Sonya Collins
Fueled by celebrity endorsements, the increasing popularity of semaglutide injection (Wegovy—Novo Nordisk and Ozempic—Novo Nordisk) as a highly effective weight loss drug helped land it on FDA’s shortage list last year, where it remains today.
In the event of an FDA-recognized shortage, 503A compounding pharmacies are authorized to produce “essential copies” of the drug for patients who have a prescription. However, some facilities may be producing unauthorized “look-alikes.” Drugmaker NovoNordisk and some state boards of pharmacy have begun to issue warnings and take action against these alleged bad actors.
The controversy
Federal regulations allow 503A compounding facilities to use active pharmaceutical ingredients to make compounded versions of drugs that are in FDA-recognized shortage for patient-specific prescriptions. But FDA has received reports of adverse reactions with compounded semaglutide. It has also received reports of compounded products containing semaglutide salts, which may or may not be behind the adverse reactions.
“Salt forms, such as semaglutide sodium or semaglutide acetate, may have different aqueous solubility than that of the base form of semaglutide,” said Jasmine Gonzalvo, PharmD, a clinical professor in the College of Pharmacy and director of the Center for Health, Equity and Innovation at Purdue University in Indiana. “These differences in solubility could affect the rate and extent of absorption of the compounded formulations, particularly when combined with other ingredients. The safety and effectiveness risks associated with these differences are unknown at this time.”
In response to reports of salt-based compounded semaglutide products, FDA’s F. Gail Bromel, RPh, JD, director of the Center for Drug Evaluation and Research Office of Compounding Quality and Compliance, wrote a letter to the executive director of the National Association of Boards of Pharmacy. She wrote, “We also wish to ensure [the executive director is] aware that the active pharmaceutical ingredient in Wegovy and Ozempic is semaglutide in its base form. We are aware that in some cases compounders may be using salt forms of semaglutide, including semaglutide sodium and semaglutide acetate. We are not aware of any basis for compounding a drug using these semaglutide salts that would meet federal law requirements that limit the types of active ingredients that can be used in compounding.”
Some state boards of pharmacy have released statements or issued warnings reiterating the FDA’s position on semaglutide salts. NovoNordisk has started legal action against some facilities, including med spas and clinics, believed to be producing unauthorized semaglutide products.
Some facilities claim to have received cease-and-desist letters from the drugmaker, though they are in compliance with FDA regulations.
“Any compounding pharmacies who have received warnings from the drug manufacturer should seek legal counsel,” Gonzalvo said.
Looking ahead
While Novo Nordisk is currently producing and shipping all dose strengths of Wegovy, prescribing continues to outpace production. According to its website, Novo Nordisk anticipates it will be unable to fully meet demand for 0.25 mg, 0.5 mg, and 1 mg dose strengths through September 2023. It does not expect any interruptions in the supply of its 1.7 mg and 2.4 mg products.
Until supply once again surpasses patient and provider demand, Gonzalvo said that for pharmacists compounding semaglutide, legal ramifications should be prioritized.
In the face of safety concerns about compounded semaglutide, community pharmacists who are unable to fill patient prescriptions for semaglutide as written, might explore alternative strategies with prescribers, such as
- Using one to two doses of available lower doses to achieve a higher prescribed dose
- Changing to another GLP-1 agonist
- Prescribing another medication class for weight loss
“Currently, insufficient data are available to support the safe or effective use of compounded formulations of GLP-1 agonists,” said Gonzalvo. “Safety risks can likely be minimized if patients get their prescriptions filled at state-licensed compounding pharmacies that are able to obtain the base form of semaglutide from FDA-registered facilities, ensure sterility during the compounding process, and avoid the addition of other ingredients with unknown potential for interactions.” ■