Stiripentol ' s chemical structure
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Stiripentol

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. more...

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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 & 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 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%.

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Severe Myoclonic Epilepsy Responds Well to Stiripentol - Brief Article
From Family Pratice News, 3/15/00 by Sharon Worcester

ORLANDO, FLA. - An investigational antiepilepsy drug was an effective add-on therapy for controlling seizures in children with severe myoclonic epilepsy in infancy, the results of a double-blind, placebo-controlled study have shown.

Stiripentol, which is believed to inhibit the activity of several P-450 cytochromes, resulted in the highest response rate ever reported for severe myoclonic epilepsy, one of the most intractable epilepsy syndromes, Dr. Catherine Chiron reported at the annual meeting of the American Epilepsy Society.

Of 41 refractory patients aged 3-20 years, 15 of 21 treated with stiripentol in addition to clobazam and valproate responded with at least a 50% reduction in clonic seizures. One patient became seizure free during treatment. Only 1 of the 20 patients in the group taking placebo plus clobazam and valproate responded, said Dr. Chiron of St. Vincent de Paul Hospital in Paris.

Those patients treated with stiripentol had an average of 6.4 seizures per month, compared with 13.9 per month in the placebo group. After 2 months of treatment, patients in the stiripentol group had an average 62% reduction in seizures, compared with an 8% increase with placebo.

Side effects occurred in all 21 patients on stiripentol versus 8 patients on placebo. Side effects in the stiripentol group included only drowsiness and loss of appetite. These were moderate in most patients and usually were related to overdose of clobazam; dose reductions led to resolution of the side effects in some patients, and other cases were transient, Dr. Chiron noted.

COPYRIGHT 2000 International Medical News Group
COPYRIGHT 2001 Gale Group

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