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Clinicians, Pharmacists Should Work to Ensure Safety Compounded GLP-1 Medications
Key Takeaways
- GLP-1 agonists face shortages, leading to increased use of compounded versions, which are not FDA-approved and pose safety risks.
- Compounded GLP-1 agonists offer cost benefits but may involve dosing errors and counterfeit products, raising safety concerns.
Pharmacists can educate patients about how to recognize unsafe online sources of medications and ensure patients are properly educate on how to administer their medications.
Introduction
There is no question that glucagon-like peptide-1 (GLP-1) agonists are among the most widely used medications in the US. According to a recent KFF poll, 1 in 8 adults (12%) report ever taking a GLP-1 agonist.1,2 Despite the high cost, demand for GLP-1 agonists has exceeded supply, causing drug shortages and opening the door for compounded GLP-1 medications.
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Drug shortages for GLP-1 agonists have been reported for the past 2 years. Compounding pharmacies have provided access to GLP-1 agonist “copies” during official shortages. Estimates suggest that compounded versions of GLP-1 agonists may account for as much as 20% of all prescriptions for these drugs.3
The availability of compounded GLP-1 agonists can increase access to these medications at a lower financial cost to patients. Many insurances companies do not cover brand name GLP-1 agonists for weight loss, and the out-of-pocket cost of tirzepatide (Mounjaro, Zepbound; Eli Lilly) is approximately $1060 for a 28-day supply.4 Prior authorization processes required by certain insurance companies cause additional barriers to GLP-1 agonists for weight loss. Additionally, there are no generic versions of GLP-1 agonists. Many compounding pharmacies can offer GLP-1 agonists for as little as $149 per month.5
Compounded Drugs and Pharmacies
Compounded drugs are not FDA approved, although the FDA specifies that ingredients “must come from FDA-registered facilities and manufacturers.”6 Furthermore, compounded drugs must meet certain conditions to qualify for exemptions under sections 503A and 503B of the Federal Food, Drug and Cosmetic (FD&C) Act. Among those conditions are:7
- Section 503A of the FD&C Act includes restrictions on compounding drugs that are essentially copies of a commercially available drug. These drugs are neither tested nor monitored and facilities do not have to report adverse events to the FDA
- Section 503B of the FD&C Act restricts outsourcing facilities from making compounded drugs that are essentially a copy of 1 or more FDA-approved drugs. Among other things, this means the compounded drug may not be identical or nearly identical to an FDA-approved drug unless the approved drug is on FDA’s drug shortage list. These pharmacies choose to be tested by, inspected by, and report adverse events to the FDA.
FDA Rulings
The FDA has reported some concerns with compounded versions of semaglutide and tirzepatide. Adverse events have been reported due to dosing errors, including patients incorrectly measuring their intended compounded semaglutide dose and health care providers miscalculating the intended dose. Additionally, adverse events have been reported in patients prescribed compounded semaglutide (Ozempic; Novo Nordisk) or tirzepatide products at doses higher than those approved by the FDA. Some compounded semaglutide products may contain salt forms rather than base forms, which differ from the approved drug formulations.7
The FDA reported other safety concerns, including illegal online sales, counterfeit Ozempic, and versions of unapproved drugs containing semaglutide, tirzepatide, or experimental retatrutide sold falsely for “research purposes or not for human consumption”.8
The FDA placed tirzepatide on the shortage list in December 2022, and many patients’ demands were then met by compounding and outsourcing facilities. According to the FDA, GLP-1 agonists semaglutide and liraglutide are still in shortage, although the tirzepatide status was recently listed as “resolved” on October 2, 2024. After the FDA declared the tirzepatide shortage resolved, compounding pharmacies could fill no new orders and had 60 days to fill existing prescriptions.9
On October 7, 2024, a compounding trade group filed a lawsuit against the FDA claiming that the agency ignored evidence that the drug is still in short supply and did not follow reasoned rulemaking in its decision. The FDA requested a stay until November 21, 2024, to reevaluate and reconsider its decision to remove tirzepatide from the shortage list. During this stay, the FDA would not take any action plaintiff compound pharmacists.10,11
How Can Pharmacists Help Ensure Patient Safety?
Providers who choose to prescribe compounded GLP-1 agonists can take certain steps to help ensure patients receive these medications safely. Pharmacists can educate patients about how to recognize unsafe online sources of medications and ensure patients are properly educate on how to administer their medications.
Compounding pharmacies should ensure that their sources for active pharmaceutical ingredients are safe and verify that suppliers are registered with the FDA. Compounding pharmacies should also be accredited by the Pharmacy Compounding Accreditation Board, signaling that they have been assessed for processes related to quality improvement. Similarly, pharmacies should be a designated 503B compounder. When asked, pharmacies can provide a certificate of analysis detailing quality and composition information about the product.
While waiting for the FDA’s ruling in November, clinicians can verify compounding pharmacies’ credentials when prescribing much needed medications during times of shortages and pharmacists can educate patients and providers about lingering questions and challenges.
REFERENCES
1. Harris E. Poll: roughly 12% of US adults have used a GLP-1 drug, even if unaffordable. JAMA. 2024;332(1):8. doi:10.1001/jama.2024.10333
2. Tichy EM, Hoffman JM, Tadrous M, et al. National trends in prescription drug expenditures and projections for 2024. Am J Health-Syst Pharm. 2024;81(14):583-598. doi:10.1093/ajhp/zxae105
3. Tirrell M. The end of a shortage of popular weight-loss drugs may mean many people lose access to them. CNN. October 9, 2024. Accessed October 22, 2024. https://www.cnn.com/2024/10/09/health/tirzepatide-compounded-weight-loss-drugs/index.html
4. How much should I expect to pay for Zepbound? Lilly. Accessed October 22, 2024. https://pricinginfo.lilly.com/zepbound
5. Weight loss medication, the right way, with Noom. Accessed October 22, 2024. https://www.noom.com/med/
6. Einav E. The truth abount compounded GLP-1s that doctors need to know. Medscape Diabetes & Endocrinology. 2024. Accessed October 22, 2024. https://www.medscape.com/viewarticle/1000503
7. What is Pharmacy Compounding? Alliance for Pharmacy Compounding. Accessed October 22, 2024. https://a4pc.org/whatiscompounding
8. FDA’s Concerns with Unapproved GLP-1 Drugs Used for Weight Loss. FDA. Updated October 2, 2024. Accessed October 22, 2024. https://www.fda.gov/drugs/postmarket-drug-safety-information-patients-and-providers/fdas-concerns-unapproved-glp-1-drugs-used-weight-loss
9. FDA clarifies policies for compounders as national GLP-1 supply begins to stabilize. News release. FDA. October 2, 2024. Accessed October 22, 2024. https://www.fda.gov/drugs/drug-safety-and-availability/fda-clarifies-policies-compounders-national-glp-1-supply-begins-stabilize
10. Gallagher A. Outsourcing Facilities Association sues FDA over sudden removal of tirzepatide from drug shortage list. Pharmacy Time. October 14, 2024. Accessed October 22, 2024. https://www.pharmacytimes.com/view/outsourcing-facilities-association-sues-fda-over-sudden-removal-of-tirzepatide-from-drug-shortage-list
11. FDA reconsiders on tirzepatide, big questions remain. News release. Alliance for Pharmacy Compounding. October 15, 2024. Accessed October 22, 2024. https://a4pc.org/2024-10/fda-reconsiders-on-tirzepatide-big-questions-remain/
