PHENERGAN
Clinical safety rating: caution
Comprehensive clinical and safety monograph for PHENERGAN (PHENERGAN).
Phenergan (promethazine) is a phenothiazine derivative that acts as a potent histamine H1 receptor antagonist. It also has anticholinergic, antiemetic, and sedative properties. Its antiemetic effect is mediated by blocking dopamine D2 receptors in the chemoreceptor trigger zone (CTZ) and possibly by H1 antagonism in the vestibular system.
| Metabolism | Primarily metabolized in the liver via oxidation and conjugation. The major metabolic pathway involves S-oxidation to promethazine sulfoxide, and N-demethylation by CYP2D6 (minor pathway). Other enzymes include CYP1A2, CYP2B6, and possibly CYP2C19. |
| Excretion | Primarily hepatic metabolism; renal excretion of metabolites accounts for approximately 70% of elimination, with about 6% excreted unchanged. Fecal excretion is minimal (<1%). Biliary excretion is negligible. |
| Half-life | 10 to 14 hours in adults; clinical context: allows twice-daily dosing for antihistamine effects, but may accumulate with chronic use due to long half-life. |
| Protein binding | 90-93% bound, primarily to albumin. |
| Volume of Distribution | Approximately 6-12 L/kg; indicates extensive tissue distribution, with high concentration in lungs, spleen, and brain. |
| Bioavailability | Oral: approximately 25% due to extensive first-pass metabolism; IM: 80-90%; IV: 100%. |
| Onset of Action | Oral: 20 minutes; IM: 15-20 minutes; IV: 3-5 minutes; rectal: 20-60 minutes. |
| Duration of Action | Antihistamine effects: 4-6 hours; sedative effects: up to 12 hours; antiemetic effects: 4-6 hours. Note: duration may be prolonged in elderly or hepatic impairment. |
| Action Class | H1 Antihistaminics (First Generation) |
| Brand Substitutes | Phenamin Syrup, Phenzee 5mg/5ml Syrup, Premagan Syrup, Prompt Syrup, Emispan Syrup, Promet 25mg Injection, Phenamin 25mg Injection, Pakzine 25mg Injection, Promipen 25mg Injection, Premagan Injection |
25-50 mg intramuscular or intravenous every 4-6 hours; oral 25 mg every 4-6 hours as needed; maximum 200 mg/day.
| Dosage form | SUPPOSITORY |
| Renal impairment | No specific dose adjustment required; use with caution in severe renal impairment (GFR < 10 mL/min) due to risk of accumulation and increased sedation. |
| Liver impairment | Child-Pugh A: no adjustment. Child-Pugh B: reduce dose by 50% or use with caution. Child-Pugh C: contraindicated or use lowest possible dose with careful monitoring. |
| Pediatric use | 2 years and older: 1.1 mg/kg per dose orally, intramuscularly, or intravenously every 6 hours as needed; maximum 25 mg/dose. |
| Geriatric use | Start at 12.5 mg orally or intramuscularly every 6 hours; increase cautiously due to increased risk of sedation, confusion, and anticholinergic effects; avoid in patients with dementia. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for PHENERGAN (PHENERGAN).
| Breastfeeding | Promethazine is excreted in breast milk in small amounts; M/P ratio unknown. Potential for infant drowsiness, apnea, or irritability. Use with caution, especially in preterm infants. Consider alternatives for breastfeeding mothers. |
| Teratogenic Risk | Phenergan (promethazine) is FDA Pregnancy Category C. First trimester: limited human data; animal studies show no teratogenicity but fetal toxicity at high doses. Second/third trimesters: risk of maternal respiratory depression and neonatal withdrawal. Avoid in late pregnancy due to potential for extrapyramidal signs in neonate. |
■ FDA Black Box Warning
Phenergan should not be used in children younger than 2 years because of the risk of respiratory depression (including fatal). It is contraindicated for use in children younger than 2 years. Also, it should not be used in comatose patients or in patients with CNS depression.
| Serious Effects |
["Hypersensitivity to phenothiazines or any component","Children <2 years of age","Comatose patients","CNS depression (e.g., from alcohol, barbiturates, or opioids)","Concomitant use of MAO inhibitors (rare, but caution)","Symptomatic prostatic hypertrophy and narrow-angle glaucoma (relative, due to anticholinergic effects)"]
| Precautions | ["Respiratory depression: Use with caution in patients with asthma, COPD, or sleep apnea.","Pediatric use: Do not use in children <2 years; use extreme caution in older children with respiratory symptoms.","CNS depression: May impair mental/physical abilities; avoid alcohol and other CNS depressants.","Extrapyramidal symptoms: Rare but possible, especially with high doses.","Photosensitivity: Avoid excessive sun exposure.","Tardive dyskinesia: Possible with prolonged use.","Neuroleptic malignant syndrome: Discontinue if signs occur.","Anticholinergic effects: Caution in patients with glaucoma, prostatic hyperplasia, etc.","Pregnancy: Use only if clearly needed (category C).","Lactation: Excreted in breast milk; caution."] |
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| Fetal Monitoring | Monitor maternal respiratory status (risk of CNS depression), blood pressure, and fetal heart rate if used during labor. Observe neonate for signs of extrapyramidal symptoms, respiratory depression, or withdrawal (jitteriness, hypertonia). |
| Fertility Effects | No specific human data on fertility impairment. Antiemetic use may interfere with ovulation detection (by masking pregnancy symptoms). Animal studies show no significant reproductive toxicity. |