Trade names Diacomit ATC code N03AX17 (WHO) CAS Number 49763-96-4 | Routes ofadministration Oral Legal status AU: Unscheduled CAS ID 49763-96-4 | |
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AHFS/Drugs.com International Drug Names | ||
Use of stiripentol in dravet syndrome with dr ben menachem
Stiripentol (marketed as Diacomit by Laboratoires Biocodex) is an anticonvulsant drug used in the treatment of epilepsy. It is approved for the treatment of Dravet syndrome, an epilepsy syndrome. It is unrelated to other anticonvulsants and belongs to the group of aromatic allylic alcohols.
Contents
Mechanism of action
As with most anticonvulsants, the precise mechanism of action is unknown. Regardless, stiripentol has been shown to have anticonvulsant effects of its own.
Stiripentol increases GABAergic activity. At clinically relevant concentrations, it enhances central GABA neurotransmission through a barbiturate-like effect, since it increases the duration of opening of GABA-A receptor channels in hippocampal slices. It has also been shown to increase GABA levels in brain tissues by interfering with its reuptake and metabolism. Specifically, it has been shown to inhibit lactate dehydrogenase, which is an important enzyme involved in the energy metabolism of neurons. Inhibition of this enzyme can make neurons less prone to fire action potentials, likely through activation of ATP-sensitive potassium channels.
Stiripentol also improves the effectiveness of many other anticonvulsants, possibly due to its inhibition of certain enzymes, slowing the drugs' metabolism and increasing blood plasma levels.
History
In December 2001 the European Medicines Agency (EMA) granted stiripentol orphan drug status (designation number EU/3/01/071) for the treatment of severe myoclonic epilepsy of infancy (SMEI, also known as Dravet's syndrome). On 4 January 2007, the EMA granted the drug a marketing authorisation that is valid throughout the European Union.
Indications and usage
It is indicated as an adjunctive therapy with sodium valproate and clobazam for treating Dravet syndrome whose seizures are not adequately controlled with clobazam and valproate. Children with SMEI develop often intractable seizures during their first year of life and developmental delay follows. Small-scale trials have shown 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 (250 mg, 500 mg) and as a sachet of powder to make a drinkable suspension (250 mg, 500 mg).
Initial dose is 50 mg/kg per day. This may be increased up to 100 mg/kg per day, with a maximum of 4 g/day. The dose is to be divided into two or three and to be taken with meals. The dose of other anticonvulsants may have to be reduced (possibly down 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 dose 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 while reducing the dose by 50%.