PROMETHAZINE VC PLAIN
Clinical safety rating: safe
CNS depressants may enhance sedative effects Can cause respiratory depression in children and extrapyramidal symptoms.
Promethazine is a phenothiazine derivative with antihistaminic (H1 receptor antagonist), sedative, antiemetic, and anticholinergic effects. Phenylephrine is a sympathomimetic amine acting primarily on alpha-1 adrenergic receptors, causing vasoconstriction.
| Metabolism | Promethazine is extensively metabolized in the liver via oxidation (CYP2D6) and conjugation. Phenylephrine is primarily metabolized by monoamine oxidase (MAO) and sulfate conjugation. |
| Excretion | Primarily renal as inactive metabolites; approximately 70-80% excreted in urine, with about 20-30% in feces via biliary secretion. Less than 1% excreted unchanged. |
| Half-life | Terminal elimination half-life is approximately 9–16 hours (mean ~12 hours) in adults; may be prolonged in hepatic impairment or elderly patients. |
| Protein binding | Approximately 88-93% bound, primarily to albumin. |
| Volume of Distribution | Approximately 9-13 L/kg; indicates extensive tissue distribution and accumulation in tissues. |
| Bioavailability | Oral bioavailability is approximately 25% due to extensive first-pass metabolism; IM bioavailability is close to 100%. |
| Onset of Action | Oral: 15–60 minutes; IM: 20–30 minutes; IV: 3–5 minutes; rectal: 30–60 minutes. |
| Duration of Action | Duration of clinical effect is 4–6 hours for antihistaminic and antiemetic effects; sedative effects may persist up to 12 hours. |
| Molecular Weight | 284.42 |
| Action Class | Antihistamine (first-generation), Antiemetic, Phenothiazine |
Adults: 1 tablet (promethazine 6.25 mg, phenylephrine 10 mg) orally every 4-6 hours as needed, not to exceed 4 tablets in 24 hours.
| Dosage form | SYRUP |
| Renal impairment | GFR < 10 mL/min: Avoid use due to risk of accumulation and anticholinergic effects. GFR 10-50 mL/min: Use with caution, consider dose reduction or extended interval; no specific guidelines established. |
| Liver impairment | Child-Pugh Class A: No adjustment necessary. Child-Pugh Class B: Reduce dose by 50% or extend dosing interval to every 8 hours. Child-Pugh Class C: Avoid use due to risk of hepatic encephalopathy and accumulation. |
| Pediatric use | Children 2-12 years: 0.25-0.5 mg/kg promethazine (max 25 mg) plus phenylephrine 0.1-0.2 mg/kg orally every 6 hours as needed; not to exceed 4 doses per 24 hours. Children <2 years: Contraindicated due to risk of respiratory depression. |
| Geriatric use | Initiate at lowest effective dose (e.g., half tablet) every 6-8 hours due to increased sensitivity to anticholinergic effects, dizziness, hypotension, and confusion. Avoid in patients with prostatic hypertrophy or bladder obstruction. |
| 1st trimester | Avoid due to potential teratogenic effects; case-control studies suggest possible association with congenital malformations, particularly cleft palate. |
| 2nd trimester | Use only if clearly needed; no well-controlled studies, but limited data suggest minimal risk. |
| 3rd trimester | Avoid near term due to risks of respiratory depression, extrapyramidal signs, and withdrawal symptoms in neonates. |
Clinical note
CNS depressants may enhance sedative effects Can cause respiratory depression in children and extrapyramidal symptoms.
| FDA category | Animal |
| Placental transfer | Promethazine crosses the placenta; detectable levels in fetal serum and amniotic fluid. Animal studies show fetal toxicity at high doses. |
| Breastfeeding |
■ FDA Black Box Warning
Promethazine should not be used in children younger than 2 years because of the risk of fatal respiratory depression. Use in children 2 years and older should be with caution and at the lowest effective dose.
| Common Effects | nausea/vomiting |
| Serious Effects | Respiratory depression (especially in children and with high doses), Severe tissue injury (including gangrene) with intravenous administration due to perivascular extravasation, Neuroleptic malignant syndrome (rare), Seizures, Cholestatic jaundice, Agranulocytosis, Leukopenia, Thrombocytopenia, QT prolongation and torsades de pointes (rare) |
Hypersensitivity to promethazine or any phenothiazineComatose statesCentral nervous system depression due to alcohol, barbiturates, or other CNS depressantsChildren under 2 years of age (risk of fatal respiratory depression)Use in pediatric patients with Reye's syndromeLocal or regional anesthesia in children (risk of respiratory depression)
| Precautions | Respiratory depression: Use with caution in patients with respiratory impairment, especially children., CNS depression: May impair mental and physical abilities; avoid hazardous activities., Anticholinergic effects: Use with caution in patients with glaucoma, prostatic hypertrophy, or urinary retention., Cardiovascular effects: Phenylephrine may cause hypertension, bradycardia, and arrhythmias; use cautiously in cardiovascular disease. |
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| Promethazine is excreted into breast milk in small amounts; it may cause drowsiness or irritability in the infant. The manufacturer recommends caution due to potential for apnea and SIDS in neonates. Avoid use while breastfeeding if possible, especially in preterm or low-birth-weight infants. |
| Lactation Rating | L4 - Possibly Hazardous; alternative drugs are preferred. |
| Teratogenic Risk | FDA Pregnancy Category C. First trimester: Limited human data; animal studies show no teratogenic effect but increased fetal loss at high doses. Second and third trimesters: Potential for respiratory depression and extrapyramidal symptoms in neonate if used near term; avoid in preterm labor due to possible placental hypoperfusion. |
| Fetal Monitoring | Maternal: Blood pressure, heart rate, respiratory rate, level of consciousness. Fetal/neonatal: Heart rate monitoring during labor if used; assess for respiratory depression, hypotonia, or extrapyramidal signs in neonate after delivery if used near term. |
| Fertility Effects | No specific human data on fertility impairment. Animal studies (rodents) at high doses have shown decreased fertility and increased embryolethality. Clinical relevance unknown. |
| Food/Dietary | Avoid alcohol. Grapefruit juice may increase phenylephrine levels, but clinical significance is unclear. No specific dietary restrictions. |
| Clinical Pearls | Promethazine VC Plain contains promethazine (phenothiazine antihistamine) and phenylephrine (alpha-1 agonist). Avoid in children <2 years due to risk of fatal respiratory depression. Monitor for dystonic reactions and neuroleptic malignant syndrome. Use with caution in patients with asthma, glaucoma, or urinary retention. May cause false-positive urine drug screens for amphetamines. |
| Patient Advice | Do not use in children under 2 years old. · Avoid driving or operating machinery until you know how this medication affects you, as it may cause drowsiness or dizziness. · Do not drink alcohol while taking this medication. · Report immediately any stiff muscles, fever, confusion, or involuntary movements. · Do not take with other medications that cause drowsiness (e.g., sleep aids, tranquilizers). · Use caution if you have asthma, glaucoma, or difficulty urinating. |