Moving beyond promethazine: Advancing precision in antiemetic therapy.

Abstract

Promethazine has long been a cornerstone in the management of nausea and vomiting (N/V) in emergency medicine; however, its safety profile-including risks of severe tissue injury and respiratory depression-has prompted renewed scrutiny. Nausea and vomiting arise from complex interactions between central and peripheral pathways involving the chemoreceptor trigger zone, vagal afferents, and multiple neurotransmitter systems, including dopamine (D2), serotonin (5-HT3), histamine (H1), muscarinic (M1), and neurokinin-1 (NK1) receptors. This manuscript presents a focused narrative review and expert commentary examining the evolving role of promethazine in modern clinical practice. Drawing on regulatory guidance, contemporary literature, and institutional experience, we evaluate the risks associated with injectable promethazine and the rationale for transitioning toward safer alternatives. At our institution, removal of injectable promethazine from the formulary was guided by multidisciplinary consensus and aligned with updated safety recommendations. Alternative agents, including dopamine antagonists and 5-HT3 receptor antagonists, provide comparable or superior efficacy with improved safety profiles. Advances in antiemetic therapy now support a multimodal, receptor-targeted approach, combining agents that act on complementary pathways to improve symptom control while minimizing adverse effects. While clinical contexts such as chemotherapy-induced and postoperative nausea and vomiting differ in etiology and guideline-based management, they share overlapping receptor pathways that allow for a unified pharmacologic framework. Although intravenous promethazine remains in use in some settings, evolving safety data and regulatory guidance have led to progressive restriction and, in many institutions, elimination of its parenteral use. Given the availability of safer and more targeted therapies, the continued routine use of injectable promethazine warrants critical reassessment. This shift reflects a broader movement toward precision, safety, and evidence-based practice in antiemetic management and highlights the importance of aligning clinical practice with contemporary pharmacologic understanding.