stiripentol (Rx)

Brand and Other Names:Diacomit
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Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

capsule

  • 250mg
  • 500mg

powder for oral suspension

  • 250mg/packet
  • 500mg/packet

Seizures

Indicated for seizures associated with Dravet syndrome in patients taking clobazam

There are no clinical data to support the use of stiripentol as monotherapy in Dravet syndrome

50 mg/kg/day PO administered in 2 or 3 divided doses (ie, 16.67 mg/kg TID or 25 mg/kg BID); not to exceed 3000 mg/day 

Round to the nearest possible dosage (usually within 50-150 mg of the recommended 50 mg/kg/day)

If the exact dosage is not achievable given the available strengths, a combination of the 2 strengths can be used to achieve this dosage

Also see Administration

Dosage Modifications

Renal and hepatic impairment

  • There is no formal study of the pharmacokinetics and metabolism in patients with renal or hepatic impairment
  • Since metabolites are eliminated mainly through the kidney and metabolized by the liver, administration to patients with moderate or severe renal or hepatic impairment is not recommended

Dosing Considerations

Prior to starting treatment, obtain a hematologic test

Gradual withdrawal

  • As advised for most antiepileptic drugs (AEDs), if treatment is discontinued, gradually withdraw stiripentol to minimize the risk of increased seizure frequency and status epilepticus
  • In situations in which rapid withdrawal is medically required, appropriate monitoring is recommended

Dosage Forms & Strengths

capsule

  • 250mg
  • 500mg

powder for oral suspension

  • 250mg/packet
  • 500mg/packet

Seizures

Indicated for seizures associated with Dravet syndrome in patients ≥2 years taking clobazam

There are no clinical data to support the use of stiripentol as monotherapy in Dravet syndrome

<2 years: Safety and efficacy not established

≥2 years

  • 50 mg/kg/day PO administered in 2 or 3 divided doses (ie, 16.67 mg/kg TID or 25 mg/kg BID); not to exceed 3000 mg/day  
  • Round to the nearest possible dosage (usually within 50-150 mg of the recommended 50 mg/kg/day)
  • If the exact dosage is not achievable given the available strengths, a combination of the 2 strengths can be used to achieve this dosage
  • Also see Administration

Dosage Modifications

Renal and hepatic impairment

  • There is no formal study of the pharmacokinetics and metabolism in patients with renal or hepatic impairment
  • Since metabolites are eliminated mainly through the kidney and metabolized by the liver, administration to patients with moderate or severe renal or hepatic impairment is not recommended

Dosing Considerations

Prior to starting treatment, obtain a hematologic test

Gradual withdrawal

  • As advised for most antiepileptic drugs (AEDs), if treatment is discontinued, gradually withdraw stiripentol to minimize the risk of increased seizure frequency and status epilepticus
  • In situations in which rapid withdrawal is medically required, appropriate monitoring is recommended
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Interactions

Interaction Checker

and stiripentol

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            Adverse Effects

            >10%

            Somnolence (67%)

            Decreased appetite (46%)

            Decreased weight (27%)

            Ataxia (27%)

            Agitation (27%)

            Hypotonia (18%)

            Nausea (15%)

            Tremor (15%)

            Dysarthria (12%)

            1-10%

            Vomiting (9%)

            Fatigue (9%)

            Aggression (9%)

            Pyrexia (6%)

            Bronchitis (6%)

            Nasopharyngitis (6%)

            Salivary hypersecretion (6%)

            Increased weight (6%)

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            Warnings

            Contraindications

            None

            Cautions

            Decreased appetite and weight may occur; nausea and vomiting also occurred more frequently in treated patients; given the frequency of these adverse reactions, carefully monitor growth of pediatric patients treated with stiripentol

            Significant decline in neutrophil and platelet count reported; hematologic testing should be obtained prior to starting treatment and then every 6 months

            Like many AEDs, gradually withdraw drug to minimize the risk of increased seizure frequency and status epilepticus (see Dosing Considerations)

            AEDs, including stiripentol, increase the risk of suicidal thoughts or behavior in patients taking these drugs for any indication; monitor for the emergence or worsening of depression, suicidal thoughts or behavior, and/or any unusual changes in mood or behavior

            Phenylketonuria

            • Phenylalanine can be harmful to patients with phenylketonuria (PKU); oral suspension contains phenylalanine, a component of aspartame
            • Each 250-mg packet contains 1.4 mg phenylalanine; each 500-mg packet contains 2.8 mg phenylalanine
            • Prior to prescribing the oral suspension to a patient with PKU, consider the combined daily amount of phenylalanine from all sources, including stiripentol oral suspension; capsules do not contain phenylalanine

            Somnolence

            • In controlled studies in patients with Dravet syndrome, the incidence of somnolence was 67% in treated patients, compared with 23% in patients on placebo; all patients in both groups were on concomitant clobazam, which is also known to cause somnolence
            • Caution patients against engaging in hazardous activities requiring mental alertness, such as operating dangerous machinery or motor vehicles, until the effects on mental alertness is known

            Drug interactions overview

            • Effect of stiripentol on other drugs
              • In vitro data show that stiripentol is a CYP1A2, CYP2B6, and CYP3A4 inhibitor/inducer
              • Consider dose adjustment of CYP1A2 substrates (eg, theophylline, caffeine), CYP2B6 substrates (eg, sertraline, thiotepa), and CYP3A4 substrates (eg, midazolam, triazolam, quinidine), as clinically appropriate, when coadministered with stiripentol
              • Because of potential inhibition of enzyme/transporter activity, consider a reduction in dosage of substrates of CYP2C8, CYP2C19 (eg, diazepam, clopidogrel), P-gp (eg, carbamazepine), and BCRP (eg, methotrexate, prazosin, glyburide) if adverse reactions are experienced when administered concomitantly with stiripentol
              • Coadministration with clobazam results in increased plasma concentrations of clobazam (a substrate of CYP3A4) and norclobazam, the active metabolite of clobazam (a substrate of CYP2C19); may increase the risk of clobazam-related adverse reactions; consider a reduction in dosage of clobazam if adverse reactions are experienced when coadministered with stiripentol
            • Effect of other drugs on stiripentol
              • Induction-based interactions leading to decreases in concentrations are possible when coadministered with a potent CYP1A2, CYP3A4, or CYP2C19 inducer, such as rifampin, phenytoin, phenobarbital, or carbamazepine, as these enzymes all metabolize stiripentol; avoid concomitant use of strong inducers with stiripentol, or dosage adjustments should be made
            • CNS depressants
              • Other CNS depressants, including alcohol, could potentiate the somnolence effect of stiripentol; monitor patients for somnolence
              • If somnolence occurs during coadministration with clobazam, consider an initial reduction of clobazam by 25%
              • If somnolence persists, consider further clobazam reduction by an additional 25% and adjust dosage of other concomitant anticonvulsant drugs with sedating properties
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            Pregnancy & Lactation

            Pregnancy

            There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to AEDs during pregnancy

            Recommend pregnant patients to enroll in the North American Antiepileptic Drug (NAAED) Pregnancy Registry; register by calling the toll free number 1-888-233-2334, and this must be done by patients themselves or their caregiver

            Information on the registry can also be found at the website http://www.aedpregnancyregistry.org/

            There are no adequate data on the developmental risks associated with the use in pregnant women

            Animal data

            • Administration of stiripentol to pregnant animals produced evidence of developmental toxicity, including increased incidences of fetal malformations, increased embryofetal and pup mortality, and decreased embryofetal and pup growth, at maternal doses lower than the recommended clinical dose

            Lactation

            There are no data on the presence of stiripentol in human milk, the effects on the breastfed infant, or the effects on milk production

            Consider the developmental and health benefits of breastfeeding along with the mother’s clinical need for the drug, and any potential adverse effects on the breastfed infant from the drug or from the underlying maternal condition

            Pregnancy Categories

            A:Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

            B:May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

            C:Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

            D:Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

            X:Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

            NA:Information not available.

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            Pharmacology

            Mechanism of Action

            Anticonvulsant effect in humans is unknown

            Possible mechanisms of action include direct effects mediated through the gamma-aminobutyric acid (GABA) A receptor and indirect effects involving inhibition of cytochrome P450 activity with resulting increase in blood levels of clobazam and its active metabolite

            Absorption

            Peak plasma time: 2-3 hr

            Distribution

            Protein binding: 99%

            Metabolism

            Metabolized in the liver by CYP1A2, CYP2C19, and CYP3A4

            Elimination

            Half-life (healthy adults): 4.5-13 hr, increasing with doses of 500 mg, 1000 mg, and 2000 mg

            Half-life (children [median age 7.3 years] with Dravet syndrome): 8.5 hr (10-kg patient); 23.5 hr (60-kg patient)

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            Administration

            Oral Administration

            Capsules

            • Swallow whole with a glass of water during a meal
            • Capsule should not be broken or opened

            Powder for oral suspension

            • Mix in a glass of water (100 mL) and take immediately after mixing during a meal
            • To be sure there is no medicine left in the glass, add a small amount of water (25 mL) to the drinking cup and drink all of the mixture
            • Do not store mixture after it is mixed; must be administered immediately after mixing

            Missed dose

            • A missed dose should be taken as soon as possible
            • If it is almost time for the next dose, do not take the missed dose; instead, the next scheduled dose should be taken
            • Do not double-dose

            Storage

            Store in a dry place at 20-25°C (68-77°F); excursions permitted to 15-30°C (59-86°F)

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            Formulary

            FormularyPatient Discounts

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            The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

            Tier Description
            1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
            2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
            3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
            4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            NC NOT COVERED – Drugs that are not covered by the plan.
            Code Definition
            PA Prior Authorization
            Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
            QL Quantity Limits
            Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered.
            ST Step Therapy
            Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
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            Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.