PHERAZINE VC

Clinical safety rating: caution

Comprehensive clinical and safety monograph for PHERAZINE VC (PHERAZINE VC).

How it works

Phenylephrine is a selective alpha-1 adrenergic receptor agonist causing vasoconstriction; chlorpheniramine is a first-generation antihistamine that antagonizes histamine H1 receptors; promethazine is a phenothiazine derivative with antihistamine, sedative, antiemetic, and anticholinergic effects.

What the body does with it

Metabolism	Phenylephrine: primarily metabolized by monoamine oxidase (MAO) in the liver and gut; chlorpheniramine: extensively metabolized in the liver via CYP2D6, CYP1A2, and CYP3A4; promethazine: metabolized in the liver via CYP2D6 and other pathways.
Excretion	Primarily renal as metabolites and unchanged drug; about 70% excreted in urine, 20% in feces via biliary elimination.
Half-life	Terminal elimination half-life is approximately 9-16 hours; clinical context: steady-state achieved in 2-3 days.
Protein binding	Approximately 90% bound to serum albumin and alpha-1 acid glycoprotein.
Volume of Distribution	Vd approximately 15 L/kg; indicates extensive tissue distribution, particularly in lungs, spleen, and brain.
Bioavailability	Oral: 25-35% due to first-pass metabolism; Intramuscular: nearly 100%.
Onset of Action	Oral: 30-60 minutes; Intramuscular: 20-30 minutes. Onset of antihistamine and antiemetic effects.
Duration of Action	Antihistamine effects: 6-12 hours; antiemetic effects: 4-6 hours. Clinical note: Duration may be prolonged in hepatic impairment.

Classification & Brands

Dosing & administration

10 mg orally every 6 hours as needed; maximum 60 mg per day.

Dosage form	SYRUP
Renal impairment	No dose adjustment required for GFR ≥50 mL/min; for GFR <50 mL/min, use with caution and consider dose reduction (e.g., 5 mg every 6 hours) due to increased drug accumulation.
Liver impairment	Child-Pugh A: no adjustment; Child-Pugh B: reduce dose by 50% (e.g., 5 mg every 6 hours); Child-Pugh C: avoid use or use 2.5 mg every 8 hours if necessary.
Pediatric use	Children >2 years: 0.25 mg/kg orally every 6 hours as needed; maximum 20 mg per day. Children >12 years: adult dosing.
Geriatric use	Initiate at 5 mg orally every 6 hours; increase cautiously due to increased sensitivity and risk of anticholinergic effects, sedation, and orthostatic hypotension. Maximum 40 mg per day.

Use during pregnancy

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

Clinical note

Comprehensive clinical and safety monograph for PHERAZINE VC (PHERAZINE VC).

Breastfeeding	Excreted in breast milk; M/P ratio unknown. Potential for sedation, irritability in infant. Use caution; monitor for drowsiness and feeding difficulties.
Teratogenic Risk	FDA Pregnancy Category C. First trimester: Animal studies suggest increased risk of skeletal anomalies; no adequate human data. Second trimester: Limited data, no clear malformation risk. Third trimester: May cause extrapyramidal signs, respiratory depression, hypotonia in neonates if used near term.
Fetal Monitoring

Warnings & precautions

■ FDA Black Box Warning

Promethazine should not be used in children less than 2 years of age due to the risk of respiratory depression (including fatal cases).

Side Effect Profile

Serious Effects

Absolute Contraindications

["Children < 2 years of age (due to promethazine)","Comatose states or CNS depression","Hypersensitivity to any component","Concurrent use of MAO inhibitors or within 14 days","Severe hypertension or coronary artery disease","Narrow-angle glaucoma","Urinary retention (due to phenylephrine and anticholinergics)","Pyloroduodenal obstruction"]

Clinical Precautions

Precautions

["Risk of respiratory depression, especially in children and the elderly","CNS depression: May cause sedation and impair mental/physical abilities","Anticholinergic effects: Worsening of conditions like glaucoma, urinary retention, and hyperthyroidism","Cardiovascular effects: Caution in patients with hypertension, heart disease, or diabetes","Extrapyramidal symptoms: Possible with promethazine","Photosensitivity: Avoid prolonged sun exposure"]

Clinical Tips & Counseling

Drug interactions

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PHERAZINE VC

Clinical safety rating: caution

Comprehensive clinical and safety monograph for PHERAZINE VC (PHERAZINE VC).

How it works

What the body does with it

Metabolism	Phenylephrine: primarily metabolized by monoamine oxidase (MAO) in the liver and gut; chlorpheniramine: extensively metabolized in the liver via CYP2D6, CYP1A2, and CYP3A4; promethazine: metabolized in the liver via CYP2D6 and other pathways.
Excretion	Primarily renal as metabolites and unchanged drug; about 70% excreted in urine, 20% in feces via biliary elimination.
Half-life	Terminal elimination half-life is approximately 9-16 hours; clinical context: steady-state achieved in 2-3 days.
Protein binding	Approximately 90% bound to serum albumin and alpha-1 acid glycoprotein.
Volume of Distribution	Vd approximately 15 L/kg; indicates extensive tissue distribution, particularly in lungs, spleen, and brain.
Bioavailability	Oral: 25-35% due to first-pass metabolism; Intramuscular: nearly 100%.
Onset of Action	Oral: 30-60 minutes; Intramuscular: 20-30 minutes. Onset of antihistamine and antiemetic effects.
Duration of Action	Antihistamine effects: 6-12 hours; antiemetic effects: 4-6 hours. Clinical note: Duration may be prolonged in hepatic impairment.

Classification & Brands

Dosing & administration

10 mg orally every 6 hours as needed; maximum 60 mg per day.

Dosage form	SYRUP
Renal impairment	No dose adjustment required for GFR ≥50 mL/min; for GFR <50 mL/min, use with caution and consider dose reduction (e.g., 5 mg every 6 hours) due to increased drug accumulation.
Liver impairment	Child-Pugh A: no adjustment; Child-Pugh B: reduce dose by 50% (e.g., 5 mg every 6 hours); Child-Pugh C: avoid use or use 2.5 mg every 8 hours if necessary.
Pediatric use	Children >2 years: 0.25 mg/kg orally every 6 hours as needed; maximum 20 mg per day. Children >12 years: adult dosing.
Geriatric use	Initiate at 5 mg orally every 6 hours; increase cautiously due to increased sensitivity and risk of anticholinergic effects, sedation, and orthostatic hypotension. Maximum 40 mg per day.

Use during pregnancy

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

Clinical note

Comprehensive clinical and safety monograph for PHERAZINE VC (PHERAZINE VC).

Breastfeeding	Excreted in breast milk; M/P ratio unknown. Potential for sedation, irritability in infant. Use caution; monitor for drowsiness and feeding difficulties.
Teratogenic Risk	FDA Pregnancy Category C. First trimester: Animal studies suggest increased risk of skeletal anomalies; no adequate human data. Second trimester: Limited data, no clear malformation risk. Third trimester: May cause extrapyramidal signs, respiratory depression, hypotonia in neonates if used near term.
Fetal Monitoring

Warnings & precautions

■ FDA Black Box Warning

Promethazine should not be used in children less than 2 years of age due to the risk of respiratory depression (including fatal cases).