Diacomit for treating seizures in Dravet syndrome

Diacomit contains stiripentol and is prescribed to treat seizures associated with Dravet syndrome in patients 6 months and older who are also taking clobazam and weigh at least 7 kg. It is available as capsules and as a powder for oral suspension.

Diacomit is used as an add-on therapy for controlling seizures in patients diagnosed with Dravet syndrome, specifically those 6 months of age and older weighing 7 kg or more who are already taking clobazam. It is not approved for use as monotherapy.

stiripentol

The exact mechanism of stiripentol's anticonvulsant effect is unknown. It may act directly on the GABAA receptor to enhance inhibitory neurotransmission and indirectly by inhibiting liver enzymes that metabolize clobazam, thereby increasing blood concentrations of clobazam and its active metabolite.

The recommended dosage of Diacomit is 50 mg/kg/day divided into 2 or 3 doses, depending on age and weight. For patients 6 months and older weighing 7 kg or more, dosing is typically 25 mg/kg twice daily or 16.67 mg/kg three times daily, not exceeding 3000 mg per day total.

Capsules must be swallowed whole with water during a meal and should not be broken or opened. The powder for oral suspension should be mixed with 100 mL of water and taken immediately with a meal, followed by rinsing the cup with 25 mL water to ensure full dose ingestion.

Missed doses should be taken as soon as possible unless it's near the next scheduled dose; doses should never be doubled. Treatment should be tapered gradually to reduce seizure risk. Hematologic monitoring is recommended before starting and every 6 months during treatment.

DIACOMIT (Stiripentol) Capsules and Oral Suspension

There are no known contraindications for DIACOMIT in any of its available oral formulations (capsules or powder for suspension). Neither the capsules nor the oral suspension list any specific patient conditions or characteristics that prohibit use.

Somnolence: Diacomit can cause significant sleepiness, especially when combined with clobazam or other CNS depressants. Dosage reduction of clobazam by 25% may be needed if somnolence occurs.

Decreased Appetite and Weight Loss: Patients, especially children, should be monitored for decreased appetite and weight loss; dose adjustment of co-administered valproate may help.

Neutropenia and Thrombocytopenia: Blood counts should be checked before starting and every 6 months thereafter, as Diacomit can cause notable decreases in neutrophil and platelet counts.

Withdrawal: Gradual tapering is important to minimize risk of increased seizures or status epilepticus.

Phenylketonuria (PKU): The oral suspension contains phenylalanine; its daily intake must be considered in patients with PKU. Capsules do not contain phenylalanine.

Suicidal behavior and ideation: All antiepileptic drugs increase the risk of suicidal thoughts or behavior. Monitor patients closely and counsel patients and caregivers on this risk.

The most common side effects occurring in at least 10% of Diacomit-treated patients include somnolence (67%), decreased appetite (46%), agitation (27%), ataxia (27%), weight loss (27%), hypotonia (24%), nausea (15%), tremor (15%), dysarthria (12%), and insomnia (12%).

Other reported adverse reactions include vomiting, salivary hypersecretion, fatigue, fever, bronchitis, nasopharyngitis, aggression, and in postmarketing reports, pneumonia.

Diacomit increases blood levels of clobazam and its active metabolite by inhibiting CYP3A4 and CYP2C19, which may increase risk of clobazam-related side effects; dose reduction of clobazam should be considered if adverse effects occur.

It affects multiple liver enzymes and transporters (CYP1A2, CYP2B6, CYP3A4, CYP2C8, CYP2C19, P-glycoprotein, and BCRP), necessitating dose adjustments of coadministered drugs that are substrates of these enzymes and transporters if adverse reactions arise.

Strong inducers of CYP1A2, CYP3A4, or CYP2C19 (e.g., rifampin, phenytoin, phenobarbital, carbamazepine) can reduce Diacomit levels; coadministration should be avoided or dose adjusted.

Concomitant use with other CNS depressants, including alcohol, may increase sedation risk.

Pregnancy

There are no adequate data on use in pregnant women. Animal studies have shown developmental toxicity including fetal malformations and decreased survival at doses lower than the recommended human dose. Women who are pregnant or intend pregnancy should be advised of potential risks and encouraged to enroll in the North American Antiepileptic Drug (NAAED) Pregnancy Registry.

Lactation

It is unknown whether stiripentol is present in human milk or its effects on a breastfed infant. The benefits of breastfeeding should be weighed against the mother's clinical need for Diacomit and potential risks to the infant.

No human data on overdose are available. In animal studies, high doses caused decreased motor activity and respiration. Management of overdose should be supportive with symptomatic measures in intensive care.

Store Diacomit capsules and oral suspension powder in a dry place at 20°C to 25°C (68°F to 77°F) with allowed excursions between 15°C and 30°C (59°F to 86°F). Keep in original packaging protected from light.