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. |
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 | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
CNS depressants may enhance sedative effects Can cause respiratory depression in children and extrapyramidal symptoms.
| FDA category | Animal |
| Breastfeeding | Probably compatible. Promethazine is excreted in human milk in small amounts; M/P ratio not reported. American Academy of Pediatrics considers compatible but caution with prolonged use due to potential sedation or apnea in infants. Monitor for drowsiness or feeding difficulties. |
| Teratogenic Risk |
■ 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 |
["Hypersensitivity to promethazine, phenylephrine, or any component","Children younger than 2 years","Concomitant use of monoamine oxidase inhibitors (MAOIs) or within 14 days of such treatment"]
| 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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| 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. |