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. |
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 | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for PROMETHEGAN (PROMETHEGAN).
| Breastfeeding | Excreted in breast milk (M/P ratio unknown); potential for drowsiness in infant. Use caution, avoid prolonged use. |
| 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 |
■ 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 |
["Children younger than 2 years (risk of fatal respiratory depression)","Comatose patients","Severe central nervous system depression","Concurrent use of large amounts of alcohol or other CNS depressants","Known hypersensitivity to promethazine or other phenothiazines","Concurrent use with monoamine oxidase inhibitors (MAOIs) (risk of hypertensive crisis)","Narrow-angle glaucoma","Prostatic hypertrophy","Bladder neck obstruction","History of sleep apnea"]
| 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)"] |
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| 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. |