The FDA has requested that a boxed warning for promethazine hydrochloride injection products should be provided to better communicate the risks of severe tissue injury associated with the intravenous administration of this drug. Perivascular extravasation, unintentional intra-arterial injection and intraneuronal or perineuronal infiltration of the drug may result in irritation and tissue damage, including gangrene. The boxed warning will also remind practitioners that due to the risks of IV injection, the preferred route of administration is deep IM injection and that subcutaneous injection is contraindicated. This action follows the Agency’s analysis of post-marketing reports of severe tissue injury, including gangrene, requiring amputation following intravenous administration of promethazine, as well as its review of the current prescribing information for these products.