PROMETHEGAN
Clinical safety rating: caution
Comprehensive clinical and safety monograph for PROMETHEGAN (PROMETHEGAN).
Promethazine is a phenothiazine derivative that acts as a competitive antagonist at histamine H1 receptors, exerting antihistaminic, sedative, antiemetic, anticholinergic, and local anesthetic effects. Its antiemetic effect is mediated via blockade of dopamine D2 receptors in the chemoreceptor trigger zone.
| Metabolism | Primarily hepatic metabolism via glucuronidation, N-demethylation (CYP2D6), and sulfoxidation; major metabolites are promethazine sulfoxide and N-desmethylpromethazine; less than 1% excreted unchanged in urine. |
| Excretion | Primarily renal (urinary) as conjugated metabolites; about 70-80% of a dose is excreted in urine within 48 hours. Small amounts appear in feces via biliary elimination (approximately 5-10%). |
| Half-life | Terminal elimination half-life: 9-16 hours in adults, with an average of 12 hours. In children, half-life may be shorter (6-9 hours). Clinical context: dosing interval typically every 8-12 hours; accumulation possible with repeated dosing. |
| Protein binding | Approximately 85-90% bound to plasma proteins, primarily albumin and possibly alpha1-acid glycoprotein. |
| Volume of Distribution | 13-20 L/kg (adults); extensive tissue distribution, particularly in lungs, spleen, and brain, indicating high lipophilicity and penetration into CNS. |
| Bioavailability | Oral: variable, approximately 25-70% due to extensive first-pass hepatic metabolism; Intramuscular: approximately 70-100%; Rectal: approximately 30-50%. |
| Onset of Action | Oral: 15-60 minutes; Intramuscular: 10-30 minutes; Intravenous: 3-5 minutes; Rectal: 20-60 minutes. |
| Duration of Action | Oral: 4-6 hours (antiemetic, antihistaminic), up to 12 hours for sedation; Intramuscular: 4-6 hours; Intravenous: 2-4 hours; Rectal: 4-6 hours. Note: Sedative effects may persist longer. |
| Molecular Weight | 340.48 |
IV: 25-50 mg every 4-6 hours; IM: 25-50 mg every 4-6 hours; PO: 25-50 mg every 4-6 hours; PR: 25-50 mg every 4-6 hours; Maximum: 300 mg/day.
| Dosage form | SUPPOSITORY |
| Renal impairment | GFR 10-50 mL/min: Administer every 6-12 hours; GFR <10 mL/min: Administer every 12-18 hours. |
| Liver impairment | Child-Pugh Class A: No adjustment; Class B: Reduce dose by 50%; Class C: Avoid use or use with extreme caution. |
| Pediatric use | Weight-based: 0.25-1 mg/kg/dose IV/IM/PO/PR every 4-6 hours; Maximum single dose: 25 mg; Maximum daily: 100 mg. |
| Geriatric use | Initial dose: 12.5-25 mg every 6-12 hours; Titrate cautiously due to increased sensitivity to anticholinergic effects and sedation; Maximum daily dose: 150 mg. |
| 1st trimester | Avoid; risk of teratogenicity (cleft palate, neural tube defects) based on animal data and human retrospective studies. |
| 2nd trimester | Avoid; may cause maternal sedation and hypotension; use only if benefit outweighs risk. |
| 3rd trimester | Avoid; risk of neonatal respiratory depression, hypotonia, withdrawal symptoms, and QT prolongation. |
Clinical note
Comprehensive clinical and safety monograph for PROMETHEGAN (PROMETHEGAN).
| Placental transfer | Crosses placenta; achieves fetal concentrations similar to maternal levels. Detected in amniotic fluid. |
| Breastfeeding | Excreted in breast milk in low amounts; however, due to potential for sedation and respiratory depression in the infant, caution is advised. Monitor infant for drowsiness, lethargy, and poor feeding. |
■ FDA Black Box Warning
Promethazine should not be used in children younger than 2 years due to the risk of respiratory depression and death. Caution should be exercised in children aged 2-6 years. It should not be used in patients with known hypersensitivity to promethazine or other phenothiazines.
| Serious Effects |
Hypersensitivity to promethazine or any phenothiazineComatose statesSevere CNS depressionConcurrent use of large doses of other CNS depressants (e.g., barbiturates, alcohol)Children younger than 2 years (risk of respiratory depression)Intra-arterial or subcutaneous injection
| Precautions | Respiratory depression (especially in children, elderly, or with respiratory compromise), Severe tissue injury (including gangrene) with intra-arterial administration or extravasation, Central nervous system depression; avoid concurrent use with alcohol or other CNS depressants, Neuroleptic malignant syndrome (NMS) (rare), Anticholinergic effects (constipation, urinary retention, blurred vision), Lower seizure threshold; caution in epilepsy, Bone marrow suppression (agranulocytosis, leukopenia), Photosensitivity, May cause extrapyramidal symptoms (dystonia, akathisia), Use in pregnancy only if clearly needed (risk of fetal respiratory depression if used near term) |
Loading safety data…
| Lactation Rating |
| L3 (Moderately Safe) |
| Teratogenic Risk | First trimester: Risk of neural tube defects (NTDs) with animal studies showing fetal malformations; human data limited but caution advised. Second/third trimester: Risk of neonatal respiratory depression, hypotonia, and withdrawal if used near term (especially high doses). |
| Fetal Monitoring | Monitor fetal heart rate and maternal sedation levels, especially during labor. Avoid in women with preeclampsia or fetal distress. |
| Fertility Effects | No specific human data; animal studies show no significant impairment. May slightly increase prolactin but effect on fertility unclear. |
| Food/Dietary |
| No significant food interactions. However, taking with food may reduce GI upset. Avoid grapefruit juice as it may inhibit metabolism (though less studied). Alcohol should be strictly avoided due to additive CNS depression. |
| Clinical Pearls | Promethazine is a phenothiazine derivative with strong antihistaminergic, antiemetic, and sedative properties. It can cause significant respiratory depression, especially in children and elderly, and should not be used in patients with asthma or COPD. Avoid intra-arterial injection due to risk of gangrene; administer deep intramuscularly. Can cause extrapyramidal symptoms, particularly in geriatric patients. Monitor for QT prolongation in susceptible individuals. |
| Patient Advice | This medication may cause drowsiness; do not drive or operate machinery until you know how it affects you. · Avoid alcohol and other CNS depressants while taking promethazine. · Report any involuntary muscle movements or restlessness to your healthcare provider. · Do not exceed the recommended dose; overdose can cause severe sedation and respiratory depression. · Store at room temperature away from moisture and light. |