Diacomit (stiripentol)
Last reviewed · Source: First Databank (FDB) drug data
Overview
Stiripentol, an aromatic allylic alcohol, is an anticonvulsant.
Stiripentol, an aromatic allylic alcohol, is an anticonvulsant. The drug is structurally distinct from other currently available anticonvulsant agents.
The exact mechanism of action by which stiripentol exerts its anticonvulsant effects has not been fully elucidated, but may involve multiple direct and indirect mechanisms including enhancement of gamma-aminobutyric acid (GABA) neurotransmission and potentiation of the effects of concomitantly administered anticonvulsants (e.g., clobazam) through pharmacodynamic and pharmacokinetic interactions. In vitro studies indicate that the drug acts as a positive allosteric modulator of the GABA type A (GABAA) receptor at a site distinct from benzodiazepines, thereby acting independently and additively with benzodiazepines at GABAA receptors. Stiripentol enhances the opening duration rather than the opening frequency of GABAA receptor-dependent chloride channels.
Stiripentol also can increase plasma concentrations of clobazam (and its norclobazam metabolite) via inhibition of cytochrome P-450 (CYP) enzymes; because these drugs are used in combination, the pharmacokinetic interaction may contribute indirectly to the anticonvulsant activity of stiripentol. (See Clobazam under Drug Interactions: Anticonvulsants.)
Stiripentol exhibits nonlinear pharmacokinetics; systemic exposure increases in a greater than dose-proportional manner over the dose range of 500 mg to 2 g. Stiripentol is rapidly and extensively absorbed following oral administration. Peak plasma concentrations occur within 2-3 hours following oral administration.
Peak plasma concentrations are 23% higher when the drug is administered as an oral suspension compared with administration as capsules; however, the area under the concentration-time curve (AUC) and time to peak plasma concentrations are similar between the dosage forms. Plasma protein binding of stiripentol is 99%. Stiripentol is extensively metabolized.
Although the metabolic pathway of stiripentol has not been fully characterized, in vitro studies indicate that the metabolism of stiripentol is principally mediated by several CYP isoenzymes including CYP1A2, 2C19, and 3A4. The elimination half-life of stiripentol ranges from 4.5-13 hours. Stiripentol is mainly eliminated in the urine; following oral administration, approximately 73% of the dose was recovered in urine as metabolites and 13-24% was recovered in feces as unchanged drug.
USES: Stiripentol is used to treat seizures in people with a certain medical condition (Dravet syndrome).
Generic name: stiripentol
Pronunciation: (STIR-i-PEN-tol)
Reference product & biosimilars
No reference, biosimilar or interchangeable associated with this drug.
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Indications
The following indications are listed for Diacomit:
- Dravet Syndrome
Also known as: Severe Myoclonic Epilepsy In Infancy.
Dosing
For the adjunctive treatment of seizures associated with Dravet syndrome in adults and pediatric patients 2 years of age or older taking clobazam, the recommended dosage of stiripentol is 50 mg/kg daily, divided in 2 or 3 doses (i.e., 16.67 mg/kg 3 times daily or 25 mg/kg twice daily). Dosage titration is not necessary. The maximum recommended daily dosage is 3 g.
The calculated dosage should be rounded to the nearest achievable dosage strength (usually within 50-150 mg of the recommended daily dosage) using stiripentol capsules or packets of powder for oral suspension. A combination of the 2 commercially available strengths of stiripentol (250 and 500 mg) may be used to achieve the dosage.
Stiripentol is administered orally (as capsules or oral suspension) in 2 or 3 divided doses with meals.
Stiripentol capsules must be swallowed whole with a glass of water during a meal; the capsules should not be broken or opened.
To prepare the oral suspension, the appropriate number of packets of powder should be mixed in a glass containing 100 mL of water and consumed immediately after mixing during a meal. To ensure that the entire dose is consumed, a small amount of water (25 mL) should be added to the glass and then swallowed.
If a dose is missed, the missed dose should be taken as soon as possible. If it is almost time for the next dose, the missed dose should be skipped and the next dose should be taken at the regularly scheduled time. The dose should not be doubled to replace a missed dose.
No dosing information is available for this tab.
No dosing information is available for this tab.
Drug interactions
Stiripentol is a substrate of cytochrome P-450 (CYP) isoenzymes 1A2, 2C19, and 3A4 in vitro. In vitro data indicate that stiripentol may inhibit and induce CYP isoenzymes 1A2, 2B6, and 3A4, and also inhibit CYP2C8 and CYP2C19. Stiripentol also can inhibit drug transporters, including P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP).
There are no contraindication interactions for this drug.
There are no severe interactions for this drug.
There are no moderate interactions for this drug.
Contraindications
The manufacturer states that there are no known contraindications to the use of stiripentol.
There are no contraindication contraindications for this drug.
There are no severe contraindications for this drug.
There are no moderate contraindications for this drug.
Adverse reactions
Adverse effects reported in at least 10% of patients with Dravet syndrome receiving stiripentol in addition to clobazam and valproate in controlled clinical trials and more frequently than with placebo include somnolence, decreased appetite, agitation, ataxia, decreased weight, hypotonia, nausea, tremor, dysarthria, and insomnia.
There are no severe adverse reactions for this drug.
There are no less severe adverse reactions for this drug.
Precautions
No enhanced messaging available.
Safety and efficacy of stiripentol for the treatment of seizures associated with Dravet syndrome have been established in pediatric patients 2 years of age or older receiving clobazam. The principal efficacy studies included pediatric patients 3 years of age or older. Efficacy of stiripentol in patients 2-3 years of age was extrapolated from the demonstration of effectiveness in older pediatric patients.
Safety and efficacy of stiripentol have not been established in pediatric patients younger than 2 years of age.
Clearance and volume of distribution of stiripentol are affected by body weight in pediatric patients. Elimination half-life increased from 8.5 hours for a 10-kg patient to 23.5 hours in a 60-kg patient. Compared with children older than 12 years of age, mean stiripentol concentrations are decreased by approximately 40% in children 6-12 years of age and by 57.5% in children younger than 6 years of age. Some clinicians suggest that dosage adjustments be considered in adolescents to reduce toxicity and adverse effects associated with higher plasma concentrations of the drug. (See Description.)
Based on animal data, stiripentol may cause fetal harm. There are no adequate data on the developmental risks associated with the use of stiripentol in pregnant women. Stiripentol produced developmental toxicity (e.g., fetal malformations, embryofetal mortality) when administered orally to pregnant animals at doses lower than those recommended in humans.
Women who are pregnant while receiving stiripentol should be encouraged to enroll in the North American Antiepileptic Drug (NAAED) Pregnancy Registry at 888-233-2334 or http://www.aedpregnancyregistry.org/.
It is not known whether stiripentol is distributed into milk, affects milk production, or affects the breast-fed infant. The benefits of breast-feeding should be considered along with the importance of stiripentol to the woman and any potential adverse effects on the breast-fed infant from the drug or underlying maternal condition.
There is no experience with use of stiripentol in patients 65 years of age or older to determine whether these patients respond differently than younger adults. When stiripentol is used in patients 65 years of age or older, potential age-related abnormalities in hepatic and renal function should be considered.
ICD codes
No ICD codes are available for this drug.
Formulary status
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Last reviewed · Source: First Databank (FDB) drug data
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