FDA issues promethazine warning

Sep 27, 2009

Promethazine (Phenadoz, Phenergan, Promethegan) can cause gangrene and should only be used in a deep intramuscular injection, according to a warning from the U.S. FDA.

Promethazine is used in dentistry for control of postextraction edema, pain, trismus, and preoperative sedation. Perivascular extravasation, unintentional intra-arterial injection, and intraneuronal or perineuronal infiltration of the drug may result in irritation and tissue damage, including gangrene, according to the FDA.

The agency is telling manufacturers of the drug promethazine to include a boxed warning regarding the injectable form of the drug.

It is requesting that the drug makers revise the dosage and administration section of the label to state that if healthcare professionals choose to administer promethazine intravenously, they should limit the drug's concentration and rate of administration and ensure a properly functioning intravenous line.

The companies that make promethazine are required to submit the requested safety label changes to the FDA within 30 days or provide a reason why they do not believe such changes are necessary. If they do not submit new language, or the FDA disagrees with the language proposed by the companies, the agency can order the label change as deemed appropriate to address the new safety information.

Promethazine was previously sold under the brand name Phenergan, but that formulation was discontinued by Wyeth Pharmaceuticals. A number of companies currently market generic formulations of promethazine hydrochloride injection.

The FDA previously informed consumers and healthcare professionals about the risks of incorrect administration of promethazine in the December 2006 and February 2008 editions of FDA Patient Safety News. Current prescribing information for the drug contains information about the risk of tissue injury, possibly including gangrene, if the drug is inadvertently administered in the artery, but that information was not highlighted in a boxed warning.

Promethazine first went on the market in 1956. The FDA has reviewed the published literature and postmarketing adverse event reports submitted to its Adverse Event Reporting System from 1969 to 2009 and identified cases of gangrene requiring amputation associated with administration of the drug, according to the FDA.

More information is available on the FDA Web site.