PROMETH VC PLAIN

Clinical safety rating: caution

Comprehensive clinical and safety monograph for PROMETH VC PLAIN (PROMETH VC PLAIN).

How it works

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.

What the body does with it

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.

Classification & Brands

Dosing & administration

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.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for PROMETH VC PLAIN (PROMETH VC PLAIN).

Breastfeeding	Promethazine is excreted into breast milk in small amounts; M/P ratio unknown. Caution suggested; avoid in infants with apnea, respiratory issues, or in mothers of preterm infants.
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

Warnings & precautions

■ 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).

Side Effect Profile

Serious Effects

Absolute Contraindications

Hypersensitivity to promethazine or phenothiazines; children <2 years; comatose patients; CNS depression (e.g., alcohol, barbiturates); Reye's syndrome (avoid in children with viral illness due to risk of Reye's? – actually contraindicated in patients with suspected Reye's). Also contraindicated for intra-arterial or subcutaneous injection.

Clinical Precautions

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).

Clinical Tips & Counseling

Drug interactions

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PROMETH VC PLAIN

Clinical safety rating: caution

Comprehensive clinical and safety monograph for PROMETH VC PLAIN (PROMETH VC PLAIN).

How it works

What the body does with it

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.

Classification & Brands

Dosing & administration

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.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for PROMETH VC PLAIN (PROMETH VC PLAIN).

Breastfeeding	Promethazine is excreted into breast milk in small amounts; M/P ratio unknown. Caution suggested; avoid in infants with apnea, respiratory issues, or in mothers of preterm infants.
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