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. |
| Molecular Weight | 284.4 |
| 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 | Avoid use in first trimester due to potential teratogenic effects (cleft palate, skeletal malformations) based on animal studies and limited human data. Use only if clearly needed. |
| 2nd trimester | Use with caution; limited data suggest no major malformations, but consider risk-benefit. Avoid near term due to potential adverse effects in neonate. |
| 3rd trimester | Avoid use in third trimester especially after 37 weeks gestation or during labor due to increased risk of neonatal respiratory depression, extrapyramidal signs, and withdrawal symptoms. |
Clinical note
Comprehensive clinical and safety monograph for PHENERGAN (PHENERGAN).
| Placental transfer | Promethazine crosses the placenta freely as documented by detection in cord blood and fetal tissues. Distribution to fetal liver and other organs occurs. |
| Breastfeeding | Promethazine is excreted into breast milk in small amounts. Potential for infant sedation, apnea, and irritability. Use caution especially in neonates or preterm infants. Monitor infant for drowsiness and feeding difficulties. |
■ 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 |
Coma or severe CNS depressionConcurrent use of large doses of other CNS depressantsHypersensitivity to promethazine or phenothiazinesNewborn or premature infants (risk of severe respiratory depression)Treatment of lower respiratory tract symptoms (including asthma)Narrow-angle glaucomaProstatic hypertrophy with urinary retentionSevere hepatic impairment
| 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. |
Loading safety data…
| Lactation Rating | L3 |
| 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. |
| 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. |
| Food/Dietary | Avoid alcohol; may enhance sedative effects. No significant food interactions known. |
| Clinical Pearls | Administer deep IM injection to avoid tissue necrosis; IV route contraindicated due to risk of severe tissue injury. Monitor for anticholinergic effects, especially in elderly. Use lowest effective dose to minimize sedation. May cause false-positive urine pregnancy tests. Avoid in patients with known CYP2D6 poor metabolizer status due to increased risk of QT prolongation. |
| Patient Advice | This medication may cause drowsiness and impair your ability to drive or operate machinery; avoid alcohol. · Report any injection site pain, redness, or swelling immediately. · Do not take with other medications that cause drowsiness unless directed by your doctor. · Inform your doctor if you have glaucoma, enlarged prostate, or breathing problems like asthma. · Use sun protection as this drug may increase sensitivity to sunlight. |