and age patterns of allostatic load scores among blacks and whites in the United States. Am J Public Health. 2006;96(5):826-833. doi:10.2105/AJPH.2004.060749
16. Johnson-Agbakwu, C.E., Ali, N.S., Oxford, C.M. et al. Racism, COVID-19, and Health Inequity in the USA: a Call to Action. J. Racial Ethn Health Disparities. 2022;9: 52–58.
17. López L, Betancourt JR. Racial and Ethnic Disparities in Health Care. In: Loscalzo J, Fauci A, Kasper D, Hauser S, Longo D, Jameson J. eds. Harrison's Principles of Internal Medicine, 21e. McGraw Hill; 2022. Accessed April 10, 2023. https://accesspharmacy.mhmedical.com/content.aspx?bookid=3095§ionid=263343935
18. Henry, P. Institutional Bias. In: Dovidio JF, Hewstone M, Glick P, Esses VM, eds. Handbook of Prejudice, Stereotyping, and Discrimination. Sage; 2010:426-440
19. Olinger J, Capatosto K, McKay MA, et al. Challenging Race as Risk: How Implicit Bias Undermines Housing Opportunity in America. Ohio State University; 2017:1-85. Accessed July 20, 2023. https://kirwaninstitute.osu.edu/research/challenging-race-risk-implicit-bias-housing
20. FBI. Number of Victims of Hate Crime in The United States in 2021, by Motivation. Statista. Published March 13, 2023, Accessed April 10, 2023. https://www.statista.com/statistics/737648/number-of-hate-crime-victims-in-the-us-by-motivation/
21. Hoyert DL. Maternal mortality rates in the United States, 2020. NCHS Health E-Stats. 2022. doi.org/10.15620/cdc:113967
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23. Baffoe JO, Moczygemba LR, Brown CM. Perceived discrimination in the community pharmacy: A cross-sectional, national survey of adults. J Am Pharm Assoc. 2022;63(2):518-528. doi:10.1016/j.japh.2022.10.016
24. Kunstman JW, Plant EA. Racing to help: Racial bias in high emergency helping situations. J Pers Socl Psych. 2008;95(6)1499-1510. doi.org/10.1037/a0012822
25. Lee P, Le Saux M, Siegel R, et al. Racial and ethnic disparities in the management of acute pain in US emergency departments: Meta-analysis and systematic review. Am J Emerg Med. 2019;37(9):1770-1777. doi:10.1016/j.ajem.2019.06.014
26. Ngo-Metzger Q, Legedza AT, Phillips RS. Asian Americans' reports of their health care experiences. Results of a national survey. J Gen Intern Med. 2004;19(2):111-119. doi:10.1111/j.1525-1497.2004.30143.x
27. van Ryn M, Burke J. The effect of patient race and socio-economic status on physicians' perceptions of patients. Soc Sci Med. 2000;50(6):813-828. doi:10.1016/s0277-9536(99)00338-x
28. Lewis NJW, Batra P, Misiolek BA, Rockafellow S, Tupper C. Transgender/gender nonconforming adults' worries and coping actions related to discrimination: Relevance to pharmacist care. Am J Health Syst Pharm. 2019;76(8):512-520. doi:10.1093/ajhp/zxz023
29. Human Rights Campaign Foundation, APhA. Providing Inclusive Care and Services for the Transgender and Gender Diverse Community: A Pharmacy Resource Guide. Published March 2021. Accessed April 10, 2023. https://www.thehrcfoundation.org/professional-resources/transgender-pharmacy-guide#overview
30. Hippensteele A. Expert: 'we all hold implicit biases' that may contradict explicit beliefs, impact patient health. Pharmacy Times. Published October 2, 2022. Accessed April 10, 2023. https://www.pharmacytimes.com/view/expert-we-all-hold-implicit-biases-that-may-contradict-explicit-beliefs-impact-patient-health
31. Graham J. 'they treat me like I'm old and stupid': Seniors decry health providers' age bias. KFF Health News. Published October 20, 2021. Accessed April 10, 2023. https://kffhealthnews.org/news/article/ageism-health-care-seniors-decry-bias-inappropriate-treatment/
32. Boone R. Civil rights complaint targets Idaho Health Care Rationing. AP News. Published September 24, 2021. Accessed April 10, 2023. https://apnews.com/article/coronavirus-pandemic-business-discrimination-race-and-ethnicity-idaho-4a152d4f4f809bfb6588b9025c400d6b
33. Santee J, Barnes K, Borja-Hart N, et al. Correlation Between Pharmacy Students' Implicit Bias Scores, Explicit Bias Scores, and Responses to Clinical Cases. Am J Pharm Educ. 2022;86(1):8587. doi:10.5688/ajpe858
34. Miller CS, Scott SD, Beck M. Second victims and mindfulness: A systematic review. J Pat Saf Risk Manag. 2019;24(3):108-117. doi:10.1177/2516043519838176
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36. Everly GS. Psychological first aid to support healthcare professionals. J Pat Saf Risk Manag. 2020;25(4):159-162. doi:10.1177/2516043520944637
37. Sukhera J, Bertram K, Hendrikx S, et al. Exploring implicit influences on interprofessional collaboration: a scoping review. J Interprof Care. 2022;36(5):716-724. doi:10.1080/13561820.2021.1979946
38. Simpson A. The impact of team processes on psychiatric case management. J Adv Nurs. 2007;60(4):409-418 doi:10.1111/j.1365-2648.2007.04402.x
39. Huecker MR, Shreffler J, McKeny PT, Davis D. Imposter Phenomenon. In: StatPearls. Treasure Island (FL): StatPearls Publishing; September 9, 2022.
40. Sullivan JB, Ryba NL. Prevalence of impostor phenomenon and assessment of well-being in pharmacy residents. Am J Health Syst Pharm. 2020;77(9):690-696. doi:10.1093/ajhp/zxaa041
41. Wenger LM, Rosenthal M, Sharpe JP, Waite N. Confronting inequities: A scoping review of the literature on pharmacist practice and health-related disparities. Res Social Adm Pharm. 2016;12(2):175-217. doi:10.1016/j.sapharm.2015.05.011
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All “Prior Authorizations” are Not Created Equal: A Guide to Medicare Part D Prescription Drug Coverage

After completing this application-based continuing education activity, pharmacists will be able to

Describe the different types of prescription drug coverage available to Medicare patients
Explain the patient costs associated with Medicare Part D prescription drug coverage
Demonstrate use of a patient’s Medicare Part D formulary to determine the appropriate type of coverage determination
Identify prescriptions that Medicare Part D does not cover

After completing this application-based continuing education activity, pharmacy technicians will be able to:

Describe the different types of prescription drug coverage available to Medicare patients
Explain the patient costs associated with Medicare Part D prescription drug coverage
Identify the types of coverage determinations available for Medicare Part D prescriptions
Outline the timeframes involved in Medicare Part D coverage determination and appeal decisions

Millions of Americans are enrolled in Medicare Part D, with hundreds of specific Part D plans available across the country. The Centers for Medicare & Medicaid Services (CMS) regulates Part D coverage. Part D plans must submit their plan costs and formularies, including formulary restrictions, to CMS for annual approval. Patient costs for Part D coverage vary based on the specific choice of plan and the benefit phase. All Part D plans must provide a process for requesting coverage of prescription medications that are not on the formulary or on the formulary with restrictions. Pharmacists and pharmacy technicians are valuable resources and can advise Part D patients and prescribers about prescription costs and the options available for non-covered medications.

Content

INTRODUCTION

As of April 2023, more than 51 million Americans were enrolled in prescription drug coverage through Medicare, with the number of enrollees steadily increasing every year.¹Private insurance companies contracted by the Centers for Medicare & Medicaid Services (CMS) provide Medicare prescription drug coverage. Although specific plans’ details differ, CMS requires that all plans offer certain features.

Pharmacists and pharmacy technicians can assist patients in navigating these features to maximize their prescription benefits. This continuing education activity will review the types of Medicare prescription drug coverage, associated patient costs, formulary structure, and the options available when a patient’s Part D plan does not cover a medication.

MEDICARE AND PRESCRIPTION DRUG COVERAGE

CMS provides “Original Medicare” to most Americans aged 65 and older. Original Medicare includes²:

Part A: Most Americans are eligible for Medicare Part A at no additional cost, as long as they or their spouses have paid sufficient Medicare taxes. Medicare Part A includes coverage for inpatient hospital stays, hospice, and skilled nursing facility care.
Part B: Medicare Part B is optional and usually requires additional fees. Part B coverage includes outpatient and home health care, preventive services, and durable medical equipment.

CMS contracts with private insurance companies to provide prescription drug coverage. Individuals enrolled in Original Medicare may purchase a standalone Part D Prescription Drug plan (PDP) for outpatient prescription drug coverage.

Rather than using CMS coverage, individuals may purchase Medicare-approved private insurance called Medicare Advantage (MA), also known as Part C. With this arrangement, the MA Plan supersedes Medicare Part A and Part B for most coverage. MA plans often have lower patient costs and extra benefits compared to Original Medicare but may have fewer covered hospitals and physicians.² Medicare Advantage Prescription Drug (MAPD) plans are MA plans that include prescription drug coverage and eliminate the need for a separate PDP.

SIDEBAR: Patient Costs Defined

Monthly Premium: a monthly payment that maintains enrollment in the plan; not impacted by deductible, copay, or coinsurance amounts

Annual Deductible: a yearly dollar amount the patient pays before insurance starts to contribute

Copayment (or Copay): a specific, pre-determined dollar amount the patient pays for each prescription, office visit, or other type of care after satisfying the deductible

Coinsurance: an alternative to a copay, the percentage of the total cost the patient pays for each prescription, office visit, or other type of care after satisfying the deductible

Medicare plans are associated with various costs to the enrollee (see SIDEBAR: Patient Costs Defined). Individuals with income higher than a predefined threshold pay a higher premium for their Part B coverage due to Medicare’s Income Related Monthly Adjustment Amount (IRMAA). IRMAA does not change any of the other costs associated with Medicare coverage. CMS may also issue a late enrollment penalty (LEP) to people who do not sign up for Part D (from either a PDP or MAPD) as soon as they become eligible for Medicare. Once assigned, CMS adds the LEP to the patient’s monthly Part D premium for the remainder of their enrollment in Part D, regardless of which Part D plan they choose. Even people not actively taking prescription medications should consider choosing a Part D plan with a low monthly premium and/or no annual deductible to avoid incurring LEP.²

Individuals and couples with incomes and assets less than an annual threshold set by CMS may qualify for a Low Income Subsidy (LIS), also known as “extra help.” For people who qualify, the LIS reduces or eliminates the Part D monthly premium, deductible, and copay/coinsurance. CMS automatically enrolls most qualified patients into extra help, but a manual application process is also available. Pharmacy personnel should refer patients to 1-800-MEDICARE or https://www.medicare.gov/basics/costs/help/drug-costs to see if they qualify for LIS.³

Once a patient decides between Original Medicare or MAPD coverage, the next step is choosing a specific plan. CMS provides a comprehensive platform, called Medicare Plan Finder (MPF) for patients to shop and compare costs for PDP and MAPD plans. Patients can enter their medication list and see detailed cost information for each prescription. MPF also includes information about participating pharmacies and Star Ratings, a system CMS uses to measure each Part D plan’s performance in the areas of customer service, member experience, drug safety, and drug pricing accuracy. CMS rates plans on a scale of one to five stars, with five stars indicating the highest level of performance.⁴

The MPF tool is located at www.medicare.gov/plan-compare.

It is not necessary for pharmacy personnel to distinguish between MAPD and PDP coverage before processing prescription claims. The member’s prescription drug card provides the details needed to submit pharmacy claims to either type of Part D plan. If the member’s prescription drug card is not available, CMS provides a process known as an E1 transaction that returns Part D coverage information using basic demographic information. Pharmacists and technicians should consult their employer’s training materials for specific instructions on submitting an E1 transaction.⁵

The Part D Coverage Cycle

The Part D coverage cycle runs January to December each year. Regardless of when an individual reaches each phase of coverage, summarized in Figure 1, they start over in the deductible phase each year on January 1^st. Only “True Out-of-Pocket” (TrOOP) costs as defined by CMS go toward the thresholds to move patients through each of the four coverage phases. Patient costs excluded from TrOOP are⁶

Medications not covered by the Part D plan
Prescriptions obtained at non-participating (i.e., out-of-network [OON]) pharmacies, except those specifically allowed under the Part D plan’s rules
Costs reimbursed by an organization other than the Part D plan

PAUSE AND PONDER: Some patients with lower prescription costs do not complete their annual deductible until November or December. They are surprised when their out-of-pocket costs increase again in January. How would you explain the increase?

Patients with higher prescription costs may also be subject to the coverage gap, commonly known as the “Donut Hole” (see SIDEBAR: Explaining the Donut Hole). The coverage gap occurs when a patient’s prescription drug costs exceed a defined threshold under Medicare Part D. In the coverage gap, a patient’s out-of-pocket cost for brand name prescriptions may increase.⁷ Patients with very high prescription drug costs may reach the end of the coverage gap to enter catastrophic coverage, where they pay nothing out of pocket. The Inflation Reduction Act of 2022 removed patient costs from the catastrophic phase starting in 2024 and eliminated the coverage gap starting in 2025.⁸

SIDEBAR: Explaining the Donut Hole

Have you ever wondered why the Medicare Part D coverage gap is called the “Donut Hole?”

Imagine a giant donut, a circle with a hole in the middle, big enough to drive through. Half of the donut is plain, but the other half has frosting and sprinkles. In January, you start driving in a straight line through the plain half of the donut, toward the frosted half. Your drug costs determine your speed.

The plain half of the donut represents the annual deductible and initial coverage phases where you are subject to normal coverage amounts.

If high drug costs cause you to drive faster, you exit the plain half of the donut and enter the donut’s hole before the end of the year. You are now driving where there is no donut, and you must pay more than the normal amount for brand name drugs.

If your drug costs are high enough that you speed to the other side of the hole before the end of the year, then you enter the frosting and sprinkles half of the donut. Frosting and sprinkles represent the additional Part D contributions in the catastrophic phase and you pay nothing out of pocket.

Unfortunately, your car has only a 365-day warranty, so when January comes, you must start all over at the plain side of the donut.

An annual bidding process determines the specific costs for each Part D plan. Each year, CMS sets limits and thresholds for certain aspects of Part D coverage but allows flexibility within these parameters for both PDP and MAPD plans. Insurance companies submit bids that demonstrate how their plans comply with CMS’s annual limits and thresholds. The financial information that contributes to each plan’s annual bid is highly complex, and CMS can either accept or reject each bid.

As part of the annual bidding process, CMS defines standard prescription drug coverage. For a “basic” Part D plan, a bid must either match or be financially equivalent to the CMS definition of standard coverage. Table 1 provides the 2023 and 2024 standard benefit parameters, as defined by CMS.⁹

Table 1. Limits and Thresholds for 2023 and 2024 Medicare Part D Plans⁹

	2023	2024
Annual Deductible Limit	$505	$545
Initial Coverage Limit (starts the coverage gap)	$4660 total drug costs	$5030 total drug costs
Out-of-Pocket Limit (ends the coverage gap and starts catastrophic phase)	$7400 patient cost	$8000 patient cost

Insurance companies may also offer “enhanced” Part D plans with coverage that is more robust than the defined standard. Most plans with enhanced coverage have higher monthly premiums compared to basic plans but offer corresponding advantages such as reduced deductibles, lower copays/coinsurance, and lower costs in the coverage gap.

Individuals should choose their Part D plans carefully because they can only sign up or change Part D plans during certain periods²:

During the 3-month initial enrollment period that starts 1 month before and ends 1 month after an individual’s 65^th birthday; coverage starts the month after initial enrollment
During the annual open enrollment period that runs from mid-October to early December each year; coverage starts on January 1 of the following year for people who enroll during annual open enrollment
During the Medicare Advantage open enrollment period that runs from January through March each year; during this time, CMS only allows certain types of changes
During special enrollment periods for qualifying events such as relocation or the loss of employer or Medicaid coverage. Natural disasters that disrupt the initial or annual enrollment period may also create special enrollment periods

Prescription Coverage Under Medicare Parts A and B

Original Medicare provides prescription drug coverage under very limited circumstances and CMS prohibits Part D from covering anything covered under Medicare Parts A or B.

Medicare Part A covers hospice care, including medications related to the hospice diagnosis. Hospice providers receive payment for these medications from CMS and are responsible for paying the pharmacy. Medicare Part D is prohibited from covering medications related to any hospice diagnosis.¹⁰

Medicare Part B provides the only coverage options for some items, such as diabetic testing supplies and certain vaccines. Coverage for other items may fall under Part B or Part D, depending on the specific circumstances. Table 2 compares Part B and Part D coverage for the most common examples.¹⁰

Table 2. Medicare Part B and Part D Coverage of Common Products

Product(s)	Part B Coverage	Part D Coverage^a
Nebulizer Solutions (such as albuterol sulfate and ipratropium bromide)	For patients residing at home.	For patients residing in a long-term care facility.
Influenza, Hepatitis B, Pneumonia, and Coronavirus (COVID-19) Vaccines	Yes	No
Immunosuppressants (such as cyclosporine and mycophenolate mofetil)	When used to prevent rejection of a Medicare-covered transplant.	When used for a medically accepted indication other than a Medicare-covered transplant.
Oral Anti-Cancer Drugs (such as cyclophosphamide and methotrexate)	When used to treat cancer.	When used to treat a medically accepted indication other than cancer.
Oral Anti-Emetic Drugs (such as ondansetron and promethazine)	When used to treat or prevent chemotherapy-related nausea and vomiting.	When used to treat or prevent medically accepted indications other than chemotherapy-related nausea and vomiting.
Insulin	When used in an insulin pump.	When not used in an insulin pump.
Diabetic Testing Supplies (such as test strips and lancets)	Yes	No
Insulin Injection Supplies (such as needles and alcohol swabs)	No	Yes
^aCoverage may be subject to formulary restrictions.

Part D plans are responsible for rejecting pharmacy claims for medications that may be covered under Part A or Part B. Pharmacy personnel should refer to claim reject messaging and redirect the claim appropriately.

Other Prescription Drug Coverage

Most people who qualify for Medicare are covered by some combination of Parts A, B, C, and D as described above. However, other prescription drug coverage options are available under special circumstances:

Employer Group Waiver plans (EGWPs): Employers may choose to provide prescription drug coverage for their retirees by contracting with a Part D plan for EGWP coverage. Retirees with EGWP plans that start as soon as they become eligible for Medicare are exempt from LEP. When providing an EGWP plan for their retirees, employers may also add additional benefits paid either through Part D or by the employer themselves.¹¹
Medicare Supplemental Insurance (Medigap): Medigap coverage helps with costs not covered by Medicare Parts A and B, such as copays and deductibles. Certain Medigap plans also help with skilled nursing facility or hospice costs and emergency care while traveling outside of the United States. Individuals who enrolled in Medigap prior to 2006 may have prescription drug coverage included, but those who are newer to Medigap should purchase separate Part D coverage to avoid LEP.¹²
Employer Coverage: Individuals who are actively employed (not retired) may have coverage through their employer to replace Medicare or use Medicare as secondary coverage. Covered employees are exempt from the LEP if the employer coverage is equivalent to at least a basic Part D plan.²
Consolidated Omnibus Budget Reconciliation Act (COBRA): People who have recently separated from an employer may be eligible for COBRA. Individuals enrolled in COBRA may still be subject to LEP because COBRA is usually not equivalent to Medicare coverage.²
Medicaid: People with low incomes who qualify for both Medicaid and Medicare receive the LIS and have Part D coverage with reduced patient costs. In most cases, Medicare pays first and Medicaid helps with remaining costs.²
Manufacturer Discount Programs: Many drug manufacturers provide coupons, discount cards, and patient assistance programs to help cover their products’ cost. Federal law prohibits using these manufacturer payments in combination with Medicare prescription drug coverage.¹³ Medicare patients may choose manufacturer coupons or patient assistance programs for certain prescriptions only when they do not use their Part D coverage.
Prescription Discount Cards: Unlike manufacturer discounts, which are limited to products produced by that manufacturer, prescription discount cards offer discounts on a wide range of medications. Also known as “cash cards”, prescription discount cards reduce the cash price of prescriptions, but are not used in combination with insurance, including Medicare.¹⁴ Patients who choose a prescription discount card cannot use it in combination with their Part D coverage for the same medication.

MEDICARE PART D FORMULARIES

CMS requires Part D plans to maintain a list of covered drugs, called a formulary. CMS reviews each Part D formulary to ensure sufficient coverage under each drug class. The copay or coinsurance for each medication on the formulary is determined by its “tier.” Medications on lower tiers generally cost less than drugs on higher tiers.¹⁵ CMS allows some flexibility on how Part D plans define their formulary tiers, so tier structure differs between plans. Figure 2 provides an example of a formulary tier arrangement.

Drug Placement and Formulary Restrictions

Specialty medications are high-cost prescription products used to treat complicated medical conditions. CMS limits the patient cost portion for these medications and Part D plans typically place all specialty mediations into designated formulary tiers.¹⁰

CMS requires that Part D plans cover adult vaccines (excluding those covered under Part B) recommended by The Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices at no cost to the patient, regardless of formulary tier or benefit phase.¹⁶

In 2023, CMS began setting a maximum copay for insulin products covered under Part D. Currently, the maximum copay is $35 for a one-month supply and is subject to change on an annual basis. Insulin copays may be lower if a Part D plan includes specific insulin products on a formulary tier where the monthly copay is lower than the CMS maximum. A similar program exists for insulin used in an insulin pump and covered under Part B.¹⁶

Part D plans may put restrictions on formulary medications to ensure appropriate coverage and to control costs. CMS reviews the restrictions and will not allow overly restrictive formularies. Plans may place four types of restrictions on formulary medications¹⁰:

Quantity Limit: Quantity limit restrictions define the maximum number of dosage units allowed for a specific time period.
Step Therapy: Step therapy restrictions require patients to first try a different medication, usually a lower cost alternative, before the prescribed medication.
Prior Authorization: Prior authorizations require patients to meet specific criteria, which may be as simple as providing the diagnosis or more complicated (e.g., specific lab tests, involvement of a specialist physician).
Drug Utilization Review (DUR): May be “hard edits” that require a coverage determination or “soft edits” that require the dispensing pharmacist to obtain clinical information and enter a set of codes into the prescription claim.

CMS defines six drug classes—those used to treat disorders where changes or interruptions in therapy involve higher risk—as “protected class.” CMS requires that Part D formularies include most medications within these classes with at least one medication on a preferred tier and no restrictions. Plans are not, however, required to include all variations of each medication (i.e., brand name and generic or immediate and extended-release versions). The six protected classes are¹⁰

immunosuppressants (used to prevent organ transplant rejection)
antidepressants (used to treat depression)
antipsychotics (used to treat mental health disorders)
anticonvulsants (used to treat seizure disorders)
antiretrovirals (used to treat human immunodeficiency virus)
antineoplastics (used to treat cancer)

CMS allows plans to add medications and make other positive changes to their formulary throughout the year but restricts medication removal and other negative changes until the following January. This restriction protects patients from losing coverage for their prescriptions during the time when they cannot switch to a different Part D plan. Marketplace removal, safety concerns, and the availability of a new generic are examples of situations when CMS would allow removal of a medication from a Part D formulary during the year.

Part D plans must provide patients with ongoing access to their formulary information. Most Part D plans post formularies online and only provide paper copies upon request. Patients can also see the formulary status for their specific medications when comparing Part D plans using the MPF website.

COVERAGE DETERMINATIONS AND APPEALS

Patients and pharmacy personnel commonly generalize the term “prior authorization” to describe any situation that requires insurance approval before insurance covers a prescription. Under Medicare Part D, this is known as the coverage determination process. Part D patients may use the coverage determination process to request approval for a non-formulary medication or a formulary medication with restrictions.

Who hasn’t been frustrated after contacting a prescriber to change a non-formulary prescription to a formulary medication, only to have the formulary medication require prior authorization? Part D plans usually include messaging within rejected claims to help determine which type of coverage determination is needed. When faced with a prescription rejection, pharmacists and pharmacy technicians who understand the nuances of the coverage determination process are equipped to advise their Part D patients on the best course of action.

Several specific types of coverage determinations are available and each type of coverage determination has specific criteria for approval.^16,17 Table 3 provides a summary of coverage determination types, their uses, and the information required for approval.

Table 3. Types of Coverage Determinations and Their Uses^16,17

Medication Status	Coverage Determination	Requirements for Approval
On the formulary, but dosing regimen requires more than the formulary allowance or requires tablet splitting	Quantity Limit Exception	The quantity allowed by the plan’s formulary is not effective in treating the patient’s condition or requires tablet-splitting to achieve the prescribed dosing regimen.
On the formulary with step therapy restrictions	Step Therapy Exception	The patient tried the step medication and either did not achieve therapeutic effect or experienced an adverse outcome.
On the formulary with step therapy restrictions	Step Therapy	The patient is likely to experience an adverse outcome if they must first try the step medication.
On the formulary with prior authorization or “hard” DUR restrictions	Prior Authorization	The patient meets the Part D plan’s specific criteria for the prescribed medication.
On the formulary with a “soft” DUR restriction	None	DUR “soft edits” may require dispensing pharmacists to contact prescribers and obtain clinical information, but do not require a coverage determination.
Sometimes by Medicare Part B	Prior Authorization	Why the patient’s situation warrants coverage under Part D for the prescribed medication.
On the formulary, but the patient cannot afford the copay/coinsurance	Tier Exception	The required number^† of lower tier drugs for the same condition are less effective or likely to result in an adverse outcome. Not available for specialty or non-formulary medications and cannot provide a brand name medication at the generic cost.
Not on the formulary	Non-formulary Exception	The required number^† of formulary alternative medication(s) were ineffective or likely to result in an adverse outcome.

^†Patients should consult their specific plan information to find out how many alternatives are required for tier or non-formulary exceptions.

Part D plans will only approve a coverage determination request if the product is medically necessary and if the information submitted by the prescriber meets the plan’s criteria. Prescribers may submit information over the phone, by fax, or by mail. Most Part D plans also have an electronic portal to accept information from prescribers. Dispensing pharmacists are only permitted to supply information in place of the prescriber under limited circumstances, such as prior authorizations to determine Part B versus Part D coverage.

Approval and Denial Parameters

For exception requests that meet approval criteria, CMS requires Part D plans to maintain the approval at least through the end of the year. Part D plans may approve prior authorizations for a shorter time only if clinically appropriate and approved by CMS as part of the annual formulary approval process.

Part D plans will deny requests with incomplete information and requests that do not meet approval criteria. Part D plans will also deny any type of coverage determination if the medication is being used for a non-medically accepted indication. Medically accepted indications are uses approved by the United States Food and Drug Administration or listed in one of the references that CMS defines as approved compendia¹⁰:

American Hospital Formulary Service Drug Information
DRUGDEX Information System
Peer-reviewed medical literature (only allowed for biologics and anti-cancer chemotherapy medications)

Common examples of medications prescribed for non-medically accepted indications include the use of fentanyl lollipops/lozenges for non-cancer pain and hydroxychloroquine for coronavirus disease 2019 (COVID-19). Federal and state laws may allow prescriptions for non-medically accepted indications, but patients cannot use their Part D coverage to pay for them. Part D plans must block medication coverage if the determination process reveals a non-medically accepted indication, even for previously covered medications, quantities less than the predetermined limit, and any tier cost after a tier exception request.¹⁰ Pharmacists are not required to confirm medically accepted indications before dispensing prescriptions because CMS considers this a plan responsibility. As a result, Part D plans will often reject claims and require a prior authorization for medications commonly prescribed for non-medically accepted indications. Pharmacists and pharmacy technicians can assist patients and prescribers by communicating rejected claim information and explaining the CMS requirement for medically accepted indications. ¹⁰

In addition to medications covered under Part A or B, CMS specifically excludes certain types of medications from Part D coverage¹⁰:

Products used for weight loss or weight gain
Fertility medications
Cosmetic and hair growth products
Treatments for the symptomatic relief of cough and colds
Non-prescription medications
Prescription vitamins, except prenatal and fluoride products
Erectile dysfunction treatments

Bulk powders and inert excipients used for compounded prescriptions are also excluded from Part D coverage. Compounds may contain other ingredients that are covered with or without restrictions under Part D. When pharmacies bill some of a compound’s ingredients to Part D, CMS prohibits them from charging patients for the non-Part D portion.¹⁰

Patients cannot obtain Part D coverage for excluded medications using the coverage determination process. Employers may cover some of these medications and manufacturer coupons or prescription discount cards may help make these products more affordable for individuals without employer coverage.

PAUSE AND PONDER: Generic sildenafil is prescribed for both erectile dysfunction (excluded from Part D coverage) and pulmonary hypertension (eligible for Part D coverage). Can a dispensing pharmacist distinguish between the two to bill Part D for the appropriate product?

Part D plans may dismiss requests that are inappropriate, unnecessary, or filed incorrectly. CMS requires Part D plans to provide written notification and a reason for the dismissal to the patient and prescriber.¹⁷

If the patient or prescriber decides that a request is unnecessary, they can withdraw the request before a decision is issued. Withdrawing a request does not prevent the patient or prescriber from submitting a later request for the same medication.¹⁷

When a Part D plan denies a coverage determination, CMS requires them to send the specific reason(s) for the denial to the patient and the prescriber. Part D plans may choose to also send a copy of this information to the dispensing pharmacy.¹⁷ Depending on the reason for the denial, the patient or prescriber may choose to appeal the Part D plan’s decision.

Appeal requests must be within 60 days of the denial, unless good cause is established for missing the 60-day deadline. If the Part D plan denies the appeal, beneficiaries have up to four additional opportunities to appeal through entities outside of their Part D plan. After the second level, higher levels of appeal are only available if the drug cost meets a specific threshold set by CMS.¹⁸ Figure 3 outlines the five levels of appeal available to Part D patients.

A patient or prescriber can request a re-opening instead of the next level appeal if they feel that a coverage determination or appeal decision is in error. Part D plans may also initiate a re-opening if they identify a decision error.

Direct Member Reimbursements

Patients who pay for a covered Part D prescription without using their Part D Insurance may be eligible for reimbursement from their Part D plan through a process called Direct Member Reimbursement (DMR). To qualify for DMR, the prescription must meet the Part D plan’s coverage requirements and not be covered by any other type of insurance or discount card. Prescriptions obtained at an OON pharmacy must meet the Part D plan’s OON rules to qualify for reimbursement.¹⁹

Pharmacies should submit Part D prescriptions to the patient’s Part D plan whenever possible because a DMR reimbursement may not result in a full refund of the cash price.

Timeframes

Part D plans must offer both standard and expedited timeframes for coverage determination and appeal requests (listed in Table 4). Expedited requests are available when the standard timeframe could result in a significant adverse outcome. DMR requests do not qualify for expedited timeframes because the patient has already received the medication.¹⁷

Table 4. Plan Timeframes for Medicare Part D Requests¹⁶

Request Level	Request Urgency	Request Type	Required Timeframe
Initial Coverage Determination	Standard	Quantity Limit Exception Step Therapy Exception Tier Exception Non-Formulary Exception	72 hours from supporting statement but no longer than 14 days from request received
Initial Coverage Determination	Expedited	Quantity Limit Exception Step Therapy Exception Tier Exception Non-Formulary Exception	24 hours from supporting statement but no longer than 14 days from request received
Initial Coverage Determination	Standard	Prior Authorization Step Therapy (non-exception)	72 hours from request received
Initial Coverage Determination	Expedited	Prior Authorization Step Therapy (non-exception)	24 hours from request received
Initial Coverage Determination	N/A	Direct Member Reimbursement	14 days from request received
First Level Appeal	Standard	Quantity Limit Exception Step Therapy Exception Tier Exception Non-Formulary Exception Prior Authorization	7 days from request received
First Level Appeal	Expedited	Quantity Limit Exception Step Therapy Exception Tier Exception Non-Formulary Exception Prior Authorization	72 hours from request received
First Level Appeal	N/A	Direct Member Reimbursement	Notification of Decision: 14 days from request received Payment (if approved): 30 days from request received

Part D plans may automatically apply the expedited timeframe if the clinical information submitted for the coverage determination indicates that waiting may harm the patient’s health. Alternatively, Part D plans may downgrade an expedited request if they determine that the patient’s health will not be harmed by using the standard timeframe. CMS requires Part D plans to notify the patient if a request is downgraded from expedited to standard.¹⁷

All Part D timeframes are based on calendar hours/days and include weekends and holidays. Timeframes start as soon as the Part D plan receives a non-exception coverage determination or any type of valid appeal request, regardless of how much clinical information is included with the request. For exception requests, the timeframe starts as soon as the Part D plan receives clinical information from the prescriber to support the request (known as the prescriber’s supporting statement). When a supporting statement is missing from an exception request, CMS allows up to 14 days for plans to obtain it.¹⁷The following examples demonstrate Part D timeframes over weekends and holidays:

A patient requests a standard prior authorization on Friday afternoon, December 23. The prescriber’s office is closed for the three-day holiday weekend. The plan must deny the request in 72 hours (on Monday afternoon), even though the prescriber’s office was not available to provide information during that timeframe.
A different patient requests a standard non-formulary exception the same day. Their prescriber’s office is also closed for the three-day holiday weekend but contacts the plan with the supporting information on Tuesday morning. Since this is an exception request, 72 hour timeframe starts on Tuesday morning and the plan has until Friday morning to complete the request.

When clinical information is incomplete, CMS requires that Part D plans make reasonable efforts to contact the prescriber and obtain the missing information. Once the timeframe has started, making outreach attempts and waiting for additional information does not extend the request timeframe. The Part D plan will deny the request if they do not receive sufficient clinical information by the end of the allotted timeframe.¹⁷

PAUSE AND PONDER: It’s late Friday afternoon and your patient is anxious to request a prior authorization for her medication. The physician’s office is closed for the weekend. Could requesting an expedited coverage determination at this point cause more of a delay?

When a Part D plan does not process a request within the required timeframe, they must send the request to the IRE as an “auto-forward.” This is the same IRE that processes Part D second-level appeals. Part D plans must notify patients in the event of an auto-forward. CMS monitors Part D plans’ timeliness and issues penalties for excessive numbers of auto-forwards.

How to Submit Requests

CMS requires that Part D plans accept coverage determination requests via phone, fax, or mail. For appeals, plans must accept both standard and expedited requests via fax or mail. Verbal requests by phone are required for expedited appeals but optional for standard appeals.¹⁷ Many plans also choose to accept electronic requests via an online portal.

Patients should follow the instructions from their specific Part D plan for requesting a DMR. Part D plans usually require hard copies of payment receipts, so most patients file DMR requests by mail.

CMS does not permit Part D plans to require a specific form to submit a coverage determination, appeal, or DMR request.¹⁷ Although optional, using a form provided by the plan usually streamlines the process and reduces the risk of submitting incomplete information.

CMS does not allow dispensing pharmacists or pharmacy technicians to request a Part D coverage determination or appeal on behalf of the patient. Only the patient, the patient’s appointed representative, the prescriber, or the prescriber’s staff can request a coverage determination or appeal. Only patients or their appointed representative can request a DMR.¹⁷

The handout entitled “Medicare Prescription Drug Coverage and Your Rights” that dispensing pharmacies supply to patients when prescriptions cannot be filled under their Part D plan provides additional instructions for submitting requests.^17,20

CONCLUSION

Medicare patients have many choices available for their prescription drug coverage. CMS requires that all Part D plans conform to a set of common standards while allowing specific plans to offer a wide range of benefit options.

Pharmacists and pharmacy technicians with a basic understanding of Part D coverage options, patient costs, formulary structure, and the coverage determination and appeals process can help patients maximize the benefit from their Part D plan. Although CMS does not allow them to initiate coverage determinations and appeals, pharmacy personnel can advise Part D patients and their physicians on the most effective next steps when faced with a non-covered prescription.

Pharmacist Post Test (for viewing only)

All “Prior Authorizations” are Not Created Equal: A Guide to Medicare Part D Prescription Drug Coverage

Pharmacists Post-test

After completing this continuing education activity, pharmacists will be able to
1. Describe the different types of prescription drug coverage available to Medicare patients.
2. Explain the patient costs associated with Medicare Part D prescription drug coverage.
3. Demonstrate use of a patient’s Medicare Part D formulary to determine the appropriate type of coverage determination.
4. Identify prescriptions that Medicare Part D does not cover.

1. Which of the following is the correct description for the type of Medicare coverage?
A. Medicare Part A: Covers outpatient and home health care, preventative services, and durable medical equipment.
B. Medicare Part B: Offered by private insurance companies for prescription drug coverage.
C. Medicare Part C: Offered by private insurance companies to provide Part A and Part B coverage.

2. What is an appropriate combination of coverage?
A. Medicare Part A + Medicare Part B + Medicare Part D
B. Medicare Part A + Medicare Part B + MAPD
C. Employer Coverage + Medigap + MAPD

3. A patient who is turning 65 next month asks you about delaying Part D coverage because she only takes two prescriptions that are very low cost using a prescription discount card. What is the possible risk of this approach when she eventually signs up for Part D coverage at a later date?
A. She may pay higher monthly premiums due to the coverage gap.
B. She may pay higher annual deductibles due to the late enrollment penalty.
C. She may pay higher monthly premiums due to the late enrollment penalty.

4. It’s January and a patient who paid a $10 copay for his prescription last month now has to pay 100% of the cost. What is the most likely explanation?
A. He is paying the annual deductible
B. He is in the coverage gap
C. His Part D plan doesn’t cover his medication

5. A patient who takes several expensive medications experiences a sharp increase in her out-of-pocket costs around midyear. What is the most likely explanation?
A. She has entered the deductible phase
B. She has entered the coverage gap phase
C. She has entered the catastrophic coverage phase

6. A patient’s Part D Plan is rejecting a prescription for apixaban. You locate its formulary online and find that dabigatran is listed, but not apixaban. What type of coverage determination does this patient need from this Part D Plan?
A. Step Therapy
B. Non-formulary
C. Prior Authorization

7. A patient’s Part D Plans is rejecting a prescription for alirocumab. You locate the formulary online and find that alirocumab is on the formulary but is not covered unless simvastatin has been tried first. What type of coverage determination does this patient need from this Part D Plan?
A. Step Therapy
B. Prior Authorization
C. Tier Exception

8. A Part D patient is struggling to afford his medication, even after the Part D Plan approved a non-formulary exception. What is their best option for lowering costs?
A. Talk to the prescriber about switching to an alternative on a lower formulary tier.
B. Ask their Part D Plan for a tier exception.
C. Find a manufacturer discount coupon to cover their Part D copay.

9. A Part D patient presents a prescription for a highly advertised diabetic medication and confides in you that she is not diabetic but hoping the medication will help with weight loss. Her Part D Plan requires prior authorization to establish medically accepted indication. What coverage option is available to them?
A. Part D after prior authorization approval
B. Manufacturer discount program
C. Medicare Advantage

10. A Medicare Part D Plan is rejecting claims for your patient’s diabetic test strips and lancets. What do you recommend as the next course of action?
A. Call the Part D Plan and request a coverage determination.
B. Pay out of pocket and ask the Part D Plan for direct member reimbursement.
C. Compile the documentation required to submit the claims to Part B.

Pharmacy Technician Post Test (for viewing only)

All “Prior Authorizations” are Not Created Equal: A Guide to Medicare Part D Prescription Drug Coverage

Pharmacy Technician Post-test

After completing this continuing education activity, pharmacy technicians will be able to
1. Describe the different types of prescription drug coverage available to Medicare patients.
2. Explain the patient costs associated with Medicare Part D prescription drug coverage.
3. Identify the types of coverage determinations available for Medicare Part D prescriptions.
4. Outline the timeframes involved in Medicare Part D coverage determination and appeal decisions.

2. What is an appropriate combination of coverage?
A. Medicare Part A + Medicare Part B + Medicare Part D
B. Medicare Part A + Medicare Part B + MAPD
C. Employer Coverage + MAPD

5. A patient who takes several expensive medications experiences a sharp increase in her out-of-pocket costs around midyear. What is the most likely explanation?
A. She has entered the deductible phase.
B. She has entered the coverage gap phase.
C. She has entered the catastrophic coverage phase.

6. Which of the following combinations of coverage determinations may be required for a single prescription?
A. Non-formulary + Quantity Limit
B. Quantity Limit + Prior Authorization
C. Tier Exception + Non-formulary

7. Which type of reject requires a Part D coverage determination?
A. Non-formulary
B. Refill too soon
C. DUR soft edit

8. Which of the following is the correct description for a type of coverage determination under Medicare Part D?
A. Non-formulary exceptions: Used to request larger quantities of a medication
B. Tier Exceptions: Used to request a lower copay for a medication
C. Prior Authorization: Used to request a non-formulary medication

9. A patient called her Part D plan yesterday morning to request an urgent appeal for their medication. This afternoon, she has not received a response and the claim is still rejecting. How much longer might she have to wait for a response?
A. The appeal is already out of timeframe because it has been longer than 24 hours
B. 6 more days, for a total of 7 days
C. 2 more days, for a total of 3 days

10. You are working on a prescription that the Part D Plan is rejecting due to a quantity limit. The patient is not out of medication, so you advise him to call and ask for a standard quantity limit exception. How long should the patient expect to wait for the Part D Plan to make a decision?
A. 24 hours after the patient calls their Part D Plan to request the coverage determination
B. 24 hours after their prescriber provides clinical information to the Part D Plan
C. 72 hours after their prescriber provides clinical information to the Part D Plan

Full List of References

References

1. Centers for Medicare & Medicaid Services. Medicare Enrollment Dashboard. Accessed August 28, 2023. https://data.cms.gov/tools/medicare-enrollment-dashboard
2. Centers for Medicare & Medicaid Services. Medicare & You Handbook. Accessed September 5, 2023. https://www.medicare.gov/medicare-and-you
3. Centers for Medicare & Medicaid Services. Help with Drug Costs. Accessed September 6, 2023. https://www.medicare.gov/basics/costs/help/drug-costs
4. Centers for Medicare & Medicaid Services. Explore Your Medicare Coverage Options. Accessed September 13, 2023. www.medicare.gov/plan-compare
5. RelayHealth. Medicare Eligibility Verification Transaction. Accessed December 28, 2023. https://medifacd.mckesson.com/e1/
6. Centers for Medicare & Medicaid Services. Medicare Prescription Drug Benefit Manual Chapter 5: Benefits and Beneficiary Protections. September 20, 2011. Accessed September 5, 2023. https://www.cms.gov/medicare/prescription-drug-coverage/prescriptiondrugcovcontra/downloads/memopdbmanualchapter5_093011.pdf
7. Centers for Medicare & Medicaid Services. Costs in the Coverage Gap. Accessed September 6, 2023. https://www.medicare.gov/drug-coverage-part-d/costs-for-medicare-drug-coverage/costs-in-the-coverage-gap
8. Kaiser Family Foundation. Changes to Medicare Part D in 2024 and 2025 Under the Inflation Reduction Act and How Enrollees Will Benefit. Accessed December 27, 2023. https://www.kff.org/medicare/issue-brief/changes-to-medicare-part-d-in-2024-and-2025-under-the-inflation-reduction-act-and-how-enrollees-will-benefit
9. Centers for Medicare & Medicaid Services. Announcement of Calendar Year (CY) 2024 Medicare Advantage (MA) Capitation Rates and Part C and Part D Payment Policies. March 31, 2023. Accessed September 6, 2023. https://www.cms.gov/files/document/2024-announcement-pdf.pdf
10. Centers for Medicare & Medicaid Services. Medicare Prescription Drug Benefit Manual Chapter 6 – Part D Drugs and Formulary Requirements. January 15, 2026. Accessed August 23, 2023. https://www.cms.gov/medicare/prescription-drug-coverage/prescriptiondrugcovcontra/downloads/part-d-benefits-manual-chapter-6.pdf
11. Centers for Medicare & Medicaid Services. Medicare Prescription Drug Benefit Manual Chapter 12 – Employer/Union Sponsored Group Health plans. November 7, 2008. Accessed September 5, 2023. https://www.cms.gov/regulations-and-guidance/guidance/transmittals/downloads/dwnlds/r6pdbpdfpdf
12. Centers for Medicare & Medicaid Services. Learn How Medigap Works. Accessed October 25, 2023. https://www.medicare.gov/health-drug-plans/medigap/basics/how-medigap-works
13. Office of Inspector General. Special Advisory Bulletin, Pharmaceutical Manufacturer Copayment Coupons. September 2014. Accessed September 5, 2023. https://oig.hhs.gov/documents/special-advisory-bulletins/878/SAB_Copayment_Coupons.pdf
14. Dr Christina Polomoff discusses the complex world of medication discount cards. Am J Manag Care. April 13, 2021. Accessed September 5, 2023. www.ajmc.com/view/dr-christina-polomoff-discusses-the-complex-world-of-medication-discount-cards
15. Centers for Medicare & Medicaid Services. What Medicare Pat D plans Cover. Accessed September 7, 2023. https://www.medicare.gov/drug-coverage-part-d/what-medicare-part-d-drug-plans-cover
16. Centers for Medicare & Medicaid Services. Final Contract Year (CY) 2024 Part D Bidding Instructions. April 4, 2023. Accessed September 6, 2023. https://www.cms.gov/files/document/final-cy-2024-part-d-bidding-instructions.pdf
17. Centers for Medicare & Medicaid Services. Parts C&D Enrollee Grievances, Organization/Coverage Determinations, and Appeals Guidance. August 3, 2022. Accessed September 10, 2023. https://www.cms.gov/medicare/appeals-and-grievances/mmcag/downloads/parts-c-and-d-enrollee-grievances-organization-coverage-determinations-and-appeals-guidance.pdf
18. Centers for Medicare & Medicaid Services. Medicare Appeals. Accessed August 23, 2023. https://www.medicare.gov/Pubs/pdf/11525-Medicare-Appeals.pdf
19. Centers for Medicare & Medicaid Services. Medicare Prescription Drug Benefit Manual Chapter 14 – Coordination of Benefits. September 17, 2018. Accessed September 11, 2023. https://www.cms.gov/Medicare/Prescription-Drug-Coverage/PrescriptionDrugCovContra/Downloads/Chapter-14-Coordination-of-Benefits-v09-14-2018.pdf
20. Centers for Medicare & Medicaid Services. Medicare Prescription Drug Coverage and Your Rights. Accessed September 12, 2023. https://www.cms.gov/outreach-and-education/outreach/partnerships/downloads/yourrightsfactsheet.pdf

Patient Safety: Herbal Products and Potential Organ Dysfunction

After completing this application-based continuing education activity, pharmacists will be able to

List herbal products associated with liver, kidney, and heart damage

Describe potential drug interactions with herbal medications

Discuss the potential for contaminants in herbal products

After completing this application-based continuing education activity, pharmacy technicians will be able to

List herbal products associated with liver, kidney, and heart damage

Recognize the potential for herbal products to be unsafe

Describe certificates of analysis and how to retrieve them from manufacturers

As part of complementary and alternative medicine, herbal products are gaining popularity in the United States. Approximately one in five Americans use herbal products. Although people may perceive them as harmless due to their "natural" origin, studies and case reports on herbal toxicity dispute that belief. Injuries to liver, kidney, and heart; herb-drug interactions; and contamination and mislabeling are grave health risk concerns with some herbal products. Although non-prescription, herbal products' ubiquitous presence in all kinds of
shops, pharmacies, and Internet vendors causes many people to consider them important to their overall well-being. Pharmacists and technicians can help patients reduce health risks associated with herbal products. Ample knowledge of popular herbal products will help pharmacy teams identify health risks quickly.

Pharmacist Post Test (for viewing only)

Herbal Products and Health Risks

Pharmacist Post-test

After completing this continuing education activity, pharmacists will be able to
• List herbal products associated with liver, kidney and heart damage
• Describe potential drug interactions with herbal medications
• Discuss the potential for contaminants in herbal products

1. Which of the following agencies reviews and inspects herbal products before coming to market?
A. United States Food and Drug Administration
B. National Center for Complementary and Alternative Medicine
C. International Association of Traditional Chinese Medicine

2. John Goodman, a frequent customer at your pharmacy, comes to the counter to pick up his monthly medications. He asks, “Would it be a bother to have you check out the rest of my items here as well?” Always one to help a customer, you tell him, “Of course, that’s fine!” You notice he has a botanic extract tincture that claims to help with heartburn. The ingredient list includes greater celandine (Chelidonium majus). Mr. Goodman is also picking up his 30-day supply of Questran (cholestyramine). What organ dysfunction could be a concern?
A. Liver injury
B. Kidney injury
C. Heart damage

3. A patient presents to the emergency room suffering from acute kidney injury and liver injury. Lab tests show glutathione depletion, and the physician recommends N-acetylcysteine as a possible antidote. Upon opening the patient’s bag, you notice three natural product supplements: pennyroyal essential oils, germander weight loss tea, and impila fertility boost capsules. Which product may be responsible for BOTH the kidney and liver injury?
A. Pennyroyal essential oils
B. Germander weight loss tea
C. Impila fertility boost capsules

4. Mr. Goodman returns to your pharmacy. He explains he has been trying to live a healthier lifestyle, but has been feeling exceptionally tired after taking his as-needed alprazolam. When asked what over-the-counter products he uses, Mr. Goodman tells you, “Oh, you know the usual stuff: echinacea, garlic, ginger…” You are concerned because an interaction between alprazolam and ______ could be causing the excessive drowsiness.
A. Echinacea
B. Garlic
C. Ginger

5. Johnathan Bravo comes to the counter with a melancholic look on his face. “You know… getting older is not easy, especially when your wife looks so much better than you. I have tried everything: gym, new haircut, self-help books; and nothing seems to work.” He then proceeds to tell you about this supplement used in Southeast Kazakhstan that his gym buddy recommended. “Yeah, he says he’s seen guys lose weight, look better than ever and… well… you know… have a better relationship with their wife.” This sounds too good to be true; you are concerned this product has been _____________.
A. Mishandled
B. Mistaken
C. Mislabeled

6. Which of the following are chemists mainly concerned about when they look for contaminants in herbal products?
A. Metal
B. Glutathione
C. Poisons

7. Which of the following patients is most at risk of a serious adverse event associated with henbane (Hyoscyamus niger)?
A. A 27-year-old female with an irregular menstrual cycle
B. A 48-year-old male with a history of atrial fibrillation
C. A 62-year-old male with new onset major depressive disorder

8. Mrs. Jin is a longtime customer of your pharmacy who is on warfarin therapy for her atrial fibrillation. Her dose has been stable for quite some time, but today, you are surprised to see a change to her warfarin dosing. You call her cardiologist to double check the prescription and she tells you, “Yeah, it’s really crazy; three years no change in INR and out of nowhere a 0.2-point decrease.” Upon picking up her prescription, you ask Mrs. Jin about complementary and alternative medicine use. What herbal supplement might be a possible explanation for Mrs. Jin’s INR decrease?
A. Chamomile
B. Kava kava
C. American ginseng

9. “These kids nowadays takin’ that codeine, and that awful dextromethorphan!” exclaimed Mr. O’Timer. “When I was a kid, and even now, all I ever took was licorice. My mom, bless her soul, would never let any poison enter MY body. To this day that’s all I use when I get a cold.” Trying to move him along before he inevitably tries to talk to you about politics, you stop as he mentions his busy day full of specialist appointments. Which specialist would be MOST LIKELY to know Mr. O’Timer is using licorice for his colds?
A. Dentist
B. Podiatrist
C. Cardiologist

10. Which of the following patients would be at greatest risk if they accidentally took Asian ginseng instead of American ginseng?
A. A 23-year-old female taking fluvoxamine for obsessive compulsive disorder
B. A 40-year-old female taking ondansetron for chemotherapy-induced nausea
C. A 67-year-old male taking clopidogrel after a myocardial infarction

Pharmacy Technician Post Test (for viewing only)

Pharmacy Technician Post-test

After completing this continuing education activity, pharmacy technicians will be able to
• List herbal products associated with liver, kidney and heart damage
• Recognize the potential for herbal products to be unsafe
• Describe certificates of analysis and how to retrieve them from manufacturers

1. Which of the following agencies review and inspect herbal products before coming to market?
A. United States Food and Drug Administration
B. National Center for Complementary and Alternative Medicine
C. International Association of Traditional Chinese Medicine

2. John Goodman, a frequent customer at your pharmacy, comes to the counter to pick up his monthly medications. He asks, “Would it be a bother to have you check out the rest of my items here as well?” Always one to help a customer, you tell him, “Of course, that’s fine!” You notice he has a botanic extract tincture that claims to help with heartburn. The ingredient list includes greater celandine (Chelidonium Majus). What organ dysfunction has been associated with this herb?
A. Liver injury
B. Kidney injury
C. Heart damage

3. A patient brings a brown bag of herbs and supplements for you to list on his profile. Which product may increase this patient’s risk for BOTH kidney and liver injury?
A. Pennyroyal essential oils
B. Germander weight loss tea
C. Impila fertility boost capsules

4. Mr. Goodman returns to your pharmacy. He explains he has been trying to live a healthier lifestyle, but has been feeling exceptionally tired after taking his as-needed alprazolam. Mr. Goodman goes on to tell you he’s added a new herbal supplement to his daily routine. You refer the patient to the pharmacist because you know and interaction between alprazolam and ______ could be causing the excessive drowsiness.
A. Echinacea
B. Garlic
C. Ginger

5. A customer at your pharmacy asks you for help in the herbal supplement aisle. She wants to take echinacea to boost her immune system, but she’d like more information about the manufacturer’s quality testing. You call the manufacturer for a certificate of analysis (CoA) only to be told they do not release them. Which of the following is most appropriate to tell this customer?
A. All herbal manufacturers are held to the same standards, so this brand is safe to use
B. This company likely has no quality assurance process; we should look for a better brand
C. This means the company uses an in-house laboratory for testing, so it is trustworthy

6. Your pharmacy is now selling a new herbal product. Curious about the contents, you decide to search for a certificate of analysis. On the bottle, you are looking for what three pieces of information?
A. product name, lot number, and expiration date
B. product name, manufacturer, and country of production
C. manufacturer, lot number, and date of production

8. Mrs. Jin is a longtime customer of your pharmacy who is on warfarin therapy for her atrial fibrillation. You ask to update her medication list in the system, including prescription, over-the-counter, and herbal supplements. Which of the following herbals would prompt you to refer Mrs. Jin to the pharmacist for counseling?
A. Chamomile
B. Kava kava
C. American ginseng

9. “These kids nowadays takin’ that codeine, and that awful dextromethorphan!” exclaimed Mr. O’Timer, “When I was a kid, and even now, all I ever took was licorice. My mom, bless her soul, would never let any poison enter MY body. To this day that’s all I use when I get a cold.” Trying to move him along before he inevitably tries to talk to you about politics, you stop as he mentions his busy day full of specialist appointments. Which specialist would be MOST LIKELY toned to know Mr. O’Timer is using licorice for his colds?
A. Dentist
B. Podiatrist
C. Cardiologist

Patient Safety: The Risk of Treatment: Antibiotic-Induced Adverse Events

After completing this application-based continuing education activity, pharmacists will be able to

· Describe mechanisms of action that cause antibiotic induced adverse effects

· Analyze risks and sequelae to determine adverse event or causative medication

· Recommend appropriate treatment for antibiotic induced adverse effect

· Discuss counseling points for outpatient antibiotic use

After completing this application-based continuing education activity, pharmacy technicians will be able to

· List adverse effects induced by antibiotics

·Recognize patients at risk of adverse effects

· Recall medications used to treat adverse effects

· Identify when to refer patient to pharmacist for recommendation or referral

When a patient is diagnosed with an infection, an antibiotic is usually the first line of treatment to cure the ailment. Antibiotics are effective treatments when patients have validated infections. Most often, treatment with antibiotics is benign. Typically, it does not pose a risk to patients, but antibiotics are associated with several risks to consider before initiating treatment. Risks of antibiotic use range from mild adverse effects of gastrointestinal upset and mild rash to life-threatening allergy development, toxic megacolon, and death. Recognizing and understanding the risks associated with antibiotic use is crucial in preventing severe patient complications.

Content

INTRODUCTION

An injury or response that results in any harm to a patient after medication administration is an adverse drug reaction (ADR). Every medication can potentially cause ADRs, but antibiotics are notorious for causing several individual and class-wide type reactions. A 2017 study (N = 1488) showed that 20% of all inpatients who receive antibiotics will develop an ADR within 24 hours of therapy. That risk increases by 3% every ten days of therapy.¹ Education and recognition of ADRs from antibiotics are essential components in the campaign against antibiotic resistance. The Centers for Disease Control and Prevention (CDC) developed the Core Elements of Antibiotic Stewardship to optimize antibiotic use by decreasing unnecessary antibiotic prescribing and helping fight antibiotic resistance in different practice settings. One Core Element is education directed at prescribers, nurses, pharmacists, and patients about the adverse reactions associated with antibiotic use.²

Antibiotic Resistance

One of the most noxious antibiotic-induced ADRs is the development of antibiotic resistance. Antibiotic resistance is a global health threat to the world population and affects food security.³ Antibiotic resistance develops when a bacteria is no longer susceptible to a previously effective antibiotic, which can stem from unnecessary antibiotic use.¹ A 2011 study that surveyed American acute care hospitals found that almost half of all inpatients will receive at least one day of antibiotic therapy.⁴ A separate U.S. study found that one-third of all antibiotic treatment days are inappropriate.⁵

Antibiotic resistance kills at least 1.27 million people worldwide every year.⁶ The United States (U.S.) has reported more than 2.8 million antimicrobial-resistance infections yearly, with 35,000 deaths.⁷ Antimicrobial resistance can affect anyone at any age, at all different types of healthcare facilities, and in veterinary and agricultural industries.⁶ Antibiotic resistance prevents patients from using first or second-line therapy for indicated infections, making patients more susceptible to severe ADRs.

Antibiotic Allergies

Allergic reactions reportedly account for 20% of adverse drug events and are seen in about 8% of the population.⁸ Antibiotics are the most common medication reported as an allergy.⁹ Elderly and female patients are more likely to report antibiotic allergies.^9,10 Typically, antibiotic allergic reactions present as mild rash and hives but approximately 3% of the population’s health records documented past anaphylaxis.¹¹

In the 1960s, Robert Coombs and Philip Gell established a classification system for hypersensitivity reactions. Coombs is most notable for developing the Coombs test that detects anti-Rh antibodies on red blood cells in 1945.¹² Their classification system has four presentations of hypersensitivity reactions involving different immune mediators that develop into various manifestations. Table 1 summarizes the Coombs classification.

Table 1 - Classification of Allergic Reactions^13-15
Type	Description	Mechanism	Timing	Clinical features
I	IgE-mediated, immediate-type hypersensitivity	IgE serves to protect and eliminate parasitic infections. IgE antibodies form after exposure to allergens, such as food, drugs, or other environmental elements. Re-exposure triggers an immediate hypersensitivity reaction.	Minutes to hours after exposure	· Anaphylaxis · Angioedema · Bronchospasm · Hives · Hypotension · Asthma · Allergic rhinitis
II	Antibody-dependent cytotoxicity	The drug binds to the surface of the cell. Antibodies then bind to the cell surface and are targeted for clearance by macrophages. Usually involves IgG or IgM	Appear 5-8 days after exposure but can take longer	· Hemolytic anemia · Thrombocytopenia · Neutropenia
III	Immune complex disease	Soluble drug in bloodstream forms a complex with IgG or IgM. The immune complexes can activate complement and then deposits in various tissue like small blood vessels, joints, and renal glomeruli	One or more weeks to develop after drug exposure	· Serum sickness · Arthralgias · Acute glomerulonephritis · Vasculitis
IV	Cell-mediated hypersensitivity	Stimulation of T cells	At least 48-72 hours, but can take days to weeks following exposure	· Stevens-Johnson syndrome/ toxic epidermal necrolysis (SJS/TEN) · Drug rash with eosinophilia and systemic symptoms (DRESS) · Contact dermatitis

Antibiotic allergy reporting is essential to prevent patients from severe adverse effects, but it also comes with a risk. Prescribers overuse and overprescribe antibiotics. Overprescribing of antibiotics is associated with a higher incidence of new antibiotic allergies.⁹ In countries with low antibiotic usage, antibiotic allergies are less prevalent.⁹ Antibiotic overprescribing is especially notorious at urgent care facilities. A study showed that in patients presenting to urgent care for upper respiratory infections, healthcare providers prescribed antibiotics approximately twice as much as in emergency departments and nearly three times as much in primary care.¹⁶ This is concerning; nationwide, there are more than 10,000 urgent care facilities, and that number is growing.¹⁶

Inaccurate allergy documentation is another concern with antibiotic allergy reporting. Five percent to 15% of patients have documented penicillin allergies; however up to 90% of those patients can safely receive a penicillin antibiotic.^17,18 Antibiotic allergies prevent patients from receiving first-line therapy, which can increase health care costs, and increase the risk of treatment failures and adverse events.¹⁷ A study from 2003 showed that patients labeled with a penicillin allergy had a 63% greater cost for antibiotics than patients without a penicillin allergy.¹⁹

PAUSE AND PONDER: What are some individual antibiotics that make up penicillins and cephalosporins?

The best treatment for allergies is prevention. Before initiating any new antibiotic, the prescriber should obtain an allergy history. Pharmacists must review patients' profiles for allergies to beta-lactams and consider cross-reactivity. There is about a 2% risk of cross-sensitivity between penicillins and cephalosporins.¹⁷ Treatment for allergies depends on the type of reaction. Type I reactions are usually a medical emergency, and patients need immediate care. Antibiotic rechallenge is appropriate for patients with mild reactions like gastrointestinal distress or mild itching or rashes but should not occur for any patient who develops a severe reaction, like anaphylaxis, Stevens-Johnson syndrome, toxic epidermal necrolysis, or hemolytic anemia.¹⁰ Reactions that occur need documentation with sufficient detail, including medication used and time to reaction.¹⁷

Antibiotic-Associated Diarrhea

A frequent adverse event associated with antibiotic use is diarrhea, defined as three or more loose stools in 24 hours.^20-22 Antibiotic-associated diarrhea reportedly occurs in 5% to 30% of patients while receiving or up to two months after receiving treatment.²³ Antibiotic-associated diarrhea’s clinical presentation can range from mild diarrhea to pseudomembranous colitis.^23,24 Essentially all antibiotics can cause diarrhea, especially those that cover anaerobic microorganisms (organisms that grow without oxygen) like amoxicillin/clavulante, cephalosporins, and clindamycin.^21-23

Antibiotic-associated diarrhea can occur from multiple mechanisms. First, antibiotics disrupt normal microflora, allowinge overgrowth of microorganisms known to cause diarrhea.²³ Clostridium difficile (C. diff), which will be discussed later, is the most common of those pathogens. Other pathogens are Salmonella, C. perfringens type A, Staphylococcus aureus, and Candida albicans.^20,24 Antibiotics can directly affect the intestinal mucosa, independent of any antibiotic activity. For example, erythromycin stimulates a receptor that increases contractions in the stomach and small intestines, and clavulanate can activate small bowel motility.^20,24 Last, antibiotics can decrease normal fecal flora that breakdown carbohydrates and bile acids in the colon. The increase of carbohydrates and bile acid causes an influx of water into the colon, causing osmotic diarrhea.^20,24

Treatment of antibiotic-associated diarrhea depends on its severity. Mild to moderate disease treatment should focus on rehydration, discontinuation of the provoking antibiotic, or changing to a lower-risk antibiotic like quinolones, sulfamethoxazole/trimethoprim, or aminoglycosides, if appropriate.^22,23 Clinicians should order C. diff testing in patients with severe or persistent disease or any microbes mentioned above.²³

Probiotics are an alternative method to decrease antibiotic-associated diarrhea, but mixed evidence surrounds their use. A 2021 meta-analysis reviewed 82 randomized controlled trials and found a statistically significant association between probiotic administration and the reduction of antibiotic-associated diarrhea.²⁵ The results are difficult to translate to a specific recommendation as the meta-analysis included many randomized controlled trials that did not document the exact probiotics used. In addition, the study excluded antibiotics that are more likely to cause diarrhea and specific subsets of patients like geriatrics.²⁵ Probiotic use is low risk for most patients, but immunocompromised patients should use caution when considering therapy.^26,27Probiotics are associated with rare secondary bacterial and fungal infections, which can be more prevalent in immunocompromised patients.^28-30 The most ideal way to prevent antibiotic-associated diarrhea is to limit antibiotic use.²

C. diff is a spore-forming bacteria that produces two separate exotoxins, A and B, that cause mucosal damage and inflammation.^22,23 Patients with C. diff infection (CDI) account for 10% to 25% of antibiotic-associated diarrhea cases, but CDI causes the majority of pseudomembranous colitis associated with antibiotic therapy.^23,24 Patients with CDI typically present with fever, lower abdominal pain, and cramping. CDI stool usually contains visible mucous and is foul-smelling.²² Significant risk factors include age older than 65, hospitalization, proton pump inhibitor use, and previous diagnosis of CDI.^22,24 Patients older than 60 have a much greater risk of developing CDI than patients aged 10 to 20 years.^24,31 Prescribers should consider C. diff testing after a patient has three or more unformed new or unexplained stools in 24 hours.¹²

Multiple diagnostic criteria confirm CDI. Lab results from CDI patients show elevated white blood cell count, decreased albumin, and fecal leukocytes.²⁴ Imaging with a CT scan can show inflammation and thickening of the colon, but it is not specific to CDI.²⁴ The Gold Standard testing for CDI is to test for toxins A and B with polymerase chain reaction (PCR) tests, but patients need to have unformed stool (bowel movement that is watery or soft) for this test. Patients with solid-formed stools do not have diarrhea and therefore do not have CDI, so testing is not warranted. Enzyme immunoassay (EIA) is another option that produces results much faster than the PCR test but has much lower sensitivity.^22,32

Providers should start treatment for C. diff after a positive test or before positive testing if a strong clinical suspicion exists.^24,32 Clinical guidelines do not recommend routine testing of C. diff in asymptomatic patients as C. diff colonization frequently occurs, especially in hospitalized patients and residents of long-term care facilities.³² Severity of disease, initial or recurrent occurrence, and other risk factors determine treatment. Disease severity can be non-severe, severe, or fulminant. In severe illness, the patient will have leukocytosis with a white blood cell count (WBC) of at least 15,000 cells/mL and a serum creatinine (Scr) level higher than 1.5 mg/dL. In non-severe disease, WBC and Scr levels are less than that of severe. Fulminant severity presents with hypotension or shock, ileus (an obstruction of the intestines), or megacolon (abnormal widening of the colon that is not caused by an obstruction).¹² Vancomycin and metronidazole have been the mainstay of treatment for more than 30 years until the development of newer medications. Fidaxomicin and bezlotuxumab are newer agents recently added to the Infectious Disease Society of America (IDSA) guidelines for CDI treatment.³³ Refer to 2021 IDSA guidelines for specific treatment recommendations.

Antibiotic-Induced Kidney Injury

Medications cause an estimated 20% to 40% of cases of acute kidney injury, with that estimation reaching almost 60% in the elderly population.^34,35 Antibiotics are a well-known cause of medication-induced renal dysfunction. Antimicrobials cause kidney dysfunction through tubular injury, severe tubular necrosis with cellular death, intratubular obstruction from crystal formation, and other mechanisms.³⁴ The direct cause is increased drug concentration, decreased excretion, and genetic differences predisposing some individuals to increased cell death or mitochondrial injury after exposure to certain antibiotics. In addition, patients with underlying kidney disease, acid-base disorders, and dehydration are at a greater risk of crystal formation with antibiotics that are insoluble in urine.^34,36 Most classes of antibiotics have varying degrees of risk for the development of renal dysfunction, but it is most commonly associated with aminoglycosides, beta-lactams, and vancomycin.^34,37

Renal dysfunction will develop in 10% to 25% of patients on aminoglycosides.^34,38 Symptoms of renal dysfunction develop five to seven days after initiation of therapy and will take up to 20 days for complete recovery after discontinuation of the aminoglycoside.^34,38 The risk for AKI increases in patients with longer therapy durations, exposure to concomitant nephrotoxins, and other comorbidities like chronic kidney disease.³⁸ Patients on aminoglycosides most commonly develop renal toxicity in the proximal tubule. Gentamicin has the highest potential to cause nephrotoxicity, followed by tobramycin and amikacin. Clinical practice has moved away from using neomycin systemically as it has an increased risk of causing nephrotoxicity, neurotoxicity, and ototoxicity.³⁴

Beta-lactams have a high risk of causing renal dysfunction, with carbapenems causing more renal toxicity than penicillins or cephalosporins.³⁴ Beta-lactams cause a wide range of renal toxicity, including acute glomerulonephritis, acute tubular necrosis, and acute interstitial nephritis.^34,39 Prolonged infusions of beta-lactams possess a similar risk of AKI compared to intermittent infusions.³⁹

Vancomycin’s incidence of nephrotoxicity is between 5% and 43%.^38,37,40 Vancomycin nephrotoxicity was initially associated with manufacturing impurities, but new manufacturing methods have eliminated this cause.^41-43 Onset occurs four to eight days after initiation of vancomycin and improves after discontinuation.^34,43 The overall pathophysiology of vancomycin-induced AKI is poorly understood as several mechanisms most likely contribute. Most patients who develop AKI on vancomycin do not undergo renal biopsies, and it is commonly prescribed with other nephrotoxic agents, which hinders a conclusive diagnosis.^34,38,43 Patients with pre-existing kidney disease, severe illness, a combination of nephrotoxic agents, obesity, and daily cumulative doses greater than four grams are at a higher risk of AKI.^34,41,44 Adjusting the vancomycin dose based on weight, levels, and renal function can help decrease the risk of kidney injury.³⁴ Pharmacists monitor vancomycin levels as trough and peaks which are low and high measurements of the actual medication in the patient.

Evidence of the risk of nephrotoxicity from the combination of vancomycin and piperacillin/tazobactam (VPT) has been conflicting. Previous evidence has shown VPT to carry a two to three-fold higher risk than vancomycin alone, but this is unclear due to piperacillin/tazobactam being a pseudo-nephrotoxin.^42,45 Prescribing information states that piperacillin/tazobactam can increase serum creatinine causing a pseudo-nephrotoxicity.⁴⁶ Most studies that reported increased risk of nephrotoxicity used increased creatinine as an indicator of acute kidney injury (AKI). ^45,47 A 2022 study looked at levels of cystatin C (a biomarker used to test kidney function) and found no significant change in its value for patients on VPT. Further, it also showed VPT combination did not lead to higher rates of dialysis or death.⁴⁸ Most recently in 2023, Chen et al. looked retrospectively at 35,644 patients receiving either VPT, vancomycin plus meropenem, or vancomycin plus cefepime. This study found that the combination of VPT has a greater risk of AKI, dialysis, and mortality in patients receiving treatment for greater than 48 hours.⁴⁹ At this time, available research on the VPT combination’s nephrotoxicity is conflicting. Clinicians should exercise caution when using VPT and consider other therapies in patients at high risk of renal dysfunction, especially if the combination will continue for longer durations.

Overall, antibiotics pose a significant risk to renal function, so the clinical team must assess risk factors of age and co-morbid conditions before initiating therapy.³⁴ A few ways to prevent the development of AKI are^34,38

dosages adjusted based on creatinine clearance and glomerular filtration rate (GFR)
changing the dose based on trough or random levels
adequate hydration, especially when using agents that form crystals in the urine
avoiding concomitant nephrotoxins (i.e., NSAIDs, contrast, etc.) and
regular monitoring of kidney function for long-term antibiotic use or when a patient has known risk factors for developing kidney dysfunction.

Clinicians must always practice good antimicrobial stewardship by prescribing shorter therapy courses to lower nephrotoxic agent exposure to the kidneys.³⁴

Sulfamethoxazole/Trimethoprim-Induced Hyperkalemia

The early 1980s through 1990s saw a significant rise worldwide of the human immunodeficiency virus (HIV) which also coincided with the first reported cases of hyperkalemia (high potassium levels) from sulfamethoxazole/trimethoprim (SMX/TMP). The CDC published a report in Morbidity and Mortality Weekly Report (MMWR) in June of 1981 describing the incidence of Pneumocystis carinii pneumonia (PCP; now known as Pneumocystis jirovecii), in five previously healthy young men.⁵⁰This CDC report documents the first known cases of HIV. Before the discovery of HIV, P. jirovecii was a disease associated with malnourished and immunocompromised patients. Premature and malnourished infants often contracted P. jirovecii during World War II, and patients with hematologic malignancies in later years.⁵¹ Dr. Walter Hughes, known for his research with P. jirovecii, first recommended SMX/TMP for prophylaxis in 1977 and then for treatment in 1989.^52-54 Emerging cases of hyperkalemia associated with SMX/TMP usage increased significantly at the start of the HIV epidemic as P. jirovecii treatment requires high doses and HIV patients are prone to the development of hyperkalemia.^55,56

SMX/TMP causes hyperkalemia because trimethoprim is structurally similar to the potassium-sparing diuretics amiloride and triamterene.^55,57 Trimethoprim blocks channels that excrete potassium into the urine, causing a potential 40% reduction of urinary potassium excretion.^58,59 Inhibition of urinary potassium excretion also decreases potassium in the urine.^55,58 Hyperkalemia will subside after discontinuation of trimethoprim.⁵⁸

Although SMX/TMP-induced hyperkalemia is low risk for most outpatients, it is essential to recognize risk factors and drug interactions because hyperkalemia is a medical emergency if untreated.⁶⁰Trimethoprim is excreted in the kidneys and will accumulate during acute and chronic kidney disease, which can increase the risk of hyperkalemia.⁶¹ Chronic kidney disease increases potassium levels, making it the most critical factor to consider when assessing risk for hyperkalemia.^57,62 Age greater than 65 and dose of greater than 20 mg/kg of trimethoprim for longer than a week also increases risk.^57,58

Risk assessment should include a review of any disease states or concomitant medications that could cause hyperkalemia (see Table 2). Studies have examined spironolactone’s effect when taken concurrently with SMX/TMP. A 2011 Canadian study examined patients receiving spironolactone and SMX/TMP prescriptions over 18 years. The study found that elderly patients treated with both medications had a 12-fold increased risk of hospital admission.⁶³ A 2015 Canadian study over 17 years looked at 206,319 patients to find an association between sudden death for patients taking spironolactone and antibiotics. Patients taking SMX/TMP were twice as likely to suffer from sudden death when compared to amoxicillin.⁵⁹

Table 2. Alternate Causes of Increased Risk of Hyperkalemia ^57,60,62
Disease States	Medications
Renal insufficiency	NSAIDs
AIDS patients	ACE/ARBs
Diabetes Mellitus	Direct Renin Inhibitors
Congestive Heart Failure	Beta-blockers
Metabolic Acidosis	Heparin
Congenital Adrenal Hyperplasia	Digoxin
Hypoaldosteronisim & Pseudohypoaldosteronism	Cyclosporine and tacrolimus
	Pentamidine
	Potassium-sparing Diuretics

Prevention of hyperkalemia from SMX/TMP should include decreasing the dose in patients with impaired renal function. SMX/TMP is contraindicated in patients with severe hepatic damage and severe renal disease if the patient does not have monitoring of renal function and electrolytes.^57,61 If hyperkalemia develops, prescribers should discontinue SMX/TMP and treat hyperkalemia following guideline recommendations.⁵⁸

Daptomycin-Induced Eosinophilic Pneumonia

The FDA approved daptomycin, a lipopeptide antibiotic, in 2003. Providers use it to treat complicated infections due to methicillin-resistant staph and vancomycin-resistant enterococci. Daptomycin has been an effective treatment alternative for patients who cannot use vancomycin due to intolerance or drug resistance.⁶⁴Daptomycin’s approved labeling lists eosinophilic pneumonia and myopathies as severe adverse events.

Eosinophilic pneumonia (EP) is a rare respiratory illness that can present with severe dyspnea, hypoxemia, and respiratory failure.^65-67 It is caused by eosinophil accumulation in the lungs as an acute or chronic process. Acute EP symptoms last less than one month and typically less than one week, while chronic presentation can take an average of five months before diagnosis.⁶⁸ Patients with acute EP present with a varying range in the presentation of symptoms. Some patients may have very mild symptoms and require no treatment, while some studies have shown much more severe manifestations, with more than 50% of patients requiring mechanical ventilation.^68,69 Patients typically present with a dry cough, chest pain, and fever.⁶⁸

EP develops when alveolar macrophages detect an antigen, which initiates an inflammatory process, eventually producing eosinophils and their subsequent migration to the lungs. Eosinophils are white blood cells that provide an essential defense against helminth parasites (worms). Reactions will develop in humans to presumably benign agents that incite a release of eosinophils.⁷⁰ In daptomycin-induced eosinophilic pneumonia, daptomycin is the inciting agent.

Accumulating eosinophils in the lungs or any tissue can cause significant damage.⁷¹ Eosinophils release toxic granule products like major basic protein and eosinophil peroxidase that can damage epithelial cells and nerves. They also release cytokines like transforming growth factors (TGF)-alpha and beta, which are associated with tissue remodeling and fibrosis.⁷¹ Alveolar macrophages, pulmonary endothelial cells, and airway smooth muscle cells also produce eotaxin, a potent chemoattractant of eosinophils.^65,72

EP’s primary causes are idiopathic.^68,72 Secondary reasons for EP are drugs or toxins and less commonly, parasitic or fungal infections.^68,72 The most frequently cited medications causing EP are daptomycin, mesalamine, sulfasalazine, and minocycline.⁶⁸ Daptomycin-induced EP was initially reported in 2007 after the drug’s approval.⁶⁵ Its pathophysiology is poorly understood. One proposed mechanism is that daptomycin may bind to human surfactant and accumulate in the alveolar space causing injury to the epithelium and subsequent eosinophil migration to the damaged tissue.^65,66,73 The second proposed mechanism is that daptomycin interacts with surfactant resulting in abnormal lipids. This contact induces an allergic reaction causing the release of several inflammatory markers and eventually shifts eosinophils into the respiratory tissue at least one week after the start of daptomycin therapy.^65,66,73

The Food and Drug Administration (FDA) has issued guidance for the diagnosis of daptomycin-induced EP with all of the following sequelae confirming a diagnosis of EP⁷⁴:

Concurrent exposure to daptomycin
Fever
Dyspnea with increasing oxygen demands requiring mechanical ventilation
New infiltrates on chest X-ray or CT
Bronchoalveolar lavage (BAL) with >25% eosinophils
Clinical improvement with daptomycin withdrawal

Risk factors have not been well established for daptomycin-induced EP. A 2016 study that reviewed 43 cases in systematic literature found that most patients were male (83%) and elderly (mean age of 65 years old). The same study found that dose or duration was not a risk factor.⁶⁶ A 2020 review looked specifically for risk with daptomycin and EP and found no association with age and sex. It also did not find an increased risk with high treatment doses. The study found, however, that around 30% of patients had diabetes or renal impairment.⁷⁵

Discontinuation of daptomycin should occur after a probable or definitive diagnosis of daptomycin-induced EP. Patients can experience respiratory failure from EP and may require oxygen supplementation or mechanical ventilation. Treatment can include a steroid taper starting with methylprednisolone and converting to prednisone over two to six weeks if appropriate.^65,66

Daptomycin-Induced Myopathy

Skeletal muscle effects are a rare but serious adverse event associated with daptomycin use. This adverse event presents as muscle weakness and pain, typically preceded by creatine phosphokinase (CPK) elevations.⁷⁶ In clinical trials, up to 6.7% of patients had elevated CPK levels, and daptomycin-associated myopathy occurred in 2% to 14% of patients.^77,78 During early clinical trials in the 1990s, researchers used 12-hour dosing intervals, but adverse skeletal muscle effects prohibited the trials from continuing.⁷⁹ Trials eventually restarted when once-daily dosing in dogs showed a lower incidence of CPK elevations.⁸⁰ Dosing frequency has a more direct relationship on skeletal muscle than peak plasma concentrations, making once daily daptomycin safer to administer than twice daily.⁸⁰

Skeletal muscle releases CPK from cells after various circumstances, including infections, intramuscular injections, and intense physical activity.⁸¹ The effect of daptomycin on skeletal muscle is thought to be from the drug's mechanism of action. Daptomycin works by breaking down the cell wall of bacteria, creating an opening, and causing a release of intracellular ions. In skeletal muscle, daptomycin also opens the cell wall and causes a release of intracellular CPK.⁸² Less frequent administration of daptomycin decreases the likelihood of CPK release as it allows skeletal muscle cells more time to repair.⁸²

Patients on concurrent statin therapy or who are obese (BMI >30) are at an increased risk of developing myopathies.⁷⁸ Daptomycin-induced myopathy is more likely to be seen with elevated daptomycin trough levels, but testing trough levels is expensive. Monitoring recommendations include weekly CPK levels to prevent skeletal muscle adverse events. More frequent monitoring should occur in patients with risk factors.^64,76 Holding statins when appropriate can help prevent adverse events during daptomycin administration.⁷⁸ Adverse skeletal muscle effects are reversible upon discontinuation of daptomycin.⁷⁶ Clinicians should discontinue daptomycin when CPK levels are more than 2000 U/L in asymptomatic patients or patients with CPK levels greater than 1000 U/L in symptomatic patients with no other reasoning for myopathies.⁶⁴

QT Prolongation

Medications are the most common cause of QT prolongation.⁸³ Medications can block specific outward potassium channels (IKr channels) in the heart, leading to QT prolongation. The slowing of outward potassium increases the plateau phase of the action potential, and electrocardiograms show a longer QT interval.⁸⁴ When potassium remains in the heart, the heart is kept at a positive charge that can prolong the repolarization phase. During this time, an ectopic beat generated by the heart can lead to Torsades de Pointe (TdP), a very dangerous and sometimes fatal arrhythmia.⁸⁵ Antibiotics like fluoroquinolones (FQ) and macrolides block IKr channels and can cause QT prolongation, which can potentially cause harm in patients with risk factors.

Macrolides and FQs are the most widely prescribed drugs in the inpatient and outpatient setting.⁸³ Levofloxacin and erythromycin have been cited most frequently for prescriptions in critical care and outpatient settings that cause QT prolongation.^86,87 A 2003 study found that a single dose of FQ administered to healthy patients can significantly prolong the QT interval when compared to placebo. The study demonstrated that moxifloxacin caused the most notable change, followed by levofloxacin and ciprofloxacin.⁸⁸ Ciprofloxacin and levofloxacin have more case reports of TdP than other fluoroquinolones but have a lower risk of QT prolongation. Their widespread use plays a more significant role in the incidence of TdP than their actual risk of developing QT prolongation.⁸³

A study reviewed the FDA Adverse Event Reporting System for patients who developed TdP. One-half of reports included macrolide use with no other concurrent QT-prolonging medications.⁸⁹ Of all the reports, 53% involved erythromycin use, while clarithromycin and azithromycin were 36% and 11%, respectively; further, in all of the reports that included erythromycin, 49% used intravenous (IV) erythromycin.⁸⁹ Of note, IV erythromycin use accounts for much less than other dosage forms with ointment at 66.1% of all prescriptions in 2020, oral dosages at 29.8% and all other forms including IV at 4.1%.⁹⁰

PAUSE AND PONDER: What medications can indirectly affect QT?

The risk of QT prolongation with antibiotics is difficult to assess as several factors can influence risk. Potassium channel blockade is concentration dependent; anything that increases the medication’s concentration will increase risk of QT prolongation.⁸³ Examples are rapid intravenous administration and impaired clearance through inhibition of hepatic metabolism.^83,91 Another important risk factor to consider is female sex, especially elderly females.^83,84,91,92 Female patients have consistently developed prolonged QT at a rate much higher than males and are more commonly prescribed medications that prolong the QT interval than males.⁸⁷ Older patients are more at risk for QT prolongation but are also more likely to have structural heart disease, drug interactions, and decreased drug clearance.⁹³ Risk assessments for QT prolongation should consider structural heart disease, subclinical long QT syndrome or genetic abnormalities, electrolyte abnormalities like hypokalemia and hypomagnesium, and patients with a family history of sudden death.^83,91,92 Pharmacists need to review concurrent medications for drug interactions that cause direct QT prolongation and medications that can affect QT indirectly, like diuretics, which can lead to electrolyte abnormalities.⁹²

For inpatients, baseline and subsequent electrocardiogram monitoring is an option for patients at high risk for QT prolongation, but it is too expensive to perform on every patient.⁹² Counseling for outpatients should include warning signs of arrhythmias like palpitations and near-syncope or syncope and other conditions that can affect potassium levels, like gastroenteritis or the addition of a diuretic.⁹² A risk assessment for QT prolongation is imperative for every patient started on a fluoroquinolone or macrolide.

Tendinopathy with Fluoroquinolones

In 1995, the FDA warned about the possibility of tendon rupture with fluoroquinolones.⁹⁴ Since then, several studies have looked at the risk of tendinopathies with FQ and found that they are associated with a two to four times increased risk of acute tendinopathy and tendon rupture. The risk is highest in the first month after drug exposure.^94,95 The Achilles tendon is most commonly involved as it is a weight-bearing tendon and more susceptible to injury, but any can occur in any tendon.^95-97

The mechanism of action of tendinopathy from fluoroquinolones needs to be better understood and may be multifactorial. One proposed mechanism is that fluoroquinolones increase substances known to cause tendons’ breakdown. In a study, matrix metalloproteinase (MMPs) increased after exposure to ciprofloxacin. MMPs cause collagen breakdown, which makes up 70% of tendons.⁹⁸ Another proposed mechanism is chelation. A study looked at connective tissue of magnesium-deficient dogs and found that the tissue had a similar damaged appearance to tissue treated with FQs. The study hypothesized that because FQs chelate with cations like magnesium, its effect on joints is similar to magnesium deficiency.⁹⁹

Patients are at a higher risk of developing tendinopathies with FQs if they are older than 60 years, transplant recipients, or on concurrent corticosteroid therapy.⁹⁴ Prescribers should avoid concurrent use of steroids and FQ as the risk of tendon rupture increases by 14-fold.⁹⁴ Treatment recommendations are discontinuing the offending agent and using supportive therapy like analgesia and physical therapy.⁹⁵ Approximately 90% of patients recover without surgery in one month, but 10% develop long-term adverse effects like difficulty walking, decreased mobility, and pain.⁹⁶

Cefepime-Induced Neurotoxicity

Cefepime is a 4^th generation cephalosporin available since 1997.¹⁰⁰ The package insert for cefepime warns against neurotoxicity, but it is a potential adverse effect with all beta-lactam antibiotics.¹⁰¹ Beta-lactams cause neurotoxicity because they antagonize the gamma-aminobutyric acid (GABA) receptor to varying degrees.¹⁰² Beta-lactams all have an affinity for GABA receptors because they are all structurally similar to GABA.^103,104 Cephalosporins, including cefepime, competitively inhibit the GABA receptor by binding directly to the receptor.^105,106

Cefepime-induced neurotoxicity (CIN) typically presents as encephalopathy, somnolence, agitation, confusion, and disorientation, while aphasia and hallucinations are less common.^107-109 Patients occasionally will develop convulsions or non-convulsive status epilepticus.¹¹⁰

The most significant risk factor for CIN is renal dysfunction.^100,104,108 When a patient with poor renal function receives cefepime, a higher concentration of unbound medication stays within the cerebrospinal fluid, causing symptoms when it enters the central nervous system.¹⁰⁸ A study of 42 patients with CIN found that 93% of patients with neurotoxicity had abnormal renal function, and 76% of the studied patients had their cefepime dose adjusted appropriately.¹⁰² A study has shown that CIN occurred despite dose reductions and even in dosages of 500 mg daily in patients with ESRD.¹¹¹

In addition to renal dysfunction, several other risk factors for CIN need review. Overdose or use of excessive dosages puts patients at risk for CIN, and it is much more likely to be seen in patients without appropriate dose adjustments.^108,109 Drug monitoring sometimes includes measurement of the medication in the blood called a peak (highest) and trough (lowest) levels. A study has associated CIN with high trough levels. The study showed neurotoxicity did not occur at troughs of less than 7.7 mg/L, while it always manifested at troughs at or exceeding 38.1 mg/L. The study’s author has suggested a trough of 7.5mg/L as a potential target.¹¹² Patients 65 and older are at risk because of pharmacokinetic changes.^100,113 Although age is a significant risk factor, CIN will occur in 25% of patients younger than 65.¹⁰⁰ Last, patients with underlying brain diseases like cerebrovascular accident, Korsakoff’s syndrome, small-vessel disease, Alzheimer’s disease, benign brain tumor, malignancy, or previous seizures are at risk for CIN.^108,114

Prescribers should discontinue cefepime in patients who develop suspected CIN.^100,108 It typically takes two to three days to resolve symptoms.^100,108 Providers can initiate dialysis in patients experiencing severe symptoms as it can rapidly decrease the concentration of cefepime.¹¹⁴ Medications that stimulate the GABA receptor, like benzodiazepines or barbiturates, are more effective than phenytoin in patients who develop seizures.¹⁰⁴ Last, switching antibiotics can sometimes resolve symptoms, but symptom prolongation can occur with other beta-lactams like piperacillin and meropenem. Consider alternative antibiotic classes in appropriate patients.¹⁰⁸

Linezolid-Induced Thrombocytopenia

Linezolid belongs to a class of medications called oxazolidinones. The discovery and investigation of oxazolidinones occurred in the late 1980s, but development did not continue due to severe adverse events in animals.¹¹⁵ In the 1990s, scientists from the Pharmaca Corporation derived linezolid from the oxazolidinones class, and the FDA approved its use in April 2000 after clinical safety testing.¹¹⁶ Linezolid has a considerable advantage for treating severe gram-positive infections as it is available intravenous (IV) but also has 100% oral bioavailability.¹¹⁷ Another advantage of linezolid is it’s relatively safe to use, with only 0.4% of patients experiencing severe adverse effects in phase 3 trials.¹¹⁵ Several case reports of adults experiencing varying types of myelosuppression, like anemia or pancytopenia, emerged following linezolid’s clinical approval, but thrombocytopenia (low platelets) is the most prevalent.¹¹⁵

Linezolid-induced thrombocytopenia (TP) takes approximately seven to 14 days before onset.^115,118 Reports of TP differ depending on geographical location or definition used.^118-120 TP typically takes around 14 days to develop because the platelet has a seven to ten day life cycle.¹¹⁵ Although studies have proposed several mechanisms, a definitive cause has yet to be established.¹²⁰

Patients with the following risk factors need monitoring for the development of thrombocytopenia^{115,118,121,120}:

Prolonged treatment course greater than 14 days
Underlying disease with a predisposition to hematologic abnormalities
Renal dysfunction, CrCl less than 30 ml/min, and dialysis. Linezolid is not primarily cleared renally but metabolized into two compounds. These compounds are renally eliminated and can accumulate in patients with renal dysfunction and may play a role in the development of thrombocytopenia
Chronic liver failure
History of vancomycin use
Low baseline platelet level of less than 200
Low body weight–Linezolid dosing does not change for adults nor require renal or hepatic impairment adjustment. When body weight decreases and total mg/kg of linezolid increases, the risk of thrombocytopenia increases. A study found that daily mg/kg doses between 22-27 (body weight between 55-70 kg) had a 48% chance of developing thrombocytopenia versus 72% in dosages greater than 27 mg/kg (body weight less than or equal to 45kg).

Discontinuation of linezolid should occur for patients who develop thrombocytopenia or any myeloid cell abnormality while on therapy.¹¹⁵ Myelosuppression is reversible after discontinuation of linezolid. Patients actively receiving therapy should have weekly monitoring of complete blood count and renal function monitoring.¹²¹ Monitoring is essential in patients receiving treatment for longer than 14 days, have pre-existing myelosuppression, take concurrent medications that cause myelosuppression, or have received prior antibiotic therapy from a chronic infection.¹¹⁷

Reporting ADRs

Identifying ADRs as they occur is vital to comprehensive patient care, but reporting ADRs is equally essential. The FDA established MedWatch in 1993 as a tool for healthcare providers and consumers to voluntarily report ADRs. ADRs can be reported through MedWatch or directly to drug manufacturers, who then are required to report ADRs to the FDA. The FDA uses the reported ADRs to make up the Adverse Event Reporting System (AERS), a postmarketing surveillance database. The information entered into AERS helps identify trends that are useful in determining causes and preventing prospective events.^122,123

PAUSE AND PONDER: Why is it important to include so much information when reporting ADRs?

The FDA defines a serious Adverse Drug Event (ADE) as fatal, life-threatening, incites hospitalization or prolongation of existing admission, causes significant disability, or congenital disability or anomaly to the patient.¹²⁴ The FDA asks healthcare providers and manufacturers to report all serious ADEs. Healthcare providers, including pharmacists, should also report any non-serious unexpected ADEs. These reports are helpful, even if the reaction is not directly related to the drug, as the reports may help discover unidentified ADEs. Healthcare providers should submit as much information as possible that is relevant to the ADE.¹²² Table 3 includes essential information to include in ADE reporting.

Table 3. Key-Inclusions for High-Quality ADE Report¹²⁵

· Clear description of event or outcome, include time to onset of signs and symptoms;

· Suspected and concurrent medications details: dose, lot number, schedule, dates, duration (Include non-prescription medications, dietary supplements, and any recently discontinued medications);

· Patient characteristics, including demographics (e.g., age, sex, race), baseline medical condition prior to treatment, co-morbid conditions, medication allergies, relevant family history, other risk factors;

· Documentation of diagnosis, including methods of making diagnosis;

· Clinical course of event and outcome (e.g., death, hospitalization, treatment);

· Relevant objective information (e.g., laboratory data) at baseline, during therapy, and after therapy;

· Response to discontinuation of therapy and re-initiation if available;

· Any other relevant information.

Conclusion

This continuing education activity discusses only a fraction of commonly experienced adverse drug reactions associated with antibiotics. It is not an exhaustive list, but it provides valuable guidance for healthcare providers for antibiotics with established reactions and serves as a reminder to report any serious or atypical reactions that may occur while using new antibiotics.

Antibiotic-associated adverse drug reactions are a significant concern in healthcare. These reactions occur when antibiotics lead to unintended harmful effects, such as allergic reactions, organ damage, or antibiotic resistance. Inappropriate use or overuse of antibiotics increases risk of adverse reactions. Decreased renal and hepatic function, elderly patients, and drug interactions are common risks of developing ADRs in antibiotics. Recognizing risks and following recommended monitoring can help prevent ADRs from occurring. Anyone directly involved in direct patient care should report suspected ADRs and educate patients on the impact of these events to ensure the safe and effective use of antibiotics.

Pharmacist Post Test (for viewing only)

Title: Patient Safety: The Risk of Treatment: Antibiotic induced adverse events
Objectives
Pharmacists
• DESCRIBE mechanisms of action that can cause antibiotic induced adverse effects
• ANALYZE risks and sequelae to determine adverse event or causative medication
• RECOMMEND appropriate treatment for antibiotic induced adverse effect
• DISCUSS counseling points for outpatient antibiotic use

1. A patient recently filled penicillin for treatment of strep throat. She returns back to the pharmacy the following day with a prescription for a new antibiotic and an epi-pen. She describes having a sudden reaction of hives, shortness of breath and facial swelling after a dose of penicillin and having to go to the hospital for treatment. What type of reaction did the patient have?
A. Type I
B. Type II
C. Type III

2. What type of reaction is appropriate to consider re-challenging an antibiotic if a patient develops an allergy?
A. Steven Johnsons Syndrome
B. Mild Itching
C. Anaphylaxis

3. A 40-year-old female with history of kidney transplant on immunosuppressants was started on antibiotics for pneumonia. The patient is afebrile has developed mild to moderate diarrhea from antibiotics and the medical team is looking for recommendations. What is appropriate treatment for this patient?
A. Probiotics
B. Start treatment for C diff infection
C. Rehydration

4. Sara is an 80-year-old female who has recently been diagnosed with a UTI and started on sulfamethoxazole/trimethoprim. She also has heart failure, DVT and COPD and also uses spironolactone, apixiban and albuterol nebulizer. What comorbid condition and medication increase her risk of hyperkalemia from SMX/TMP?
A. Heart failure patient on spironolactone
B. DVT on apixiban
C. Asthma exacerbation on albuterol nebulizers

5. Paul is a 75-year-old male who was admitted to the hospital for septic arthritis and started on vancomycin. After three doses of vancomycin, Paul develops an allergic reaction and he is switched to daptomycin. Five days later, Paul starts coughing, develops a fever, and his oxygenation levels drop. The attending physician orders a BAL; it shows an increase of eosinophils. He is diagnosed with eosinophilic pneumonia from daptomycin. What is an appropriate treatment recommendation?
A. An alternative antibiotic to treat the pneumonia
B. Albuterol to increase oxygenation levels
C. Discontinuation of daptomycin and start steroids

6. At a community pharmacy, a patient asks what you recommend for pain medication for muscle aches. Upon further questioning, you find that the patient has been on outpatient infusions of daptomycin for a diabetic foot infection for a few weeks. The patient is obese and says he thinks the muscle aches must just be from getting old. What is this patient most likely experiencing?
A. Daptomycin induced myopathy
B. Diabetes induced neuropathy
C. Muscle aches from infection

7. What laboratory value increases when patients develop daptomycin-related myopathy?
A. Scr
B. CPK
C. Eosinophils

8. What medication causes an indirect risk for this patient to develop QT prolongation?
A. Furosemide
B. Acetaminophen
C. Amiodarone

9. You have phoned Cecelia’s provider and determined he wants to continue ciprofloxacin despite the risk of QT prolongation. What is appropriate to include when counseling?
A. Patient needs daily EKG monitoring while taking ciprofloxacin and can use her iWatch to do the monitoring
B. Any new diarrhea does not need to be reported to the provider as its expected with antibiotics
C. Patient should be aware of warning signs of arrhythmias like palpitations and near-syncope or syncope
.
10. What medication should be avoided concurrently with fluoroquinolones because it increases the risk of tendon rupture?
A. Magnesium
B. Ibuprofen
C. Prednisone
.
11. Why are beta-lactams associated with causing neurotoxicity?
A. They deplete the availability of GABA
B. They increase the production of GABA
C. They are structurally similar to GABA
.
12. Paul is a 41 YO male with a history of end stage renal disease admitted to the hospital for pneumonia. He is initially started on dose adjusted cefepime and vancomycin and starts to improve. Three days after initial therapy cultures come back growing pseudomonas sensitive to cefepime, ciprofloxacin, and piperacillin/tazobactam but he has altered mental status and is very somnolent. What is your recommendation for treatment?
A. Discontinue cefepime and switch to non-beta lactam antibiotic
B. Discontinue cefepime and switch to alternative beta-lactam antibiotic
C. Continue cefepime and discontinue vancomycin

13. Patti comes to your pharmacy with a prescription for a brand new antibiotic that has recently been approved for UTI. After discussing expected adverse effects, what is also important to include about adverse effects?
A. She should ignore any other adverse effects she experiences as they have not been reported so they could not possibly be from the new antibiotic
B. She should report any undocumented adverse effects to her prescriber or pharmacist as it can help discover unidentified adverse drug reactions
C. She should post about any new adverse effects on her social media because all drug companies use artificial intelligence to screen for new adverse effects

Pharmacy Technician Post Test (for viewing only)

Title: Patient Safety: The Risk of Treatment: Antibiotic induced adverse events
Objectives
Technicians
• LIST adverse effects induced by antibiotics #6
• RECOGNIZE patients at risk of adverse effects #3
• RECALL medications used to treat adverse effects #2
• IDENTIFY when to refer patient to pharmacist for recommendation or referral #2

1. What is the most common pathogen known to cause antibiotic-associated diarrhea?
A. Clostridium difficile
B. Staphylococcus aureus
C. Candida albicans
.
2. A patient comes to the pharmacy to drop off a new prescription for cephalexin. When reviewing the profile, you notice an allergy for amoxicillin. There is no information about what the reaction is to amoxicillin. What is the appropriate action?
A. Ignore the allergy and fill the prescription, the risk of cross-reactivity is low.
B. Instruct the patient to contact the prescriber for a different antibiotic
C. Alert the pharmacist and let them determine the appropriate actions
.
3. Which of the following conditions can be treated with fidaxomicin?
A. C difficile infection
B. Antibiotic allergies
C. Kidney dysfunction
.
4. Which antibiotic is more likely to cause kidney injury
A. Clindamycin
B. Metronidazole
C. Gentamicin
.
5. What electrolyte does sulfamethoxazole/trimethoprim increase?
A. Magnesium
B. Potassium
C. Sodium

6. What medication can be used to treat daptomycin-induced eosinophilic pneumonia?
A. Methylphenidate
B. Methylprednisolone
C. Methylnaltrexone
.
7. What patient is at increased risk for daptomycin induced myopathy?
A. BMI <18.5 B. BMI 18.5-30 C. BMI >30
.
8. Macrolides and quinolones cause a certain cardiac side effect. What is it?
A. Congestive heart failure
B. Endocarditis
C. QT prolongation
.
9. What tendon is most often associated with tendon rupture from fluoroquinolones?
A. Achilles Tendon
B. Quadriceps Tendon
C. Biceps Tendon
.
10. Which antibiotic has been associated with neurotoxicity as an adverse effect?
A. Clindamycin
B. Cefepime
C. Clarithromycin

11. What organ dysfunction makes patients more at risk for adverse drug reactions associated with cefepime?
A. Kidney
B. Liver
C. Heart
.
12. Which of the following increases patients’ risks for linezolid induced thrombocytopenia?
A. Short therapy course
B. Obesity
C. Low baseline platelets
.
13. A patient comes to the pharmacy stating that ever since he started taking a new antibiotic, sarecycline, he has lost his appetite and found it difficult to eat. The patient tried to research if the medication causes that reaction but could not find any information. What should you do?
A. Refer the patient to the pharmacist; this reaction may need to be reported as a potential adverse drug event to the drug manufacturer and FDA
B. Tell the patient to not worry as if he cannot find any information about it, this adverse effect is not related to the medication
C. Instruct the patient to not trust information from the Internet because in most cases, an unreliable source posted the information

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76. Bhavnani SM, Rubino CM, Ambrose PG, Drusano GL. Daptomycin exposure and the probability of elevations in the creatine phosphokinase level: Data from a randomized trial of patients with bacteremia and endocarditis. Clinical Infectious Diseases. 2010;50(12):1568-1574. doi:10.1086/652767
77. Fowler VG, Boucher HW, Corey GR, et al. Daptomycin versus standard therapy for bacteremia and endocarditis caused bystaphylococcus aureus. New England Journal of Medicine. 2006;355(7):653-665. doi:10.1056/nejmoa053783
78. Dare RK, Tewell C, Harris B, et al. Effect of Statin Coadministration on the Risk of Daptomycin-Associated Myopathy. Clin Infect Dis. 2018;67(9):1356-1363. doi:10.1093/cid/ciy287
79. Tally FP, DeBruin MF. Development of daptomycin for gram-positive infections. Journal of Antimicrobial Chemotherapy. 2000;46(4):523-526. doi:10.1093/jac/46.4.523
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81. Dvorchik BH, Brazier D, DeBruin MF, Arbeit RD. Daptomycin pharmacokinetics and safety following administration of escalating doses once daily to healthy subjects. Antimicrob Agents Chemother. 2003;47(4):1318-1323. doi:10.1128/AAC.47.4.1318-1323.2003
82. Odero RO, Cleveland KO, Gelfand MS. Rhabdomyolysis and acute renal failure associated with the co-administration of Daptomycin and an HMG-COA reductase inhibitor. Journal of Antimicrobial Chemotherapy. 2009;63(6):1299-1300. doi:10.1093/jac/dkp127
83. Abo-Salem E, Fowler JC, Attari M, et al. Antibiotic-induced cardiac arrhythmias. Cardiovascular Therapeutics. 2014;32(1):19-25. doi:10.1111/1755-5922.12054
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94. Alves C, Mendes D, Marques FB. Fluoroquinolones and the risk of tendon injury: a systematic review and meta-analysis. Eur J Clin Pharmacol. 2019;75(10):1431-1443. doi:10.1007/s00228-019-02713-1
95. Baggio D, Ananda-Rajah MR. Fluoroquinolone antibiotics and adverse events. Aust Prescr. 2021;44(5):161-164. doi:10.18773/austprescr.2021.035
96. Khaliq Y, Zhanel GG. Fluoroquinolone-associated tendinopathy: a critical review of the literature. Clin Infect Dis. 2003;36(11):1404-1410. doi:10.1086/375078
97. Wildermuth A, Holmes M. A preventable, life-altering case of fluoroquinolone-associated tendonitis. JAAPA. 2022;35(11):33-36. doi:10.1097/01.JAA.0000873776.37967.9b
98. Tsai WC, Hsu CC, Chen CP, et al. Ciprofloxacin up-regulates tendon cells to express matrix metalloproteinase-2 with degradation of type I collagen. J Orthop Res. 2011;29(1):67-73. doi:10.1002/jor.211962010;29(1):67-73. doi:10.1002/jor.21196
99. Shakibaei M, de Souza P, van Sickle D, Stahlmann R. Biochemical changes in Achilles tendon from juvenile dogs after treatment with ciprofloxacin or feeding a magnesium-deficient diet. Arch Toxicol. 2001;75(6):369-374. doi:10.1007/s002040100243
100. Maan G, Keitoku K, Kimura N, et al. Cefepime-induced neurotoxicity: systematic review. J Antimicrob Chemother. 2022;77(11):2908-2921. doi:10.1093/jac/dkac271
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103. Roger C, Louart B. Beta-Lactams Toxicity in the Intensive Care Unit: An Underestimated Collateral Damage?. Microorganisms. 2021;9(7):1505. Published 2021 Jul 14. doi:10.3390/microorganisms9071505
104. Chow KM, Hui AC, Szeto CC. Neurotoxicity induced by beta-lactam antibiotics: from bench to bedside. Eur J Clin Microbiol Infect Dis. 2005;24(10):649-653. doi:10.1007/s10096-005-0021-y
105. Amakhin DV, Soboleva EB, Zaitsev AV. Cephalosporin antibiotics are weak blockers of GABAa receptor-mediated synaptic transmission in rat brain slices. Biochem Biophys Res Commun. 2018;499(4):868-874. doi:10.1016/j.bbrc.2018.04.008
106. J10#. Sugimoto M, Uchida I, Mashimo T, et al. Evidence for the involvement of GABA(A) receptor blockade in convulsions induced by cephalosporins. Neuropharmacology. 2003;45(3):304-314. doi:10.1016/s0028-3908(03)00188-6
107. J7#. Triplett JD, Lawn ND, Chan J, Dunne JW. Cephalosporin-related neurotoxicity: Metabolic encephalopathy or non-convulsive status epilepticus?. J Clin Neurosci. 2019;67:163-166. doi:10.1016/j.jocn.2019.05.035
108. Deshayes S, Coquerel A, Verdon R. Neurological Adverse Effects Attributable to β-Lactam Antibiotics: A Literature Review. Drug Saf. 2017;40(12):1171-1198. doi:10.1007/s40264-017-0578-2
109. Fugate JE, Kalimullah EA, Hocker SE, Clark SL, Wijdicks EF, Rabinstein AA. Cefepime neurotoxicity in the intensive care unit: a cause of severe, underappreciated encephalopathy. Crit Care. 2013;17(6):R264. Published 2013 Nov 7. doi:10.1186/cc13094
110. Bhattacharyya S, Darby RR, Raibagkar P, Gonzalez Castro LN, Berkowitz AL. Antibiotic-associated encephalopathy [published correction appears in Neurology. 2016 May 31;86(22):2116]. Neurology. 2016;86(10):963-971. doi:10.1212/WNL.0000000000002455
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LAW: THE OPIOID CRISIS: CAN REDUCING HARM SUPPLEMENT REDUCING SUPPLY?

The drug overdose crisis continues to worsen even as prescribing of controlled substances continues a decade long trend of decreasing. It is apparent that different strategies besides discouraging prescribing are necessary to reduce fatalities. One method is harm reduction which has been shown to be effective in addressing public health epidemics. Harm reduction approaches for drug overdose include medical treatment of opioid use disorder and measures to increase the safety of injectable drug use and can be enriched by pharmacist participation. This continuing education activity will review harm reduction approaches and discuss their application and the legal restrictions that may impede their implementation.

Content

INTRODUCTION

“This downward trend (in life expectancy) could be reversed if we make progress in controlling the COVID-19 pandemic and opioid epidemic.”¹

--Robert H. Shmerling, MD, Senior Faculty Editor, Harvard Health Publishing

Data on life expectancy in the United States (U.S.) has been collected since 1900 and, with rare exceptions, has consistently increased.^1,2 Life expectancy in 1900 was 47 years, reached 68 years in 1950, and by 2019, had risen to 79 years.¹ However, in 2020 it fell to 77 and dropped again in 2021 to 76, the sharpest two-year decline in almost 100 years.^1,3

Many factors contributed to the decline in life expectancy in the U.S., which was not seen in other parts of the world. These include diseases of the heart and liver, but about two-thirds of the decline can be accounted for by increased rates of COVID-19, drug overdoses, and accidental deaths.^1,4 This reflects a continuation of disturbing trends in increases in what are termed “deaths of despair” (chronic pain, drug and alcohol dependency, and suicides).⁴

Harm reduction approaches have been shown to be effective in addressing public health epidemics including preventing death, injury, disease, overdose, and substance misuse.⁵ Harm reduction emphasizes direct engagement with people who use drugs to improve their physical, mental, and social well being, and prevent overdose and infectious disease transmission. It also simplifies accessing substance use disorder treatment and other health care services.⁵

Pharmacists have played an important role over the past few years in reducing the harm from COVID through vaccination, testing, and offering anti-viral drugs.⁵ Public health efforts to reduce tobacco consumption contributed significantly to the increase in life expectancy during the 1990s and 2000s, as fewer people died from complications related to smoking and nicotine.² Community pharmacists contributed to this successful effort by providing support to individuals trying to stop smoking.⁶ Can pharmacists also help reduce the harm associated with the record number of drug overdose deaths?

This continuing education activity will review some harm reduction strategies that may be useful in coping with the drug overdose epidemic and describes current legal and regulatory issues that may be barriers to more widespread application.

PAUSE AND PONDER: How can pharmacists reduce harm from opioids?

OPIOID CRISIS

Drug overdose deaths have become the number one cause of accidental deaths in the U.S., surpassing even motor vehicle mishaps.⁷ Deaths from drug overdose have risen dramatically, increasing from 16,849 in 1999 to a new record of 104,000 in the 12-month period ending February 2022.⁸ These numbers represented more than a 6-fold increase over this period. The overwhelming majority of drug overdose deaths are associated with an overdose of an opioid. In 2020, approximately three of four overdose deaths involved opioids,⁹compared with an opioid-related impact of 50% in 1999.¹⁰

The modern opioid crisis has occurred in three waves (so far). The first wave began in 1996 and was largely due to overdose from prescription opioids, fueled by what was perceived to be a widespread problem of undertreatment of chronic pain.¹¹ Health care providers began prescribing more opioid pain relievers and the increased supply and diversion to non-medical use created an opportunity for more overdoses.^11,12

This was addressed by clamping down on opioid prescribing. The overall national opioid dispensing rate significantly declined after 2012; by 2020, the dispensing rate had fallen to its lowest level in 15 years.⁶ Despite these efforts, overdose deaths from prescription opioids were higher in 2021 (16,706) than they were in 2012.¹³

Opioid overdose deathrates have continued to soar, suggesting that other factors have emerged and measures in addition to reducing supply are necessary to confront the epidemic.

The second wave began around 2010 as prescription opioids became harder to obtain and heroin’s price dropped; heroin became more attractive and popular.^12,14 The third and current wave started in 2013 and is associated with an increased supply of illicitly manufactured and trafficked synthetic opioids, especially fentanyl and its analogs.^12,14 (Evidence indicates a fourth wave is materializing characterized by polydrug abuse, typically the use of illegally manufactured opioids in combination with psychostimulants such as cocaine and methamphetamine.^12,15)

DECREASING SUPPLY

As noted, it was believed that an oversupply of prescription opioids was fueling the overdose crises. (Indeed, opioid prescriptions per capita increased 7.3% from 2007 to 2012 and 259 million prescriptions for opioid analgesics were written in 2012 alone, roughly one prescription for every adult in the U.S.¹⁶) Abatement efforts were geared towards reducing the supply and diversion of opioids. These “supply side” approaches include prescribing limits, prescription drug monitoring programs (PDMPs), and regulation of pain clinics.¹⁷

This approach corresponded with the development of an opioid prescribing guideline by the Centers for Disease Control and Prevention (CDC) in 2016, which provided recommendations for primary care clinicians prescribing opioids for chronic pain outside of active cancer treatment, palliative care, and end-of-life care.¹⁶ The guideline’s focus on when to initiate or continue opioids for chronic pain; assessing risk and addressing harms of opioid use; and opioid selection, dosage, duration, follow-up, and discontinuation is detailed in Table 1.

Table 1. Summary of Centers for Disease Control and Prevention Guideline

Clinicians should

Prescribe the lowest effective dosage when initiating opioid therapy
Use caution when prescribing opioids at any dosage
Carefully reassess benefits and risks when increasing dosage to 50 morphine milligram equivalents (MME)/day
Avoid increasing dosage to 90 MME/day

Many states codified these voluntary recommendations through statutes or regulations that imposed enforceable limitations on medical professionals’ ability to prescribe or dispense opioids for pain treatment.¹⁸ The number of states with such restrictions increased from ten in 2016 to 39 by the end of 2019. States differed in their limits. At the end of 2019, the most common duration limit was seven days, with a range of three to 31. Fourteen states imposed limits on the daily dosage of opioids that could be prescribed, ranging from 30 MME to 120 MME.¹⁸

Enforced application of the CDC guideline, which was meant to serve as a guide for primary care providers, led to fewer opioid prescriptions along with reduced dosages, opioid tapering, and discontinuation of treatment among patients prescribed long-term opioid therapy.¹⁹ These actions resulted in multiple adverse outcomes including poor pain control and mental health issues for some patients. It forced many patients with pain to seek illicit sources as an alternative source of relief and resulted in an accompanying increase in overdose deaths.¹⁹

The most significant illicit substance emerging as the primary driver of the current overdose is fentanyl. Although technically a prescription drug, fentanyl’s primary source in overdose situations derives from illicit manufacture and importation.²⁰

Fentanyl is a powerful mu-opioid receptor agonist that is 75–100 times more potent than morphine.²¹Fentanyl rose to prominence as an alternative to morphine as an analgesic and anesthetic for surgeries more than 50 years ago due to its rapid onset, short duration of action, high potency, and limited cardiovascular risks compared to morphine. The potential for fentanyl misuse was initially believed to be minimal but it has emerged as a dangerous recreational substance.²¹ Although the media commonly describes it as a recent phenomenon, fentanyl has been used as a contaminant in illicit drug supplies since at least 1979.²² Fentanyl and its analogs have become the predominant factor in drug overdose deaths, accounting for almost two-thirds of overdose fatalities in 2021.²²

Fentanyl is sold by itself and is also used as an adulterant in other products due to its high potency which permits dealers to traffic smaller quantities that retain the expected opioid effect.^20,22 It is much more profitable for dealers to cut a kilogram of fentanyl compared to a kilogram of heroin. The drug is also made into counterfeit pills that resemble legitimate prescription opioids.²⁰ Since there is no regulatory oversight nor quality control, the pills can contain lethal quantities of fentanyl.²⁰

The COVID-19 pandemic made matters worse. Social isolation, loss of economic opportunity, boredom, despair, disruption of normal routines, and political polarization increased distress. Simultaneously, it became more difficult to access treatments, resources, and emergency services that help people suffering from opioid use disorder (OUD).^19,23,24 Lockdowns and distancing efforts made it less likely that an individual who overdosed would be discovered and given rescue naloxone in time to prevent lasting injury or death.²⁴ The decreased access to interventions and treatment led some patients to seek remedies on their own.¹⁹

In addition, COVID-19 mobility restrictions made it more challenging to smuggle illegal drugs into the country and border restrictions made it harder to move bulkier drugs.²⁵ As a result, smugglers increased their reliance on fentanyl which, due to its potency, can be transported in small quantities and is easier to traffic by mail.^22,25 This helped increase fentanyl’s availability in areas of the U.S. that had not previously been as impacted by the drug.²⁵ Prior to the pandemic, fentanyl mainly affected urban areas in the eastern regions of the U.S. where it could be easily mixed with the powdered heroin popular there.²⁵ Mortality rates from synthetic opioids more than doubled every two years in 28 states between 1999 and 2016; in Washington, D.C., mortality from opioids more than tripled every year from 2013-2016.²⁶

HARM REDUCTION MEASURES

It is apparent that reducing supply has had limited success in reversing the upward trend in overdose deaths. Could another strategy be more successful? It is generally believed that harm and demand reduction strategies can contribute to stemming the opioid overdose crisis.^5,17,23Relevant harm reduction activities that can lessen the risk of adverse outcomes associated with drug misuse include medical treatment of OUD, provision of sterile syringes, overdose prevention sites, fentanyl testing, safe supply, overdose education, expanded availability of naloxone, and Good Samaritan laws.^5,17,23 However, harm reduction approaches are underutilized; the CDC estimates that two-thirds of drug overdose deaths in 2021 had at least one potential opportunity for intervention.⁹

Medication Assisted Treatment of Opioid Use Disorder

Substance use disorders (SUD) are chronic conditions associated with many biologic, environmental, and social conditions.²⁷ SUD frequently co-occurs with other mental illnesses including depression, anxiety, and post-traumatic stress disorder; half of people with mental illnesses will have an SUD at some point in their lives.²⁷

OUD is a persisting and often relapsing condition requiring long-term care that is adjusted to meet individual patients’ needs by allowing changes in treatment designed to address fluctuations in symptomology.^27,28 OUD requires medical and psychosocial therapy similar to the treatment of other chronic disorders.^27,28 Opioid withdrawal, although very unpleasant and uncomfortable, is rarely life-threatening and is characterized by autonomic hyperactivity, and signs and symptoms which include anxiety, insomnia, nausea, vomiting, diarrhea, cramping, back pain, hot and cold flashes, and lacrimation.^27,28 Treatment is generally directed at alleviating these signs and symptoms of withdrawal.^27,28

Currently, three medications in the U.S. are Food and Drug Administration (FDA)-approved for use in Medication Assisted Treatment (MAT) of OUD: methadone, buprenorphine, and naltrexone.²⁹ Medically supervised withdrawal or detoxification can both improve the patient’s health and facilitate participation in a rehabilitation program.³⁰ It can also help patients accept abstinence from opioids after the acute withdrawal phase has subsided.³⁰

Traditionally, medically supervised withdrawal was only offered as a hospital-based treatment of varying duration. Today, medically supervised withdrawal is most often provided in outpatient and residential treatment settings and is usually managed by tapering doses of an opioid agonist or partial agonist over a period of between one week to several months.^27,28 Slower reductions over longer periods of time generally lead to less illicit use during the medically supervised withdrawal. Longer duration of treatment allows restoration of social connections and is associated with better outcomes.^28,31

Studies have suggested that MAT reduces overdose mortality by 3- to 4-fold, reduces the incidence of HIV and hepatitis-C transmission by half, doubles adherence to HIV antiviral therapy, and reduces drug-related crime.^27,28 However, it is usually not sufficient to produce long-term recovery by itself and may also increase the risk of overdose due to a loss of tolerance following abstinence.³⁰

Medically supervised withdrawal can also involve the use of nonopioid medications on an off-label basis to help control symptoms. α2-adrenergic agonists such as clonidine (Catapres), tizanidine (Zanaflex), or lofexidine (Lucemyra) can decrease anxiety, piloerection (erection or bristling of hairs due to the involuntary contraction of small muscles at the base of hair follicles, often called goose bumps), and other signs and symptoms of autonomic overactivity.^27,28,30 Adjunct therapy with medications such as anti-anxiety drugs, analgesics, sleep aids, anti-emetics, and anti-diarrheal products can also decrease the predominant withdrawal symptoms and decrease discomfort.^27,28

Long-Acting Opioid Agonists: Methadone and Buprenorphine

Prescribing a long-acting oral opioid, such as methadone or buprenorphine, is the most effective approach to treating a patient who is experiencing withdrawal.³⁰ These treatments relieve symptoms. Gradually reducing the dose allows the patient to adjust to the absence of an opioid.

Oral methadone has the strongest evidence for effectiveness. Methadone has been used since 1964 when it was introduced as a medical response to the post-War heroin epidemic in New York City and its use has spread to many countries.^27,28,32 Methadone is a full opioid agonist and N-methyl-D-aspartate receptor antagonist producing dose-dependent analgesia and sedation, with a risk of respiratory depression in overdose. It has a long half-life relative to abused forms of opioids, averaging about 24 hours with a variable range of 12-50 hours.³¹ It is typically delivered under direct daily supervision, at least initially, and treatment usually begins with a low dose that is slowly escalated.^27,28

Methadone maintenance is used to relieve narcotic craving, suppress the abstinence syndrome, and block the euphoric effects associated with opioids. Treatment occurs for an indefinite period, since methadone maintenance is considered corrective rather than curative for addiction.³²

When methadone is discontinued, it can lead to withdrawal which may be protracted due to its long duration of action.^27,28 Consequently, methadone treatment is gradually reduced over several weeks or months. Methadone is primarily metabolized by CYP3A (along with CYP2D6 and CYP1A2) and inhibitors and inducers of these enzymes can affect therapy.^27,28

Although methadone is highly effective as an MAT, it has certain disadvantages related to being a full mu-receptor agonist.³³ First, it has the potential to produce or maintain opioid dependence creating a risk of abrupt withdrawal if a patient misses a scheduled dose. This can be discouraging to patients who are trying to detoxify. In addition, there is no ceiling (or leveling off of effect) to the level of respiratory depression or sedation produced by a full agonist, and this can lead to fatal overdose.³³

An alternative to methadone is buprenorphine which has a different pharmacologic profile. It is a partial agonist at mu-opioid receptors, an antagonist of kappa and delta opioid receptors, and an agonist at opioid-like receptor-1 (nociceptin).³⁴ Despite being a partial agonist, it reportedly produces analgesic efficacy comparable to that of full μ-opioid receptor agonists in moderate to severe post-operative pain and pain associated with cancer.³⁴ It shares the beneficial properties of methadone being orally active with a long functional half-life (20 to 73 hours) and produces similar improvement of opioid withdrawal while producing less respiratory depression and sedation.³⁰ Buprenorphine maintenance may also result in a gentler withdrawal phase and the possible option of alternate-day dosing, due to its long duration of action.³⁴ However, as a partial agonist, it can produce a competitive antagonism of a concurrently administered full opioid agonist. Buprenorphine should be initiated at least 12 to 18 hours after the last dose of opioids in patients who misuse shorter-acting drugs to avoid precipitating abrupt and more intense withdrawal.³⁰

Buprenorphine is also available as a combination with the opioid antagonist naloxone, which minimizes intravenous misuse.³¹ Due to the low oral bioavailability of naloxone, it produces little opioid antagonism when the combination is taken orally or sublingually. However, if the preparation is crushed and injected, naloxone will block the reinforcing effects of buprenorphine and may also precipitate opioid withdrawal in a dependent individual.³¹

Studies comparing buprenorphine and methadone have reported mixed results, some showing no difference in efficacy between the two therapies, some showing methadone to be superior, and others finding buprenorphine to be superior.³³

Opioid Antagonists

Opioid antagonists block the reinforcing effects of opioids and help maintain opioid abstinence in highly motivated patients.³⁰ Naltrexone is an orally active long-acting mu- and kappa- opioid receptor antagonist, with effects lasting 24 to 36 hours.^27,28,30 It is also available as an extended-release intramuscular injectable form with effects lasting one month.³⁰ Oral naltrexone is used to treat both OUD and alcohol use disorder.³⁶ However, oral naltrexone is not commonly prescribed for OUD because there is poor compliance and evidence suggests that it may not be more effective than placebo in treating OUD. Since naltrexone can precipitate withdrawal in opioid-dependent individuals, it is recommended that patients wait at least seven days after their last use of short-acting opioids and 10 to 14 days for long-acting opioids, before starting naltrexone.^27,28,30,36 This presents a challenge for patients. An FDA-approved Risk Evaluation and Mitigation Strategy (REMS) that includes a Medication Guide is required for the long acting injectable, but it may otherwise be prescribed and administered by any practitioner licensed to prescribe.³⁶

Pharmacists are familiar with the protype opioid antagonist, naloxone, which is also an important harm reduction measure. Naloxone is a short acting antagonist originally used by injection to reverse opioid-induced postoperative respiratory depression and later used to reverse potentially fatal respiratory depression in individuals who overdosed on opioids.³⁶ Earlier rescue drugs such as nalorphine and levallorphan were partial agonists and, unlike naloxone, produced some respiratory depression.³⁷

Naloxone’s onset of action in adults is less than two minutes when administered intravenously, and its apparent duration of action is on the order of 20 to 90 minutes; significantly, this is a shorter duration than that of many opioid agonists⁸⁸ so that in some cases, the antagonism may decay before the agonist has been fully eliminated, placing users at risk of delayed respiratory depression.³⁹ In other words, naloxone reverses the effect of the agonist drug but since naloxone wears off quickly, there can still be sufficient drug in the system to re-initiate the toxicity.

Pharmacists should note that medication treatments are also being developed and evaluated for other types of drug misuse, such as naltrexone plus buprenorphine for methamphetamine use disorder.²⁷

Regulatory Issues

In the early 1900s, opiate drugs could be easily obtained from pharmacies. Diacetylmorphine, synthesized in 1874, was not often prescribed before 1900, but favorable reports of its effects stimulated interest from the medical profession.⁴⁰ The German pharmaceutical company Bayer (yes, the aspirin people) started commercial production of the compound in 1898 and marketed it under the name, “Heroin.”⁴⁰

Heroin was considered to be a “wonder drug” and the medical profession enthusiastically received it. The interest in heroin was prompted by the high occurrence of tuberculosis and other respiratory diseases and the need to find an effective remedy for cough and to induce sleep. Heroin was also believed to combat morphine addiction, but the inaccuracy of this approach became apparent after a few years.⁴⁰

The drug quickly caught the attention of criminal elements and smugglers who recognized that its rewarding properties surpassed those of morphine, the then-dominant abused drug.⁴⁰ Heroin also had the advantage of being able to be delivered by sniffing without the complications associated with intravenous injection.⁴⁰ A new societal problem emerged.

The Harrison Act passed in 1914 brought about one of the first federal controls on opioids. The Act regulated “narcotics” (defined as opiates and cocaine) by imposing a special tax upon anyone who produced, imported, manufactured, sold, dispensed, distributed, or compounded these substances.⁴¹ It mandated special order forms and record keeping whenever narcotic drugs were sold and products could only be provided from packages bearing a government stamp.⁴²

Physicians interpreted regulatory terms such "legitimate medical purposes," "professional practice," and "prescribed in good faith” to mean that they could provide narcotics to ease the suffering of withdrawal in addicts who were regarded as having a disease.⁴² However, the Treasury Department interpreted the Harrison Act to mean that any prescription for an addict for the purpose of relieving the trauma of addiction was illegal, and the Courts supported this position.⁴² Consequently, the only source available for an addict to obtain narcotics was through illegal means and physicians who used opioids to treat addicts risked federal and/or state criminal prosecution.^42,43 A law intended to regulate commerce effectively led to criminalization of OUD treatment.

In 1972 the US Food and Drug Administration (FDA) approved methadone treatment for OUD and established methadone maintenance as a legitimate medical practice.^43,44 However, concern about methadone diversion and accidental overdose fatalities, combined with political pressure from government agencies and groups committed to drug-free treatments, led to the development of detailed and unprecedented FDA regulations.⁴³ The Narcotic Addict Treatment Act in 1974 created the first federal law governing methadone for OUD while state and local governments placed additional regulatory requirements on methadone.^44,45 Congress granted the Drug Enforcement Agency (DEA) additional oversight of methadone treatment programs. Both the DEA and existing treatment providers have resisted efforts to relax the FDA regulations.⁴³

Administration of opioids to treat opioid-use disorders can only be performed by licensed addiction-treatment programs (either office-based or inpatient treatments) or by physicians who have completed specific opioid drug training.³⁰ Medical providers (physicians or advance practice providers such as physician assistants or nurse practitioners) may not use their DEA registration to prescribe methadone for OUD, but they can prescribe methadone tablets as a treatment for chronic pain.⁴⁵

Federal law also requires an in-person medical evaluation prior to patient enrollment in an opioid treatment program (OTP).⁴⁵ Initially, patients receiving methadone must return to the clinic a minimum of six days per week for medication administration with appropriate supervision for at least the first 90 days of treatment.⁴⁵ Afterwards, they can qualify for additional take-home doses under certain conditions. After the first 90 days the take home supply may increase to two doses per week. After 180 days, they may receive three take home doses per week. By 270 days, they may qualify for six take home doses per week for the remainder of the first year. In the second year of continuous treatment, a patient may be given a maximum 2-week supply of take-home medication. In the third year, a patient may be given a maximum one-month supply of take-home medication, but must make monthly visits. States have the authority to further restrict administration and dispensing policies.^44.45

However, in response to the COVID-19 pandemic, some impediments to methadone treatment were relaxed. In March 2020, the Substance Abuse and Mental Health Services Administration (SAMHSA) issued guidance allowing states to request that patients who are on a stable methadone dose be permitted to receive 28 days of take-home medication, and for patients who are less stable to receive 14 days of take-home medication.²⁴

In contrast, buprenorphine can be prescribed by certified physicians, without the requirement for direct supervision of administration since diversion is associated with significantly less risk of fatal overdose than methadone.³¹

Patients being treated with MAT also encounter the restrictions of the Ryan Haight Act, named after a minor who overdosed on a controlled substance he obtained over the Internet with a prescription from a physician who did not conduct a proper medical examination. The law requires practitioners issuing a prescription for a controlled substances to first conduct an in-person medical evaluation.⁴⁶

During the COVID public health emergency, the DEA waived the requirement that patients receiving buprenorphine must have an in-person consultation with a prescriber and permitted the consultation to occur via telemedicine.²⁴

PAUSE AND PONDER: Should pharmacists be involved in facilitating access to OUD medications?

The Drug Addiction Treatment Act of 2000 (DATA) was enacted to permit physicians who meet certain qualifications to treat opioid dependence with FDA-approved C-III – C-V opioid medications, including buprenorphine, in treatment settings other than OTPs.⁴⁷ DATA restricted the outpatient treatment of OUD with buprenorphine to clinicians receiving an “X- [or DATA] waiver.”⁴⁸ To receive the waiver, clinicians were required to attend an eight hour training session and submit a Notice of Intent to SAMHSA; other eligible practitioners, including nurse practitioners and physician assistants, were required to obtain an additional 16 hours of training.^48,49 Pharmacists and X Prescriptions were required to have the prescribers’ X-number in addition to their DEA registration number and pharmacists were expected to verify a practitioner's certification, but there were no other requirements for pharmacists beyond those for other Schedule III medications, such as special credentials.

In 2023, the Mainstreaming Addiction Treatment Act (MAT Act) eliminated the need for a special waiver to treat patients with OUD.⁵⁰ Any practitioner with current DEA registration that includes Schedule III authority may prescribe buprenorphine for OUD. The MAT Act also removed other federal requirements associated with the waiver. However, pharmacists should be aware that state requirements may differ.⁴⁹

Naloxone has also transitioned, becoming a more readily available substance. The FDA approved naloxone in 1971 as a prescription-only medication for intravenous, intramuscular, and subcutaneous administration to reverse postoperative respiratory depression induced by opioid analgesics.^36,51 Overdose rescue was originally limited to emergency departments, but its use expanded to first responders and distribution by community groups to individuals with OUD or their family and acquaintances for emergency use.⁵² Reluctance to administer the drug with a needle led to improvised homemade intranasal naloxone delivery devices.⁵¹ FDA approval of a standardized, pre-assembled intranasal delivery form in 2015 significantly improved and simplified naloxone use.⁵³ Pharmacists in all states were also granted authority to dispense naloxone through collaborative agreements or blanket standing orders.⁵⁴The FDA approved naloxone for OTC distribution in 2023.⁵⁵

Safer Injection

Another harm reduction strategy is to make the experience of injecting opioids safer. Several different approaches may enhance the safety of injections.

Needle/Paraphernalia Exchange

Syringe services programs (SSPs) are community-based prevention programs which are thought to be a critical component of harm reduction interventions for injectable drug users.^56,57 SSPs provide access to and disposal of sterile syringes and injection equipment and may also include offering referrals to medication-assisted treatment, as well as vaccination, testing, and links to care and treatment for infectious diseases.⁵⁶ The majority of new hepatitis C virus infections are related to injection drug use and 10% of new HIV infections in the U.S. are attributed to injection drug use. Infections occur because needles, syringes, or other equipment used for injections may be contaminated with blood that can carry viruses. HIV can survive in a used syringe for up to 42 days, depending on temperature and other factors.⁵⁸ In addition, people under the influence of substances are more likely to engage in risky sexual behaviors which can increase the risk of transmitting an infection.^56,57

SSPs have the added benefit of protecting the public and first responders by facilitating the safe disposal of used needles and syringes. Many SSPs also provide “overdose prevention kits” containing naloxone.^56,58

Safe Injection Facilities

Safe injection facilities (SIF; AKA overdose prevention centers, supervised consumption services, supervised injection facilities, drug consumption rooms, or safe havens) provide a sanctioned, safe space where people can inject drugs obtained elsewhere in a controlled setting under the supervision of trained staff with a goal of preventing fatal overdoses.^59,60 Staff at the facility do not directly assist with injections or handle any drugs brought in by clients, but are present to provide sterile injection supplies, answer questions on safe injection practices and vein care, administer first aid if needed, and monitor for overdose. Participants can also receive health care and general medical advice, counseling, and referrals to health and social services, including drug treatment options.^59,60

SIFs have operated in Europe since the 1980s.⁵⁹ They generally target high-risk, socially marginalized injectable drug users who would otherwise inject in public spaces or shooting galleries. Reports generally show that SIFs have led to fewer risky injection behaviors and fewer overdose deaths among clients, increased enrollment in drug treatment services, and reduced the incidence of public nuisances associated with open injection.⁵⁹ Although SSPs reduce the risks associated with contaminated needles and syringes, they do not address the harm created by users’ fear of the criminal justice system and stigma.⁵⁹

In the U.S., states and some municipalities have the power to authorize SIFs under state law, However, they are still prohibited by the federal Controlled Substances Act.^59,81A Philadelphia non-profit planned to open consumption sites where individuals could inject controlled substances under supervision, but the Department of Justice (DOJ) sought to prevent it.⁶¹ The DOJ argued that a “consumption room” is intended to be a place where people consume drugs and would therefore be in violation of the CSA which prohibits any person from knowingly and intentionally maintaining a place for the purpose of illegal drug use. The District Court ruled that the CSA does not apply, but the decision was reversed on appeal. The Appellate Court ruled that the safehouse would violate the law because people will visit its facility with the purpose of using drugs. The law requiring CSA oversight of places where there is illegal drug use was originally passed to shut down crack houses. Despite the organization’s “admirable” motives and the need for “innovative solutions” to combat the opioid crisis, the court held that “courts are not arbiters of policy” and “local innovations may not break federal law.”⁶¹ The decision was appealed to the Supreme Court, but they rejected the request to hear the case; some issues are still pending.

In November 2021, New York City opened the first supervised injection site in the U.S., six weeks after the Supreme Court decision.⁶² In its first three months, approximately 800 people used the center more than 9500 times and it averted at least 150 overdoses. The site supplies syringes, alcohol wipes, straws for snorting, other paraphernalia, and oxygen and naloxone in case of an overdose.⁶² A few other cities and the state of Rhode Island have also established a pilot program for safe injection sites.⁶²

Despite the results in the Philadelphia court case, the DOJ has indicated a willingness to relax its opposition to safe sites, saying that it was evaluating them and discussing “appropriate guardrails.”⁶² Some members of Congress have expressed opposition to permitting sites to operate and a former DEA official has stated that “the goal has to be to stop doing drugs” and encourage treatment.⁶²

Safer Supply Prescribing

Another possible risk mitigation approach that could impact pharmacists is safer supply prescribing. This expanding movement in Canada allows prescribers at recognized sites to write prescriptions for government-funded, pharmaceutical-grade products, primarily opioids.^63,64 The most commonly offered products at the sites studied were injectable and tablet hydromorphone, and medical grade heroin.⁶³ Some clinics are supplying pharmaceutical-grade fentanyl to offset the unregulated street supply.⁶⁴ One site delivers medication to multiple clients quarantined in a motel.⁶³

Pharmacy models included hospital-based pharmacies and partnerships with a service site to either provide the site with medication or provide it directly to clients.⁶³ In some instances, users can select their own pharmacy. There are also machine-dispensed services offering prescribed opioids for up to 15 clients without the barriers of daily observation or check-ins.

This practice is currently illegal in the U.S. but has its advocates such as a Yale addiction medicine physician who said “(w)e need to be doing everything possible to try, at a minimum, to make a dent in the unrelenting deaths that in large part have been due to changes in the unregulated drug supply.”⁶⁴

Some preliminary studies have suggested that these programs can lower overdose risk. Providing drugs to participants when other treatment strategies haven’t worked can reduce illicit drug use, reduce emergency department visits and hospital admissions, and connect users to care.⁶⁴

Critics, including addiction specialists, argue that users should be directed toward treatment for their dependence and that providers should focus on reducing drug use rather than providing drugs. Some people are concerned about the potential for diversion and have likened these programs to the overprescribing of opioids that initially helped fuel the overdose crisis.⁶⁴

PAUSE AND PONDER: Would you participate in a safe supply program?

Test Kits

Another approach to harm reduction is the use of test strips that can detect contaminants such as fentanyl in street drug samples.⁶⁵ Test strips are prefabricated strips of a carrier material containing dry reagents that are activated by applying a fluid sample. They can detect the presence of substances within a matter of minutes.⁶⁶ Strips are available to detect many different illicit drugs and are similar to commonly used test kits for detecting pregnancy, failure of internal organs (e.g., heart attack, renal failure, or diabetes), infection or contamination with specific pathogens, or the presence of toxic compounds in food or the environment.⁶⁶ The strips rely on a lateral flow chromatographic immunoassay technology for the qualitative detection of fentanyl and many analogs at concentrations above 200 ng/mL.⁶⁷ The strips have no significant cross reactivity to other opiates and the interpretation of test results is simple: positive (one line), negative (two lines), invalid (no lines or no control line).⁶⁷

The strips were created in 2011 to detect prescription fentanyl in urine as part of a clinical identification of recent drug use. As fentanyl was found more frequently in analyses from drug overdoses, the harm reduction community began using the tests off-label, especially in syringe services sites, to test samples. This empowered drug users to understand what substances they were consuming, making them safer.⁶⁸ A study of drug users in North Carolina found that receiving a positive test result was associated with changes in drug use behavior and perceptions of overdose safety.⁶⁸ Behavioral changes included using less drug, administering a test shot, injecting more slowly, or snorting the sample instead of injecting it. They introduce an element of caution for the drug user.⁶⁹

The use of test strips is restricted in many areas. It is clearly legal to possess some or all drug checking equipment in 22 states, and clearly legal to distribute it to adults in 19 states.⁶⁵ In 14 states where distribution of drug checking equipment is not generally legal, it is legal when the equipment is obtained from a syringe services program.⁶⁵ Tools used to detect fentanyl are classified as drug paraphernalia in more than a dozen states, making it a crime to possess or distribute them.⁷⁰ These state laws emerged in the 1970s at the urging of the DEA claiming that distributing paraphernalia serves to facilitate drug use. Many states continue to maintain a hardline posture.⁷⁰ While laws define drug paraphernalia broadly, they are not always rigorously enforced.⁶⁸ However, violators may face potential penalties ranging from small civil fines to multi-year jail sentences.⁶⁵

PAUSE AND PONDER: What reservations might you have about advising a patient to purchase fentanyl test strips?

Although these devices have some legal restrictions, demand in the U.S. has grown more than 430% in the past three years.⁷¹ They are becoming available in clubs, bars, restaurants, and pizza shops and are frequently distributed for free. Some advocates equate strips to condoms as a public health measure. The FDA warns that it doesn’t actively regulate fentanyl test strips, which places the burden of determining their reliability on buyers.

The strips are available from Amazon and can be obtained from public vending machines in some areas.

SUMARY AND CONCLUDING COMMENTS

The opioid overdose crisis continues to worsen. Despite many efforts over the past decade to reduce the supply of prescription opioids, overdose deaths continue to climb from drugs obtained via illicit sources. While efforts to reduce supply continue, there are also attempts to institute harm mitigation programs. However, existing laws and regulations can make accessing these measures difficult.

Recent efforts have eased the prescribing and use of MAT. This provides pharmacists with a potential opportunity to become more involved with SUD treatment. MAT is underutilized with evidence suggesting that only 13% of people with drug use disorders receive any treatment, and more than half of those with co-occurring conditions receive treatment for neither. Other measures involving pharmacists include increased naloxone access, and availability of test kits in pharmacies.

More controversial models have also gained some acceptance, but strong opposition remains. Pharmacists are or may become involved with programs such as needle/syringe exchange, safe sites, and, as aways, there are opportunities for education and counseling. Pharmacists should also be prepared for the possible, albeit unlikely, introduction of the Canadian model of supplying pharmaceutical grade opioids and other controlled substances to users.

Pharmacists have demonstrated value in implementing harm reduction strategies for many disease states and interested pharmacists should be prepared to be involved with the growing number of opportunities to reduce the opioid overdose crisis.

Pharmacist & Pharmacy Techician Post Test (for viewing only)

POST-TEST

OBJECTIVES:
After completing this activity, participants should be better able to:
1. Review how controlling the supply of opioids has affected the drug overdose crisis.
2. Describe strategies that reduce the harm from misusing opioids.
3. Discuss how medication assisted treatment of opioid use disorder reduces overdose risk.
4. Characterize how regulatory decisions affect access to harm reduction measures.

1. According to CDC estimates, what percentage of drug overdose deaths in 2021 had at least one potential opportunity for intervention?
A. 25%
B. 50%
C. 67%

2. What is currently driving the drug overdose crisis?
A. Prescription opioids
B. Heroin
C. Illicitly manufactured fentanyl

3. In what year did the prescribing of opioids reach its peak?
A. 2012
B. 2019
C. 2021

4. How did the 1914 Harrison Act change the distribution of opiate medications?
A. It made it illegal to prescribe heroin.
B. It created the five schedules of controlled substances.
C. Any prescription for addicts to relieve addiction trauma was illegal.

5. What is an advantage of buprenorphine compared with methadone for opioid use disorder?
A. Buprenorphine is more effective than methadone in treating OUD.
B. Buprenorphine is less likely to produce respiratory depression than methadone if misused.
C. Buprenorphine is less likely to precipitate withdrawal than methadone when administered to someone who is currently misusing street opioids.

6. The DEA recently modified the regulations for buprenorphine. What did they do?
A. They eliminated the requirement for a special (X-) waiver to prescribe buprenorphine for OUD.
B. They reduced the number of patents that a prescriber may treat with buprenorphine at any one time.
C. They created special licensure to permit certified pharmacist to prescribe buprenorphine for OUD.

7. Approximately what percentage of people with substance use disorders receive any treatment in the U.S.?
A. 13%
B. 25%
C. 50%

8. A patient with OUD has been offered naltrexone at his treatment clinic and asks you if it differs from the naloxone that he picked up at the pharmacy last week. What could you tell him?
A. Naltrexone is longer acting than naloxone.
B. Naltrexone can only be administered by IV injection at the clinic.
C. Naltrexone effects are similar to methadone’s.

9. What is the Canadian Safe Prescribing model?
A. Removing restrictions on prescribing methadone for OUD.
B. Prescribing pharmaceutical grade heroin.
C. Making buprenorphine over-the-counter in pharmacies.

10. A patient enters the pharmacy looking for fentanyl test strips, but you practice in a state where they are illegal to purchase. Why are fentanyl test strips illegal in some states?
A. They have not been approved by the Food and Drug Administration.
B. They are considered drug paraphernalia that facilitates drug use.
C. There is no evidence that the strips alter risky behavior in drug users.

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Joudrey PJ, Gordon AJ. Inflexible Methadone Regulations Impede America’s Efforts to Reduce Overdose Deaths. Stat News. Dec. 22, 2021. Accessed October 23, 2023. https://www.statnews.com/2021/12/22/inflexible-methadone-regulations-impede-efforts-reduce-overdose-deaths/
Drug Enforcement Administration. Temporary Extension of COVID-19 Telemedicine Flexibilities for Prescription of Controlled Medications. Fed Reg. 2023;88:30037-30043.
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Patient Safety: Gabapentin and Trazadone: Off-label Use is Out of Control-Recorded Webinar

The University of Connecticut School of Pharmacy is accredited by the Accreditation Council for Pharmacy Education as a provider of continuing pharmacy education.

Pharmacists and Pharmacy Technicians are eligible to participate in this knowledge-based activity and will receive up to 1.0 CE Hours (or 0.1 CEUs) for completing the activity ACPE UAN 0009-0000-23-044-H05-P, passing the quiz with a grade of 70% or better, and completing an online evaluation. Statements of credit are available via the CPE Monitor online system and your participation will be recorded with CPE Monitor within 72 hours of submission.

Patient Safety: Gabapentin and Trazodone, Off-label Use is Out of Control
LEARNING OBJECTIVES
At the end of this continuing education activity, pharmacists will be able to
1. LIST the numerous off label uses of gabapentin and trazodone
2. DESCRIBE which of those uses are supported by actual evidence
3. INDICATE the potential adverse effects and medication related problems that patients who take these drugs may experience
4. ARTICULATE ways to approach prescribers with alternative suggestions

1. Which of the following is an off-label use for gabapentin?
A. Postherpetic neuralgia
B. Adjunctive therapy in partial seizures
C. Migraine prophylaxis

2. Which of the following is an off-label use for trazodone?
A. Chronic insomnia
B. Major depressive disorder
C. Pruritis

3. Which of gabapentin’s off-label uses has the strongest evidence to support it?
A. Bipolar disorder
B. Alcohol withdrawal syndrome
C. Pain syndromes

4. Which of trazodone’s off-label uses has the strongest evidence to support it?
A. Little evidence is available to support the use of trazodone in any of its purported off-label uses.
B. The best evidence supports its use in chronic insomnia, with more than 15 RCTs indicating it is effective.
C. A surprise finding has been that it is effective for behavioral issues in kids who have ADHD; it may help adults, too.

5. Which if the following links gabapentin and trazodone to a most common adverse effect?
A. Gabapentin = dose-dependent CNS and respiratory depression; trazodone = nausea/vomiting, xerostomia, dizziness, drowsiness
B. Gabapentin = dose-dependent CNS priapism and suicidal ideation; trazodone = hypersensitivity reactions and peripheral edema
C. Gabapentin = cardiac arrythmias and QT prolongation; trazodone = cumulative depressant effects when given with SSRIs

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Disclosure of Discussions of Off-label and Investigational Drug Use

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Disclosure of Discussions of Off-label and Investigational Drug Use

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Disclosure of Discussions of Off-label and Investigational Drug Use

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Disclosure of Discussions of Off-label and Investigational Drug Use

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Disclosure of Discussions of Off-label and Investigational Drug Use

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Disclosure of Discussions of Off-label and Investigational Drug Use

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Disclosure of Discussions of Off-label and Investigational Drug Use

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Disclosure of Discussions of Off-label and Investigational Drug Use

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