China
Africa
Explore chapters and articles related to this topic
Antiepileptic Drugs
Published in Sahab Uddin, Rashid Mamunur, Advances in Neuropharmacology, 2020
Stiripentol is used clinically as an add-on therapy for Dravet syndrome (refractory generalized tonic–clonic seizures in patients with severe myoclonic epilepsy in infancy) in patients where valproate and clobazam are unable to control symptoms satisfactorily (Plosker, 2012; Aneja and Sharma, 2013). It is still not approved by USFDA for Dravet syndrome because of many pharmacokinetic and pharmacodynamic drug interactions (Misty et al., 2018). Stiripentol also decreases the severity and frequency of tonic–clonic seizures as well as status epilepticus with a variety of epilepsy syndromes in infants and children (Goossens et al., 1999; Perez et al., 1999; Inoue et al., 2009).
Antiepileptic Drug Interactions: An Overview
Published in Carl L. Faingold, Gerhard H. Fromm, Drugs for Control of Epilepsy:, 2019
Because of risks involved to patients from use of an unproven new drug as monotherapy, published guidelines for AED trials recommend that the test drug be added to current treatment. Drug interactions thus become important variables which must be controlled for. Methods have been developed to permit unblinded monitors to adjust doses of the standard AED to maintain concentrations of these within a specified range, usually ±20%.44 Pharmacodynamic interactions have not yet been reported, but some very dramatic pharmacokinetic interactions have been observed. Nafimidone (l-[2-naphthoyl methyl] imidazole hydrochloride) is a very potent inhibitor of both carbamazepine and phenytoin.45 The inhibition was of such magnitude that clinical toxicity was observed within one or two days of initiating nafimidone. It is this dramatic interaction which may significantly limit the further development of this drug.46 Felbamate (2-phenyl-l,3-propanediol dicarbamate) on the other hand, inhibits phenytoin metabolism by approximately 20% but increases carbamazepine clearance.47 MK-801, active at the NMDA receptor, has its clearance markedly increased by phenytoin and carbamazepine, but not valproate. Persons receiving the former needed doses of MK-801 five to ten times higher to attain effective concentrations of greater than 1200 ng/ml as compared to volunteers or a patient on valproate monotherapy.48 Even more complex are the interactions of stiripentol. Its metabolism is markedly induced by phenytoin, carbamazepine, and phenobarbital, while it inhibits the metabolism of phenytoin, carbamazepine, and phenobarbital. In fact, in the presence of these medications, achievement of clinically effective stiripentol concentrations may not be possible.49
Stiripentol for the treatment of seizures associated with Dravet syndrome in patients 6 months and older and taking clobazam
Published in Expert Review of Neurotherapeutics, 2023
Alejandra Vasquez, Elaine C Wirrell, Paul E Youssef
A prospective multicenter, open-label, add-on study evaluated the efficacy of STP persons with DS in Japan [42]. This study included 24 patients between 1–30 years of age in whom seizures remained refractory to clobazam and VPA. Eligible patients entered in a 4-week baseline phase, followed by a 4-week stiripentol dose-adjustment and 12-week fixed-dose phase. In the fixed-dose phase, the dose of stiripentol was maintained at 50 mg/kg/day (maximum 2500 mg/day). Sixteen of 24 subjects (67%) were responders, and four (16.7%) achieved freedom from tonic and tonic-clonic seizures. The authors also noted that the duration of tonic-clonic and clonic seizures decreased when compared to baseline in patients 18 years and younger (p = 0.0019). The effect of STP was durable for up to 56 weeks, as demonstrated by a 54% responder rate from the patients who entered the long-term extension phase of this study [43].
Stiripentol for the treatment of seizures in Dravet syndrome
Published in Expert Review of Clinical Pharmacology, 2019
Krista Eschbach, Kelly G Knupp
Stiripentol is a novel anti-seizure medication recently approved in the United States with an indication as adjunctive therapy for the treatment of seizures in children with Dravet syndrome. This paper provides a literature review of the current treatment of seizures in children with Dravet syndrome with a specific focus on the pharmacology, clinical efficacy, safety and tolerability of stiripentol.