Description

Simple

An antihistamine used for a number of allergic reactions, and to prevent nausea, vomiting and motion sickness.

Clinical

A first-generation antihistamine used for the treatment of allergic conditions, nausea and vomiting, and motion sickness.

Overview

Promethazine, originally known as 3,277 R.P., is an N-dimethylaminopropyl derivative of [phenothiazine] that was developed in France in 1946.[1] Promethazine antagonizes a variety of receptors, allowing it to be used for a number of indications including allergic reactions, pain, sedation, nausea, and vomiting.[2,8,9,7,10]

Promethazine was granted FDA a... Read more

Pharmacology

Indication

Promethazine tablets and suppositories are indicated to treat rhinitis, allergic conjunctivitis, allergic reactions to blood or plasma, dermographism, anaphylactic reactions, sedation, nausea, vomiting, pain, motion sickness, and allergic skin reactions.[ Read more

Pharmacodynamic

Promethazine is is a histamine H1 antagonist that can be used for it's ability to induce sedation, reduce pain, and treat allergic reactions.[12] Promethazine'... Read more

Mechanism of action

Promethazine is a an antagonist of histamine H1, post-synaptic mesolimbic dopamine, alpha adrenergic, muscarinic, and NMDA receptors.[2, Read more

Absorption

A 25mg dose of intramuscular promethazine reaches a Cmax of 22ng/mL.[ Read more

Protein binding

Promethazine is 93% protein bound in serum,[ Read more

Volume of distribution

The volume of distribution of promethazine is approximately 970L or 30L/kg.[ Read more

Clearance

The intravenous clearance of promethazine is approximately 1.14L/min.[ Read more

Half life

The elimination half life of promethazine is approximately 12-15h.[ Read more

Route of elimination

An intravenous dose of promethazine is 0.64% eliminated in the urine as the unchanged parent drug, 0.02-2.02% in the urine as desmethylpromethazine, 10% in the urine as promethazine sulfoxide.[ Read more

Toxicity

The intraperitoneal LD50 in rats is 170mg/kg and in mice is 160mg/kg.[14] The subcutaneous LD50 in rats is 400mg/kg and in mice is 240mg/kg.[ Read more

Adverse Effects

Contraindications

  • Route:
    • Intramuscular
    • Intravenous
    • Oral
    • Rectal
  • Dose Form:
    • Injection
    • Suppository
    • Tablet
  • Regions: US
  • Patient Conditions:
      • Name: Lower respiratory tract symptoms
      • Drugbank Id: DBCOND0108184
  • Route:
    • Intramuscular
    • Intravenous
    • Oral
    • Rectal
  • Dose Form:
    • Injection
    • Suppository
    • Tablet
  • Regions: US
  • Patient Conditions:
      • Name: Asthma
      • Drugbank Id: DBCOND0013565
  • Route:
    • Intramuscular
    • Intravenous
    • Oral
    • Rectal
  • Dose Form:
    • Injection
    • Suppository
    • Tablet
  • Regions: US
  • Patient Conditions:
      • Name: Intra-arterial route of administration
      • Drugbank Id: DBCOND0108185
  • Route:
    • Intramuscular
    • Intravenous
    • Oral
    • Rectal
  • Dose Form:
    • Injection
    • Suppository
    • Tablet
  • Regions: US
  • Patient Conditions:
      • Name: Subcutaneous route of administration
      • Drugbank Id: DBCOND0108186
  • Route:
    • Intramuscular
    • Intravenous
    • Oral
    • Rectal
  • Dose Form:
    • Injection
    • Suppository
    • Tablet
  • Regions: US
  • Patient Conditions:
      • Name: Comatose states
      • Drugbank Id: DBCOND0107802
  • Route:
    • Oral
    • Rectal
  • Dose Form:
    • Suppository
    • Tablet
  • Regions: US
  • Age Groups:
    • pediatric
  • Below Age:
    • Amount: 2
    • Unit: year

Food Interactions

  • Avoid alcohol. Alcohol may increase the sedation caused by promethazine.

Interactions

Type in a drug name to check for interaction with Promethazine
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  • Paracetamol(acetaminophen)
  • Paxil(paroxetine)
  • Pamelor(nortriptyline)
  • Panadol(acetaminophen)
  • Patanol(olopatadine ophthalmic)
  • Pataday(olopatadine ophthalmic)
  • Parnate(tranylcypromine)
  • Pazeo(olopatadine ophthalmic)
(R)-warfarin
The metabolism of (R)-warfarin can be decreased when combined with Promethazine.
(S)-Warfarin
The metabolism of (S)-Warfarin can be decreased when combined with Promethazine.
1-(2-Phenylethyl)-4-phenyl-4-acetoxypiperidine
The metabolism of Promethazine can be decreased when combined with 1-(2-Phenylethyl)-4-phenyl-4-acetoxypiperidine.
1,10-Phenanthroline
The therapeutic efficacy of Promethazine can be decreased when used in combination with 1,10-Phenanthroline.
2,5-Dimethoxy-4-ethylamphetamine
2,5-Dimethoxy-4-ethylamphetamine may decrease the sedative and stimulatory activities of Promethazine.
2,5-Dimethoxy-4-ethylthioamphetamine
2,5-Dimethoxy-4-ethylthioamphetamine may decrease the sedative and stimulatory activities of Promethazine.
4-Bromo-2,5-dimethoxyamphetamine
4-Bromo-2,5-dimethoxyamphetamine may decrease the sedative and stimulatory activities of Promethazine.
4-hydroxycoumarin
The risk or severity of adverse effects can be increased when Promethazine is combined with 4-hydroxycoumarin.
4-Methoxyamphetamine
The risk or severity of adverse effects can be increased when Promethazine is combined with 4-Methoxyamphetamine.
5-methoxy-N,N-dimethyltryptamine
The risk or severity of adverse effects can be increased when Promethazine is combined with 5-methoxy-N,N-dimethyltryptamine.
7-Nitroindazole
The risk or severity of adverse effects can be increased when Promethazine is combined with 7-Nitroindazole.
7,8-Dichloro-1,2,3,4-tetrahydroisoquinoline
The risk or severity of extrapyramidal symptoms can be increased when Promethazine is combined with 7,8-Dichloro-1,2,3,4-tetrahydroisoquinoline.
Abacavir
Abacavir may decrease the excretion rate of Promethazine which could result in a higher serum level.
Abafungin
Promethazine can cause a decrease in the absorption of Abafungin resulting in a reduced serum concentration and potentially a decrease in efficacy.
Abatacept
The metabolism of Promethazine can be increased when combined with Abatacept.
Abediterol
The risk or severity of Tachycardia can be increased when Promethazine is combined with Abediterol.
Abexinostat
The risk or severity of QTc prolongation can be increased when Promethazine is combined with Abexinostat.
Abiraterone
The metabolism of Promethazine can be decreased when combined with Abiraterone.
Acarbose
Acarbose may decrease the excretion rate of Promethazine which could result in a higher serum level.
Acebutolol
The serum concentration of Acebutolol can be increased when it is combined with Promethazine.
14 References
  1. 1 . HALPERN BN, HAMBURGER J: A new synthetic anti-histamine substance derived from phenothiazine; phenergan, 3,277 R.P. Can Med Assoc J. 1948 Oct;59(4):322-6.PubMed: 18886695
  2. 2 . Southard BT, Al Khalili Y: Promethazine .PubMed: 31335081
  3. 3 . Nakamura K, Yokoi T, Inoue K, Shimada N, Ohashi N, Kume T, Kamataki T: CYP2D6 is the principal cytochrome P450 responsible for metabolism of the histamine H1 antagonist promethazine in human liver microsomes. Pharmacogenetics. 1996 Oct;6(5):449-57.PubMed: 8946477
  4. 4 . Taylor G, Houston JB, Shaffer J, Mawer G: Pharmacokinetics of promethazine and its sulphoxide metabolite after intravenous and oral administration to man. Br J Clin Pharmacol. 1983 Mar;15(3):287-93. doi: 10.1111/j.1365-2125.1983.tb01501.x.PubMed: 6849764
  5. 5 . Cantisani C, Ricci S, Grieco T, Paolino G, Faina V, Silvestri E, Calvieri S: Topical promethazine side effects: our experience and review of the literature. Biomed Res Int. 2013;2013:151509. doi: 10.1155/2013/151509. Epub 2013 Nov 19.PubMed: 24350243
  6. 6 . He LL, Wang ZX, Wang YX, Liu XP, Yang YJ, Gao YP, Wang X, Liu B, Wang X: Studies on the interaction between promethazine and human serum albumin in the presence of flavonoids by spectroscopic and molecular modeling techniques. Colloids Surf B Biointerfaces. 2016 Sep 1;145:820-829. doi: 10.1016/j.colsurfb.2016.06.001. Epub 2016 Jun 2.PubMed: 27315330
  7. 7 . Authors unspecified: Promethazine .PubMed: 31643746
  8. 8 . Smith HS, Cox LR, Smith BR: Dopamine receptor antagonists. Ann Palliat Med. 2012 Jul;1(2):137-42. doi: 10.3978/j.issn.2224-5820.2012.07.09.PubMed: 25841474
  9. 9 . Adolph O, Koster S, Georgieff M, Georgieff EM, Moulig W, Fohr KJ: Promethazine inhibits NMDA-induced currents - new pharmacological aspects of an old drug. Neuropharmacology. 2012 Aug;63(2):280-91. doi: 10.1016/j.neuropharm.2012.03.006. Epub 2012 Apr 7.PubMed: 22507664
  10. 10 . Flake ZA, Linn BS, Hornecker JR: Practical selection of antiemetics in the ambulatory setting. Am Fam Physician. 2015 Mar 1;91(5):293-6.PubMed: 25822385
  11. 11 . AVERY JL: Treatment of enterobiasis with one oral dose of promethazine hydrochloride. J Am Med Assoc. 1956 Jun 23;161(8):681-3. doi: 10.1001/jama.1956.02970080011004.PubMed: 13318985
  12. 12 . FDA Approved Drug Products: Phenergran Promethazine Oral Tablets (Discontinued) Link
  13. 13 . FDA Approved Drug Products: Promethazine with Phenylephrine and Codeine Oral Syrup Link
  14. 14 . Cayman Chemical: Promethazine MSDS Link