Phenergan (Promethazine): Mechanism, Uses, and Considerations
Promethazine (Phenergan) is a phenothiazine derivative that functions primarily as a histamine H1-receptor antagonist with additional antiemetic, sedative, and anticholinergic properties, but is not recommended as routine treatment for conditions like BPPV due to its side effect profile and lack of evidence for efficacy in vestibular disorders. 1, 2, 3
Mechanism of Action
- Promethazine works through competitive histamine H1-receptor antagonism, blocking most pharmacologic effects of histamine, making it effective as an antihistamine, antiemetic, and sedative agent 1
- It blocks postsynaptic dopaminergic receptors in the brain, contributing to its antiemetic properties 1, 4
- Promethazine has strong alpha-adrenergic inhibitory effects, contributing to its sedative properties and potential hypotensive side effects 1, 4
- It possesses anticholinergic effects that contribute to both its clinical effects and side effect profile 1
Pharmacokinetics
- Promethazine is well absorbed from the gastrointestinal tract with clinical effects appearing within 20 minutes after oral administration 2
- For intravenous administration, effects are evident within 5 minutes 1
- Effects generally last 4-6 hours but may persist for up to 12 hours 2, 1
- The plasma half-life of promethazine is 9-16 hours 1
- It is metabolized by the liver, with sulfoxides of promethazine and N-demethylpromethazine being the predominant urinary metabolites 2
Clinical Applications
- Management of postoperative nausea and vomiting 1
- Treatment of allergic reactions and anaphylaxis 1
- Adjuvant for postoperative pain and sedation 1
- Motion sickness prevention and treatment 5
- Adjunct for sedation during minor surgical and endoscopic procedures 4
- Breakthrough treatment of chemotherapy-induced nausea/vomiting (12.5-25 mg PO or IV every 4 hours) 4
Dosing and Administration
- Usual dose is 12.5-25 mg intravenously, infused slowly (25 mg/min) to minimize hypotension risk 1
- For oral administration, available in 25 mg or 50 mg tablets 2
- Low-dose intravenous promethazine (6.25 mg) has been shown to relieve nausea and vomiting as effectively as ondansetron 4 mg with similar sedation profiles 6
Important Adverse Effects and Precautions
- Respiratory depression, particularly when combined with other central nervous system depressants 1, 4
- Hypotension, especially with rapid intravenous administration 1, 4
- Extrapyramidal effects ranging from restlessness to oculogyric crises 1
- Risk of neuroleptic malignant syndrome 1, 4
- Significant sedation, especially when used with narcotic analgesics 6
- FDA black box warning for injectable form due to risk of serious tissue injury, including thrombophlebitis, when administered incorrectly 5, 7
- Contraindicated in children younger than 2 years due to risk of fatal respiratory depression 4, 8
- Common side effects include dizziness, blurred vision, and dry mouth 4
Clinical Considerations
- Promethazine is not recommended for routine treatment of benign paroxysmal positional vertigo (BPPV) or other vestibular disorders 3
- The preferred parenteral route of administration is deep intramuscular injection to avoid vascular complications 5
- When administering intravenously, use large and patent veins, consider drug dilution, and administer slowly 5
- Ondansetron may be preferred over promethazine in many emergency settings due to its more favorable side effect profile (no sedation or akathisia) 9, 7
- In tactical combat casualty care, ondansetron has replaced promethazine for treatment of opioid- and trauma-related nausea and vomiting due to safety concerns 7