PROMETHAZINE HYDROCHLORIDE 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 that acts as a competitive antagonist at histamine H1 receptors, thereby blocking the effects of histamine. It also has anticholinergic, antiemetic, and sedative properties. In the CNS, it inhibits the chemoreceptor trigger zone and vestibular apparatus, contributing to its antiemetic effect.
| Metabolism | Extensively metabolized in the liver via oxidation, primarily by CYP2D6, and via N-demethylation and sulfoxidation. Metabolites include promethazine sulfoxide and N-desmethylpromethazine. |
| Excretion | Primarily hepatic metabolism; renal excretion of metabolites accounts for ~70% of elimination, with 20-30% as unchanged drug in urine. Fecal excretion is minimal (~5%). |
| Half-life | Terminal elimination half-life is approximately 10-19 hours in adults (mean ~16 hours). In children, half-life is shorter (~7-14 hours). Clinical context: Once-daily dosing may be insufficient for continuous sedation; requires every 6-8 hour dosing for sustained effect. |
| Protein binding | 85-93% bound primarily to albumin (HSA), with minor binding to alpha1-acid glycoprotein. |
| Volume of Distribution | Vd ranges from 3-5 L/kg (mean ~4 L/kg) indicating extensive tissue distribution. Clinical meaning: High tissue binding; large loading dose may be needed for rapid effect. |
| Bioavailability | Oral: ~25-40% (extensive first-pass metabolism); IM: ~70-80%; Rectal: ~50-60%; IV: 100%. |
| Onset of Action | IV: 3-5 minutes; IM: 20 minutes; Oral: 20-30 minutes; Rectal: 30-45 minutes. Clinical effect (sedation/antiemetic) correlates with peak plasma levels at 1-2 hours (oral). |
| Duration of Action | Duration of clinical effect (sedation/antiemesis) is 4-12 hours depending on route and dose. IV/IM: 2-8 hours; Oral: 4-12 hours. Note: Prolonged duration in elderly or hepatic impairment. |
Adults: 25 mg orally or intramuscularly every 4 to 6 hours as needed; for motion sickness, 25 mg taken 30-60 minutes before departure, then every 12 hours as needed.
| Dosage form | SYRUP |
| Renal impairment | No specific GFR-based dose adjustment recommended; use caution in severe renal impairment (eGFR <30 mL/min) due to risk of accumulation and CNS adverse effects. |
| Liver impairment | Child-Pugh Class A: No adjustment; Child-Pugh Class B: Reduce dose by 50% or extend dosing interval; Child-Pugh Class C: Avoid use or use lowest dose with caution (e.g., 12.5 mg every 6-12 hours). |
| Pediatric use | Children 2 years and older: 0.5 mg/kg orally or intramuscularly every 6 hours as needed, not to exceed 25 mg per dose (max 50 mg/day); for motion sickness: 0.5 mg/kg given 30-60 minutes before departure, then every 12 hours as needed. |
| Geriatric use | Initiate at lower doses (e.g., 12.5 mg orally or intramuscularly every 6-8 hours) due to increased sensitivity to CNS depressant effects, anticholinergic side effects (confusion, urinary retention), and risk of falls; avoid in patients with dementia or cognitive impairment. |
| 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 | Excreted into breast milk; M/P ratio approximately 0.5-1.0. Limited data suggest low risk with occasional use, but may cause sedation, apnea, or irritability in neonate; avoid in breastfeeding mothers of preterm or compromised infants. Monitor infant for drowsiness. |
| Teratogenic Risk | Pregnancy category C. First trimester: Potential risk of teratogenicity based on animal studies; human data limited but not associated with major malformations in large cohort studies. Second/third trimester: Use near term may cause respiratory depression, extrapyramidal signs in neonate; avoid during labor due to potential adverse effects on uterine contractility. |
■ FDA Black Box Warning
Do not use in children younger than 2 years due to the risk of respiratory depression (including fatal cases). Promethazine should not be used in combination with other respiratory depressants.
| Common Effects | nausea/vomiting |
| Serious Effects |
["Hypersensitivity to promethazine or other phenothiazines.","Children <2 years (increased risk of respiratory depression).","Comatose states or severe CNS depression.","Concurrent use with large amounts of CNS depressants (e.g., alcohol, barbiturates).","Intra-arterial or subcutaneous administration (risk of tissue necrosis)."]
| Precautions | ["Respiratory depression: Use caution in patients with respiratory compromise (e.g., COPD, sleep apnea).","CNS depression: Avoid concurrent use with alcohol or other CNS depressants.","Extrapyramidal symptoms: Rare but reported, particularly with high doses.","Neuroleptic malignant syndrome: Discontinue if signs occur.","Photosensitivity: Avoid excessive sun exposure.","Seizure threshold: May lower seizure threshold; use with caution in seizure disorders.","Hepatic impairment: Monitor liver function; may accumulate in severe disease.","Use in elderly: Increased sensitivity; risk of falls, confusion, hypotension.","Pregnancy: Avoid in labor and preterm labor due to possible effects on uterine contractility."] |
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| Fetal Monitoring | Monitor maternal blood pressure, heart rate, and respiratory status; assess for sedation or extrapyramidal symptoms. Fetal monitoring: heart rate and uterine activity if used during labor; observe neonate for respiratory depression, hypotonia, and extrapyramidal signs for 48 hours after exposure near delivery. |
| Fertility Effects | No known significant effect on human fertility based on limited data; in animal studies, high doses caused reduced fertility, but clinical relevance unknown. |