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Registry Hub
Peer-Reviewed Evidence
HomeDrug RegistryComparePROMETHAZINE HYDROCHLORIDE vs PHENERGAN VC
Comparative Pharmacology

PROMETHAZINE HYDROCHLORIDE vs PHENERGAN VC Comparison

Head-to-head clinical analysis & difference comparison: details on mechanism of action, dosing, half-life, interactions, and maternal-fetal safety.

Clinical EssentialsPharmacokineticsSpecial PopulationsSafety & MonitoringPregnancy & LactationClinical Insights
Differential Analysis

PROMETHAZINE HYDROCHLORIDE vs PHENERGAN VC

Head-to-head clinical comparison of therapeutic indices and safety profiles.

View PROMETHAZINE HYDROCHLORIDE Monograph View PHENERGAN VC Monograph
PROMETHAZINE HYDROCHLORIDE
Antihistamine / Antiemetic
Category A/B
PHENERGAN VC
Antihistamine/Decongestant Combination
Category C

Clinical Essentials

PROMETHAZINE HYDROCHLORIDE
PHENERGAN VC
Mechanism of Action
PROMETHAZINE HYDROCHLORIDE

Promethazine is a phenothiazine derivative that acts as a histamine H1 receptor antagonist, blocking the effects of histamine at H1 receptors. It also has anticholinergic, antiemetic, sedative, and antidopaminergic properties.

PHENERGAN VC

Phenergan VC is a combination of promethazine (a phenothiazine derivative with antihistaminic, sedative, antiemetic, and anticholinergic effects) and phenylephrine (a sympathomimetic amine that acts as a decongestant via alpha-1 adrenergic receptor agonism). Promethazine antagonizes H1 receptors, thereby suppressing allergic reactions and motion sickness. Phenylephrine causes vasoconstriction in the nasal mucosa, reducing congestion.

Indications
PROMETHAZINE HYDROCHLORIDE

Allergic conditions (e.g., rhinitis, urticaria),Nausea and vomiting,Motion sickness,Sedation (preoperative, postoperative, or obstetrical),Off-label: Anxiety, insomnia

PHENERGAN VC

Symptomatic relief of upper respiratory symptoms associated with allergic rhinitis or the common cold,Nasal congestion,Sneezing,Rhinorrhea,Off-label: sedation, nausea/vomiting (promethazine component)

Standard Dosing
PROMETHAZINE HYDROCHLORIDE

25-50 mg intramuscular or intravenous injection every 4-6 hours as needed; also 12.5-25 mg orally every 4-6 hours.

PHENERGAN VC

10-20 m L orally every 4-6 hours as needed; each 5 m L contains 6.25 mg promethazine HCl and 5 mg phenylephrine HCl.

Direct Interaction
PROMETHAZINE HYDROCHLORIDE
No Direct Interaction
PHENERGAN VC
No Direct Interaction

Pharmacokinetics

PROMETHAZINE HYDROCHLORIDE
PHENERGAN VC
Half-Life
PROMETHAZINE HYDROCHLORIDE

Terminal elimination half-life is 10-19 hours in adults; prolonged in hepatic impairment (up to 30+ hours) and in elderly.

PHENERGAN VC

9-16 hours; prolonged in hepatic impairment.

Metabolism
PROMETHAZINE HYDROCHLORIDE

Primarily hepatic metabolism via CYP2D6 to promethazine sulfoxide and other metabolites; also undergoes S-oxidation and N-demethylation.

Special Populations

PROMETHAZINE HYDROCHLORIDE
PHENERGAN VC
Renal Adjustments
PROMETHAZINE HYDROCHLORIDE

No specific dose adjustment recommended; use with caution in severe renal impairment (Cr Cl <10 m L/min) due to risk of accumulation.

PHENERGAN VC

GFR 30-60 m L/min: administer with caution; GFR <30 m L/min: avoid use due to risk of accumulation of promethazine metabolites.

Hepatic Adjustments
PROMETHAZINE HYDROCHLORIDE

Safety & Monitoring

PROMETHAZINE HYDROCHLORIDE
PHENERGAN VC
Black Box Warnings
PROMETHAZINE HYDROCHLORIDE
FDA Black Box Warning

Promethazine is contraindicated in children less than 2 years of age due to risk of fatal respiratory depression. Use in children 2 years and older should be avoided with other respiratory depressants.

Pregnancy & Lactation

PROMETHAZINE HYDROCHLORIDE
PHENERGAN VC
Teratogenic Risk
PROMETHAZINE HYDROCHLORIDE

First trimester: Limited human data, no increased risk of major malformations from population-based studies. Second and third trimesters: Use associated with transient neonatal extrapyramidal signs, sedation, withdrawal symptoms if used near term. May inhibit neonatal platelet aggregation.

PHENERGAN VC

First trimester: Limited human data; animal studies show no consistent malformations. Second/third trimester: Risk of neonatal respiratory depression, hypotonia, and withdrawal if used near term. Avoid in late pregnancy due to risk of Kernicterus in jaundiced neonates (sulfite component).

Clinical Insights

PROMETHAZINE HYDROCHLORIDE
PHENERGAN VC
Clinical Pearls
PROMETHAZINE HYDROCHLORIDE

Promethazine hydrochloride is a phenothiazine derivative with strong antihistaminic, antiemetic, sedative, and anticholinergic properties. It is contraindicated in children under 2 years due to risk of fatal respiratory depression. Avoid intra-arterial or subcutaneous administration due to risk of tissue necrosis. Use with caution in patients with asthma, COPD, sleep apnea, myasthenia gravis, and prostate hypertrophy. May cause QT prolongation; monitor ECG in at-risk patients. For severe extravasation, treat with phentolamine. Can interfere with urine glucose tests and pregnancy tests.

PHENERGAN VC

PHENERGAN VC combines promethazine (an antihistamine/antiemetic) and phenylephrine (a decongestant). Avoid use in children <2 years due to risk of fatal respiratory depression. Monitor for CNS depression, especially with concurrent CNS depressants. Contraindicated in patients with severe hypertension or coronary artery disease due to phenylephrine component.

Safety Verification

Known Interactions

PROMETHAZINE HYDROCHLORIDE Risks

No interactions on record

PHENERGAN VC Risks

No interactions on record

Clinical Q&A

Frequently Asked Questions

1. What is the primary difference between PROMETHAZINE HYDROCHLORIDE and PHENERGAN VC?

PROMETHAZINE HYDROCHLORIDE and PHENERGAN VC are distinct pharmacological agents. PROMETHAZINE HYDROCHLORIDE belongs to the Antihistamine / Antiemetic class and is primarily used for Allergic conditions (e.g., rhinitis, urticaria)Nausea and vomitingMotion sicknessSedation (preoperative, postoperative, or obstetrical)Off-label: Anxiety, insomnia. PHENERGAN VC belongs to the Antihistamine/Decongestant Combination class and is primarily used for Symptomatic relief of upper respiratory symptoms associated with allergic rhinitis or the common coldNasal congestionSneezingRhinorrheaOff-label: sedation, nausea/vomiting (promethazine component). Their specific mechanisms of action, pharmacokinetic characteristics, and side effects differ.

2. Are PROMETHAZINE HYDROCHLORIDE and PHENERGAN VC safe during pregnancy?

The maternal-fetal safety profiles of these drugs differ. PROMETHAZINE HYDROCHLORIDE carries a safety status of Category A/B, whereas PHENERGAN VC safety is classified as Category C. Consult a board-certified physician or healthcare specialist to establish an accurate, individualized pregnancy risk assessment before starting either therapy.

PHENERGAN VC

Promethazine undergoes hepatic metabolism primarily via CYP2D6 and to a lesser extent by other CYP enzymes. Phenylephrine is metabolized in the liver by monoamine oxidase (MAO) and sulfotransferase.

Excretion
PROMETHAZINE HYDROCHLORIDE

Primarily hepatic metabolism; renal excretion of metabolites accounts for <1% of unchanged drug; biliary/fecal excretion of metabolites ~70-80%.

PHENERGAN VC

Renal: 70-80% as metabolites; biliary/fecal: 20-30%.

Protein Binding
PROMETHAZINE HYDROCHLORIDE

93% bound primarily to albumin.

PHENERGAN VC

76-90% bound to albumin.

VD (L/kg)
PROMETHAZINE HYDROCHLORIDE

9-16 L/kg; indicates extensive tissue distribution and accumulation in tissues.

PHENERGAN VC

13-18 L/kg; extensive tissue distribution.

Bioavailability
PROMETHAZINE HYDROCHLORIDE

Oral: ~25% due to first-pass metabolism; IM: ~70-80%; IV: 100%; rectal: ~25-30%.

PHENERGAN VC

Oral: 25-70% due to first-pass effect; IM: 85-95%.

Child-Pugh Class A: no adjustment; Class B: reduce dose by 50%; Class C: avoid use or reduce dose by 75%.

PHENERGAN VC

Child-Pugh Class A: no adjustment needed; Child-Pugh Class B: reduce dose by 50%; Child-Pugh Class C: contraindicated.

Pediatric Dosing
PROMETHAZINE HYDROCHLORIDE

2-6 years: 5-6.25 mg orally every 4-6 hours; 6-12 years: 6.25-12.5 mg orally every 4-6 hours; >12 years: as adult; intramuscular: 0.25-0.5 mg/kg every 4-6 hours.

PHENERGAN VC

Children 2-5 years: 5-10 m L orally every 4-6 hours; 6-12 years: 10-15 m L orally every 4-6 hours; not recommended for children under 2 years due to risk of respiratory depression.

Geriatric Dosing
PROMETHAZINE HYDROCHLORIDE

Start at lowest effective dose (e.g., 12.5 mg orally or 12.5-25 mg IM/IV); increase cautiously due to increased risk of sedation, confusion, and anticholinergic effects.

PHENERGAN VC

Initiate at the lower end of the dosing range (e.g., 10 m L orally every 6 hours) due to increased sensitivity to anticholinergic effects and risk of sedation, confusion, and hypotension; avoid prolonged use.

PHENERGAN VC
FDA Black Box Warning

WARNING: RESPIRATORY DEPRESSION IN CHILDREN. Promethazine is contraindicated in children younger than 2 years due to the risk of fatal respiratory depression. Use in children aged 2 years and older with caution and at lowest effective dose.

Warnings/Precautions
PROMETHAZINE HYDROCHLORIDE
  • Risk of respiratory depression, especially in children
  • CNS depression; avoid with alcohol or other sedatives
  • May cause bone marrow suppression, agranulocytosis
  • Anticholinergic effects (e.g., urinary retention, blurred vision)
  • Extrapyramidal reactions, tardive dyskinesia
  • Neuroleptic malignant syndrome (rare)
  • May elevate prolactin levels
  • Interference with pregnancy test
PHENERGAN VC
  • Respiratory depression: Avoid in children <2 years; use caution in patients with respiratory conditions like asthma or COPD.
  • CNS depression: May cause drowsiness; avoid with alcohol or other CNS depressants.
  • Anticholinergic effects: Use caution in patients with glaucoma, prostatic hypertrophy, or pyloroduodenal obstruction.
  • Cardiovascular effects: Phenylephrine may cause hypertension, arrhythmias; use caution in heart disease, hyperthyroidism, diabetes.
  • Extrapyramidal symptoms: Rare but possible with promethazine.
  • Neuroleptic malignant syndrome: Discontinue if suspected.
  • Drug interactions: MAO inhibitors, beta-blockers, other antihypertensives.
Contraindications
PROMETHAZINE HYDROCHLORIDE
  • Hypersensitivity to promethazine or other phenothiazines
  • Children less than 2 years of age
  • Comatose patients or those receiving large doses of other CNS depressants
  • Seizure disorders (may lower seizure threshold)
  • Prostatic hypertrophy, bladder neck obstruction
  • Angle-closure glaucoma
  • Symptomatic prostatic hypertrophy
PHENERGAN VC
  • Children younger than 2 years (black box warning)
  • Hypersensitivity to promethazine, phenylephrine, or any component
  • Asthma or other lower respiratory tract disease
  • Comatose states
  • Concurrent use of MAO inhibitors or within 14 days
  • Narrow-angle glaucoma
  • Symptomatic prostatic hypertrophy
  • Bladder neck obstruction
  • Hypertension or coronary artery disease (severe)
Adverse Reactions
PROMETHAZINE HYDROCHLORIDE
Data Pending
PHENERGAN VC
Data Pending
Food Interactions
PROMETHAZINE HYDROCHLORIDE

Avoid alcohol and CNS depressants. No significant food interactions; may be taken with food if gastric upset occurs. Grapefruit juice may increase systemic exposure? (Not well established; consider monitoring for increased sedation).

PHENERGAN VC

Avoid alcohol and grapefruit juice. Alcohol increases CNS depression; grapefruit juice may enhance phenylephrine effects. No significant food restrictions otherwise.

Lactation Summary
PROMETHAZINE HYDROCHLORIDE

Promethazine is excreted in breast milk in low concentrations; M/P ratio not established. Due to risk of drowsiness and irritability in nursing infants avoid use, especially in neonates or preterm infants. AAP classifies as compatible but caution advised.

PHENERGAN VC

Excreted in breast milk in low amounts (M/P ratio unknown for promethazine; phenylephrine M/P ratio ~0.3). Potential for infant sedation, irritability, and decreased milk supply (phenylephrine). Use only if benefit outweighs risk.

Pregnancy Dosing
PROMETHAZINE HYDROCHLORIDE

No pharmacokinetic data necessitating dose adjustment; however, use lowest effective dose due to potential fetal risks.

PHENERGAN VC

No specific dose adjustment recommended; use lowest effective dose for shortest duration. Avoid in preeclampsia/hypertension due to phenylephrine. Pharmacokinetic changes in pregnancy (increased volume of distribution, enhanced clearance) may require higher doses but not systematically studied.

Maternal Safety Status
PROMETHAZINE HYDROCHLORIDE
Category A/B
PHENERGAN VC
Category C
Patient Counseling
PROMETHAZINE HYDROCHLORIDE

Do not use in children under 2 years old; use with caution in children over 2.,May cause severe drowsiness; do not drive or operate heavy machinery.,Avoid alcohol and other CNS depressants.,Report any muscle stiffness, tremor, or involuntary movements.,If using for motion sickness, take at least 30 minutes before travel.,Do not take with other antihistamines or cold medications.,May cause dry mouth; use sugar-free candy or ice chips.,If you have a history of seizures, asthma, or glaucoma, discuss with your doctor.

PHENERGAN VC

Do not use in children under 2 years old due to risk of serious breathing problems.,May cause drowsiness; avoid driving or operating heavy machinery until you know how this medication affects you.,Avoid alcohol and other sedatives while taking this medication.,Phenylephrine can raise blood pressure; monitor if you have high blood pressure or heart problems.,Take folic acid as directed to prevent neural tube defects.,Do not exceed recommended dose; consult your doctor if symptoms persist.