PROMETH VC PLAIN
Clinical safety rating: caution
Comprehensive clinical and safety monograph for PROMETH VC PLAIN (PROMETH VC PLAIN).
Promethazine is a phenothiazine derivative that acts as a potent histamine H1 receptor antagonist, blocking allergic reactions; it also has anticholinergic, antiemetic, sedative, and local anesthetic effects.
| Metabolism | Primarily hepatic metabolism via CYP2D6 and other pathways; metabolites include promethazine sulfoxide and N-demethylated derivatives. |
| Excretion | Primarily renal; promethazine is excreted in urine as unchanged drug (approximately 6%) and as metabolites (promethazine sulfoxide and N-demethylpromethazine); less than 1% excreted in feces. Phenylephrine is primarily metabolized by MAO and COMT; renal excretion of metabolites and unchanged drug (about 16%). |
| Half-life | Promethazine: terminal half-life 9-16 hours (mean 12 hours) in adults; longer in elderly (13.5-18 hours) and in hepatic impairment. Phenylephrine: half-life 2-3 hours. |
| Protein binding | Promethazine: approximately 93% bound to plasma proteins (mainly albumin). Phenylephrine: approximately 95% bound to plasma proteins (mainly albumin). |
| Volume of Distribution | Promethazine: Vd 5-17 L/kg (mean ~12 L/kg), indicating extensive tissue distribution. Phenylephrine: Vd 4-5 L/kg, also widely distributed. |
| Bioavailability | Oral promethazine: approximately 25% due to extensive first-pass metabolism. Intramuscular: nearly 100%. Rectal: approximately 70% of oral. Phenylephrine: oral bioavailability is low (about 38%) due to first-pass metabolism by MAO in gut and liver. |
| Onset of Action | Oral: promethazine onset 20-30 minutes for sedation; phenylephrine onset 15-30 minutes for decongestant effect. Intramuscular: promethazine 15-20 minutes. Rectal: promethazine 30-60 minutes. |
| Duration of Action | Oral promethazine: sedation lasts 4-6 hours (up to 12 hours in some). Phenylephrine: decongestant effect 4-6 hours. Duration can be extended in hepatic or renal impairment. |
| Molecular Weight | 378.52 |
Adults: 1-2 tablets (each containing Promethazine 6.25 mg and Phenylephrine 5 mg) orally every 4-6 hours; maximum 12 tablets per day.
| Dosage form | SYRUP |
| Renal impairment | No specific guidelines; use with caution in renal impairment (CrCl <30 mL/min) due to potential accumulation of promethazine; consider dose reduction or extended intervals. |
| Liver impairment | Child-Pugh Class A-C: Use with caution; reduce dose or avoid in severe hepatic impairment (Child-Pugh Class C) due to decreased metabolism of promethazine. |
| Pediatric use | Children aged 6-12 years: 1 tablet orally every 4-6 hours; maximum 6 tablets per day. Not recommended for children under 6 years due to risk of respiratory depression. |
| Geriatric use | Elderly patients: Initiate at lower doses (e.g., 1 tablet orally every 6-8 hours) and titrate carefully; monitor for anticholinergic effects, sedation, and orthostatic hypotension. |
| 1st trimester | Avoid due to potential teratogenic effects; limited data suggest possible association with neural tube defects. |
| 2nd trimester | Use only if clearly needed; may cause maternal sedation and potential for neonatal withdrawal. |
| 3rd trimester | Avoid near term due to risks of maternal respiratory depression, neonatal toxicity, and potential for premature closure of ductus arteriosus (anticholinergic effects). |
Clinical note
Comprehensive clinical and safety monograph for PROMETH VC PLAIN (PROMETH VC PLAIN).
| Placental transfer | Crosses placenta; distribution similar to maternal plasma levels. |
| Breastfeeding | Excreted into breast milk in small amounts; may cause drowsiness or irritability in infants. Use caution, especially in neonates or preterm infants. |
■ FDA Black Box Warning
Promethazine should not be used in children younger than 2 years due to risk of respiratory depression, including fatalities. Use in children aged 2+ with caution. Not for intra-arterial or subcutaneous injection (risk of severe tissue injury).
| Serious Effects |
Hypersensitivity to promethazine or any excipientComatose patientsConcomitant use of monoamine oxidase inhibitors (MAOIs)Severe central nervous system depressionPediatric patients <2 years of age (risk of fatal respiratory depression)
| Precautions | Risk of respiratory depression (especially in children, elderly, or with CNS depressants); use caution in asthma, sleep apnea, respiratory insufficiency. May impair cognitive/motor function; avoid alcohol. Extrapyramidal symptoms (rare). Caution in glaucoma, prostatic hyperplasia, urinary retention. Use in pregnancy (only if clearly needed). |
| Food/Dietary | No clinically significant food interactions. However, taking with food may reduce gastrointestinal upset. Avoid grapefruit juice as it may theoretically increase sedation. |
Loading safety data…
| Lactation Rating |
| L3 (Moderately Safe) |
| Teratogenic Risk | First trimester: Avoid. Inadequate studies; animal studies not sufficient. Second/third trimester: Use only if clearly needed; may cause neonatal respiratory depression, irritability, and tremors if used near term. |
| Fetal Monitoring | Monitor maternal sedation, respiratory depression, and blood pressure. Fetal heart rate monitoring recommended during labor if used near term. |
| Fertility Effects | No known significant effects on fertility in humans; animal studies have not shown impairment. |
| Clinical Pearls | Promethazine is a phenothiazine derivative with antihistamine, antiemetic, sedative, and anticholinergic properties. Administer deep IM if parenteral route required; avoid intra-arterial or subcutaneous injection due to risk of severe tissue damage. Monitor for extrapyramidal symptoms in children and elderly. Use with caution in patients with asthma, COPD, or sleep apnea due to respiratory depression risk. Do not use in children <2 years due to risk of fatal respiratory depression. |
| Patient Advice | Do not drive or operate heavy machinery until you know how this medication affects you, as it can cause drowsiness and dizziness. · Avoid alcohol and other central nervous system depressants while taking this medication. · Take exactly as prescribed; do not exceed recommended dose or duration. · Contact your healthcare provider if you experience difficulty breathing, involuntary muscle movements, or signs of jaundice (yellowing of skin/eyes). |