DIACOMIT

What it is

DIACOMIT is stiripentol, available in 250 mg and 500 mg capsules and 250 mg and 500 mg powder for oral suspension.

Approved indications

— Adjunctive treatment of generalised tonic-clonic and clonic seizures associated with severe myoclonic epilepsy in infancy (SMEI, also known as Dravet syndrome) in patients whose seizures are not adequately controlled with a benzodiazepine (usually clobazam) and valproate.

Dosing overview

The recommended dose of stiripentol is 50 mg/kg/day, achieved through gradual upward dose escalation. Dosage escalation should start with 20 mg/kg/day for one week, then 30 mg/kg/day for one week. Further escalation is age-dependent: children less than six years should receive an additional 20 mg/kg/day in the third week to achieve 50 mg/kg/day in three weeks; children from six to less than twelve years should receive an additional 10 mg/kg/day each week to achieve 50 mg/kg/day in four weeks; children and adolescents twelve years and older should receive an additional 5 mg/kg/day each week until the optimum dose is reached based on clinical judgement. The daily dose should be split into two or three daily intakes. Capsules should be swallowed whole with a glass of water during a meal. The powder should be mixed in a glass of water and taken immediately after mixing during a meal.

Key safety warnings

Neutropenia may be associated with the administration of stiripentol, clobazam and valproate. Blood counts should be assessed prior to starting treatment with stiripentol, and unless otherwise clinically indicated, should be checked every six months. Patients should be monitored for somnolence and drowsiness, particularly when stiripentol is used concomitantly with other central nervous depressants. An adjustment of the dosage of concomitant clobazam or other anti-epileptic drugs could be considered. Movement disorders including ataxia, hypotonia, tremor, hyperkinesia, dysarthria and equilibrium disorders have been reported in patients treated with DIACOMIT for Dravet syndrome. Raised γGT (notably when combined with valproate) are observed with common frequency, whilst abnormal liver function tests (increases in aspartate aminotransferase and/or alanine aminotransferase) are reported with rare frequency. Liver function should be assessed prior to starting treatment with stiripentol and, unless otherwise clinically indicated, should be checked every six months. Suicidal ideation and behaviour have been reported in patients treated with antiepileptic agents in several indications. All patients treated with antiepileptic drugs, irrespective of indication, should be monitored for signs of suicidal ideation and behaviour and appropriate treatment should be considered.

Contraindications

Hypersensitivity to the active substance or to any of the excipients. A past history of psychoses in the form of episodes of delirium.

PBS listing

DIACOMIT is listed on the PBS in four items: 250 mg capsule, 250 mg powder for oral suspension, 500 mg capsule, and 500 mg powder for oral suspension. All have streamlined restriction. The ex-manufacturer price is A$293.00 for 250 mg formulations and A$586.00 for 500 mg formulations.

Regulatory history

DIACOMIT was first registered on the Australian Register of Therapeutic Goods on 13 September 2019 with four registrations covering capsule and powder for oral suspension formulations in 250 mg and 500 mg strengths. The Pharmaceutical Benefits Scheme Advisory Committee recommended DIACOMIT for listing in March 2020 for adjunctive treatment of generalised clonic and tonic-clonic seizures associated with Dravet syndrome not adequately controlled by prior lines of therapy.