FDA notified healthcare professionals that a Boxed Warning is being added to the prescribing information for Promethazine Hydrochloride products, describing the risks of severe tissue injury, including gangrene, requiring amputation following intravenous administration of promethazine. The Boxed Warning will remind practitioners that due to the risks of intravenous injection, the preferred route of administration is deep intramuscular injection and that subcutaneous injection is contraindicated.

Perivascular extravasation, unintentional intra-arterial injection and intraneuronal or perineuronal infiltration of the drug may result in irritation and tissue damage. Healthcare professionals should be alert for signs and symptoms of potential tissue injury including burning or pain at the site of injection, phlebitis, swelling, and blistering.

Considerations for Healthcare Professionals:

Intravenous administration of promethazine can cause severe tissue injury, including gangrene, requiring fasciotomy, skin graft, and/or amputation

Severe tissue injury can occur from perivascular extravasation, unintentional intra-arterial injection, and intraneuronal or perineuronal infiltration

Deep intramuscular injection is the preferred way to administer promethazine hydrochloride injection, USP products

Intra-arterial and subcutaneous administration of promethazine are contraindicated

Promethazine hydrochloride injection, USP is available in two strengths, 25 mg/mL and 50 mg/mL

The 50 mg/mL promethazine hydrochloride injection, USP product is for deep intramuscular injection only

The 25 mg/mL promethazine hydrochloride injection, USP product may be administered by deep intramuscular injection or intravenous injection (see maximum dosage and rate below)

If intravenous administration of promethazine is required, the maximum recommended concentration is 25 mg per mL and the maximum recommended rate of administration is 25 mg per minute through the tubing of an intravenous infusion set known to be functioning properly

Be alert for signs and symptoms of potential tissue injury including burning or pain at the site of injection, phlebitis, swelling, and blistering

Injections should be stopped immediately if a patient complains of pain during injection

Inform patients that side effects may occur immediately while receiving the injection or may develop hours to days after an injection

Refer to the prescribing information for additional information on warnings, contraindications, adverse events, and dosage and administration of promethazine hydrochloride injection, USP products

Promethazine should not be used in patients less than 2 years of age due to the risk of fatal respiratory depression

Information for Patients:

Discuss any concerns you may have about the risks and benefits of promethazine with a health care professional

Pay close attention for any signs or symptoms of adverse events including burning or pain at the injection site, redness, swelling, and blistering, and report these symptoms immediately

Understand that side effects may occur immediately while receiving a promethazine