[Durgical](https://durgical.com/en/) › [DurgiPedia](https://durgical.com/en/durgipedia/) › [Pharmacology](https://durgical.com/en/pharmacology/) › [H1 antihistamines](https://durgical.com/en/pharmacology/classes/h1-antihistamines/) › Promethazine # Promethazine ## H1 antihistamines? H1 antihistamines ## High alert? An error with this medicine can cause serious harm: double checks and protocols are used. A strongly sedating phenothiazine antihistamine for nausea, allergy and sedation; never under age 2, and the injection can cause gangrene. Updated Nov 1, 2026 ## Quick facts **Group** [H1 antihistamines](https://durgical.com/en/pharmacology/classes/h1-antihistamines/) **Target** Histamine H1 receptor **Used for** Nausea and vomiting · Motion sickness **Key effects** Marked drowsiness · Dry mouth · Confusion **Monitor** Respiratory rate · Injection site · Blood pressure **ATC** R06AD02 No doses: the clinician sets them by the current guideline. On this page - The basics Mechanism of action - Indications - Adverse effects - Pharmacokinetics - Memory aid - Clinical What the labels mean - Safety Contraindications - Key interactions - What is monitored - Administration and safety - Pregnancy and breastfeeding - Nursing care - Study Test yourself - Connections Connections ## Mechanism of action ◎**Histamine H1 receptor**Promethazine ⓘ The figure shows doxepin, a tricyclic first-generation H1 blocker, in the human H1 receptor; promethazine, also tricyclic, binds the same site. **Target in 3D:** Histamine H1 receptor. PDB structure 3RZE (RCSB PDB, public domain). [View the structure at RCSB PDB](https://www.rcsb.org/structure/3RZE) · Drag to rotate · pinch to zoom Promethazine is a phenothiazine H1 inverse agonist with strong sedative, antimuscarinic and anti-emetic effects. It also blocks dopamine D2 receptors (anti-emetic action, but also extrapyramidal effects and, rarely, neuroleptic malignant syndrome) and alpha-adrenergic receptors (low blood pressure). It is very irritating to tissues, which explains the severe injuries when the injection leaks or enters an artery. - Promethazine blocks H1 receptors in body and brain: deep sedation - Muscarinic and D2 block in the vomiting centre: less nausea - Alpha block can lower blood pressure - It irritates tissue: leaks can cause necrosis ## Indications - Nausea and vomiting, including after surgery - Motion sickness - Allergic conditions, and anaphylaxis as an add-on to epinephrine [Allergic rhinitis →](https://durgical.com/en/conditions/allergic-rhinitis/) - Sedation before or after surgery and in labour (with an analgesic) ## Adverse effects ### Common - Marked drowsiness - Dry mouth, blurred vision, constipation - Dizziness and low blood pressure - Confusion ### Serious (rare, important) - Fatal respiratory depression in children under 2 years - Severe tissue injury, including gangrene, after leakage, intra-arterial or subcutaneous injection - Neuroleptic malignant syndrome; extrapyramidal reactions - Lowered seizure threshold; bone marrow suppression (rare) ## Contraindications - Children under 2 years - Intra-arterial or subcutaneous injection - Comatose states - Hypersensitivity to phenothiazines ## Key interactions **Alcohol, benzodiazepines, opioids and other CNS depressants** Additive sedation and slowed breathing **Other anticholinergic drugs (tricyclic antidepressants, oxybutynin, antipsychotics)** Additive dry mouth, urinary retention, constipation and confusion **Antipsychotics** Neuroleptic malignant syndrome has been reported with the combination **MAO inhibitors** Prolong and intensify the anticholinergic effects ## What is monitored - Respiratory rate, oxygen saturation and sedation - Injection site: pain, burning, swelling, colour change - Blood pressure - Abnormal movements, fever and rigidity ## Administration and safety - Preferred injection route is deep intramuscular - Intravenous only after dilution, slowly, through a well-running line in a large vein; stop at once if the patient reports pain or burning - Never subcutaneous or intra-arterial - Look-alike risk with other phenothiazines (prochlorperazine, chlorpromazine) ## Pregnancy and breastfeeding Promethazine has been used in pregnancy and in labour; near delivery it can affect the newborn and platelet function, so use is weighed with the clinician. ## Nursing care - Confirm the patient is not under 2 years old - Check the vein and injection site before, during and after an intravenous dose - Monitor breathing and sedation, especially with opioids - Fall precautions; teach to rise slowly ## Pharmacokinetics **Absorption** Well absorbed by mouth, with first-pass loss; also rectal, intramuscular or intravenous **Metabolism** Liver **Elimination** Urine and bile as metabolites **Onset and duration** Within minutes intravenously, longer by mouth; sedation can last many hours ## Memory aid PROMethazine: PROfoundly sleepy, Many receptors, and never under two or into an artery. ## Test yourself Think of the answer, then tap the question to see it. ## Below which age is promethazine never given, and why? Under 2 years, because of fatal respiratory depression. ## What is the preferred injection route for promethazine? Deep intramuscular; never subcutaneous or intra-arterial. ## Which receptor blockade explains extrapyramidal reactions with promethazine? Dopamine D2 blockade, as with other phenothiazines. ## A patient getting intravenous promethazine reports burning at the site. What is done? The injection is stopped at once and the site assessed for extravasation or arterial injury. [Add to my cards (4)](https://durgical.app/estudiar/?add=/en/pharmacology/promethazine/) [More Pharmacology questions →](https://durgical.com/en/practice/?f=pharmacology) ## What the labels mean **High alert** An error with this medicine can cause serious harm: double checks and protocols are used. ## Connections ## Related drugs 3 - [Diphenhydramine](https://durgical.com/en/pharmacology/diphenhydramine/) - [Hydroxyzine](https://durgical.com/en/pharmacology/hydroxyzine/) - [Meclozine](https://durgical.com/en/pharmacology/meclozine/) ## Related conditions 1 - [Allergic rhinitis](https://durgical.com/en/conditions/allergic-rhinitis/) [← Back to the class: H1 antihistamines](https://durgical.com/en/pharmacology/classes/h1-antihistamines/) Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given. Sources: [DailyMed - PROMETHAZINE HYDROCHLORIDE injection](https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=7ce351d8-47be-4937-aad2-153208c93b53) (DailyMed (U.S. National Library of Medicine), 2026); [Promethazine: MedlinePlus Drug Information](https://medlineplus.gov/druginfo/meds/a682284.html) (MedlinePlus (U.S. National Library of Medicine), 2026); [Promethazine: drowsy (sedating) antihistamine that relieves allergy symptoms - NHS](https://www.nhs.uk/medicines/promethazine/) (NHS, 2026); [ATCDDD - ATC/DDD Index](https://atcddd.fhi.no/atc_ddd_index/?code=R06AD02) (WHO Collaborating Centre for Drug Statistics Methodology, 2026). ## **Spotted a mistake?** We are always improving for the community. Tell us what is wrong and our team will review it. Report a mistake Representative model, for educational purposes only. --- Source: https://durgical.com/en/pharmacology/promethazine/ License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/pharmacology/promethazine/