While glucagon-like peptide-1 (GLP-1) agonists for diabetes and weight loss remain in short supply, some clinicians have turned to compounding pharmacies to fill prescriptions. Yet news reports and social media posts have called compounded products "knockoffs" and "counterfeit" and lumped them in with illicit products.
Meanwhile, Novo Nordisk and Eli Lilly, makers of semaglutide and tirzepatide, respectively, have filed several lawsuits against compounding pharmacies alleging various claims, including that they are violating marketing rules and producing unauthorized products.
Compounding pharmacies are pushing back. The industry says it is being confused with unregulated companies selling purported semaglutide and tirzepatide, the active ingredients in blockbuster diabetes and weight loss drugs.
Scott Brunner, CEO of the Alliance for Pharmacy Compounding (APC), said misconceptions about the industry may make clinicians reluctant to prescribe any compounded drug, even when a patient could benefit from a custom dosage or when an essential drug is in shortage, as is the case with GLP-1 agonists.
"What these online sites are doing is selling directly to a patient without a prescription, and they're telling the patient, 'Hey, this is semaglutide.' In some instances, it may well be — it's often marked 'research grade,' " Brunner said, adding that unlike with a compounded medication, a purchaser cannot verify what they are buying. "It's absolutely sketchy stuff. But that's not pharmacy, and that's not compounding."
The US Food and Drug Administration allows compounding pharmacies, normally tasked with making custom formulations, to produce "essentially a copy of a commercially available drug" when that drug is in short supply.
APC, which represents about 130 facilities, issued a statement in October to correct "misstatements and errors" it said have appeared in media stories and communications from state boards of pharmacy.
APC also said scammers posing as legal compounding pharmacies may be contributing to perceptions that compounded drugs are unsafe. It recently alerted FDA regulators about a flyer advertising "GLP-1 mimickers" faxed to physician offices by a company falsely claiming to be an accredited compounder.
Provider Trepidation
The worry of the APC is not unfounded: some clinicians said they do not prescribe compounded GLP-1 drugs, citing a lack of certainty about ingredients and safety.
Fatima Cody Stanford, MD, MPH, MPA, an obesity specialist at Massachusetts General Hospital and Harvard Medical School, told Medscape Medical News she "won't consider compounding," even as some of her patients wait months to receive their first doses of branded GLP-1 drugs.
"I don't have any data to support the compounded medication," Stanford said. Without the ability to show her patients clinical trial data that go with FDA approval, she said, "I won't use it."
Stanford said she often prescribes older drugs that are commercially available, such as phentermine-topiramate or naltrexone-bupropion combinations, while a patient waits for a GLP-1 product. That way, she said, her patients "are not just sitting there, not on anything."
According to the FDA, compounded drugs do pose a greater risk of contamination and dosing errors than commercially available drugs because compounded versions do not undergo a premarket review for safety, effectiveness, or quality. Compounding pharmacies bulk order the same active ingredients found in an FDA-approved drug and prepare them on site, usually in much smaller batches made to order.
Compounding advocates acknowledge that prescribers should opt for a commercially available drug when possible, but resist the idea that compounded drugs are inherently risky. Brunner said compound pharmacies operate under a rigorous compliance framework.
For semaglutide, the manufacturer's clinical trial data offer " some reasonable level of confidence to support the use of the [active ingredient] in a compounded preparation," Brunner said.
The extent of safety issues with compounded GLP-1 drugs is unclear, according to the FDA, which in May cautioned that it received adverse event reports associated with compounded semaglutide. It also cited accounts of compounders using a different active ingredient than that in the commercially available drug.
Charles Kohler, a spokesperson for the agency, told Medscapethat as of October 27, the agency had received more than 95 reports of adverse events linked to compounded semaglutide.
"While many of the events appear to be consistent with certain adverse events included in labeling for FDA-approved semaglutide products, the FDA is unable to determine how or if other factors, such as differences in ingredients and formulation between FDA-approved and compounded semaglutide products, may have contributed," Kohler said.
Compounding pharmacies that distribute bulk orders to facilities such as hospitals are required to report "serious and unexpected" adverse events to the FDA, but community compounding pharmacies that fill prescriptions for individual patients do not have the same rule.
Kohler said the FDA's "ability to derive conclusions about safety concerns," is limited by the variable quality and low number of reports.
Ultimately, individual clinicians must decide whether they want to prescribe a compounded drug, Rita Jew, PharmD, MBA, president of the nonprofit Institute for Safe Medication Practices, told Medscape Medical News. Compounding pharmacies tend to use less automation, which Jew said can increase the chance for errors with potency or contamination, including lapses in sterilization. In addition, she noted that states have varying levels of regulatory oversight.
As with any intervention, "the doctor needs to balance the risk vs the benefit," in prescribing a compounded drug, Jew said.
A Boon for Patients
Despite widespread hesitancy about compounded drugs, some clinicians say these versions are a boon for patients, who pay about a third of what they would for brand-name products, which run $900 to $1350 for a four-week supply. Insurers often do not pay for the drugs.
Using a compounder allows physicians to precisely tailor doses to minimize side effects and control the rate of weight loss, David Wertheimer, MD, a cardiologist and internist at the Wertheimer Center for Functional Medicine in Franklin Lakes, New Jersey, told Medscape.
Wertheimer said he has prescribed compounded weight loss drugs to more than 50 of his patients, many of whom have found the versions "incredibly effective." He said he has confidence in his local compounding pharmacy, which he has worked with for years.
"The one I use is accredited. It's a state-regulated facility, and they're very fastidious about the work they do," including sending a sample of each batch of semaglutide to an independent lab to assure purity and formula accuracy , he said.
Wertheimer said he dreads the day the shortages end.
"You just hope that if compounders are stopped from doing this, that there's going to be a cost-effective alternative for people," he said.
To an extent, manufacturers are already trying to curb compounding. Last month Novo Nordisk sued two compounding pharmacies in Florida, claiming the facilities sold products with impurities and incorrect potency.
Vetting a Pharmacy
For clinicians who want to prescribe compounded drugs, experts suggested several steps for vetting a pharmacy and its products:
- For a community pharmacy that dispenses individual prescriptions, verify on the state board of pharmacy website that it is licensed in the state where the patient resides and has a clean disciplinary record.
- For an outsourcing facility that distributes bulk products, check its FDA registration and inspection records.
- Request a facility tour.
- Check whether the company has Pharmacy Compounding Accreditation Board accreditation, which is based on compliance with quality and safety standards set by United States Pharmacopeia (USP).
- Ask where ingredients are sourced and whether they meet USP requirements. Ask for a certificate of analysis to verify a drug's active ingredient.
- Ask for documentation that the drug has undergone potency and sterility testing.
Wertheimer recommends maintaining a dialogue with compounding pharmacists for both clinical advice and to provide confidence in the quality of the operation.
"Like in any area of medicine, there are ethical players and there are people who don't play by the rules," he said.
Brunner, Jew, Kohler, and Wertheimer report no relevant financial relationships. Stanford accepted payments for consulting, travel and lodging, and food and beverage from Novo Nordisk and Eli Lilly, according to Open Payments.
Mary Chris Jaklevic is a healthcare journalist in the Midwest.
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