Therapeutic Classification: anticonvulsants
Absorption: 68–74% absorbed following oral administration.
Distribution: Widely distributed to extravascular tissues.
Metabolism/Excretion: Primarily metabolized by the liver via CYP1A2, CYP2B6, and CYP2D6 isoenzymes to norfenfluramine (active metabolite); CYP2C9, CYP2C19, and CYP3A involved to a minor extent. Primarily excreted in urine (>90%) as fenfluramine, norfenfluramine, and other metabolites.
Half-Life: 20 hr.
Without Concurrent Stiripentol Therapy
- PO (Adults and Children ≥2 yr): 0.1 mg/kg twice daily (max dosage = 26 mg/day); may ↑ to 0.2 mg/kg twice daily (max dosage = 26 mg/day) in 7 days and then ↑ to 0.35 mg/kg twice daily (max dosage = 26 mg/day) after another 7 days. If rapid titration is needed, may titrate dosage every 4 days. Concurrent use of strong CYP1A2 or CYP2D6 inhibitor: Not to exceed 20 mg/day.
Renal Impairment
- PO (Adults and Children ≥2 yr): CCr 15–29 mL/min/1.73 m2: Not to exceed 20 mg/day.
Hepatic Impairment
- PO (Adults and Children ≥2 yr): Mild or moderate hepatic impairment: Not to exceed 20 mg/day. Severe hepatic impairment: Not to exceed 17 mg/day.
With Concurrent Stiripentol and Clobazam Therapy
- PO (Adults and Children ≥2 yr): 0.1 mg/kg twice daily (max dosage = 17 mg/day); may ↑ to 0.15 mg/kg twice daily (max dosage = 17 mg/day) in 7 days and then ↑ to 0.2 mg/kg twice daily (max dosage = 17 mg/day) after another 7 days. Concurrent use of strong CYP1A2 or CYP2D6 inhibitor: Dose should not exceed 17 mg/day.
Renal Impairment
- PO (Adults and Children ≥2 yr): CCr 15–29 mL/min/1.73 m2: Not to exceed 17 mg/day.
Hepatic Impairment
- PO (Adults and Children ≥2 yr): Mild hepatic impairment: Not to exceed 13 mg/day. Moderate or severe hepatic impairment: Use not recommended.
