FDA Warns of Overdoses With Compounded Semaglutide

Overdoses, some even requiring hospitalization, have occurred due to patient and physician confusion around compounded semaglutide, the FDA detailed in an alert.

Adverse events reported to the agency have ranged from gastrointestinal events like nausea, vomiting, and abdominal pain — the most common side effects with GLP-1 receptor agonists — to fainting, headache, migraine, dehydration, acute pancreatitis, and gallstones.

While FDA-approved injectable semaglutide (Ozempic, Wegovy) is dosed in milligrams and only comes in prefilled pens, compounded semaglutide can come in varying concentrations (depending on the compounder or even by the same compounder) and uses multiple-dose vials.

Both patients’ incorrect self-administration and healthcare providers’ dose miscalculations have been at play.

“Many of the patients who received vials of compounded semaglutide lacked experience with self-injections, according to the adverse event reports,” the FDA explained. “Unfamiliarity with withdrawing medication from a vial into a syringe and coupled with confusion between different units of measurement (e.g., milliliters, milligrams, and ‘units’) may have contributed to dosing errors.”

In some cases, patients have administered five- to 20-times more than the intended dose of semaglutide after mistakenly drawing up more than the prescribed dose from a multiple-dose vial. As noted in several reports, patients were instructed to use a U-100 (1 mL) insulin syringe to draw up small doses like a 5-unit (0.05 mL) dose but mistakenly administered 50 units instead.

“In one reported case, it was difficult for the patient to obtain clarity on dosing instructions from the telemedicine provider, who prescribed the compounded semaglutide, leading the patient to conduct an online search for medical advice and resulting in the patient taking five times the intended dose,” the FDA added.

Other reports described how healthcare providers were the ones incorrectly calculating the intended dose when converting from milligrams to units or milliliters, leading to doses five- to 10-times higher than the intended dose. For example, one healthcare provider intended to dose 0.25 mg (5 units) but accidentally prescribed 25 units instead, leading to severe vomiting for the patient.

Another healthcare provider prescribed 20 units instead of 2 units to three patients, all of whom later experienced nausea and vomiting. One healthcare provider who self-prescribed the drug tried to recalculate their own dose in units and accidentally self-administered a dose 10-times higher than intended.

The FDA said healthcare providers should “be vigilant” when prescribing compounded semaglutide and to contact the compounder about calculating the dose if there is any uncertainty. Providers and compounders should also give patients the appropriate syringe size for the intended dose and teach patients how to measure the intended dose using the syringe.

Compounded semaglutide grew in popularity over the past few years due to the spike in demand for GLP-1 receptor agonists that led to supply and access issues. But, the FDA said, compounded drugs should only be used for patients whose medical needs cannot be met by an available FDA-approved drug.

Compared with Novo Nordisk’s branded semaglutide, compounded versions can pose higher risks to patients because they don’t undergo the same FDA premarket review for safety, quality, or effectiveness.

Novo Nordisk has taken legal action on compounded semaglutide. One review found high levels of known impurities and the presence of unknown impurities in some compounded semaglutide products. And one product tested consisted of more than 24% impurities, including unknown ones.

Once-weekly injectable semaglutide was first approved for type 2 diabetes (Ozempic) in 2017. In 2021, it was approved in a higher dose for chronic weight management (Wegovy) in adults with obesity (BMI ≥30) or who are overweight (BMI ≥27) with at least one weight-related condition. Most recently, it gained an indication to reduce the risk of cardiovascular death, heart attack, and stroke in adults with cardiovascular disease and either obesity or overweight.

The FDA said it’s aware of compounded semaglutide products that are being marketed for weight loss and recognizes the “substantial” interest.

The agency asked compounders, healthcare providers, and patients to report adverse events and errors with compounded semaglutide to its MedWatch Adverse Event Reporting program.

Kristen Monaco is a senior staff writer, focusing on endocrinology, psychiatry, and nephrology news. Based out of the New York City office, she’s worked at the company since 2015.

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