Version May 2024
Note: FDA approved in combination with clobazam; international labeling (European Medicines Agency, Health Canada) recommends combination with clobazam and valproic acid (Diacomit European Medicines Agency 2021; Diacomit Canadian product monograph). Not appropriate for monotherapy. Clinical trial data are limited to patients taking stiripentol with both clobazam and valproic acid (Brigo 2017; Chiron 2000). The dosage of concomitant clobazam and valproate may need to be adjusted. Systemic exposure is slightly higher with the powder for suspension than that observed with capsules; patient monitoring is recommended when switching between dosage forms (Diacomit Canadian product monograph).
Dravet syndrome–associated seizures (adjunctive therapy): Oral: Usual: 50 mg/kg/day given in 2 or 3 divided doses; some experts initiate with 10 to 15 mg/kg/day and increase to a target dose of 50 mg/kg/day over 2 to 4 weeks (Wirrell 2016; manufacturer’s labeling). Maximum dose: 3 g/day.
Discontinuation of therapy: In chronic therapy, withdraw gradually to minimize the potential of increased seizure frequency and status epilepticus, unless safety concerns require a more rapid withdrawal.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
There are no dosage adjustments provided in the manufacturer's labeling (has not been studied). Use with caution with mild impairment and titrate dose per seizure control and tolerability; metabolites primarily undergo renal elimination. Avoid use in patients with moderate to severe renal impairment.
There are no dosage adjustments provided in the manufacturer's labeling (has not been studied). Use with caution with mild impairment and titrate dose per seizure control and tolerability; metabolism is primarily hepatic. Avoid use in patients with moderate to severe hepatic impairment.
Refer to adult dosing.
(For additional information see "Stiripentol: Pediatric drug information")
Note: Systemic exposure is slightly higher with the powder for suspension than that observed with capsules; patient monitoring is recommended when switching between dosage forms (Diacomit prescribing information [Canada 2012]). Two strengths of powder packets are available (250 mg and 500 mg); may combine the two strengths to achieve the appropriate dosage; ensure appropriate product selection.
Dravet syndrome; adjunctive therapy:
Note: In the United States, FDA approved for adjunct treatment of Dravet syndrome in combination with clobazam; international labeling (European Medicines Agency, Health Canada) recommends combination with clobazam and valproic acid. Other concomitant antiseizure agents have also been studied (eg, topiramate) and efficacy data are evolving, although experts suggest avoiding sodium channel blockers (eg, carbamazepine) which may exacerbate seizures (Wirrell 2016). The concomitant dosage of clobazam and/or valproate may need to be adjusted with initiation of stiripentol.
Infants ≥6 months weighing ≥7 kg: Oral: 50 mg/kg/day in 2 divided doses; round dose to the nearest available dosage form; to prevent stiripentol overexposure and limit free water consumption due to volume required to administer each dose, do not administer more frequently than twice daily in infants.
Children and Adolescents weighing ≥7 kg:
≥7 to <10 kg: Oral: 50 mg/kg/day in 2 divided doses; round dose to nearest available dosage form; to prevent stiripentol overexposure and limit free water consumption due to volume required to administer each dose, do not administer more frequently than twice daily.
≥10 kg: Oral: 50 mg/kg/day in 2 or 3 divided doses; round dose to nearest available dosage form; maximum daily dose: 3,000 mg/day.
Some experts recommend initiating at a lower dosage of 10 to 15 mg/kg/day in divided doses and titrating to initial target dose of 50 mg/kg/day over a 2- to 4-week period (Wirrell 2016). Higher doses were reported in one open-label, multicenter trial of patients with Dravet syndrome (n=23; ages: 1 to 22 years); the initial dose was 50 mg/kg/day in divided doses in patients <20 kg and a fixed dose of 1,000 mg/day in divided doses in patients ≥20 kg; after 4 weeks, dosage was adjusted based on clinical response up to a maximum of 100 mg/kg/day (or 4,000 mg/day) in divided doses. In patients 1 to 8 years (n=15), mean daily dose was 59 mg/kg/day (range: 30 to 100 mg/kg/day) and in patients 13 to 22 years (n=8), mean daily dose was 1,469 mg/day (range: 500 to 3,000 mg/day) (Inoue 2009). Pharmacokinetic modeling studies indicate adolescents may require lower doses of 20 to 30 mg/kg/day (May 2012; Wirrell 2016).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
There are no dosage adjustments provided in the manufacturer's labeling (has not been studied). Metabolites primarily undergo renal elimination; use with caution in patients with mild impairment; use not recommended in patients with moderate to severe renal impairment.
There are no dosage adjustments provided in the manufacturer's labeling (has not been studied). Metabolism is primarily hepatic; use with caution in patients with mild impairment; use not recommended in patients with moderate to severe hepatic impairment.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Adverse reactions reported with combination (clobazam) therapy.
>10%:
Central nervous system: Drowsiness (67%), agitation (27%), ataxia (27%), hypotonia (18% to 24%), dysarthria (12%), insomnia (12%)
Endocrine & metabolic: Weight loss (27%)
Gastrointestinal: Decreased appetite (45% to 46%), nausea (15%)
Hematologic & oncologic: Decreased platelet count (13%), neutropenia (13%)
Neuromuscular & skeletal: Tremor (15%)
1% to 10%:
Central nervous system: Aggressive behavior (9%), fatigue (9%)
Endocrine & metabolic: Weight gain (6%)
Gastrointestinal: Vomiting (9%), sialorrhea (6%)
Respiratory: Bronchitis (6%), nasopharyngitis (6%)
Miscellaneous: Fever (6%)
There are no contraindications listed in the US manufacturer's labeling.
Canadian labeling: Additional contraindications (not in US labeling): Hypersensitivity to stiripentol or any component of the formulation.
Concerns related to adverse effects:
• Appetite/weight loss: Loss of appetite and weight loss have been observed in 46% and 27% of patients (mean age: 9.2 years), respectively, during clinical trials; monitor the growth rate of pediatric patients closely. Valproate dose reduction by 30% may help minimize appetite and weight loss.
• Blood dyscrasias: Neutropenia and thrombocytopenia have been observed in clinical trials; monitor CBC during therapy.
• CNS depression: May cause CNS depression (eg, drowsiness, sleepiness) and impair physical or mental abilities; patients must be cautioned about performing tasks that require mental alertness (eg, operating machinery or driving). If CNS depression occurs during co-administration with clobazam, consider dosage adjustment of clobazam and/or other concomitant antiseizure drugs.
• Suicidal ideation: Pooled analysis of trials involving various antiseizure medications (regardless of indication) showed an increased risk of suicidal thoughts/behavior (incidence rate: 0.43% treated patients compared to 0.24% of patients receiving placebo); risk observed as early as 1 week after initiation and continued through duration of trials (most trials ≤24 weeks). Monitor all patients for notable changes in behavior that might indicate suicidal thoughts or depression; notify health care provider immediately if symptoms occur.
Disease-related concerns:
• Hepatic impairment: Use with caution in patients with mild impairment; primarily undergoes hepatic metabolism. Avoid use in patients with moderate to severe hepatic impairment.
• Renal impairment: Use with caution in patients with mild impairment; elimination of metabolites is primarily renal. Avoid use in patients with moderate to severe renal impairment.
Dosage form specific issues:
• Powder for suspension: Systemic exposure is slightly higher with the powder for suspension than that observed with capsules; may consider patient monitoring when switching between dosage forms. Powder for suspension contains phenylalanine; use caution in patients with phenylketonuria.
Other warnings:
• Appropriate use: Use in conjunction with clobazam and valproate (Chiron 2000; Wirrell 2016); not approved for use as monotherapy.
• Withdrawal: Antiseizure medications should not be discontinued abruptly because of the possibility of increasing seizure frequency; therapy should be withdrawn gradually (over at least 1 month) to minimize the potential of increased seizure frequency, unless safety concerns require a more rapid withdrawal.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule, Oral:
Diacomit: 250 mg [contains fd&c blue #2 (indigotine,indigo carmine)]
Diacomit: 500 mg
Packet, Oral:
Diacomit: 250 mg (60 ea); 500 mg (60 ea) [contains aspartame]
No
Capsules (Diacomit Oral)
250 mg (per each): $37.53
500 mg (per each): $75.05
Pack (Diacomit Oral)
250 mg (per each): $37.53
500 mg (per each): $75.05
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Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule, Oral:
Diacomit: 250 mg [contains fd&c blue #2 (indigotine,indigo carmine)]
Diacomit: 500 mg
Packet, Oral:
Diacomit: 250 mg (1 ea) [contains aspartame]
Oral: Administer with meals.
Capsule: Swallow whole with a glass of water. Do not crush, chew, or open capsule.
Powder for suspension: Two strengths of powder packets are available (250 mg and 500 mg); may combine the 2 strengths to achieve the appropriate dosage; ensure appropriate product selection. Mix powder packet(s) required for the dose with a glass of water (~100 mL), stir, and consume immediately. More than 1 packet may be required for appropriate dose. After administering the dose, add a small amount of water (25 mL) to glass to suspend any remaining drug and consume remaining liquid immediately.
Oral: Administer with food.
Capsule: Swallow whole with a glass of water; do not crush, chew, or open capsule.
Powder for suspension: Note: Two strengths of powder packets are available (250 mg and 500 mg); may combine the two strengths to achieve the appropriate dosage; ensure appropriate product selection. Mix powder packet(s) required for the dose with a 100 mL of water, stir, and consume immediately. More than one packet may be required for appropriate dose. After administering the dose, add a small amount of water (25 mL) to glass to suspend any remaining drug and consume remaining liquid immediately.
This medication is not on the NIOSH (2016) list; however, it may meet the criteria for a hazardous drug. Stiripentol may cause teratogenicity.
Use appropriate precautions for receiving, handling, storage, preparation, dispensing, transporting, administration, and disposal. Follow NIOSH and USP 800 recommendations and institution-specific policies/procedures for appropriate containment strategy (NIOSH 2016; USP-NF 2020).
Note: Facilities may perform risk assessment of some hazardous drugs to determine if appropriate for alternative handling and containment strategies (USP-NF 2020). Refer to institution-specific handling policies/procedures.
An FDA-approved patient medication guide, which is available with the product information and at https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/206709s000,207223s000lbl.pdf#page=17, must be dispensed with this medication.
Dravet syndrome-associated seizures: Adjunctive treatment of seizures associated with Dravet syndrome in conjunction with clobazam in patients ≥6 months of age and weighing ≥7 kg; not indicated for monotherapy.
Note: FDA approved in combination with clobazam; international labeling (European Medicines Agency, Health Canada) recommends combination with clobazam and valproic acid (Diacomit European Medicines Agency 2021; Diacomit Canadian product monograph). Clinical trial data are limited to patients taking stiripentol with both clobazam and valproic acid (Brigo 2017; Chiron 2000).
Substrate of CYP1A2 (minor), CYP2C19 (minor), CYP3A4 (minor); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential; Inhibits CYP1A2 (moderate), CYP2C19 (moderate), CYP3A4 (weak)
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Abrocitinib: CYP2C19 Inhibitors (Moderate) may increase the serum concentration of Abrocitinib. Risk C: Monitor therapy
Agomelatine: CYP1A2 Inhibitors (Moderate) may increase the serum concentration of Agomelatine. Risk C: Monitor therapy
Alcohol (Ethyl): Stiripentol may enhance the sedative effect of Alcohol (Ethyl). Risk X: Avoid combination
Alizapride: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Alosetron: CYP1A2 Inhibitors (Moderate) may increase the serum concentration of Alosetron. Management: Avoid concomitant use of alosetron and moderate CYP1A2 inhibitors whenever possible. If combined use is necessary, monitor for increased alosetron effects/toxicities. Risk D: Consider therapy modification
ALPRAZolam: CYP3A4 Inhibitors (Weak) may increase the serum concentration of ALPRAZolam. Risk C: Monitor therapy
Anagrelide: CYP1A2 Inhibitors (Moderate) may increase serum concentrations of the active metabolite(s) of Anagrelide. CYP1A2 Inhibitors (Moderate) may increase the serum concentration of Anagrelide. Risk C: Monitor therapy
Azelastine (Nasal): May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination
Belzutifan: CYP2C19 Inhibitors (Moderate) may increase the serum concentration of Belzutifan. Risk C: Monitor therapy
Bendamustine: CYP1A2 Inhibitors (Moderate) may increase the serum concentration of Bendamustine. Management: Consider alternatives to moderate CYP1A2 inhibitors during therapy with bendamustine due to the potential for increased bendamustine plasma concentrations and increased bendamustine toxicity. Risk D: Consider therapy modification
Blonanserin: CNS Depressants may enhance the CNS depressant effect of Blonanserin. Management: Use caution if coadministering blonanserin and CNS depressants; dose reduction of the other CNS depressant may be required. Strong CNS depressants should not be coadministered with blonanserin. Risk D: Consider therapy modification
Brexanolone: CNS Depressants may enhance the CNS depressant effect of Brexanolone. Risk C: Monitor therapy
Brimonidine (Topical): May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Brivaracetam: CYP2C19 Inhibitors (Moderate) may increase the serum concentration of Brivaracetam. Risk C: Monitor therapy
Bromazepam: CYP1A2 Inhibitors (Moderate) may increase the serum concentration of Bromazepam. Risk C: Monitor therapy
Bromopride: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Bromperidol: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination
Buprenorphine: CNS Depressants may enhance the CNS depressant effect of Buprenorphine. Management: Consider reduced doses of other CNS depressants, and avoiding such drugs in patients at high risk of buprenorphine overuse/self-injection. Initiate buprenorphine at lower doses in patients already receiving CNS depressants. Risk D: Consider therapy modification
Caffeine and Caffeine Containing Products: CYP1A2 Inhibitors (Moderate) may increase the serum concentration of Caffeine and Caffeine Containing Products. Risk C: Monitor therapy
Cannabidiol: Stiripentol may increase the serum concentration of Cannabidiol. Cannabidiol may increase the serum concentration of Stiripentol. Risk C: Monitor therapy
Cannabinoid-Containing Products: CNS Depressants may enhance the CNS depressant effect of Cannabinoid-Containing Products. Risk C: Monitor therapy
CarBAMazepine: May decrease the serum concentration of Stiripentol. Stiripentol may increase the serum concentration of CarBAMazepine. Management: Avoid the use of stiripentol and carbamazepine when possible. If combined, monitor for both reduced stiripentol efficacy and increased carbamazepine concentrations and toxicities. Dose adjustments of both drugs may be needed. Risk D: Consider therapy modification
Carisoprodol: CYP2C19 Inhibitors (Moderate) may decrease serum concentrations of the active metabolite(s) of Carisoprodol. CYP2C19 Inhibitors (Moderate) may increase the serum concentration of Carisoprodol. Risk C: Monitor therapy
Chlormethiazole: May enhance the CNS depressant effect of CNS Depressants. Management: Monitor closely for evidence of excessive CNS depression. The chlormethiazole labeling states that an appropriately reduced dose should be used if such a combination must be used. Risk D: Consider therapy modification
Chlorphenesin Carbamate: May enhance the adverse/toxic effect of CNS Depressants. Risk C: Monitor therapy
Cilostazol: CYP2C19 Inhibitors (Moderate) may increase serum concentrations of the active metabolite(s) of Cilostazol. CYP2C19 Inhibitors (Moderate) may increase the serum concentration of Cilostazol. Management: Reduce the cilostazol dose to 50 mg twice daily in patients who are also receiving moderate inhibitors of CYP2C19. Monitor clinical response to cilostazol closely. Risk D: Consider therapy modification
Citalopram: CYP2C19 Inhibitors (Moderate) may increase the serum concentration of Citalopram. Management: Limit citalopram dose to a maximum of 20 mg/day if used with a moderate CYP2C19 inhibitor. Patients using this combination should be monitored closely for evidence of citalopram toxicity (eg, serotonin syndrome, QT prolongation). Risk D: Consider therapy modification
CloBAZam: CYP2C19 Inhibitors (Moderate) may increase serum concentrations of the active metabolite(s) of CloBAZam. CYP2C19 Inhibitors (Moderate) may increase the serum concentration of CloBAZam. Risk C: Monitor therapy
ClomiPRAMINE: CYP1A2 Inhibitors (Moderate) may increase the serum concentration of ClomiPRAMINE. Risk C: Monitor therapy
Clopidogrel: CYP2C19 Inhibitors (Moderate) may decrease serum concentrations of the active metabolite(s) of Clopidogrel. Risk C: Monitor therapy
CloZAPine: CYP1A2 Inhibitors (Moderate) may increase the serum concentration of CloZAPine. Risk C: Monitor therapy
CNS Depressants: May enhance the adverse/toxic effect of other CNS Depressants. Risk C: Monitor therapy
CycloSPORINE (Systemic): CYP3A4 Inhibitors (Weak) may increase the serum concentration of CycloSPORINE (Systemic). Risk C: Monitor therapy
CYP3A4 Inducers (Strong): May decrease the serum concentration of Stiripentol. Management: Avoid concomitant use of stiripentol and strong CYP3A4 inducers when possible. If combined, monitor for reduced stiripentol efficacy and increase the stiripentol dose as needed. Risk D: Consider therapy modification
Daridorexant: May enhance the CNS depressant effect of CNS Depressants. Management: Dose reduction of daridorexant and/or any other CNS depressant may be necessary. Use of daridorexant with alcohol is not recommended, and the use of daridorexant with any other drug to treat insomnia is not recommended. Risk D: Consider therapy modification
Desmopressin: Hyponatremia-Associated Agents may enhance the hyponatremic effect of Desmopressin. Risk C: Monitor therapy
Dexlansoprazole: CYP2C19 Inhibitors (Moderate) may increase the serum concentration of Dexlansoprazole. Risk C: Monitor therapy
DexmedeTOMIDine: CNS Depressants may enhance the CNS depressant effect of DexmedeTOMIDine. Management: Monitor for increased CNS depression during coadministration of dexmedetomidine and CNS depressants, and consider dose reductions of either agent to avoid excessive CNS depression. Risk D: Consider therapy modification
DiazePAM: CYP2C19 Inhibitors (Moderate) may increase the serum concentration of DiazePAM. Risk C: Monitor therapy
Difelikefalin: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Dimethindene (Topical): May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Dofetilide: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Dofetilide. Risk C: Monitor therapy
Doxylamine: CNS Depressants may enhance the CNS depressant effect of Doxylamine. Risk C: Monitor therapy
DroPERidol: May enhance the CNS depressant effect of CNS Depressants. Management: Consider dose reductions of droperidol or of other CNS agents (eg, opioids, barbiturates) with concomitant use. Risk D: Consider therapy modification
DULoxetine: CYP1A2 Inhibitors (Moderate) may increase the serum concentration of DULoxetine. Risk C: Monitor therapy
Escitalopram: CYP2C19 Inhibitors (Moderate) may increase the serum concentration of Escitalopram. Risk C: Monitor therapy
Esketamine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Etravirine: CYP2C19 Inhibitors (Moderate) may increase the serum concentration of Etravirine. Risk C: Monitor therapy
Fenfluramine: Stiripentol may increase the serum concentration of Fenfluramine. Management: If coadministered with stiripentol and clobazam, initate fenfluramine at 0.1 mg/kg twice daily, then on day 7 increase fenfluramine to 0.15 mg/kg twice daily, and on day 14 increase fenfluramine to 0.2 mg/kg twice daily. Max dose 17 mg/day. Risk D: Consider therapy modification
Fezolinetant: CYP1A2 Inhibitors (Moderate) may increase the serum concentration of Fezolinetant. Risk X: Avoid combination
Finerenone: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Finerenone. Risk C: Monitor therapy
Flibanserin: CYP2C19 Inhibitors (Moderate) may increase the serum concentration of Flibanserin. Risk C: Monitor therapy
Flunarizine: CNS Depressants may enhance the CNS depressant effect of Flunarizine. Risk X: Avoid combination
Flunitrazepam: CNS Depressants may enhance the CNS depressant effect of Flunitrazepam. Management: Reduce the dose of CNS depressants when combined with flunitrazepam and monitor patients for evidence of CNS depression (eg, sedation, respiratory depression). Use non-CNS depressant alternatives when available. Risk D: Consider therapy modification
Fosphenytoin-Phenytoin: May decrease the serum concentration of Stiripentol. Stiripentol may increase the serum concentration of Fosphenytoin-Phenytoin. Management: Avoid this combination when possible. If combined, monitor for decreased stiripentol concentrations and effects and monitor for increased phenytoin concentrations and effects. Dose adjustments of either medication may be needed. Risk D: Consider therapy modification
HydrOXYzine: May enhance the CNS depressant effect of CNS Depressants. Management: Consider a decrease in the CNS depressant dose, as appropriate, when used together with hydroxyzine. Increase monitoring of signs/symptoms of CNS depression in any patient receiving hydroxyzine together with another CNS depressant. Risk D: Consider therapy modification
Ixabepilone: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Ixabepilone. Risk C: Monitor therapy
Kava Kava: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Kratom: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination
Lansoprazole: CYP2C19 Inhibitors (Moderate) may increase the serum concentration of Lansoprazole. Risk C: Monitor therapy
Lemborexant: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Lemborexant. Management: The maximum recommended dosage of lemborexant is 5 mg, no more than once per night, when coadministered with weak CYP3A4 inhibitors. Risk D: Consider therapy modification
Lemborexant: May enhance the CNS depressant effect of CNS Depressants. Management: Dosage adjustments of lemborexant and of concomitant CNS depressants may be necessary when administered together because of potentially additive CNS depressant effects. Close monitoring for CNS depressant effects is necessary. Risk D: Consider therapy modification
Lisuride: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Lofexidine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Lomitapide: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Lomitapide. Management: Patients on lomitapide 5 mg/day may continue that dose. Patients taking lomitapide 10 mg/day or more should decrease the lomitapide dose by half. The lomitapide dose may then be titrated up to a max adult dose of 30 mg/day. Risk D: Consider therapy modification
Lonafarnib: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Lonafarnib. Management: Avoid concurrent use of lonafarnib with weak CYP3A4 inhibitors. If concurrent use is unavoidable, reduce the lonafarnib dose to or continue at a dose of 115 mg/square meter. Monitor for evidence of arrhythmia, syncope, palpitations, or similar effects. Risk D: Consider therapy modification
Magnesium Sulfate: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Mavacamten: CYP2C19 Inhibitors (Moderate) may increase the serum concentration of Mavacamten. Risk X: Avoid combination
Mefloquine: May diminish the therapeutic effect of Antiseizure Agents. Mefloquine may decrease the serum concentration of Antiseizure Agents. Management: Mefloquine is contraindicated for malaria prophylaxis in persons with a history of seizures. If antiseizure drugs are being used for another indication, monitor antiseizure drug concentrations and treatment response closely with concurrent use. Risk D: Consider therapy modification
Melatonin: CYP1A2 Inhibitors (Moderate) may increase the serum concentration of Melatonin. Risk C: Monitor therapy
Methotrimeprazine: CNS Depressants may enhance the CNS depressant effect of Methotrimeprazine. Methotrimeprazine may enhance the CNS depressant effect of CNS Depressants. Management: Reduce the usual dose of CNS depressants by 50% if starting methotrimeprazine until the dose of methotrimeprazine is stable. Monitor patient closely for evidence of CNS depression. Risk D: Consider therapy modification
Metoclopramide: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
MetyraPONE: Antiseizure Agents may diminish the diagnostic effect of MetyraPONE. Management: Consider alternatives to the use of the metyrapone test in patients taking antiseizure agents. Risk D: Consider therapy modification
MetyroSINE: CNS Depressants may enhance the sedative effect of MetyroSINE. Risk C: Monitor therapy
Mianserin: May diminish the therapeutic effect of Antiseizure Agents. Risk C: Monitor therapy
Midazolam: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Midazolam. Risk C: Monitor therapy
Minocycline (Systemic): May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Moclobemide: CYP2C19 Inhibitors (Moderate) may increase the serum concentration of Moclobemide. Risk C: Monitor therapy
Nabilone: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination
NiMODipine: CYP3A4 Inhibitors (Weak) may increase the serum concentration of NiMODipine. Risk C: Monitor therapy
OLANZapine: CYP1A2 Inhibitors (Moderate) may increase the serum concentration of OLANZapine. Risk C: Monitor therapy
Olopatadine (Nasal): May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination
Omeprazole: CYP2C19 Inhibitors (Moderate) may increase the serum concentration of Omeprazole. Risk C: Monitor therapy
Opioid Agonists: CNS Depressants may enhance the CNS depressant effect of Opioid Agonists. Management: Avoid concomitant use of opioid agonists and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Risk D: Consider therapy modification
Orlistat: May decrease the serum concentration of Antiseizure Agents. Risk C: Monitor therapy
Orphenadrine: CNS Depressants may enhance the CNS depressant effect of Orphenadrine. Risk X: Avoid combination
Oxomemazine: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination
Oxybate Salt Products: CNS Depressants may enhance the CNS depressant effect of Oxybate Salt Products. Management: Consider alternatives to this combination when possible. If combined, dose reduction or discontinuation of one or more CNS depressants (including the oxybate salt product) should be considered. Interrupt oxybate salt treatment during short-term opioid use Risk D: Consider therapy modification
OxyCODONE: CNS Depressants may enhance the CNS depressant effect of OxyCODONE. Management: Avoid concomitant use of oxycodone and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Risk D: Consider therapy modification
Paraldehyde: CNS Depressants may enhance the CNS depressant effect of Paraldehyde. Risk X: Avoid combination
Pentoxifylline: CYP1A2 Inhibitors (Moderate) may increase the serum concentration of Pentoxifylline. Risk C: Monitor therapy
Perampanel: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Pimozide: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Pimozide. Risk X: Avoid combination
Pirfenidone: CYP1A2 Inhibitors (Moderate) may increase the serum concentration of Pirfenidone. Management: Avoid concomitant use of pirfenidone and moderate CYP1A2 inhibitors whenever possible. If combined, decrease the pirfenidone dose to 1,602 mg per day (534 mg three times daily) and monitor for increased pirfenidone toxicities. Risk D: Consider therapy modification
Piribedil: CNS Depressants may enhance the CNS depressant effect of Piribedil. Risk C: Monitor therapy
Pomalidomide: CYP1A2 Inhibitors (Moderate) may increase the serum concentration of Pomalidomide. Risk C: Monitor therapy
Pramipexole: CNS Depressants may enhance the sedative effect of Pramipexole. Risk C: Monitor therapy
Procarbazine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Proguanil: CYP2C19 Inhibitors (Moderate) may decrease serum concentrations of the active metabolite(s) of Proguanil. CYP2C19 Inhibitors (Moderate) may increase the serum concentration of Proguanil. Risk C: Monitor therapy
Propranolol: CYP1A2 Inhibitors (Moderate) may increase the serum concentration of Propranolol. Risk C: Monitor therapy
Ramelteon: CYP1A2 Inhibitors (Moderate) may increase the serum concentration of Ramelteon. Risk C: Monitor therapy
Ramosetron: CYP1A2 Inhibitors (Moderate) may increase the serum concentration of Ramosetron. Risk C: Monitor therapy
Rasagiline: CYP1A2 Inhibitors (Moderate) may increase the serum concentration of Rasagiline. Management: Limit rasagiline dose to 0.5 mg once daily in patients taking moderate CYP1A2 inhibitors. Risk D: Consider therapy modification
Ropeginterferon Alfa-2b: CNS Depressants may enhance the adverse/toxic effect of Ropeginterferon Alfa-2b. Specifically, the risk of neuropsychiatric adverse effects may be increased. Management: Avoid coadministration of ropeginterferon alfa-2b and other CNS depressants. If this combination cannot be avoided, monitor patients for neuropsychiatric adverse effects (eg, depression, suicidal ideation, aggression, mania). Risk D: Consider therapy modification
ROPINIRole: CNS Depressants may enhance the sedative effect of ROPINIRole. Risk C: Monitor therapy
ROPINIRole: CYP1A2 Inhibitors (Moderate) may increase the serum concentration of ROPINIRole. Risk C: Monitor therapy
ROPivacaine: CYP1A2 Inhibitors (Moderate) may increase the serum concentration of ROPivacaine. Risk C: Monitor therapy
Rotigotine: CNS Depressants may enhance the sedative effect of Rotigotine. Risk C: Monitor therapy
Rufinamide: May enhance the adverse/toxic effect of CNS Depressants. Specifically, sleepiness and dizziness may be enhanced. Risk C: Monitor therapy
Simvastatin: CYP3A4 Inhibitors (Weak) may increase serum concentrations of the active metabolite(s) of Simvastatin. CYP3A4 Inhibitors (Weak) may increase the serum concentration of Simvastatin. Risk C: Monitor therapy
Sirolimus (Conventional): CYP3A4 Inhibitors (Weak) may increase the serum concentration of Sirolimus (Conventional). Risk C: Monitor therapy
Sirolimus (Protein Bound): CYP3A4 Inhibitors (Weak) may increase the serum concentration of Sirolimus (Protein Bound). Management: Reduce the dose of protein bound sirolimus to 56 mg/m2 when used concomitantly with a weak CYP3A4 inhibitor. Risk D: Consider therapy modification
Suvorexant: CNS Depressants may enhance the CNS depressant effect of Suvorexant. Management: Dose reduction of suvorexant and/or any other CNS depressant may be necessary. Use of suvorexant with alcohol is not recommended, and the use of suvorexant with any other drug to treat insomnia is not recommended. Risk D: Consider therapy modification
Tacrolimus (Systemic): CYP3A4 Inhibitors (Weak) may increase the serum concentration of Tacrolimus (Systemic). Risk C: Monitor therapy
Tasimelteon: CYP1A2 Inhibitors (Moderate) may increase the serum concentration of Tasimelteon. Risk C: Monitor therapy
Thalidomide: CNS Depressants may enhance the CNS depressant effect of Thalidomide. Risk X: Avoid combination
Theophylline Derivatives: CYP1A2 Inhibitors (Moderate) may increase the serum concentration of Theophylline Derivatives. Management: Consider avoidance of this combination. If coadministration is necessary, monitor for increased theophylline serum concentrations and toxicities when combined. Theophylline dose reductions will likely be required. Risk D: Consider therapy modification
TiZANidine: CYP1A2 Inhibitors (Moderate) may increase the serum concentration of TiZANidine. Management: If combined use cannot be avoided, initiate tizanidine in adults at 2 mg and increase in 2 to 4 mg increments based on patient response. Monitor for increased effects of tizanidine, including adverse reactions. Risk D: Consider therapy modification
Triazolam: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Triazolam. Risk C: Monitor therapy
Trimeprazine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Ubrogepant: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Ubrogepant. Management: In patients taking weak CYP3A4 inhibitors, the initial and second dose (given at least 2 hours later if needed) of ubrogepant should be limited to 50 mg. Risk D: Consider therapy modification
Valerian: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Voriconazole: CYP2C19 Inhibitors (Moderate) may increase the serum concentration of Voriconazole. Risk C: Monitor therapy
Zolpidem: CNS Depressants may enhance the CNS depressant effect of Zolpidem. Management: Reduce the Intermezzo brand sublingual zolpidem adult dose to 1.75 mg for men who are also receiving other CNS depressants. No such dose change is recommended for women. Avoid use with other CNS depressants at bedtime; avoid use with alcohol. Risk D: Consider therapy modification
Zuranolone: May enhance the CNS depressant effect of CNS Depressants. Management: Consider alternatives to the use of zuranolone with other CNS depressants or alcohol. If combined, consider a zuranolone dose reduction and monitor patients closely for increased CNS depressant effects. Risk D: Consider therapy modification
Adverse events have been observed in animal reproduction studies. Information related to the use of stiripentol in pregnancy has not been located (de Jong 2016).
Stiripentol is used in combination with clobazam and valproic acid; refer to individual monographs for additional information.
Data collection to monitor pregnancy and infant outcomes following exposure to stiripentol is ongoing. Patients may enroll themselves in the North American Antiepileptic Drug (NAAED) Pregnancy Registry (1-888-233-2334 or http://www.aedpregnancyregistry.org).
It is not known if stiripentol is present in breast milk.
Stiripentol is used in combination with clobazam and valproic acid; refer to individual monographs for additional information.
According to the manufacturer, the decision to continue or discontinue breastfeeding during therapy should take into account the risk of infant exposure, the benefits of breastfeeding to the infant, and benefits of treatment to the mother.
Some products may contain phenylalanine; use with caution in patient with phenylketonuria.
CBC (prior to initiation and every 6 months or as clinically indicated thereafter); weight; growth rate in children.
Precise mechanism behind antiseizure effects is unknown. May enhance GABAergic inhibitory neurotransmission by weak partial agonism and/or positive allosteric modulation of gamma-aminobutyric acid (GABA)-A receptors (Fisher 2009). Also inhibits multiple cytochrome P450 isoenzymes involved in the metabolism of other antiseizure medications; concurrent use may increase their systemic exposure and efficacy.
Absorption: Well absorbed; extensive first-pass metabolism (Walker 1995). Maximum concentration obtained with powder for suspension is slightly higher than that observed with capsules (Diacomit Canadian product monograph).
Protein binding: ~99% to plasma proteins
Metabolism: Hepatic through demethylenation, primarily by CYP1A2, 2C19, 3A4, and glucuronidation (Moreland 1986)
Bioavailability: 30% (Walker 1995)
Half-life elimination: Adults: 4.5 to 13 hours (dose-dependent)
Time to peak: Median: 2 to 3 hours
Excretion: Urine (73%, primarily metabolites); feces (18% as unchanged drug) (Moreland 1986)
Pediatric: In a pharmacokinetic study of children (n=35; median age: 7.3 years) with Dravet syndrome, clearance and volume of distribution were related to body weight and elimination half-life increased from 8.5 hours (10 kg) to 23.5 hours (60 kg). Adolescents may require lower dosing than younger children (May 2012).
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