Stiripentol

Stiripentol is a prescription medication used for the treatment of seizures associated with Dravet syndrome in patients taking clobazam.

• Stiripentol is available under the following different brand names: Diacomit

Common side effects of Stiripentol include:

• drowsiness
• decreased appetite
• agitation
• loss of coordination
• weight loss
• low muscle tone ("floppy baby syndrome")
• nausea
• tremor
• difficulty speaking
• insomnia

Serious side effects of Stiripentol include:

• loss of coordination
• trouble speaking
• tremor
• mental/mood disorders (such as confusion, agitation, aggression)
• easy bruising/bleeding
• signs of infections (such as sore throat that doesn't go away, fever, chills)

Rare side effects of Stiripentol include:

• none 

Seek medical care or call 911 at once if you have the following serious side effects:

• Severe headache, confusion, slurred speech, arm or leg weakness, trouble walking, coordination loss, unsteady, very stiff muscles, high fever, profuse sweating, or tremors
• Serious eye symptoms such as sudden vision loss, blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights
• Serious heart symptoms include fast, irregular, or pounding heartbeats; fluttering in the chest; shortness of breath; sudden dizziness, light-headedness, or passing out

This is not a complete list of side effects and other serious side effects or health problems that may occur because of the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may report side effects or health problems to FDA at 1-800-FDA-1088.

Adult and pediatric dosage

Capsule

• 250 mg
• 500 mg

Powder for oral suspension

• 250 mg/packet
• 500 mg/packet

Seizures

Adult dosage

• There are no clinical data to support the use of stiripentol as monotherapy in Dravet syndrome
• 50 mg/kg/day orally administered in 2 or 3 divided doses (ie, 16.67 mg/kg three times a day or 25 mg/kg two times a day); 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 two strengths can be used to achieve this dosage

Pediatric dosage

• Children aged younger than 6 months: Safety and efficacy not established
• Children aged 6 months and older
  • 50 mg/kg/day orally administered in 2 or 3 divided doses (ie, 16.67 mg/kg three times a day or 25 mg/kg two times a day); 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
• Children aged 6 months to younger than 1 year
  • Children weighing 7 kg and more: 25 mg/kg orally two times a day; do not exceed twice daily dosing frequency to limit free water administration and avoid overexposures
  • Children weighing 7 kg to less than 10 kg: 25 mg/kg orally two times a day; do not exceed twice daily; dosing frequency to avoid overexposures
• Children aged 1 year and older
  • Children weighing 10 kg and more: 25 mg/kg orally two times a day; or 16.67 mg/kg orally three times a day
  • Not to exceed 3000 mg/day

Dosage Considerations – Should be Given as Follows:

• See "Dosages"

If your medical doctor is using this medicine to treat your pain, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, healthcare provider, or pharmacist first.

• Stiripentol has severe interactions with the following drugs:
  • fezolinetant
  • finerenone
  • idelalisib
  • isavuconazonium sulfate
  • lonafarnib
  • mavacamten
  • voclosporin
• Stiripentol has serious interactions with at least 77 other drugs.
• Stiripentol has moderate interactions with at least 512 other drugs.
• Stiripentol has minor interactions with the following drugs:
  • acetazolamide
  • anastrozole
  • aspirin
  • cenobamate
  • cyclophosphamide
  • ganaxolone
  • larotrectinib

This information does not contain all possible interactions or adverse effects. Visit the RxList Drug Interaction Checker for any drug interactions. Therefore, before using this product, tell your doctor or pharmacist about all the products you use. Keep a list of all your medications with you and share this information with your doctor and pharmacist. Check with your healthcare professional or doctor for additional medical advice, health questions, or concerns.

Contraindications

• None

Effects of drug abuse

• None

Short-Term Effects

• See “What Are Side Effects Associated with Using Stiripentol?”

Long-Term Effects

• See “What Are Side Effects Associated with Using Stiripentol?”

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 the growth of pediatric patients treated with stiripentol
• Significant decline in neutrophil and platelet count reported; hematologic testing should be obtained before starting treatment and then every 6 months
• Like many antiepileptic drugs (AEDs), gradually withdraw the drug to minimize the risk for increased seizure frequency and status epilepticus
• AEDs, including stiripentol, increase the risk for 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 (PKU)
  • Phenylalanine can be harmful to patients with 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
  • Before 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 are 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 for 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
  • Central nervous system (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 the dosage of other concomitant anticonvulsant drugs with sedating properties

Pregnancy and Lactation

• 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 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
• Lactation
  • There are no data on the presence of stiripentol in human milk, the effects on the breastfed infant, or 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 the underlying maternal condition