PROMETH PLAIN
Clinical safety rating: caution
Comprehensive clinical and safety monograph for PROMETH PLAIN (PROMETH PLAIN).
Antagonist at histamine H1 receptors; also exhibits anticholinergic, antiemetic, and sedative effects.
| Metabolism | Hepatic metabolism via CYP2D6; metabolites are excreted renally. |
| Excretion | Primarily renal (approximately 70%) as metabolites and unchanged drug; biliary/fecal excretion accounts for ~20%. |
| Half-life | Terminal elimination half-life is 10-14 hours in adults; may be prolonged in elderly or hepatic impairment. |
| Protein binding | Approximately 93% bound primarily to albumin. |
| Volume of Distribution | Approximately 9-12 L/kg, indicating extensive tissue distribution. |
| Bioavailability | Oral: ~25% due to significant first-pass metabolism; IM: 70-85%. |
| Onset of Action | Oral: 30-60 min; IM: 20-30 min; IV: 5-10 min. |
| Duration of Action | 4-6 hours for antihistamine effects; sedative effects may persist longer. |
| Molecular Weight | 284.42 |
12.5-25 mg intramuscularly or intravenously every 4-6 hours as needed; maximum 100 mg/day.
| Dosage form | SYRUP |
| Renal impairment | No specific adjustment required; use with caution in severe renal impairment (eGFR <30 mL/min) due to potential accumulation. |
| Liver impairment | Child-Pugh Class A: No adjustment. Child-Pugh Class B: Reduce dose by 50%. Child-Pugh Class C: Avoid use or reduce dose by 75% with careful monitoring. |
| Pediatric use | Weight-based: 0.25-0.5 mg/kg intramuscularly or intravenously every 4-6 hours; maximum 10 mg for children <5 years or 25 mg for children 5-12 years. |
| Geriatric use | Lower initial doses recommended (6.25-12.5 mg) due to increased sensitivity and risk of sedation, hypotension, and anticholinergic effects; maximum 50 mg/day. |
| 1st trimester | Avoid if possible. Animal studies suggest risk, but human data limited. Use only if benefit outweighs risk. |
| 2nd trimester | Limited data; generally avoided due to potential anticholinergic effects and risk of premature labor. |
| 3rd trimester | Avoid near term due to risk of neurobehavioral depression and potential respiratory depression in neonate. |
Clinical note
Comprehensive clinical and safety monograph for PROMETH PLAIN (PROMETH PLAIN).
| Placental transfer | Promethazine crosses the placenta readily; detectable in fetal blood after maternal administration. |
| Breastfeeding | Small amounts excreted in breast milk; may cause irritability or drowsiness in infant. Use caution, especially with high doses or prolonged therapy. |
| Lactation Rating |
■ FDA Black Box Warning
Do not use in children younger than 2 years due to risk of respiratory depression and death; use with caution in children 2 years and older.
| Serious Effects |
Hypersensitivity to promethazine or phenothiazinesComatose statesSevere CNS depressionConcurrent use of large amounts of CNS depressantsPediatric patients <2 years (risk of fatal respiratory depression)
| Precautions | May cause CNS depression and impair mental alertness, Avoid concurrent use with other CNS depressants, Use with caution in patients with asthma, COPD, or sleep apnea, Risk of extrapyramidal symptoms, especially in children, May cause anticholinergic effects (e.g., dry mouth, urinary retention) |
| Food/Dietary | No significant food interactions with promethazine. Avoid concomitant consumption of alcohol or grapefruit juice, as these may enhance adverse effects (e.g., sedation, hypotension). Patients should maintain adequate hydration but no specific dietary restrictions are required. |
Loading safety data…
| L3 (Moderately Safe) - Limited data but potential for adverse effects in infant. |
| Teratogenic Risk | FDA Pregnancy Category C. First trimester: No adequate studies; animal studies show no teratogenicity, but embryocidal effects at high doses. Second/third trimester: Prolonged use near term may cause extrapyramidal signs or withdrawal in neonate; potential for respiratory depression if used with other CNS depressants. |
| Fetal Monitoring | Monitor maternal blood pressure, heart rate, and respiratory status; assess for excessive sedation. Fetal monitoring: Nonstress test and biophysical profile in third trimester if chronic use. Neonatal monitoring for extrapyramidal signs, sedation, and respiratory depression after delivery. |
| Fertility Effects | No established effect on human fertility. Animal studies show no impairment of fertility at therapeutic doses. Theoretical risk due to hyperprolactinemia from dopamine antagonism, but clinical significance is minimal. |
| Clinical Pearls | Promethazine is a phenothiazine antiemetic with strong sedative and anticholinergic properties. Use with caution in elderly due to risk of confusion, hypotension, and extrapyramidal symptoms. Avoid intra-arterial injection due to risk of severe vasospasm and gangrene. IV administration should be through a running IV line at a concentration not exceeding 25 mg/min to minimize venous irritation. Do not use in children under 2 years due to risk of respiratory depression. May cause QT prolongation; avoid in patients with known QTc prolongation or concomitant use of other QT-prolonging agents. Has anti-serotonergic effects; may worsen serotonin syndrome. Onset of sedation is rapid (15-30 min) when given parenterally; use as a one-time dose for sedation/anxiety is common in emergency settings. |
| Patient Advice | Take this medication exactly as prescribed. Do not increase the dose or frequency without consulting your doctor. · Drowsiness is a common side effect; avoid driving, operating machinery, or engaging in hazardous activities until you know how the drug affects you. · Do not drink alcohol or use other central nervous system depressants (e.g., benzodiazepines, opioids) while taking this medication, as it may increase sedation and respiratory depression. · If you are using this medication for motion sickness, take it 30-60 minutes before travel. · Report any signs of extrapyramidal reactions (e.g., muscle stiffness, tremors, unusual movements) or tardive dyskinesia (e.g., repetitive facial movements) to your healthcare provider. · May cause photosensitivity; avoid excessive sun exposure and use sunscreen. · Do not use in children under 2 years of age due to risk of severe breathing problems. · If you are pregnant or breastfeeding, discuss risks and benefits with your doctor before using promethazine. |