Is Phenergan (promethazine) safe to use?

Is Phenergan (Promethazine) Safe to Use?

Phenergan (promethazine) can be used safely in adults when prescribed appropriately, but it carries significant risks including fatal respiratory depression in young children, CNS depression, QTc prolongation, and tissue injury with IV administration—requiring careful patient selection and monitoring. 1

Absolute Contraindications

Do not use promethazine in:

• Children under 2 years of age due to risk of fatal respiratory depression 1
• Comatose patients 1
• Patients with known hypersensitivity to promethazine or phenothiazines 1
• Treatment of lower respiratory tract symptoms including asthma 1

Critical Safety Warnings

Respiratory Depression Risk

• Fatal respiratory depression can occur, particularly in pediatric patients under 2 years 1
• In children 2 years and older, use the lowest effective dose and avoid combining with other respiratory depressants 1
• Avoid in patients with compromised respiratory function (COPD, sleep apnea) 1

CNS Depression

• Promethazine impairs mental and physical abilities required for driving or operating machinery 1
• Concomitant use with alcohol, sedatives, barbiturates, narcotics, tricyclic antidepressants, or tranquilizers amplifies impairment 1
• When combining with narcotics, reduce narcotic dose by one-quarter to one-half; reduce barbiturate dose by at least one-half 1

Cardiovascular Effects

• Promethazine prolongs QTc interval (mean effect at therapeutic doses), which may lead to torsades de pointes 2, 3
• Directly blocks hERG potassium channels with IC50 of 1.46 μM at physiologic temperature 3
• However, minimal effects on autonomic cardiovascular mechanisms and baroreflex function were observed in healthy subjects 4
• Use cautiously in patients with cardiovascular disease 1

Neuroleptic Malignant Syndrome

• A potentially fatal syndrome characterized by hyperpyrexia, muscle rigidity, altered mental status, and autonomic instability 1
• Requires immediate discontinuation of promethazine and intensive supportive care 1

Seizure Risk

• Promethazine lowers seizure threshold 1
• Use with caution in patients with seizure disorders or those taking medications that affect seizure threshold (narcotics, local anesthetics) 1

Use with Caution In

Patients with the following conditions require careful risk-benefit assessment:

• Narrow-angle glaucoma, prostatic hypertrophy, stenosing peptic ulcer, pyloroduodenal obstruction, bladder-neck obstruction (due to anticholinergic properties) 1
• Cardiovascular disease 1
• Impaired liver function 1
• Bone marrow depression (leukopenia and agranulocytosis reported) 1

Drug Interactions to Monitor

Avoid or Use Reduced Doses With:

• Epinephrine: Do NOT use to treat promethazine-associated hypotension, as promethazine reverses epinephrine's vasopressor effect 1
• MAOIs: Increased incidence of extrapyramidal effects when used concomitantly 1
• Other anticholinergic agents: Use together with caution 1

Pregnancy and Breastfeeding

• Pregnancy Category C: Teratogenic effects not demonstrated in rat studies at doses 2.1-4 times human dose, but adequate human studies lacking 1
• Use only if benefits outweigh risks 1

Clinical Efficacy Context

When promethazine is appropriate, consider:

• For nausea/vomiting in emergency settings, prochlorperazine (10 mg IV) works significantly better than promethazine (25 mg IV), with faster symptom relief, fewer treatment failures (9.5% vs 31%), and less sedation (38% vs 71%) 5
• For cyclic vomiting syndrome, promethazine 12.5-25 mg every 4-6 hours can be used as abortive therapy, though peripheral IV administration risks tissue injury including gangrene 6
• For hyperemesis gravidarum, promethazine is considered first-line pharmacologic treatment alongside doxylamine-pyridoxine, though metoclopramide causes less sedation and fewer adverse events 6

Monitoring Requirements

When prescribing promethazine:

• Monitor for excessive sedation and respiratory depression, especially in elderly patients 6
• Assess for involuntary muscle movements (extrapyramidal symptoms) 1
• Consider baseline ECG in patients with cardiac risk factors given QTc prolongation risk 2, 3
• Avoid prolonged sun exposure (photosensitivity risk) 1

Common Side Effects

• Drowsiness and sedation (60-73% of patients) 6
• Anticholinergic effects: dry mouth, constipation 6
• CNS depression 6
• Extrapyramidal symptoms 6