FDA Alerts on Overdosing Risks with Compounded Semaglutide Due to Dosing Errors and Variability

On July 26, the FDA issued a warning after receiving reports of dosing mistakes with compounded semaglutide injectable products dispensed from multidose vials. These errors have led to adverse effects such as gastrointestinal issues, fainting, dehydration, headaches, gallstones, and acute pancreatitis, with some patients requiring hospitalization.

FDA-approved semaglutide products are standardized in milligram dosages and come only in prefilled pens, ensuring consistency and reducing the risk of dosing errors. In contrast, compounded semaglutide products may vary significantly. They can come in multidose vials or prefilled syringes, and their concentrations can differ depending on the compounder. Some compounders may offer multiple concentrations, complicating accurate dosing.

Semaglutide is a medication classified as a glucagon-like peptide-1 (GLP-1) receptor agonist. Currently, there are three FDA-approved semaglutide products:

• WEGOVY: Available as single-dose pre-filled pens, WEGOVY is designed for weekly administration with a preset dose.
• OZEMPIC: This product comes in multiple-dose pre-filled pens intended for single-patient use, and also for once-weekly dosing.
• RYBELSUS: Offered as oral tablets, RYBELSUS is used for daily administration.

Instructions for compounded drugs may specify doses in "units" rather than milligrams, and these units can vary with concentration. This discrepancy can lead to patients receiving syringes with volumes much larger than prescribed.

The FDA has documented instances where patients inadvertently took doses from multidose vials that were 5 to 20 times higher than prescribed. Errors often occur when clinicians miscalculate doses during conversions from milligrams to units or milliliters. For example, one patient, unable to clarify dosing instructions from a telemedicine provider, sought online advice and ended up taking five times the intended dose.

In another case, a clinician prescribed 20 units instead of the correct dose of 2 units, leading to three patients receiving ten times the intended dose and experiencing symptoms like nausea and vomiting. Additionally, a clinician, who also used semaglutide, mistakenly administered a dose ten times higher than intended.

The FDA has previously cautioned about the risks associated with compounded drugs, especially during shortages like that of semaglutide. While compounded drugs can be beneficial in some cases, they generally pose a higher risk than FDA-approved drugs because they do not undergo the same rigorous premarket review for safety, effectiveness, or quality.

"FDA recognizes the substantial consumer interest in using compounded semaglutide products for weight loss. However, compounded drugs pose a higher risk to patients than FDA-approved drugs because compounded drugs do not undergo FDA premarket review for safety, effectiveness, or quality," the FDA stated.

"Therefore, compounded drugs should only be used to meet a patient's needs if they cannot be met by an available FDA-approved drug," the agency concluded.