Drug interactions of Stiripentol

1.Effect of Stiripentol on Other Drugs

CYP1A2, CYP2B6, CYP3A4, CYP2C8, CYP2C19, P-glycoprotein (P-gp) and Breast Cancer Resistance Protein (BCRP) Substrates

In vitro data show that stiripentol is both an inhibitor and inducer of CYP1A2, CYP2B6, and CYP3A4. Because of potential drug-drug interactions, consider dose adjustment of CYP1A2 substrates (e.g., theophylline, caffeine), CYP2B6 substrates (e.g., sertraline, thiotepa), and CYP3A4 substrates (e.g., midazolam, triazolam, quinidine), as clinically appropriate, when administered concomitantly with Stiripentol. Because of potential inhibition of enzyme/transporter activity, consider a reduction in dosage of substrates of CYP2C8, CYP2C19 (e.g., diazepam, clopidogrel), P-gp (e.g., carbamazepine), and BCRP (e.g., methotrexate, prazosin, glyburide), if adverse reactions are experienced when administered concomitantly with Stiripentol.

Clobazam

Co-administration of Stiripentol (which inhibits CYP 3A4 and 2C19) with clobazam results in increased plasma concentrations of clobazam (a substrate of CYP3A4) and norclobazam, the active metabolite of clobazam (a substrate of CYP2C19). This may increase the risk of clobazam-related adverse reactions. Consider a reduction in dosage of clobazam if adverse reactions are experienced when co-administered with Stiripentol.

7.2 Effect of Other Drugs on Stiripentol

Induction-based interactions leading to decreases in Stiripentol concentrations are possible when co-administered with a potent CYP1A2, CYP3A4, or CYP2C19 inducer, such as rifampin, phenytoin, phenobarbital and carbamazepine, as these enzymes all metabolize stiripentol. Concomitant use of strong inducers with Stiripentol should be avoided, or dosage adjustments should be made.