DIACOMIT Hard capsule Ref.[7680] Active ingredients: Stiripentol

Diacomit should only be administered under the supervision of a paediatrician/paediatric neurologist experienced in the diagnosis and management of epilepsy in infants and children.

Posology

Paediatric population

The dose of stiripentol is calculated on a mg/kg body weight basis.

The daily dosage may be administered in 2 or 3 divided doses.

The initiation of adjunctive therapy with stiripentol should be undertaken gradually using upwards dose escalation to reach the recommended dose of 50 mg/kg/day administered in conjunction with clobazam and valproate.

Stiripentol dosage escalation should be gradual, starting with 20mg/kg/day for 1 week, then 30mg/kg/day for 1 week. Further dosage escalation is age dependent:

• children less than 6 years should receive an additional 20 mg/kg/day in the third week, thus achieving the recommended dose of 50 mg/kg/day in three weeks;
• children from 6 to less than 12 years should receive an additional 10 mg/kg/day each week, thus achieving the recommended dose of 50 mg/kg/day in four weeks;
• children and adolescents 12 years and older should receive an additional 5 mg/kg/day each week until the optimum dose is reached based on clinical judgment.

The recommended dose of 50 mg/kg/day is based on the available clinical study findings and was the only dose of Diacomit evaluated in the pivotal studies (see section 5.1).

Stiripentol must always be taken with food as it degrades rapidly in an acidic environment (e.g. exposure to gastric acid in an empty stomach).

Stiripentol should not be taken with milk or dairy products (yoghurt, soft cream cheese, etc.), carbonated drinks, fruit juice or food and drinks that contain caffeine or theophylline.

Children aged less than 3 years

The pivotal clinical evaluation of stiripentol was in children of 3 years of age and over with SMEI. The clinical decision for use of stiripentol in children with SMEI less than 3 years of age needs to be made on an individual patient basis taking into consideration the potential clinical benefits and risks. In this younger group of patients, adjunctive therapy with stiripentol should only be started when the diagnosis of SMEI has been clinically confirmed (see section 5.1). Data are limited about the use of stiripentol under 12 months of age. For these children the use of stiripentol will be done under the close supervision of the doctor.

Patients aged ≥18 years of age

Long-term data has not been collected in a sufficient number of adults to confirm maintenance of effect in this population. Treatment should be continued for as long as efficacy is observed.

Dose adjustments of other antiepileptics used in combination with stiripentol

Despite the absence of comprehensive pharmacology data on potential drug interactions, the following advice regarding modification of the dose and dosage schedules of other anti-epileptic medicinal products administered in conjunction with stiripentol is provided based on clinical experience.

Clobazam

In the pivotal studies, when the use of stiripentol was initiated, the daily dose of clobazam was 0.5 mg/kg/day usually administered in divided doses, twice daily. In the event of clinical signs of adverse reactions or overdose of clobazam (i.e., drowsiness, hypotonia, and irritability in young children), this daily dose was reduced by 25% every week. Approximately two to three-fold increases in clobazam and five-fold increases in norclobazam plasma levels respectively have been reported with co-administration of stiripentol in children with Dravet’s syndrome.

Valproate

The potential for metabolic interaction between stiripentol and valproate is considered modest and thus, no modification of valproate dosage should be needed when stiripentol is added, except for clinical safety reasons. In the pivotal studies in the event of gastrointestinal adverse reactions such as loss of appetite, loss of weight, the daily dose of valproate was reduced by around 30% every week.

Abnormal laboratory findings

In the event of an abnormal blood count or liver function test finding, the clinical decision for continuing use or adjusting the dose of stiripentol in conjunction with adjusting the doses of clobazam and valproate needs to be made on an individual patient basis taking into consideration the potential clinical benefits and risks (see section 4.4).

Effect of formulation

The sachet formulation has a slightly higher C_max than the capsules and thus the formulations are not bioequivalent. It is recommended that if a switch of formulations is required this is done under clinical supervision, in case of problems with tolerability (see section 5.2).

Renal and hepatic impairment

Stiripentol is not recommended for use in patients with impaired hepatic and/or renal function (see section 4.4).

Method of administration

Oral use.

The capsule should be swallowed whole with a glass of water.

To ensure that the whole amount of powder is taken by the patient, the capsule should not be opened.

For the interaction of stiripentol with food, please see section 4.5.

Data on clinical overdose are not available. Treatment is supportive (symptomatic measures in intensive care units).

3 years.

Store in the original package in order to protect from light.

Polypropylene bottle with tamper-evident seal and polyethylene screw cap containing 30 and 90 capsules.

An opaque polyethylene bottle closed with a child-resistant tamper-evident polypropylene screw cap containing 60 capsules.

Bottles are packed in cardboard cartons.

Not all pack sizes may be marketed.

No special requirements.

Any unused medicinal product or waste material should be disposed of in accordance with local requirements.