FDA flags compounded injectable labels tied to 5- to 50-fold dosing errors

The Food and Drug Administration says differences in how compounders and conventional manufacturers display drug strength on small-volume injectable labels have led health care professionals to give patients 5 to 50 times the intended dose, and the agency recommends a specific label format to reduce that risk ^[1].

Conventional manufacturers generally print the strength per total volume as the primary, prominent number on the label. Some compounders instead lead with the strength per milliliter in large type and print the strength per total volume below it in smaller type, according to the alert ^[1]. FDA's compounding risk alert page carries an update date of May 21, 2024; the case reports it describes are dated September 24, 2018 ^[1][2].

Two MedWatch reports describe what happened.

In the first, a patient was prescribed 50 micrograms of fentanyl. The IV bag was labeled with 50 mcg/mL in large font and 2,500 mcg/50 mL below in smaller font, the alert says. The patient received 2,500 mcg, or 50 times the prescribed dose. The product was compounded by an undisclosed facility location owned by Central Admixture Pharmacy Services, according to the report ^[1].

In the second, a patient was prescribed 5 to 10 mg of ketamine as needed for pain. The syringe was labeled Ketamine HCl 10 mg/mL, highlighted in yellow, with the strength per total volume printed beneath in smaller font. The patient received 50 mg, or 5 to 10 times the prescribed dose, and became somnolent, meaning abnormally drowsy. The product was compounded by QuVa Pharma, Inc., of Sugar Land, Texas ^[1].

FDA also described complaints that did not involve a reported overdose. They include phenylephrine 200 mcg/5 mL syringes labeled with 40 mcg per mL in large font, compounded by New England Lifecare Inc. dba Advanced Compounding Solutions of Woburn, Massachusetts; neostigmine 1 mg/mL and succinylcholine 20 mg/mL syringes compounded by KRS Global Biotechnology, Inc., of Boca Raton, Florida; and an IV bag of 4 mg norepinephrine bitartrate in 250 mL 5% dextrose, or 16 mcg per mL, tied to a pump programmed at 16 mg/mL when the ordered concentration was 4 mg/250 mL, compounded by PharMEDium Services, LLC, of Sugar Land, Texas ^[1].

FDA recommends that for small-volume injection products, strength be expressed as quantity per total volume as the primary and prominent expression on the principal display panel, followed in close proximity by quantity per milliliter in parentheses ^[1]. The agency says the advice traces to a draft guidance issued in April 2013, which applies to marketed prescription drugs and CDER-regulated biological products, and to a final guidance issued in May 2022, and is consistent with United States Pharmacopeia General Chapter <7> on labeling ^[1]. The Institute for Safe Medication Practices raised the same concern in a March 22, 2018 newsletter ^[1].

The alert notes that compounded drugs are not evaluated by FDA for safety, effectiveness and quality, and that labels of compounded products are not reviewed by the agency before marketing ^[1].

Why it matters for patients

For an injectable drug, the number that determines how much drug a person receives is the total amount in the container, not the amount in each milliliter. When a label shows only a per-milliliter strength in large type, the total amount in the vial or syringe is not the prominent figure, and FDA's case reports show what happens when the per-milliliter number is read as the total ^[1].

The drugs in the alert's examples are fentanyl, ketamine, phenylephrine, neostigmine, succinylcholine and norepinephrine, not GLP-1 medications. FDA issued a separate alert on July 26, 2024 about dosing errors associated with compounded injectable semaglutide products ^[2]. That alert's title does not state that label strength was the cause, and FDA has not disclosed that link. Whether the compounded semaglutide products involved in the later alert used the labeling format described in the May 2024 alert has not been reported.

FDA encourages patients, consumers and health care professionals to report medication errors and quality problems with compounded drugs to its MedWatch program ^[1][2]. The labeling alert does not announce new enforcement action or a compliance deadline ^[1].

What happens next

The May 21, 2024 labeling alert remains part of FDA's compounding risk alerts list, which the agency uses to notify health care professionals and compounders about risks tied to compounded drugs ^[2]. The alert does not say FDA will require the recommended label format. It says health care professionals should be vigilant when administering compounded products and may consider asking compounders to use the recommended format ^[1].