Promethazine: A Review of Therapeutic Uses and Toxicity

Promethazine was first approved in 1951 and has since been used as a treatment option for a variety of indications. A histamine H₁ receptor competitive antagonist with antihistaminic, sedative, anti-kinetotic, antiemetic, and antimuscarinic effects, promethazine is utilized for the treatment of nausea and vomiting, a common reason for emergency department (ED) visits.

This review of promethazine explores its pharmacology and history of toxicities, and discusses current recommendations from patient safety organizations, which implicate its role in therapy.

Injectable promethazine utilization should take into consideration patient-specific factors, institutional policies, medication shortages of alternative agents, and the efficacy and toxicities of injectable promethazine itself. For decades, injectable promethazine has been associated with rare but serious limb-threatening adverse effects after extravasation or inadvertent intra-arterial injection. Patient safety organizations have called for hospitals to remove injectable promethazine from formularies, and the U.S. Food and Drug Administration acted in December of 2023 to change the product labeling, adding dilution and administration recommendations for intravenous administration and stating a preference for intramuscular administration.

Promethazine offers a suitable alternative antiemetic for use in the ED due to its distinct mechanism of action. Injectable promethazine, however, must be used with caution to minimize risk of serious patient harm in the event of intra-arterial or perivascular extravasation when given parenterally.