Stiripentol's journey to FDA approval in the USA
Stiripentol, an anticonvulsant used in Europe for years, gained U.S. availability through a multi-year process. It received Orphan Drug designation for rare diseases. Compassionate use programs allowed access for some patients before formal approval.
The FDA approved stiripentol (Diacomit) in August 2018 as an add-on treatment for Dravet syndrome-related seizures in patients two and older taking clobazam. In 2022, the approval expanded to include patients as young as six months.
Mechanism of action and pharmacological properties
Stiripentol has a unique mechanism of action compared to other anticonvulsants. It enhances GABAA receptor activity, increasing inhibitory neurotransmission. It also inhibits CYP450 enzymes (CYP3A4, CYP2C19, CYP1A2), increasing the levels of other drugs, particularly clobazam, which is essential for its efficacy. Other potential effects include inhibiting T-type calcium channels and lactate dehydrogenase.
How to access stiripentol in the USA
As an orphan drug for a rare condition, stiripentol is not available in standard pharmacies. Access requires a prescription from a healthcare provider, usually a neurologist specializing in epilepsy. The manufacturer, Biocodex, exclusively distributes Diacomit through Pantherx Rare Pharmacy. This specialty pharmacy handles prescription filling, benefit verification, patient support, and home delivery.
Comparison with other Dravet syndrome treatments
Stiripentol is one of several add-on therapies for Dravet syndrome. A 2024 network meta-analysis compared stiripentol, fenfluramine (Fintepla), and cannabidiol (Epidiolex).
| Feature | Stiripentol (Diacomit) | Fenfluramine (Fintepla) | Cannabidiol (Epidiolex) |
|---|---|---|---|
| FDA Approved for DS | Yes (2018; expanded 2022) | Yes (2020) | Yes (2018) |
| Required Concomitant Med | Clobazam | Optional (often used with other ASMs) | Optional (often used with clobazam) |
| Adjunctive Status | Yes | Yes | Yes |
| Mechanism of Action | GABAA positive allosteric modulator, CYP450 inhibitor | Serotonin receptor agonist | Multiple, not fully understood (possibly via GPR55, adenosine) |
| Efficacy (≥50% reduction in convulsive seizures) | High probability ranking (indirect comparison) | High probability ranking (indirect comparison) | Lower probability ranking (indirect comparison) |
| Seizure-Free Intervals | Statistically superior to fenfluramine and cannabidiol | Inferior to stiripentol (indirect comparison) | Inferior to stiripentol (indirect comparison) |
| Discontinuation due to Adverse Events | Lower risk compared to fenfluramine and cannabidiol | Lower risk than cannabidiol, higher than stiripentol (indirect comparison) | Highest risk (indirect comparison) |
Real-world usage and considerations
Real-world data on stiripentol use in the USA show that doses are often lower than maximum recommendations, and some patients do not take clobazam concomitantly, despite the FDA label. Common side effects include drowsiness, decreased appetite, agitation, weight loss, and nausea. Due to the interaction with clobazam, clobazam dose reduction may be needed to manage side effects. Careful monitoring and dosage adjustments are crucial. The high cost of Diacomit as an orphan drug is a consideration, and the specialty pharmacy assists with insurance and financial support programs.
Conclusion
Stiripentol (Diacomit) is available in the USA by prescription as an FDA-approved add-on therapy for seizures in Dravet syndrome patients aged six months and older taking clobazam. Access is exclusively through Pantherx Rare specialty pharmacy. Comparative studies indicate stiripentol is effective, particularly for achieving seizure-free periods, but managing drug interactions with clobazam is important. It provides a valuable treatment option for individuals with this condition. For further information, consult resources like the Epilepsy Foundation.
