Stiripentol

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Stiripentol
Stiripentol Wiki Str.png
Clinical data
Routes of
administration
Oral
ATC code
Identifiers
CAS Number
PubChem CID
E number{{#property:P628}}
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Chemical and physical data
FormulaC14H18O3
Molar mass234.30 g·mol−1

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Overview

Stiripentol (marketed as Diacomit by Laboratoires BIOCODEX) is an anticonvulsant drug used in the treatment of epilepsy. It is unrelated to other anticonvulsants and belongs to the group of aromatic allylic alcohols.

Mechanism of action

As with most anticonvulsants, the precise mechanism is unknown. It has been shown to have anticonvulsant effects on its own. It can prevent the reuptake of GABA and inhibit its metabolism.

It also improves the effectiveness of many other anticonvulsants, possibly due to it inhibiting certain enzymes. This slows the drug's metabolism, increasing blood plasma levels.

Approval history

E.U.

  • December 2001 - Treatment of severe myoclonic epilepsy in infancy (SMEI). EU orphan designation number EU/3/01/071.

Stiripentol has very limited availability.

Indications and usage

It is indicated as an adjunctive therapy with sodium valproate and clobazam for treating severe myoclonic epilepsy in infancy (SMEI, also know as Dravet's syndrome). Children with SMEI develop often intractable seizures during their first year of life and mental retardation follows. Small-scale trials have show remarkably high response rates, with a significant minority of those treated becoming seizure free.

In addition, it may be used to treat refractory childhood epilepsy in conjunction with carbamazepine. It appears to be less effective in adolescents and adults.

Dosing

Stiripentol is available as a gelatine capsule (250mg, 500mg) and as a sachet of powder to make a drinkable suspension (250mg, 500mg).

Initial dose is 50 mg/kg per day. This may be increased up to 100 mg/kg per day, with a maximum of 4g. The dose to be divided into two or three with meals. The does of other anticonvulsants may have to be reduced (possibly up to 50%).

Side effects

Side effects are largely due to the increase in plasma concentrations of other anticonvulsants and can be reduced by lowering the does of those drugs. Nausea and vomiting are particularly noted when used in combination with sodium valproate.

Drug interactions

Stiripentol inhibits several cytochrome P450 isoenzymes and so interacts with many anticonvulsants and other medicines. This is both a strength and weakness. It appears to increase the potency of phenobarbital, primidone, phenytoin, carbamazepine, clobazam and diazepam. For example, blood levels of carbamazepine can be maintained whist reducing the dose by 50%.

References

Tran A, Vauzelle-Kervroedan F, Rey E, Pous G, d'Athis P, Chiron C, Dulac O, Renard F, Olive G. (1996)
[Abstract]. European Journal Clinical Pharmacology. 1996;50(6):497–500.
Perez J, Chiron C, Musial C, Rey E, Blehaut H, d'Athis P, Vincent J, Dulac O. (1999)
[Abstract]. Epilepsia. 1999 Nov;40(11):1618–26.
C. Chiron, M. Marchand, A. Tran, E. Rey, P. d'Athis, J. Vincent, O. Dulac, G. Pons. (2000)
[Abstract]. The Lancet 2000 Nov 11, Volume 356, Issue 9242, Pages 1638–1642
Thanh TN, Chiron C, Dellatolas G, Rey E, Pons G, Vincent J, Dulac O. (2002)
[Abstract]. Arch Pediatr. 2002 Nov;9(11):1120–7.
Chiron C. (2005)
[Abstract]. Expert Opinion on Investigational Drugs July 2005, Vol. 14, No. 7, Pages 905–911]
Trojnar MK, Wojtal K, Trojnar MP, Czuczwar SJ. (2005)
[Full Text]. Pharmacological Reports, 2005, 57, 154-160

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