What are the indications, adult dosing, contraindications, adverse effects, and alternative therapies for Avomine (promethazine)?

Avomine (Promethazine): Clinical Overview

Indications

Promethazine is indicated for allergic reactions, postoperative nausea and vomiting, motion sickness, and as a sedative adjunct during endoscopic and minor surgical procedures. 1

• Antiemetic use: Effective for postoperative nausea and vomiting, with 89% of patients reporting symptom improvement in the post-discharge period 2
• Procedural sedation: Used as adjunct to narcotics and benzodiazepines during endoscopy, bronchoscopy, and colonoscopy, allowing dose reduction of primary sedatives 1
• Antihistamine: Treatment of allergic symptoms and anaphylaxis 1

Adult Dosing

Administer 12.5–25 mg intravenously per single dose, infused at a rate not exceeding 25 mg per minute, with cumulative doses up to 25–100 mg when used as a sedative adjunct. 3

• Onset of action: Within 5 minutes of IV administration 3
• Duration of effect: 4–6 hours 3
• Plasma half-life: 9–16 hours 1
• Intramuscular dosing: 25–100 mg has been used for procedural sedation 1
• Rectal suppositories: 25 mg suppositories are effective for home management of postoperative nausea and vomiting 2

Contraindications

Promethazine is contraindicated in patients with elevated intra-ocular pressure, prostatic hypertrophy, and children under 2 years of age. 4, 5

• Angle-closure glaucoma risk: Anticholinergic activity can precipitate acute angle-closure events in patients with elevated intra-ocular pressure 4
• Urinary retention: Patients with prostatic hypertrophy have markedly increased risk 4
• Pediatric safety: Associated with significant sedation, agitation, hallucinations, seizures, dystonic reactions, and possibly sudden infant death syndrome in young children 5
• Cognitive impairment: Elderly patients or those with pre-existing cognitive deficits are at higher risk for worsening cognition, anticholinergic side effects, and falls 4

Adverse Effects

The most serious adverse effects include tissue necrosis and gangrene from extravasation or inadvertent intra-arterial injection, extrapyramidal symptoms, and respiratory depression. 4, 6

Severe Tissue Injury

• Extravasation or intra-arterial injection can cause thrombophlebitis, tissue necrosis, and gangrene requiring amputation 4, 6, 7
• Repeated or prolonged IV courses should be avoided due to heightened risk of serious tissue injury 3
• The FDA changed product labeling in December 2023 to emphasize dilution requirements and preference for intramuscular administration 6

Neurological Effects

• Extrapyramidal symptoms: Dystonia, akathisia, restlessness, and oculogyric crises may occur; have diphenhydramine 25–50 mg readily available for treatment 4
• Neuroleptic malignant syndrome is a rare but serious complication 1
• Sedation, agitation, hallucinations, and seizures have been reported, particularly in vulnerable populations 5

Cardiovascular Effects

• Hypotension: Minimize risk by infusing slowly at ≤25 mg/min 1, 3
• Strong α-adrenergic inhibitory effect contributes to blood pressure reduction 1

Other Common Effects

• Respiratory depression when combined with opioids or benzodiazepines 1
• Anticholinergic effects: Dry mouth, blurred vision, urinary retention 1
• Confusion and uncooperative behavior during procedures (9% and 2% respectively in one series) 1

Alternative Therapies

Ondansetron, metoclopramide, and diphenhydramine are safer alternatives that avoid the tissue injury risks associated with injectable promethazine. 8, 7

Antiemetic Alternatives

• Ondansetron: Equally effective for postoperative nausea and vomiting; the combination of ondansetron 2 mg plus promethazine 12.5 mg reduced vomiting incidence from 74% to 29% (p=0.003), but ondansetron alone is safer 8
• Metoclopramide: Dopamine antagonist with prokinetic properties, suitable for nausea and vomiting 7
• Diphenhydramine: H1-receptor antagonist with sedative properties; 50 mg IV improved sedation scores and reduced meperidine and midazolam requirements during colonoscopy without serious adverse effects 1

Sedation Alternatives

• Dexmedetomidine: α2-agonist for procedural sedation, though associated with bradycardia and hypotension 1
• Benzodiazepines and opioids: Standard sedation agents that can be used without promethazine adjunct 1

Critical Safety Considerations

Patient safety organizations including the Institute for Safe Medication Practices and American Society of Health-System Pharmacists have advocated for removing all injectable promethazine from inpatient and outpatient settings. 7

• Tissue injury prevention: Use intramuscular route when possible; if IV administration is necessary, ensure proper line placement, dilute appropriately, and infuse slowly 6
• Have reversal agents available: Keep diphenhydramine 25–50 mg accessible for extrapyramidal reactions 4
• Screen for contraindications: Assess for glaucoma, prostatic hypertrophy, cognitive impairment, and age-related vulnerabilities before prescribing 4