Promethazine, sold under the brand name Phenergan among others, is a first-generation antihistamine, sedative, and antiemetic used to treat allergies, insomnia, and nausea.

It may also help with some symptoms associated with the common cold[4] and may also be used for sedating people who are agitated or anxious, an effect that has led to some recreational use (especially with codeine).

[4] Common side effects of promethazine include confusion and sleepiness;[4] consumption of alcohol or other sedatives can make these symptoms worse.

[25] Anticholinergic effects like dry mouth, dilated pupils, flushing, gastrointestinal symptoms, and delirium may occur as well.

[2] Despite structural differences, promethazine exhibits a strikingly similar binding profile to promazine,[26] another phenothiazine compound.

[43] The team was seeking to improve on diphenhydramine; the same line of medical chemistry led to the creation of chlorpromazine.

[44] As of July 2017, it is marketed under many brand names worldwide: Allersoothe, Antiallersin, Anvomin, Atosil, Avomine, Closin N, Codopalm, Diphergan, Farganesse, Fenazil, Fenergan, Fenezal, Frinova, Hiberna, Histabil, Histaloc, Histantil, Histazin, Histazine, Histerzin, Lenazine, Lergigan, Nufapreg, Otosil, Pamergan, Pharmaniaga, Phenadoz, Phenerex, Phenergan, Phénergan, Pipolphen, Polfergan, Proazamine, Progene, Prohist, Promet, Prometal, Prometazin, Prometazina, Promethazin, Prométhazine, Promethazinum, Promethegan, Promezin, Proneurin, Prothazin, Prothiazine, Prozin, Pyrethia, Quitazine, Reactifargan, Receptozine, Romergan, Sominex, Sylomet, Xepagan, Zinmet, and Zoralix.

In September 2009, the FDA required a boxed warning be put on promethazine for injection, stating the contraindication for subcutaneous administration.

The preferred administrative route is intramuscular, which reduces the risk of surrounding muscle and tissue damage.