SEIZALAM
Clinical safety rating: caution
Comprehensive clinical and safety monograph for SEIZALAM (SEIZALAM).
Binds to benzodiazepine site on GABA-A receptors, enhancing chloride ion conductance and neuronal hyperpolarization.
| Metabolism | Hepatic via CYP3A4 and glucuronidation; active metabolite N-desmethylclobazam. |
| Excretion | Primarily hepatic metabolism; less than 1% excreted unchanged in urine. Metabolites are excreted renally (approx. 70%) and fecal/biliary (approx. 30%). |
| Half-life | Terminal elimination half-life is 15–20 hours in adults; prolonged in elderly and hepatic impairment (up to 40 hours). |
| Protein binding | Approximately 98% bound to albumin. |
| Volume of Distribution | 1.0–1.5 L/kg; reflects extensive tissue distribution. |
| Bioavailability | Oral: 70–90%; Intramuscular: 80–95% (relative to IV). |
| Onset of Action | Intravenous: 2–5 minutes; Oral: 15–30 minutes; Intramuscular: 10–20 minutes. |
| Duration of Action | 4–6 hours for anxiolytic effect; anticonvulsant effect may last 30 minutes to 1 hour after IV bolus. |
| Molecular Weight | 284.74 |
0.5 mg orally twice daily, titrated weekly by 0.5 mg/day to a maximum of 4 mg/day
| Dosage form | SOLUTION |
| Renal impairment | GFR 30-89 mL/min: no adjustment; GFR <30 mL/min: reduce dose by 50%; hemodialysis: 0.25 mg daily |
| Liver impairment | Child-Pugh A: no adjustment; Child-Pugh B: reduce dose by 50%; Child-Pugh C: contraindicated |
| Pediatric use | 0.01 mg/kg/dose (up to 0.5 mg) twice daily, titrate weekly to max 0.1 mg/kg/day (not to exceed adult max) |
| Geriatric use | 0.25 mg once daily initially; titrate slowly to 0.5 mg twice daily; max 2 mg/day |
| 1st trimester | Avoid due to increased risk of congenital malformations, particularly neural tube defects and oral clefts, based on human data. |
| 2nd trimester | Avoid due to risk of fetal growth restriction and neurodevelopmental effects; use only if benefit outweighs risk. |
| 3rd trimester | Avoid due to risk of neonatal withdrawal syndrome and respiratory depression; use only if clearly needed. |
Clinical note
Comprehensive clinical and safety monograph for SEIZALAM (SEIZALAM).
| Placental transfer | Crosses placenta readily, achieving fetal serum concentrations equal to or greater than maternal levels. |
| Breastfeeding | Seizalam (diazepam) is excreted into breast milk. Drowsiness, feeding difficulties, and weight loss have been reported in infants. Consider alternative anticonvulsants with a safer profile during lactation. |
■ FDA Black Box Warning
Risk of respiratory depression, hypotension, and cardiac arrest; coadministration with CNS depressants increases risk.
| Serious Effects |
Severe hepatic impairmentAcute narrow-angle glaucomaMyasthenia gravisKnown hypersensitivity to benzodiazepines
| Precautions | Respiratory depression, hypotension, sedation, tolerance, withdrawal seizures, abuse potential, paradoxical reactions. |
| Food/Dietary | Grapefruit and grapefruit juice may increase midazolam levels; avoid concurrent use. High-fat meals may reduce absorption of oral formulation; administer on empty stomach if possible. |
| Clinical Pearls |
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| Lactation Rating | L3 (Moderately Safe) or 'Use Caution' |
| Teratogenic Risk | First trimester: Increased risk of major congenital malformations, particularly neural tube defects and orofacial clefts (OR 2.0-3.0). Second/third trimester: Fetal growth restriction, preterm birth, neurodevelopmental deficits. Chronic use: Neonatal withdrawal syndrome, floppy infant syndrome. |
| Fetal Monitoring | Maternal: Serum drug levels, liver function tests, complete blood count, seizure frequency. Fetal: Ultrasound for growth and anatomy, nonstress test, biophysical profile in third trimester, neonatal assessment for withdrawal. |
| Fertility Effects | May cause menstrual irregularities and anovulation by altering hypothalamic-pituitary-ovarian axis. Reversible upon discontinuation. No evidence of permanent infertility. |
| SEIZALAM (midazolam) is a short-acting benzodiazepine used for acute seizure control. Administer IV/IM; intranasal formulation available. Onset within 2-5 minutes. Monitor respiratory depression, especially with concurrent opioids. Flumazenil is reversal agent. Avoid in narrow-angle glaucoma. Dose adjust in elderly and hepatic impairment. |
| Patient Advice | Take exactly as prescribed; do not stop abruptly to avoid withdrawal seizures. · May cause drowsiness, dizziness; avoid driving or operating machinery. · Avoid alcohol and other CNS depressants. · Report any difficulty breathing, severe sedation, or rash immediately. · Store at room temperature away from light and moisture. |