BLACK BOX WARNING
- respiratory depression; contraindicated in children under 2 years; use lowest effective dose in older children
- severe tissue damage with IV administration (preferred route is deep IM or oral/rectal)
promethazine
Brand: Phenergan
⚠ BBW ISMP High Alert Beers Criteria
Drug Class: phenothiazine / antihistamine
Drug Family: antiemetic
Subclass: first-generation H1 antihistamine with dopamine antagonism
Organ Systems: gastrointestinalcns
Mechanism of Action
Blocks H1 receptors and D2 dopamine receptors in the chemoreceptor trigger zone to suppress nausea and vomiting; also has sedating antihistamine, anticholinergic, and alpha-1 adrenergic blocking properties contributing to its anti-nausea and sedative effects.
H1 histamine receptorsD2 dopamine receptors (CTZ)muscarinic receptorsalpha-1 adrenergic receptors
Indications
- nausea and vomiting
- motion sickness
- allergic conditions
- sedation (preoperative)
- adjunct to analgesia
Contraindications
- children under 2 years (risk of fatal respiratory depression)
- IV administration (tissue necrosis risk)
- comatose patients
- concurrent MAOIs
Adverse Effects
Common
- sedation
- drowsiness
- dry mouth
- blurred vision
- constipation
- orthostatic hypotension
Serious
- respiratory depression (especially in children)
- neuroleptic malignant syndrome
- tardive dyskinesia
- severe tissue damage with IV extravasation
Pharmacokinetics (ADME)
| Absorption | oral and rectal bioavailability ~25% due to first-pass; IM has higher bioavailability |
| Distribution | widely distributed; crosses BBB and placenta |
| Metabolism | hepatic via CYP2D6 and CYP2B6; extensively metabolized |
| Excretion | renal (as metabolites) |
| Half-life | 16–19 hours |
| Onset | 20 minutes (IM/PO) |
| Peak | varies |
| Duration | 4–6 hours |
| Protein Binding | 93% |
| Vd | 9–17 L/kg |
Drug Interactions
| Drug / Agent | Mechanism | Severity |
|---|---|---|
| CNS depressants | additive sedation and respiratory depression | major |
| MAOIs | risk of hypertensive crisis and seizures | contraindicated |
| anticholinergic agents | additive anticholinergic toxicity | moderate |
Nursing Considerations
- NEVER administer promethazine IV; administer only by deep IM injection or oral/rectal routes to prevent severe tissue necrosis and gangrene.
- Do not administer to children under 2 years; use with extreme caution in children aged 2–6 due to risk of fatal respiratory depression.
- Monitor respiratory rate and oxygen saturation, especially in elderly patients or those on concurrent CNS depressants.
- Implement fall precautions due to significant sedation, orthostatic hypotension, and blurred vision.
Clinical Pearls
- The FDA issued a boxed warning against IV administration following numerous reports of severe tissue necrosis and limb amputations from IV extravasation.
- Promethazine is on the ISMP high-alert medication list due to its risk of serious patient harm; institutions are encouraged to restrict IV access.
Safety Profile
Pregnancy use-with-caution
Lactation avoid
Renal Adjustment Not required
Hepatic Adjustment Required
TDM Not required
Concordance Terms
Cross-referenced clinical concepts — click any term to see all content where it appears.