Stiripentol

Actions

• Increases the duration of opening of GABA-A receptor channels.
• Increases GABA levels by interfering with its reuptake.
• Inhibits lactate dehydrogenase and through this mechanism probably activates ATP-sensitive potassium channels.

Metabolism

Hepatic

Enzymes involved

• CYP1A2
• CYP2C19
• CYP3A4

Elimination

Renal ~73%

Half-life

4.5-13 hours

Plasma protein binding

99%

Important side-effects

Blood dyscrasias

Indications

Adjunctive therapy for infants with Dravet syndrome, or Severe Myoclonic Epilepsy in Infancy (SMEI) when seizure control is inadequate with valproate and clobazam.

Dosing recommendation

Start with 20 mg/kg/day on week 1.

Children <6 years: Increase to 30 mg/kg/day on week 2 and 50 mg/kg/day on week 3.

Children >6 years: Increase by 10 mg/kg/day per week until target dose is reached.

Children >12 years: Increase by 5 mg/kg/day per week until target dose is reached.

Target dose: 50 mg/kg/day.

Renal impairment

Stiripentol is not recommended in patients with renal impairement.

Hepatic impairment

Stiripentol is not recommended in patients with hepatic impairement.