What in the World: A Global Look at Healthcare and Drugs-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 application-based activity and will receive up to 1.0 CE Hours (or 0.1 CEUs) for completing the activity ACPE UAN 0009-0000-22-055-H04-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.

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.

World Health Post Test – CE Finale

After completing this continuing education activity, pharmacists will be able to
1. Describe the key components of global healthcare systems
2. Discuss the performance indicators of global health systems
3. Compare pharmaceutical drug spending levels and trends globally
4. Define medical tourism and analyze its associated risks and benefits

Which of the following are key components in global health systems?

a. Wait times, patient satisfaction, propensity to result in personal bankruptcy, number of healthcare professionals employed, accreditation

b. Type of ownership (public vs. private), patient’s financial obligations, extent of coverage (e.g., preventive, inpatient, outpatient care, etc.)

c. Antibiotic resistance, risk of exposure to blood borne diseases, long distance travel, exposure to unusual infections

What is a common problem encountered in the universal payer model that is frequently used as a performance measure?

a. High out of pocket cost of care

b. Long wait times

c. Higher mortality rates

In comparison to other high-income countries, where does the U.S system’s administrative efficiency rank?

a. 9th

b. 10th

c. 11th

A student under your supervision is filling a prescription for a newly approved drug. She asks if it is a biologic and you say no, it is a drug (also called a small molecule) and explain the difference between a drug and a biologic, most of which are specialty medications. She says that she heard that long patent lives on innovative drugs fuel pharmaceutical drug spending. What do you tell her?

a. “You are incorrect. The largest contributor to increased spending for pharmaceuticals is specialty medications”

b. “You are incorrect. The largest contributor to increased spending for pharmaceuticals is COVID-19 therapeutics.”

c. “You are incorrect. The largest contributor to increased spending for pharmaceuticals is over the counter medications.”

First-Line Medication Therapy for Type 2 Diabetes: Time for a Change? -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 application-based activity and will receive up to 1.0 CE Hours (or 0.1 CEUs) for completing the activity ACPE UAN 0009-0000-22-058-H01-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.

First-Line Therapy for Type 2 Diabetes: Time for a Change?

1. What is the MOST IMPORTANT therapeutic goal in the management of diabetes?
a. Reduce the A1c to <7%
b. Prevent the development of long-term complications of diabetes
c. Save money from costly treatments

2. What is the most common cause of mortality in people with uncontrolled type 2 diabetes?
a. Complications of atherosclerotic cardiovascular disease
b. Neuropathic pain
c. Diabetic eye disease

3. Tirzepatide belongs to which of the following drug class?
a. GLP-1 receptor agonists
b. Dual GIP/GLP-1 receptor agonist
c. SGLT2 inhibitors

4. Mr. N, the hypothetical patient from the presentation, is prescribed tirzepatide by his PCP. Which of the following would be expected as a COMMON side effect of tirzepatide?
a. Pancreatitis
b. Neuropathic pain
c. Nausea

5. Which of the following statements is TRUE according to the 2023 American Diabetes Association’s diabetes guidelines?
a. Four areas are equally emphasized: glycemic management, weight management, cardiovascular risk factor management, and cardiorenal protection.
b. Glycemic control is the most important therapeutic goal and prescribers should encourage all patient to strive for a HbA1c lower than 6.
c. Prevention of kidney complications of diabetes should be emphasized above other management strategies.

6. Which of the following drug class is associated with the LOWEST potential for weight loss (hint: see the tables at the end of the presentation)?
a. Biguanide (metformin)
b. SGLT2 inhibitors
c. GLP-1 receptor agonists

Immunization: Is Winter Here? – An Update on Monkey Pox and Covid Vaccines-RECORDED WEBINAR

Upon completion of this application based CE Activity, a pharmacist will be able to:

1. Discuss trends in the epidemiology of the COVID-19 pandemic and Monkeypox outbreak.

2. Discuss current clinical data on the safety and effectiveness of (i) the bivalent COVID-19 booster vaccines and (ii) the JYNNEOS or ACAM2000 vaccines for Monkeypox.

3. Explain whether a person would be eligible for receipt of (i) the bivalent COVID-19 booster vaccines and/or (ii) the JYNNEOS or ACAM2000 vaccines for Monkeypox.

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 application-based activity and will receive up to 1.0 CE Hours (or 0.1 CEUs) for completing the activity ACPE UAN 0009-0000-22-059-H06-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.

Good news! News reporters and Internet sites began announcing in the spring and summer of 2022 that the global pandemic had ended. What do you think of that?
1. YAY! Science prevailed and we obliterated that bad boy and sent it away!
2. FAKE NEWS. Approximately 2,000 Americans still die each week from (or with) active COVID-19 disease.
3. CORRECT, but COVID is still a major concern in our socially inclined young adults.

What does the data say about adverse effects associated with the bivalent COVID-19 boosters?
1. The most common adverse effects are systemic (fever, chills, fatigue)
2. The most common adverse effects are central (headache, mental fogginess)
3. The most common adverse effects are local (pain, erythema, swelling)

Based on current vaccination statistics about populations that have the poorest booster coverage for COVID-19, which of the following population should pharmacists be encouraging to GET VACCINATED!?!
1. Children age 5 or younger in the Great Lakes regions
2. People older than 65 in the Pacific northwest
3. Everybody everywhere
4. Monkeypox is the name and name-changing is the game. What has the World Health organization decided to call this infection and why?
5. It will be monk's disease, which will remove some of the stigmatizing language and remind people to live like a monk until the lesions disappear.
6. It will be mpox, which is intended to dissuade people from using racist and stigmatizing language to describe people infected with this virus.
7. It will be var-vac-human, reflecting its similarity to variola (smallpox) and vaccinia (viral vaccine for smallpox) and its zoonotic transmission.

What is eczema vaccinatum?
A complication of the ACAM2000 vaccination that can occur in patients who have eczema/atopic dermatitis, in which vaccinia virus disseminates to cause an extensive rash and systemic illness.
A complication of the JYNNEOS vaccination that can occur in patients who have eczema/atopic dermatitis, in which vaccinia virus disseminates to cause an extensive rash and systemic illness.
A complication of the ACAM2000 vaccination that can occur in patients who have any chronic skin condition, in which vaccinia virus disseminates to cause an extensive rash and systemic illness.

Andi is a person living with HIV infection who also is prone to keloids. This patient wants the JYNNEOS vaccination for mpox. What is the best course of action?
1. Administer the vaccine intradermally
2. Administer the vaccine subcutaneously
3. Recommend using ACAM2000 instead

Patient Safety: Seven Secrets for Patient Safety with Dietary Supplements

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

· Discuss the importance of knowing about a patient’s dietary supplement usage

· Identify commonly used dietary supplements, their regulation, and the value of certification

· Recognize potential medication-dietary supplement interactions

· Demonstrate the ability to locate different sources of information about dietary supplements

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

· Discuss the importance of knowing about a patient’s dietary supplement usage

· Identify commonly used dietary supplements, their regulation, and the value of certification

· Recognize potential medication-dietary supplement interactions

· Recognize the need for pharmacist counseling when a patient is taking a dietary supplement

Consumer consumption of dietary supplements is at an all-time high. Available products number in the tens of thousands, generating millions in annual spending. Increasing interest in overall health and wellness, preventive medicine, and immune function contribute to the rise in usage. It is a common misconception that dietary supplements are safe because they are “natural.”
Ingestion of dietary supplements poses serious health risks including adverse reactions, drug interactions, and toxicity. Adulterated, mislabeled, and contaminated products exist in the marketplace, further increasing consumer risk. Existing federal regulation and oversight for supplements differs from prescription and over-the-counter medications, occurring primarily on a post-marketing basis. Self-reporting by consumers, healthcare professionals, and industry personnel identifies these issues. Patients often omit dietary supplements from medication histories, leaving healthcare professionals unaware that patients are using them. While misinformation abounds on the Internet, many online clinically-backed sources exist.

Introduction

Consuming natural substances to produce a desired effect on the body dates back thousands of years to ancient Egypt, Rome, China, and many other cultures. Records from early Mesopotamia include written formulas using many oils still in use today, including cedar, cypress, and licorice. Around 300 B.C., the Greek philosopher Theophrastus described the medicinal benefits of natural substances in his History of Plants. Throughout the centuries, many philosophers, scientists, and physicians continued collecting, combining, and documenting the use of natural products to treat different illnesses.¹

As the science of medicine developed, so did the science of pharmacology. Isolation of the active ingredients found in herbal substances lead to the development of synthetic compounds with similar properties. The first synthetic medication, chloral hydrate, derived from chloroform and discovered in the 1800s by German chemist Justus von Lieberg, is still in use today.²

Fast forward to modern day, and the interest and use of prescription medications, over-the-counter (OTC) products, and dietary supplements are at an all-time high. In 2020, consumers filled 6.3 billion prescriptions in the United States³ (U.S.) and purchased more than 6 billion OTC products.⁴ The dietary supplement market reached an unprecedented level in 2020 with a global spend of $61.2 billion. Experts predict it will reach $128.64 billion by 2028.⁵

The COVID-19 pandemic, caused by the SARS-CoV-2 acute respiratory coronavirus, significantly impacted our perception and approach to healthcare.⁶ More and more people use complementary and alternative approaches to healthcare than ever before.⁷ For example, sales of elderberry supplements more than doubled and zinc products quadrupled shortly after the pandemic's start.⁸

Pharmacists, widely recognized as drug information experts, and pharmacy technicians routinely field consumers' questions about dietary supplements. Many pharmacists lack the necessary knowledge or don't know where to look to answer these questions. Pharmacy schools educate future pharmacists on prescription and OTC medications with courses about nutrition and dietary supplementation, if offered, available as electives. This continuing education activity presents information about dietary supplements through a series of seven common pharmacy situations and lets learners in on seven secrets they can apply to their practices.

Situation: Continuing education is a professional requirement many pharmacists find tedious. Looking through the UCONN online CE library and seeing a new continuing education activity entitled ‘Seven Secrets of Patient Safety with Dietary Supplements,’ a pharmacist remarks to the pharmacy team, "What a waste, no one even takes dietary supplements."

Secret #1: Almost 60% of people in the United States used a dietary supplement in the last 30 days.^11,12

Dietary supplements crowd the aisles in drug stores, supermarkets, warehouse clubs, and even corner convenience stores. The sheer number of products is staggering. The Dietary Supplement Database (DSLD) is an online, searchable database developed by the Office of Dietary Supplements (ODS) at the National Institutes of Health (NIH). The database contains product labeling information on dietary supplements sold in the United States, including both on and off-market products. DSLD currently lists more than 140,000 labels.⁹

In the early 1960s, the National Center for Health Statistics began a program named the National Health and Nutrition Examination Survey (NHANES). NHANES is a continuous program focusing on various health and nutritional measurements and assesses adults' and children's health and nutritional status in the U.S.¹⁰ Scientific and technical journals publish the study results.

One section of the program assesses dietary supplement use among adults. Results from the 2017-2018 NHANES show that^11,12

57.6% of adults 20 years or older used a dietary supplement in the past 30 days
Women (63.8%) had a higher utilization than men (50.8%)
Use of dietary supplements increased with age, with women 60 years or older reporting the highest usage at 80.2%
Use of multiple dietary supplements increased with age
Most common dietary supplements used by all age groups include multivitamin-mineral supplements, vitamin D, and omega-3 fatty acids

The Council for Responsible Nutrition (CRN) is a trade association for the dietary supplement and functional food industry. Annually, the CRN performs a survey gathering data on consumer use of dietary supplements. The 2019 survey conducted by the CRN underscored dietary supplement usage with the following results¹³:

77% of US adults take dietary supplements, including 79% of American women and 74% of males
Top reasons for taking supplements included:
- Energy
- Immune health
- Filling nutrient gaps
- Healthy aging
- Heart health

The COVID-19 pandemic significantly impacted our perception and approach to healthcare.⁶ As of August 5, 2022, SARS-CoV-2 has infected more than 580 million people worldwide.¹⁴ Interest in boosting our overall immunity and protecting ourselves from viral infections has dramatically increased as a result.⁷ Many vitamins and minerals play essential roles in proper immune function.^7,15 Sales of supplements associated with boosting immunity increased over the last two years, including vitamins C and D, zinc, omega-3, garlic, ginger, and turmeric.¹⁶

Table 1. Common Dietary Supplements and Potential Uses^7,17,18

Dietary Supplement	Potential Use
Black Cohosh	Menopausal symptoms
Calcium	Dyspepsia Osteoporosis Premenstrual syndrome
Echinacea	Prevention and treatment of the common cold Promotion of wound healing
Elderberry	Prevention of upper respiratory tract infections Reduction in duration and severity of symptoms of the common cold
Folic acid	Folate deficiency Kidney failure Neural tube defects
Ginkgo	Anxiety Dementia Memory improvement Premenstrual syndrome
Ginger	Dysmenorrhea Nausea and vomiting Osteoarthritis
Ginseng	Cognitive function Erectile dysfunction
Iron	Anemia Restless leg syndrome
Magnesium	Constipation Dyspepsia
Melatonin	Sleep disorders
Multivitamin with minerals	General supplementation
Omega-3 fatty acids	Alzheimer’s disease Cardiovascular disease Dementia Depression Reduction of triglycerides
Potassium	Hypokalemia Hypertension Kidney stones
Probiotics	Atopic dermatitis Antibiotic-associated diarrhea Irritable bowel syndrome
St. John’s Wort	Anti-depressant Menopausal symptoms
Turmeric	Allergic rhinitis Osteoarthritis Pruritis
Valerian	Insomnia
Vitamin A	Aging skin Healthy vision
Vitamin B-12	Vitamin B-12 deficiency
Vitamin C	Anemia Antioxidant effects Prevention of the common cold Vitamin C deficiency
Vitamin D	Osteomalacia Osteoporosis Vitamin D deficiency
Vitamin E	Alzheimer's disease Dysmenorrhea Premenstrual syndrome
Zinc	Acne Depression Diabetes Diarrhea Treatment of common cold

Eating a healthy diet is essential for good health and nutrition. The Dietary Guidelines for Americans advise professionals, including policymakers, health care providers, and nutrition educators, about what to eat to meet the body’s nutritional needs. It emphasizes eating a diet rich in nutrient-dense foods, such as fruits and vegetables, as the best way to meet the body’s nutritional needs. The guideline identifies specific populations in which dietary supplementation may be necessary, such as women who are pregnant or lactating and adults older than 50.¹⁹

In addition to these defined special populations, many pharmacy patients may find it necessary to take specific vitamins or minerals due to medication-induced nutrient deficiencies.

Table 2. Examples of Nutrient Depletion Induced by Medications^7,17

Nutrient	Medication(s)	Mechanism
Vitamin D	Anticonvulsants	Increase hepatic metabolism
	Bile acid sequestrants	Decrease absorption
	Orlistat	Decrease absorption
Magnesium	Estrogens	Decrease serum levels by increasing uptake into tissues
	Loop diuretics	Increase excretion
	Proton pump inhibitors	Decrease absorption
Vitamin B₁₂	Biguanides	Decrease absorption
	Proton pump inhibitors	Decrease absorption
	H-2 blockers	Decrease absorption
Potassium	Loop diuretics	Increase excretion
	Thiazide diuretics	Increase excretion
	Corticosteroids	Increase excretion

The pharmacist's dismissal of dietary supplement education is understandable. No one wants to waste precious time on irrelevant continuing education. However, the facts presented here illustrate the need for pharmacist education on dietary supplements.

Pause and ponder: A patient presents information about taking lemon and baking soda tea to prevent COVID-19 infection and asks you if it really works. How would you approach this conversation?

Situation: Sunday afternoons sometimes (but not often!) present the opportunity to catch up on administrative activities. While completing an inventory reconciliation of the vitamin section, a technician inquires, "Why does the FDA approve so many different products?" Looking up distractedly from the CII safe count, the pharmacist pauses, then replies in a weary voice, "You know, I’m not sure, probably just to make it more confusing for us."

Secret #2: Regulatory oversight of dietary supplements differs from prescription and OTC medications.

What is a Dietary Supplement?

On the most basic level, a dietary supplement is a substance consumed to add nutrients to a diet or to lower the risk of certain health problems. The use of natural substances has been around for millennia, but it is only within the last five decades that countries worldwide have formalized language and regulations around dietary supplements. Terminology, quality control, and safety assessment differ depending on the country and governing legislative body.²⁰

In 1994, the United States Congress passed the Dietary Supplement Health and Education Act (DSHEA), an amendment to the Food, Drug, and Cosmetic Act. DSHEA defines the term dietary supplement as a product intended for ingestion and containing an ingredient that supplements the diet. Dietary supplement labeling must include the term ‘dietary supplement’ or an equivalent term such as ‘herbal supplement’ or ‘magnesium supplement.’ DSHEA also stipulates that a dietary supplement must be free of contamination, adulteration, and properly labeled.²¹ We will discuss dietary supplement product integrity and labeling later in this activity.

According to DSHEA, dietary supplements include vitamins, minerals, herbs, other botanicals, amino acids, and live microbials (probiotics).Dietary supplements are available in many different formulations including tablets, capsules, soft gels, gel caps, powders, and liquids.²¹

DSHEA defined the term ‘new dietary ingredient’ as an ingredient that meets the above criteria and was unavailable in the U.S. before October 15, 1994. If manufacturers want to market a product containing a new dietary ingredient, they must notify the U.S. Food and Drug Administration (FDA) before marketing. The FDA then reviews the product for safety but not effectiveness.²¹

Regulation of Dietary Supplements

The FDA and the Federal Trade Commission (FTC) share regulation and oversight of dietary supplements. The FDA is responsible for the information provided on dietary supplement product labeling, including the package labeling, product inserts, and information available at the point of sale. The FTC monitors dietary supplement advertising, ensuring advertisements are truthful, substantiated, and not misleading. Both agencies have the authority to address violations and work together to ensure their efforts are consistent with one another.²²

The FDA does not have the authority to approve dietary supplement products before manufacturers market, distribute, and sell them to consumers. Manufacturers are responsible for ensuring the products they produce and distribute meet all quality standards defined by federal law. Quality standards include²²

Ensuring the safety of the dietary ingredients used in the product
Following current Good Manufacturing Practices (cGMP)
Meeting all product labeling requirements
Ensuring substantiation of all claims made about the product
Ensuring products are free of adulteration or misbranding

cGMP, defined and regularly updated by the FDA, establish the minimum requirements for manufacturing, packaging, and labeling products to ensure product quality. cGMP includes guidance on obtaining quality ingredients, operating procedures, and quality controls.²³ Failure to follow cGMP results in possible product contamination.

While the FDA may not have the authority to approve dietary supplements before the product marketing and distribution, it can monitor products via post-marketing surveillance and auditing. The FDA routinely performs manufacturer inspections, monitors the marketplace, and investigates adverse event reports. Follow-up includes working with the manufacturer to bring the product into compliance, issuing warning letters, and recalling products.²¹

Reporting Issues with Dietary Supplements

Post-marketing surveillance is essential for documenting and monitoring any issues with dietary supplements. Information about severe reactions and product quality are important issues to report. The FDA Safety Reporting Portal is an online tool used to report safety issues on several categories of products, including pet or livestock foods, tobacco products, animal drugs, and dietary supplements.²⁴

The website address for the portal is https://safetyreporting.hhs.gov. Anyone can use the portal to report issues, including consumers, healthcare professionals, manufacturers, and researchers. Generating a new report starts on the home screen. The reporter chooses to file the report as a guest or by creating an account. Creating an account streamlines data entry and allows the reporting individual to save a draft of the report, follow up on a report, and view previous submissions.²⁴

Generation of an Individual Case Safety Report ID (ICSR) occurs after report submission. The ICSR allows the reporter to identify the report for future reference including submission of a follow-up report with additional information. FDA reviewers assess the seriousness of the reported issue and assign follow-up. Submission of this information allows the FDA to identify potentially dangerous products and potentially remove them from the market.²⁴

Traditionally, insurance companies limit coverage to prescription medications. Recent trends show an expansion of coverage to include some dietary supplements. Insurance coverage of dietary supplements blurs the regulatory differences between prescription medications and dietary supplements. Understanding the differences in oversight is beneficial and allows the pharmacy staff to counsel patients effectively.

Situation: While running back to the pharmacy after a much-needed bathroom break, a pharmacist stops when approached by a customer asking for advice about an iron supplement. Overhearing the inquiry, another customer comments, "You should buy that online; it’s cheaper, and the quality is just as good." The pharmacist nods assent, turns, and hurries back to the pharmacy amid the erupting sounds of chaos behind the counter.

Secret #3: Product integrity fluctuates between manufacturers and sources of dietary supplements.

Integrity of Dietary Supplements

The lack of government oversight opens the door for substandard products to flood the market. Poor ingredient quality, heavy metal or microbial contamination, adulteration, and mislabeling occur regularly. In the current economy, with rising prices, consumers are turning to less expensive options, and cheaper is not necessarily better, especially with dietary supplements.

In the literature, many studies exist that analyze dietary supplement product integrity. A study published in 2021 tested multiple bottles of 29 herbal supplements for consistency of ingredient activity and the presence of metal and fungal contaminants. The analysis showed inconsistent ingredient activity not only between bottles of the same product manufactured by the same company, but also between bottles manufactured by different companies. Assaying for metal contamination found zinc in 88% of bottles and nickel in 40% of bottles. In 37 of 58 bottles tested, fungal contamination was present, with 21 bottles having multiple strains.²⁵

Another study analyzed 41 dietary supplements for the presence of cadmium, lead, and mercury. Results revealed that 68.3% of samples contained contamination with cadmium and lead, and 29.3% with mercury.²⁶ One research team evaluated 121 dietary supplements along with 49 prescription drugs for levels of toxic element contamination. A small percentage of the dietary supplement products exceeded safety levels for mercury, lead, cadmium, arsenic, or aluminum. None of the prescription products exceeded these safety levels.²⁷

Adulterated products contain substances not listed on the product labeling, substitution of inferior materials for active ingredients, or may contain a lesser amount of ingredients. Weight loss, sports enhancement, and sexual function supplements commonly contain banned substances.²⁸

The FDA created and currently maintains the Health Fraud Product Database to increase awareness. This database contains information about products cited in warning letters, advisory letters, recalls, public notifications, and press announcements for various issues. Issues cited include products claiming to cure, treat, or prevent a disease and products containing undeclared ingredients or a new dietary ingredient.²⁹ The database is available in the consumer section of the FDA website at https://www.fda.gov/consumers/health-fraud-scams/health-fraud-product-database.

On January 2, 2022, the FDA issued a warning letter to the manufacturers of Nasitrol, a nasal spray based on the ingredient iota carrageenan. A review of the product’s website found claims that the product is intended to mitigate, prevent, treat, diagnose, or cure COVID-19 in people. Federal regulations define products making these claims as drugs and subject to review by the FDA before approval and subsequent marketing. As discussed earlier, this is in direct violation of federal regulations.³⁰

In another example, on July 15, 2022, the FDA issued a public notice advising consumers to refrain from purchasing Adam’s Secret Extra Strength Amazing Black, a product promoted for sexual enhancement. Laboratory analysis found that the product contained tadalafil, a prescription medication used for erectile dysfunction.³¹ Due to the potential for severe side effects such as hypotension, tadalafil administration requires medical supervision by a physician.³²

A study published in 2018 analyzed FDA warning letters issued from 2007 through 2016, using data from the Health Fraud Product Database. During this time frame, the FDA found 776 adulterated dietary supplements from 146 different companies. A total of 157 products contained more than one unapproved ingredient. Products marketed for sexual enhancement accounted for 45.5% of letters, weight loss 40.9%, and muscle building 11.9%. Unapproved ingredients included sildenafil in sexual enhancement, sibutramine in weight loss, and synthetic steroids or steroid-like ingredients in muscle building supplements.³³

One way for consumers to know they are purchasing a valid product is by looking for a certified product. The certification process involves an independent, third-party company testing a company’s products, offering quality assurance for dietary supplements. Parameters tested include³⁴

Product contains the ingredients stated on the label
Presence of harmful ingredients
Presence of contamination
Proper dissolution
cGMP followed during manufacture

Three independent, private, third-party certifying organizations operate in the United States: the US Pharmacopeial Convention (USP), NSF International, and Consumerlabs.com. All three companies offer product certification programs for a fee. Each company allows products passing certification to display a seal on product labeling. Table 3 summarizes information about each organization.

Table 3. Dietary Supplement Certification Organizations

Certifying Organization	US Pharmacopeial Convention	NSF International	Consumerlab.com
Website	www.usp.org www.qualitysupplements.org	www.nsf.org	www.consumerlab.com
Services offered	Dietary supplement verification program including GMP facility audits, product QCM process evaluation, and product testing	Product and ingredient certification GMP Certification Certified for Sport	Product reviews Quality Certification Program
Information available on the website	Program information, list of verified products, and educational resources	Program information, product search engine, and educational resources	Product reviews, health condition information
GMP = Good Manufacturing Practice

Source: adapted from reference 33

Online product ordering is a convenient shopping option rapidly gaining popularity in recent years, especially during the pandemic. While tempting to order the least expensive product, investigating the source and quality of dietary supplements available online is essential. Proactive training of the entire pharmacy team aids in providing patients with accurate information.

Situation: A weary technician finally finishes ringing out the last customer after two hours straight at the register. A sigh of relief quickly turns into a disgruntled groan as another customer approaches. With a bottle labeled ‘Menopausal Support’ in hand, the customer points to the bottle label and asks, "What does ‘proprietary blend’ mean?" The technician glances over her shoulder, sees the pharmacist engaged in an intense phone conversation, and replies to the customer, "The bottle label clearly lists the ingredients."

Secret #4: Federal regulations define required dietary supplement label information. Unfortunately, ambiguity still exists, making it challenging to identify exactly what the product contains.

Federal regulations define the information required on dietary supplement product labeling in detailed, specific terms. Product labeling must include³⁵

Product name
The term ‘dietary supplement’ or similar term (i.e., herbal supplement)
Name and location of the manufacturer, along with a domestic address and phone number for reporting serious adverse events
Nutrition labeling in the form of a “Supplement Facts” panel with the following information (see Figure 1):
- Serving size
- Number of servings per container
- Listing of each dietary ingredient in the product
- Amount of dietary ingredient per serving (Exception: ingredients in a proprietary blend)
- Amount per serving listed as a quantitative amount by weight, as a percentage of the Daily Value, or as both
A list of other ingredients not declared on the Supplement Facts label (usually excipients such as preservatives or dyes)
Net quantity of contents

Figure 1. Supplemental Facts Label (sourced from reference 36)

One area of ambiguity in dietary supplement product labeling is the listing of a proprietary blend. The term proprietary blend refers to a blend of dietary ingredients unique to a manufacturer and product. Federal labeling regulations allow the listing of proprietary blends on dietary supplement products, however, only the total weight of the blend is required, not the weight of individual ingredients.³⁵ There is no way for the healthcare professional or consumer to know exactly how much of a particular ingredient the proprietary blend contains.

Consumerlabs.com cautions consumers about products containing proprietary blends or formulas. In many instances, the blend's name sounds like a desired, expensive ingredient that is only a small part of the formula. Marketing of products containing proprietary blends may mislead the consumer with claims meant to impress the consumer and drive sales of the product.³⁷

FDA regulations do allow structure/function claims on dietary supplement labeling. Structure/function claims describe how a nutrient or dietary ingredient may affect or act to maintain the structure or function of the body.³⁵Examples of structure/function claims include³⁵

Calcium builds strong bones
Antioxidants maintain cell integrity
Fiber maintains bowel integrity

If a dietary supplement label contains a structure/function claim it must also contain the following statement: "This statement has not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease."³⁵

The example in this situation involved a product marketed for menopausal support. Menopausal symptoms affect more than 1 million women in the US annually and include symptoms such as hot flashes and sleep disturbances.³⁸ A search of the DSLD using the term ‘menopausal support’ and filtering for on-market products containing the ingredient ‘proprietary blend’ returned almost 3,000 products.⁹ This abundance of products illustrates the ambiguity that exists on dietary supplement labeling.

Pharmacy technicians are often the first line of contact at the pharmacy. Training and development of pharmacy technicians on the facts surrounding dietary supplements empower technicians, allowing them to answer factual questions and provide effective patient education.

Situation: The pharmacy phone constantly rings throughout the day, and today is no exception. The new COVID vaccine is out, and everyone wants to know if the pharmacy has it in stock. Answering yet another call, the technician is surprised when a patient asks to talk to the pharmacist, complaining about dizziness. The pharmacist checks the patient’s profile, finding no underlying causative medication. Further questioning the patient, the pharmacist uncovers the recent addition of melatonin at night for sleep.

Secret #5: Like prescription medications, dietary supplements have pharmacologic and physiologic effects on the body, potentially resulting in health risks and side effects.

Consumers perceive dietary supplements as safe due to their source from natural substances. While generally well tolerated, dietary supplements affect the body like prescription medications, capable of producing an undesired effect. Lack of regulatory oversight allows products to reach consumers without adequate safety evaluation.

Information describing adverse effects of dietary supplements is anecdotal, derived from case reports and reports submitted through the FDA Safety Reporting Portal. Most dietary supplements have not been studied in pregnant or lactating women or children.

A study published in 2015 evaluated ten years of emergency room data to assess the number of annual visits resulting from dietary supplement adverse events. The authors calculated an average of more than 23,000 emergency room visits stemmed from the consumption of dietary supplements, resulting in more than 2,000 hospitalizations annually.³⁹

Events in older adults accounted for the highest percentage of visits, with 40% of visits due to difficulty swallowing. Incidence in young adults aged 20 to 34 was significant at 28% and primarily involved weight loss and energy products. Side effects reported include heart palpitations, chest pain, and tachycardia.³⁹

Unsupervised child ingestions accounted for 21% of visits. Unlike prescription medications, regulations do not require child-resistant packaging for dietary supplements, except for iron-containing products.³⁹ The authors note the numbers evaluated in the study are likely underreported as patients do not always include dietary supplements with the current medication list.³⁹

Table 4. Adverse Effects of Common Dietary Supplements^7,17

Supplement	Adverse Effects
Black Cohosh	Breast tenderness, diarrhea, gastrointestinal upset, nausea/vomiting
Calcium	Burping, constipation, gastrointestinal upset
Echinacea	Diarrhea, constipation, gastrointestinal upset/pain, heartburn, nausea/vomiting, skin rashes
Ginseng	Gastrointestinal side effects, headache, sleep difficulty
Ginger	Burping, diarrhea, heartburn
Iron	Abdominal pain, constipation, diarrhea, nausea/vomiting
Magnesium	Diarrhea, gastrointestinal irritation, nausea/vomiting
Melatonin	Dizziness, drowsiness, headache
Omega-3 fatty acids	Bad breath, headache, heartburn, nausea, diarrhea, unpleasant taste
Potassium	Abdominal pain, burping, diarrhea, nausea/vomiting
St. John’s Wort	Diarrhea, dizziness, dry mouth, fatigue, headache, insomnia
Turmeric	Constipation, dyspepsia, gastrointestinal reflux, nausea/vomiting
Vitamin C	Abdominal cramping, heartburn, kidney stones (if history of kidney stones)
Zinc	Abdominal cramping, diarrhea, metallic taste, nausea/vomiting

Patients often fail to report usage of dietary supplements and most pharmacy software lacks the ability to note dietary supplement usage in the patient profile. In this situation, the pharmacist took the extra time to further question the patient about dietary supplement usage and successfully identified the causative agent.

Pause and Ponder: In what ways could you incorporate activities into the daily workflow to increase awareness of patients’ use of dietary supplements?

Situation: Today, the workload in the pharmacy is lighter than usual. With a grateful sigh, the pharmacist sinks onto a stool reaching for a quick snack. Then the phone rings… The caller is a triage nurse from the local hospital to verify a patient’s medication profile. Pulling up the profile, the pharmacist verifies the list of medications, including digoxin. The triage nurse confirms atrial fibrillation as the cause for admission, adding that the patient recently started taking St. John’s Wort for depression.

Secret #6: Some dietary supplements affect the CYP450 liver enzymes, potentially altering the pharmacokinetics of medications, leading to treatment failure and/or toxicity.

Dietary supplement-drug interactions

Drug-drug interactions result in altered absorption, metabolism, or excretion. Drug-dietary supplement interactions occur through the same pathways as those used by FDA-approved drugs. The cytochrome P450 (CYP P450) enzymes in the liver are responsible for the metabolism of most medications.^41,42 The ability of a drug to either induce or inhibit these enzymes is a significant factor in drug-drug interactions. The natural ingredients found in dietary supplements are capable of inhibition or induction, also having the potential to interact with medications.

St. John’s Wort, an herbal commonly taken for the relief of mild to moderate depression, induces the activity of CYP3A4.^43,44 This induction increases the clearance of medications metabolized by CYP3A4. Examples of medications cleared by CYP3A4 include alprazolam, atorvastatin, cyclosporine, oral contraceptives, oxycodone, and warfarin.^43,44 Patients need counseling about potential drug interactions with St. John’s Wort.

Limited clinical studies evaluating the impact of drug-dietary supplement interactions exist. Many interactions are theoretical, based on limited clinical evidence, animal research, and case reports.⁷

Table 5. Examples of Potential Drug-Dietary Supplement Interactions^7,17

Dietary Supplement	Medication	Interaction
Calcium	Quinolone and tetracycline antibiotics	Decreased antibiotic efficacy Take antibiotic 2 hours before or 4-6 hours after calcium
Calcium	Dolutegravir Elvitegravir	Reduced serum levels Take medication 2 hours before or 2 hours after calcium
Ginseng	Diabetes medications	Increase risk of hypoglycemia
Ginseng	Immunosuppressants	Decreased effectiveness of immunosuppressant
Ginkgo	Anticoagulants	Increased risk of bleeding
Iron	Quinolone and tetracycline antibiotics	Decreased levels of antibiotics due to decreased absorption Take antibiotics 2 hours before or 4-6 hours after iron
Magnesium	Bisphosphonates	Decreased absorption
Magnesium	Levodopa/carbidopa	Decreased bioavailability of levodopa/carbidopa
Niacin	Statins	Increased risk of myopathy or rhabdomyolysis
	Thyroid hormones	Antagonize the effects of thyroid hormone replacement
	Antihypertensive medications	Increased risk of hypotension due to niacin’s vasodilating effects
St. John’s Wort	Alprazolam	Decreased effects of alprazolam
	Oral Contraceptives	Decreased efficacy Counsel patients to use other forms of contraception
	Digoxin	Decreased levels of digoxin
	Omeprazole	Decreased effects of omeprazole
Valerian	CNS depressant drugs	Additive sedative effects
Vitamin B6	Phenytoin	Decrease levels and clinical effects of phenytoin
Vitamin D	Atorvastatin	Decreased absorption of atorvastatin
Vitamin E	Anticoagulants	Increased risk of bleeding
Zinc	Quinolone antibiotics	Decreased levels and effects of antibiotics Take antibiotic 2 hours prior or 4-6 hours after zinc

Pharmacy training emphasizes the importance of drug-drug interactions. It is important to remember that any substance introduced to the body, including food, beverages, and dietary supplements, has the potential to interact with medications.

Situation: It is another busy day in the pharmacy; prescriptions cover the bench, the phone rings constantly, and a pickup queue extends around the corner. A technician nervously approaches the pharmacist about a patient at the counter with a question regarding a supplement. The pharmacist throws down the spatula, muttering angrily about lacking the knowledge and training to answer the question properly. Sighing, he says, "I’ll just Google it."

Secret #7: Many websites provide clinically backed information on dietary supplements (and Google is not one of them!).

The vast amount of health information available via the Internet with just a few clicks of the keyboard is both a blessing and a curse. Google is now a verb, and a simple search returns millions of results in seconds. While this may seem like a blessing, the curse lies in the searcher's inability to recognize valid, accurate sources of information. In many searches, ads appear as search results adding to the confusion.

In addition to the Internet, consumers turn to social media for health information. Social media use increased from 27% in 2009 to 86% in 2019.⁴⁵ Information posted on social media provides communication about healthcare issues, potentially resulting in improved health care.⁴⁵ Unfortunately, inaccurate information abounds on the Internet and social media platforms, leading to consumer misinformation.^47-49

The FDA recently launched a new dietary supplement education initiative geared towards consumers, healthcare professionals, and teachers. The program, Supplement Your Knowledge, presents information about dietary supplements through a series of three videos. Educational materials, including fact sheets and infographics, are available in English and Spanish.⁵⁰

Many government agencies provide free access to information about dietary supplements and their side effects, toxicity, and drug interactions. There are also several paid subscription resources available. Table 6 lists many of the available information options.

Table 6. Sources of Information about Dietary Supplements

Resource	Website	Information
Dietary Supplement Education Program	https://www.fda.gov/food/healthcare-professionals/dietary-supplement-continuing-medical-education-program	Continuing medical education program Collaboration between FDA and AMA Series of 3 videos about dietary supplements Also contains links to educational materials and other websites with information about dietary supplements
Dietary Supplement Label Database	https://dsld.od.nih.gov	Current and historical label information on dietary supplement products marketed in the United States Useful to determine the contents of dietary supplement products
Food and Drug Administration	https://www.fda.gov/food/dietary-supplements/information-consumers-using-dietary-supplements	Information for consumers on using dietary supplements Links to educational resources and materials, consumer updates, alerts, recalls and other information
Google Scholar	https://scholar.google.com/	Source of information from many avenues including journals, books, and conference proceedings
Lexi-Comp Natural Products Database	Available via mobile app	Requires a paid subscription Alphabetical, searchable natural product database
Memorial Sloane Kettering Cancer Center	https://www.mskcc.org/cancer-care/diagnosis-treatment/symptom-management/integrative-medicine/herbs	Information on herbs, botanicals, and other products for both consumers and healthcare professionals Dietary supplement monographs IOS app: About Herbs Part of an online integrative medicine resource center
National Cancer Institute Office of Cancer Complementary and Alternative Medicine	https://cam.cancer.gov	Information for consumers and healthcare professionals about CAM as it relates to cancer therapy Information on current NCI CAM research
National Center for Complementary and Integrative Health	https://www.nccih.nih.gov	Information for both consumers and healthcare professionals about complementary health products and practices
National Library of Medicine - Medline Plus	https://medlineplus.gov/druginfo/herb_All.html	Online health information about drugs, herbs, and supplements for consumers Information sourced from the National Center for Complementary and Integrative Health and Natural Medicines Comprehensive Database
Natural Medicines Comprehensive Database	https://naturalmedicines.therapeuticresearch.com	Requires a paid subscription Professional monographs including information about effectiveness, safety, adverse effects, and interactions Information on specific commercial products Interaction checker Patient handouts in English, Spanish and French
Office of Dietary Supplements	https://ods.od.nih.gov	Information for both consumers and healthcare professionals General supplement information Information on supplements for specific purposes Fact sheets on dietary supplements and their ingredients
PubMed	https://pubmed.ncbi.nlm.nih.gov	Search engine for the National Library of Medicine Source of information from journals
United States Department of Agriculture	https://www.nutrition.gov/topics/dietary-supplements	Links to general information and resources on dietary supplements

Performing an Internet search via Google may seem like the quickest and easiest way to find the answer to an inquiry. Engaging with the patient, gaining additional information, and knowing where to look ultimately saves time. It is not necessary for one to be an expert in all dietary supplements, just to self-educate one supplement at a time.

Pause and Ponder: A patient shares the unfortunate news about a recent cancer diagnosis. He asks you about the use of herbs in the treatment of cancer. What advice would you give?

Conclusion

You may have noticed a recurring theme throughout this activity. Education. Dietary supplement education is essential to patient safety given the current usage patterns and accessibility of the retail pharmacy team. Education needs to include the entire pharmacy team. Technicians are often the first point of contact at the pharmacy, commonly fielding patient questions. Knowing when to answer questions and when to involve the pharmacist is a necessary skill. Understanding the differences in oversight, the physiological effects of dietary supplement consumption, and the potential for drug interactions allows effective management and counseling of patients. It is important for healthcare providers to solicit information regarding patient consumption of dietary supplements.

Sidebar: Tips for Counseling Patients about Dietary Supplements

Carefully inspect the product to ensure intact product labeling

Ensure the safety seal is intact

Check for an expiration date or best used by date

Check for customer service or return information before ordering

Buy direct from a reputable company; many reputable companies sell through Amazon, avoid 3^rd party resellers

Check for the presence of a third-party certification seal

Before purchase, check the company’s website for information on quality standards

Pay attention to the appearance and smell of the product upon opening

Child-resistant packaging is not a requirement for dietary supplements; advise on proper storage of product

Reinforce the importance of including dietary supplements on a current medication list

Seven Secrets for Patient Safety with Dietary Supplements

Pharmacist post-test

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

1. Discuss the importance of knowing about a patient’s dietary supplement usage (K)
2. Identify commonly used dietary supplements, their regulation, and the value of certification (K, or A?)
3. Recognize potential medication-dietary supplement interactions (K)
4. Demonstrate the ability to locate different sources of information about dietary supplements (A)

1. According to The National Health and Nutrition Examination Survey more than what percentage of adults have used a dietary supplement in the last 30 days?

A. 45%
B. 50%
C. 55%

2. Which of the following is a commonly used dietary supplement?

A. Boswellia
B. Turmeric
C. Quercetin

3. Which government agencies regulate dietary supplements?

A. USDA, FDA
B. FTC, DEA
C. FTC, FDA

4. Patient MW fills a new prescription for bumetanide. Which potential nutrient depletion may occur?

A. Magnesium
B. Vitamin D
C. Vitamin B12

5. While completing an inventory reconciliation of the vitamin section, a technician inquires, ‘Why does the FDA approve so many different products?’ Which of the following is the most appropriate answer?

A. ‘The FDA does not have the authority to approve dietary supplements, the FTC approves dietary supplements, including vitamins.’
B. ‘The FDA does not have the authority to approve dietary supplements before they are marketed, allowing manufacturers to flood the market with products.’
C. ‘You know, I’m not sure, probably just to make it more confusing for us.’

6. Which of the following companies offer independent third-party dietary supplement certification services?

A. Consumer Reports
B. NSF International
C. Certified Naturally Grown

7. Patient ED is a 58-year-old male new to your pharmacy. He provides the pharmacy team with a list of his current medications including:
• Warfarin 3 mg PO QD
• Atorvastatin 10 mg PO QD
• Donepezil 10 mg PO QHS
• Metformin 1,000 mg PO BID
Use of which of the following supplements would be cause for concern in this patient?

A. Ginkgo
B. Omega-3 fatty acids
C. Niacin

8. A patient calls with questions about a supplement recommended by a friend. The name of the supplement is Mind and Memory Essentials, and the patient does not know the product ingredients. Where would you go to find this information?

A. Dietary Supplement Label Database
B. Office of Dietary Supplements
C. United States Department of Agriculture

9. A patient asks you about the potential side effects of taking turmeric. Where would you go to find this information?

A. Google
B. PubMed
C. Office of Dietary Supplements

10. You are verifying a new birth control prescription for a patient, recalling that the patient strongly believes in alternative medicine and dietary supplementation. Thankfully her profile contains a list of dietary supplements. You see St. John’s Wort listed and suspect a drug-supplement interaction. Where would you go to find more information?

A. Natural Medicines Database
B. Google Scholar
C. National Library of Medicine

11. One of your regular patients stops by the counter to ask your opinion on a dietary supplement product purchased on the Internet. What should you assess when looking over the product?

A. Product labeling, color of bottle, structure/function disclaimer, certification
B. Certification, expiration date, product labeling, intact seal
C. Expiration date, product price, certification, product labeling

12. Pharmacy patient ML approaches the pharmacy counter to purchase several bottles of oral glucose tablets. When questioned, the patient reveals the recent occurrence of several hypoglycemic episodes. The patient confirms compliance with taking their prescription for metformin 1 gm PO BID. ML reports no changes in other prescriptions or dietary habits but does state they started taking a dietary supplement a few days ago but cannot recall the name. Which product would you suspect based on the information provided?

A. Vitamin E
B. Valerian
C. Ginseng

Pharmacy Technician

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

1. Discuss the importance of knowing about a patient’s dietary supplement usage (K)
2. Identify commonly used dietary supplements (A)
3. Define dietary supplement oversight and different levels of quality (K)
4. Recognize the need for pharmacist counseling when a patient is taking a dietary supplement (K)

1. Why is it important to ask about a patient’s usage of dietary supplements?

A. It is not important to ask about dietary supplement usage.
B. To identify which dietary supplements the pharmacy should feature on the front counter.
C. Dietary supplements potentially interact with prescription medications.

2. Which of the following is a commonly used dietary supplement?

A. Boswellia
B. Turmeric
C. Quercetin

3. Which government agencies regulate dietary supplements?

A. USDA, FDA
B. FTC, DEA
C. FTC, FDA

4. A patient approaches the counter with 2 different magnesium products and asks your opinion on which to purchase. Which of the following is an appropriate answer?

A. Let’s look at these a little closer.
B. Neither, it’s better to buy supplements online.
C. The one that’s on sale.

5. Reasons for dietary supplementation include which of the following?

A. To supplement a poor diet.
B. Promotion of optimal immune health
C. No one needs to take dietary supplements.

6. Which of the following companies offer independent third-party dietary supplement certification services?

A. Consumer Reports
B. NSF International
C. Certified Naturally Grown

7. You are entering a new patient into the pharmacy system. In addition to asking about allergies, demographics, and current medications, what else should you ask?

A. How many hours of sleep do you average a night?
B. Do you take any over-the-counter medications or dietary supplements?
C. How many children do you have and how old are they?

8. You are finally heading out for a lunch break and walk past a pharmacy patient in the aisle looking at 2 different brands of St. John’s Wort. What should you do?

A. Keep going, you already punched out and only have 30 min to eat your lunch.
B. Stop and offer to accompany them to the pharmacy to talk to the pharmacist.
C. Stop and help them make a choice between the products.

9. A patient picks up a medication and purchases a bottle of magnesium at the same time. What should you do?

A. Advise the patient that there may be an interaction between the prescription and the magnesium.
B. Ring out the patient as usual.
C. Touch base with the pharmacist to make sure there are no potential interactions between the products.

10. Where should adverse reactions or issues with dietary supplements be reported?

A. FDA Safety Reporting Portal
B. Federal Trade Commission
C. Office of Dietary Supplements

References

1. Cragg GM, Newman DJ. Natural products: a continuing source of novel drug leads. Biochim Biophys Acta. 2013;1830(6):3670-3695. doi:10.1016/j.bbagen.2013.02.008

2. Jones AW. Early drug discovery and the rise of pharmaceutical chemistry. Drug Test Anal. 2011;3(6):337-344. doi:10.1002/dta.301

3. Aitken M, Kleinrock M. The Use of Medicines in the U.S. Spending and Usage Trends and Outlook to 2025. IQVIA Institute for Human Data Science. May 2021. Accessed August 5, 2022. https://www.iqvia.com/-/media/iqvia/pdfs/institute-reports/the-use-of-medicines-in-the-us/iqi-the-use-of-medicines-in-the-us-05-21-forweb.pdf

4. OTC Sales Statistics. Consumer Healthcare Products Association. Accessed June 22, 2022. https://www.chpa.org/about-consumer-healthcare/research-data/otc-sales-statistics

5. Dietary Supplements Market Size, Share & COVID-19 Impact Analysis, By Type (Vitamins, Minerals, Enzymes, Fatty Acids, Proteins, and Others), Form (Tablets, Capsules, Liquids, and Powders), and Regional Forecasts, 2021-2028. Fortune Business Insights. Accessed June 22, 2022. https://www.fortunebusinessinsights.com/dietary-supplements-market-102082

6. Moynihan R, Sanders S, Michaleff ZA, et al. Impact of COVID-19 pandemic on utilisation of healthcare services: a systematic review. BMJ Open. 2021;11(3):e045343. Published 2021 Mar 16. doi:10.1136/bmjopen-2020-045343

7. Dietary Supplements in the Time of COVID-19. Fact Sheet for Health Professionals. National Institutes of Health, Office of Dietary Supplements. Accessed July 20, 2022. https://ods.od.nih.gov/factsheets/COVID19-HealthProfessional/.

8. Adams KK, Baker WL, Sobieraj DM. Myth Busters: Dietary Supplements and COVID-19. Ann Pharmacother. 2020;54(8):820-826. doi:10.1177/1060028020928052

9. US Department of Health and Human Services, National Institutes of Health, Office of Dietary Supplements. Dietary Supplement Label Database (DSLD). Accessed August 5, 2022. https://ods.od.nih.gov/Research/Dietary_Supplement_Label_Database.aspx

10. About the National Health and Nutrition Examination Survey. National Center for Health Statistics. Accessed July 20, 2022. https://www.cdc.gov/nchs/nhanes/about_nhanes.htm

11. Mishra S, Stierman B, Gahche JJ, Potischman N. Dietary supplement use among adults: United States, 2017–2018. NCHS Data Brief, no 399. Hyattsville, MD: National Center for Health Statistics. 2021. DOI: https://doi.org/10.15620/cdc:101131external icon

12. Gahche JJ, Bailey RL, Potischman N, et al. Federal Monitoring of Dietary Supplement Use in the Resident, Civilian, Noninstitutionalized US Population, National Health and Nutrition Examination Survey. J Nutr. 2018;148(Suppl 2):1436S-1444S. doi:10.1093/jn/nxy093

13. 2019 CRN Consumer Survey on Dietary Supplements. Council for Responsible Nutrition. https://www.crnusa.org/2019survey. Published September 30, 2019. Accessed June 1, 2022.

14. Johns Hopkins Coronavirus Resource Center. https://coronavirus.jhu.edu/. Accessed August 5, 2022.

15. Calder PC, Carr AC, Gombart AF, Eggersdorfer M. Optimal Nutritional Status for a Well-Functioning Immune System Is an Important Factor to Protect against Viral Infections. Nutrients. 2020;12(4):1181. Published 2020 Apr 23. doi:10.3390/nu12041181

16. Hamulka J, Jeruszka-Bielak M, Górnicka M, Drywień ME, Zielinska-Pukos MA. Dietary Supplements during COVID-19 Outbreak. Results of Google Trends Analysis Supported by PLifeCOVID-19 Online Studies. Nutrients. 2020;13(1):54. Published 2020 Dec 27. doi:10.3390/nu13010054

17. Natural Medicines. Therapeutic Research Center. Accessed August 2, 2022. https://naturalmedicines.therapeuticresearch.com.

18. Office of Dietary Supplements Dietary Supplement Fact Sheets. Accessed August 2, 2022. https://ods.od.nih.gov/factsheets/list-all/

19. U.S. Department of Agriculture and U.S. Department of Health and Human Services. Dietary Guidelines for Americans, 2020-2025. 9th Edition. December 2020. Available at DietaryGuidelines.gov. https://www.dietaryguidelines.gov/sites/default/files/2021-03/Dietary_Guidelines_for_Americans-2020-2025.pdf

20. Thakkar S, Anklam E, Xu A, et al. Regulatory landscape of dietary supplements and herbal medicines from a global perspective. Regul Toxicol Pharmacol. 2020;114:104647. doi:10.1016/j.yrtph.2020.104647
21. FDA 101: Dietary supplements. United States Food and Drug Administration. Accessed July 31, 2022. https://www.fda.gov/consumers/consumer-updates/fda-101-dietary-supplements.
22. Questions and Answers on Dietary Supplements. U.S. Food and Drug Administration. Accessed July 31, 2022. https://www.fda.gov/food/information-consumers-using-dietary-supplements/questions-and-answers-dietary-supplements.

23. Facts About the Current Good Manufacturing Practices (cGMPs). U.S. Food and Drug Administration. Accessed July 22, 2022.
https://www.fda.gov/drugs/pharmaceutical-quality-resources/facts-about-current-good-manufacturing-practices-cgmps

24. Safety Reporting Portal. Food and Drug Administration. Accessed August 10, 2022. https://www.safetyreporting.hhs.gov/SRP2/en/Home.aspx?sid=da6dc761-7962-4743-82cd-2e62985492d0

25. Veatch-Blohm ME, Chicas I, Margolis K, Vanderminden R, Gochie M, Lila K. Screening for consistency and contamination within and between bottles of 29 herbal supplements. PLoS One. 2021;16(11):e0260463. Published 2021 Nov 23. doi:10.1371/journal.pone.0260463

26. Ćwieląg-Drabek M, Piekut A, Szymala I, et al. Health risks from consumption of medicinal plant dietary supplements. Food Sci Nutr. 2020;8(7):3535-3544. Published 2020 May 19. doi:10.1002/fsn3.1636

27. Genuis SJ, Schwalfenberg G, Siy AK, Rodushkin I. Toxic element contamination of natural health products and pharmaceutical preparations. PLoS One. 2012;7(11):e49676. doi:10.1371/journal.pone.0049676

28. Tucker J, Fischer T, Upjohn L, Mazzera D, Kumar M. Unapproved Pharmaceutical Ingredients Included in Dietary Supplements Associated With US Food and Drug Administration Warnings [published correction appears in JAMA Netw Open. 2018 Nov 2;1(7):e185765]. JAMA Netw Open. 2018;1(6):e183337. Published 2018 Oct 5. doi:10.1001/jamanetworkopen.2018.3337

29. Health Fraud Product Database. United States Food and Drug Administration. Accessed August 10, 2022. https://www.fda.gov/consumers/health-fraud-scams/health-fraud-product-database

30. Warning Letter: Amcyte Pharma, Inc. United States Food and Drug Administration. January 03, 2022. Accessed August 12, 2022. https://www.fda.gov/inspections-compliance-enforcement-and-criminal-investigations/warning-letters/amcyte-pharma-inc-623474-01032022

31. Public Notification: Adam’s Secret Extra Strength Amazing Black contains hidden drug ingredient. United States Food and Drug Administration. July 15, 2022. Accessed August 12, 2022. https://www.fda.gov/drugs/medication-health-fraud/public-notification-adams-secret-extra-strength-amazing-black-contains-hidden-drug-ingredient

32. Coward, RM, Carson CC. Tadalafil in the treatment of erectile dysfunction. Ther Clin Risk Manag. 2008;4(6):1315-1329. Accessed October 3, 2022. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2643112/pdf/TCRM-4-1315.pdf

33. Tucker J, Fischer T, Upjohn L, Mazzera D, Kumar M. Unapproved Pharmaceutical Ingredients Included in Dietary Supplements Associated With US Food and Drug Administration Warnings [published correction appears in JAMA Netw Open. 2018 Nov 2;1(7):e185765]. JAMA Netw Open. 2018;1(6):e183337. Published 2018 Oct 5. doi:10.1001/jamanetworkopen.2018.3337

34. Akabas SR, Vannice G, Atwater JB, Cooperman T, Cotter R, Thomas L. Quality Certification Programs for Dietary Supplements. J Acad Nutr Diet. 2016;116(9):1370-1379. doi:10.1016/j.jand.2015.11.003

35. Dietary Supplement Labeling Guide, U.S. Food and Drug Administration. https://www.fda.gov/food/dietary-supplements-guidance-documents-regulatory-information/dietary-supplement-labeling-guide Accessed July 15, 2022.

36. Frequently Asked Questions for Industry on Nutrition Facts Labeling Requirements. United States Food and Drug Administration. Accessed August 12, 2022. https://www.fda.gov/media/99158/download

37. Cooperman, T. 6 Red Flags to Watch Out For When Buying Vitamins & Supplements. October 9, 2021. Accessed August 12, 2022. https://www.consumerlab.com/answers/what-to-watch-out-for-when-buying-vitamins-and-supplements/vitamin-and-supplement-red-flags

38. Research explores the impact of menopause on women’s health and aging. National Institute of Aging. May 6, 2022. Accessed September 6, 2022. https://www.nia.nih.gov/news/research-explores-impact-menopause-womens-health-and-aging

39. Geller AI, Shehab N, Weidle NJ, et al. Emergency Department Visits for Adverse Events Related to Dietary Supplements. N Engl J Med. 2015;373(16):1531-1540. doi:10.1056/NEJMsa1504267

40. Code of Federal Regulations. Title 16, Chapter II, Subchapter E, Part 1700. Amended September 6, 2022. Accessed September 6, 2022. https://www.ecfr.gov/current/title-16/chapter-II/subchapter-E/part-1700/section-1700.14

41. Zanger UM, Turpeinen M, Klein K, Schwab M. Functional pharmacogenetics/genomics of human cytochromes P450 involved in drug biotransformation. Anal Bioanal Chem. 2008;392(6):1093-1108. doi:10.1007/s00216-008-2291-6

42. Matura JM, Shea LA, Bankes VA. Dietary supplements, cytochrome metabolism, and pharmacogenetic considerations [published online ahead of print, 2021 Nov 4]. Ir J Med Sci. 2021;10.1007/s11845-021-02828-4. doi:10.1007/s11845-021-02828-4

43. Chrubasik-Hausmann S, Vlachojannis J, McLachlan AJ. Understanding drug interactions with St John's wort (Hypericum perforatum L.): impact of hyperforin content. J Pharm Pharmacol. 2019;71(1):129-138. doi:10.1111/jphp.12858

44. Zhou S, Chan E, Pan SQ, Huang M, Lee EJ. Pharmacokinetic interactions of drugs with St John's wort. J Psychopharmacol. 2004;18(2):262-276. doi:10.1177/0269881104042632

45. Chen J, Wang Y. Social Media Use for Health Purposes: Systematic Review. J Med Internet Res. 2021;23(5):e17917. Published 2021 May 12. doi:10.2196/17917

46. Moorhead SA, Hazlett DE, Harrison L, Carroll JK, Irwin A, Hoving C. A new dimension of health care: systematic review of the uses, benefits, and limitations of social media for health communication. J Med Internet Res. 2013;15(4):e85. Published 2013 Apr 23. doi:10.2196/jmir.1933

47. Swire-Thompson B, Lazer D. Public Health and Online Misinformation: Challenges and Recommendations. Annu Rev Public Health. 2020;41:433-451. doi:10.1146/annurev-publhealth-040119-094127

48. Chou WS, Oh A, Klein WMP. Addressing Health-Related Misinformation on Social Media. JAMA. 2018;320(23):2417-2418. doi:10.1001/jama.2018.16865

49. Suarez-Lledo V, Alvarez-Galvez J. Prevalence of Health Misinformation on Social Media: Systematic Review. J Med Internet Res. 2021;23(1):e17187. Published 2021 Jan 20. doi:10.2196/17187

50. Supplement Your Knowledge. Dietary Supplement Education Initiative. United States Food and Drug Administration. May 25, 2022. Accessed July 20, 2022. Reference the Supplement your knowledge program

Only Skin Deep: The Pharmacist’s Guide to Intradermal Vaccine Administration

Researchers have studied intradermal vaccination for various diseases for over a decade, so it was only a matter of time before pharmacists would be asked to learn this route of administration. This is arguably the most challenging method of vaccine administration, and inaccurate technique could render an immunization ineffective. Given the need for intradermal administration of the monkeypox vaccine, pharmacists should be prepared to offer intradermal vaccination to eligible individuals to increase immunization rates, slow viral spread, and improve outcomes for affected individuals.

INTRODUCTION

Major developments to vaccines and vaccine administration in recent years have demanded a great deal from pharmacists. The coronavirus disease-19 pandemic asked us to fight misinformation and vaccine hesitancy to educate the public about a new virus and new vaccine technology. We’ve been challenged to keep up with booster recommendations and the increased workflow that comes with vaccine administration. Many of us also taught our pharmacy technicians how to immunize.

Now, with the emergence of monkeypox comes yet another new vaccine with an unfamiliar method of administration (see our FREE monkeypox activity for a more in-depth discussion about this virus). In August 2022, the United States (U.S.) declared monkeypox a public health emergency and ramped up efforts to vaccinate at-risk individuals subcutaneously (a method with which pharmacists are generally familiar).¹ Shortly thereafter, the U.S. Food and Drug Administration (FDA) recognized that the country’s supply of monkeypox vaccine was unable to meet the current demand given the rapid spread of the virus.² Administering the vaccine intradermally only requires one-fifth of the subcutaneous dose, so the FDA issued an emergency use authorization (EUA) allowing healthcare providers to use this method of administration. This effectively increased the total number of available doses by up to five-fold.²

In September 2022, the U.S. Department of Health and Human Services authorized pharmacists, pharmacy interns, and pharmacy technicians, as appropriate, to administer monkeypox vaccines and therapeutics, under certain conditions.³ Pharmacists should be prepared to offer intradermal vaccination to eligible individuals to increase vaccination rates, slow viral spread, and improve outcomes both for this virus and any future viruses for which this applies.

THE ROLE OF INTRADERMAL ADMINISTRATION

Researchers have studied intradermal vaccination for a range of viral diseases, but only a few things are administered intradermally including^4,5

tuberculosis skin testing
BCG (tuberculosis) vaccine
rabies vaccine
allergy skin testing

Intradermal administration occurs in the dermis just below the epidermis (see Figure 1).⁴ The epidermis—the thinnest layer—is made up mostly of epithelial cells, but also contains melanocytes (pigment-producing cells), Merkel cells (for light-touch stimuli), and Langerhans cells (tissue-resident macrophages).⁵ The dermis is a thicker layer containing cells of the adaptive and innate immune systems including macrophages, mast cells, Langerhans cells, and dermal dendritic cells. Cells of the dermis are essential in processing incoming antigens to decide if they are harmful and activate the immune system accordingly.⁵

Figure 1. Methods of Vaccine Administration

High levels of antigen-presenting cells in the dermis induce a more potent immune response, making this an attractive (and potentially superior) vaccination site.^5,6 This significant reactivity in the dermis also prompts a strong immune response to a smaller quantity of vaccine antigen—as little as one-fifth to one-tenth the dose—compared to intramuscular or subcutaneous administration.^5,7 For this reason, intradermal administration is dose-sparing and potentially cost saving.⁵ Intradermal administration also avoids the rare risk of nerve, blood vessel, or joint space injury.⁷

Clinical studies are evaluating intradermal delivery of other vaccines, but none are currently available in the U.S. aside from monkeypox under the recent EUA.⁵ In years past, an intradermal influenza vaccine was available, but the manufacturer stopped production after the 2017-2018 flu season for unknown reasons.⁸ Of all parenteral routes, intradermal injections have the longest absorption time due to the lack of blood vessels and muscle tissue in this area. This is attractive for sensitivity testing, as reactions are easier to visualize and assess for severity.⁴

While intradermal administration is more efficient and cost-effective, it requires more skill and practice compared to subcutaneous or intramuscular administration.⁹ If incorrectly administered, the vaccine may enter the subcutaneous tissue instead and be ineffective because the dose is too small.

INTRADERMAL ADMINISTRATION TECHNIQUE

The most common intradermal injection sites are the volar aspect (inner surface) of the forearm and the upper back below the scapula (shoulder blade).⁴ Intradermal injection is not the best choice for every patient. Skin should be free of lesions, rashes, moles, or scars that could alter visual inspection of the injection site (or interpretation of test results, when applicable).⁴ In the case of the monkeypox vaccine, intradermal administration is only authorized for patients 18 years or older without a history of keloids (thick, raised scars).¹⁰

Researchers have developed various devices for intradermal drug delivery, but in the absence of specialized devices, individuals can employ the Mantoux technique using a hypodermic needle.⁵ The Mantoux technique is named for French physician Charles Mantoux who used this method for tuberculosis testing in the early 1900s.¹¹ The optimum needle size for this method is 26 to 27 gauge and ¼ to ½ inch long.⁴

The Mantoux technique is new to pharmacists (we know because we could only find information about administration technique in nursing resources), so listen up, take notes, and remember that practice makes perfect^4,10:

Inspect the injection site and select an area that is free from lesions, rashes, moles, or scars. Avoid vaccination in an area where there is a recent tattoo (less than one month old). If tattoos cover both arms, select an area without pigment (ink) if possible. If the tattoo is unavoidable, administer through it.
Clean the site with an alcohol or antiseptic swab using a firm, circular motion. Allow the site to dry completely to prevent alcohol from entering the tissue, which can cause stinging and irritation.
Using the nondominant hand, spread the skin taut at the injection site. Taut skin provides easy entrance for the needle. This is especially important in older individuals with less elastic skin.
Hold the syringe in the dominant hand between the thumb and forefinger at a 5- to 15-degree angle at the selected injection site with the bevel of the needle facing up.
Place the needle almost flat against the patient’s skin and insert the needle into the skin no more than 1/8-inch (about 3 mm) to cover the bevel. Keeping the bevel side up allows the needle to smoothly pierce the skin and deliver the medication to the dermis.
Once the needle is in place, use the thumb of the nondominant hand to slowly push the plunger to inject the medication.
Inspect the injection site for a bleb (small blister) which should appear under the skin. The presence of a bleb indicates that the medication is correctly placed in the dermis. The bleb is desired but not required, so if it doesn't appear, don't panic. Simply adjust your technique for next time.
Withdraw the needle at the same angle it was placed so as not to disturb the bleb and to minimize patient discomfort and tissue damage. Safely discard the syringe in a sharps container.

For more visual learners, the Centers for Disease Control and Prevention provides a video demonstrating how to administer a vaccine intradermally at https://www.cdc.gov/wcms/video/low-res/poxvirus/2022/53345334Monkeypox-Vaccine-Administration.mp4.

CONCLUSION

Vaccines work, that much we know. However, this is only true if they’re accessible, trusted, and used appropriately. Pharmacists can help promote access, education, and vaccine uptake if they have the knowledge and skills to do so. New vaccines and administration recommendations are challenging, but don’t let it get under your skin. We hope this quick-and-dirty overview of intradermal vaccines boosted your confidence and made it easier for you to give it a shot.

Only Skin Deep: The Pharmacist’s Guide to Intradermal Vaccine Administration

Learning Objectives
• DISCUSS the potential benefits of intradermal vaccine delivery
• IDENTIFY how to administer intradermal injections

1. Which of the following is a benefit of intradermal vaccine delivery?
A. It can deliver a larger vaccine dose
B. It has the fastest rate of absorption
C. It avoids the risk of nerve injury

2. Which of the following makes the dermis a good site for vaccine administration?
A. High levels of Merkel cells
B. High levels of antigen-presenting cells
C. Low levels of Langerhans cells

3. About how far should you insert the needle to administer an intradermal injection via the Mantoux technique?
A. 1/8-inch
B. 1/4-inch
C. 1/2-inch

4. Travis Barker comes into your pharmacy asking for an intradermal vaccine. You inspect his forearms full of tattoos and find a small space without ink. You complete intradermal administration and notice a small bubble form under his skin. What does this mean?
A. You administered the vaccine subcutaneously
B. You administered the vaccine too close to a tattoo
C. You administered the vaccine correctly

5. Which of the following is appropriate technique for intradermal administration?
A. Insert the needle at a 5- to 15-degree angle with the bevel facing up
B. Pinch the skin between the thumb and forefinger of the nondominant hand
C. Remove the needle slowly at a 45-degree angle to reduce discomfort

Only Skin Deep: The Pharmacist’s Guide to Intradermal Vaccine Administration

Learning Objectives
• DISCUSS the potential benefits of intradermal vaccine delivery
• IDENTIFY how to administer intradermal injections

1. Which of the following is a benefit of intradermal vaccine delivery?
A. It can deliver a larger vaccine dose
B. It has the fastest rate of absorption
C. It avoids the risk of nerve injury

2. Which of the following makes the dermis a good site for vaccine administration?
A. High levels of Merkel cells
B. High levels of antigen-presenting cells
C. Low levels of Langerhans cells

3. About how far should you insert the needle to administer an intradermal injection via the Mantoux technique?
A. 1/8-inch
B. 1/4-inch
C. 1/2-inch

References

REFERENCES
1. U.S. Department of Health and Human Services. Biden-Harris Administration Bolsters Monkeypox Response; HHS Secretary Becerra Declares Public Health Emergency. August 4, 2022. Accessed October 26, 2022. https://www.hhs.gov/about/news/2022/08/04/biden-harris-administration-bolsters-monkeypox-response-hhs-secretary-becerra-declares-public-health-emergency.html
2. U.S. Food and Drug Administration. Monkeypox Update: FDA Authorizes Emergency Use of JYNNEOS Vaccine to Increase Vaccine Supply. August 9, 2022. Accessed October 26, 2022. https://www.fda.gov/news-events/press-announcements/monkeypox-update-fda-authorizes-emergency-use-jynneos-vaccine-increase-vaccine-supply
3. U.S. Department of Health and Human Services. Notice of Amendment to the January 1, 2016 Republished Declaration under the Public Readiness and Emergency Preparedness Act. October 3, 2022. Accessed October 26, 2022. https://public-inspection.federalregister.gov/2022-21412.pdf
4. Administering intradermal medications. Open Resources for Nursing (Open RN). Accessed October 26, 2022. https://wtcs.pressbooks.pub/nursingskills/chapter/18-4-administering-intradermal-medication/
5. Kim YC, Jarrahian C, Zehrung D, Mitragotri S, Prausnitz MR. Delivery systems for intradermal vaccination. Curr Top Microbiol Immunol. 2012;351:77-112.
6. Hickling JK, Jones KR, Friede M, Zehrung D, Chen D, Kristensen D. Intradermal delivery of vaccines: potential benefits and current challenges. Bull World Health Organ. 2011;89(3):221-226.
7. Brooks JT, Marks P, Goldstein RH, Walensky RP. Intradermal Vaccination for Monkeypox - Benefits for Individual and Public Health. N Engl J Med. 2022;387(13):1151-1153.
8. Influenza vaccine. Aetna Clinical Policy Bulletins. Reviewed August 1, 2022. Accessed October 26, 2022. https://www.aetna.com/cpb/medical/data/1_99/0035.html
9. Miller K. What Is an Intradermal Injection, the New Way the Monkeypox Vaccine Is Being Given? Prevention. August 12, 2022. Accessed October 26, 2022. https://www.prevention.com/health/health-conditions/a40869782/what-is-intradermal-injection/
10. Centers for Disease Control and Prevention. JYNNEOS Smallpox and Monkeypox Vaccine:
ALTERNATE REGIMEN Preparation and Administration Summary (Intradermal Administration). Updated September 27, 2022. Accessed October 26, 2022. https://www.cdc.gov/poxvirus/monkeypox/files/interim-considerations/guidance-jynneos-prep-admin-alt-dosing.pdf
11. Kis EE, Winter G, Myschik J. Devices for intradermal vaccination. Vaccine. 2012;30(3):523-538.

Ketamine and Its Kissing Cousins

Ketamine is Food and Drug Administration-approved as a general anesthetic. Researchers found higher dose ketamine therapy had a more desirable adverse effect profile than the previously used anesthetic phencyclidine (PCP). N-methyl-D-aspartate (NMDA) antagonism from subanesthetic ketamine doses produces dissociative and analgesic effects. As such, prescribers are exploring off-label uses for ketamine in patients with agitation, depression, and pain while considering potential risks to multiple organ systems. Ketamine has the potential to cause complications and providers need to monitor patients closely. Illicit and inappropriate use by abusers and untrained law enforcement officers highlight ketamine’s potentially harmful effects. Educating patients and healthcare providers is vital to allow potential benefits while minimizing harm.

Introduction

Consider this: It’s 10:30 PM on a Friday night, 30 minutes before you leave for the weekend. Suddenly, from across the emergency department you hear, “Get OFF me! No, I have not t-t-taken anything! If you come ANY CLOSER, things are going to get physical!” Not a moment later, an order pops up for ketamine hydrochloride 500 mg intramuscularly (IM) for severe agitation. Concerned, a colleague asks you, “Is this safe? Is this effective? I have never seen a dose this high before. Isn’t this just for horses?”

Ketamine made its debut in human clinical practice in the 1960s when several chemists at Parke Davis Company were searching for an anesthetic with similar effects to phencyclidine (PCP). PCP, ketamine’s notorious kissing cousin, was a promising new anesthetic in the 1950s because of its dissociative effects. However, the chemists quickly became unimpressed with its adverse effect profile (i.e., long-lasting psychoactive effects after anesthesia). Humans experienced intense prolonged emergence delirium following PCP anesthesia, relegating its use to veterinary practice.¹ Chemists searched for a better anesthetic and found ketamine, which has similar dissociative effects without PCP’s negative consequences. Ketamine is a more desirable anesthetic because it has a shorter half-life (2.5 hours) compared to PCP (21 hours) and it causes less delirium.^1,2

Prescribers have begun using ketamine for several off-label uses and patients have also started using the drug or structural analogs in a variety of formulations illicitly. Pharmacists and technicians can ensure ketamine’s safe use by keeping current with new formulations and indications, both approved and unapproved. This continuing education activity will dive into the clinical and social consequences of ketamine use.

What’s Ketamine?

Ketamine is a schedule III-controlled substance approved by the U.S. Food and Drug Administration (FDA) for use as a general anesthetic for diagnostic and surgical procedures.²Ketamine is commercially available in the United States as a solution/injection under its brand (Ketalar) and as generic ketamine.² Healthcare providers most often use intravenous (IV) ketamine, but it may be used IM or compounded into an oral solution.

Healthcare providers also use ketamine off-label for analgesia, agitation, and major depressive disorder. These indications emanate from ketamine’s mechanism of action: it acts specifically on the N-methyl-D-Aspartate (NMDA) receptor as a non-competitive antagonist to block glutamate binding.³Glutamate, a major excitatory neurotransmitter, binds to receptors throughout the nervous system. The NMDA receptor is an ionotropic receptor responsible for the brain’s neuroplasticity, memory, learning, and recovery.^4-6 Blocking this receptor with high ketamine doses (ranging from 0.5 to 2 mg/kg) results in dissociation, decreases in spinal reflexes, and produces a cataleptic state (loss of voluntary movements and reduced consciousness) that is applicable to its current clinical use in anesthesia.² However, at low doses, ketamine can produce analgesia and stimulate new pathways within the brain that reduce depressive symptoms and improve mood.

Although ketamine has useful applications in medicine, prescribers must be aware of the adverse effects and risk factors associated with use and should consider how these effects apply to their patients before initiating the medication. Ketamine adversely impacts multiple organ systems (see Table 1), including but not limited to the cardiovascular system. Increases in blood pressure and heart rate are important cardiovascular effects associated with ketamine therapy.² These cardiovascular effects make it a drug of choice for anesthesia induction in patients with cardiovascular shock, where it anesthetizes patients while improving blood pressure and improving organ perfusion. However, clinicians must avoid ketamine use in patients with preexisting hypertensive conditions or other patients who have limited baroreceptor buffering capacity (baroreceptor buffering is the body’s ability to sense blood pressure) because of those same effects mentioned above.⁶

Table 1. General Adverse Effects of Ketamine^2,6

System	Adverse effects
Cardiovascular	Cardiac arrhythmias, increased blood pressure,* increased heart rate
Central nervous system	Prolonged emergence from anesthesia,* psychosis,* dissociation,* drug dependence, increased intracranial pressure
Dermatologic	Injection site irritation
Gastrointestinal	Nausea,* vomiting, anorexia
Genitourinary	Lower urinary tract dysfunction, bladder dysfunction
Respiratory	Laryngospasm,* respiratory depression,* apnea
Immunologic	Anaphylaxis
Other	Hypersalivation, diplopia (double vision), nystagmus (uncontrollable rapid eye movement)

*Common or serious adverse effects of ketamine use

Further contraindications include hypersensitivity to ketamine or its components.⁷ The American College of Emergency Physicians (ACEP) does not recommend ketamine use in patients with schizophrenia or in children younger than three months of age. The ACEP also advises against solely using ketamine as an anesthetic in procedures involving the pharynx, larynx, and bronchial tree. This recommendation primarily applies to patients with airway instability because ketamine can cause laryngospasms.⁵ Table 2 lists additional considerations in special populations.

Table 2. Special Population Considerations with Ketamine^2,6-8

Special population	Concerns	Recommendation
Pregnancy	Crosses the placenta; may have potential risk to fetus	Avoid use; evaluate benefits vs risk
Breastfeeding	Compatibility and safety unknown	Avoid breastfeeding to children with respiratory risk factors
Pediatrics	Can be given with anticholinergics to minimize hypersalivation	Refer to pediatric dosing. Avoid in infants < 3 months of age
Elderly	May be sensitive to dissociative adverse effects	Refer to adult dosing
Kidney dysfunction	No additional concerns	Refer to dosing parameters
Liver dysfunction	Hepatobiliary dysfunction with recurrent use	Refer to dosing parameters; monitor LFTs with repeated ketamine use
LFTs = liver function tests

Healthcare providers should monitor patients' vital signs closely during treatment with ketamine. Anesthesiologists and pharmacists must continuously watch patients undergoing surgical or diagnostic procedures for proper induction and maintenance of dissociative effects.² In patients who must take repeated doses of ketamine (e.g., for chronic pain management or psychiatric disorders), healthcare providers should order liver function tests at baseline and every one to two days during treatment.^2,6,9,10

Ketamine’s Kissing Cousins

As shown in Figure 1, ketamine is structurally related to many compounds. The drugs in Figure 1 antagonize the NMDA receptor and exhibit a dissociative effect.¹ PCP is one of the most notoriously abused drugs. Compared with ketamine, PCP is 10 times more potent and has a longer duration of action due to its strong affinity for the NMDA receptor. Both ketamine and PCP can replicate schizophrenia’s positive, negative, and cognitive symptoms and exacerbate underlying schizophrenia. But because ketamine has lower potency and a shorter duration of action, it induces fewer severe psychiatric effects than PCP.¹

Figure 1. Molecular structure of ketamine and structurally related dissociative drugs¹¹

Although ketamine’s labeling includes many precautions, it is an emerging option because of its therapeutic benefits. Xi Biopharmaceuticals is developing a sublingual wafer to treat acute pain while Janssen Pharmaceuticals has developed a nasal spray formulation for treatment resistant depression.^12,13 Table 3 compares the current ketamine formulations that are FDA-approved or under investigation.

Table 3. Ketamine Counterparts^12-14

Cousins	Formulation	Use & Dose	Approval or Trial Phase
Ketalar (ketamine hydrochloride)	Injectable	Anesthesia 0.25 – 0.35 mg/kg followed by CIVI 1 mg/kg/hr	FDA-approved
Wafermine (ketamine)	Sublingual Wafer	Acute Pain 25 mg, 50 mg & 75 mg PRN for 12 hrs	End-of-Phase 2 Clinical Trials
Spravato (esketamine)	Nasal Spray	Treatment Resistant Depressive Disorder 28 mg, 56 mg, 84 mg twice a week	FDA-approved
ABBREVIATION: CIVI = continuous intravenous infusion

ABUSE, ADDICTION, DEPENDENCE

Why is Ketamine Dangerous?

Long-term ketamine abuse is associated with memory, attention, and judgment impairment. The actual risk of ketamine abuse in the general population is low compared to other substances of abuse, but patients with polysubstance abuse disorder tend to use it.¹⁵ A study examining polysubstance abuse conducted in New York City found that polydrug use occurred because of an unexpected opportunity to use ketamine after already consuming other drugs. Researchers also determined that polysubstance abusers purposefully used ketamine with another substance to achieve an individually desired effect. Oftentimes polydrug-using events occurred within a group and each member contributed something: ketamine, knowledge, other drugs, or space to use drugs.¹⁶

Currently, ketamine is only commercially available as an injectable liquid. Dealers illegally sell ketamine as a recreational injectable substance or a white powder that resembles cocaine. The Department of Justice and Drug Enforcement Administration report that illegally distributed ketamine is diverted or stolen from veterinary clinics or smuggled into the United States from Mexico.¹⁷ Dealers can then synthesize ketamine into a powder or sell it as an injectable liquid.¹⁸ Prices average from $20-$25 per dose (50 mg to 100 mg).¹⁹ Drug abusers find ketamine’s dissociative sensations and hallucinations appealing. Users can inject liquid ketamine, or snort or smoke powdered ketamine.¹⁷ Ketamine is a popular drug to facilitate physical or sexual assault because it is a colorless, tasteless, and odorless liquid making it difficult for victims to detect. Additionally, ketamine is known to cause impaired coordination, confusion, and memory loss.²⁰

Ketamine’s IV administration started in the early 1990s. Injection events occur most frequently in large cities with high rates of homelessness, like New York City and Los Angeles.¹⁸ Researchers conducted a study with 213 people who abused IV ketamine.¹⁸ Among these users, 84% admitted to abusing ‘harder’ drugs first, with heroin predominating. Users reported their first ketamine injection happening among a group of people. This group often included people well known to them who provided knowledge and the materials for injecting.¹⁸

What attracts people to a dissociative drug with unknown psychoactive effects? Exactly that: the unknown. With most abused drugs, the user understands the effects they will experience. When someone takes ketamine, the reaction to each dose is unknown. Some users seek variety. Ketamine users have described an out of body experience that expands internal and external realms and realities.¹⁸ On the other hand, abusers also describe a “K-Hole”—an experience that they describe as near-death that results when they ingest too much ketamine.¹⁷

Timothy Wyllie, a spiritualist, describes ketamine doses as a curve over time through realms. He describes the domains abusers experience as they dose ketamine²¹:

The realm “I,” for internal reality, occurs at doses 30 to 75 mg roughly 10 minutes after injection.
The extraterrestrial reality realm, “They,” occurs at doses 75 to 150 mg approximately 15 minutes after injection.
The realm “We,” for network creation realm, occurs at doses from 150 to 300 mg mg approximately 15 minutes after injection.
An unknown realm exists at doses of more than 300 mg.

The doses studied for depression fall in the realm of internal reality. At these doses, users can see areas needing self-improvement that they were unaware they had the ability to fix. Drug users prefer subanesthetic doses but those that are higher than doses studied for treating depression. As the dose increases, users become so far removed from reality that “extraterrestrial” experiences begin.²¹

KETAMINE USES

Anesthesia

Patients unable to maintain and protect their airways require endotracheal intubation. Healthcare providers use ketamine as a sedative to facilitate rapid sequence induction and intubation (RSII), by inducing an anesthetized state, prior to paralyzing the patient. The decision to intubate is based on the patient’s Glasgow Coma Score.^22,23A score of 8 or less qualifies a patient to receive endotracheal intubation.²³ Healthcare providers follow a RSII strict algorithm, shown in Table 4, detailing the order in which medications should be administered based upon the onset and duration of action.

Table 4. Algorithm of Rapid Sequence Induction & Intubation^22,23

Step of RSII	What and Why	Medications Used
Premedication^*	Airway manipulation causes a sympathetic activation due to a pressor response. This sympathetic response leads to an increase in intracranial pressure and mean arterial pressure.	alfentanil, fentanyl, lidocaine, sufentanil
Sedation	Used to induce an anesthetic state before a paralytic is used and the airway manipulated. Crucial that a patient is properly sedated before paralyzed.	Also known as induction agents: etomidate, ketamine, midazolam, propofol
Paralytics^±	Neuromuscular blocking agents are given to relax pharyngeal and diaphragmatic muscles allowing for an endotracheal tube to be placed.	rocuronium, succinylcholine, vecuronium

*: Based upon time constraints/needs this step may be omitted

±: It is imperative to confirm a patient is properly sedated before beginning paralysis because if the patient is awake, they may feel the tube insertion

The drugs used in RSII possess unique characteristics, including IV use, quick onset, and short duration of action.²³ Traditionally, etomidate has been the gold standard for RSII, but ketamine is quickly becoming a commonly used alternative.²³ Table 5 highlights the differences between etomidate and ketamine.

Table 5. Comparison of Etomidate and Ketamine^22,23

	Etomidate	Ketamine
Dose for Induction	0.3 mg/kg	1.5 mg/kg or 0.1-0.5 mg/kg/min with 10% given as induction bolus
Onset of Action	10-15 seconds	< 30 seconds
Duration of Action	4-10 minutes	10-15 minutes
Benefits	Stable hemodynamic profile, decreases metabolic rate, decreases cerebral blood flow, increases generalized seizure threshold	Sedative and analgesic properties,^* cardiovascular and respiratory stimulation, and smooth muscle relaxation (beneficial in reactive airway disease, hypotensive, volume depleted, and septic patients)
Risks	Adrenal suppression, do not use in septic shock, lowers focal seizure threshold, increased incidence of ARDS	Potentiates effect of epinephrine, increases cardiac oxygen demand, may increase ICP,** emergent reactions, infusion related respiratory depression, hypersalivation
ABBREVIATIONS: ARDS = acute respiratory distress syndrome, ICP = intracranial pressure * Ketamine can be used as a combined premedication and induction step ** Data is conflicting, however, may not be suitable for patients with head trauma

The differences between etomidate and ketamine create a significant role in RSII for both drugs, but for different presenting conditions. Ketamine is gaining popularity for its use in septic patients, hypotensive patients, and those with reactive airway diseases. Choosing etomidate is preferable for patients with a hemodynamically stable profile and patients with traumatic brain injury where it could be cerebroprotective.

Analgesia (pain)

Ketamine’s use in pain management is controversial due to limited data, but this dataset is growing.^15,24 Before considering subanesthetic ketamine doses, prescribers should collaborate with patients and other clinical team members to try other approved pain regimens.²⁵ Using ketamine for its analgesic properties should be based on patient-specific criteria. The prescriber must assess the patient’s treatment goals, current medical conditions, pain types, and available protocols.

Ketamine is not discussed in available pain guidelines. Some literature recommends its use after unsuccessful trials of at least two opioids. Data supporting ketamine’s use in both acute and chronic pain management is mixed in its findings.^26,27 Most trials conclude ketamine can reduce acute pain exacerbations but note that prescribers must be cautious of its adverse effects.¹⁵ Data from small trials indicate using ketamine to overcome opioid withdrawal and opioid-induced-hyperalgesia (neuropathic pain) may be possible. Ketamine has a unique ability to counteract the unfavorable responses patients might experience on chronic high-dose opioids by its mechanism of action.^24,28 Overstimulated opioid receptors from high dose opioid use causes more hyperalgesia. Several small case reports describe patients on high-dose chronic opioid therapy who reduced their opioid doses after low-dose ketamine administration.²⁹

An open labeled audit determined that IV ‘burst’ ketamine therapy improved analgesia in neuropathic pain and painful bone metastases. Researchers enrolled 39 cancer patients who were refractory to opioid therapy. Patients received bursts of low-dose ketamine (100 to 500 mg/day) over three to five days and reported somatic and neuropathic pain relief for up to eight weeks.¹⁵

Limited evidence supports oral ketamine’s effect in chronic pain and most studies that examine its use are case reports or non-comparative trials. Compared to IV administration, lower oral ketamine concentrations are associated with analgesic effects. Oral ketamine has been associated with higher serum levels of its metabolite, norketamine. This metabolite seems to contribute to oral ketamine’s analgesic effects due to its shorter half-life and ability to reach much higher peak plasma concentrations than after IV administration. However, researchers have not extensively explored this in current literature.²⁹

Healthcare providers and patients face many hurdles when using ketamine for pain relief. Prescribers should avoid high ketamine doses that may cause a range of serious adverse effects. Unlike opioids, ketamine has a ceiling effect and maximum dose. Oral ketamine administration has a low bioavailability and is directly linked with a high rate of adverse effects.^15,27

Agitation

Due to ketamine’s dissociative properties, clinicians are increasingly using ketamine for treating pre-hospital and in-hospital agitation. Lacking a uniform definition for agitation, healthcare providers, institutions, and organizations may use different criteria to choose medication intervention in an agitated patient. Although the picture of agitation may change depending on the situation, validated scales like the Altered Mental Status Scale (AMSS) can define agitation’s severity.³⁰ The AMSS translates agitation into a quantifiable, real concept. The line between agitation and delirium is often unclear but has major ramifications for a patient’s treatment and outcome.³⁰ For example, excited delirium, an agitation subtype, classifies a patient’s agitation past the emotional component and includes psychomotor, metabolic, and contributing disease states as possible reasons for agitation.³⁰

As with most psychiatric disorders, identifying and treating agitation has been suboptimal. Since the 1980s, a popular cocktail of medications, known among emergency department physicians as the “B-52” order, has been the mainstay of agitation treatment in psychiatric facilities and emergency departments.³¹ When examining the B-52 order’s components, it is easy to see the correlation between the regimen and the American jet-powered strategic bomber from which it derives its name: Benadryl 50 mg IM, haloperidol 5 mg IM, lorazepam 2 mg IM.³¹ The B-52 order serves as a reminder of the suboptimal approach traditionally taken when confronted with an agitated patient.

Ketamine’s different routes of administration have benefits and disadvantages. Although less invasive, oral ketamine takes a longer time to reach the therapeutic range, something that is undesirable in an overly aggressive patient. Intravenous administration has the quickest onset but is the most invasive. Securing IV access may not always be possible. The IM route is the most often used method for agitation control for its quick “on/off” onset and duration of action, and its applicable dosage form.

A review explains ketamine’s uses and benefits in comparison to other, more traditional agitation treatments.³⁰ In terms of agitation efficacy, ketamine provides the same, if not better, response when compared to its more traditional counterparts.³⁰ Ketamine has a significantly faster onset of action when compared to haloperidol (5 minutes versus 17 minutes) and requires less redosing (5% of patients re-dosed versus 20% of patients re-dosed, respectively).³⁰ However, ketamine continues to show a higher incidence of adverse effects when compared to its anti-psychotic counterpart (percent incidence calculated from six studies where adverse events were recorded as a secondary outcome):³⁰

emergence reaction 12.3% (8/65 patients)
- An “emergence reaction” is an often hostile, psychiatric episode brought about by ketamine use
hypersalivation 31.8% (22/69 patients)
nausea and vomiting 8.5% (7/82 patients)
respiratory complications 7.6% (9/118 patients)

Although studies report a higher incidence of adverse reactions when using ketamine for agitation, it is important to consider study limitations: small patient populations, co-administration of drugs, and lack of adverse event reporting (only half of 12 studies included adverse reactions).³⁰ If used properly, ketamine can be a safe, quick-acting drug to stop agitation when compared to traditional treatments.

Some law enforcement agencies use ketamine. However, when they use ketamine improperly, or when adverse effects arise, ketamine can have dangerous consequences. Over a four-day period during late August of 2020 in Colorado, police gave 23-year-old Elijah McClain and 25-year-old Elijah McKnight excessive ketamine doses for agitation.³² McClain died from cardiac arrest and McKnight survived but required life support in the hospital.³² It is inappropriate to allow untrained police officers to inject ketamine as a law enforcement tool. However, police defend using ketamine saying suspects with mental health issues or suspects taking drugs can be belligerent and dangerous. A Minnesota whistleblower lawsuit filed by a former emergency medical services worker claims police pressured them to allow ketamine use uneccessarily.³² In Minneapolis, ketamine used by police rose from four incidents per year in 2015 to 62 in 2017.³² This marked increase in ketamine use is upsetting many healthcare professionals. Dr. Mary Dale Peterson, president of the American Society of Anesthesiologists, says that ketamine can have “dangerous complications,” just like any other anesthetic. Dr. Peterson points out that justifiably using ketamine occurs very rarely.³²

Whistleblowers cite complications from unwarranted ketamine use are associated with emergence reactions, and improper dosages.³² McClain died when he was given a ketamine dose for a 200-pound man but only weighed 143 pounds.³² Pharmacists can play a role in educating other healthcare professionals about proper dosing and management of ketamine’s serious adverse effects.

Major Depressive Disorders

Generally, major depressive disorder’s (MDD) treatment focuses on pathophysiology and regulates serotonin, norepinephrine, and dopamine.³² Medications such as selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibits (SNRIs), tricyclics, tetracyclics, and serotonin modulators all target an increase in synaptic neurotransmitter levels.³² Unfortunately, these drugs are not consistently effective for all patients, require an 8-week trial period, and have unfavorable adverse effects. For many providers and their patients, MDD treatment can feel like an awful waiting game—one that they sometimes lose.

Ketamine is becoming increasingly popular for its use in treating refractory depression. However, it requires healthcare providers to understand how it works to avoid putting patients into a “K-hole.” It offers a different approach to the current FDA-approved drugs for MDD. Ketamine prevents glutamate reuptake; excess glutamate produces an antidepressant effect. Ketamine, at subanesthetic doses, produces euphoria, and improves symptoms within 24 hours after infusion.^4,14,32,33 Depressive symptoms improve rapidly, but the effects last only a few days to weeks. As a result, ketamine is most useful as an adjunctive treatment option. Patients feel better for a brief period, giving their antidepressants a chance to start working.

In addition, prescribers have few options for patients with MDD who have suicidal behaviors and ideation. Ketamine seems promising for patients at an elevated risk for self-harm. The Ketamine for Rapid Reduction of Suicidal Thoughts in Major Depression trial examined ketamine’s potential benefits for 80 suicidal patients with MDD. The results of this randomized controlled study showed that ketamine was superior to midazolam in improving the Scale for Suicidal Ideation (SCI). Patients’ SCI scores improved 4.96 points within 24 hours after a ketamine infusion of 0.5 mg/kg over 40 minutes.³² This suggests clinical use of ketamine as an adjuvant agent for acute episodes of suicide ideation in patients maintained on guideline recommended therapy for MDD may be appropriate. However, patient safety remains a concern (e.g., dissociative effects, abuse potential, respiratory, and cardiovascular effects).

As mentioned earlier, esketamine (Spravato) is ketamine’s S-enantiomer and FDA-approved for treatment-resistant depression.³³ In the TRANSFORM-1 randomized controlled trial, the antidepressant/esketamine groups did not have a statistically significant change in Montgomery-Asberg Depression Rating Scale (MADRS) total score (from baseline to study day 28) when compared to the antidepressant placebo group.^34,35 However, the changes based on the MADRS were clinically meaningful and showed that esketamine has a beneficial role in treatment-resistant depression when used as an adjuvant agent.^36,37 The combination of esketamine with an antidepressant produced desirable outcomes while minimizing adverse effects. Although adverse effects were low, several adverse effects are possible: vertigo, nausea, vomiting, anxiety, sedation, abuse potential, increased blood pressure, dissociation, and suicidal thoughts/behaviors.³³

CONCLUSION

To paraphrase the father of toxicology, Paracelsus, it’s all about the dose. Ketamine is the poster child drug for this statement. Ketamine has the potential to be an important adjuvant therapy for the treatment of a range of conditions. Those listed in this CE—anesthesia, analgesia, and major depressive disorder—are currently the most studied disorders where ketamine and its derivatives may be useful. Due to ketamine’s dissociative and analgesic effects through NMDA antagonism, there may be additional future potential uses for ketamine in pain control and psychiatric disorders. Simply, ketamine treats not only the physical manifestations of these conditions but the emotional component that providers can easily overlook. However, the current data sets are small, many use rating scales instead of final health outcomes, and a larger and longer term series of trials are required to fully determine the place of ketamine in the treatment armamentarium for patients.

Pharmacists and other healthcare providers will need to distinguish between therapeutic use and addiction. Often, these lines are muddled. Providing education is a first step to preventing abuse. Usually, addiction is a manifestation of an untreated, or undertreated, medical condition. Pharmacist intervention helps patients and healthcare providers to make the safest, most informed decisions possible to ensure the best possible outcomes.

Pharmacist Post-Test
Objectives:
1. Identify patient populations in which ketamine use is justified based on its FDA approved indications and for off-labeled use where it has been sufficiently studied
2. Compare the different formulations of ketamine and its “kissing cousins”
3. Describe potential risks associated with ketamine use

1. Patient AV has a GCS score of 8 and requires intubation. He presents with volume depletion, hypotension, and sepsis. What drug would the anesthesiologist probably use for sedation?
a. Fentanyl
b. Etomidate
c. Ketamine

2. In which patients would you avoid recommending ketamine?
a. Patients with reactive airway disease
b. Patients with sepsis or hypotension
c. Patients with traumatic brain injury

3. Which formulation of esketamine is FDA-approved for treatment resistant depressive disorder?
a. Injectable
b. Nasal spray
c. Infusion

4. What is the most commonly used route of administration when using ketamine for agitation?
a. IV
b. IM
c. PO

5. A clinician asks you about ketamine’s adverse effects. What would you say to start?
a. Ketamine can cause cardiac arrythmias.
b. Ketamine can decrease blood pressure.
c. Ketamine can worsen peptic ulcers.

6. What is the correct order of administration for RSII medications?
a. Premedication, sedative, paralytic
b. Premedication, paralytic, sedative
c. Sedative, premedication, paralytic

7. When should prescribers monitor liver function in patients who receive repeated ketamine doses?
a. At baseline and every 1 to 2 months
b. At baseline and every 1 to 2 weeks
c. At baseline and every 1 to 2 days

8. What is a “K-hole?”
a. A networking experience
b. A near-death experience
c. An extraterrestrial experience

9. What is a limitation of using ketamine in MDD?
a. Depressive symptoms improve slowly
b. Requires an 8-week trial period first
c. Effects last only a few days to weeks

10. A police officer asks you to discuss ketamine and asks why you refer to similar drugs as “kissing cousins.” How would you explain it?
a. They all have similar potency and antagonize NMDA receptor
b. They are used in similar doses and act as a NMDA receptor agonist
c. They are structurally similar and antagonize NMDA receptor

Technician Post-Test
Objectives:
1. Identify patient populations in which ketamine use is justified based on its FDA approved indications and for off-labeled use where it has been sufficiently studied
2. Compare the different formulations of ketamine and its “kissing cousins”
3. Describe potential risks associated with ketamine use

1. In which patient should prescribers avoid using ketamine?
a. patient with serious peptic ulcer
b. patient older than 3 months old
c. patient with uncontrolled hypertension

2. What ketamine dose results in dissociation?
a. 0.1 to 0.5 mg/kg
b. 0.5 to 2 mg/kg
c. 2 to 3.5 mg/kg

3. What is a risk associated with using ketamine in RSII?
a. adrenal suppression
b. increase ARDS incidence
c. emergent reactions

4. What ketamine formulation is currently available by prescription?
a. sublingual tablet
b. injectable solution
c. 24-hour patch

5. What risk is associated with ketamine use?
a. exacerbates underlying schizophrenia
b. lowers focal seizure threshold
c. increases incidence of ARDS

6. What is a key difference between PCP and ketamine?
a. PCP has a shorter duration of action than ketamine
b. PCP is 10 time more potent than ketamine
c. PCP has less severe psychiatric effects than ketamine

7. What is a benefit of using ketamine for agitation in comparison to haloperidol?
a. faster onset
b. more redosing
c. fewer side effects

8. What is ketamine’s FDA-approved indication?
a. agitation
b. analgesia
c. anesthesia

9. What can be expected when people use oral ketamine?
a. high bioavailability
b. high rate of adverse effects
c. low plasma peak concentrations

10. What is ketamine’s role in RSII?
a. premedication
b. sedative
c. paralytic

References

1. Li L, Vlisides PE. Ketamine: 50 Years of modulating the mind. Front Hum Neurosci. 2016;10:612. Published 2016 Nov 29. doi:10.3389/fnhum.2016.00612

2. Ketalar. Prescribing information. Par Pharmaceutical; 2022. Accessed July 25, 2022. https://www.parpharm.com/pdfs/catalog/sterile/Ketalar_PI_20220613.pdf

3. Institute of Medicine (US) Forum on Neuroscience and Nervous System Disorders. Glutamate-Related Biomarkers in Drug Development for Disorders of the Nervous System: Workshop Summary. Washington (DC): National Academies Press (US); 2011.

4. Aleksandrova LR, Phillips AG, Wang YT. Antidepressant effects of ketamine and the roles of AMPA glutamate receptors and other mechanisms beyond NMDA receptor antagonism. Journal of Psychiatry Neuroscience. 2017;42(4):222-229. DOI: 10.1503/jpn.160175.

5. Vyklicky V, Korinek M, Smejkalova T, et al. Structure, function, and pharmacology of NMDA receptor channels. Physiol Res. 2014;63(Suppl 1):S191-S203. doi:10.33549/physiolres.932678

6. Godwin SA, Burton JH, Gerardo CJ, et al. American College of Emergency Physicians. Clinical policy: procedural sedation and analgesia in the emergency department. Ann Emerg Med. 2014;63(2):247-258.e18. doi:10.1016/j.annemergmed.2013.10.015[PubMed 24438649]

7. Ellingson A, Haram K, Sagen N, Solheim E. Transplacental passage of ketamine after intravenous administration. Acta Anaesthesiol Scand. 1977;21(1):41-44.[PubMed 842268]

8. Visser E, Schug SA. The role of ketamine in pain management. Biomed Pharmacother. 2006;60(7):341-348. doi:10.1016/j.biopha.2006.06.021

9. Zhu X, Kohan LR, Goldstein RB. substantial elevation of liver enzymes during ketamine infusion: a case report. A Pract. 2020;14(8):e01239. doi:10.1213/XAA.0000000000001239

10. Wilkinson ST, Sanacora G. Considerations on the Off-label Use of Ketamine as a Treatment for Mood Disorders. JAMA. 2017;318(9):793-794. doi:10.1001/jama.2017.10697

11. Ho JH, Dargan PI. Arylcyclohexamines (Ketamine, Phencyclidine, and Analogues). In: Critical Care Toxicology. Brent J, Burkhart K, Dargan P, Hatten B, Megarbane B, Palmer R, eds. Springer; 2016. https://doi.org/10.1007/978-3-319-20790-2_124-1

12. Lodge D, Mercier MS. Ketamine and phencyclidine: the good, the bad and the unexpected. Br J Pharmacology. 2015;172(17):4254-4276. doi:10.1111/bph.13222

13. Study of Wafermine™ for post-bunionectomy or abdominoplasty pain. ClinicalTrials.gov identifier: NCT03246971. Updated July 23, 2018. Accessed Jul 25, 2022. https://clinicaltrials.gov/ct2/show/study/NCT03246971

14. Treating major depressive disorder: a quick reference guide. American Psychiatric Association. Published October 2010. Accessed July 25, 2022. https://psychiatryonline.org/pb/assets/raw/sitewide/practice_guidelines/guidelines/mdd-guide.pdf

15. Visser E, Schug SA. The role of ketamine in pain management. Biomed Pharmacother. 2006;60(7):341-348. doi:10.1016/j.biopha.2006.06.021

16. Lankenau SE, Clatts MC. Patterns of polydrug use among ketamine injectors in New York City. Subst Use Misuse. 2005;40(9-10):1381-1397. doi:10.1081/JA-200066936

17. Drug Fact Sheet: Ketamine. Department of Justice and Drug Enforcement Administration. Published April 2020. Accessed July 25, 2022. https://www.dea.gov/sites/default/files/2020-06/Ketamine-2020.pdf

18. Lankenau SE, Sanders B, Bloom JJ, et al. First injection of ketamine among young injection drug users (IDUs) in three U.S. cities. Drug Alcohol Depend. 2007;87(2-3):183-193. doi:10.1016/j.drugalcdep.2006.08.015

19. Average Cost of Illicit Street Drugs. AddictionResource.net. Updated June 21, 2021. Accessed July 25, 2022. https://www.addictionresource.net/cost-of-drugs/illicit/

20. Świądro M, Stelmaszczyk P, Lenart I, Wietecha-Posłuszny R. The Double Face of Ketamine-The Possibility of Its Identification in Blood and Beverages. Molecules. 2021;26(4):813. Published 2021 Feb 4. doi:10.3390/molecules26040813

21. Morris, H. Hamilton’s Pharmacopeia Ketamine: Realms and Realities. [Video]. Vice TV. December 26, 2017. Accessed July 25, 2022. https://www.vicetv.com/en_us/video/hamiltons-pharmacopeia-ketamine-realms-and-realities/59cd5d0b7752d1ac3e90aacf

22. Kurdi MS, Theerth KA, Deva RS. Ketamine: Current applications in anesthesia, pain, and critical care. Anesth Essays Res. 2014;8(3):283-290. doi:10.4103/0259-1162.143110

23. Scarponcini TR, Edwards CJ, Rudis MI, Jasiak KD, Hays DP. The role of the emergency pharmacist in trauma resuscitation. J Pharm Pract. 2011;24(2):146-159. doi:10.1177/0897190011400550

24. Lee M, Silverman SM, Hansen H, Patel VB, Manchikanti L. A comprehensive review of opioid-induced hyperalgesia. Pain Physician. 2011;14(2):145-161.

25. Johnstone-Petty, M. Ketamine use for complex pain in the palliative care population. J Hosp Palliat Nurs. 2018;20(6):561-567. doi: 10.1097/NJH.0000000000000488.

26. Mercadante S, Caruselli A., Casuccio A. The use of ketamine in a palliative-supportive care unit: a retrospective analysis. Ann Palliat Med. 2018;7(2): 205-210. doi: 10.21037/apm.2018.01.01

27. Bell RF, Kalso EA. Ketamine for pain management. Pain Rep. 2018;3(5):e674. Published 2018 Aug 9. doi:10.1097/PR9.0000000000000674

28. Lalanne L, Nicot C, Lang JP, et al. Experience of the use of Ketamine to manage opioid withdrawal in an addicted woman: a case report. BMC Psychiatry. 2016;16(1):395. doi:10.1186/s12888-016-1112-2

29. Blonk MI, Koder BG, Van Den Bemt PMLA, Huygen FJPM. Use of oral ketamine in chronic pain management: a review. Eur J Pain. 2012;14(5): 466-472. https://doi-org.ezproxy.lib.uconn.edu/10.1016/j.ejpain.2009.09.005

30. Linder LM, Ross CA, Weant KA. Ketamine for the acute management of excited delirium and agitation in the prehospital setting. Pharmacotherapy. 2018;38(1):139-151. doi:10.1002/phar.2060

31. Lulla AA, Singh M. The Art of the ED Takedown. emDOCs.net - Emergency Medicine Education. Published March 4, 2015. Accessed July 25, 2022. http://www.emdocs.net/the-art-of-the-ed-takedown/

32. Young R, McMahon S. Some States Allow Authorities to Use Ketamine to Subdue Suspects in The Field. But Is It Safe? Some States Allow Authorities to Use Ketamine to Subdue Suspects in The Field. But Is It Safe? | Here & Now. Published September 8, 2020. Accessed July 25, 2022. https://www.wbur.org/hereandnow/2020/09/08/ketamine-police-safety-elijah-mcclain

33. Ketamine. In: Lexi-Drugs. Lexi-Comp, Inc. Updated July 20, 2022. Accessed July 25, 2022. http://usj-ezproxy.usj.edu:2099/lco/action/doc/retrieve/docid/patch_f/7135?cesid=a8n33eDrj1M&searchUrl=%2Flco%2Faction%2Fsearch%3Fq%3Dketamine%26t%3Dname%26acs%3Dfalse%26acq%3Dketamine#rfs

34. Montgomery-Asperg Depression Rating Scale. Accessed July 27, 2022. https://www.mdcalc.com/calc/4058/montgomery-asberg-depression-rating-scale-madrs

35. Fedgchin M, Trivedi M, Daly EJ, et al. Efficacy and safety of fixed-dose esketamine nasal spray combined with a new oral antidepressant in treatment-resistant depression: results of a randomized, double-blind, active-controlled study (TRANSFORM-1). Int J Neuropsychopharmacol. 2019;22(10):616-630. doi:10.1093/ijnp/pyz039

36. Spravato. Prescribing information. Janssen Pharmaceutical Companies; 2019. Accessed July 25, 2022. https://www.janssenlabels.com/package-insert/product-monograph/prescribing-information/SPRAVATO-pi.pdf

37. Fedgchin M, Trivedi M, Daly EJ, et al. Efficacy and safety of fixed-dose esketamine nasal spray combined with a new oral antidepressant in treatment-resistant depression: results of a randomized, double-blind, active-controlled study (TRANSFORM-1). Int J Neuropsychopharmacol. 2019;22(10):616-630. doi:10.1093/ijnp/pyz039

The Mediterranean Diet’s Effect on Health

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

· Review the Mediterranean diet’s history and essential components

· Discuss the relationship between culture, associated foods, and proven health benefits

· Describe the relationship between the Mediterranean diet and the human microbiome

· Discuss the pharmacist’s role as a resource for disseminating accurate, concise information to patients about the Mediterranean diet

Pharmacist Post-Test
1. Ancel Keys was considered an icon in:
a. Coronary heart disease
b. Cardiovascular nutrition
c. Influencing diet

2. Why did Ancel Keys become interested in studying cholesterol?
a. He was a vegetarian, which is notoriously a low-cholesterol diet
b. He was Italian and thought everyone should eat like Italians do
c. He noticed a significant increase in heart disease mortality

3. What did Ancel Keys observe while traveling to Europe in the 1950s?
a. Individuals born and raised in France or Germany experienced almost no cardiovascular disease or dyslipidemia
b. There was a stark difference in the foods consumed and the health in Mediterranean countries compared to the United States
c. In both France and Germany, the wealthy had high rates of cardiovascular disease, but the working class poor people had almost no cardiovascular problems

4. At what meeting did Keys present his ideas?
a. World Health Organization
b. UNESCO
c. PREDIMED

5. What percentage of calories come from a carbohydrate source for the Mediterranean diet?
a. 20%-30%
b. 45%-55%
c. 60%-70%

6. What disease states can benefit from the Mediterranean diet?
a. Kidney disease, diabetes, asthma, Crohn’s, ulcerative colitis
b. Ulcerative colitis , cardiovascular disease, GERD, asthma
c. Cardiovascular disease, diabetes, hypertension, kidney disease

7. What is the human microbiome?
a. The human microbiome is the complete population of all microbial organisms in and on our body
b. The human microbiome is the microbial composition in our gastrointestinal tract, their genes and the environment that they live in within our bodies
c. The human microbiome is the complete species list of all organisms that could pose a potential threat to our bodies

8. Which disease states are likely to benefit from the microbiome?
a. Kidney disease, diabetes, asthma, Crohn’s
b. Ulcerative colitis , cardiovascular disease, GERD, migraines
c. Cardiovascular disease, celiacs disease, obesity

9. Which of the following is NOT a function of the microbiome?
a. The microbiome strengthens the impermeability of the intestine
b. The microbiome helps produce sex hormones to provide optimal fertility
c. The microbiome contributes to immune system function

10. Which of the following food groups provides the most amount of microbes to our bodies?
a. Grains and cereals
b. Meats
c. Fruits and vegetables

11. What is the effect of Bifidobacterium and Lactobacillus in the microbiome?
a. They create the perfect environment for bacteria to grow by enhancing the pH and water saturation throughout the GI tract
b. They defend the intestines against opportunistic pathogens
c. They stimulate the growth of other beneficial species

12. Which of the following is a major factor contributing to intestinal and extra intestinal diseases?
a. Inadequate fluid intake
b. Dysbiosis
c. High sugar intake

13. What is the effect of re-diversifying a dysbiotic microbiome?
a. New disease states will occur
b. Loss of function in the microbiome
c. Prevention of intestinal diseases

14. Which of the following best describes the Mediterranean Diet?
a. Low carbohydrate, low fat, high animal protein diet
b. High carbohydrate, high fat, low animal protein diet
c. Low carbohydrate, high fat, high animal protein diet

15. The Historic Centre of Florence is an example of a ____________________.
a. UNESCO Intangible Cultural Heritage
b. UNESCO Cultural Heritage
c. UNESCO Natural Heritage

16. What was the purpose of the PREDIMED trial?
a. To test the efficacy of the Mediterranean diet on decreasing all-cause mortality
b. To test the efficacy of the Mediterranean diet on cardiovascular health
c. To test the efficacy of the Mediterranean diet on the composite endpoint

17. What did the Aging and Adherence to the Mediterranean Diet find?
a. An association between adherence to the Mediterranean Diet and adherence to medication
b. An inverse association between adherence to the Mediterranean Diet and adherence to medication
c. An inverse association between adherence to the Mediterranean Diet, polypharmacy and cardiometabolic disorders

18. Which of the following is an example of a typical meal based on the normative Mediterranean diet?
a. Bread with olive oil, charcuterie, cheese, a glass of wine
b. Bread with olive oil, lentil salad, a glass of wine
c. Bread with olive oil, grilled chicken, lentil salad

19. Which of the following can help pharmacists and pharmacy technicians analyze a patient’s diet?
a. The Cardiac Rehabilitation UK Mediterranean Diet Scorecard
b. The Oldways Diet online site
c. The Mayo Clinic’s webpage on eating

20. Select the statement that is TRUE:
a. The Mediterranean diet builds on inexpensive food that the poor, working class people ate traditionally.
b. If researchers look at other regions of the world, no similar diets or health implications exist.
c. Most pharmacists and techs instinctively follow a Mediterranean diet and can explain it to patients.

Technician Post-Test
1. Ancel Keys was considered an icon in:
a. Coronary heart disease
b. Cardiovascular nutrition
c. Influencing diet

4. At what meeting did Keys present his ideas?
a. World Health Organization
b. UNESCO
c. PREDIMED

5. What percentage of calories come from a carbohydrate source for the Mediterranean diet?
a. 20%-30%
b. 45%-55%
c. 60%-70%

10. Which of the following food groups provides the most amount of microbes to our bodies?
a. Grains and cereals
b. Meats
c. Fruits and vegetables

12. Which of the following is a major factor contributing to intestinal and extra intestinal diseases?
a. Inadequate fluid intake
b. Dysbiosis
c. High sugar intake

13. What is the effect of re-diversifying a dysbiotic microbiome?
a. New disease states will occur
b. Loss of function in the microbiome
c. Prevention of intestinal diseases

15. The Historic Centre of Florence is an example of a ____________________.
a. UNESCO Intangible Cultural Heritage
b. UNESCO Cultural Heritage
c. UNESCO Natural Heritage

LAW: Can Anything Be Done To Make A Century-Old Drug More Affordable?

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

· Discuss the effect of high insulin costs on public health

· Describe the development of insulin as a treatment for diabetes and how its cost has evolved

· Characterize the factors contributing to the high costs of insulin

· Review the regulatory and legal issues which have had or will have an effect on the cost of insulin

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

· Discuss the effect of high insulin costs on public health

· Describe the development of insulin as a treatment for diabetes and how its cost has evolved

· Characterize the factors contributing to the high costs of insulin

· Review the regulatory and legal issues which have had or will have an effect on the cost of insulin

More than 100 years ago, insulin was found to be an effective treatment for diabetes, yet the disease continues to be a major public health concern. Many patients with diabetes undertreat the disease despite insulin’s ready accessibility, due, in part, to the rapidly increasing cost of the medication. Significantly, the cost of insulin is subject to a complex, opaque price setting process with many stakeholders that encourages high list prices. There is also little competition in the insulin market, manufacturers aggressively protect their markets, and there are few alternatives to brand name products. Meanwhile, Congress is grappling with measures to lower out-of-pocket insulin costs, including capping co-pays on insulin products. This continuing education activity will review many of the factors that influence the cost of insulin and the consequences of high prices. It will also discuss regulatory and public health efforts to control costs and the role of the pharmacy team.

INTRODUCTION

“The skyrocketing cost of insulin has become a crisis in the US. Some people are dying because they can't afford the life-saving drug.” Columnist Rachel Gillett.¹

Diabetes is a rapidly growing global health problem with enormous health, social, and economic consequences.^1-3 This chronic metabolic disorder is characterized by prolonged hyperglycemia due to inadequate pancreatic production or utilization of the hormone insulin.³ Approximately 6.5% of the global population (almost 300 million people) suffer from diabetes.² In the U.S., the Centers for Disease Control and Prevention (CDC) estimates that 10.5% of the population (34 million people) have diabetes and that the prevalence rises to 26.8% among those aged 65 years or older.⁴ Direct medical costs and lost productivity attributable to diabetes was estimated to be $327 billion in 2017, making it the most expensive chronic disease in the nation.^5,6

Complications from diabetes are a serious public health concern. Diabetes is a principal cause of retinopathy, kidney failure, heart attacks and stroke, lower limb amputation, and ketoacidosis which can be fatal.³ Individuals with diabetes are twice as likely to have heart disease or stroke than those without diabetes.⁵ A total of 16 million emergency department (ED) visits were reported with diabetes as a listed diagnosis among adults aged 18 years or older in 2016.⁴

Management of diabetes is critical to preventing complications and high health care costs from the disease. However, many patients do not adequately manage their diabetes, in part due to high treatment costs. This continuing education activity will discuss some of the reasons behind the high costs of treating the disease and the impact that high prices have on patients. It will also review regulatory and public health efforts to reign in the rising costs of insulin.

INSULIN

Diabetes can be managed, and its consequences avoided or delayed with diet, physical activity, tobacco avoidance, and regular screening and treatment for complications.^3,5 Medication, of course, is also a key to management. Prescribers use many different classes of oral medications to manage diabetes,⁷ but the emphasis in this activity will be on insulin. Insulin is the mainstay of therapy for individuals with type 1 diabetes, and many patients with type 2 diabetes also benefit from insulin therapy.⁸ Prior to the discovery of insulin in 1921, diabetes was difficult to manage. The primary treatment consisted of highly restrictive diets, which compromised the immune system and stunted growth, and often led to death by starvation.⁹

In 1921, Frederick Banting, a Toronto surgeon without laboratory training, medical student Charles Best, physiologist John Macleod, and biochemist James Collip successfully isolated and purified insulin from a dog’s pancreas and showed that it would normalize blood glucose levels when administered to diabetic animals.¹⁰ Later, insulin was extracted in larger amounts from cattle and was first given to a 14-year-old dying diabetic patient who developed an allergic reaction. After the Canadian researchers purified it further, they gave a second dose to the patient 12 days later; the patient showed dramatic improvement as his blood glucose dropped to near normal levels with no obvious adverse effects.¹⁰ This observation spurred widespread use of insulin in patients with diabetes. Banting and Macleod were jointly awarded the 1923 Nobel Prize in Physiology or Medicine in recognition of their life-saving discovery (The committee did not recognize Best, the lowly med student, for his contribution).¹⁰ Banting, Collip, and Best were also awarded patents on insulin and the method used to make it in 1923. They all sold their patents to the University of Toronto for $1 each.¹⁰ Banting famously said, “Insulin does not belong to me, it belongs to the world,” proclaiming his desire that everyone who needed it should have access to it.¹⁰

Researchers at the university tried to manufacture insulin for distribution but realized they could not meet the demands of the North American market.¹¹ The university licensed the technology to Eli Lilly which possessed the expertise to produce large batches of insulin. Under the arrangement, Lilly was allowed to apply for U.S. patents on any improvements to the manufacturing process.¹¹ The university also established licensing agreements to produce insulin with other companies, including Nordisk and Novo which laid the foundation for the future domination of the insulin market by a few companies.¹¹ When the animal-based insulin patents began to expire, researchers developed new technologies. They bioengineered human insulin in 1982 and then analog insulin (insulin which has been genetically modified to improve its pharmacokinetic profile) and created new therapies and continued patent protection.¹¹ Today, approximately 7.4 million Americans use insulin, including roughly 1.4 million people who use it to treat type 1 diabetes.⁹

Pharmacists and technicians are aware that patients with type 1 and type 2 diabetes use a combination of short-acting, rapid-acting, intermediate-acting, and long-acting insulins to control their glucose levels. Today, the insulin analogs are widely prescribed and are the standard of care for people with type 1 diabetes and also a component of care for people with type 2 diabetes; the analogs are generally more expensive than other, older types of insulin.⁹

Even though diabetes is treatable and has been for more than a century, it remains the 7^th leading cause of death in the U.S., accounting for 87,647 fatalities in 2019.^5,9 Despite the availability of this century-old treatment, many patients undertreat their diabetes, contributing to complications and high mortality from the disease. Results from an international survey of patients with type 1 diabetes found that approximately 25% of patients in the U.S. had rationed insulin in the previous year.¹² Why would patients show such low adherence to a proven, lifesaving medication?

One reason is cost. High-list prices, health plan structures, and high out-of-pocket costs make it difficult for many diabetic patients to adhere to their medications, especially insulin. Some patients maintain that they spend an estimated 50% of their monthly income on insulin and diabetes products.¹¹ Studies have found that approximately one of every four survey respondents in the U.S. report underuse of their insulin at least once within the previous year due to high cost.^12,13 This is the highest rate of insulin rationing of any high-income country in the world.¹⁴ An international survey found that only 6.5% of respondents from high income countries excluding the U.S. reported rationing in the previous year, compared with roughly 25% in the U.S.¹⁴ In addition to rationing insulin, 33.5% of individuals from the U.S. reported rationing of blood glucose testing supplies.¹⁴

The financial burden is, not unexpectedly, especially acute for economically disadvantaged individuals who have a higher rate of diabetes. Rates of diabetes are higher among people living in impoverished regions of the U.S., such as Appalachia and the Mississippi Delta, and also among those who are eligible for Medicare and Medicaid.⁹ Adults with less than a high school education are also more likely to be diagnosed with diabetes than those with at least a high school diploma.⁹ Similarly, minority communities are also disproportionally affected by this disease, with Native Americans, Hispanics, Black Americans, and Asian Americans representing more than 45% of those diagnosed with the disease, despite these groups making up 39% of the U.S. population.⁹ Cost-related rationing of insulin was the leading cause of hospital admissions for diabetic ketoacidosis among inner-city minority patients.¹⁴ Approximately 24% of adults with diabetes earning below the poverty level use insulin, either alone or in combination with oral medications.¹⁵

An online survey performed by the American Diabetes Association in 2018 also found that a quarter of respondents reported that the cost of insulin had affected their purchase or use of insulin during the previous year. The percentage was even higher for dependent child insulin users (34%).¹⁶ More than 20% of users admitted missing doses monthly or even weekly. They also had to choose between buying insulin or other health-related purchases such as physician visits (32%), health insurance (26%), or other medications (36%). Many also had to choose between purchasing insulin or other essential items such as utilities (30%), housing (27%), transportation (32%), as well as non-essential purchases like vacations (41%) and entertainment (43%).¹⁶ Patients have also made employment decisions based on the availability of adequate health insurance to cover the cost of their insulin.¹¹ Patients also claim that they have been forced to make unhealthy food choices that can worsen the disease, purchasing cheaper alternatives due to spending on insulin.¹¹ The excessive costs also caused 23% of individuals to change to a less expensive insulin type or brand, while many skipped filling at least one insulin prescription.¹⁶

Moreover, surveys have found that insulin users for whom cost affected their purchase or use of insulin experience adverse health effects at higher rates than those for whom cost was not an issue. When cost was a factor, 72% of individuals experienced episodes of poor blood glucose control during the previous three months (compared with 42% in users who were not affected by the cost), and 80% had their most recent A1C level measured at 7.5 or higher (59% when cost was not a factor).¹⁶ Patients have also claimed that they have intentionally allowed themselves to reach a state of diabetic ketoacidosis so that they would receive insulin in an ED instead of purchasing it.¹¹

Not unexpectedly, 73% of individuals dealing with price increases also experience negative emotions (e.g., stress or anxiety), more than twice the rate of those not facing a price increase (31%).¹⁶ There have even been reports of deaths in patients with type 1 diabetes due to a lack of affordable insulin.^14,17 The underutilization of insulin due to concerns over cost not only produces serious avoidable short- and long-term health consequences, but also raises overall costs for the U.S. health care system.^9,15 It is remarkable that this has occurred with a medication whose discoverers refused to profit from it.

PAUSE AND PONDER: How would you start a conversation about economic stress with a patient who appears to be underusing insulin?

ARE COSTS REALLY THAT HIGH?

There is a public perception that the cost of prescription drugs is out of control; indeed, Americans pay an average of three times as much as patients in the U.K. for the world’s top 20 medications.¹⁸ But is insulin, in the words of Representative Tom Reed (R., N.Y.), “the poster child of this broken marketplace”?¹⁸

Insulin in the U.S. is more expensive than anywhere else in the world. The average manufacturer price of insulin is more than four times higher in the U.S. than it is in the next most expensive country (Chile) and more than 10 times the average cost in the 32 developed countries surveyed.¹⁹ In 2018, spending on insulin in the U.S. was $28 billion, compared with $484 million in Canada.²⁰ The average American insulin user spends almost five times as much annually than their Canadian counterparts. The average cost per unit of insulin in the United States increased by 10.3% between 2016 and 2019 compared with an increase of only 0.01% in Canada during the same time period.²⁰ By comparison, in 1923, two years after the introduction of insulin therapy, the U.S. had the lowest global price of insulin.²¹ As recently as the 1960s, vials of insulin were available in the U.S. for 84¢, equivalent to $7.36 in today’s dollars.¹⁸

The list price of insulin per milliliter in the United States increased, on average, 2.9% annually between 1991-2001, 9.5% per year from 2002 and 2012, 20.7% annually between 2012 and 2016, with a smaller increase from 2016 to 2018.⁶ Analog insulins have seen the largest price increase, rising more than 1000% since the 1990s.^14,17 The average annual per capita cost of insulin now approaches $6,000.⁶ (Note that the average yearly social security benefit in the U.S. is $18,458.)

The cost of insulin contributes an estimated $48 billion to the direct costs of treating diabetes (before accounting for any rebates or discounts) which represents 20% of the total spending.⁶ If current trends continue, the cost of insulin could reach $121.2 billion by 2024, or $12,446 annually for each patient receiving insulin.⁶

WHY?

The reasons for the enormous increase in the retail price of insulin are complex and varied. It has been argued that one of the common justifications for the high price tag on prescription drugs, research and development costs, is not applicable to insulin.¹⁷ Insulin is not a new drug and even the most commonly used modern analogs are 20 years old or more.¹⁷ In addition, over the past 60 years, the increase in the cost of insulin exceeds the rate of inflation by nearly 43-fold.¹⁸ If research and development costs are not driving the price increase, what is?

Notably, there is little competition in the insulin market. Only three companies, Eli Lilly, Novo Nordisk, and Sanofi, manufacture over 90% of the world’s insulin and investigations have found that they generally raise their prices at the same time.^17,21-23 It should be pointed out, however, that the manufacturing of biologics, compared with small molecules, involves a higher level of engineering and facility requirements. Additional steps are needed to ensure compliance with good manufacturing practices, regulatory requirements and to minimize batch-to-batch variability, all of which would affect production costs.²¹ The scale and optimization of production processes are also important to reduce the overall cost of the finished product which hinders smaller pharmaceutical manufacturers from entering the market.²¹

Other factors also contribute to rising insulin prices. An important trend over the past decade is a shift in insulin prescribing from less expensive human insulins to more expensive human insulin analogs.¹⁵ More than 90% of privately insured patients with type 2 diabetes in the U.S. who receive insulin are currently prescribed the more expensive analog version.^17,21

Price Setting

Another significant factor affecting the price of insulin is the large number of stakeholders (e.g., manufacturers, wholesalers, pharmacy benefit management services [PBMs], pharmacies, health plans, employers, and the Federal government) involved in the insulin supply chain and price setting, all of whom use varying degrees of negotiating power.^9,15 Multiple transactions occur among these stakeholders during distribution and payment and there is no one agreed-upon price for any insulin formulation.¹⁵

Although pharmacy staff are generally aware of the pricing dynamics, a brief review will place the insulin costs into context. Prices, rebates, and fees are negotiated among the stakeholders affecting the ultimate price paid by the patient with diabetes at the point of sale. The true cost of insulin can be difficult to pinpoint because of the complex nature and lack of transparency in the financial agreements among the stakeholders.^11,24

Manufacturers set a list price for their product, but the list price is usually not what payers pay nor what the manufacturers receive.^15,24 The manufacturers, generally, receive the net price which is the list price minus fees paid to wholesalers, discounts paid to pharmacies, and rebates paid to PBMs or health plans.¹⁵ While manufacturers control the list price of insulin, a substantial portion of the negotiating power has shifted from manufacturers to PBMs.¹⁵

PBMs attempt to lower costs by leveraging formulary coverage. PBMs administer the prescription medication benefit for more than 266 million Americans and 70% of all prescription claims are managed by the top three PBMs.¹⁵ PBMs have the power to provide exclusive formulary coverage and use this discretion to give them substantial clout in negotiations with manufacturers.¹⁵ Insulin manufacturers compete fiercely, attempting to gain favorable formulary placement and maximize market share and revenue for their products.^9,15 They use rebates as one bargaining chip.^9,15

These interactions give PBMs little incentive to discourage manufacturers from increasing their list prices since rebates, discounts, and fees PBMs negotiate are typically based on a percentage of a drug’s list price.⁹ There is an advantage for manufacturers to raise the list prices to provide bigger incentives (discounts) for the participants in the supply chain.¹¹ In other words, PBMs benefit when there is a larger “spread” between the list price and the real price paid by the health plan, so both the PBMs and manufacturer gain from higher list prices.^9,11,15 Since payers ultimately pay the “real” (discounted) price and not the list price, inflating the benchmark price does not increase the cost to the PBMs.¹¹

A Senate investigation found instances in which insulin manufacturers were apparently discouraged from setting lower list prices for their products, which would likely lower out-of-pocket costs for patients, due to concerns that PBMs and health plans would react negatively.⁹ Although it might be expected that rebates would reduce patient costs at the point-of-sale, they may be used instead by the employer or the health plan to reduce insurance premiums.¹¹ Significantly, insulin list prices have tended to rise more rapidly than the net price due to increasing rebates and discounts negotiated between stakeholders. In some cases, rebates and discounts may approach half of the insulin list price.^15,25 This suggests that participants in the distribution system are largely responsible for the increase in insulin costs.²⁵ It has been estimated that proceeds from insulin sales flowing to insulin manufacturers and insurers have decreased over time, while PBMs, pharmacies, and wholesalers have substantially increased their share of the funds.²⁵

Many participants in the pricing system benefit from the arrangement, but one essential participant who does not is the patient who needs insulin and is paying the artificially inflated list price. In particular, patients with high deductible insurances, Medicare recipients in the “donut hole,” patients subject to co-insurance, and especially patients without health insurance are in jeopardy.^11,24 Over the past decade there has been a shift away from traditional health plans, which provided broad coverage, to high-deductible health plans, and the deductibles themselves have risen; even plans available under the Affordable Care Act can have high deductibles depending on the “tier.” ¹¹ Thus, it would seem that decisions made from negotiations between stakeholders that affect formulary choice may not be based on the patient’s best financial or medical interest.¹⁵

Recently, the Federal Trade Commission (FTC) voted unanimously to conduct an in-depth probe of PBMs since, according to one commission member, “(f)or most Americans, pharmacy middlemen control what medicine you get, how you get it, when you get it, and how much you pay for it. Yet PBM practices are cloaked in secrecy, opacity, and almost impenetrable complexity.”²⁶

Patent Issues

Not only do a few companies dominate the market, they also maintain significant patent protection that limits incursion of competitive alternatives into the market. Currently, there are no patents on human insulin and most patents on first generation insulin analogs have also expired.²¹ Manufacturers have made improvements with new formulations providing more reliable control of diabetes and more convenience for users. However, the newer formulations prolong the patent life and provide up to 37 years of market protection.¹⁷ Companies also engage in what is known as “patent evergreening,” where they continually apply for renewed patents for their drugs after making incremental (in some cases, insignificant) changes to their medications.^17,18,23,27

For example, the long-acting insulin product insulin glargine (Lantus) was first patented in 1994 and was due to expire in 2015. Sanofi filed 74 patents for newer versions of the drug that can provide protection until 2031.^11,17,18 Sanofi maintains that the newer patents “are related to new and unique inventions” although there is evidence suggesting that the improvements are mostly minimal.¹⁸ Sanofi also points out that while the list price for its insulin has increased, the actual price paid by consumers is lower than it was in 2006, due to the nature of the market.¹⁸ In addition to modifying the insulin product, manufacturers have also filed and received patents for insulin delivery devices which effectively extends the patent life of the delivered insulin.^18,21

Patent disputes can influence cost in many ways. The threat of a lawsuit alleging patent infringement would discourage other manufacturers from developing competing products even if the suit is without merit.¹⁷ Even if the suit is litigated and found to be without merit, large litigation costs and marketing delays would occur.²² In 2014, Sanofi filed a suit against Lilly alleging a violation of its patent on insulin glargine. The companies reached a deal under which Lilly agreed to delay the launch of its product until 2016 and pay royalties to Sanofi.²⁸

Even more disturbing is the strategy of “pay-for-delay” patent dispute in which a competing manufacturer acknowledges the original patent and agrees to defer marketing its product for a specified period of time.^17,22 In return, the competing manufacturer receives a payment from the patent holder, a legal means for a manufacturer to pay a competitor not to enter the market.²² When Merck filed a new drug application for its rival to insulin glargine, Sanofi filed a suit claiming that Merck violated 10 of its patents, including ones for the drug and its insulin delivery device.²⁸ After the suit was filed, Merck announced it would no longer pursue its interest in the drug, possibly reaching a deal to receive payments from the suing company.²²

Biosimilars

Patents are not the only barrier to the introduction of alternatives to brand-name insulin. Insulin is a therapeutic biologic (not a chemically synthesized small molecule/drug) and the FDA treats alternative biologic products as biosimilars and not as generics; this leads to a more cumbersome and expensive regulatory approval process.^17,23 The FDA defines biosimilars as “a biological product that is highly similar to, and has no clinically meaningful differences from, a biological product already approved by the FDA.” ²⁹ Production and approval of biosimilars costs nearly as much as a new drug and requires similar testing and regulatory approval.^22,23 The development of a biosimilar takes five to nine years and costs at least $100 million,³⁰ leaving little financial incentive to develop cheaper options. The first insulin biosimilar, Basaglar, was introduced in the U.S. in December 2016, almost two years after the first biosimilar was approved in Europe, and requires that a prescriber supplies a new prescription.¹⁷ A second biosimilar (Admelog) was approved in 2018.¹⁷

In 2021, the FDA approved Semglee (insulin glargine-yfgn) as the first interchangeable insulin biosimilar.²⁹ The “interchangeable” designation means that it can be substituted for Lantus (insulin glargine, approved in 2000) without the intervention of a prescriber, similar to pharmacist-initiated generic drug substitution for small molecules.^27,29

PAUSE AND PONDER: What factors would you consider before substituting an interchangeable insulin? Would cost be one?

CAN ANYTHING BE DONE TO CONTAIN INSULIN COSTS?

The soaring cost of insulin has caught the attention of legislators, healthcare advocates, and the public.

Rising drug prices are a concern to the public at large. More than half of respondents in a March 2022 poll by the Kaiser Family Foundation agreed that limiting how much drug companies can increase the price of prescription drugs each year to the rate of inflation should be a “top priority” for Congress.³¹ A majority of respondents also say placing a limit on out-of-pocket costs for seniors (52%) and, specifically, capping out-of-pocket costs for insulin at $35 a month (53%) should be top priorities for Congress in the coming months.³¹ Several different approaches to reigning in costs involving multiple stakeholders have been proposed.

Congressional Actions

The most far-reaching proposal is the Build Back Better Act (BBBA) which was passed by the U.S. House of Representatives on November 19, 2021, but stalled in the Senate. This is a broad and complex 2,135-page bill with many provisions that would commit $2.2 trillion to a long list of health, social, and environmental proposals.³² The BBBA includes several provisions that would lower prescription drug costs for people with Medicare and private insurance and reduce drug spending by the federal government and private payers.^32,33

The key proposals dealing with drug costs, if eventually passed, would include³³

Allowing the Federal Government to negotiate prices for some high-cost drugs covered under Medicare Part B and Part D
Requiring rebates to limit annual increases in drug prices in Medicare and private insurance for drugs whose prices rise faster than the inflation rate
Cap out-of-pocket spending for Medicare Part D enrollees by instituting a hard cap of $2,000 in 2024
Eliminate cost sharing for adult vaccines covered under Medicare Part D
Limit cost sharing for insulin for individuals with Medicare and private insurance. Currently, Part D and private insurance plans vary in terms of the insulin products they cover and what enrollees pay for insulin products. Under the BBBA, participating plans would cover insulin products at a monthly copayment of $35. Participating plans would not have to cover all insulin products at the $35 monthly copayment but would include one of each dosage form (vial, pen) and insulin type (rapid-acting, short-acting, intermediate-acting, and long-acting).

Since the large BBBA endeavor has not progressed in Congress, the House of Representatives passed a scaled back version (Affordable Insulin Now Act) in March of 2022 that specifically addressed insulin costs.³⁴ The bill would cap cost-sharing under the Medicare prescription drug benefit for a month's supply of covered insulin products at $35 and cap private health insurance cost sharing for selected insulin products at $35 or 25% of a plan's negotiated price (after any price concessions). The cap would become effective in 2023. At the time this activity was prepared, the effort was awaiting Senate action. A modified bipartisan Senate bill with a $35 co-pay cap has been introduced.

The industry trade group, the Pharmaceutical Research and Manufacturers of America (PhRMA), does not favor the act, calling the proposed law heavy-handed and flawed. PhRMA’s position is that it would make the “broken insurance system worse and throw sand in the gears of medical progress” and “doesn’t address perverse incentives in the system that are leading to higher costs for patients.”³⁵

Biosimilars

The previously discussed biosimilars also aim to encourage more affordable insulin substitutes.²³ Before 2010, the U.S. lacked a regulatory pathway for the development of biosimilar medications.^15,36 In 2010, the Biologics Price Competition and Innovation Act (BPCIA) was signed into law as part of the Affordable Care Act. This new law created an FDA approval pathway for biosimilar and interchangeable biologic products while preserving incentives for the development of new medications.^36,37 Typically, biosimilars marketed in the U.S. have launched with initial list prices 15% to 35% lower than comparable list prices of the original reference products.²⁹ The BPCIA provides two separate pathways for a biological product to compete with a reference product: either as a biosimilar or as an interchangeable. Interchangeable products are subject to more stringent requirements.^23,36

To be considered a biosimilar, the route of administration, dosage form, and strength must be the same as the reference product.^36,38 The sponsor must show that it is “highly similar” to the reference product and that no clinically meaningful differences between the biosimilar and the reference product exist in terms of safety, purity, and potency of the product.³⁸ Only minor differences in clinically inactive components are permitted in biosimilar products.³⁰

The biosimilar must also possess the same mechanism of action as the reference product for the condition it is intended to treat, and the manufacturing conditions and facilities must meet standards to ensure safety, purity, and potency.^36,38 To be interchangeable, the manufacturer must demonstrate two things^36,38:

That the product produces the same clinical result as the reference product in patients.
If it is to be used more than once in a given individual, any safety risks or diminished efficacy from switching between the reference substance and the biosimilar is no greater than the risks from using the reference product alone.

Pharmacists should take note of an important difference between biosimilars and generics. Generics (small molecules) only need to demonstrate bioequivalence, while biosimilars need to demonstrate therapeutic equivalence.³⁶ The equivalence must be based on data derived from animal studies, clinical studies, and analytics that show a similarity to the reference product.³⁶ As noted above, meeting the biosimilar criteria requires much more time and expense than substantiating generic equivalency. Pharmacists also need to appreciate that even if a product is defined as “interchangeable,” it is not possible to create identical versions of reference biologic medicines due to their complexity.³⁰

The BPCIA also has market exclusivity provisions that address manufacturers’ concerns.³⁶ Applicants for biosimilar products cannot submit an application until four years after the date on which the reference product was first licensed. Further, the FDA cannot approve the biosimilar or interchangeable until 12 years after the date on which the reference product was first licensed. In addition, the applicant must provide the manufacturer of the reference product with notice of intent 180 days before marketing the product. The first interchangeable product also has market exclusivity for at least a year.³⁶

FDA approval of biosimilars, however, is not the only obstacle to marketing insulin substitutes. As noted above, biosimilars must contend with patent evergreening.^17,27 Biosimilars will also not necessarily grab a large market share.²⁷ Lilly, Novo Nordisk and Sanofi have launched their own “authorized generics,” essentially their own drugs repackaged and marketed at discounted prices.²⁷ Lilly and Sanofi produced the first two (Basaglar and Admelog), which provides little in the way of competition; they are priced only about 15% to 20% less than their respective original forms.^17,39

More significantly, the complex price setting maneuvering that affects the cost of insulin could also impede cheaper biosimilar acceptance. Since PBMs can make more money from discounts on brand name products, they have more to gain from prioritizing the dominant brands and little incentive to include biosimilars in formularies.^17,27,39 In addition, since pharmacists can substitute interchangeable products, pharmacists have the discretion whether or not to dispense the less expensive formulation.

Over the Counter

Pharmacy personnel should recall that when Congress established federal prescription drug regulations in 1951, the types of insulin available at that time, unlike the more recent analogs, did not require a prescription.⁴⁰ Human insulin injection is available over the counter in 49 U.S. states and the District of Columbia and about 15% percent of U.S. patients who buy insulin purchase it over the counter without a prescription.^40,41 This presents a dilemma for patients and clinicians.^40,41 On one hand, this provides an opportunity for patients to obtain insulin without delay, especially in an urgent situation,⁴¹ at a more affordable price (average price of $54.09, compared with $114.40 for prescription short-acting insulins.¹⁹). On the other hand, it could be dangerous for a patient to adequately assess the appropriate dosage and timing for optimal glucose control without training or guidance from a health care provider especially if they are switching between different versions of insulin.⁴⁰ Physicians may not be aware that insulin can still be purchased OTC and may be puzzled by a patient’s sudden change in blood glucose.⁴¹ The FDA maintains that the older insulins were approved for OTC sale because they are less concentrated and did not require medical supervision for safe use.⁴¹

State Activities

States have also taken measures to influence insulin cost and use while waiting for federal actions.

In 2019, Colorado became the first state to limit co-pays for patients who use insulin, capping individual prescription at $100 for a 30-day supply ($200 if patients use two types of insulin), although payers have exploited some loopholes.⁴² The law applies to private insurers but not to patients on Medicare. Since then, seven other states (Illinois, Maine, New Mexico, New York, Utah, Washington, West Virginia) have enacted similar measures and five others (Connecticut, Florida, Kentucky, Tennessee, Virginia) are contemplating similar legislation.⁴² In New Mexico, the cap is set at $25.

Pharmacy staff are also reminded that, generally, individual state laws govern generic substitution.⁴² Some states have become concerned that biosimilars are not “identical” to the reference product, consequently pharmacy staff should become familiar with their state’s regulations regarding biosimilar substitution.⁴³ At least one U.S. state (Indiana) does not permit OTC sales of insulin due to the safety concerns noted above.^19,41

Individuals

Insulin prices have risen to such an extent that patients have taken matters into their own hands. The disparity in price has motivated many Americans to travel to Canada to purchase their insulin where the price may be as little as 1/10 the cost in the U.S.^1,9,44 Governmental policy controls insulin prices in Canada, including price caps and negotiations with manufacturers and often insulin does not require a prescription.⁴⁴

PAUSE AND PONDER: How would you advise a patient who is contemplating purchasing insulin from Canada as a cost-saving measure?

In another approach to reducing the cost of insulin, biohackers have been attempting to make insulin by converting proinsulin obtained from yeast to insulin with the hope of providing a method for do-it-yourself production that could be shared online.^18,45 If they are successful, anyone, hypothetically, could construct a lab and manufacture open-source insulin in a garage at a lower cost.¹⁸ However, they could still run afoul of FDA regulations and need to conform to Good Manufacturing Practices.^18,45

PAUSE AND PONDER: How would you respond to a patient who asks you about OTC or “homemade” insulin?

Patients are also filing lawsuits challenging manufacturer’s “schemes” to unlawfully inflate the benchmark prices of rapid- and long-acting insulins.¹¹

SUMMARY AND CONCLUDING REMARKS

Insulin maintains a critical place in the treatment of diabetes more than 100 years after the discovery of its beneficial effects, yet the disease is poorly managed in many patients, in part due to the escalating cost of newer forms of the drug. Insulin prices in the U.S. are far higher than in the rest of the world, fueled by a pricing system riddled with disincentives to keep prices low. Patients with no or low-quality health insurance are particularly impacted. Congress and states are examining possible solutions to the problem, notably by placing caps on out-of-pocket spending on insulin.

Pharmacy staff, as the point of contact with patients receiving insulin, are ideally situated to help patients who are struggling with adherence to their medication. Patients would benefit from pharmacists who can advise them about the different forms of insulin and delivery devices.⁴⁶ The Endocrine Society recommends that pharmacists learn about lower cost options offered by manufacturers and share their findings with patients and prescribers.²⁴ Pharmacists should also be ready to discuss the pros and cons of OTC insulin products. Pharmacists have also gained an opportunity (and responsibility) to manage costs with the approval of the first interchangeable insulin product.

Another helpful role would be to educate patients about available patient assistance programs especially since many patients may be unfamiliar with them or unsure about whether they qualify and how to apply.⁴⁶ This is a function that pharmacy technicians can fulfill. It is also vital that pharmacy staff remain familiar with Congressional and State efforts to lower out-of-pocket costs of insulin described above and some may choose to serve as patient advocates. Finally, if open-source methods of manufacturing insulin prove to be successful, it could potentially introduce opportunities for compounding pharmacies to make insulin at a lower cost.¹⁸ Insulin may never be as affordable as Frederick Banting hoped, but at least encouraging signs suggest that fewer patients will find it necessary to forego their life-saving treatment because of the expense.

As this activity was being prepared for posting, the Senate passed the long-debated Inflation Reduction Act which dealt with climate, taxes, and health care. The relevant features will allow the government to negotiate costs for certain drugs paid for by Medicare (10 in 2026 and 20 in 2029) and will cap out-of-pocket expenses for insulin at $35 per month for Medicare patients but not for private insurers.

LAW: CAN ANYTHING BE DONE TO MAKE A CENTURY-OLD DRUG MORE AFFORDABLE?

Post-test-Pharmacists and Technicians

Learning Objectives
After completing this activity, participants should be able to  

1. Discuss the effect of high insulin costs on public health
2. Describe the development of insulin as a treatment for diabetes and how its cost has evolved
3. Characterize the factors contributing to the high costs of insulin
4. Review the regulatory and legal issues which have had or will have an effect on the cost of insulin

1. Where does diabetes rank among the leading causes of death in the U.S.?
A. Third
B. Seventh
C. Fifteenth

2. Approximately how many patients report that they have rationed their insulin (during the previous year)?
A. 5%
B. 10%
C. 25%

3. Banting, Best, and Macleod received patents for developing methods to produce injectable insulin in 1923. What did they do with their patents?
A. They started a pharmaceutical company that is still making insulin.
B. They sold their patents to the University of Toronto for $1 each.
C. They licensed the technology to a major pharmaceutical company

4. The average manufacturer price of insulin in the U.S. is approximately how much higher than the average price in the rest of the world?
A. Double
B. Six-fold
C. Ten-fold

5. The price of insulin changes frequently. Which of the following statements is correct?
A. The net price (after discounts have been applied) has been increasing more rapidly than the manufacturer’s list price
B. The uninsured patient pays the net price at the pharmacy
C. Manufacturers compete to gain preferred formulary coverage for their insulin by offering PBMs the largest differential between list and net price

6. Which of the following applies to the commercial development of a biosimilar?
A. It is less expensive to develop a biosimilar than a generic drug because the technology is more straightforward
B. The manufacturer of the original product has a period of market exclusivity before an application for a biosimilar can be approved
C. Biosimilars, like generic drugs, only need to demonstrate bioequivalence to obtain approval from the FDA.

7. What does it mean if an insulin product is “interchangeable”?
A. It is identical to a product made by another manufacturer, basically a generic version
B. It can be substituted for a brand name product if the prescriber issues a new prescription
C. It can be substituted for a brand name product at the discretion of the pharmacist

8. Which of the following is correct regarding patents on insulin?
A. All but one insulin analog is currently protected by its original patent, and the one for which the patent expired is rarely used
B. Most commercially available insulin analogs still have patent protection from their original patent.
C. Manufacturers file numerous modifications to their insulin formulations to extend patent protection by as much as 37 years.

9. What effect would a proposed act recently passed by the U.S. House of Representatives have on the price of insulin?
A. It would mandate that CMS negotiates prices for some high-cost drugs covered under Medicare
B. It would cap cost-sharing under the Medicare prescription drug benefit for a month's supply of covered insulin products at $35
C. It would make most current insulin analogs OTC

10. Colorado became the first state to cap insulin prescriptions prices. The Colorado law does which of the following?
A. It caps out-of-pocket costs for insulin prescriptions at $100 for a 30-day supply for all patients
B. A patient pays one capped monthly price regardless of how many different types of insulin they use
C. The cap applies to anyone who uses insulin regardless of insurance coverage (self-pay, Medicare, and private insurance)

11. What is the percentage increase in the cost of analog insulins over the past three decades?
A. 100%
B. 500%
C. 1000%

LAW: CAN ANYTHING BE DONE TO MAKE A CENTURY-OLD DRUG MORE AFFORDABLE?

Post-test-Pharmacists and Technicians

Learning Objectives
After completing this activity, participants should be able to  

1. Where does diabetes rank among the leading causes of death in the U.S.?
A. Third
B. Seventh
C. Fifteenth

2. Approximately how many patients report that they have rationed their insulin (during the previous year)?
A. 5%
B. 10%
C. 25%

4. The average manufacturer price of insulin in the U.S. is approximately how much higher than the average price in the rest of the world?
A. Double
B. Six-fold
C. Ten-fold

11. What is the percentage increase in the cost of analog insulins over the past three decades?
A. 100%
B. 500%
C. 1000%

References

1. Gillett R, Gal S. One Chart Reveals How the Cost of Insulin Has Skyrocketed in the US, Even Though Nothing About It Has Changed. Business Insider. September 18, 2019. Accessed September 15, 2022.
https://www.businessinsider.com/insulin-price-increased-last-decade-chart-2019-9
2. Kaul K, Tarr JM, Ahmad SI, Kohner EM, Chibber R. Introduction to diabetes mellitus. Adv Exp Med Biol. 2012;771:1-11.
3. World Health Organization. Diabetes. November 10, 2021. Accessed September 15, 2022. https://www.who.int/en/news-room/fact-sheets/detail/diabetes
4. Centers for Disease Control and Prevention. National Diabetes Statistics Report, 2020. Accessed September 15, 2022.
https://www.cdc.gov/diabetes/pdfs/data/statistics/national-diabetes-statistics-report.pdf
5. America’s Health Rankings – Diabetes. United Health Foundation 2021 Annual Report.
AmericasHealthRankings.org. Accessed September 15, 2022.
https://www.americashealthrankings.org/explore/annual/measure/Diabetes
6. Hayes TO, Farmer J. Insulin Cost and Pricing Trends. American Action Forum. April 7, 2020. Accessed September 15, 2022. https://www.americanactionforum.org/research/insulin-cost-and-pricing-trends/
7. Nauck MA, Wefers J, Meier JJ. Treatment of type 2 diabetes: challenges, hopes, and anticipated successes. Lancet Diabetes Endocrinol. 2021;9(8):525-544.
8. American Diabetes Association Position Statement. Approaches to Glycemic Treatment. Diabetes Care. 2016;39(Suppl 1):S52-S59.
9. Insulin: Examining the Factors Driving the Rising Cost of a Century Old Drug. United States Senate Finance Committee Staff Report. January 14, 2021. Accessed September 15, 2022.
https://www.finance.senate.gov/imo/media/doc/Grassley-Wyden%20Insulin%20Report%20(FINAL).pdf
10. Diabetes UK. 100 Years of Insulin. Accessed September 15, 2022.
https://www.diabetes.org.uk/research/research-impact/insulin
11. Class Action Complaint. Chaires v Sanofi. United States District Court District of Massachusetts. Filed January 30, 2017. Accessed September 15, 2022.
https://static01.nyt.com/science/01-30-17_Insulin_Class_Action_Complaint_Hagens_Berman.PDF
12. Pfiester E, Braune K, Thieffry A, et al. Costs and underuse of insulin and diabetes supplies: Findings from the 2020 T1International cross-sectional web-based survey. Diabetes Res Clin Pract. 2021;179.
https://doi.org/10.1016/j.diabres.2021.108996 Accessed September 15, 2022. https://www.sciencedirect.com/science/article/pii/S0168822721003557
13. Herkert D, Vijayakumar P, Luo J, et al. Cost-Related Insulin Underuse Among Patients with Diabetes. JAMA Intern Med. 2019;179(1):112–114.
14. Costs and Rationing of Insulin and Diabetes Supplies: Findings from the 2018 T1international Patient Survey. T1International. Accessed September 15, 2022.
https://www.t1international.com/media/assets/file/T1International_Report_-_Costs_and_Rationing_of_Insulin__Diabetes_Supplies_2.pdf
15. Cefalu WT, Dawes DE, Gavlak G, et al. Insulin Access and Affordability Working Group: Conclusions and Recommendations. Diabetes Care. 2018;41(6):1299–1311.
16. American Diabetes Association. Insulin Affordability Survey, 2018. Accessed September 15, 2022. http://main.diabetes.org/dorg/PDFs/2018-insulin-affordability-survey.pdf
17. Rajkumar SV. The High Cost of Insulin in the United States: An Urgent Call to Action. Mayo Clin Proc. 2020;95(1):22-28.
https://www.mayoclinicproceedings.org/article/S0025-6196(19)31008-0/fulltext
18. Burningham G. The Price of Insulin Has Soared. These Biohackers Have a Plan to Fix It. Time. October 24, 2019. Accessed September 15, 2022. https://time.com/5709241/open-insulin-project/
19. Mulcahy AW, Schwam D, Edenfield N. Comparing Insulin Prices in the United States to Other Countries: Results from a Price Index Analysis. Santa Monica, CA: RAND Corporation, 2020. Accessed September 15, 2022. https://www.rand.org/pubs/research_reports/RRA788-1.html
20. Schneider T, Gomes T, Hayes KN, et al. Comparisons of Insulin Spending and Price Between Canada and the United States. Mayo Clin Proc. 2022;97(3):573-578.
21. Keeping the 100-year-old Promise: Making Insulin Access Universal. Geneva: World Health Organization; 2021. Licence: CC BY-NC-SA 3.0 IGO Accessed September 15, 2022.
https://www.who.int/publications/i/item/9789240039100 Link to download.
22. 8 Reasons Why Insulin is so Outrageously Expensive. T1 International. January 20, 2019. Accessed September 15, 2022.
https://www.t1international.com/blog/2019/01/20/why-insulin-so-expensive/
23. Zelitt J. Pay or Die: Evaluating the United States Insulin Pricing Crisis and Realistic Solutions to End It. Stetson Law Rev. 2021;50:453-489. Accessed September 15, 2022.
https://www2.stetson.edu/law-review/wp-content/uploads/2021/04/Zelitt.PayorDie.pdf
24. The Endocrine Society, Addressing Insulin Access and Affordability: An Endocrine Society Position Statement. J Clin Endocrin Metab. 2021;106(4):935–941.
25. Van Nuys K, Ribero R, Ryan M, Sood N. Estimation of the Share of Net Expenditures on Insulin Captured by US Manufacturers, Wholesalers, Pharmacy Benefit Managers, Pharmacies, and Health Plans From 2014 to 2018. JAMA Health Forum. 2021;2(11):e213409. doi:10.1001/jamahealthforum.2021.3409 Accessed September 15, 2022. https://jamanetwork.com/journals/jama-health-forum/fullarticle/2785932
26. Rowland D. FTC Agrees to 'Shine A Light' on How Drug Middlemen Impact Your Prescription Prices. Columbus Dispatch. June 9, 2022. Accessed September 15, 2022.
https://www.dispatch.com/story/news/2022/06/08/drug-prices-heart-new-ftc-investigation-pharmacy-benefit-managers-pbms/10002565002/
27. Insulin — the New Battleground for Drug Pricing. Nat Biotechnol. 2022;40:1. https://doi.org/10.1038/s41587-021-01203-z Accessed September 15, 2022.
https://www.nature.com/articles/s41587-021-01203-z
28. Bisserbe N, Landouro I. Sanofi Files Suit Against Merck, Claiming Patent Infringements. WSJ. September 19, 2016. Accessed September 15, 2022.
https://www.wsj.com/articles/sanofi-files-suit-against-merck-on-patent-infringements-1474285467
29. U.S. Food and Drug Administration. FDA Approves First Interchangeable Biosimilar Insulin Product for Treatment of Diabetes. July 28, 2021. Accessed September 15, 2022.
https://www.fda.gov/news-events/press-announcements/fda-approves-first-interchangeable-biosimilar-insulin-product-treatment-diabetes
30. Pfizer. Let’s Take a Closer Look at the Characteristics of Biosimilars. Accessed September 15, 2022.
https://www.pfizerbiosimilars.com/characteristics-of-biosimilars
31. Kirzinger A, Kearney A, Quasem M, et al. KFF Health Tracking Poll – March 2022: Economic Concerns and Health Policy, The ACA, and Views of Long-term Care Facilities. Kaiser Family Foundation. March 31, 2022. Accessed September 15, 2022.

KFF Health Tracking Poll – March 2022: Economic Concerns and Health Policy, The ACA, and Views of Long-term Care Facilities

32. H.R.5376 - Build Back Better Act. 117th Congress (2021-2022). Accessed September 15, 2022.
https://www.congress.gov/bill/117th-congress/house-bill/5376
33. Cubanski J, Neuman T, Freed M. Explaining the Prescription Drug Provisions in the Build Back Better Act. Kaiser Family Foundation. November 23, 2021. Accessed September 15, 2022.

Explaining the Prescription Drug Provisions in the Build Back Better Act

34. H.R.6833 — 117th Congress (2021-2022). Affordable Insulin Now Act. Accessed September 15, 2022.
https://www.congress.gov/bill/117th-congress/house-bill/6833
35. Pharmaceutical Research and Manufacturers of America. House Drug Pricing Plan Will “Throw Sand in the Gears of Medical Progress.” November 19,2021. Accessed September 15, 2022.
https://phrma.org/resource-center/Topics/Cost-and-Value/House-Drug-Pricing-Plan-Will-Throw-Sand-in-the-Gears-of-Medical-Progress
36. Koballa KE. The Biologics Price Competition and Innovation Act: Is a Generic Market for Biologics Attainable? Wm & Mary Bus Law Rev. 2018;9(2):479-520. Accessed September 15, 2022.
https://scholarship.law.wm.edu/cgi/viewcontent.cgi?referer=https://www.google.com/&httpsredir=1&article=1150&context=wmblr
37. Biologics Price Competition and Innovation Act. Accessed September 15, 2022. https://www.dpc.senate.gov/healthreformbill/healthbill70.pdf
38. Regulation of Biological Products 42 U.S. Code § 262. Accessed September 15, 2022.
https://www.law.cornell.edu/uscode/text/42/262
39. Bagley D. Devil in the Details: The Impact of the First Interchangeable Biosimilar Insulin. Endocrine News. August 2021. Accessed September 15, 2022.

Devil in the Details: The Impact of the First Interchangeable Biosimilar Insulin

40. Goldstein JN, McCrary M, Lipska KJ. Is the Over-the-Counter Availability of Human Insulin in the United States Good or Bad? JAMA Intern Med. 2018;178(9):1157–1158.
41. Tribble SJ. You Can Buy Insulin Without a Prescription, But Should You? Kaiser Health Network. December 14, 2015. Accessed September 15, 2022.
https://khn.org/news/you-can-buy-insulin-without-a-prescription-but-should-you/
42. Yan K. Eight States Pass Legislation to Place Caps on Insulin Price; Five More Await Ruling. diaLogue.
diaTribe Foundation. Accessed September 15, 2022.
https://diatribe.org/foundation/about-us/dialogue/eight-states-pass-legislation-place-caps-insulin-price-five-more-await-ruling
43. National Conference of State Legislatures. State Laws and Legislation Related to Biologic Medications and Substitution of Biosimilars. May 3, 2019. Accessed September 15, 2022.
https://www.ncsl.org/research/health/state-laws-and-legislation-related-to-biologic-medications-and-substitution-of-biosimilars.aspx
44. Rauhala E. As Price of Insulin Soars, Americans Caravan to Canada for Lifesaving Medicine. Wash Post. July 31, 2019. Accessed September 15, 2022.
https://www.washingtonpost.com/world/the_americas/as-price-of-insulin-soars-americans-caravan-to-canada-for-lifesaving-medicine/2019/06/14/0a272fb6-8217-11e9-9a67-a687ca99fb3d_story.html
45. Osterath B. Do-It-Yourself Insulin: Biohackers Aim to Counteract Skyrocketing Prices. DW. May 24, 2019. Accessed September 15, 2022.
https://www.dw.com/en/do-it-yourself-insulin-biohackers-aim-to-counteract-skyrocketing-prices/a-48861257
46. Gogineni HP, Gogineni RV. Increasing Insulin Prices - Role of Pharmacists in Assisting Patients with Diabetes to Enhance Access. Biomed. J. Sci. & Tech. Res. 2018;8(2) :1-4.
DOI: 10.26717/ BJSTR.2018.08.001633. Accessed September 15, 2022. https://biomedres.us/pdfs/BJSTR.MS.ID.001633.pdf

Inhalers: A Demonstration is Worth One Thousand Words

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

· DESCRIBE the different types of inhalers currently available in the United States

· OUTLINE the relationship between the inhaler type and patient characteristics

· DESCRIBE how to order demonstration devices

· IDENTIFY the ideal time and place to employ a demonstration device with patients

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

· DESCRIBE the different types of inhalers currently available in the United States

· OUTLINE the relationship between the inhaler type and patient characteristics

· DESCRIBE how to order demonstration devices

· IDENTIFY the ideal time and place to employ a demonstration device with patients

Asthma and chronic obstructive pulmonary disease (COPD) are chronic conditions affecting millions of people worldwide. Patients frequently have suboptimal inhaler technique, leading to less effective treatment, inadequate disease control, and reduced quality of life. Patient education and ongoing assessment and support are vital to improving outcomes, but healthcare professionals are often unable to provide this level of care effectively. This continuing education activity reviews the various types of inhaler devices along with important counseling points for each. It offers guidance on choosing appropriate devices based on patient characteristics. It also provides some guidance for how pharmacy personnel can teach, assess, and reinforce proper inhaler technique. Finally, it gives suggestions for ordering and using demonstration devices.

The Accreditation Counsel for Pharmacy Education prefers the use of generic names in continuing education activities to eliminate bias. In this activity, we made the decision to use brand names because of the large number of drugs, combination products, and device combinations currently available.

INTRODUCTION

Asthma and chronic obstructive pulmonary disease (COPD) are common conditions that affect many individuals’ daily functioning. Worldwide, roughly 340 million people have asthma, and 390 million people have COPD.^1,2 It’s well-known that patients often have suboptimal inhaler technique, and numerous professional organizations have advocated for more counseling at every point in the healthcare system.^3,4 Although several new and improved pulmonary inhalation devices are available, inhaler use skills have lagged.⁵

Two systematic reviews analyzed studies of inhaler technique among patientsand healthcare professionals from 1975 to 2014.^5,6 Each review divided the studies into an earlier (1975 to 1994) and a later (1995 to 2014) period to assess changes over time. The review of 54,354 patients over 144 studies found that approximately 30%, 40%, and 30% percent of patients had correct, acceptable, and poor technique, respectively. There was no significant difference in inhaler use skill between the earlier and later time periods.⁵ The review of 6,304 healthcare professionals over 55 studies found that correct inhaler technique among healthcare professionals declined from around 20.5% in the earlier time period to just 10.8% in the later time period.⁶

Using inhalers correctly is essential to disease control. A systematic literature review found an association between inhaler use errors and worsened disease outcomes for patients with asthma and COPD in almost all included studies.⁷ Longitudinal studies found that reductions in inhaler use errors improved disease outcomes.

Ultimately, most patients receive their inhalers from a pharmacy. Research shows that community pharmacists can positively impact inhaler technique, asthma control, quality of life, and medication adherence with educational interventions.⁸ Pharmacy personnel are strategically positioned to improve outcomes for people with asthma and COPD by

Being familiar with the various inhalers available, understanding how to use them, and knowing the counseling points for each
Recognizing patient-specific factors that could impact inhaler administration
Understanding the importance of educating and evaluating patients on inhaler technique, and planning how to best deliver this care

Medication Classes Found in Inhalers

Several pharmacologic classes of medications (and combinations of these classes) are available in inhaler products:

Short-acting beta-agonists (SABA) and long-acting beta-agonists (LABA) relax airway smooth muscles by stimulating beta_2-adrenergic receptors.⁴ Patients with asthma and/or COPD can use beta agonist medications as needed for relief of acute symptoms, and on a regular schedule for symptom prevention.^3,4
Short-acting muscarinic antagonists (SAMA) and long-acting muscarinic antagonists (LAMA) cause bronchodilation by inhibiting muscarinic receptors in the airway smooth muscles.⁴ Patients with COPD can use SAMA and LAMA medications as maintenance therapy.^4,9 Patients with asthma who are already using a LABA and an inhaled corticosteroid (ICS) can add on a LAMA maintenance medication if needed.³
ICS reduce airway inflammation and are used as daily maintenance medications to prevent asthma exacerbations.³ Patients with COPD may also use ICS in combination with LABA or LABA plus LAMA as a daily maintenance medication. Prescribing information for corticosteroid inhalers advises patients to rinse their mouths with water after inhalation and to spit the water out afterward to reduce the risk of fungal infection in the mouth and pharynx.^10-12

TYPES OF INHALER DEVICES

Pressurized Metered Dose Inhalers

A pressurized metered dose inhaler (pMDI) has two components: a plastic actuator with mouthpiece, and a pressurized canister which may contain^13,14

the active medication
a spray-generating propellant to move the medication out of the inhaler
co-solvents to allow the inhaler ingredients to mix well
surfactants to stabilize the mixture and prevent drug particles from clumping together or sticking to the canister

The propellant is typically hydrofluoroalkane (HFA), a replacement for the chlorofluorocarbon (CFC) propellants used in many early inhalers.¹³ The Montreal Protocol of 1987 called for phasing out CFCs due to their ozone-depleting properties. The liquid inside a pMDI canister may be formulated as a solution or as a suspended micronized powder. Each time a patient actuates the inhaler (i.e., presses the button to release a spray), a metering chamber in the canister measures the correct liquid volume for that dose. The device releases large particles (about 45 micrometers) from the mouthpiece in a cloud of vapor, and particle size decreases to between 0.5 and 5.5 micrometers as the aerosol evaporates.

Pause and ponder: How do you think the ban on chlorofluorocarbons impacted the inhaler market?

To maximize lung deposition of medication from a pMDI, patients should take a slow, deep breath lasting about four to six seconds and actuate the inhaler at the start of (or immediately after starting) this breath.¹³ If patients mistime the actuation or inhale too quickly, medication is more likely to deposit on the tongue or the back of the throat and patients will swallow it instead. This phenomenon—also known as oropharyngeal deposition—can reduce the effective medication dose and increase adverse effects (e.g., oral thrush and hoarseness with inhaled corticosteroids).¹³ Table 1 lists the medications available as pressurized metered dose inhalers.

Table 1. Pressurized Metered Dose Inhalers^9,10,15-24

Class	Medication (Trade name[s]/generic availability)	Dose/actuation
Class	Medication (Trade name[s]/generic availability)	Dose/actuation
SABA	albuterol HFA (Ventolin HFA, ProAir HFA, Proventil HFA, generic)	90 mcg
SABA	levalbuterol HFA (Xopenex HFA, generic)	45 mcg
SAMA	ipratropium HFA (Atrovent)	17 mcg
ICS	ciclesonide HFA (Alvesco)	80 mcg 160 mcg
	fluticasone HFA (Flovent HFA, generic)	44 mcg 110 mcg 220 mcg
	mometasone HFA (Asmanex HFA)	100 mcg 200 mcg
ICS/LABA	fluticasone/salmeterol HFA (Advair HFA)	45 mcg/21 mcg 115 mcg/21 mcg 230 mcg/21 mcg
	budesonide/formoterol HFA (Symbicort, generic)	80 mcg/4.5 mcg 160 mcg/4.5 mcg
	mometasone/formoterol HFA (Dulera)	50 mcg/5 mcg 100 mcg/5 mcg 200 mcg/5 mcg
LAMA/LABA	glycopyrrolate/formoterol HFA (Bevespi Aerosphere)	9 mcg/4.8 mcg
ICS/LAMA/LABA	budesonide/glycopyrrolate/formoterol HFA (Breztri Aerosphere)	160 mcg/9 mcg/4.8 mcg

HFA = hydrofluoroalkane; ICS = inhaled corticosteroid; LABA = long-acting beta-agonist; LAMA = long-acting muscarinic antagonist; SABA = short-acting beta-agonist; SAMA = short-acting muscarinic antagonist

Spacers and Valved Holding Chambers

A spacer is a tube or bag, often made of plastic, that a patient connects to a pMDI before use.²⁵ Medication particles traveling through these devices slow down before reaching the mouth. This also allows the aerosol propellant more time to evaporate, leaving smaller particles to be inhaled. Lower velocity and smaller particle sizes reduce oropharyngeal deposition, so more medication reaches the lungs. However, patients still need to time inhalation with actuation, and they should avoid exhaling into the spacer to prevent dilution (weakening) of the dose.

Valved holding chambers (VHC) are like spacers, but they have a one-way valve between the chamber and the mouthpiece.²⁵ VHCs trap the aerosols in the chamber, allowing time for patients with poor hand-breath coordination to inhale their medication. The one-way valve blocks exhalations from reaching the aerosols in the chamber, allowing patients to use multiple inhalations or tidal (restful) breathing if needed. For doses requiring multiple medication puffs, healthcare providers should counsel patients to prepare, actuate, and inhale each puff separately rather than spraying multiple puffs into the spacer or VHC at once.¹³

Due to gravity, impaction, and electrostatic charge, some medication is lost in a spacer or VHC before reaching the patient.²⁵ Washing a spacer or VHC with detergent (a water-soluble cleansing agent) and letting it air dry before first use can reduce the electrostatic charge and limit drug particle loss to the device walls. Some spacers and VHCs are made with anti-static material, but often come at a higher cost to the patient.

The Global Asthma Network (which aims to improve asthma care, particularly in low- and middle-income countries) advises that people can make effective spacers from 500 ml plastic bottles if commercial spacers are unavailable or too expensive.¹ A cost-effectiveness analysis determined home-made spacers (most of which were made from plastic water bottles) to be more cost-effective than commercial spacers in Columbia (a middle-income country).²⁶ The study found lower overall treatment costs and no difference in hospital admission rates.

Breath-Actuated pMDIs

A breath-actuated pMDI of beclomethasone dipropionate HFA (Qvar Redihaler) is available to overcome the problem of hand-breath coordination.²⁷ This inhaler is available in 40 mcg/actuation and 80 mcg/actuation. As the name implies, it actuates when the patient takes a breath, but it does not rely on a high inspiratory flow rate to deliver the medication. An inspiratory flow rate of just 20 L/min activates the inhaler, which then uses the HFA propellant to assist with dose delivery. Other breath-activated inhalers (discussed below) require up to 88 L/min for activation, which may be difficult for individuals with asthma or COPD who are already having trouble breathing. Young children and adults have tidal breathing inspiratory flow rates of 8 to 16 L/min and 13 to 18 L/min respectively.²⁷ Therefore, a breath-activated pMDI may require only a bit more inspiratory effort than the patients’ usual breathing.

Soft Mist Inhalers

Soft mist inhalers (SMIs) do not contain a propellant.²⁵ Instead, these inhalers use a spring to create pressure and spray the drug solution through a nozzle, forming two jets of liquid that collide to create a slow-moving mist. The mist’s low velocity increases drug deposition in the lungs rather than the oropharynx. An SMI’s aerosol cloud lasts about six times longer than a pMDI’s, increasing the window for effective inhalation in patients who have trouble coordinating actuation and inhalation. Table 2 shows the medications available as soft mist inhalers.

Table 2. Soft Mist Inhalers^28-31

Class	Medication (Trade name)	Dose/actuation
Class	Medication (Trade name)	Dose/actuation
SAMA/SABA	ipratropium bromide/albuterol sulfate (Combivent Respimat)	20 mcg/100 mcg
LAMA	tiotropium (Spiriva Respimat)	1.25 mcg 2.5 mcg
LABA	olodaterol (Striverdi Respimat)	2.5 mcg
LAMA/LABA	tiotropium/olodaterol (Stiolto Respimat)	2.5 mcg/2.5 mcg

LABA = long-acting beta-agonist; LAMA = long-acting muscarinic antagonist; SABA = short-acting beta-agonist; SAMA = short-acting muscarinic antagonist

Dry Powder Inhalers

Dry powder inhalers (DPI) are breath-actuated and breath-powered inhaler devices. To improve powder flow and accurate dose metering, manufacturers combine the active medication with a carrier powder or formulate it into spherical agglomerates (small sphere-shaped particles).³² Patients’ inspiratory flow and the resistance inside the inhaler generate turbulent energy that disaggregates (separates) the medication. Quick inhalation optimizes this process. The resulting tiny drug particles (less than 5 micrometers) can reach the lungs, while the larger carrier particles land in oropharynx and are swallowed.

DPIs typically require an inspiratory flow rate of at least 30 to 60 L/min, which some patients may have difficulty achieving.²⁵ There is also a possibility of decreased medication delivery from a DPI during disease exacerbations (periods of worsening), when patients’ ability to generate a forceful inspiration may be impaired.³²Table 3 lists available dry powder inhalers.

Table 3. Dry Powder Inhalers^15,33-46

Class	Medication (Trade name[s]/generic availability)	Dose/actuation
Class	Medication (Trade name[s]/generic availability)	Dose/actuation
SABA	albuterol (ProAir RespiClick, ProAir Digihaler)	117 mcg
LABA	salmeterol (Serevent Diskus)	50 mcg
ICS	budesonide (Pulmicort Flexhaler)	90 mcg 180 mcg
	fluticasone propionate (Flovent Diskus)	50 mcg 100 mcg 250 mcg
	fluticasone furoate (ArmonAir Digihaler)	55 mcg 113 mcg 232 mcg
	fluticasone furoate (Arnuity Ellipta)	50 mcg 100 mcg 200 mcg
	mometasone (Asmanex Twisthaler)	110 mcg 220 mcg
ICS/LABA	fluticasone/salmeterol (Advair Diskus, Wixela Inhub, generic)	100 mcg/50 mcg 250 mcg/50 mcg 500 mcg/50 mcg
	fluticasone/salmeterol (AirDuo RespiClick, AirDuo Digihaler, generic)	55 mcg/14 mcg 113 mcg/14 mcg 232 mcg/14 mcg
	fluticasone/vilanterol (Breo Ellipta, generic)	100 mcg/25 mcg 200 mcg/25 mcg
LAMA	aclidinium bromide (Tudorza Pressair)	400 mcg
	tiotropium bromide (Spiriva Handihaler)	18 mcg (per capsule)
	umeclidinium (Incruse Ellipta)	62.5 mcg
LAMA/LABA	umeclidinium/vilanterol (Anoro Ellipta)	62.5 mcg/25 mcg
ICS/LAMA/LABA	fluticasone/umeclidinium/vilanterol (Trelegy Ellipta)	100 mcg/62.5 mcg/25 mcg 200 mcg/62.5 mcg/25 mcg

ICS = inhaled corticosteroid; LABA = long-acting beta-agonist; LAMA = long-acting muscarinic antagonist; SABA = short-acting beta-agonist

INHALER TECHNIQUE EDUCATION

Consider that participants in most randomized controlled trials receive thorough education on inhaler use, must demonstrate competence to be included, and receive ongoing evaluations of their technique.⁴ This is the context in which inhaler efficacy is established. Ideally, all patients would have access to similar standards of care to ensure maximum benefit of inhaled medications. Inhaler technique support can also improve adherence. If patients are using inhalers incorrectly and not seeing clinical improvement, they may discontinue them due to perceived lack of efficacy.⁴⁷ A survey of patients with COPD found significantly greater adherence and confidence in treatment among patients whose inhaler technique had been checked by a healthcare professional within the past two years.⁴⁸

Healthcare providers must consider patient preferences, health literacy, and language barriers when choosing appropriate education methods.⁴⁷ A survey of inhaler-using adults seen at a pulmonary clinic or outpatient pharmacy compared education preferences between English and non-English speakers.⁴⁹ Both groups shared a preference for in-person, active learning methods but had low interest in participating in education sessions outside of regular clinic visits. The aforementioned survey of patients with COPD found that 83% thought a demonstration was “very helpful” for learning inhaler technique.⁴⁸ Only 58% and 34% thought the same about a video or leaflet, respectively.

Pharmacists Can Improve Inhaler Use

Pharmacists are best placed to provide in-person, active demonstrations to patients where they already come to pick up their medications. Research shows that pharmacists can provide effective inhaler use education (if and when their workflow allows for it). A 2017 systematic review of critical inhaler errors in asthma and COPD found that pharmacist-led inhaler education interventions produced statistically significant improvements in patients’ inhaler technique in seven out of eight studies.⁵⁰

Published studies of pharmacist-led interventions provide examples of counseling methods that have proven effective. A pre- and post-intervention study of 211 patients with COPD in Vietnam examined the efficacy of face-to-face inhaler training with a pharmacist. Training followed this format⁵¹:

Patients demonstrated technique on a placebo inhaler device
Pharmacists corrected each mistake and explained why the correction was important
Pharmacists demonstrated every step verbally and physically with a placebo inhaler
Patients performed the technique again
Patients and pharmacists repeated this process until patients could complete all steps correctly

This procedure took about six minutes for initial training and three minutes for follow-up trainings.⁵¹ Pharmacists provided training monthly for three months, once at six months, and once at 12 months. They also included label stickers on inhalers with a summary of the steps for use. The percentage of patients using correct inhaler technique increased by over 40% from baseline to six months but declined somewhat between six and 12 months. Researchers concluded that patients benefit from an initial intensive period of repeated training sessions, followed by long-term follow-up at least every three months.⁵¹

Another study of 72 subjects examined the efficacy of different inhaler training methods by assigning patients to do one of the following⁵²:

Read an MDI package insert pamphlet
Watch a Centers for Disease Control and Prevention video demonstrating technique
Watch a YouTube video demonstrating technique
Receive direct instruction from a pharmacist

Only two minutes were allotted for the interventions (to mimic what might be feasible in a community pharmacy setting).⁵² The pharmacist-led counseling sessions were loosely scripted based on a checklist of proper inhaler technique. After a pharmacist explained and demonstrated inhaler use, subjects could ask questions if time permitted. Study investigators (including the pharmacists performing the direct instruction sessions) used a standardized checklist to assess all participants immediately following the training. There was a statistically significant difference between pharmacist-led instruction and each of the other interventions but not between any of the three other intervention groups. More than 70% of patients in the pharmacist-led intervention group demonstrated correct inhaler use after training compared with less than 20% of patients in the other intervention groups.⁵²

Pause and Ponder: Why might a live demonstration provide better training than a video demonstration of the same time duration?

The 2022 GINA report emphasizes the importance of providing patients with ongoing inhaler technique training and assessment. The report recommends that pharmacists, nurses, and other healthcare workers³

physically demonstrate using placebo inhalers (and spacers or VHCs, if applicable)
check against a device-specific checklist as patients demonstrate technique
supply a take-home handout with steps for inhaler use (ideally including pictures)
check and re-train patients at every opportunity, as errors frequently recur four to six weeks after training

Pause and ponder: In your workplace, would it be feasible to provide two minutes of counseling with every inhaler refill? How might you identify patients who most need inhaler use training?

Of note, devices exist to evaluate patients’ inspiratory flow and inhalation technique when prescribing, training, or assessing.⁴⁷ Although these may not be feasible to use in most community pharmacy settings (and are outside the scope of this continuing education module), they may be very useful in other settings (e.g., a pulmonary clinic). Devices include the AIM (Aerosol Inhalation Monitor), the In-Check DIAL, and the 2-Tone trainer.⁴⁷

Inhaler Administration Counseling

pMDIs

Most pMDIs require users to prime (release sprays into the air) before first use (see Table 4).^17-20When priming a pMDI, users should spray it in the air away from the face. If the inhaler requires shaking, they should also be sure to shake well before each priming spray. Most pMDIs require shaking prior to actuation but some, including Atrovent HFA and Alvesco, do not.^9,10 Patients should always avoid spraying pMDIs into their eyes; the package insert for Atrovent HFA instructs users to close their eyes during inhaler actuation.⁹

Table 4. Priming Requirements for pMDIs^10,15-24

Product(s)	Prime before first use and if not used for more than:	Number of Sprays
Advair HFA^a	28 days	4 sprays
Proventil HFA Ventolin HFA^b	14 days
Bevespi Aerosphere^b Breztri Aerosphere^b Flovent HFA^a	7 days
Asmanex HFA Dulera	5 days
Xopenex HFA	3 days
ProAir HFA^b	14 days	3 sprays
Alvesco	10 days	3 sprays
Symbicort^a	7 days	2 sprays
Atrovent HFA	3 days	2 sprays

^aAlso need to be primed if dropped; ^bAlso need to be primed after cleaning; HFA = hydrofluoroalkane

The following are general administration instructions for pMDIs^17-20:

Check for a firm fit of the canister in the actuator
Remove cap from mouthpiece and check mouthpiece for any foreign objects
If product requires shaking, shake well (typically for 5 seconds)
Facing away from the inhaler, exhale completely
Holding inhaler upright with mouthpiece down, place mouthpiece in mouth
Form a tight seal with lips, keep tongue below mouthpiece, and tilt head back slightly
While breathing in deeply and slowly through the mouth, press down on the canister until it stops moving and has released a puff and remove finger from the canister
Continue to breathe in as long as possible, then remove the mouthpiece
Hold breath as long as is comfortable (up to 10 seconds)
Breathe out gently, away from the inhaler
Replace cap right away

Patients should never use the canister of one inhaler with the actuator of another inhaler.^9,23,24 Patients should clean pMDIs at least once a week. Cleaning instructions for pMDIs vary by product (see Table 5).

Table 5. pMDI Cleaning Requirements^10,15-24

Product	Cleaning instructions
Proventil HFA	Remove the canister from the actuator; DO NOT let the canister get wet. Remove the cap from the mouthpiece. Run warm water through the top and bottom of actuator for 30 seconds in each direction. Thoroughly shake dry. Check the mouthpiece for remaining medication buildup. Let air-dry completely (overnight if possible). If not fully air-dried before next dose, shake the plastic actuator as dry as possible, insert the canister, shake the inhaler, and actuate it twice. Repeat the original cleaning procedure after taking the necessary dose(s).
Ventolin HFA
Xopenex HFA
ProAir HFA
Atrovent HFA
Bevespi Aerosphere
Breztri Aerosphere
Flovent HFA	Clean after evening dose. DO NOT remove the canister from the actuator. Use a water-dampened cotton swab to clean the small circular opening where medicine sprays out of the canister, twisting in a circular motion. Repeat with a new damp swab. Wipe the inside of the mouthpiece with a clean, damp tissue. Let air dry overnight.
Advair HFA
Asmanex HFA	DO NOT remove the canister from the actuator. Wipe inside and outside surfaces of the actuator with a dry, lint-free tissue or cloth. DO NOT wash or put any parts in water. Use a dry folded tissue to wipe over the front of the small hole where the medicine comes out of the Alvesco inhaler.
Alvesco
Symbicort
Dulera

HFA = hydrofluoroalkane

All available MDI inhalers have dose counters built into either the canister or the actuator. For most products, the dose counter’s numbers or background will change to red when the inhaler is running low, reminding patients to refill their medication. Healthcare providers should counsel patients not to use inhalers after the dose counter reads zero, even if the canister does not feel empty and still operates. People should not put canisters in water to see if they float as a means of gauging whether medication remains (an old trick that is no longer recommended) or try to alter dose counters. They should also never use a sharp object to unblock an actuator or throw a pMDI into a fire or incinerator. All pMDI inhalers require storage at room temperature, and most should be stored with the mouthpiece down so that the tip of the canister valve is facing down. This keeps the gasket inside of the canister wet so that it does not become brittle and allow outside moisture to enter the canister.⁵³

In addition to general counseling for pMDIs, specific counseling points for breath-actuated pMDIs include four points⁵⁴:

There is no button to press; opening the cap prepares the dose. If patients leave the cap open for more than two minutes, they will need to close and reopen the cap before inhaling their dose.
Do not shake (especially not with the cap open, as this may actuate the inhaler). Do not prime or use with a spacer or VHC.
Clean weekly with a clean, dry tissue or cloth
Do not take the inhaler apart

SMIs

To set up an SMI (Respimat inhaler), remove the clear base, label the cartridge with the discard date (three months from first use), and insert the narrow end of the cartridge into the inhaler.^28-31 With the inhaler on a firm surface, push down until the cartridge clicks into place (this often takes more force than patients expect). Replace the clear base so that it clicks into place. Do not take the inhaler apart after assembly. To actuate the inhaler, patients should remember the acronym TOP:

Turn the clear base half a turn in the direction of the arrows until it clicks
Open the cap fully
Press the dose-release button and close the cap.

Before first use, repeat the actuation steps until a mist is visible.^28-31 Then repeat three more times. To take an inhalation

Turn the base and open the top
Fully exhale away from the inhaler
Put mouthpiece in mouth and form a tight seal with lips, keeping mouthpiece above the tongue and pointing towards the back of the throat; be sure not to block air vents with lips or fingers
While taking a slow, deep breath through the mouth, press the dose-release button and breathe in as long as possible
Remove inhaler from mouth and hold breath as long as is comfortable (up to 10 seconds)
Breathe out slowly away from the inhaler
Close cap

Pharmacists should counsel patients to prime the device with one puff if not used for more than three days or four visible puffs if not used for more than 21 days.^28-31 Patients should clean the SMI’s mouthpiece (including the metal part inside) once a week with a damp cloth or tissue. These inhalers have dose indicators and automatically lock when empty. Patients should not spray the device into their eyes or use the SMI with a spacer or VHC. SMIs require room temperature storage.

DPIs

To administer DPIs^33-36

Open cover or remove cap and check mouthpiece for foreign objects

Prepare dose (see Table 6)
Fully exhale away from the inhaler
Put mouthpiece in mouth and form a tight seal with lips, keeping tongue below mouthpiece; be sure not to block air vents with lips or fingers
Breathe in quickly and deeply, generating a forceful breath right from the start of inhalation
After breathing in all the way, remove inhaler from mouth and hold breath for as long as is comfortable (up to 10 seconds)
Breathe out slowly away from the inhaler
Cover mouthpiece

Table 6. Preparing and Administering DPI Doses^{15,33-37,39-46}

DPI Type	Dose Preparation and Related Notes
Digihaler	Holding inhaler upright, open cap fully until it clicks (the click can be felt and heard). Built in sensors track adherence and inspiratory flow rates. The inhaler sends information to an application using Bluetooth technology. The inhalers work even if they are not wirelessly connected to the mobile application.
Diskus	Hold inhaler in left hand with thumb of right hand in thumb grip. Push thumb grip away to snap mouthpiece into place. Hold in a level, flat, horizontal position. Slide lever away from mouthpiece until it clicks. Keep holding Diskus level during inhalation. To close after inhalation, patients put their thumb in the thumb grip and pull back towards themselves until the inhaler clicks shut over the mouthpiece. Do not close before inhaling, tilt, play with the lever, or move the lever more than once; doses may be lost.
Ellipta	Open the cover until it clicks. If patients open and close the cover without inhaling the medicine, the dose will be lost inside the inhaler, but patients will not receive a double dose.
Flexhaler	Hold brown grip in one hand and use the other to twist off white cover. Hold inhaler upright with one hand still on brown grip and the other in the middle of the inhaler. Twist brown grip as far as possible in one direction, and then back all the way in the other direction. Priming is required before first use (follow instructions for preparing a dose twice). The inhaler will click in the process of preparing a dose. Do not click the brown grip multiple times without inhaling. The dose indicator will count down with each click. However, it is not possible to receive more than one dose at a time. Do not shake the inhaler after preparing a dose.
Handihaler	Press green button and pull cap away to uncover mouthpiece. Then pull mouthpiece away to uncover center chamber. Remove a capsule from blister packaging (without using sharp instruments) and place it in the center chamber. (Discard unused capsules accidentally exposed to air. Close mouthpiece until it clicks. With mouthpiece pointing up, press green piercing button until flat against base only once, then release. Do not shake. When the capsule is pierced, small pieces of gelatin may be created. These may end up in the mouth or throat and are not harmful. Hold inhaler horizontally when inhaling and inhale twice from the same capsule. The capsule should rattle during inhalation. Do not swallow or manually open capsules.
Pressair	Hold inhaler horizontally with green button on top. Press and release the green button to prepare dose. Do not tilt inhaler. Check that control window changes to green. Do not hold green button down when inhaling. Correct inhalation causes an audible click and control window changes from green to red. Pushing green button multiple times before inhaling does nothing; patients will not lose a dose or get a double dose.
RespiClick	Holding inhaler upright, open cap fully until it clicks (the click can be felt and heard). Always close the cap after each inhalation. Patients will waste the medication if they open and close the cap without inhaling.

Patients may or may not taste or feel the powder from a DPI upon inhalation. It is fine if they do, and they should not take an extra dose if they don’t. Patients cannot use spacers, VHCs, or masks with DPIs. Manufacturers formulate most DPIs with lactose powder as an ingredient, so patients with severe milk protein allergies should not use them.

Individuals should not wash DPIs. If cleaning is necessary, using a dry tissue or cloth is appropriate. Patients should store DPIs at room temperature and protect them from heat and humidity; they are more sensitive to humidity than are other inhalers. They should not store the Tudorza Pressair inhaler on a vibrating surface.

DEVICE SELECTION TO MATCH PATIENT NEEDS

Individualizing delivery device selection is crucial for optimizing outcomes of aerosol drug therapy. Healthcare professionals must consider patient-, drug-, device-, and environmental-related factors. A good starting point may be to observe a patient’s natural inhalation.⁵⁵ For example, if the patient instinctively takes slow, deep breaths, a pMDI or SMI might be a good fit. If the patient tends to inhale quickly and deeply, a DPI may be ideal. Table 7 discusses other important factors to consider.

Table 7. Inhaler Suggestions Based on Patient-Specific Factors^25,27,56-58

For people with…	…Consider
Inability to achieve a good lip seal around an inhaler’s mouthpiece (e.g., pediatric, facial weakness, cognitive impairment)	pMDI with spacer/VHC and facemask
Inability to learn and perform specific breathing techniques	pMDI with VHC
Difficulty generating an inspiratory flow rate of at least 30 to 60 L/min (e.g., older age, female gender, airflow limitation, respiratory muscle weakness, lung hyperinflation, history of COPD exacerbations requiring hospitalization)	pMDI; breath-actuated pMDI; SMI
Poor manual dexterity or limited hand strength	Breath-actuated pMDI; SMI (may need help with initial cartridge installation); DPI (one that does not require complicated manipulations for dose preparation)
Difficulty with hand-breath coordination	Breath-actuated pMDI; pMDI with VHC; DPI; SMI
Inability to store inhaler away from heat and humidity	Non-DPI inhaler (particularly sensitive to heat and humidity)

COPD = chronic obstructive pulmonary disease; DPI = dry powder inhaler; pMDI = pressurized metered dose inhaler; SMI = soft mist inhaler; VHC = valved holding chamber

Patients often use multiple inhaled medications for asthma and COPD. Prescribing the same inhaler type for all a patient’s inhaled medications eliminates confusion over varying administration techniques.⁵⁹ Clinicians can also prescribe combination products where appropriate to simplify treatment regimens.

Consider the Cost

Affordability is another vital consideration and will depend on the patient’s insurance status. While most inhalers are brand-name only, a few generic inhalers are available (see examples in Tables 1-3). Prioritizing patient preference when selecting inhalers can improve adherence.⁶⁰ Central to patient satisfaction are issues such as simplicity of use, treatment time, comfort, portability, cleaning requirements, taste, and effect on the throat. If a patient remains unable to use a device effectively after several training visits, consider switching to another inhaler type.

INHALER USE MISTAKES

A literature review and meta-analysis of inhaler use errors in patients with asthma and COPD found that 50% to 100% of patients made at least one error when using their inhaler. Error rates were higher for patients⁶¹

using MDIs compared to those using DPIs
with COPD compared to those with asthma
with a longer history of device use compared to patients new to inhaler treatment
using multiple inhalers compared to those using only one inhaler

Errors are also common in patients using SMIs. A systematic literature review and meta-analysis of patients with COPD, bronchitis, or emphysema found that nearly 60% made at least one error when using a SMI.⁶² Other factors associated with higher error rates include^50,61

older age
lower education level
female gender
lower socioeconomic status
having two or more comorbidities

Pause and ponder: In your workplace, would it be feasible to provide training and technique assessment with every inhaler refill? If not, how might you identify and prioritize patients who most need inhaler use training?

While perfect inhaler use is ideal, patients often have complex medication regimens and healthcare professionals often have heavy workloads. It’s vital to prioritize the most essential steps in the inhaler use process, including those that have a proven impact on patient outcomes. The CRITIKAL study used data from the iHARP asthma review service (a multicenter cross-sectional study of adults with asthma) to identify inhaler use errors associated with worsening asthma control.⁶³ Investigators used data from 3660 patients to pinpoint these critical errors which included⁶³

not opening the cover or removing cap from mouthpiece
insufficient inspiratory effort
incorrect position of head
not breathing out before inhalation
not holding breath after inhaling medication, or holding for less than three seconds
not sealing lips around mouthpiece
incorrectly priming, timing, or inhaling the second dose (if needed)

Demonstration Devices

Demonstration devices are placebo inhalers, meaning they contain no active medication. They may be available free of charge from device manufacturers. These are ideal for training since the lack of active drug allows for repeated cycles of education and patient demonstration (“teach-back”). Many demonstration inhalers are specifically marked as “only for use by a single patient” to prevent the possible spread of disease.⁶⁴ Keep demonstration inhalers in a separate area of the pharmacy, and do not send them home with patients to avoid any confusion.⁶⁵

We collected the following information by calling inhaler manufacturers directly. Typically, anyone in a healthcare provider’s office or pharmacy is allowed to order demonstration devices on behalf of a prescriber or pharmacy. To order demonstration devices

Determine the patient population and disease state you will be addressing
Generate a list of common devices your patients use
Identify the manufacturer of each device and visit the manufacturer’s website or the website for the specific product
Obtain the email and phone number for customer service representatives and note days and times available (keep in mind the time zone)
Reach out to the company’s local representative or customer care representative to request demonstration devices
Provide all information required (generally your full name, title, state license number, phone number, address of the pharmacy or office you plan to have the devices delivered to and the facility’s secondary contact information [e.g., fax, email])

When making a demonstration device request, pharmacy staff should allow several weeks for processing and device delivery. The number of devices available also varies. For example, one inhaler manufacturer provides 15 or 20 demonstration devices in response to requests, while another requires a manager review of any request for more than three devices.

Appendix 1 provides contact information for the manufacturers of several inhaler devices. Demonstration device availability can change over time; some companies have demonstration devices in stock only periodically and will advise calling back another time. Companies may also stop carrying demonstration devices for their older products. The GOLD report identifies a lack of placebo inhalers as a common barrier to educating patients.⁴ However, if efforts to obtain demonstration devices are unsuccessful, pharmacists can teach patients using their own devices instead.

Manufacturers may also provide patient assistance programs and co-pay assistance to help with affordability. Patients with commercial or private health insurance are often eligible to participate in co-pay assistance programs and receive a savings card to help lower the cost of the prescription. Healthcare providers can also request additional educational materials and pamphlets to hand out. Referring patients who may be struggling with affording their medications to the manufacturer for assistance and to investigate the patients’ benefits to determine discounts available is highly recommended.

CONCLUSION

Pharmacy personnel are well positioned to help patients maximize the benefit of their inhaled medications. An awareness of available inhalers and the requirements and techniques for their use can help healthcare professionals identify whether patients and their devices are a good match. Recognizing the importance of ongoing training and assessment, pharmacy staff can encourage brief yet frequent counseling sessions with patients as they refill their inhaled medications. Pharmacy personnel should proactively order inhaler demonstration devices from manufacturers (if available) to facilitate patient education.

Good

Better

Best

1. Be familiar with different inhaler devices, including counseling points and potential barriers to use for each

2. Encourage any patient picking up an inhaler to speak with the pharmacist about technique

3. Provide pictorial instructions for use with every inhaler

1. Obtain inhaler demonstration devices and use them with patients

2. Based on refill patterns, recognize patients who may be over- or under- using inhalers and assess for suboptimal technique

3. Check against a device-specific checklist when assessing patient technique

1. Check and re-train on inhaler technique at every opportunity

2. Explain the reason behind any corrections

3. Repeat the teach-back/correction cycle until patients are confident and competent

Appendix I. Inhaler Manufacturer Contact List (Current as of July 1, 2022)

Company	Products (demo device unavailable)	Business Contact
AstraZeneca	Symbicort HFA Pulmicort Flexhaler Bevespi Aerosphere Breztri Aerosphere	1-800-236-9933 Monday-Friday, 8am-6pm ET https://www.astrazeneca-us.com/az-in-us/Contact-us.html Discount card eligibility: https://www.azandmeapp.com/home.html
Boehringer Ingelheim Pharmaceuticals, Inc.	Spiriva Respimat Striverdi Respimat Combivent Respimat Stiolto Respimat Atrovent HFA Spiriva Handihaler	Direct Representative Line: 1-800-243-0127 https://www.boehringer-ingelheim.us/contact-form Patient assistance program: 1-800-556-8317 or www.bipatientassistance.com
GlaxoSmithKline (GSK)	Breo Ellipta Ventolin HFA Trelegy Ellipta Flovent HFA Anoro Ellipta Advair HFA Incruse Ellipta Flovent Diskus Arnuity Ellipta Serevent Diskus Advair Diskus	GSK Response Team: 1-888-825-5249 Monday-Friday, 8:30am-5:30pm ET https://www.contactus.gsk.com/callback/hcp.html Discount card eligibility: www.gskforyou.com
Organon & Co.	Asmanex HFA Dulera HFA Asmanex Twisthaler	Service Center: 1-844-674-3200 Coupons for patients with private insurance: www.asmanex.com ; www.dulera.com
Mylan	Wixela Inhub	Customer Relations Team: 1-800-796-9526 Discount card eligibility: www.wixela.com
Sunovion	Xopenex HFA	Customer Service (Respiratory): 1-844-276-8262
Teva	albuterol sulfate HFA (generic) ProAir RespiClick levalbuterol tartrate HFA (generic) fluticasone propionate/salmeterol inhalation powder, USP QVAR Redihaler	Clinician Support Line: 1-877-867-3034 Patient assistance program: 1-800-896-5855

HFA = hydrofluoroalkane

All information was obtained by calling companies directly and was up to date as of July 1, 2022.

Pharmacist Post-test

Learning Objectives
After completing this continuing education activity, pharmacists will be able to
• DESCRIBE the different types of inhalers currently available in the United States
• OUTLINE the relationship between the inhaler type and patient characteristics
• DESCRIBE how to order demonstration devices
• IDENTIFY the ideal time and place to employ a demonstration device with patients

Questions 1-3 pertain to the following case:
MG, a 76-year-old male, is picking up a refill of his Advair HFA. He mentions that this medication has worked well for him for a couple years now, but he’s having difficulty actuating his inhaler lately due to worsening arthritis in his hands. He isn’t always able to time the spray well with his breathing.

1. Which of the following changes do you recommend that MG discuss with his doctor?
A. Using a VHC with the Advair HFA
B. Switching to Wixela Inhub
C. Switching to Anoro Ellipta

2. MG discusses your suggestion with his doctor, and obtains a prescription for Wixela Inhub. However, he wants to try a demonstration device before filling the prescription to ensure it is easy for him to use. If you don’t have any on hand, which of the following is TRUE?
A. MG should come back in a few days, since you can quickly order the demonstration device through your wholesaler
B. It will likely take a few weeks to order and receive the demonstration device from the manufacturer, if it is available
C. You will need to get a prior authorization before you can order him a demonstration device, so you can teach him with his own inhaler

3. Actually, you do have a demonstration device on hand, and you instruct MG on its use. He demonstrates good technique and decides to fill his prescription. To ensure that MG maintains good technique, which of the following should you do?
A. Send the demonstration device home with MG for ongoing practice; ask him to bring the demonstration device back when he comes to refill his inhaler so you can recheck his technique, ideally in 4 to 6 weeks
B. Send the demonstration device home with MG for ongoing practice; ask him to bring the demonstration device back so you can recheck his technique, ideally in 2 to 3 weeks
C. Do not send the demonstration device home; when MG comes to refill his inhaler, use a new demonstration device or his own prescribed device to recheck his technique, ideally in 4 to 6 weeks

4. JM is a 20-year-old male who admits he doesn’t follow the cleaning instructions for his Flovent HFA inhaler and says it’s just not going to happen. He will wipe it with a tissue if it looks dirty, but that’s about it. Given JM’s cleaning preferences, which of the following inhalers would be the best alternative to his Flovent HFA?
A. Arnuity Ellipta
B. Stiolto Respimat
C. Alvesco

5. Which of the following inhalers requires a slow, deep breath?
A. Tudorza Pressair
B. Spiriva Handihaler
C. Striverdi Respimat

6. A patient is using Anoro Ellipta and Flovent Diskus daily. Which of the following would be the best option to simplify her treatment regimen and improve adherence?
A. Trelegy Ellipta (flutica/umec/vilan)
B. Breztri Aerosphere (budes/glycol/formo)
C. Incruse Ellipta (umec) + Breo Ellipta (flu/vil)

7. Which of the following patient attributes is appropriately matched with an inhaler type?
A. Limited hand strength; pMDI
B. Poor hand-breath coordination; DPI
C. Maximum inspiratory flow of 20 L/min; DPI

8. Which of the following is TRUE about soft mist inhalers?
A. They contain a stronger propellant than pMDIs
B. They do not require a high inspiratory flow rate
C. They require good manual dexterity for actuation

9. Which of the following is correct technique for Spiriva Handihaler administration?
A. Using scissors to carefully open only one blister at a time
B. Taking only one inhalation from each capsule to avoid overdose
C. Listening for the capsule to rattle during inhalation

10. Which of the following is an appropriate counseling point for Alvesco?
A. Clean the actuator with running water weekly
B. Prime before first use and if not used for more than 3 days
C. Rinse with water and spit out after each use

Pharmacy Technician Post-test

Learning Objectives
After completing this continuing education activity, pharmacy technicians will be able to
• DESCRIBE the different types of inhalers currently available in the United States
• OUTLINE the relationship between the inhaler type and patient characteristics
• DESCRIBE how to order demonstration devices
• IDENTIFY the ideal time and place to employ a demonstration device with patients

1. Which of the following inhalers can be used with a spacer or VHC?
A. Advair HFA
B. Wixela Inhub
C. Anoro Ellipta

2. Which of the following is TRUE about ordering an inhaler demonstration device?
A. You can always order them through your wholesaler for next day delivery
B. It will likely take a few weeks to order and receive one from the manufacturer, if it is available
C. You will likely need to get a prior authorization before you can order one

3. Which of the following is TRUE regarding inhaler demonstration devices?
A. Pharmacies should send them home with patients to allow for continued practice
B. Pharmacies should store them next to their medication-containing counterparts
C. Many are labeled for single-patient use to prevent the risk of disease transmission

4. A patient mentions to you that he uses running water to wash the mouthpiece of his inhaler each week. For which inhaler would this be a problem?
A. Breztri Aerosphere
B. ProAir HFA
C. Asmanex HFA

5. Which of the following inhalers requires a slow, deep breath?
A. Tudorza Pressair
B. Spiriva Handihaler
C. Striverdi Respimat

6. A patient tells you he has trouble remembering whether he has taken his inhalers in a given day and he wishes there was an inhaler that could track his use and send the information right to his cell phone. What type of inhaler has this feature?
A. Respimat inhalers
B. Digihaler inhalers
C. Ellipta inhalers

7. You work in a very humid part of Florida. A patient picking up his inhaler confides in you that he is currently living out of his car and that he stores his medications in his glove compartment. Which inhaler type would prompt you to refer this patient to the pharmacist?
A. Pressurized metered dose inhaler
B. Dry powder inhaler
C. Soft mist inhaler

8. Which of the following would prevent a patient from using a dry powder inhaler?
A. The patient can’t get a good seal around a mouthpiece
B. The patient is unwilling to perform routine inhaler cleaning
C. The patient has poor hand-breath coordination

10. Which patients should you advise to review their inhaler technique with the pharmacist?
A. Only patients with questions about inhaler technique
B. Only patients who are starting on a new inhaler or switching devices
C. All patients using inhalers, ideally every four to six weeks

References

1. Global Asthma Network. The Global Asthma Report 2018. 2018. Accessed July 6, 2022. http://globalasthmareport.org/resources/Global_Asthma_Report_2018.pdf
2. Adeloye D, Song P, Zhu Y, et al. Global, regional, and national prevalence of, and risk factors for, chronic obstructive pulmonary disease (COPD) in 2019: a systematic review and modelling analysis. Lancet Respir Med. 2022;10(5):447-458. doi:10.1016/S2213-2600(21)00511-7
3. Global Initiative for Asthma. Global strategy for asthma management and prevention. 2022. Accessed July 6, 2022. https://ginasthma.org/wp-content/uploads/2022/07/GINA-Main-Report-2022-FINAL-22-07-01-WMS.pdf
4. Global Initiative for Chronic Obstructive Lung Disease. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: 2022 report. 2021. Accessed July 6, 2022. https://goldcopd.org/2022-gold-reports-2/
5. Sanchis J, Gich I, Pedersen S; Aerosol Drug Management Improvement Team (ADMIT). Systematic review of errors in inhaler use: has patient technique improved over time?. Chest. 2016;150(2):394-406. doi:10.1016/j.chest.2016.03.041
6. Plaza V, Giner J, Rodrigo GJ, et al. Errors in the use of inhalers by health care professionals: a systematic review. J Allergy Clin Immunol Pract. 2018;6(3):987-995. doi:10.1016/j.jaip.2017.12.032
7. Kocks JWH, Chrystyn H, van der Palen J, et al. Systematic review of association between critical errors in inhalation and health outcomes in asthma and COPD. NPJ Prim Care Respir Med. 2018;28(1):43. Published 2018 Nov 16. doi:10.1038/s41533-018-0110-x
8. Mahdavi H, Esmaily H. Impact of educational intervention by community pharmacists on asthma clinical outcomes, quality of life and medication adherence: A systematic review and meta-analysis. J Clin Pharm Ther. 2021;46(5):1254-1262. doi:10.1111/jcpt.13419
9. Atrovent HFA [package insert]. Ridgefield, CT: Boehringer Ingelheim Pharmaceuticals, Inc.;2020
10. Alvesco [package insert]. Zug, Switzerland: Covis Pharma; 2020.
11. Flovent Diskus [package insert]. Research Triangle Park, NC: GlaxoSmithKline; 2022.
12. Asmanex Twisthaler [package insert]. Jersey City, NJ: Organon & Co.; 2021.
13. Blake K, Lang J. Chapter 43:Asthma. In: DiPiro JT, Yee GC, Posey L, Haines ST, Nolin TD, Ellingrod V. eds. Pharmacotherapy: A Pathophysiologic Approach, 11e. McGraw Hill; 2020:32-38. Accessed July 6, 2022. https://accesspharmacy.mhmedical.com/content.aspx?bookid=2577§ionid=228901475
14. Myrdal PB, Sheth P, Stein S. Advances in metered dose inhaler technology: formulation development. AAPS PharmSciTech. 2014;15(2):434-455
15. Albuterol. Lexi-Drugs. Lexicomp Online. Lexicomp; 2020. Updated August 6, 2022. Accessed August 16, 2022. https://online.lexi.com.
16. Levalbuterol. Lexi-Drugs. Lexicomp Online. Lexicomp; 2020. Updated July 6, 2022. Accessed August 16, 2022. https://online.lexi.com.
17. Flovent HFA [package insert]. Research Triangle Park, NC: GlaxoSmithKline; 2021.
18. Asmanex HFA [package insert]. Jersey City, NJ: Organon & Co.; 2021
19. Advair HFA [package insert]. Research Triangle Park, NC: GlaxoSmithKline; 2021.
20. Symbicort [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2017
21. Budesonide and Formoterol. Lexi-Drugs. Lexicomp Online. Lexicomp; 2020. Updated August 6, 2022. Accessed August 16, 2022. https://online.lexi.com.
22. Dulera [package insert]. Jersey City, NJ: Organon & Co.; 2021.
23. Bevespi Aerophere [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2019.
24. Breztri Aerophere [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2021.
25. Hess D, Dhand R. The use of inhaler devices in adults. In: Post TW, ed. UpToDate. UpToDate; 2022. Last Updated September 29, 2020. Accessed July 6, 2022. https://www.uptodate.com/contents/the-use-of-inhaler-devices-in-adults
26.Rodríguez-Martínez CE, Sossa-Briceño MP, Sinha IP. Commercial valved spacers versus home-made spacers for delivering bronchodilator therapy in pediatric acute asthma: a cost-effectiveness analysis. J Asthma. 2021;58(10):1340-1347. doi:10.1080/02770903.2020.1784195
27. Teva Respiratory LLC. About QVAR RediHaler® (beclomethasone dipropionate HFA Maintenance Inhaler). Updated February 2022. Accessed July 6, 2022. https://hcp.qvar.com/about-qvar-redihaler/
28. Combivent Respimat [package insert]. Ridgefield, CT: Boehringer Ingelheim Pharmaceuticals, Inc.; 2021.
29. Spiriva Respimat [package insert]. Ridgefield, CT: Boehringer Ingelheim Pharmaceuticals, Inc; 2021.
30. Striverdi Respimat [package insert]. Ridgefield, CT: Boehringer Ingelheim Pharmaceuticals, Inc; 2021.
31. Stiolto Respimat [package insert]. Ridgefield, CT: Boehringer Ingelheim Pharmaceuticals, Inc.; 2021.
32. Azouz W, Chrystyn H. Clarifying the dilemmas about inhalation techniques for dry powder inhalers: integrating science with clinical practice. Prim Care Respir J. 2012;21(2):208-213. doi:10.4104/pcrj.2012.00010
33. Serevent Diskus [package insert]. Research Triangle Park, NC: GlaxoSmithKline; 2022.
34. Pulmicort Flexhaler [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2019.
35. ArmonAir Digihaler [package insert]. Parsippany, NJ: Teva Pharmaceuticals USA; 2020.
36. Arnuity Ellipta [package insert]. Research Triangle Park, NC: GlaxoSmithKline; 2018.
37. Advair Diskus [package insert]. Research Triangle Park, NC: GlaxoSmithKline; 2020.
38. Wixela Inhub [package insert]. Morgantown, WV: Mylan Pharmaceuticals Inc.; 2021.
39. AirDuo RespiClick [package insert]. Parsippany, NJ: Teva Pharmaceuticals USA, Inc.; 2021.
40. AirDuo Digihaler [package insert]. Parsippany, NJ: Teva Pharmaceutical USA, Inc.; 2021.
41. Breo Ellipta [package insert]. Research Triangle Park: GlaxoSmithKline; 2019.
42. Tudorza Pressair [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2019.
43. Spiriva Handihaler [package insert]. Ridgefield, CT: Boehringer Ingelheim Pharmaceuticals, Inc.; 2021.
44. Incruse Ellipta [package insert]. Research Triangle Park, NC: GlaxoSmithKline; 2019.
45. Anoro Ellipta [package insert]. Research Triangle Park, NC: GlaxoSmithKline; 2020.
46. Trelegy Ellipta [package insert]. Research Triangle Park, NC: GlaxoSmithKline; 2020.
47. Kaplan A, Price D. Matching inhaler devices with patients: the role of the primary care physician. Can Respir J. 2018;2018:9473051. Published 2018 May 23. doi:10.1155/2018/9473051
48. Price D, Keininger DL, Viswanad B, et al. Factors associated with appropriate inhaler use in patients with COPD - lessons from the REAL survey [published correction appears in Int J Chron Obstruct Pulmon Dis. 2018 Jul 25;13:2253-2254]. Int J Chron Obstruct Pulmon Dis. 2018;13:695-702. Published 2018 Feb 26. doi:10.2147/COPD.S149404
49. Kher S, Landau H, Hon SM, et al. Inhaler use and education characteristics among English and non-English speaking patients: A pilot needs assessment survey. Patient Educ Couns. 2019;102(5):932-936. doi:10.1016/j.pec.2018.12.016
50. Usmani OS, Lavorini F, Marshall J, et al. Critical inhaler errors in asthma and COPD: a systematic review of impact on health outcomes. Respir Res. 2018;19(1):10. Published 2018 Jan 16. doi:10.1186/s12931-017-0710-y
51. Nguyen TS, Nguyen TLH, Van Pham TT, et al. Pharmacists' training to improve inhaler technique of patients with COPD in Vietnam. Int J Chron Obstruct Pulmon Dis. 2018;13:1863-1872. Published 2018 Jun 11. doi:10.2147/COPD.S163826
52. Axtell S, Haines S, Fairclough J. Effectiveness of various methods of teaching proper inhaler technique. J Pharm Pract. 2017;30(2):195-201. doi:10.1177/0897190016628961
53. Cogan P, Sucher B. Appropriate use of pressurized metered-dose inhalers for asthma. US Pharm. 2015;40(7):36-41. Accessed August 16, 2022. https://www.uspharmacist.com/article/appropriate-use-of-pressurized-metereddose-inhalers-for-asthma
54. Qvar Redihaler [package insert]. Parsippany, NJ: Teva Pharmacceuticals USA, Inc.; 2021.
55. Haughney J, Price D, Barnes NC, et al. Choosing inhaler devices for people with asthma: current knowledge and outstanding research needs. Respir Med. 2010;104(9):1237-1245. doi:10.1016/j.rmed.2010.04.012
56. Choosing an inhaler device to suit the individual. National Asthma Council Australian Asthma Handbook. Accessed July 6, 2022. https://www.asthmahandbook.org.au/management/devices/device-choice
57. Gardenhire DS, Burnett D, Strickland S, Myers TR. A guide to aerosol delivery devices for respiratory therapists, 4th edition. American Association for Respiratory Care. 2017. Accessed July 6, 2022. https://www.aarc.org/wp-content/uploads/2018/03/aersol-guides-for-rts.pdf
58. Petite SE, Hess MW, Wachtel H. The role of the pharmacist in inhaler selection and education in chronic obstructive pulmonary disease. J Pharm Technol. 2021;37(2):95-106. doi:10.1177/8755122520937649
59. Price D, Chrystyn H, Kaplan A, et al. Effectiveness of same versus mixed asthma inhaler devices: a retrospective observational study in primary care. Allergy Asthma Immunol Res. 2012;4(4):184-191. doi:10.4168/aair.2012.4.4.184
60. Dekhuijzen PN, Lavorini F, Usmani OS. Patients' perspectives and preferences in the choice of inhalers: the case for Respimat or HandiHaler. Patient Prefer Adherence. 2016;10:1561-1572. Published 2016 Aug 18. doi:10.2147/PPA.S82857
61. Chrystyn H, van der Palen J, Sharma R, et al. Device errors in asthma and COPD: systematic literature review and meta-analysis. NPJ Prim Care Respir Med. 2017;27(1):22. Published 2017 Apr 3. doi:10.1038/s41533-017-0016-z
62. Navaie M, Dembek C, Cho-Reyes S, et al. Device use errors with soft mist inhalers: A global systematic literature review and meta-analysis. Chron Respir Dis. 2020;17:1479973119901234. doi:10.1177/1479973119901234
63. Price DB, Román-Rodríguez M, McQueen RB, et al. Inhaler errors in the CRITIKAL study: Type, frequency, and association with asthma outcomes. J Allergy Clin Immunol Pract. 2017;5(4):1071-1081.e9. doi:10.1016/j.jaip.2017.01.004
64. Weller T. Placebo inhaler devices and infection risks. Nursing Times.2005;101(42):50. Accessed August 16, 2022. https://www.nursingtimes.net/archive/placebo-inhaler-devices-and-infection-risks-18-10-2005/
65. Institute for Safe Medication Practices (ISMP). Correct use of inhalers: help patients breathe easier. July 14, 2016. Accessed July 6, 2022. https://www.ismp.org/resources/correct-use-inhalers-help-patients-breathe-easier

Screening, Brief Intervention and Referral to Treatment (SBIRT): An effective approach to identify persons at risk for substance use disorders

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

· Discuss the prevalence and consequences of SUDs

· Describe the components of SBIRT

· Recognize motivational interviewing skills to promote readiness to change

· Discuss harm reduction and how it pertains to SUDs

· Describe barriers associated with the use of SBIRT in the community setting

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

· Discuss the prevalence and consequences of SUDs

· Describe the components of SBIRT

· Discuss harm reduction and how it pertains to SUDs

· Describe barriers associated with the use of SBIRT in the community setting

Hazardous use of alcohol and or opioids can result in harm. If not treated, this hazardous use could develop into a Substance Use Disorder (SUD). SUDs are associated with poor health related outcomes and increased healthcare costs. Screening, brief intervention and referral to treatment (SBIRT), is a public health approach to identify persons with at-risk behaviors and minimize the development of SUDs. The premise behind SBIRT is to promote early intervention with at-risk users and minimize harm. The screening process determines the severity and risk level of a person’s substance use and risk of misuse. Based on the results, healthcare professionals can perform a brief intervention and or a referral to treatment. Healthcare professionals such as pharmacists and pharmacy technicians can use SBIRT to identify and intervene on behalf of persons that are at risk of an SUD. Healthcare providers can perform SBIRT in many healthcare settings including community pharmacies, hospitals, and primary care offices.

Introduction

Substance Use Disorders (SUDs), continue to be a major concern in the United States. In 2017, nearly 20 million people reported an SUD because of alcohol or illicit drug use.¹ Costs associated with substance abuse are approximately $249 billion dollars for alcohol and $193 billion dollars for illicit drugs.^2-4

Alcohol use is second to nicotine for substance use among all substances misused.¹ In 2017, 140 million persons aged 12 and older reported alcohol use. A total of 16.7 million reported heavy alcohol use of five or more days over a 30-day timespan. Heavy alcohol use is defined as drinking four or more drinks on one occasion for females and five or more drinks in males. Heavy alcohol use can result in several health-related concerns, to include cirrhosis, depression, cancer, neuropathy, and pancreatitis to name a few.⁵

Typically, clinicians often treat people who have SUDs after they have developed the condition.^6,7 Other approaches include inpatient or outpatient treatment programs for those with SUDs and prevention programs to educate and inform the public of the dangers associated with substance use.

An alternative approach to these methods is to identify persons with at-risk behaviors for substance misuse and provide interventions to reduce long-term use and harm. This approach is called SBIRT. SBIRT stands for Screening, Brief Intervention, and Referral to Treatment.⁷ This evidence-based approach addresses harmful behaviors BEFORE they escalate to a full-blown SUD.

Who can perform SBIRT?

Many healthcare professionals can perform SBIRT, including doctors, nurses, pharmacists, pharmacy technicians, and behavioral health specialists. SBIRT is also adaptable to a team-based approach. Pharmacists and pharmacy technicians are in a particularly good position to perform SBIRT, as they are accessible, especially in community pharmacy settings.⁸ SBIRT can also be applied in several clinical settings, such as hospitals and ambulatory care clinics.

SBIRT’s first step involves the screening process. Using a universal screening approach is an important point of the screening process. A universal approach means screening everyone, regardless of who they are, or how they look or act. This makes sense because clinicians cannot determine if someone is using alcohol or other substances based on appearance and behavior. Pharmacists and pharmacy technicians can screen patients in any pharmacy setting to include community, hospital, and ambulatory care. In busy community settings, a targeted approach may be necessary. With targeted approaches, pharmacy teams might screen individuals who are on opioids, benzodiazepines, and other medications that have the potential for abuse. Ideally, however, the universal approach is better. If we focus only on certain populations, we may target individuals who don’t have an SUD and overlook someone who has an SUD but takes no prescription medications. The initial screening question is simple: a single yes/no question that determines if further screening is necessary.

PAUSE AND PONDER: When and where would you use SBIRT in your pharmacy practice?

How to Perform SBIRT in a Community Pharmacy Setting

Many pharmacy team members think that they cannot or should not perform SBIRT in their settings. With pharmacy teams expanding their responsibilities, it’s entirely possible to add SBIRT to the community pharmacy tool kit.

Community pharmacy teams need to note that they do not need to perform SBIRT in its entirety. In some cases, pharmacists and technicians may only perform the screening and then refer the patient to a provider for treatment. Pharmacists can perform a brief intervention if opioid misuse is a concern. For example, the pharmacist may access the prescription drug-monitoring program and recognize the patient is seeing multiple providers and using several pharmacies to fill opioid prescriptions. In this case, the pharmacist can perform a screening and brief intervention with the patient to discuss safe opioid use and possible referral to treatment.

Roberta is a 27-year-old female who presents to the pharmacy with a prescription for oxycodone. The pharmacy technician enters the prescription information and notices that Roberta picked up a 30-day supply two weeks ago. The technician informs the pharmacist about the early refill. The pharmacist refers to the prescription drug-monitoring program and notices that Roberta filled two other opioid prescriptions from different doctors at two different pharmacies. The pharmacist screens Roberta and provides a brief intervention.

Pharmacists can refer a patient to treatment or provide information on treatment centers based on the discussion. For example, while engaging with the patient the pharmacist may recognize that the patient is purchasing needles/syringes for illicit drug use. This is a perfect opportunity for the pharmacist to provide a referral to treatment.

When screening for alcohol and drugs, healthcare providers use pre-screening questions developed by the National Institute of Alcohol Abuse and Alcoholism for alcohol and the National Institute of Drug Abuse for drugs. Pre-screening questions determine whether additional screenings are necessary.

For alcohol the pre-screening question is, “Do you sometimes drink beer, wine, or other alcoholic beverages?” If the individual answers no, no further screening is necessary. If the individual answers in the affirmative or screens positive for alcohol, the screener would perform additional screening based on the Alcohol Use Disorders Identification Test (AUDIT) to evaluate alcohol use further.⁹

The same holds true for pre-screening for drug use. If an individual answers in the affirmative to the pre-screening question, “How many times in the past year have you used an illegal drug or a prescription medication for nonmedical reasons?” then the screener would use the Drug Abuse Screening Test (DAST-10) questionnaire to evaluate drug use further.¹⁰ (See Figure 1)

Figure 1. DAST-10 Questionnaire¹⁰

Let’s start with the AUDIT questionnaire. This 10-question screening tool addresses recent alcohol use, dependence symptoms, and harmful behaviors. (See Figure 2) Once the screening is complete, the scoring will determine next steps.

Figure 2. AUDIT Questionnaire⁹

Some key points to consider when using the AUDIT are the recommended drinking limits and size of the beverage. Did you know that the serving size of a glass of wine is five ounces, and that one bottle of wine typically contains five glasses? A serving of beer is 12 ounces, and a serving of spirits (hard liquor) is one and one-half ounces. The screener should explain serving sizes to the patient to ensure an accurate account of alcohol consumption and score of the AUDIT.

Recommended drinking limits for men are two drinks/day and no more than 14 drinks/week and for women one drink/day and no more than seven drinks/week. For those 65 or older, the recommended limits are similar to women: one drink/day and no more than seven drinks/week.¹¹ Consuming more than the recommended limits can result in binge drinking which is associated with greater harm and dependence. Binge drinking is five or more drinks for men or four or more drinks for women, and people who are 65 or older.¹²

The AUDIT score determines the severity and next steps that may include a brief intervention or referral to treatment. Individuals scoring between 0 and 7 are low risk and individuals scoring 20 or greater are considered dependent use and would benefit from a referral to treatment.

Pharmacy teams who are familiar with other screening methods may recall that a positive binge drinking finding would require an intervention using those methods. Using the AUDIT, binge drinking alone may not require an intervention. The intervention or referral to treatment would depend on the overall score of the AUDIT.

Scoring the AUDIT

Dependent Use (20+)

Harmful Use (16‒19)

At-Risk Use (8‒15)

Low Risk (0‒7)

The screening process for drugs is like that used for alcohol. The DAST-10 questionnaire assesses drug use in the past 12 months. (See Figure 1) Interpretation of the results determines the suggested action. Figure 3 describes screening results and suggested intervention. For example, a score of between 3 and 5 using the DAST-10 suggests harmful use and moderate degree of problems related to drug use.

Scoring the DAST-10

High Risk (6+)

Harmful Use (3‒5)

Hazardous Use (1‒2)

Abstainers (0)

Once the screener completes the screening, the score determines next steps for the patient. Next steps could include feedback, brief intervention, and or a referral to treatment. (See Figure 3.) For example, in persons with a low risk, feedback can include discussing the results of screening and risk of harm. A brief intervention is recommended in persons with risky or harmful behavior based on screening results.

Perform a screening for alcohol and drug use using a patient case

Joe is a 32-year-old man who hurt his back three years ago in a car accident. He has used opioids since the accident, but he still complains of pain. He supplements his medications by purchasing additional opioids online and on the street. Joe also has a history of alcohol use. He consumes three to four beers on most days. His family is concerned with his alcohol and drug use and recommends he seek help.

Below are his responses to the AUDIT and DAST-10 questionnaires. Based on his responses to the questions calculate his risk level for alcohol and drug use. See Tables 1 and 2.

Table 1. AUDIT Screening for Joe

Question	Answer	Score
How often do you have a drink containing alcohol?	Daily	4
How many drinks containing alcohol do you have on a typical day when you are drinking?	4	1
How often do you have six or more drinks on one occasion?	Once in awhile	1
How often during the last year have you found that you were not able to stop drinking once you had started?	Never	0
How often during the last year have you failed to do what was normally expected of you because of drinking?	Monthly	2
How often during the last year have you needed a first drink in the morning to get yourself going after a heavy drinking session?	Never	0
How often during the last year have you had a feeling of guilt or remorse after drinking?	Never	0
How often during the last year have you been unable to remember what happened the night before because of your drinking?	Never	0
Have you or someone else been injured because of your drinking?	No	0
Has a relative, friend, doctor, or other health care worker been concerned about your drinking or suggested you cut down?	Yes	4
Total Score		12

Based on Joe’s responses to the AUDIT what is his score and risk level?

Based on his responses to the questions Joe scored 12 on the AUDIT, which puts him as at-risk-use.

Table 2. DAST-10 Screening for Joe

Question	Answer	Score
Have you used drugs other than those required for medical reasons?	Yes	1
Do you abuse more than one drug at a time?	No	0
Are you unable to stop using drugs when you want to?	Yes– The pain gets too great	1
Have you ever had blackouts or flashbacks as a result of drug use?	No	0
Do you ever feel bad or guilty about your drug use?	No	0
Does your spouse (or parents) ever complain about your involvement with drugs?	Yes	1
Have you neglected your family because of your use of drugs?	No	0
Have you engaged in illegal activities in order to obtain drugs?	Yes	1
Have you ever experienced withdrawal symptoms (felt sick) when you stopped taking drugs?	Yes	1
Have you had medical problems as a result of your drug use (e.g., memory loss, hepatitis, convulsions, bleeding)?	No	0
Total Score		5

Based on Joe’s responses to the DAST-10 what is his score and risk level?

Based on his responses to the questions Joe scored a five, which indicates harmful use. We will come back to Joe and determine next steps for him.

Summary of screening

Screening is an important first step to determine the severity and risk level of substance use
Use a universal screening approach
Determine the level of risk and intervention based on screening results
Pharmacists and pharmacy technicians can successfully perform screenings

Brief Intervention (BI)

Following the screening process and based on the results, a BI may be necessary. A brief intervention, also referred to as a brief negotiated interview (BNI), can be performed by a healthcare professional such as a pharmacist, doctor, nurse, or behavioral specialist. Addiction experts recommend using a BNI for those with “at risk” or harmful level of risk based on screening results. During the BNI, the healthcare professional uses motivational interviewing (MI) to have a conversation with the patient and evoke the patient’s personal motivation for change.¹³Before we talk more about BNIs, let’s talk about the five stages of change.¹⁴ Change happens gradually, and individuals can move through the different stages depending on the situation and can move in and out of the different stages. In pre-contemplation, individuals may not be ready to make a change. Figure 4 depicts the five stages of change.

Figure 4. Stages of Change¹⁴

MI has several components, which can be overwhelming and confusing. Here is a brief outline of the components.

Components of MI

Key qualities of MI
Basic Principles of MI
BNI Process
OARS Framework

What is a brief intervention’s purpose and how do we use MI to evoke change? Motivational interviewing is an evidence-based approach to changing behaviors.^13,15

Key qualities of MI include¹³

Facilitate communication between the healthcare professional and patient, where information and guidance is given
Empower individuals to change based on what’s important to them
Respect patient’s autonomy to facilitate change

Healthcare professionals can use MI to engage the patient as an equal partner. Although the name motivational interviewing suggests the healthcare professional is motivating the patient, that isn’t the case. MI is not a way to change individuals, make demands of patient, or instruct them what to do or not do. MI is a way to help examine situations and options for patients. MI is not easy to learn and takes practice. Pharmacists may find MI difficult to apply because counseling and instructing patients is part of everyday practice. MI is different and recognizes that patients are responsible for their actions and taking action to make changes.

MI can be very useful when people

Have mixed feelings or are ambivalent about change
Have low confidence about making changes
May be uncertain about whether they want to make changes, creating low desire
Are not clear about the benefits of change and concerns related to the current situation, so do not deem change important

MI is based on four basic principles^15,16:

Express empathy
Develop discrepancy
Roll with resistance
Support self-efficacy

Expressing empathy is an important first step of the MI process. You do this by seeking to understand how the person feels without judgement. (See Side Bar-tips to express empathy)

Side Bar: Tips to Express Empathy

Maintain eye contact but avoid staring
Use reflective listening to hear and understand and repeat back the information
Avoid sympathy, “I’m sorry this happened to you”
Ask clarifying questions
Avoid passing judgement

Developing discrepancy

Using this principle, the provider discusses the discrepancy between the patient’s values and behavior. This involves discussing the good and the bad related to the behavior. Most patients are aware of the dangers related to substance misuse but are ambivalent about making a change. Discrepancy between the patient’s goals and current behavior motivates change.

Roll with resistance

During the BNI, patients may become defensive when talking about their substance use. This resistance is often because of a fear to change. To decrease resistance, the healthcare professional can redirect the discussion for the patient to understand the harm associated with the behavior. Last, the provider can explore the pros and cons of the patient’s behaviors. For example, a patient may enjoy the euphoria of heroin use (pro) but conversely contracts a cellulitis infection (con).

Support self-efficacy

This guiding principle focuses on supporting patient goals. Patients may feel that they cannot meet goals or expectations. It is important that the provider believe in the patient and promote confidence to support change.

Here is an example of a brief intervention.

Cynthia is at the pharmacy having a discussion with the pharmacist. She is concerned about her alcohol use. The pharmacy technician performs the AUDIT screening and provides the results to the pharmacist for discussion. AUDIT Score: 15 “At-risk use”

Cynthia: “I have been drinking more often over the last few months.”

Pharmacist: “Tell me more about that, Cynthia.” (Reflective listening)

Cynthia: “Work has been very stressful, and alcohol helps me relax. I used to drink only socially on the weekends with friends but now I drink almost every day. My teenage daughter sees me drink every night and she tells me I should stop because it’s not good for me. I don’t want to be a bad role model for her.”

Pharmacist: “So you are saying that you drink alcohol almost every day so that you can cope with the stress at work?” (Reflective listening)

Cynthia: “Yes. I am using alcohol to cope with stress at work.”

As you can see by the conversation above, the pharmacist reflects on Cynthia’s concerns regarding stress and work, which cause her to drink alcohol to cope. The pharmacist makes no judgement on whether the behavior is bad or that she should stop drinking. The pharmacist applies reflective listening and expresses empathy.

Developing discrepancy looks at current behaviors versus future goals. Let’s continue the conversation with Cynthia and apply this principle.

Pharmacist: “It sounds like you are having a hard time at work. But you also love your daughter and want to be a good role model for her. Is that right?” (Developing discrepancy)

Here the pharmacist emphasizes Cynthia’s concerns with her alcohol use and how that affects her daughter. This is the discrepancy. This allows Cynthia to recognize the pros and cons of her alcohol use so that she may change her behavior.

In roll with resistance, patients may pushback stating that they don’t have a problem, or their drinking or drug use is not a problem. In this case, it may require further discussion of current behavior and negative effects related to that behavior. The correlation of cause and effect can motivate the patient to change.

Last, support self-efficacy, where patients are responsible for deciding on actions they will make to support change. This is important because patients take the responsibility of making changes.

Regardless of the stage, MI encourages the patient to express the desire to change or what is referred to as “change talk.” In change talk, look at the following: desire, ability, reasons and need or acronym DARN. See the example below based on the conversation with Cynthia earlier.

Desire: “I need to drink less alcohol.”

Ability: “I could find healthier ways of coping with the stress at work, like yoga or meditation.”

Reasons: “I want my daughter to be proud of me.”

Need: “I might lose my daughter.”

This “change talk” can prepare the individual to make changes and act on those changes. As mentioned earlier, MI is a collaborative approach between the patient and healthcare professional providing the brief negotiated interview and involves four fundamental processes. Let’s talk about each of the processes.

Engage
Focus
Evoke
Plan

Engage

Having an honest and open conversation that engages the patient is the first step in the process. Listening without passing judgement or trying to fix the problem is important. The OARS framework includes interactive techniques to engage the patient. OARS stands for open questions, affirmations, reflections, and summaries. Table 3 describes each element of the framework and purpose.

Table 3. OARS framework¹⁵

Interview Skill	Description	Purpose
Open-ended questions	Ask the patient open-ended question vs. yes or no	Builds trust Gathers information
Affirmations	Show empathy for the patient Acknowledge the patient’s ability to make a change in their life Emphasize key points that are important to the patient.	Discuss/encourage patient’s abilities and healthy behaviors Build the patient’s confidence and self-efficacy
Reflections	Listen and understand what the patient is saying and repeating back to the patient	Repeat back what was said Incorporate unspoken feelings thoughts or behaviors
Summaries	Review key points of the conversation Use reflective listening	Help the patient see the big picture Create an action plan Emphasize key points of the conversation

Focus

During the conversation, focus on guiding patients to identify behaviors they struggle with or ambivalent to make a change. During the conversation, understand the patient’s dilemma or ambivalence. Asking what is important to them can help to identify the target and behavior that may inhibit them from reaching their goals.

Evoke

During the evoke process, we want patients to discuss their reasons for change and incorporate “change talk” during the conversation. Let’s go back to the conversation with Cynthia. Cynthia recognizes that she drinks alcohol to cope with the stress at work. She is also concerned that her drinking upsets her daughter and Cynthia wants to be a good role model. Her reason for change is that she wants to be a good role model for her daughter. Changing her behavior for her daughter is important to her.

Plan

The patient would commit to a plan of action that is simple, realistic, specific, and attainable. The patient should also set a timeline for the plan.

The incorporation of core skills is fundamental to MI. The acronym OARS, involves four interviewing skills to enhance motivation for change.¹⁵

Asking open-ended questions allows patients to provide more information and can provide insight to their feelings and thoughts. Close-ended questions only elicit a yes or no response with no further details. Here is an example of an open-ended versus close-ended question.

Close-ended question: Do you drink alcohol often?
Open-ended question: How much alcohol do you drink per week?

Affirmations

Statements of affirmation acknowledge the patient’s ability to make a change. Statements by the provider emphasize key points most important to the patient and support the patient to make changes.

Reflections

Reflections involve listening and understanding what the patient is saying. This can be as simple as repeating back the patient’s statements and incorporating the patient’s unspoken feelings or intent. Furthermore, reflections confirm with the patient that what you are repeating back is accurate. An example might be saying, “I heard you say that you have tried to stop drinking in the past and you have not been able to do it and I sense you are frustrated. Is that correct?” The latter statement incorporates the patient’s unspoken feelings and confirms an accurate account of the reflection.

PAUSE AND PONDER: Along the substance use continuum, with whom would you negotiate a reduction in use to lower risk levels?

Performing a BNI

A BNI uses MI to raise awareness in patients with risky or harmful substance use. Here are four important steps to follow when conducting a BNI.

Build rapport-raise the subject

Open the conversation by beginning with a general conversation and ask permission to discuss the topic of substance use. For example, you could say: “Thank you for meeting with me today. Would you mind speaking with me? Could I ask you some questions about your substance use?”

This engages the patient in the conversation. The conversation could highlight the patient’s substance use and explore the pros and cons of the situation. For example, with Cynthia, her alcohol use allows her to cope with stress at work. Conversely, her alcohol use makes her daughter upset and she wants to be a good role model for her. During the BNI, the provider should use open-ended questions to allow the patient to provide more information and further explore the patient’s substance use. Incorporating reflective listening, summarizing what the patient says, and weighing the pros and cons allows for decisional balance.

Provide feedback

After listening to the patient ask permission again to offer feedback based on the conversation. Review the screening results with the patient and connect consequences to substance use. Here is an example.

Karla is a 32-year-old mother of three children. She and her children are in the emergency department because of a car accident. Karla’s alcohol level is 0.09. (Blood alcohol levels ≥ 0.08% = legally impaired)

You perform a screening on Karla using the AUDIT. Her score reveals harmful use and when asked about her alcohol use causing injury, she states in the affirmative that she was under the influence of alcohol while driving with her children and feels extremely guilty and upset. During the conversation you ask permission to speak to Karla about her alcohol use and how this may be a direct cause of the accident. Karla may recognize the impact of her alcohol use and change her behavior.

Build readiness to change

Here we ask if they may be willing to make some changes. When doing so we can ask how willing they are or how ready they are to make a change. The provider can use a visual tool to assess willingness to change. This visual tool is a readiness ruler. (See Figure 5.) When approaching the patient, clinicians can use the readiness ruler in a way similar to that of a pain scale. For example, “On scale of 1 to 10, where 1 means you are not at all ready to change to 10 meaning you are very or completely ready to change. How ready are you to make a change about your substance use?”

Figure 5. Readiness Ruler¹⁵

PAUSE AND PONDER: What would be your response to a patient that states they are a 3 on the readiness ruler?

Negotiate a plan for change

Based on the screening results, the plan can vary. It may involve reducing risky use of substances and or a referral to treatment. The plan should be simple, realistic, specific, and attainable. Following up with patients to discuss changes and reinforcing the plan for change will promote long-term success.

Referral to Treatment

Patients diagnosed with an SUD by a provider or who have behaviors that are substance dependent (e.g., substance related injuries or inability to stop) or high-risk, such as increased frequency of substance use, require treatment. Healthcare professionals can easily refer the patient to treatment. Initiating the referral process by calling a trained treatment specialist on behalf of the patient to schedule an appointment can better assist the patient. Many resources are available to find treatment centers for patients. SAMHSA’s National Treatment Facility Locator is a helpful resource to locate a treatment center:¹⁷ http://findtreatment.samhsa.gov. Treatment options include counseling, medication assisted treatment, complimentary wellness, and support groups. The level of care is individualized and based on the severity of the substance use and comorbidities.

Key points for referral to treatment

Make a plan with the patient
Use a warm handoff
Decide how you will communicate with the provider
Confirm the plan with the patient

A warm handoff involves personally introducing the patient to the treatment provider. This helps build rapport and trust and increases the patient’s willingness to schedule an appointment. Warm handoffs are also more successful than passive referrals.

SBIRT in Practice

Healthcare professionals can utilize SBIRT in many areas of practice. Pharmacists and pharmacy technicians are one of the most accessible healthcare professionals, especially in community pharmacy settings. In this setting, pharmacists and pharmacy technicians can meet with patients to perform screenings, conduct a BNI, or refer to treatment, with the ultimate goal of reducing the risk of an SUD and patient harm.

Harm reduction is key to help to minimize adverse effects related to substance use.¹⁸ Harm reduction involves policies, programs, and practices that focus on the individual’s human rights. The goal of harm reduction is to keep people safe. Providers can reinforce positive changes in patients using MI. Examples of harm reduction include drug take back programs, access to naloxone, and syringe distribution.¹⁸ Distributing clean needles/syringes not only reduces harm for the persons using them but also contributes to community safety by reducing the spread of HIV, hepatitis, and other blood borne diseases.

Sadly, in community pharmacy settings, several barriers exist. Some include lack of privacy, lack of staffing, lack of time, and stigmas.^{19, 20}A stigma is an inaccurate belief against individuals based on a specific characteristic, race, or nation of people.^22,23 Often, we see this in patients with a mental illness. Stigma towards individuals with SUDs also exist and are one of the most challenging barriers because of a misconception that an SUD is not a disease or medical condition and individuals with an SUD are at fault.²³ You may hear people say, “They don’t want to get better” or “I don’t want those kinds of people in my pharmacy.” Stigmas can impede care and harm the patient.

It is important to recognize that an SUD is a medical condition and requires treatment. Stigmatizing language like “addict” or “junkie” has a negative connotation and can lead to barriers in care. Avoid using stigmatizing language. For example, an addiction is an SUD. Clinicians need to replace the words “addict” or “junkie” with the words “person with an SUD.” This recognizes the disease and not the person with the SUD.

Patient case Joe and brief intervention.

AUDIT score: 12-At risk use

DAST-10 score: 5-Harmful use

What recommendations are appropriate based on the screening results?

Joe’s alcohol screening score of 12 shows that he is at risk use and his DAST-10 score of 5 shows that his use of drugs is harmful. In Joe’s case, he would benefit from a brief intervention and referral to treatment.

A brief intervention would be helpful for Joe. Here is an example of an intervention between Joe and the pharmacist at the ambulatory care clinic.

Pharmacist: “Good morning, Joe. Would it be OK if I speak with you for a few minutes about your screening results that you took earlier?”

Joe: “I guess that would okay.”

Pharmacist: “Based on your screening results, your alcohol use puts you at risk for harm and your drug use is possibly already harmful for your health and for those around you.”

Joe: “I don’t know what you are talking about. I don’t have a problem.”

Pharmacist: “Let me ask you this. From your perspective what is your relationship with alcohol and drugs?”

Joe: “Well I guess I do drink every day and I am on oxycodone for the pain. I was in an accident a few years ago and the pain won’t go away. I need the oxy. My family thinks I need help.”

Pharmacist: “Thank you for opening up to me and telling me how you feel after your accident and that you’re still in pain. Tell me some of the things that are good about your alcohol and drug use and some things that are not good?”

Joe: “Well alcohol helps me forget about my problems for little bit. The drugs help my pain, but I feel guilty sometimes because I buy it off the street because my doctor won’t give me enough.”

Pharmacist: “What is it about your drug use that makes you feel guilty?”

Joe: “My family means a lot to me, and I am afraid that my wife might leave me and take the kids.”

Pharmacist: “It sounds like you love your family. What changes do you think you could make about your alcohol and drug use?”

Joe: “Well I guess I could cut back on my drinking and find some other ways to deal with my stress. I rely too much on the oxy so I don’t think I could cut back on that right now.”

Pharmacist: “That’s great that you are willing to cut back on your alcohol use. Tell me what that would look like?”

Joe: “I think I could limit myself to three beers a day instead of four or five. I can start there and see how it goes.”

Pharmacist: “That’s a great start. On a scale of 1-10 where 1 means that you are not at all ready to make this change and 10 meaning that you are completely ready where do you think you would put yourself on this scale?”

Joe: “I guess I would rate myself as being a 7.”

Pharmacist: “Joe, that’s great. A 7 is very close to being completely ready to make this change. Can I ask you what is holding you back from you being at a 10?

Joe: “I don’t think that I am completely ready to make a change. I am also afraid of failing.”

Pharmacist: That is a valid fear. Speaking with someone about your alcohol use and treatment can really help. Would you be willing to meet Dr. Smith here at the office and set up an appointment with him?”

Joe: “Sure. I could meet him now while I am at the clinic.”

The pharmacist walks Joe down the hall to meet Dr. Smith who is a behavioral specialist focusing on SUDs. The pharmacist performs a warm handoff, introducing Joe to Dr. Smith.

The pharmacist engaged Joe in the conversation and reflected on what Joe said and felt. During the conversation, the pharmacist asked open-ended questions to gain more insight into Joe’s alcohol and drug use and discussed his readiness to make a change. Joe rated himself as a 7 on the readiness scale. Discussing where they are on the readiness ruler can determine patients’ willingness to change, possible resistance, and potential fears. Joe recognized the pros and cons of his alcohol and drug use and made a plan to decrease his alcohol use and meet with a behavioral specialist about his drug use.

Conclusion

SBIRT is a public health approach to intervene with individuals at risk of an SUD. SBIRT is effective in reducing alcohol use by 40% and illicit drug use by 76%.²⁴ Applying universal screening and promoting change to reduce high-risk behavior before it escalates to an SUD can greatly reduce patient harm and minimize healthcare costs.

Depending on the setting, time constraints, day-to-day workload, and staffing, SBIRT may be a challenge to perform. Pharmacists and pharmacy technicians should be knowledgeable about SBIRT and treat persons with SUDs, where feasible, in a professional, caring manner. SBIRT can be a useful approach to identify those with at risk behaviors and apply early intervention methods to minimize harm and development of an SUD.

SBIRT Exam Questions
Pharmacist
After completing this continuing education activity, pharmacists will be able to
1. Discuss the prevalence and consequences of SUDs
2. Describe the components of SBIRT
3. Recognize motivational interviewing skills to promote readiness to change
4. Discuss harm reduction and how it pertains to SUDs
5. Describe barriers associated with the use of SBIRT in the community setting

1. SBIRT is a public health approach to identify persons at risk of a substance use disorder. For the acronym SBIRT, what does BI stand for?
A. Brief Interaction
B. Brief Intervention
C. Brief Intermediation

2. In the U.S., which of the following substances is most abused?
A. Nicotine
B. Alcohol
C. Oxycodone

3. Which of the following is used to screen for alcohol use?
A. AUDIT
B. DAST
C. ADST

4. Jim, a 42-year-old man, completed the alcohol screening questionnaire and scored 17. How would you rate his alcohol use?
A. At-risk use
B. Harmful use
C. Dependent use

Use patient case Sean for questions 5-7.
Sean is 42-year-old male who presents to the emergency department after a car accident. He scores 14 on the AUDIT questionnaire and the pharmacist performs a BNI. He has not worked since COVID and drinks to forget about his problems. The pharmacist discusses Sean’s drinking habits and related harm. Sean is defensive and states that he does not have a drinking problem.

5. Which of the following is an appropriate response to Sean’s statement, that he does not have a drinking problem?
A. “It seems to me you have a drinking problem. That’s how you ended up in the hospital.”
B. “You need to stop drinking or this will happen again. I’ve seen it time and time again.”
C. “Can we talk more about how you ended up in the emergency department today?”

6. The pharmacist reflects on Sean’s statements. Which is one of the following is example of reflective listening?
A. “Let’s create an action plan to decrease your alcohol use so you can have some goals to accomplish.”
B. “ I know that you don’t want to be here today, but can you see how important it is?”
C. “Thank you for sharing how you feel about losing your job. That must be hard for you.”

7. The pharmacist wants more information about Sean’s motivation to change behavior. Which of the following promotes the BEST response?
A. “Are you willing to cut back on your alcohol use?”
B. “What are some negative effects of your alcohol use?”
C. “Do you think your alcohol use contributed to the car accident?”
8. Fill in the blank. Harm reduction involves policies, programs, and practices to focus on the individual’s ________ ________.
A. Substance Use
B. Harmful Behaviors
C. Human Rights

9. Which of the following is an example of non-stigmatizing language?
A. He has a substance use disorder
B. He is addicted to drugs
C. He is heroin junkie

10. Which of the following is a barrier to providing SBIRT in a community pharmacy setting?
A. Cost of screening
B. Safety
C. Stigmas

Pharmacy Technician Post-test
After completing this continuing education activity, pharmacist technicians will be able to
1. Discuss the prevalence and consequences of SUDs
2. Describe the components of SBIRT
3. Discuss harm reduction and how it pertains to SUDs
4. Describe barriers associated with the use of SBIRT in the community setting

2. In the U.S., which of the following substances is most abused?
A. Nicotine
B. Alcohol
C. Oxycodone

3. Which of the following is used to screen for alcohol use?
A. AUDIT
B. DAST
C. ADST

4. Which of the following is an example of non-stigmatizing language?
A. He has a substance use disorder
B. He is addicted to drugs
C. He wants to be a junkie

5. Which of the following is associated with the distribution of clean needles/syringes?
A. Reduction of blood borne diseases
B. Increase in illicit drug use
C. Increase in drug overdoses

6. What are the recommended alcohol drinking limits for men who are younger than 65 years?
A. No more than 1 drink per day and no more than 7 drinks per week
B. No more than 2 drinks per day and no more 14 drinks per week
C. No more than 4 drinks per day and no more than 14 drinks per week

7. Which of the following is used to screen for drug use?
A. AUDIT
B. DAST
C. ADST

8. What is the goal of harm reduction?
A. Keeping people safe
B. Stopping drug use
C. Giving people free needles

9. Which of the following is a barrier to providing care to those with a SUD in a community pharmacy setting?
A. Cost of screening
B. Safety
C. Stigmas

10. SBIRT is effective in reducing alcohol use by___ %
A. 40%
B. 76%
C. 20%

References

1. Substance abuse and mental health services administration. 2017 NSDUH annual national report. Accessed June 9, 2021. Available at https://www.samhsa.gov/data/report/2017-nsduh-annual-national-report
2. Centers for Disease Control and Prevention. Excessive Drinking is Draining the U.S. Economy. Updated December 2019. Accessed June 21, 2021. https://www.cdc.gov/features/costsofdrinking/
3. National Drug Intelligence Center. National Drug Threat Assessment. Washington, DC: United States Department of Justice; 2011. Accessed June 21, 2021. www.justice.gov/archive/ndic/pubs44/44849/44849p.pdf
4. Birnbaum HG, White AG, Schiller M, Waldman T, Cleveland JM, Roland CL. Societal Costs of Prescription Opioid Abuse, Dependence, and Misuse in the United States. Pain Medicine. 2011; 12:657-667.
5. Rehm J, Room R, Graham K, et al. The relationship of average volume of alcohol consumption and patterns of drinking to burden of disease: An overview. Addiction. 2003; b;98(9):1209–1228.
6. Institute of Medicine (IOM). Broadening the base of treatment for alcohol problems. Washington, DC: National Academies Press; 1990.
7. Babor TF, McRee BG, Kassebaum PA, Grimaldi PL, Ahmed K, Bray J. Screening, Brief Intervention, and Referral to Treatment (SBIRT). Subst Abuse. 2007;28(3):7–30.
8. Shonesy BC, Williams D, Simmons D, Dorval E, Gitlow S, Gustin RM. Screening, Brief Intervention, and Referral to Treatment (SBIRT) in a retail pharmacy setting: The pharmacist’s role in identifying and addressing risk of substance use disorder. J Addict Med. 2019; 13(5):403-407.
9. WHO screening and AUDIT. Accessed June 9, 2021. http://www.who.int/substance_abuse/activities/sbi/en/
10. Smith PC, Schmidt SM, Allensworth-Davies D eta. A single-question screening test for drug use in primary care. Arch Intern Med. 2010; 170(13):1155−1160.
11. Centers for Disease Control and Prevention. Alcohol use and your health. Accessed June 9, 2021. Available at: http://www.cdc.gov/alcohol/fact-sheets/alcohol-use.htm
12. National Institute of Alcohol Abuse and Alcoholism (NIAAA) for alcohol. Accessed June 9, 2021. Available at https://www.rethinkingdrinking.niaaa.nih.gov/how-much-is-too-much/is-your-drinking-pattern-risky/Drinking-Levels.aspx.
13. Miller WR, Moyers TB. Motivational Interviewing and the clinical science of Carl Rogers. J Consult Clin Psychol. 2017; 85(8):757-766. doi: 10.1037/ccp0000179.
14. Prochaska JO, Velicer WF, Rossi JS, et al. Stages of change and decisional balance for 12 problem behaviors. Health Psychol. 1994;13:39–46.
15. Miller WR, Rollnick S. Motivational Interviewing: Helping people to change (3rd Edition). Guilford Press; 2013.
16. Miller WR, Zweben A, DiClemente CC, Rychtarik RG. Motivational enhancement therapy manual: A clinical research guide for therapists treating individuals with alcohol abuse and dependence. Rockville, MD: National Institute on Alcohol Abuse and Alcoholism. Accessed June 9, 2021. Available at https://www.motivationalinterviewing.org/sites/default/files/MATCH.pdf
17. Substance Abuse and Mental Health Services Administration. Behavioral health treatment services. Accessed August 2, 2021. Available at https://findtreatment.samhsa.gov/
18. Harm reduction international. Accessed July 7, 2021. Available at https://www.hri.global/what-is-harm-reduction.
19. Hawk KF, Vaca FE, D'Onofrio G. Reducing fatal opioid overdose: Prevention, treatment and harm reduction strategies. Yale J of Biol and Med 2015;88(3):235–245.
20. Werremeyer A, Mosher S, Eukel H, et al. Pharmacists’ stigma toward patients engaged in opioid misuse: When “social distance” does not mean disease prevention. [published online ahead of print, 2021 March 22]. Subst Abuse. 2021;Mar 22; 1-8. doi: 10.1080/08897077.2021.1900988
21. Murphy A, Phelan H, Haslam S, Martin-Misener R, Kutcher SP, Gardner DM. Community pharmacists’ experiences in mental illness and addictions care: a qualitative study. Subst Abuse Treat, Prev, and Policy. 2016; 11:6 DOI 10.1186/s13011-016-0050-
22. Caddell J, Gans S. Verywellmind. What is stigma? Accessed August 5, 2021. Available at https://www.verywellmind.com/mental-illness-and-stigma-2337677
23. Fernandez L. Addiction or Substance Use Disorder? How Using the Right Language Helps Fight Stigma. Accessed August 12, 2021. Available at https://illuminaterecovery.com/blog/substance-use-disorder-stigma/
24. Aldridge A, Linford R, Bray J. Substance use outcomes of patients served by a large US implementation of Screening, Brief Intervention and Referral to Treatment (SBIRT). Addiction. 2017; Feb; 112 (Suppl. 2), 43–53 doi: 10.1111/add.13651.

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