FDA alerts health care providers, compounders and patients of dosing errors associated with compounded injectable semaglutide products

What health care providers, compounders and patients should know

FDA has received reports of adverse events, some requiring hospitalization, that may be related to overdoses due to dosing errors associated with compounded semaglutide injectable products. Dosing errors have resulted from patients measuring and self-administering incorrect doses of the drug and health care providers miscalculating doses of the drug.

FDA encourages patients to talk with their health care provider or compounder about how to measure and administer the intended dose of compounded semaglutide.

Many of the patients who received vials of compounded semaglutide lacked experience with self-injections, according to the adverse event reports. 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.

FDA encourages health care providers and compounders to provide patients with the appropriate syringe size for the intended dose and counsel patients on how to measure the intended dose using the syringe.

Additionally, health care providers should be vigilant when prescribing and administering compounded semaglutide, as there may be different concentrations available. If uncertain, health care providers should contact the compounder about calculating the correct dose of medication to prescribe or administer.

Background

Semaglutide belongs to a class of medications known as glucagon-like peptide-1 (GLP-1) receptor agonists. There are currently three FDA-approved semaglutide products:

• WEGOVY injection is available as single-dose pre-filled pens that deliver a preset dose for once weekly dosing.
• OZEMPIC injection is available as multiple-dose pre-filled pens for single-patient use, designed for once-weekly dosing.
• RYBELSUS tablet is available as oral tablets for daily dosing.

The prescribing information for FDA-approved semaglutide injection contains information about overdoses that have been reported with other GLP-1 receptor agonists. Adverse effects include severe nausea, severe vomiting and severe hypoglycemia (low blood sugar levels). A prolonged period of observation and treatment for overdose symptoms may be necessary due to the long half-life of semaglutide of about one week.

FDA is aware of compounded semaglutide products that are being marketed for weight loss.

Compounded drugs pose a higher risk to patients than FDA-approved drugs because compounded drugs do not undergo FDA premarket review for safety, quality or effectiveness. Compounded drugs should only be used for patients whose medical needs cannot be met by an available FDA-approved drug.

Compounded products containing semaglutide

There are various ways that compounded semaglutide products may differ from approved products[1] [2] that may contribute to potential medication errors. For example, FDA is aware that compounders offer semaglutide injectable products in various containers and packaging, including multiple-dose vials and prefilled syringes. Product concentrations also may vary depending on the compounder, and a single compounder may offer multiple concentrations of compounded semaglutide products.

Additionally, the instructions that accompany the compounded drug, if provided, may instruct users to administer semaglutide injections in “units” (the volume of which may vary depending on the concentration), rather than milligrams or milliliters. FDA is aware of some instances in which patients have been given syringes that are significantly larger than the prescribed volume of semaglutide (see example in Figure 1). These factors may cause confusion for health care providers when prescribing or dispensing and for patients who are measuring and self-administering these compounded products.

Adverse event summary

FDA has received reports of dosing errors involving compounded semaglutide injectable products dispensed in multiple-dose vials. Some patients sought medical attention or required hospitalization. Adverse events included gastrointestinal effects (e.g., nausea, vomiting, abdominal pain), fainting, headache, migraine, dehydration, acute pancreatitis and gallstones.

Errors related to incorrect measurement of intended compounded semaglutide dose

The majority of the reports described patients mistakenly drawing up more than the prescribed dose from a multiple-dose vial during self-administration. In these instances, patients administered five to 20 times more than the intended dose of semaglutide. Most of the reports indicated that patients were unfamiliar with how to measure the intended dose using a syringe.

In several reports, patients were instructed to use a U-100 (1 milliliter) insulin syringe to draw small doses, such as a 5-unit (0.05 milliliter) dose, from a multiple-dose vial.

As depicted in the figure below, these patients were directed to administer 5 units from a vial. However, these patients mistakenly administered 50 units instead.

Figure 1. U-100 insulin syringe with fill volume of 5 units and 50 units

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.

Errors related to compounded semaglutide dose miscalculations

FDA-approved injectable semaglutide products are dosed in milligrams, have standard concentrations and are currently only available in pre-filled pens. FDA is aware that compounders provide semaglutide in various concentrations.

Several reports describe health care providers incorrectly calculating the intended dose when converting from milligrams to units or milliliters, which resulted in patients administering five to 10 times more than the intended dose of semaglutide.

• One provider intended to dose 0.25 milligrams (5 units), but prescribed 25 units instead, leading to a patient receiving five times the intended dose and experiencing severe vomiting.
• Another provider prescribed 20 units instead of 2 units, affecting three patients who, after receiving 10 times the intended dose, experienced nausea and vomiting.
• Additionally, a patient, who is a health care provider, attempted to recalculate their own dose in units and inadvertently self-administered a dose 10 times higher than intended.

Conclusion

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. Therefore, compounded drugs should only be used to meet a patient’s needs if the patient’s medical needs cannot be met by an available FDA-approved drug.

FDA has received reports of dosing errors from patients and health care providers related to these compounded products. There may be a risk of medication dosing errors due to conversion from milligrams to other units of measurement, availability of compounded semaglutide products in varying concentrations and use of multiple-dose vials.

Some patients sought medical attention or required hospitalization after the medication error. Reported semaglutide overdose adverse events include gastrointestinal effects (e.g., nausea, vomiting, abdominal pain), fainting, headache, migraine, dehydration, acute pancreatitis and gallstones.

Report adverse events to FDA

FDA encourages compounders, health care providers and patients to report adverse events and medication errors associated with compounded semaglutide products to FDA’s MedWatch Adverse Event Reporting program.

Complete and submit the report online at MedWatch: The FDA Safety Information and Adverse Event Reporting Program, or
Download and complete the form, then submit it via fax at 1-800-FDA-0178.