The upcoming USP changes and its impact on immediate use medications

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.

The United States Pharmacopeia (USP) recently published updated guidelines on sterile compounding that become effective on November 1, 2023. These guidelines affect not only sterile medications compounded in pharmacy clean rooms, but also injectable medications that may be compounded in healthcare institutions, medical and surgical treatment sites, infusion facilities, pharmacies, and physician and veterinarian practice sites. This affects personnel such as chiropractors, dentists, naturopaths, nurses, pharmacists, pharmacy technicians, physicians, veterinarians, and any other medical professional who compounds sterile products. The USP made these changes to minimize harm, including death, to human and animal patients. By reviewing these updates, and by making changes, medical professionals will be able to comply with state and federal regulations and prevent harm to their patients.

INTRODUCTION

In 1905, a person in excruciating pain in a dentist’s office would have been thrilled to receive an injection of procaine (Novocain) delivered in a reusable glass hypodermic syringe. Besides the dentist’s white coat, it’s likely nothing else used in the procedure was clean or remotely sterile. Today, given what we know about sterile products, an educated patient would have turned and run in the opposite direction.

Yet, according to the U.S. Food and Drug Administration (FDA), the number of trendy med spas and intravenous (IV) hydration clinics, some mobile, that treat patients with medications such as injectable vitamin infusions, have exploded. Many operate under the FDA’s radar. The FDA may not be aware of which compounders are making such drugs, and some states may have insufficient resources to adequately oversee them. The FDA has recently documented varying offenses from personnel wearing street clothing and not wearing gloves while preparing injections to using toaster ovens for sterilization.²

Human drug compounding is a practice in which ingredients are combined, mixed, or altered to create a medication tailored to an individual patient’s medical needs. The Federal Food, Drug and Cosmetic Act (FD&C Act) governs human compounding. Section 503A describes the conditions under which compounded human drug products are exempt from its regulations²:

Section 505 concerning approval prior to marketing
Section 501(a)(2)(B) concerning current good manufacturing practice (CGMP) requirements
Section 502(f)(1) concerning labeling with adequate directions for use

The FDA act exempts one condition—compounds are exempt when a licensed pharmacist or physician prepares the medication in a licensed facility based on a valid patient specific prescription. An explosion of naturopathic clinics, which often use unapproved nutritional, herbal, and homeopathic products and administer them by injection, have become a growing concern for the FDA. A brief Internet search revealed that nurses run many clinics with a physician consulting offsite. The FDA has become increasingly aware of drug products compounded at medical offices and clinics that may be prepared under unsanitary conditions. The FDA has also become aware of business models, such as IV hydration clinics, medical spas, and mobile IV infusion services, that are compounding drugs that may not meet the conditions of the FD&C Act’s section 503A or comply with state regulations.²

Unsanitary conditions are more common than one would think. The FDA cites a recent example (February 2021) wherein a 50-year-old patient was hospitalized and treated for suspected septic shock with multi-organ failure after receiving an IV vitamin infusion in her home.² The patient’s blood cultures grew Pseudomonas fluorescens, which is a gram-negative bacterium of emerging concern.³ A California medical clinic that specialized in services including IV therapies and vitamin injectables, sexual health products, hormone replacement therapy, weight loss/management products, and diagnostic laboratory assays prepared and dispensed the contaminated bag.²Whenstate and federal agents inspected the facility, they observed several deficiencies²:

Lack of an International Organization for Standardization (ISO) air quality classification of ISO-5; in other words, a clean room which is certified to contain a particle count of less than 3,520 particles per cubic meter in the air, required for sterile compounding
Contamination in compounding areas including peeling paint, stained work surfaces, visibly dirty equipment, and air vents with dust and grime
Difficult-to-clean equipment and surfaces (e.g., carpeting in the IV storage and mixing room)
Standing water in a refrigerated storage area used to store sterile vials
Use of expired active pharmaceutical ingredients to prepare drug products intended to be sterile

The full extent of this nationwide problem is unknown since many practitioners operating in medical offices or clinics do not register with the FDA. The FDA encourages all patients who experience adverse effects to report them to the FDA MedWatch Adverse Event Reporting program (www.fda.gov/medwatch/report.htm).²

Defining Immediate Use Medication

According to the proposed USP<797> Pharmaceutical Compounding-Sterile Preparations, sterile compounding is defined as combining, admixing, diluting, pooling, reconstituting, repackaging, or otherwise altering a drug product or bulk drug substance to create a sterile preparation. Compounding personnel must follow aseptic techniques, processes, and procedures for preparing any sterile medication.¹

Within a hospital setting, urgent situations may arise where compounding cannot occur in a USP<797> compliant area. Often, acute care situations require STAT (meaning with no delay; at once) doses for critical patients, or medication for an unanticipated procedure.⁴ Compounders do not necessarily need to comply with all requirements detailed in USP<797> to make these immediate use medications. These frequently asked questions can help clarify when an immediate use medication may be needed and who can compound it.^1,4

Can nurses mix compounded sterile preparations (CSPs) for immediate use? Any qualified health professional can prepare an immediate use preparation as long as (1) it is within their scope of practice, (2) the facility’s policies allow it, and (3) the designated person (defined and discussed below) has documented the health care professional’s competency.
Is docking a vial onto a proprietary bag system considered an immediate use medication? Yes and no. Docking a vial onto a proprietary bag for future activation and use is considered compounding and must be performed in an ISO class 5 environment. However, docking a vial onto a proprietary bag according to manufacturer's instructions for immediate administration to a single patient is considered an immediate use medication and is not considered compounding.
Can a nurse prepare an immunoglobulin (IGG) solution in a home care setting, by reconstituting the powder vial with the sterile water supplied by the manufacturer in a kit? This is an example of preparation that is compliant with FDA-approved labeling. Preparing a sterile product in accordance with the manufacturer's approved labeling is not considered compounding as long as
- the product is prepared as a single dose for a single patient
- the approved labeling includes the following information: the diluent, the final strength, the container closure system, and storage time
If a nurse reconstitutes an antibiotic vial and adds it to a piggyback bag, is this considered immediate use? If the pharmacy is open, this should be done in a sterile clean room. If it is a STAT dose or the pharmacy is closed, then this could be considered immediate use. The nurse mixing the medication needs to have documented competency and the compound should not involve more than three products. One vial of drug, one vial of diluent, and one piggyback bag are three products, which is allowed.

In 2020, the American Society of Health Systems Pharmacists conducted a study among professionals who compounded outside of the pharmacy setting. Of the 444 respondents, 77% were nurses, and the rest were primarily anesthesia providers and decentralized pharmacists. Eighty-one percent performed compounding in a acute care settings; other locations included ambulatory surgery centers, infusion centers, physicians’ practices, and long-term care.⁵

The most frequently prepared items were⁵

IV pushes drawn directly from vials into syringes. (i.e., antibiotics, antiemetics, opioids, proton pump inhibitors)
Intermittent infusions, all of which were proprietary vial and bag systems.
Intramuscular injections including vaccines, antipsychotics, and antibiotics

Personnel and Settings Affected by USP<797>

All personnel who prepare CSPs are required to comply with USP<797> guidelines. This includes but is not limited to chiropractors, dentists, naturopaths, nurses, pharmacists, technicians, physicians, and veterinarians.¹

All sites including but not limited to hospitals, infusion facilities, medical and surgical patient treatment sites, pharmacies, physician or veterinarian sites, and other healthcare institutions must meet at least the minimum requirements in USP<797>.¹

The compounding facility must designate one or more individuals to be responsible and accountable for the facility’s performance, operation, and personnel in the preparation of CSPs and for performing other functions described in USP<797>.¹The facility’s standard operating procedures (SOPs) must identify the person deemed “the designated person.” All designated persons now have immense jobs; failure to meet the USP’s expectations comes with considerable consequences.

The Designated Person

The USP mentions the designated person more than 50 times in section <797> alone and several other chapters also refer to the designated person. Below is a list of some, but not all tasks required of a designated person, which will become effective on November 1, 2023. Many states, such as Connecticut and Texas, have already embraced the designated person. The designated person or persons must be identified in the facilities SOPs and registered with the state. In Texas and Connecticut, pharmacists must also complete 30 hours of sterile compounding training to become a designated person. Duties include¹

Overseeing a training program to ensure competency of personnel involved in compounding, handling, and preparing CNSPs
Selecting components
Monitoring and observing compounding activities and taking immediate corrective action if deficient practices are observed
Ensuring that SOPs are fully implemented. The designated person(s) must ensure that follow-up is carried out if problems, deviations, or errors are identified
Establishing, monitoring, and documenting procedures for the handling and storage of CNSPs and/or components of CNSPs.

The SIDEBAR discusses an issue of emerging importance.

SIDEBAR: Who Inspects Physicians’ Offices?⁶

In 2016, the Pew Charitable Trust conducted a study and asked boards of pharmacy in all 50 states and the District of Columbia to respond to several compounding questions. Of the 51 states, 43 responded to the questionnaire. Although the survey consisted of pages of questions, three of them were forward thinking.

Does your state have a mechanism to track which in-state physicians’ offices or clinics perform sterile compounding? The answer: 2 % yes, 74% no, 24% don’t know.
Does the state require physicians’ offices or clinics to be held to the same quality standards as pharmacies? The answer: 17% yes, 38% no, 45% don’t know.
How do states provide oversight of physician’s offices or clinics that perform sterile compounding to ensure compliance with applicable standards? The answer: 7 by the state board of medicine, 1 by the board of pharmacy (way to go, IDAHO!), 24 reported no oversight system to ensure compliance and 11 states chose not to respond to this question.

Who knew Idaho would be so revolutionary? Keep in mind that this study took place in 2016, four years after the New England Compounding mishap of 2012. The Pew study reported, “The Drug Quality and Security Act of 2013, among other reforms, added a new category of compounders called outsourcing facilities that can compound supplies of drugs without obtaining prescriptions.”

The new category—outsourcing facilities—was intended to reduce the number of medications made in offices. However, it is obvious that state policies are not uniform. Some states are still working to advance change, and others have yet to act. The Pew report concluded that we are still in a state of transition and that “The variations in sterile compounding policy across states suggest that an opportunity exists to review state oversight systems for potential weaknesses, and consequently to advance regulatory practices to better protect patients.”

Gap Analysis

In some states, as in the state of Connecticut, the designated person must be a pharmacist. That means that the designated person or persons are responsible for the oversight of all compounding within an institution including the operating room, emergency room, clinics, and nursing station medication rooms.

PAUSE AND PONDER: In what areas of your facility could people possibly be compounding without your designated person’s knowledge?

A gap analysis compares the current situation with a future state. Creating a gap analysis could help identify areas where compounding is done without the designated person’s knowledge. A gap analysis is performed in three steps⁷:

Identify objectives and goals. Most designated persons will create a sheet with three columns: current state, future state, and actions. They will need to identify who, what, where and when immediate use compounding occurs. Using a team approach and including nurses and physicians is a good place to start.
Analyze the current state. Gather data. One critical area to examine is medications in short supply or backordered. (Aren’t there always a few of these lately!?!) Checking purchasing records and delivery slips to see where medications are being used can be eye-opening. Facilities that substitute vials because the premixed bag is backordered will find that this is a target area.
Determine how to bridge the gap. Collaborating with the team to create policies and procedures for compounding and writing them into standard operating procedures is critical. Facilities should create a designated compounding area in each unit and establish a cleaning routine. They should also create a training document for nurses and other professionals who compound and set date that each person should complete training as a goal.

Immediate Use Gap Analysis

All facilities that compound need to compare the current (2008) USP<797> Pharmaceutical Compounding-Sterile Preparations guidelines with the proposed (2022) USP<797> guidelines. In short, the proposed changes are few in number but may cause significant impact throughout the facility.⁸Table 1 compares a few minor changes.

Table 1. Less Strict Changes to USP<797> ^1,8,9

Subject	Current	Proposed
Compounding Process and number of components	Only low risk level NMT 3 sterile packages	NMT 3 sterile products
Situation	Emergency use or immediate administration	No emergency stipulation
Number of manipulations	NMT 2 entries into any container/bag	Not defined
Maximum BUD	1 Hour	4 hours
Aseptic technique	Aseptic technique is followed	Aseptic technique, processes, and procedures followed per written SOPs
Risk Level	Medium and high risk not prepared as immediate use	Category 1, 2, and 3 requirements do not apply
Hazardous Drugs	Only non-hazardous drugs may be used	Must follow USP<800>

^{BUD = beyond use date; NMT = Not More Than}

A quick glance at the table shows that compounders can now assign a beyond use date (BUD) of four hours for immediate use products. Hurray! This prompts the question, “Is that all I need to implement, and can I do it right now?” Not so fast! These are changes to existing subjects within <797> guidelines, but the proposed guidelines also include many new stipulations, so let’s dig deeper. The following requirements have now been added which pertain to immediate use medications^1,8:

Written SOPs must be in place and compounding personnel must follow aseptic technique, processes, and procedures.
Personnel must be trained and demonstrate competency according to the facility SOPs.
SOPs must include methods to minimize contamination and decrease mix-up errors.
The product must be compounded in accordance with evidence-based information for physical and chemical compatibility, per labeling or stability studies.
Any unused starting component from a single use container must be discarded.
Single dose containers must not be used for more than one patient.
A compounding record is required when preparing immediate use medications for more than one patient.

Training and Evaluation

Training is the elephant in the room. Many nurses and other health professionals have mixed or prepared single use medications for ages, so it might be difficult to teach an old dog new tricks. Demonstration of competency can be difficult and perhaps this is where the nursing team can shine. Luckily, immediate use compounders need not perform fingertip and thumb sampling, or media fill tests as is required for sterile clean room staff.

All personnel who compound must now be initially trained and qualified by demonstrating their knowledge and competency of sterile compounding before they can perform their job independently. The designated person(s) is responsible for creating and implementing a training program but may assign training to other qualified personnel. The training procedure for immediate use CSPs must be written into the facilities SOPs.¹One interesting note, the proposed USP<797> states that personnel who are compounding in a clean room, or who have direct oversight of those personnel, must complete training initially, and at least every 12 months. However, immediate use compounders only need to complete training as required by the facilities SOPs.¹A best practice would be to evaluate yearly.

Skills may vary from one location to another, but at a minimum, healthcare professionals who will perform immediate use compounding must demonstrate the following core skills⁸:

Hand hygiene and proper gloving
Calculations, measuring and mixing
Aseptic technique and compounding procedures

Required skills will depend on the clinic’s location; for example, an oncology clinic will need to follow USP<800> Standards for Hazardous Drugs, along with USP<797>. Other skills may include cleaning, garbing, documentation, and labeling and should align with the immediate use procedures in the facilities SOPs.

Competency assessment must be based on the aseptic processes that are related to the tasks being performed, which can be difficult to recreate. Demonstration of a simulated manipulation may be acceptable in most cases. A simulated aseptic manipulation using empty vials, syringes, sterile water, or saline could consist of the three maximum products allowed, with no need to incubate the sample.⁷Using a convenient checklist, like the one in Table 2, helps trainers evaluate staff and document consistently.

The SIDEBAR highlights one practice that needs to end immediately.

Normal Saline Flush Prefilled Syringes^7,10

The Institute for Safe Medical Practices (ISMP) released the results of a 2018 immediate use compounding survey. Of the 977 practitioners who responded to the survey, almost all were nurses. ISMP discovered that 81% of the respondents used premixed 5 mL and 10 mL normal saline flushes to dilute medications.The FDA considers a premixed normal saline flush as a medical device and they are “not approved for dilution and administration of IV push medications.”

Some clever (but forbidden) uses of prefilled syringes include

Using prefilled syringes as vials: withdrawing and or adding part of a prefilled syringe into another prefilled syringe for administration (Example: adding 5 mL from one syringe to another 5 mL syringe to make a 10 mL syringe).
Using a prefilled syringe to reconstitute a powder vial, then drawing the dose back into the same syringe. (Example, using a 10 mL flush, adding 5 mL from the flush, reconstituting, and withdrawing the 5 mL back into the syringe to create a 10 mL dose.)

Using prefilled syringes in these ways is dangerous, since most of the time the health care professional conducting these “procedures” fail to relabel these syringes, so the syringes still have a bright yellow or white label and can be easily picked up by another person and administered in error.

Why would prefilled flushes be used for compounding? First, among the many recent drug shortages, normal saline topped the list for a very long time. Second, they are quick and easy to use, and third, healthcare professionals cling to many misconceptions. Some professionals believe that a syringe does not need to be labeled. There is also a myth that a 10 mL syringe must be used to administer IV push medications.Perhaps it is due to “telephone tag” teaching, where one procedure is passed from one to another.

So, how do we fix this? Clear procedures need to be established for compounding each medication. Staff training is a must, and a simple roll of blank labels in the compounding area can go a long way to avoiding errors.

Table 2. Sample Immediate Use Compounding Evaluation

	Name of person assessed: *Jonathan the Husky Dog*	Location: Husky Clinic
	Evaluation of Handwashing, Garbing, Gloving and Aseptic technique: In left-hand boxes, indicate for each activity _P = acceptable completion of the described activity in the correct order, X = the order is incorrect or the activity is performed incorrectly or N/O = the activity was not observed.	Notes/ Comments on any of the activities.
	Removes all jewelry and outer garments
	Uses nail pick under running water
	Washes hands with soap and water for 30 seconds
	Dries hands with approved wipe
	Dons required garb
	Applies alcohol-based hand sanitizer, allows to air dry
	Selects the correct pair of gloves
	Correctly dons sterile gloves
	Applies sterile alcohol to gloves, allows to air dry
	Disinfects compounding area with facility approved agent
	Selects proper components
	Disinfects critical sites with 70% alcohol wipe
	Punctures vial at a 45-degree angle to avoid coring
	Withdraws the correct amount of fluid from vial
	Disposes waste in proper container
	Visually inspects final product
	Demonstrates proper labeling
	Applies correct 4-hour BUD
	Name of evaluator________________________Date:_____	Pass / Fail

CONCLUSION

Whether you are the designated pharmacist or just a team member, it is important for you to recognize immediate use medications and locations where they may be compounded. With the implementation of USP<797> commencing on November 1, 2023, now is the time to look at the pharmacy clean room and all areas in your facility where compounding may be occurring. Huge changes in workflow as well and policies and procedures may need to be adopted. Create a well-balanced team of professionals and get to work!

The Upcoming USP<797> Changes: Impact on Immediate Use Medications
Post-test Pharmacists and Technicians
After completing this continuing education activity, pharmacists and pharmacy technicians will be able to:
1. Point out an immediate use medication
2. Recognize locations where immediate use medications may be compounded
3. Investigate the designated person’s responsibilities
4. Identify core competencies required for immediate use compounding

1. Jerry is the designated person for a large health system. He is preparing to implement the new USP<797> changes. Today, he is making a list of potential immediate use situations. Which of the following situations should he add to his list?
a. A technician docking ten vials onto proprietary bags
b. A pharmacist reconstituting TPA in the emergency department
c. An anesthesiologist using a premade fentanyl syringe

2. Abdul and Allyssa are having coffee at break. Abdul says that he receives e-mail notifications from the FDA’s automated system. Alyssa asks, “have they reported anything interesting lately about compounding?” What does Abdul report?
a. The FDA has seen an uptick in community-based clinics compounding under unsanitary conditions
b. The MedWatch Adverse Event Reporting reports more errors caused by choosing the wrong syringe
c. The FDA indicates that they are having trouble tracking problems when patients pay cash for infusions

3. A veterinarian works in a veterinary practice that employs a certified veterinary technician and has taken all necessary steps to be USP<797> compliant. She needs to prepare and administer an injection of an analgesic immediately for a dog that was hit by a car. Can she do this?
a. Yes, because veterinary medications do not need to comply with USP <797>
b. Yes, if the certified veterinary technician prepares the dose in the medication room
c. Yes, because the practice has taken steps to comply completely with USP<797>

4. Clara applies for a job as a “designated person” at a naturopathic clinic. The person interviewing indicates that the facility’s staff seems to prepare immediate use medications in many different (and USP<797> noncompliant) ways. She asks Clara how she would solve this problem. What is the BEST answer?
a. Training all staff personally and documenting the training in the facility’s SOPs
b. Purchasing medications from a wholesaler that is licensed by the federal government
c. Establishing, monitoring, and documenting procedures for CSP handling and storage

5. It’s October 31, 2023, at 10:22 PM and Andy needs to prepare an immediate use medication that will probably be given in the emergency department shortly after midnight. The facility’s SOPs are compliant with the revised USP<797> chapter that becomes effective on November 1, 2023. He determines that he can prepare the medication now for its administration after midnight. What do you think?
a. Since the USP <797> is not effective until tomorrow, the facility needs to use the maximum BUD allowed in the previous version (2 hours)
b. Since the facility is already USP <797> compliant and its SOPs have been updated, 4 hours is the maximum BUD
c. Andy needs to wait until midnight and prepare the immediate use medication closer to the time it will be administered.

6. Sally’s supervisor is checking her competencies as required by the USP<797>. She asks, “Which of the following represents an appropriate situation that would be considered an immediate use medication?”
a. Using a premixed normal saline syringe for reconstituting vial contents
b. Completing a compounding record for more than one patient
c. Using a single dose vial for two patients within four hours

7. Maria considers herself a responsible healthcare professional. She hasn’t needed to prepare an immediate use medication in several months, but today, she needs to compound an antibiotic on site. What should she do before compounding this medication?
a. Ensure the designated pharmacist has evaluated the facility’s training procedures
b. Complete a standard USP form that is a declaration that she knows how to compound.
c. Schedule a media fill test and thumb and fingertip test using an agar plate

8. What information is the designated person responsible for updating in the SOPs?
a. Training and competency procedures
b. Names of personnel who have been trained
c. The cost of training to the hospital

9. When must immediate use compounders have their training completed?
a. Initially and then annually
b. Initially and every 6 months
c. As required by the facilities SOPs

10. Which core competencies apply to immediate use compounding?
a. Hand hygiene and sterile filtration
b. Hand hygiene, measuring and mixing
c. Measuring, mixing and principles of high-efficiency filters

9. When must immediate use compounders have their training completed?
a. Initially and then annually
b. Initially and every 6 months
c. As required by the facilities SOPs

References

REFERENCES:
1. United States Pharmacopeia (USP). General Chapter, <797> Pharmaceutical Compounding—Sterile Preparations. (2023) USP-NF. Rockville, MD: United States Pharmacopeia. Accessed June 19, 2023.
2. FDA highlights concerns with compounding of drug products by medical offices and clinics under insanitary conditions. Oct. 25,2021. https://www.fda.gov/drugs/human-drug-compounding/fda-highlights-concerns-compounding-drug-products-medical-offices-and-clinics-under-insanitary
3. Scales BS, Dickson RP, LiPuma JJ, Huffnagle GB. Microbiology, genomics, and clinical significance of the Pseudomonas fluorescens species complex, an unappreciated colonizer of humans. Clin Microbiol Rev. 2014 Oct;27(4):927-48. doi: 10.1128/CMR.00044-14. PMID: 25278578; PMCID: PMC4187640.
4. ASHP, The sterile compounding answer book. Chapter 8, Immediate use and preparation for administration. page 33-34
5. Pedersen CA, Schneider PJ, Ganio MC, Scheckelhoff DJ. ASHP National survey of pharmacy practice in hospital settings: Dispensing and administration- 2020. Am J Health Syst Pharm. 2021;78(12):1074–93.
6. National Assessment of State Oversight of Sterile Drug Compounding. The Pew Charitable Trust. February 2016. Accessed August 7, 2023. https://www.pewtrusts.org/~/media/assets/2016/02/national_assessment_of_state_oversight_of_sterile_drug_compounding.pdf
7. Mind Tools, Gap Analysis. Accessed Jun18,2023. https://www.mindtools.com/afv9hac/gap-analysis

8. Pharmacy Purchasing & Products Magazine, USP <797> Immediate-Use CSPs: Small Changes, Big Impact. Feb.2023 Vol.20 No.2, page 10. Kevin N. Hansen, PharmD, MS, BCPS, BCSCP Amanda M. Choi, PharmD, MBA Annie Lambert, PharmD, BCSCP February 2023 - Vol.20 No. 2

9. United States Pharmacopeia (USP). General Chapter, <797> Pharmaceutical Compounding—Sterile Preparations. (2008) USP-NF. Rockville, MD: United States Pharmacopeia. Accessed June 20, 2023.

10. Institute of Safe Medical Practices. Part II Survey results suggest action is needed to improve safety with adult IV push medications. Dec. 2018, Vol.16, Issue 12. Accessed June 22, 2023.https://www.ismp.org/sites/default/files/attachments/201812/NurseAdviseERR201812.pdf

Prepping Pharmacist Preceptors on the Pharmacists’ Patient Care Process (PPCP)

Preceptors often work with students to review patient cases in an organized way. Experts developed the Pharmacists’ Patient Care Process (PPCP) in 2014 to provide a template that is consistent and concise, but also comprehensive. Using this process, students and licensed pharmacists develop SOAP notes to document the subjective and objective data they need to complete an assessment, and ultimately make a plan. PPCP stresses an important point: follow-up is critical and a well-written SOAP note can be extremely helpful in the follow-up process. This continuing education activity uses a case study to demonstrate how the PPCP process should work and emphasize areas where preceptors can provide tangential learning. It includes PRO TIPS for preceptors when they supervise students who are attempting to complete PPCP. It highlights the most common errors and suggest ways that preceptors can work with students to improve their experiential education.

INTRODUCTION: A PATIENT CASE

JM, an 8-year-old white male presents to your clinic. It’s a pediatric care clinic located in an area where many financially challenged families live. After talking with his parents, you learn he was recently diagnosed with central precocious puberty (CPP). His endocrinologist recommends initiating therapy and would like to know what treatment you recommend. His parents also have questions.

Your spry pharmacy student jumps at the opportunity to write a SOAP note using the “PPCP.” To you, PPCP sounds like an illegal drug that was abused in the 1980s. She explains that the Pharmacists’ Patient Care Process (PPCP) is a standardized model for collaborative medication management. She clarifies what it entails and how to apply the process in a clinical setting.

PPCP’s Importance

Schools of pharmacy have taught the PPCP for the past few years. Preceptors who are unfamiliar with the process may find it helpful to review the PPCP as many students will take this approach when addressing clinical problems in the workplace.

PPCP: THE DETAILS

Teamwork in healthcare has achieved major goals for many patients (although we have room for improvement): accessible, affordable, and high-quality care. In addition to the many healthcare team members, pharmacists are critical contributors to care plans. Medication expertise equips pharmacists with the knowledge to reduce drug adverse events, prevent medication errors, and provide invaluable input for decision-making.¹

In 2014, the Joint Commission of Pharmacy Practitioners (JCPP) developed a standardized process for medication management that could be used across interdisciplinary teams and dubbed it PPCP. JCPP’s members developed the approach using principles of evidence-based practice. The five steps—collect, assess, plan, implement, and follow-up—are tied together with careful communication and documentation.²Pharmacists can remember the steps as the pneumonic “CAP-IF.”

SOAP Notes

The subjective, objective, assessment, and plan (SOAP) note provides a method of documentation for the collect, assess, and plan steps of the PPCP. SOAP notes are probably familiar to most preceptors, as clinicians have used them for roughly 50 years.³ Table 1 highlights the key components of SOAP notes.

Table 1. Components of a SOAP Note¹

Objective Information	Subjective Information
· Current medication list (prescription and nonprescription) · Medical history · Physical assessments (i.e., blood pressure, heart rate, weight, height, respiratory rate, etc.) · Laboratory results	· Chief complaint · Symptoms · Patient lifestyle habits, preferences, and beliefs · Patient goals for care · Socioeconomic factors
Assessment
· Problem: statement highlighting the chief complaint or main medication-related problem · Rationale: the reasoning for the intervention cited from guidelines and supporting evidence from the collected information · Goals of care: possible barriers to adherence, socioeconomic considerations, and desired outcome of intervention
Plan
· Specific recommendation or intervention based on practice guidelines (i.e., initiation of drug therapy, referral to another provider, or non-pharmacologic lifestyle modifications) · Plan for upcoming sessions, specific monitoring parameters, and progress indicators

Collect

Thorough collection of the right information supplies pharmacists with tools to make safe, effective decisions. A combination of objective and subjective information paints a more complete picture of a patient’s clinical status. If possible, pharmacists should obtain and verify their information across multiple sources. Past medical records, active medication lists, and laboratory results are great places to start.

When soliciting subjective information, pharmacists should use open-ended questions. Prompting patients with questions formatted to avoid “yes” or “no” answers allow providers to obtain more information in less time, prioritize chief complaints better, and minimize implicit assumptions.⁴

Back to the Case

Your head is spinning trying to sort all the “P’s” in PPCP, CPP, and JCPP, but your student assures you that she will start with collecting relevant clinical information. First, you and your student perform a physical assessment of JM including taking his height and weight. JM takes no medication except an occasional antihistamine, but if he took other chronic medications, this would be the time to direct your student to perform a medication reconciliation. Next, you prompt JM’s parents with open ended questions, and they recall JM’s past medical history. You should ask your student if JM needs to be involved in the discussion (see SIDEBAR). After meeting with JM and his parents, here is the relevant information your student jots down:

Subjective information

At age 5, JM frequently soaked through his underarm clothing with pungent perspiration, so since then, he uses a strong deodorant
He is starting to develop pubic and underarm hair
He has some acne on his face and upper back
JM occasionally tells his parents he feels “different” than his classmates because he is so much bigger and taller
He has no past surgeries or hospitalizations
Takes OTC multivitamins daily and loratadine for allergies in the spring

Objective Information

Height = 4’8” inches
Weight = 102 pounds
DHEA Sulfate = Tanner stage III - 60 ug/dL (N = < 28 ug/dL)
Clinical exam findings = testicle size indicates puberty
X-ray bone age hand and wrist = greater than 2 standard deviations, 156 months (expected = 108.9 months)
Luteinizing hormone (LH) = 0.4 units/L (N = < 0.3 units/L)

SIDEBAR: Pediatric Involvement in Healthcare Decisions^5,6

In pediatric cases, clinicians may choose to consult only parents when making decisions regarding their child’s medical care. However, this practice, which is rooted in legal precedence, should shift to involve affected children to some extent. The American Academy of Pediatrics advocates that adolescents actively participate in decisions based on their ability and maturity.⁵ While research is lacking on how exactly to assess a child’s aptitude to participate in decision making, some studies show that children can participate as young as age 5.⁶Regardless, it doesn’t hurt to ask children if they have questions or concerns. In the case, JM is 8 and has voiced his concern previously about his height and size. Therefore, including him in the conversation is a possibility if his parents agree.

Preceptors can and should provide tangential learning when working with special populations. Reminding students that adolescents, older adults, people who have cognitive decline or dementia, and people for whom English is a second language will need careful counseling. Pharmacists and pharmacy staff will also need to select their words carefully and accommodate these patients’ needs. Assigning students to do some research on the various needs in these populations is an excellent way to help them develop skills and a professional identity.

Upon looking at your student’s notes so far, you assure her she has done well. However, you still have some questions. You remind her that sometimes information like height and weight requires additional evaluation and ask her to calculate JM’s BMI; she finds that it’s 22.9. You ask your student, “How does JM’s height and weight compare to the expected height and weight of boys his age?” To which she replies, “Pediatric growth charts will give us a better idea!” After consulting the growth charts, she determined and documented that JM falls within the 112th percentile for both measurements.

To make learning comprehensive, you could ask the student if the only kind of precocious puberty is central in nature. This will help your student learn to differentiate among different forms of similar diagnoses.

Assessment

An assessment of comprehensive patient information helps prioritize the problems that require attention. Pharmacists should consider all information when identifying the problem, the rationale, and the goals of therapy. Some example questions pharmacists can consider include¹

Medication appropriateness

What is the indication for each medication?
What is the correct dosing?
What are the common adverse effects?
What are the possible drug interactions?

Factors that impact access to care

What cultural factors create barriers to care?
What socioeconomic factors impact the patient?
What is the patient’s level of healthcare literacy?
What goals does the patient or his parents have?
What barriers impact patient adherence?

Additional services

What preventive care measures does the patient qualify for?
Which immunizations has the patient received?
What other concerns does the patient have?

THE CASE RESUMED...

After compiling the objective and subjective information on JM, the student finds guidelines in the Journal of Clinical Endocrinology for the management of CPP.⁷ Due to JM’s symptoms and lab values showing consistencies with CPP, the guidelines recommend initiating a gonadotropin releasing hormone (GnRH) analog. Depending on JM’s and his parents' preferences, the endocrinologist can choose either an injectable (leuprolide) or long-acting implantable device (histrelin) provided the insurance covers it or the cost is manageable.

Once again, you should have some questions for your student. For example, asking the student to list the search terms and search engines she employed can shed light on her process. Another question might be, “Are these the only guidelines available?” You can show her that you used PubMed, as she did, but when you used Google Scholar, you found an excellent review article that lists five other publications. You suggest she look at them since expert recommendations can vary. She might also contact the endocrinologist and ask if he plans to follow the guidelines she identified, and if not, why not.

The endocrinologist messages back saying he agrees leuprolide and histrelin are both reasonable options to consider for first-line therapy. However, he also cites a 2019 update published on Hormone Research in Paediatrics. These guidelines recommend a third U.S. Food and Drug Administration (FDA)-approved option for the treatment of CPP, triptorelin.⁸ He says the student should consider this choice as a potential treatment for JM as well.

After reading the endocrinologist’s note, you emphasize to your student the importance of citing multiple guidelines when drafting an assessment. In this case, the FDA approved an additional treatment, triptorelin, in 2022. You walk through your student’s process of finding clinical information to identify more ways she can improve next time. Furthermore, you point out how the endocrinologist’s insight exemplifies the importance of interdisciplinary care.

Simultaneously, you and your student read through all three monographs and discuss the major differences you’d like to share with his parents. You ask the student to practice her delivery of the information, and she says, “Leuprolide is a long acting injectable administered intramuscularly (IM) or subcutaneously. Your doctor will administer the IM formulation every month, three months, or six months. “Triptorelin is similar to leuprolide, but is only available as a six month IM formulation. The other option is for your doctor to administer the subcutaneous formulation every six-months.⁹ On the other hand, histrelin comes as a long-acting 1¼ inch implant surgically placed into the upper arm every 12 to 24 months. For the first 24 hours after the surgery, JM should avoid swimming or bathing. As long as JM avoids heavy play or exercise for the first week, he will not have to worry about any further restrictions after that. The implant also requires surgical removal.”¹⁰

Now, you prompt the student to recall that JM’s parents expressed concern about what would happen if JM experienced an adverse reaction to the long-acting implantable device. They asked, “What is the procedure like?” and “If JM has a reaction to the implant, must he continue to wear it for 12 months or can the doctor remove it easily before then?”

The student does more research and says she will assure JM’s parents that this outpatient procedure lasts only 10 minutes, though the appointment may last 60 to 90 minutes. Most surgeons will just numb the area; however, children may undergo sedation if necessary. The surgeon will insert the narrow implant into a small approximately 5 mm opening made in the skin on the inner surface of the arm. With this option, JM can return to school the same day. The student plans to mention that complications don’t commonly occur, but minor discomfort and bruising may.¹¹The student plans to continue, “The implant may be removed immediately if JM presents at any time a severe allergic reaction or adverse effect. However, this is not common.”

Before you and the student document the assessment section of your SOAP note, the student indicates she will ask JM if he has questions. He shares that he “HATES needles” but is also scared of the surgery hurting.” The student plans to tell him not to worry because he won’t feel any pain during the operation. He can also choose to sleep during the surgery if he prefers.

Here, the preceptor should step in with gentle corrections about patient-appropriate language. First, most Americans have no idea what a 5 mm incision will look like. You ask her to calculate its length in inches and explain it by comparing it to something the child will recognize, like the size of small dice or a stack of 20 playing cards. Next, it’s critical to remind the student that we must never tell patients that something won’t hurt. This is a lesson students should learn during immunization training and creates an opportunity for cross training (applying this principle to other areas of pharmacy) that applies regardless of patient age. Healthcare professionals should never say, “This will not hurt a bit!” or anything similar. People have different pain thresholds making it impossible to predict whether it will hurt. Student pharmacists need to develop language they are comfortable with and use it. A good response if people ask if it will hurt is, “It may hurt or sting a little but just for a minute or two.” In this case, the preceptor suggests saying, “The doctor will numb the area.”

Finally, the preceptor may point out that “operation” can be a scary word for children. The student needs to use a word like “procedure” or find a way to avoid either of those words.

The preceptor should also point out that JM’s parents had also said they were worried about two things: (1) potential side effects and (2) the cost of care. They heard on the news that expenses associated with these medications can add up quickly. The cost of care and determining what the patient’s insurance will cover is probably foremost in the endocrinologist’s mind, too.

In terms of potential side effects, your student says that both GnRH analogs have similar side effect profiles. From the pediatric studies she read on GnRH adverse effects, she shares that signs of puberty may increase transiently with therapy before growth velocity eventually slows down. Some children experience weight gain, changes in appetite, body aches, headaches, gastrointestinal (GI) symptoms, or signs of a common cold. Parameters like physical growth and bone mass density may decrease during treatment but usually return to normal one year after treatment discontinuation.^{9, 10}

Before selecting JM’s treatment option, it’s critical to evaluate insurance coverage since it’s on the forefront of everyone’s concerns. The student needs to determine if they have insurance and what the plan covers. She starts by finding information on ballpark cost. She reports a histrelin implant costs around $40,000. If the patient requires mild sedation when the doctor inserts the implant, the cost may increase. However, in some cases, the implant may be used for up to two years. Leuprolide’s median annual cost ranges from $20,000-$40,000 depending on the formulation.¹² A single injection of triptorelin costs roughly $19,000, making the annual cost nearly $40,000 as well. Then says she will remind JM’s parents that while this may give them an idea, the cost may vary outside of that range.

Plan

Following the assessment, pharmacists work to develop a personalized patient care plan in collaboration with other healthcare professionals. The plan should reflect recommendations from the most recent evidence-based clinical practice guidelines. Pharmacists should focus on optimization of care in a safe, effective, and cost-effective manner.

Address medication-related problems and optimize medication therapy
Set specific, measurable, achievable, realistic, and timed (SMART) goals in the context of the patient’s healthcare goals and access to care
Involve patients to engage in education, empowerment, and self-management
Support non-pharmacologic interventions as appropriate

SMART Goals. When creating an action plan for patients, pharmacists should aim to set goals that are SMART.

Specific instructions provide other clinicians with accurate information about the patient.
Measurable outcomes provide clinicians the ability to evaluate the patient’s progress and whether the plan requires adjustments
Achievable and realistic goals
A timeline for the plan ensures healthcare providers routinely follow up with their patient

A PLAN FOR JM

After you document JM’s main problem, rationale, and goals for care in the assessment section, you move on to create his plan. Following careful consideration of the assessment, you and your student decide to recommend starting histrelin to treat his CPP since his insurance will cover it once the endocrinologist completes prior authorization forms. (Here, you suggest that the student find the prior authorization forms and volunteer to complete as many sections as she can for the endocrinologist. You explain that she can expedite the process and this is a skill she can apply to many different pharmacy practice locations.) Choosing histrelin is also a needle-free option, which may make JM happy. You remind your student that the plan should also include scheduling necessary appointments and follow-ups with JM’s other providers in addition to counseling on the specific adverse effects of the medication detailed in Table 2.

Table 2. Example SOAP note for JM⁷

Name: JM Age: 8 DOB: 10/02/14 Allergies: Seasonal allergies, NKDA
Chief Complaint: Patient referred to clinic by endocrinologist for medication therapy; patient was recently diagnosed with central precocious puberty (CPP)
Subjective Information JM is an 8-year old white male presenting to the clinic. He recently met with his endocrinologist on 6/28/23 and has been referred to the clinic for drug therapy to treat CPP. His parents confirm JM’s use of deodorant to combat excessive perspiration and body odor since the age of 5. He has also developed pubic and underarm hair in addition to acne on his face and upper back. His parents are concerned regarding JM’s reported insecurities at school due to his larger size.
PMH: no surgeries or hospitalizations			Medications: daily multivitamin, OTC loratadine (prn for allergies)
Objective Information Clinical exam findings = testicle size indicates puberty 112^th percentile for weight and height Relevant Labs: Bone age of 13, LH 0.4 units/L, DHEA sulfate 60 ug/dL
Height: 55 in	Weight: 102 lbs	BMI: 22.9	BP: 110/61 mmHg	HR: 75 bpm	Temp: 98.6 ℉	RR: 15
Assessment Problem: Patient requires medication therapy for untreated indication. Rationale: According to the Journal of Clinical Endocrinology Practice Guidelines for Central Precocious Puberty, JM requires hormone suppression therapy. Symptoms of rapid linear growth, advanced skeletal maturation, and basal LH levels > 0.3 units/L require treatment with GnRH analogs until the normal age of puberty. Goals of Care: The goal of treatment is to reduce signs of premature pubertal progression while ensuring therapy is well tolerated and medication side effects are minimized. Patient’s parents would like to choose an option that is cost effective and safe.
Plan Initiate histrelin 50mg SQ implant to be administered by JM’s surgeon every 12-24 months depending on safety and efficacy parameters evaluated at follow up appointments Schedule surgery appointment with JM’s surgeon at earliest convenience Schedule follow up in 3 months to evaluate pubertal progression, growth velocity, skeletal maturation, and tolerability Counsel JM/JM’s parents on possible adverse effects including weight gain, changes in appetite, initial flare of puberty symptoms, GI symptoms, body aches/pains, and signs of common cold Counsel JM’s parents on providing support to make JM feel good about himself. Children who are undergoing rapid development at this age may feel different when comparing themselves to other children their age.

Implement

During the implementation phase, pharmacists set the action plan into motion. This may include the administration of vaccines, initiating or discontinuing a medication, or scheduling the next follow-up appointment. Pharmacists, primary care physicians, or caregivers work together to provide care based on the goals made in the planning step.¹

Follow-up and Monitor

The pharmacist in collaboration with other health care providers should follow-up with the patient as recommended in practice guidelines and referring back to the SOAP note. Continuous monitoring of medication appropriateness, adherence, safety, laboratory results, and patient concerns will indicate if the plan requires revision. Routine medication reconciliations, check-ups, or conversations with patients improve outcomes and help to achieve goals of therapy.

Putting it All Together

Upon completion of the SOAP note, you send the endocrinologist your recommendations. You contact JM’s parents to discuss scheduling a follow-up appointment in three months with the endocrinologist and counsel on histrelin.

IMPLICATIONS FOR PRECEPTORS

The Benefits. The PPCP model creates a reproducible framework that demonstrates clinical pharmacists’ contributions to medication-related outcomes.¹³ In addition to improving the quality and completeness of patient medical records, SOAP notes give pharmacists a place to start when working up a new patient. As students practice developing SOAP notes, preceptors should emphasize how the lessons they learn in one case can apply to future cases.

The Drawbacks. As more pharmacy programs integrate PPCP into their curriculum, new students will have access to courses that teach the model. But because the PPCP model is relatively new, many licensed pharmacists have not yet familiarized themselves with the process. Extracting the necessary information to write quality SOAP notes can also be time consuming. Depending on the setting, pharmacists may not have enough time to walk through every step with students. Finally, the PPCP method does not encompass all clinical situations. The framework relies on pharmacists to exercise clinical judgment and reasoning to modify the model as needed.

Uncomfortable Topics. Students often have little exposure to difficult topics. These may include end-of-life issues, psychiatric diagnoses, cultural or ethnic differences, drug abuse/misuse, and gender-related topics. In this case, students may feel strong discomfort in discussing matters related to sex and sexual development. Preceptors need to help students reduce their hesitancy when communicating with you and the patient because improper communication can lead to poor collection of relevant information. Keep in mind strong note-writing skills facilitate good care. Two things help: (1) practice, and (2) finding resources designed to help with difficult topics. The Conversation Project (https://theconversationproject.org/resources/healthcare/) is one such resource that can help students become more comfortable with difficult topics.

In addition, students may have implicit and explicit biases for uncomfortable topics such as the use of hormone blockers, which may bring to mind their use in transgender children. Creating a safe place for your student to share opinions provides a great opportunity for you to teach students how to avoid these biases. Preceptors need to remember that learning—especially if it changes a student's perspective or points out a student's mistake—can be threatening, and students can feel vulnerable while learning. It’s an emotional experience.⁶

To help guide students through these experiences, the SIDEBAR provides 10 additional tips preceptors can use when supervising the PPCP.

SIDEBAR: PRO TIPS for Preceptors Who Supervise the PPCP

(1) Don't let the acronym scare you! This is a new name for a process you've probably used knowingly or unknowingly for years.

(2) Encourage independence. Hand over the problem to the student once you've described the problem and fielded the student's questions. Establish a time for the student to be prepared to discuss it but check in periodically to see if the student is having trouble.

(3) Rescue when necessary. Some students will need more support than others. If a student is clearly flummoxed, spend more time and provide more direction.

(4) Promote interdisciplinary communication. Having students discuss a clinical problem with another clinician, either with you or on their own, fosters interdisciplinary care. Students will also learn from the other clinicians, which will lighten your load!

(5) When students present findings, always ask them to describe things like the search terms and search engines they used or the obstacles they encountered. Help them refine their processes to reduce barriers or find more appropriate resources.

(6) Consistently prompt students to determine if the case is typical or unusual. Asking questions based on a modification of the case can help students learn more globally.

(7) Don't "stay in your lane"! In this CE, the practice site is an ambulatory care location specific to pediatrics. The lessons a student learns in this rotation, if they go beyond pediatrics, will be invaluable. Helping students develop communication skills or analyze how disease states present or are treated in adults or other special populations will increase their clinical acumen in future rotations.

(8) Address implicit biases or misconceptions. Students may not know that an attitude or opinion is biased, incorrect, or simply rude.

(9) Debrief. After the PPCP is done, provide feedback, ask others who may have been involved to provide feedback, and ask the student to perform a self-assessment.

(10) Appreciate reverse mentoring. Remember that students often teach us new things!

Common Sources of Error

Collecting too little information. Not all the information pharmacists need to collect will be obvious. In the patient case, the student collected important objective information like height and weight. However, without something like growth charts to evaluate JM’s height/weight compared to other kids his age, the information does not help in the assessment. Preceptors can aid students who are new to documenting SOAP notes when they are required to dive deeper into collected information. Students should not make assumptions as to what other clinicians know off the top of their heads. In this case, other areas where the preceptor helped the student included directing her to seek other expert opinions like the endocrinologist. That puts the “inter” in “interdisciplinary” care!

Collecting too much information. Pharmacists and students should collect information worthy of appraisal. In other words, only collect the necessary information that will contribute to the identification, prevention, and resolution of either the chief complaint or medication-related problems. If pharmacists/students do not actively use collected information to make the assessment or plan, they should omit it in the note. Documenting more information does not equate to better information. This leads to overly lengthy or confusing SOAP notes. Here, as in the previous error, preceptors should ask students to examine and explain their processes.

Not verifying information. All information should be verified across multiple sources like when performing traditional medication reconciliations. This prevents possible errors in note-taking that may arise from outdated documentation.

Sourcing one guideline. Depending on the disease state, the frequency in which guidelines are updated can vary. Preceptors should emphasize the importance of looking for multiple guidelines and paying attention to their publication dates. Occasionally, the FDA may approve new treatment options after the release of clinical guidelines or updates. In this case, the student completely missed an additional treatment option as a result of sourcing a single guideline from 2013. Similar to how preceptors should encourage students to verify collected information across multiple sources, preceptors should also encourage students to cross-check sources that aid in their assessment.

The assessment lacks evidence. As mentioned above, the assessment should communicate the assessor’s thought process. The information collected by the pharmacist/student should justify why the problem is a problem. If there is no subjective or objective information to back up the assessment, the assessment has no basis.

Forgetting recommendations on current medications. Pharmacists/students should not forget to include instructions for the patient’s current medications, not just the newly prescribed medications.

Forgetting non-pharmacologic recommendations. The plan section also encompasses non-pharmacologic interventions such as referral to another provider, ordering additional laboratory tests, education, or counseling on lifestyle interventions. Pharmacists/students should remember that not all patients require initiation of a new medication.

Being vague. When initiating new therapy appropriately, pharmacists/students should always provide specific recommendations with the drug name, dose, and frequency. Vague instructions such as “Initiate hormone blocker therapy” are unhelpful. Similarly, instead of “monitor for side effects,” pharmacists/students can list the specific symptoms that present most commonly.

Poor communication. Errors due to poor communication directly hinder the PPCP. Furthermore, clinicians with experience are not necessarily better communicators. Therefore, pharmacists should engage in education/training to constantly improve communication skills. SOAP notes should effectively communicate the pertinent information used to create a plan and document important details for the patient’s medical record.

Setting it and forgetting it. The PPCP is not a linear process. While this framework provides clinicians a place to start and a checklist of sections to complete in order, pharmacists should remember to review and revise all sections at any given time. For example, pharmacists may identify new information they should go back to collect as they work on their assessments. Preceptors should encourage their students to occasionally step back and evaluate the completeness and coherence of the SOAP note. Sometimes patient cases will require students to revise sections of the SOAP note they already completed.

And a New Case

Just before the end of the month, the endocrinologist sends yet another patient with precocious puberty to you. The patient LD is a 9-year old Hispanic female. Her endocrinologist recently diagnosed her with idiopathic precocious puberty and wants to know which treatment you recommend. Her parents also want to know why this is happening to their daughter. Before taking LD’s family from the clinic waiting room, you decide to let your student take charge of this case while you supervise. You ask your student “Now that you have practiced writing SOAP notes and know a little about this disease state, how will you approach the PPCP this time?”

The student says to you...

“I stored all my notes from the last case on precocious puberty from earlier this month. I have a document containing the guidelines from the Journal of Clinical Endocrinology along with several updated publications that cite all additional first-line medications approved after the original guideline’s release. I will start with the collection of subjective information such as LD’s symptoms and medical history followed by objective information, specifically pertaining to her growth statistics. I should calculate BMI and her height/weight percentiles since precocious puberty is usually associated with accelerated growth. Next, I will examine her relevant lab values. Since the patient is female, I will be looking out for progesterone levels this time. If possible, I shall cross-reference all of the information I collect across multiple sources.”

“Before I move onto making an assessment, I understand LD’s parents may feel very concerned about their daughter's condition. I don’t want to forget to address their question. I will explain that idiopathic precocious puberty does not have a definitive cause. To help them better understand, I’ll mention that idiopathic cases may result from anything ranging from a head injury in childhood to exposure to certain chemicals. Regardless of the cause, I will assure them there are several treatment options that may be appropriate for LD at this time. I can walk them through the pros and cons of all the available options.”

“Next, I would prompt LD’s parents with open-ended questions to learn more about their major concerns, potential barriers to medication therapy, and insurance eligibility. I know these are important considerations for my assessment. It would also be appropriate for me to engage with LD using appropriate language for a 9-year-old girl. I realize the topic may be uncomfortable to discuss, but without taking initiative of the discussion I may forget to include pertinent details in my SOAP note.”

“Finally, using the information I collected about the family’s preferences and LD’s medical history, I will draft the chief complaint, rationale for treatment, goals of therapy, and eventually a completed plan. The plan will include which treatment I recommend along with the dose, frequency, and which adverse effects are most common. I will write when I recommend a follow-up with her endocrinologist and make note of which lifestyle modifications may support her specific treatment. If the endocrinologist is on board, then we can collaboratively implement and follow-up with the patient as appropriate.”

You are overjoyed to hear that your student has taken what she learned from the previous case and applied it to this case as well. Although some of the parameters were different, such as the patient’s sex, she was able to anticipate how the changes may impact her SOAP note this time. While you identify a few areas in which she can improve, you are happy that she is continuing to expand her clinical pharmacy knowledge.

Conclusion

The PPCP model can be applied to any healthcare setting in which pharmacists practice. This comprehensive approach to patient-centered care has established a streamlined method of documenting patient information to be shared among healthcare teams. As the PPCP continues to grow in clinical settings, practicing pharmacists should become familiar with its methods and applications.

Prepping Pharmacist Preceptors on the Pharmacists’ Patient Care Process (PPCP)
Post-test
Learning Objectives
After completing this continuing education activity, preceptor-pharmacist will be able to
• Describe the PPCP model and its uses
• Apply the PPCP when students address clinical problems in the workplace
• Identify areas where pharmacy students need the most guidance when using the PPCP
POST TEST
1. Which of the following correctly lists the steps of the PPCP process in order?
A. Collect, plan, assess, follow-up, implement
B. Collect, assess, plan, implement, follow-up
C. Plan, collect, assess, follow-up, implement
2. Which of the following best describes the JCPP’s reason for developing the PPCP?
A. To establish a more efficient method of medical documentation
B. To provide an opportunity for pharmacists to expand their clinical role
C. To create a reproducible method of managing patient medications

3. Which of the following examples is a common error pharmacy students make when using the PPCP?
A. Avoiding discussion involving uncomfortable topics such as those sexual in nature
B. Spending too long counseling the patient as opposed to documenting the SOAP note
C. Omitting recommendations to follow up with the patient’s primary care provider
4. Which of the following is a common source of error with the PPCP?
A. Using a single clinical guideline for recommendations
B. Spending the most time documenting the assessment section
C. Cross-referencing medication lists against too many sources
5. A nurse practitioner calls your clinic and would like you and your student to work up a patient with stage II hypertension. The patient is a 64-year-old African American male who is currently taking amlodipine 2.5 mg and chlorthalidone 6.25 mg. His blood pressure was 150/90 mmHg at his last doctors appointment. Which of the following would be an appropriate first step?
A. Increase the dose of his medications. The SOAP note does not need to be performed as his blood pressure remains elevated due to subtherapeutic dosing.
B. Ask the patient about his/her medication adherence recently. This information will dictate how you decide to approach the patient.
C. Contact the patient’s local pharmacy for a complete list of active medications. This will be valuable information to collect prior to assessing the patient.
6. A student working on a SOAP note cites a 2012 guideline from Europe. The preceptor notices the student forgets to consider a first-line treatment option that was approved in 2022. What should the preceptor do at this point?
A. Call the physician to get his/her opinion on the newly approved medication
B. Discuss the importance of citing multiple sources with the student
C. When the student finishes the note, add in the missing information
7. Laboratory values belong under which of the following sections of the PPCP?
A. Assessment
B. Objective information
C. Subjective information
8. Your student is counseling a patient who has dementia. When you ask him to practice how he would counsel the patient, he looks puzzled and asks “What for? He has dementia and he won’t understand anyway.” How do you proceed?
A. Ask the student to find guidelines on how to determine when and how dementia patients should be counseled.
B. Tell him it was a trick question and that he is correct that dementia patients should never be counseled.
C. Explain pharmacists are legally required to offer counseling and he should be prepared if the patient requests it.
9. A preceptor and student are working in an ambulatory care clinic. A patient presents to the counter and says she has been experiencing terrible adverse effects from one of her medications. The patient places a bottle of sertraline on the counter. She believes this is the medication causing her persistent insomnia. After talking with the doctor, she has switched to taking it in the morning, but she claims it does not help. How should the preceptor advise the student to continue?
A. Advise the student to counsel the patient on ways to manage this adverse effect of sertraline. The student may consult the monograph or other recent guidelines.
B. Remind the student that persistent insomnia is a flag to contact the provider. The psychiatrist can handle this as it isn’t in the scope of the preceptor’s practice.
C. Advise the student to start by evaluating the patient’s past medical history and evaluating her medications before sending her back to see her doctor.
10. A general practitioner refers a patient with mild asthma to your clinic. He has recommended the patient to start SMART therapy and would like you to supply your recommendations through a SOAP note. Under your supervision, the student finishes collecting the necessary objective and subjective information and has begun a draft of the assessment as follows:
“The patient needs medication therapy for an untreated indication. According to the GINA guidelines, the patient should initiate a low dose inhaled corticosteroid plus a long-acting beta agonist combination in low doses as needed.”
Which of the following best describes the feedback the preceptor should give the student when applying the PPCP model?
A. The student has done a good job so far. However, the assessment should also consider patient concerns such as insurance coverage.
B. The student has done a good job so far. The student should provide specific doses and monitoring parameters for completeness.
C. The student has done a good job so far. The student should call the provider to check if they follow the GINA guidelines, and if not, why.

References

REFERENCES
1. Joint Commission of Pharmacy Practitioners. Pharmacists’ Patient Care Process. Published May 29, 2014. Accessed June 21, 2023. https://jcpp.net/patient-care-process/
2. Cooley J, Lee J. Implementing the Pharmacists' Patient Care Process at a Public Pharmacy School. Am J Pharm Educ. 2018;82(2):6301. doi:10.5688/ajpe6301
3. Podder V, Lew V, Ghassemzadeh S. SOAP Notes. [Updated 2022 Aug 29]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 January. https://www.ncbi.nlm.nih.gov/books/NBK482263/
4. Takemura Y, Sakurai Y, Yokoya S, et al. Open-ended questions: are they really beneficial for gathering medical information from patients?. Tohoku J Exp Med. 2005;206(2):151-154. doi:10.1620/tjem.206.151
5. Taub S. Learning to Decide: Involving Children in their Health Care Decisions. Virtual Mentor. 2003;5(8): virtualmentor.2003.5.8. pfor3-0308. Published 2003 Aug 1. doi: 10.1001/virtualmentor.2003.5.8.pfor3-0308
6. Elnicki DM. Learning with emotion: which emotions and learning what?. Acad Med. 2010;85(7):1111. doi:10.1097/ACM.0b013e3181e20205
7. Fuqua JS. Treatment and outcomes of precocious puberty: an update. J Clin Endocrinol Metab. 2013;98(6):2198-2207. doi:10.1210/jc.2013-1024
8. Bangalore Krishna K, Fuqua JS, Rogol AD, et al. Use of Gonadotropin-Releasing Hormone Analogs in Children: Update by an International Consortium. Horm Res Paediatr. 2019;91(6):357-372. doi:10.1159/000501336
9. Lexicomp. Wolters Kluwer Health, Inc. Updated June 20, 2023. Accessed June 21, 2023. https://online-lexi-com.ezproxy.lib.uconn.edu/lco/action/doc/retrieve/docid/pdh_f/129683?cesid=afdPrd0aazi&searchUrl=%2Flco%2Faction%2Fsearch%3Fq%3Dleuprolide%26t%3Dname%26acs%3Dfalse%26acq%3Dleuprolide#rfs
10. Lexicomp. Wolters Kluwer Health, Inc. Updated June 6, 2023. Accessed June 21, 2023. https://online-lexi-com.ezproxy.lib.uconn.edu/lco/action/doc/retrieve/docid/pdh_f/128793?cesid=4Ds6TlNfgKm&searchUrl=%2Flco%2Faction%2Fsearch%3Fq%3Dhistrelin%26t%3Dname%26acs%3Dfalse%26acq%3Dhistrelin
11. Supprelin LA (Histrelin) Subcutaneous Implant Procedure. Children’s Hospital of Philidelphia. Published May 4, 2021. Accessed June 21, 2023. https://www.chop.edu/treatments/supprelin-la-histrelin-subcutaneous-implant-procedure
12. Kaplowitz P, Hoffman, R. Precocious Puberty Medication. Medscape. Updated January 24, 2022. Accessed June 21, 2023. https://emedicine.medscape.com/article/924002-medication
13. Harris IM, Phillips B, Boyce E, et al. Clinical pharmacy should adopt a consistent process of direct patient care. Pharmacotherapy. 2014;34(8):e133-e148. doi:10.1002/phar.1459
14. Silverman LA, Han X, Huang H, Near AM, Hu Y. Clinical characteristics and treatment patterns with histrelin acetate subcutaneous implants vs. leuprolide injections in children with precocious puberty: a real-world study using a US claims database. J Pediatr Endocrinol Metab. 2021;34(8):961-969. Published 2021 Jun 21. doi:10.1515/jpem-2020-0721

Patient Safety: Medication Refusal: Understanding the Why “They Just Say No”

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

Recognize and define types and leading causes of treatment/medication refusal

Describe the ethical and legal principles associated with medication refusal, covert medication, and surreptitious prescribing

Determine treatment alternatives for patients with dietary, religious, or other restrictions

Identify and implement key components of a medication refusal protocol

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

Recognize and define types and leading causes of treatment/medication refusal

Describe the ethical and legal principles associated with medication refusal, covert medication, and surreptitious prescribing

Determine treatment alternatives for patients with dietary, religious, or other restrictions

Identify and implement key components of a medication refusal protocol

Based on the principle of informed consent, competent patients always
have the right to refuse medical treatment. Patients may refuse treatment
for a variety of reasons, including dietary restrictions, religious reasons, medical
misconceptions, a desire to avoid adverse effects, and mistrust of the medical
team. Patient refusals can create serious dilemmas in the healthcare setting. On
the one hand, clinicians have an ethical and legal obligation to honor patient autonomy.
On the other hand, a patient’s refusal of treatment often leads to adverse
medical outcomes, resulting in harm to the patient. Healthcare
professionals should search for acceptable treatment alternatives that honor patients’
wishes while meeting their medical needs. Every institution—whether in
the community, long-term care, or inpatient setting—should have a protocol to
guide and standardize the approach to managing treatment refusals. In complex
cases, it may be beneficial to use expert ethics consultations.

Medication Refusal: Understanding the Why "They Just Say No"
After participating in this activity, pharmacists and pharmacy technicians will be able to
1. Recognize and define types and leading causes of treatment/medication refusal
2. Describe the ethical and legal principles associated with medication refusal, covert medication, and surreptitious prescribing
3. Determine treatment alternatives for patients with dietary, religious, or other restrictions
4. Identify and implement key components of a medication refusal protocol

1. Which of the following is an example of ACTIVE medication refusal?
a. A patient ingests her medication when the caregiver administers it, but secretly spits it out half an hour later.
b. A patient states that she does not wish to take her oral medication, then refuses to open her mouth to ingest the medication.
c. A patient initially refuses to take her medication, but concedes when the caregiver repeatedly asks her to.

2. A patient states that he is vegetarian and wishes to avoid animal products. Which of the following excipients is INAPPROPRIATE for this patient?
a. Gelatin
b. Peanut oil
c. Mannitol

3. Which of the following best describes motivational interviewing?
a. An interviewing style that involves the use of ethics counselors, who help healthcare professionals navigate complicated cases
b. The process by which patients are educated about a treatment’s risks, benefits, and alternatives
c. A behavioral technique that motivates patients to change by empowering them and motivating them with their own values

4. Which of the following statements is FALSE about the practice of covert medication?
a. It refers to administering medications without a patient’s knowledge, such as by concealing medications in food or drink.
b. It is justifiable in mentally competent patients who refuse treatment against medical advice.
c. It may be better received than more aggressive methods, such as forced injections.

5. A practicing Sikh patient tells you that her religion prevents her from consuming Medication X, which contains animal by-products. She wants to know what alternatives are available, and what she should avoid. Which of the following best describes her reasons for refusing Medication X?
a. Dietary restriction
b. Medical misconception
c. Mistrust of the medical team

6. A practicing Sikh patient tells you that her religion prevents her from consuming Medication X, which contains animal by-products. She wants to know what alternatives are available, and what she should avoid. Which is the best resource to refer her to?
a. Pillbox, so she can research medications’ ingredients and avoid those containing animal products
b. The primary literature and PubMed or GoogleScholar, so she can find the most recent data
c. The patient should not be referred; Medication X is the most effective option for her illness, and she should take it regardless of her beliefs

7. Why might an ethics consultation be useful in certain instances of treatment refusal?
a. Ethics counselors are authorized to make healthcare decisions on behalf of incompetent patients.
b. Ethics counselors are compensated based on patient outcomes, so they persuade patients to choose the most medically effective option.
c. Ethics counselors are trained in core ethics and healthcare competencies and can help navigate difficult situations.

8. Patient BT is newly diagnosed with a disease. His doctor recommends Treatment X and describes the treatment’s risks and benefits. BT refuses his doctor’s suggestion. Instead, he decides to try natural OTC products. This is an example of:
a. Beneficence
b. Primum non nocere
c. Autonomy

9. Patient BT is newly diagnosed with a disease. His doctor recommends Treatment X and describes the treatment’s risks and benefits. BT refuses his doctor’s suggestion. Instead, he decides to try natural OTC products. Which of the following is the LEAST appropriate response to BT?
a. Inform BT of the risks and benefits of OTC products, and show him how to interpret the Drug Facts labels.
b. Identify BT’s reason for refusal—ask about his beliefs, perceptions, and concerns. Counsel him accordingly.
c. Inform BT that you will request an ethics consultation to advise in this situation, which in your opinion is untenable.

10. Patient WG is prescribed a new medication and told to take one capsule twice a day. WG misunderstands—he takes two capsules once a day, instead. Which of the following best describes WG’s behavior?
a. Intentional non-adherence
b. Unintentional non-adherence
c. Passive refusal

11. Patient AU tells you, “Dr. S prescribed five different pills for me, but I’m not taking any of them. I’m a regular churchgoer and I know I should love and respect all people, but I don’t have a good feeling about Dr. S. I think she has it out for me. I’m going to get the meds from Dr. G instead.” Based on this statement, AU’s primary reason for refusal is:
a. Religious refusal
b. Lack of belief in the medications’ effect
c. Mistrust of the medical provider

12. Patient LG is a 5-year-old female who requires a life-saving blood transfusion. Her caretaker refuses to consent to the procedure since it goes against her religious beliefs. Which of the following statements is TRUE of this situation?
a. The attending physician must request an ethics consultation, since this is legally required for all cases involving a minor.
b. LG’s caretaker has the ultimate say in her medical decisions but LG’s doctors are ethically obligated do what is beneficial for the patient.
c. Since LG does not suffer from any brain disorders, she can make her own medical decisions. The medical team only needs LG’s consent, not the caretaker’s.

2. A patient states that he is vegetarian and wishes to avoid animal products. Which of the following excipients is INAPPROPRIATE for this patient?
a. Gelatin
b. Peanut oil
c. Mannitol

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

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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

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 2019 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

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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.

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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

Arthur E. Schwarting Symposium LIVE Event 2027 TBD

Arthur E. Schwarting was an internationally recognized leader in the transformation of pharmacognosy from a plant-based discipline to a science based on the chemistry of natural products. He also was the preeminent pharmacognosist in the U.S. to engage in the study of medicinal agents from microorganisms, and he was a pioneer in the use of radio isotopes to elaborate the biochemical pathways by which plants and microorganisms make medicinally active products. The Arthur E. Schwarting Symposium is now an educational conference focused on pharmacy practice for pharmacists in many settings.

Measure Twice, Cut Once: A Carpentry Approach to Pharmacy

Five hours of live streaming CE including Law, Patient Safety, and Immunization

2026 AGENDA

11:00am-12:00 pm

Load-Bearing Walls: Getting Cardiovascular Therapy Right the First Time

Katelyn Galli, PharmD, BCCP, UConn School of Pharmacy, Storrs, CT

Type of Activity: Application

ACPE UAN 0009-0000-26-009-L01-P

Learning Objectives: At the end of this presentation the learner will:

Identify high-risk cardiovascular medications that are most commonly associated with preventable adverse drug events amid transitions of care
Describe evidence-based principles for precise cardiovascular medication dosing, including clinically relevant pharmacokinetic considerations that influence drug and dose selection
Explain the benefits and limitations of clinical decision support tools in cardiovascular pharmacotherapy
Recognize common system-level and cognitive factors contributing to cardiovascular medication near misses and adverse effects

12:05-1:05 pm

LAW: The Legal Blueprint: Designing Error-Proof Pharmacy Policies

Dylan DeCandia, PharmD, RPh, Franklyn’s Pharmacy in Ho-Ho-Kus, New Jersey

Type of Activity: Application

ACPE UAN 0009-0000-26-010-L03-P

Learning Objectives: At the end of this presentation the learner will:

Describe the roles and responsibilities of each pharmacy staff member
Articulate when a pharmacist should seek legal clarification
Identify common pharmacy mistakes that may leave pharmacists liable
Construct policies and procedures that prevent future pharmacy errors

1:10-2:10 pm

Patient Safety: Blueprints Before Builds: Patient Assessment in Clinical Decision-Making

Devra Dang, PharmD, CDCES, FNAP, Clinical Professor, University of Connecticut School of Pharmacy, Storrs, CT

Type of Activity: Application

ACPE UAN 0009-0000-26-013-L05-P

Learning Objectives:

Explain the Pharmacists’ Patient Care Process and strategies to optimize the “Collect” and “Assess” steps to improve assessment and clinical decision-making
Identify common pitfalls that affect optimal patient assessment across healthcare settings
List strategies to incorporate patient-centered approaches into patient assessment and clinical decision-making

2:15-3:15 pm

Immunization: The Right Tool for the Job: Precision and Preparation in Immunization Practice

Thomas E. Buckley, RPh, MPH, FNAP; Associate Clinical Professor Emeritus, UConn School of Pharmacy, Storrs, CT

Type of Activity: Application

ACPE UAN 0009-0000-26-011-L06-P

Learning Objectives: At the end of this presentation the learner will:

Analyze contraindications as the “measurement” step
Determine the correct vaccine, dose, route, and needle length
Document and report finishing work
Detect administration errors and adverse events
Illustrate reliable vaccine information

3:20-4:20 pm

Right Fit, Tight Seal: Building Better Cancer Care

Thomas M Levay, PharmD, CSP, Yale New Haven Health, New Haven, CT

Type of Activity: Application

ACPE UAN 0009-0000-26-012-L01-P

Learning Objectives: At the end of this presentation the learner will:

Recognize ways that general education and consultation contributes to better care
Identify crucial elements of a patient’s non-clinical care for patients with cancer
Demonstrate different ways to help patients at each phase of care

Handouts will be posted 72 hours prior to the event in 2 slides per page and 6 slides per page below:

11:00am-12:00 pm Load-Bearing Walls: Getting Cardiovascular Therapy Right the First Time

12:05-1:05 pm LAW: The Legal Blueprint: Designing Error-Proof Pharmacy Policies

1:10-2:10 pm Patient Safety: Blueprints Before Builds: Patient Assessment in Clinical Decision-Making

2:15-3:15 pm Immunization: The Right Tool for the Job: Precision and Preparation in Immunization Practice

3:20-4:20 pm Right Fit, Tight Seal: Building Better Cancer Care

“The University of Connecticut School of Pharmacy is accredited by the Accreditation Council for Pharmacy Education as a provider of continuing pharmacy education.”

Continuing Education Units

The University of Connecticut, School of Pharmacy, is accredited by the Accreditation Council for Pharmacy Education as a provider of continuing pharmacy education. Statements of Credit will be awarded at CE Finale based on full sessions attended and completed online evaluations. Pharmacists can earn up to 5 contact hours (0.50 CEU) one of which is a law credit, one is an Immunization Credit, and one is a Patient Safety Credit.

Please Note: Pharmacists who wish to receive credit for the presentations MUST ACCURATELY complete the registration and online evaluations within 45 days of the live program (before February 1, 2026). Participants are accountable for their own continuing education requirements for license renewal and are required to follow up with Heather.Kleven@uconn.edu to resolve a discrepancy in a timely manner. PLEASE CHECK YOUR CPE MONITOR PROFILE within 3 days of submission to ensure that your credits have been properly uploaded. Requests for exceptions will be handled on a case-by-case basis and may result in denial of credit.

Registration Fees: 50% discount for UConn faculty/preceptors

Long-Acting Injectable Medication Products

Pharmacists possess the training and skills necessary to administer certain long-acting injectable (LAI) medications used in the management of mental illnesses and substance use disorders. Through collaborative practice agreements, pharmacists can administer Long Acting Injectables in almost every state. In some states, including the state of Connecticut, this occurs via collaborative agreements, and necessary injection and disease state training. Administration of these medications by pharmacists can increase accessibility of care for patients.

UConn has developed web-based continuing pharmacy education activity to enhance pharmacists’ skills and help them make sound clinical decisions about long acting injectables administration. This course includes eight hours of CPE (or eight hours of credit), required by the State of Connecticut. Successful completion of these eight hours (with four activities consisting of three hours online pre-requisite work and five hours of LIVE CE) will earn the pharmacist a Certificate in Long-Acting Injectables of Psychotropic Medication.

The three activities below are available separately for $17/hour each, or as pre-requisites for the entire Long-Acting Injectable Psychotropic Medication Pharmacist Certificate Training Program at $299 which includes both the prerequisites and the full day of LIVE training.

At the end of this application-based continuing education activity, the learner will be able to:

Compare and contrast among different long-acting injectable (LAI) medications currently available for the

treatment of schizophrenia, bipolar disorder and substance use disorders including:

· Dosing

· Generic and brand names

· Adverse effects

· Administration schedule

· Overlap with oral medications

· FDA-approved indications

If desired, pharmacists can register for the entire Long-Acting Injectable Psychotropic Medication Pharmacist Certificate Training Program

or for the individual activities. The Certificate consists of three activities in our online selection, and a 5 hour LIVE activity.

You may register for individual topics at $17/CE Credit Hour, or for the Entire LAIA Certificate at $299.00 which includes 5 hours of LIVE CE and the 3 online pre-requisites listed below.

You must register for ALL 4 activities to receive the bundled pricing of $299.00

In accordance with the Accreditation Council for Pharmacy Education (ACPE) Criteria for Quality and Interpretive Guidelines, The University of Connecticut School of Pharmacy requires that faculty disclose any relationship that the faculty may have with commercial entities whose products or services may be mentioned in the activity.

Dr. Waters is a consultant with Janssen Pharmaceuticals. She will discuss all drugs without bias. All financial interests with ineligible companies (as noted) have been mitigated.

Guideline-Driven Treatment for Mental Illnesses and Substance Abuse Disorders

At the end of this application-based continuing education activity, the learner will be able to:

Describe first- and second-line treatment options for the following disease states:

· Schizophrenia

· Bipolar disorder

· Alcohol use disorder

· Opioid use disorder

Identify where long-acting injectable medications fit into treatment guidelines for each disorder

Apply clinical treatment guidelines to select optimal pharmacologic treatment for a patient diagnosed with these disorders

If desired, pharmacists can register for the entire Long-Acting Injectable Psychotropic Medication Pharmacist Certificate Training Program

or for the individual activities. The Certificate consists of three activities in our online selection, and a 5 hour LIVE activity.

You may register for individual topics at $17/CE Credit Hour, or for the Entire LAIA Certificate at $299.00 which includes 5 hours of LIVE CE and the 3 online pre-requisites listed below.

You must register for ALL 4 activities to receive the bundled pricing of $299.00

Dr. Waters is a consultant with Janssen Pharmaceuticals. She will discuss all drugs without bias. All financial interests with ineligible companies (as noted) have been mitigated.

Mental Illness and Substance Use Disorders: Background

If desired, pharmacists can register for the entire Long-Acting Injectable Psychotropic Medication Pharmacist Certificate Training Program

or for the individual activities. The Certificate consists of three activities in our online selection, and a 5 hour LIVE activity.

You may register for individual topics at $17/CE Credit Hour, or for the Entire LAIA Certificate at $299.00 which includes 5 hours of LIVE CE and the 3 online pre-requisites listed below.

You must register for ALL 4 activities to receive the bundled pricing of $299.00

Dr. Waters is a consultant with Janssen Pharmaceuticals. She will discuss all drugs without bias. All financial interests with ineligible companies (as noted) have been mitigated.

Hour 1: Mental Illness and Substance Use Disorders: Background

1. A 38-year-old patient with an unknown psychiatric history is dropped off at the emergency department by police after being found wandering the streets and knocking on doors at random. The patient admits that they believe they are being monitored by the FBI and that “the mafia” wants to recruit them as a spy. The patient is observed having a conversation with themselves while alone in the examination room.

Which of the following positive symptoms is the patient likely experiencing?
A. Psychosis and auditory hallucinations
B. Auditory hallucinations and delusions
C. Delusions and anhedonia
D. Paranoia and agitation

2. Which of the following is the correct term for fixed, false beliefs that patients with schizophrenia may experience?
A. Delusions
B. Hallucinations
C. Disorganized speech
D. Catatonia

3. A patient with schizophrenia has experienced both positive and negative symptoms for several years. They are now presenting with signs of mania, including pressured speech and grandiosity. Which of the following is true?
A. The patient’s diagnosis will likely change to schizoaffective disorder, bipolar type
B. The patient’s diagnosis will likely change to schizoaffective disorder, depressive type
C. The patient will now be diagnosed with schizophrenia and bipolar disorder
D. The patient will now be diagnosed with schizophrenia and major depressive disorder

4. Which of the following is true about bipolar disorder?
A. The most common time that patients are diagnosed is during childhood
B. Most patients are initially diagnosed with schizophrenia
C. It has a higher mortality rate than major depressive disorder
D. Type II bipolar disorder is associated with more severe episodes of mania than type I

5. Most patients with bipolar disorder spend the majority of their time in which mood phase?
A. Mania
B. Depression
C. Hypomania
D. Euthymia

6. A patient with bipolar disorder presents to their outpatient provider and reports that they believe they are on the verge of a “breakthrough” and will soon become a world-famous author once their manuscript is published. They have recently stopped going to work and have been writing “all day and all night” for the past week. They also report spending thousands of dollars on a new computer so that they have “the best equipment” with which to write their manuscript.
Which of the following symptoms of mania is the patient displaying?
A. Grandiosity, decreased need for sleep, increased goal directed activity
B. Flight of ideas, distractibility, grandiosity
C. Disorganized thoughts, decreased need for sleep, flight of ideas
D. Confusion, excessive spending, distractibility

7. Patient NP was diagnosed with bipolar disorder, type II approximately 5 years ago. They have rarely missed work due to hypomanic symptoms, and are generally able to perform all day-to-day activities without impairment. Following a breakup, NP begins to display signs of grandiosity, flight of ideas, decreased sleep, and increased spending. They also begin to hear the voice of their ex-partner telling them that they are worthless.

Which of the following is most appropriate?
A. NP’s diagnosis should be changed to bipolar disorder type I
B. NP’s diagnosis should remain the same
C. NP’s diagnosis should be changed to schizoaffective disorder
D. NP’s diagnosis should be changed to bipolar disorder, mixed type

8. Which of the following is a risk factor for the development of a substance use disorder?
A. Female gender
B. Age > 65 years
C. Co-occurring psychiatric disorder
D. Parenthood

9. Which type of opioid receptor contributes to the stimulation of the dopamine-related reward system?
A. Mu-opioid receptor
B. Kappa-opioid receptor
C. Delta-opioid receptor
D. Beta-opioid receptors

Patient Safety: Pharmacy Metrics-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 0009-0000-23-026-H05-T, 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.

1. Which of the following is NOT a use for metrics in pharmacies?
A. Quantify workflow
B. Exhaust staff
C. Establish comparators

2. Patient-centered metrics are based on which of the following?
A. Profits
B. Public health initiatives
C. Patient complaints

3. _____ is a metric used to assess productivity.
A. Time-to-fill
B. Rate of medication errors
C. Out-of-stock prescriptions

4. Which of the following is a good way to reach vaccination metrics?
A. Letting the patient contact the pharmacy about vaccinations
B. Reminding patients of vaccinations at the register
C. Relying on advertising to encourage patients

5. What does SMART goals, a great way to develop an approach to improve metrics, stand for?
A. Specific, Measurable, Achievable, Relevant, Time-Bound
B. Specific, Measurable, Achievable, Resourceful, Time-Bound
C. Specific, Measurable, Accurate, Reasonable, Time-Bound

6. What is the most important skill in the workplace when tackling metrics?
A. Speed
B. Communication
C. Knowledge

7. Many metrics focus on efficiency. What other consideration is crucial?
A. Type of pharmacy
B. Patient safety
C. Workload or volume

8. Select the statement that is TRUE:
A. Metrics usually refer to a general aspect of pharmacy tasks, so they are the same in community and clinical settings.
B. While metrics often refer to a general aspect of pharmacy tasks, they can vary greatly between community and clinical settings.
C. While metrics often refer to a general aspect of pharmacy tasks, pharmacies should stay away from standard metrics and develop new approaches.

9. Super Tech is worried about her pharmacy’s time-to-fill metric. Wonder Pharmacist is focused on inventory metrics. Three months go by and they haven’t made good progress on either. Why?
A. They are working alone on each metric, but need to be working together.
B. It’s not possible to work on two metrics at the same time.
C. Improving time-to-fill metrics will adversely influence inventory metrics.

10. Which of the following activity falls heavily on pharmacy technicians and contributes heavily to pharmacy metrics in the community setting?
A. Vaccinations
B. Insurance and billing
C. In-person patient interaction

Learning Objectives

Accreditation Statements

Disclosure of Discussions of Off-label and Investigational Drug Use

Faculty

Faculty Disclosure

ABSTRACT

CONTENT

Content

Pharmacist Post Test (for viewing only)

Pharmacy Technician Post Test (for viewing only)

References

Full List of References

Learning Objectives

Accreditation Statements

Disclosure of Discussions of Off-label and Investigational Drug Use

Faculty

Faculty Disclosure

ABSTRACT

CONTENT

Content

Pharmacist Post Test (for viewing only)

References

Full List of References

Learning Objectives

Accreditation Statements

Disclosure of Discussions of Off-label and Investigational Drug Use

Faculty

Faculty Disclosure

ABSTRACT

CONTENT

Content

Pharmacist Post Test (for viewing only)

Pharmacy Technician Post Test (for viewing only)

References

Full List of References

Learning Objectives

Accreditation Statements

Disclosure of Discussions of Off-label and Investigational Drug Use

Faculty

Faculty Disclosure

ABSTRACT

CONTENT

Content

Pharmacist Post Test (for viewing only)

Pharmacy Technician Post Test (for viewing only)

References

Full List of References

Learning Objectives

Accreditation Statements

Disclosure of Discussions of Off-label and Investigational Drug Use

Faculty

Faculty Disclosure

ABSTRACT

CONTENT

Content

Pharmacist Post Test (for viewing only)

Pharmacy Technician Post Test (for viewing only)

References

Full List of References

Measure Twice, Cut Once: A Carpentry Approach to Pharmacy

2026 AGENDA

About this Course

Target Audience

Pharmacist Learning Objectives

Bundle Options

Accreditation Statement

Grant Funding

Requirements for Successful Completion

Faculty

Faculty Disclosure

Disclaimer

Program Content

Program Handouts

Post Test Evaluation

View Questions for Long-Acting Injectable Medication Products

Additional Courses Available for Long Acting Injectable Training

About this Course

Target Audience

Pharmacist Learning Objectives

Bundle Options