Stiripentol
Stiripentol is an anticonvulsant medication used primarily as an adjunctive therapy for epilepsy, particularly in treating Dravet syndrome, a rare and severe form of epilepsy that begins in infancy.
Trade Name
Stiripentol is marketed under the brand name Diacomit.
Chemical Properties
Chemical structure: Stiripentol is a cyclic molecule with structural similarities to other anticonvulsants, but it has unique properties that make it effective for specific types of epilepsy.
Molecular formula: C₁₄H₁₈O₃ Molecular weight: 234.29 g/mol
Solubility: Stiripentol has low water solubility and is typically formulated as capsules and powder for oral suspension.
Biochemical Properties
Mechanism of action: Stiripentol’s exact mechanism is not fully understood, but it is believed to enhance the activity of gamma-aminobutyric acid (GABA), an inhibitory neurotransmitter in the brain. It may also inhibit certain liver enzymes, which increases the levels and prolongs the action of other anticonvulsants, such as clobazam and valproate, when used in combination.
Pharmacology
Administration: Stiripentol is taken orally and is available in capsule or powder form for mixing with liquids.
Bioavailability: Stiripentol is well-absorbed, though its bioavailability may vary with food intake. It is generally recommended to take stiripentol with food to improve absorption and reduce gastrointestinal side effects.
Metabolism: Stiripentol is primarily metabolized by the liver. It acts as an inhibitor of several liver enzymes (CYP2C19, CYP3A4), which contributes to its interactions with other anticonvulsant medications.
Half-life: The half-life of stiripentol is approximately 4.5 to 13 hours, though this can vary depending on individual metabolism and co-administration with other drugs.
Clinical Indications
Dravet syndrome: Stiripentol is primarily indicated as an adjunctive treatment for Dravet syndrome in patients who are also taking clobazam and valproate. This combination has been shown to reduce the frequency of seizures in patients with Dravet syndrome.
Other uses: Stiripentol may be used off-label for other refractory epilepsy types, but this is less common and typically only under specialist care.
Side Effects
Drowsiness and sedation: Stiripentol can cause sedation, especially when used with other sedative anticonvulsants like clobazam.
Gastrointestinal issues: Nausea, vomiting, and loss of appetite are common, particularly when first starting the medication.
Weight loss: Some patients experience decreased appetite and weight loss.
Ataxia and tremor: Difficulty with coordination, balance, and fine motor skills may occur.
Behavioral changes: Irritability, hyperactivity, and aggression are sometimes seen, particularly in children.
Neutropenia: Stiripentol can cause a reduction in white blood cells (neutropenia), so regular blood monitoring is recommended.
Monitoring and Considerations
Therapeutic drug monitoring: Because stiripentol can interact with other anticonvulsants, drug levels and liver function tests should be monitored regularly, especially when starting treatment or adjusting doses.
Dose adjustments: Dose adjustments may be required based on therapeutic response and side effects. Stiripentol is generally started at a low dose and gradually increased.
Pregnancy: Stiripentol is classified as Category C for pregnancy, meaning it should only be used if the potential benefits justify the risks. There is limited data on its safety during pregnancy.
Drug interactions: Due to its inhibition of liver enzymes, stiripentol can interact with many medications. Careful monitoring is required when it is combined with drugs metabolized by CYP2C19 and CYP3A4 enzymes, especially clobazam and valproate.
Stiripentol is a specialized anticonvulsant mainly used in conjunction with clobazam and valproate for managing seizures in Dravet syndrome. Its role as an enzyme inhibitor means it has significant interactions with other drugs, requiring careful monitoring. While effective in reducing seizure frequency, stiripentol’s side effects, such as sedation and gastrointestinal discomfort, should be managed with regular monitoring and dose adjustments.
