Clinical data
Trade names Many[1]
AHFS/ Monograph
MedlinePlus a682284
  • AU: C
  • US: C (Risk not ruled out)
    Routes of
    Oral, rectal, IV, IM, topical
    ATC code
    Legal status
    Legal status
    Pharmacokinetic data
    Bioavailability 88% absorbed but after first-pass metabolism reduced to 25% absolute bioavailability[2]
    Protein binding 93%
    Metabolism Hepatic glucuronidation and sulfoxidation
    Elimination half-life 16–19 hours[2][3]
    Excretion Renal and biliary
    CAS Number
    PubChem CID
    ECHA InfoCard 100.000.445
    Chemical and physical data
    Formula C17H20N2S
    Molar mass 284.42 g·mol−1
    3D model (JSmol)
    Chirality Racemic mixture

    Promethazine is a first-generation antihistamine of the phenothiazine family. The drug has strong sedative and weak antipsychotic effects. It also reduces motion sickness and has antiemetic (Histamine H1 receptors but it does not block the production of histamine) and anticholinergic properties. In some countries it is prescribed for insomnia when benzodiazepines are contraindicated. It is available in many countries under many brand names.[1][4] Promethazine was developed in the mid 1940s when a team of scientists from Rhône-Poulenc laboratories were able to synthesize it from phenothiazine.[5]

    Medical uses

    Promethazine has a variety of medical uses, including:

    Side effects

    Some documented side effects include:

    • Tardive dyskinesia (effects due to dopamine D2 receptor antagonism)
    • Confusion in the elderly
    • Drowsiness, dizziness, fatigue, more rarely vertigo
    • Dry mouth
    • Respiratory depression in patients under age of two and in those with severely compromised pulmonary function
    • Constipation
    • Chest discomfort/pressure (typically in cases when patient is already taking medication for high blood pressure)
    • Akathisia [10]
    • Paresthesia
    • Short temper/irritability

    Extremely rare side effects include:

    Because of potential for more severe side effects, this drug is on the list to avoid in the elderly.[11] In many countries (including the US and UK), promethazine is contraindicated in children less than two years of age, and strongly cautioned against in children between two and six, due to problems with respiratory depression and sleep apnea.[12]

    Promethazine is listed as one of the drugs of highest anticholinergic activity in a study of anticholinergenic burden, including long-term cognitive impairment.[13]


    Promethazine, a phenothiazine derivative, is structurally different from the neuroleptic phenothiazines, with similar but different effects.[2] It acts primarily as a strong antagonist of the H1 receptor (antihistamine) and a moderate mACh receptor antagonist (anticholinergic),[2] and also has weak to moderate affinity for the 5-HT2A,[14] 5-HT2C,[14] D2,[15][16] and α1-adrenergic receptors,[17] where it acts as an antagonist at all sites, as well.

    Another notable use of promethazine is as a local anesthetic, by blockade of sodium channels.[17]


    Solid promethazine hydrochloride is a white to faint-yellow, practically odorless, crystalline powder. Slow oxidation may occur upon prolonged exposure to air, usually causing blue discoloration. Its hydrochloride salt is freely soluble in water and somewhat soluble in alcohol. Promethazine is a chiral compound, occurring as a mixture of enantiomers.[18]


    Promethazine was first synthesized by a group at Rhone-Poulenc (which later became part of Sanofi) led by Paul Charpentier in the early 1940s.[19] The team was seeking to improve on diphenhydramine; the same line on medical chemistry led to the creation of chlorpromazine.[20]

    Society and culture

    As of July 2017 it was 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.[1]

    It is also marketed in many combination drug formulations:

    Product liability lawsuit

    In 2009, the US Supreme Court ruled on a product liability case involving promethazine. Diana Levine, a woman suffering from a migraine, was administered Wyeth's Phenergan via IV push. The drug was injected improperly, resulting in gangrene and subsequent amputation of her right forearm below the elbow. A state jury awarded her $6 million in punitive damages.

    The case was appealed to the Supreme Court on grounds of federal preemption and substantive due process.[21] The Supreme Court upheld the lower courts' rulings, stating that "Wyeth could have unilaterally added a stronger warning about IV-push administration" without acting in opposition to federal law.[22] In effect, this means drug manufacturers can be held liable for injuries if warnings of potential adverse effects, approved by the US Food and Drug Administration (FDA), are deemed insufficient by state courts.

    On September 9, 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 risk of surrounding muscle and tissue damage.[23]

    See also

    • Purple drank (a recreational drug concoction containing promethazine)


    1. 1 2 3 4 "Promethazine international brands". Retrieved 17 July 2017.
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    13. Salahudeen MJ; Duffull SB; Nishtala PS; et al. (2015-03-25). "Anticholinergic burden quantified by anticholinergic risk scales and adverse outcomes in older people: a systematic review". BMC Geriatrics. 15 (31): 31. doi:10.1186/s12877-015-0029-9. PMC 4377853. PMID 25879993.
    14. 1 2 Fiorella D, Rabin RA, Winter JC (October 1995). "The role of the 5-HT2A and 5-HT2C receptors in the stimulus effects of hallucinogenic drugs. I: Antagonist correlation analysis". Psychopharmacology. 121 (3): 347–56. doi:10.1007/bf02246074. PMID 8584617.
    15. Seeman P, Watanabe M, Grigoriadis D, et al. (November 1985). "Dopamine D2 receptor binding sites for agonists. A tetrahedral model". Molecular Pharmacology. 28 (5): 391–9. PMID 2932631.
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    19. Ban, TA (2006). "The role of serendipity in drug discovery". Dialogues in clinical neuroscience. 8 (3): 335–44. PMC 3181823. PMID 17117615.
    20. "Paul Charpentier, Henri-Marie Laborit, Simone Courvoisier, Jean Delay, and Pierre Deniker". Science History Institute. August 6, 2015. Retrieved 20 March 2018.
    21. Liptak, Adam (2001-09-18). "Drug Label, Maimed Patient and Crucial Test for Justices". The New York Times. Retrieved 2008-10-31.
    22. Stout, David (2009-03-04). "Drug Approval Is Not a Shield From Lawsuits, Justices Rule". The New York Times. Retrieved 2009-03-04.
    23. "Information for Healthcare Professionals: Intravenous Promethazine and Severe Tissue Injury, Including Gangrene". 2013-08-15.
    • "Promethazine". U.S. National Library of Medicine and National Institutes of Health. 
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