HYDRAMINE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for HYDRAMINE (HYDRAMINE).
Antagonist of histamine H1 receptors, preventing histamine-mediated responses such as vasodilation, bronchoconstriction, and increased capillary permeability.
| Metabolism | Hepatic via CYP450 enzymes (primarily CYP2D6 and CYP3A4); metabolites include diphenhydramine and norfluoxetine. |
| Excretion | Primarily renal (95%) as metabolites; <5% unchanged; 5% fecal |
| Half-life | Terminal elimination half-life 5.7 hours, range 4.2-7.7 hours; prolonged in hepatic impairment (up to 15 hours in cirrhosis) |
| Protein binding | 75-85% bound to albumin, α1-acid glycoprotein, and lipoproteins |
| Volume of Distribution | 6.5-8 L/kg (0.8-1.2 L/kg in neonates); extensive tissue distribution, crosses blood-brain barrier |
| Bioavailability | Oral: 40-60% due to extensive first-pass metabolism; sublingual: not available; intramuscular: 80-100% |
| Onset of Action | Oral: 30-45 minutes; Intravenous: within minutes (rapid distribution); Intramuscular: 15-30 minutes |
| Duration of Action | Oral: 4-6 hours; Intravenous/Intramuscular: 3-4 hours. Clinical sedation often shorter (2-4 hours) due to tolerance |
| Molecular Weight | 255.4 |
50-100 mg IV/IM every 4-6 hours, maximum 400 mg per day. Also available as 50 mg oral tablets.
| Dosage form | SYRUP |
| Renal impairment | CrCl 10-50 mL/min: administer every 6-8 hours; CrCl <10 mL/min: administer every 8-12 hours. |
| Liver impairment | Child-Pugh Class B or C: reduce dose by 50% or extend dosing interval to every 8-12 hours. |
| Pediatric use | 1.25 mg/kg IV/IM every 6 hours (maximum single dose 50 mg). Oral: 5 mg/kg/day divided every 6 hours. |
| Geriatric use | Start at 25 mg every 6-8 hours; increase cautiously due to increased risk of anticholinergic effects and confusion. |
| 1st trimester | Avoid use in first trimester due to potential teratogenic effects; limited human data but animal studies show fetal abnormalities. |
| 2nd trimester | Use only if clearly needed; monitor for fetal effects; limited data suggest possible risk of premature labor or neonatal withdrawal. |
| 3rd trimester | Avoid near term due to risk of neonatal withdrawal syndrome, respiratory depression, or bradycardia. |
Clinical note
Comprehensive clinical and safety monograph for HYDRAMINE (HYDRAMINE).
| Placental transfer | Hydramine crosses the placenta readily; drug levels in fetal plasma are similar to maternal levels. Animal studies show placental transfer. |
| Breastfeeding | Hydramine is excreted into breast milk in small amounts; however, due to potential adverse effects such as sedation, irritability, or respiratory depression in the infant, caution is advised. Monitor infant for signs of sedation and poor feeding. The American Academy of Pediatrics considers it compatible with breastfeeding, but alternatives may be preferred. |
■ FDA Black Box Warning
None.
| Serious Effects |
Hypersensitivity to hydramine or any of its componentsBreastfeeding infants with apnea or sleep apneaPorphyriaSevere hypoglycaemiaMonoamine oxidase inhibitor (MAOI) therapy (concurrent or within 14 days)
| Precautions | May cause drowsiness; avoid driving or operating machinery. Use with caution in patients with asthma, glaucoma, prostatic hyperplasia, or hepatic impairment. Elderly patients more sensitive to anticholinergic effects. |
| Food/Dietary | No significant food interactions; alcohol should be avoided due to additive CNS depression. |
| Clinical Pearls |
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| Lactation Rating | L3 (Moderately Safe) |
| Teratogenic Risk | FDA Pregnancy Category C. First trimester: No adequate studies in humans; animal studies have shown teratogenic effects at high doses. Avoid use unless benefit outweighs risk. Second and third trimesters: No specific fetal risks reported, but anticholinergic effects may cause fetal tachycardia or meconium ileus. Use with caution. |
| Fetal Monitoring | Monitor for maternal anticholinergic effects (dry mouth, blurred vision, urinary retention). Fetal heart rate monitoring advised if used in third trimester due to potential for fetal tachycardia. |
| Fertility Effects | No significant effects on fertility reported in animal studies. In humans, no data available; theoretical risk due to anticholinergic effects on cervical mucus or ovulation. |
| Hydramine (diphenhydramine) is a first-generation antihistamine with strong anticholinergic effects. Use with caution in elderly due to increased risk of confusion, falls, and urinary retention. Avoid in patients with narrow-angle glaucoma, prostatic hypertrophy, or during acute asthma attacks. Sedative effects can be utilized for sleep but tolerance develops quickly; not recommended for chronic insomnia. |
| Patient Advice | Take exactly as prescribed; do not exceed recommended dose. · This medication may cause drowsiness or dizziness; avoid driving or operating machinery until you know how it affects you. · Avoid alcohol and other CNS depressants while taking this drug. · Do not use for longer than recommended for sleep; tolerance may develop. · Report any vision changes, difficulty urinating, or rapid heartbeat to your healthcare provider. · Store at room temperature away from moisture and heat. · Keep out of reach of children; overdose may be fatal. |