What diagnoses and medications should be avoided when prescribing promethazine?

Promethazine: Contraindications and Drug Interactions

Promethazine is absolutely contraindicated in children under 2 years of age due to fatal respiratory depression risk, and must be avoided with CNS depressants, epinephrine, and in patients with narrow-angle glaucoma, prostatic hypertrophy, or compromised respiratory function. 1

Absolute Contraindications by Age and Respiratory Status

• Children under 2 years old: Promethazine is contraindicated due to postmarketing reports of fatal respiratory depression, which occurs independent of weight-based dosing. 1
• Children 2 years and older: Use only the lowest effective dose and avoid all concomitant respiratory depressants. 1
• Compromised respiratory function: Avoid promethazine entirely in patients with COPD or sleep apnea, as it may lead to potentially fatal respiratory depression. 1

Critical Drug Interactions Requiring Avoidance or Dose Reduction

CNS Depressants (Reduce or Avoid)

• Barbiturates: Reduce barbiturate dose by at least one-half when co-administered with promethazine. 1
• Narcotics/opioids: Reduce narcotic dose by one-quarter to one-half to prevent excessive sedation and respiratory depression. 1
• Other CNS depressants: Alcohol, sedatives/hypnotics, narcotic analgesics, general anesthetics, tricyclic antidepressants, and tranquilizers should be eliminated or given in reduced dosage. 1
• Pediatric patients: Concomitant respiratory depressants are strongly associated with death in children and must be avoided. 1

Epinephrine (Absolute Avoidance)

• Do NOT use epinephrine to treat promethazine-associated hypotension: Promethazine reverses epinephrine's vasopressor effect, potentially worsening hypotension. 1

MAO Inhibitors (Use with Caution)

• Increased extrapyramidal effects: Drug interactions, including heightened extrapyramidal symptoms, have been reported when MAOIs and phenothiazines are used together. 1

Anticholinergic Agents (Use with Caution)

• Additive anticholinergic effects: Concomitant use of other anticholinergic agents should be undertaken with caution due to cumulative effects. 1

Medical Conditions Requiring Avoidance or Extreme Caution

Anticholinergic-Sensitive Conditions (Use with Caution)

• Narrow-angle glaucoma: Anticholinergic properties may precipitate acute angle closure. 1
• Prostatic hypertrophy: Risk of urinary retention increases significantly. 2, 1
• Bladder-neck obstruction: Anticholinergic effects worsen obstruction. 1
• Stenosing peptic ulcer or pyloroduodenal obstruction: Anticholinergic effects may exacerbate obstruction. 1
• Elevated intraocular pressure: Anticholinergic properties contraindicate use. 2

Neurological Conditions

• Seizure disorders: Promethazine lowers seizure threshold and should be used with caution, especially when combined with narcotics or local anesthetics that also affect seizure threshold. 1
• Existing cognitive impairment: Elderly patients and those with baseline cognitive deficits face higher risk of worsening impairment, anticholinergic side effects, and falls. 2

Hematologic Conditions

• Bone marrow depression: Use with caution; leukopenia and agranulocytosis have been reported, particularly when combined with other marrow-toxic agents. 1

Cardiovascular Conditions

• Cardiovascular disease: Use cautiously due to hypotension risk and QT prolongation potential. 1, 3
• QT prolongation risk: Promethazine directly blocks hERG K+ channels, which can lead to torsades de pointes. 3

Hepatic Impairment

• Liver dysfunction: Use cautiously in patients with impaired liver function. 1

Special Population Warnings

Pregnancy and Labor

• Pregnancy Category C: Use only if potential benefit justifies fetal risk; teratogenic effects have not been demonstrated in rats, but fetal mortality occurred at high doses. 1
• Within 2 weeks of delivery: May inhibit platelet aggregation in the newborn. 1

Elderly Patients

• Higher risk population: Increased likelihood of cognitive impairment, anticholinergic side effects, and falls. 2

Serious Adverse Reactions Requiring Monitoring

Extrapyramidal Effects

• Monitor for dystonia, akathisia, restlessness, and oculogyric crises: Have diphenhydramine 25-50 mg readily available for prompt treatment. 4, 2
• Neuroleptic malignant syndrome: A potentially fatal syndrome characterized by hyperpyrexia, muscle rigidity, altered mental status, and autonomic instability; discontinue promethazine immediately if suspected. 1

Tissue Damage (IV Administration)

• Thrombophlebitis, tissue necrosis, and gangrene: Can occur with extravasation or inadvertent intra-arterial injection; infuse slowly (≤25 mg/min) and avoid repeated or prolonged IV courses. 2, 5, 6

Common Pitfalls to Avoid

• Inappropriate use for uncomplicated vomiting in children: Antiemetics are not recommended for simple vomiting in pediatric patients; reserve for prolonged vomiting of known etiology. 1
• Chronic use for insomnia: Promethazine has no good evidence base for sleep, impedes cognitive-behavioral therapy effectiveness, has addictive potential, and an unacceptable side-effect profile for psychiatric patients. 7
• Excessive promethazine relative to narcotics: May lead to restlessness and motor hyperactivity in patients with pain. 1