OVERVIEW

PRODUCT INFORMATION

CHEMICAL FORMULA AND STRUCTURE

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DRUG	CAS REGISTRY NUMBER	MOLECULAR FORMULA	STRUCTURE
Stiripentol	49763-96-4	C14-H18-O3

ANNOTATED BIBLIOGRAPHY

References updated: 10 April 2019

• Zimmerman HJ. Anticonvulsants. In, Zimmerman, HJ. Hepatotoxicity: the adverse effects of drugs and other chemicals on the liver. 2nd ed. Philadelphia: Lippincott, 1999: pp. 498-516.

  (Expert review of anticonvulsants and liver injury published in 1999; stiripentol is not discussed).
• Pirmohamed M, Leeder SJ. Anticonvulsant agents. In, Kaplowitz N, DeLeve LD, eds. Drug-induced liver disease. 3rd ed. Amsterdam: Elsevier, 2013: pp 423-42.

  (Review of anticonvulsant induced liver injury; stiripentol is not discussed).
• Smith MD, Metcalf CS, Wilcox KS. Pharmacotherapy of the epilepsies. In, Brunton LL, Hilal-Dandan R, Knollman BC, eds. Goodman & Gilman’s the pharmacological basis of therapeutics. 13th ed. New York: McGraw-Hill, 2018, pp. 303-26.

  (Textbook of pharmacology and therapeutics).
• https://www​.accessdata​.fda.gov/scripts/cder/daf/

  (FDA Drug Approvals website that has product labels [package inserts], letters of approval and full FDA scientific review of the new drug application for safety and efficacy; mentions that in safety analysis in several hundred treated cases there was no increase in ALT values or discontinuations for liver test abnormalities and no instances of clinically apparent liver injury).
• Stiripentol: efficacy and tolerability in children with epilepsy. Epilepsia 1999; 40: 1618-26. [PubMed: 10565591]

  (Among 212 French children with various forms of epilepsy treated with stiripentol, 48% had troublesome adverse events, most commonly neurobehavioral [30%] or gastrointestinal [29%], but only 1 child had to discontinue therapy because of adverse events; no mention of ALT elevations or hepatotoxicity).
• Chiron C, Marchand MC, Tran A, Rey E, d'Athis P, Vincent J, Dulac O, et al. Stiripentol in severe myoclonic epilepsy in infancy: a randomized placebo-controlled syndrome-dedicated trial. STICLO study group. Lancet 2000; 356 (9242): 1638-42. [PubMed: 11089822]

  (Among 41 children with severe myoclonic epilepsy receiving valproate and clobazam to which was added stiripentol or placebo for 2 months, clinical response rates were higher in those on stiripentol [71% vs 5%] as were adverse event rates [100% vs 40%], most responding to dose reduction and none attributed to liver injury).
• Björnsson ES, Bergmann OM, Björnsson HK, Kvaran RB, Olafsson S. Incidence, presentation and outcomes in patients with drug-induced liver injury in the general population of Iceland. Gastroenterology 2013; 144: 1419-25. [PubMed: 23419359]

  (In a population based study of drug induced liver injury from Iceland, 96 cases were identified over a 2 year period, but none of the 96 were attributed to anticonvulsants).
• Wirrell EC, Laux L, Franz DN, Sullivan J, Saneto RP, Morse RP, Devinsky O, et al. Stiripentol in Dravet syndrome: results of a retrospective U.S. study. Epilepsia 2013; 54: 1595-604. [PubMed: 23848835]

  (Survey of 13 US clinicians managing 82 children with Dravet syndrome identified adverse events in 46%, which were neurobehavioral in 27% and gastrointestinal in 10%; no mention of ALT elevations or hepatotoxicity).
• Chalasani N, Bonkovsky HL, Fontana R, Lee W, Stolz A, Talwalkar J, Reddy KR, et al.; United States Drug Induced Liver Injury Network. Features and outcomes of 899 patients with drug-induced liver injury: The DILIN Prospective Study. Gastroenterology 2015; 148: 1340-52. [PMC free article: PMC4446235] [PubMed: 25754159]

  (Among 899 cases of drug induced liver injury enrolled in a US prospective study between 2004 and 2013, 40 [4.5%] were attributed to anticonvulsants, but none to clobazam or other benzodiazepine anticonvulsants).
• Inoue Y, Ohtsuka Y; STP-1 Study Group. Long-term safety and efficacy of stiripentol for the treatment of Dravet syndrome: A multicenter, open-label study in Japan. Epilepsy Res 2015; 113: 90-7. [PubMed: 25986195]

  (Among 24 Japanese children started on stiripentol of whom 19 were continued for up to 40 weeks, adverse events were frequent [91%], the common events being somnolence [79%], anorexia [67%], ataxia [58%], mild ALT elevations [17%], mild Alk P [8%] and mild-to-moderate GGT [38%], but no adverse event led to drug discontinuation).
• Nickels KC, Wirrell EC. Stiripentol in the management of epilepsy. CNS Drugs 2017; 31: 405-16. [PubMed: 28434133]

  (Review of the structure, mechanism of action, pharmacology, clinical efficacy, current uses and safety of stiripentol; mentions that adverse events can be caused by its effects on drug levels of other anticonvulsants and major problematic side effects are neurobehavioral and gastrointestinal; no mention of ALT elevations or hepatotoxicity).
• Drugs for epilepsy. Med Lett Drugs Ther 2017; 59 (1526):121-30. [PubMed: 28746301]

  (Concise review of the currently available drugs for epilepsy does not discuss stiripentol).
• Myers KA, Lightfoot P, Patil SG, Cross JH, Scheffer IE. Stiripentol efficacy and safety in Dravet syndrome: a 12-year observational study. Dev Med Child Neurol 2018; 60: 574-8. [PubMed: 29473155]

  (Among 41 children with Dravet syndrome followed at 2 epilepsy centers [in UK and Australia] who were treated with stiripentol for up to 12 years, 73% reported stiripentol related adverse events, most commonly anorexia, weight loss, sedation and behavioral changes and one case of protein-losing enteropathy and one of recurrent pancreatitis; ALT elevations and hepatotoxicity were not mentioned).
• Uchida Y, Terada K, Madokoro Y, Fujioka T, Mizuno M, Toyoda T, Kato D, et al. Stiripentol for the treatment of super-refractory status epilepticus with cross-sensitivity. Acta Neurol Scand 2018; 137: 432-7. [PubMed: 29313881]

  (Among 5 adults with refractory status epilecticus and hypersensitivity reactions to various anticonvulsants [erythema multiforme, drug rash with eosinophilia and systemic symptoms, or toxic epidermal necrolysis; 3 with hepatitis], adding stiripentol led to control of seizures without recurrence of allergic reactions).
• Yıldız EP, Ozkan MU, Uzunhan TA, Bektaş G, Tatlı B, Aydınlı N, Çalışkan M, et al. Efficacy of stiripentol and the clinical outcome in Dravet syndrome. J Child Neurol 2019; 34: 33-7. [PubMed: 30362398]

  (Among 21 Japanese children with Dravet syndrome, 86% were taking stiripentol, of whom 8 had adverse events, most commonly sedation [n=6] or ataxia [n=5], and “no patient had laboratory abnormalities in liver” function tests).