FDA alerts patients and prescribers to overdoses from compounded semaglutide unit-conversion errors

The U.S. Food and Drug Administration issued an alert on July 26, 2024, warning health care providers, compounders and patients about dosing errors with compounded injectable semaglutide products ^[3]. The agency said it had received reports of adverse events, some requiring hospitalization, tied to overdoses from products dispensed in multiple-dose vials ^[1]. FDA sent the alert to its MedWatch subscriber list on July 29 ^[2].

The errors came from two directions: patients measuring and self-administering the wrong amount, and health care providers miscalculating the dose in the first place ^[1].

What went wrong

Most of the reports described patients drawing up more than the prescribed dose from a multiple-dose vial. In those cases, patients gave themselves five to 20 times the intended dose of semaglutide ^[1]. Most reports indicated the patients did not know how to measure the intended dose with a syringe ^[1].

Many patients who received vials had no experience with self-injection, according to the adverse event reports. FDA said unfamiliarity with pulling medication from a vial into a syringe, combined with confusion between milliliters, milligrams and "units," may have contributed ^[1].

One pattern appeared repeatedly: patients were told to use a U-100 (1 milliliter) insulin syringe to draw a small dose, such as 5 units (0.05 milliliter). Some of those patients drew 50 units instead ^[1]. In another reported case, a patient could not get clear dosing instructions from the telemedicine provider who wrote the prescription, searched online for advice, and ended up taking five times the intended dose ^[1].

Providers made conversion errors too, producing doses five to 10 times too high ^[1]. FDA described three specific examples: one provider meant to prescribe 0.25 milligrams (5 units) but wrote 25 units, and the patient had severe vomiting; another prescribed 20 units instead of 2 units, affecting three patients who got 10 times the intended dose and had nausea and vomiting; and a patient who is himself a health care provider tried to recalculate his own dose in units and gave himself 10 times too much ^[1][3].

Reported harms included gastrointestinal effects such as nausea, vomiting and abdominal pain, plus fainting, headache, migraine, dehydration, acute pancreatitis and gallstones ^[1]. FDA did not publish a total number of reports or hospitalizations in the alert.

Why the vials are different

FDA-approved semaglutide injections are dosed in milligrams, come in standard concentrations, and are sold only in pre-filled pens: Wegovy in single-dose pens, Ozempic in multiple-dose pens for one patient ^[1]. Rybelsus is an oral tablet ^[1].

Compounded semaglutide is not standardized. FDA said compounders offer it in multiple-dose vials and prefilled syringes, that concentrations vary between compounders, and that a single compounder may sell several different concentrations ^[1]. Instructions, when provided, may tell users to inject a number of "units" — an amount whose actual volume depends on the concentration — rather than milligrams or milliliters ^[1]. FDA also said some patients were given syringes much larger than the volume they were supposed to draw ^[1].

Compounded drugs do not go through FDA premarket review for safety, effectiveness or quality, and the agency said they should be used only when an approved drug cannot meet a patient's needs ^[1].

Why it matters for patients

The practical difference here is not the molecule; it is the container and the arithmetic. A pen delivers a preset dose. A vial requires the person holding the syringe to convert a prescription into a volume, and FDA's reports show that conversion failing in both directions — at the prescriber's desk and at the kitchen table ^[1].

Semaglutide also has a half-life of about one week, so an overdose is not something that clears in a few hours. FDA notes that a prolonged period of observation and treatment may be needed ^[1]. Labeling for approved semaglutide injections describes overdose effects reported with other GLP-1 drugs, including severe nausea, severe vomiting and severe low blood sugar ^[1].

FDA's stated expectations were that patients talk with their provider or compounder about how to measure and give the intended dose, that compounders supply a syringe sized for that dose and counsel patients on using it, and that prescribers confirm the concentration with the compounder when unsure ^[1][2].

Poison centers have seen the same pattern. A Washington Poison Center article reports GLP-1 exposure calls nationally rising from about 2,500 in 2022 to 4,700 in 2023 and 8,500 in 2024, with many patients accidentally taking 10-fold overdoses; about half of that center's calls involved compounded semaglutide or tirzepatide dispensed in vials, with dosing in units cited as a source of confusion ^[4].

Anyone who suspects an overdose can reach a regional poison center at 1-800-222-1222 ^[4]. FDA asks that dosing errors be reported through MedWatch ^[1].