Promethazine
H1 antihistamines
H1 antihistaminesHigh 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.
Quick facts
- Group
- 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.
Mechanism of action
The figure shows doxepin, a tricyclic first-generation H1 blocker, in the human H1 receptor; promethazine, also tricyclic, binds the same site.
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 →
- 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
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
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.
Connections
← Back to the class: 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 (DailyMed (U.S. National Library of Medicine), 2026); Promethazine: MedlinePlus Drug Information (MedlinePlus (U.S. National Library of Medicine), 2026); Promethazine: drowsy (sedating) antihistamine that relieves allergy symptoms - NHS (NHS, 2026); ATCDDD - ATC/DDD Index (WHO Collaborating Centre for Drug Statistics Methodology, 2026).
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Representative model, for educational purposes only.