Stiripentol is a structurally unique oral antiepileptic indicated for the treatment of seizures associated with Dravet syndrome in patients 6 months and older weighing at least 7 kg who are also taking clobazam. There are no clinical data to support stiripentol monotherapy in Dravet syndrome; trials have only documented efficacy when it is combined with clobazam and/or valproate. In 2 placebo-controlled, double-blind, randomized trials (combined n = 64; age range: 3 to 17 years), 71% and 67% of stiripentol-treated patients had a more than 50% decrease in the number of seizures (generalized tonic or tonic-clonic) they experienced over a 30-day period, compared with 5% and 9% of placebo-treated patients. Treatment with stiripentol was also superior to placebo for the reduction in mean seizure frequency (-69% and -74% for stiripentol vs. +7.6% and -13% for placebo). In both trials, stiripentol or placebo was added to the patient's previous treatment with clobazam and/or valproate. Somnolence, decreased appetite, agitation, ataxia, weight loss, hypotonia, nausea, tremor, dysarthria, and insomnia are the most common adverse reactions reported with stiripentol. Perform hematologic testing prior to treatment initiation and every 6 months, due to the risk of significant neutropenia and thrombocytopenia.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
Route-Specific Administration
Oral Administration
-Administer during a meal.
-Missed doses: Administer missed doses as soon as possible. If it is almost time for the next dose, administer only that dose. Do not administer double doses.
Oral Solid Formulations
Capsules
-Administer whole with a glass of water during a meal.
-Do not break or open capsules.
Oral Liquid Formulations
Powder for Oral Suspension
-Mix powder in a glass of water (100 mL).
-Administer immediately after mixing during a meal.
-Add a small amount of water (25 mL) to the drinking cup and have the patient drink all the mixture, to be sure there is no medicine left in the glass.
Central nervous system reactions, in particular, drowsiness, are common with stiripentol use. Drowsiness was reported in 67% of stiripentol-treated patients compared to 23% of placebo-treated patients during clinical trials; both groups were on concomitant clobazam which also causes drowsiness. Consider an initial reduction of clobazam by 25% if drowsiness occurs. If drowsiness persists, consider an additional 25% reduction of clobazam and adjust other concomitant antiepileptic drugs with sedating properties. Other nervous system disorders including ataxia (27% vs. 23%), hypotonia (18% vs. 13%), tremor (15% vs. 10%), and dysarthria (12% vs. 0%) were also reported during clinical trials.
Agitation (27% vs. 16%) and insomnia (12% vs. 7%) were reported commonly in stiripentol-treated patients and more frequently than placebo during clinical trials. Aggression (9% vs. 0%) was also reported. Antiepileptic drugs (AEDs) such as stiripentol increase the risk of suicidal ideation and behavior. Monitor all patients taking stiripentol closely for emerging or worsening suicidal thoughts/behavior or depression. Inform patients and caregivers of the increased risk of suicidal thoughts and behaviors and advise them to immediately report the emergence or worsening of depression, the emergence of suicidal thoughts or behavior, thoughts of self-harm, or other unusual changes in mood or behavior. Epilepsy and many other illnesses for which AEDs are prescribed are themselves associated with an increased risk of suicidal thoughts and behavior. If suicidal thoughts and behavior emerge during treatment, consider whether the emergence of these symptoms may be related to the underlying illness. A pooled analysis of 199 placebo-controlled trials including 11 different AEDs showed that patients (5 years of age and older) receiving AEDs had approximately twice the risk of suicidal behavior or ideation (0.43%) as patients receiving placebo (0.24%), with an adjusted relative risk of 1.8 (95% CI 1.2 to 2.7). Four completed suicides occurred in patients treated with AEDs compared to none among controls. The relative risk for suicidality was higher in patients with epilepsy compared to those with other conditions. Age was not a determining factor and risk was generally consistent among all AEDs examined. Suicidal ideation or behavior have occurred as early as 1 week after AED initiation and may occur at any time during treatment.
Stiripentol can cause anorexia and subsequent weight loss. Decreased appetite occurred in 46% of stiripentol-treated patients compared to 10% of those treated with placebo during clinical trials. Decreased weight occurred in 27% of stiripentol-treated patients, compared to 6% of patients receiving placebo. Nausea (15% vs. 3%) and vomiting (9% vs. 0%) also occurred more commonly in stiripentol-treated patients. Because of the frequency of these adverse reactions, the growth of pediatric patients treated with stiripentol should be carefully monitored. Decreasing the dose of concomitant valproate by 30% per week can reduce the decrease in appetite and weight in some cases. Hypersalivation (6% vs. 0%) and weight gain (6% vs. 3%) were also reported during clinical trials.
Stiripentol can cause significant neutropenia and thrombocytopenia. Decreases in both neutrophil and platelet counts from normal at baseline to less than 1,500 cells/mm3 and less than 150,000/mcL, respectively, were observed in 13% of stiripentol-treated patients and no placebo-treated patients during clinical trials. Obtain hematologic testing prior to treatment initiation and every 6 months during treatment.
Fatigue (9% vs. 3%), fever (6% vs. 3%), and infection including bronchitis (6% vs. 0%) and naso-pharyngitis (6% vs. 0%) were reported more frequently in stiripentol-treated patients than those receiving placebo during clinical trials.
There is an increased risk of suicidal ideation and behavior in patients receiving antiepileptic drugs (AEDs). Suicidal ideation or behavior has occurred as early as 1 week after AED initiation and may occur at any time during treatment. Closely monitor patients treated with stiripentol for emerging or worsening depression or suicidal thoughts/behavior. Inform patients, caregivers, and families of the increased risk of suicidal thoughts and behaviors and advise them to immediately report the emergence or worsening of depression, the emergence of suicidal thoughts or behavior, thoughts of self-harm, or other unusual changes in mood or behavior. AEDs should be prescribed in the smallest quantity consistent with good patient management to reduce the risk of overdose. A pooled analysis of 199 placebo-controlled clinical studies with a total of 27,863 patients in drug treatment groups and 16,029 patients in placebo groups (5 years of age or older) was conducted. There were 4 completed suicides among patients in drug treatment groups versus none in the placebo groups. Patients receiving AEDs had approximately twice the risk of suicidal behavior or ideation as patients receiving placebo (0.43% vs. 0.24%, respectively; RR 1.8, 95% CI: 1.2 to 2.7). The relative risk for suicidality was higher in patients with epilepsy compared to those with other conditions; however, the absolute risk differences were similar in trials for epilepsy and psychiatric indications. Age was not a determining factor.
Stiripentol can cause significant neutropenia and thrombocytopenia. Obtain hematologic testing prior to treatment initiation and every 6 months during treatment.
Do not use stiripentol in patients with moderate to severe renal impairment or renal failure. There is no formal study of stiripentol pharmacokinetics and metabolism in patients with renal disease; however, its metabolites are eliminated primarily through the kidney.
Do not use stiripentol in patients with moderate to severe hepatic impairment. There is no formal study of stiripentol pharmacokinetics in patients with hepatic disease; however, the drug is metabolized primarily through the liver.
Stiripentol can cause dizziness and drowsiness. Advise patients to avoid engaging in hazardous activities requiring mental alertness (e.g., driving or operating machinery) until the effect of stiripentol on mental alertness is known. Other CNS depressants, including alcohol, could potentiate dizziness and drowsiness. Clobazam also causes drowsiness, and coadministration with stiripentol results in increased concentrations of clobazam and its active metabolite. Consider an initial reduction of clobazam by 25% if drowsiness occurs. If drowsiness persists, consider an additional 25% reduction of clobazam and adjust other concomitant antiepileptic drugs with sedating properties.
Avoid abrupt discontinuation of stiripentol to minimize the risk of increased seizure frequency and status epilepticus. If rapid discontinuation is required, monitor the patient appropriately.
Carefully monitor the growth of children and adolescents treated with stiripentol. Decreases in appetite and weight, nausea, and vomiting frequently occur in stiripentol-treated patients; hence, growth inhibition is of concern. In some cases, decreasing the dose of concomitant valproate by 30% per week can reduce the decrease in appetite and weight.
Use stiripentol powder for oral suspension with caution in patients with phenylketonuria; this formulation contains phenylalanine, a component of aspartame. Consider the combined daily amount of phenylalanine from all sources before prescribing stiripentol powder for oral suspension. Each 250 mg packet contains 1.4 mg of phenylalanine; each 500 mg packet contains 2.8 mg phenylalanine. Stiripentol capsules do not contain phenylalanine.
There are no adequate data on the developmental risks associated with the use of stiripentol during human pregnancy. Animal data has 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. Encourage pregnant patients to enroll in the North American Antiepileptic Drug (NAAED) Pregnancy Registry by calling 1-888-233-2334.
Stiripentol should be avoided during breast-feeding. 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 risk and benefit of breast-feeding, taking into account the clinical need for stiripentol and the possibility of adverse effects on the breast-fed infant.
General dosing information:
-There is no clinical data to support the use of stiripentol as monotherapy in Dravet syndrome.
-Obtain hematologic testing prior to treatment initiation.
-Avoid abrupt discontinuation to minimize the risk of increased seizure frequency and status epilepticus. If rapid withdrawal is medically necessary, monitor appropriately.
For the treatment of seizures associated with Dravet syndrome in patients taking clobazam:
Oral dosage:
Adults: 25 mg/kg/dose PO twice daily or 16.67 mg/kg/dose PO 3 times daily. If exact dose cannot be achieved, round to the nearest possible dosage, which is usually within 50 to 150 mg of the recommended 50 mg/kg/day. Max: 3,000 mg/day.
Children and Adolescents weighing 10 kg or more: 25 mg/kg/dose PO twice daily or 16.67 mg/kg/dose PO 3 times daily. If exact dose cannot be achieved, round to the nearest possible dosage, which is usually within 50 to 150 mg of the recommended 50 mg/kg/day. Max: 3,000 mg/day.
Children weighing 7 to 9 kg: 25 mg/kg/dose PO twice daily. If exact dose cannot be achieved, round to the nearest possible dosage, which is usually within 50 to 150 mg of the recommended 50 mg/kg/day.
Infants 6 to 11 months weighing 7 kg or more: 25 mg/kg/dose PO twice daily. If exact dose cannot be achieved, round to the nearest possible dosage, which is usually within 50 to 150 mg of the recommended 50 mg/kg/day.
Maximum Dosage Limits:
-Adults
50 mg/kg/day PO (Max: 3,000 mg/day).
-Geriatric
50 mg/kg/day PO (Max: 3,000 mg/day).
-Adolescents
50 mg/kg/day PO (Max: 3,000 mg/day).
-Children
50 mg/kg/day PO (Max: 3,000 mg/day).
-Infants
6 to 11 months weighing 7 kg or more: 50 mg/kg/day PO.
6 to 11 months weighing less than 7 kg: Safety and efficacy have not been established.
1 to 5 months: Safety and efficacy have not been established.
-Neonates
Safety and efficacy have not been established.
Patients with Hepatic Impairment Dosing
Use in moderate or severe hepatic impairment is not recommended.
Patients with Renal Impairment Dosing
Use in moderate or severe renal impairment is not recommended.
*non-FDA-approved indication
Acalabrutinib: (Moderate) Consider a dose adjustment of acalabrutinib when coadministered with stiripentol. Coadministration may alter plasma concentrations of acalabrutinib resulting in an increased risk of adverse reactions and/or decreased efficacy. Acalabrutinib is a sensitive CYP3A4 substrate. In vitro data predicts inhibition or induction of CYP3A4 by stiripentol potentially resulting in clinically significant interactions.
Acetaminophen; Aspirin, ASA; Caffeine: (Moderate) Consider a dose adjustment of caffeine when coadministered with stiripentol. Coadministration may alter plasma concentrations of caffeine resulting in an increased risk of adverse reactions and/or decreased efficacy. Caffeine is a sensitive CYP1A2 substrate. In vitro data predicts inhibition or induction of CYP1A2 by stiripentol potentially resulting in clinically significant interactions.
Acetaminophen; Aspirin; Diphenhydramine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of stiripentol and diphenhydramine. CNS depressants can potentiate the effects of stiripentol.
Acetaminophen; Caffeine: (Moderate) Consider a dose adjustment of caffeine when coadministered with stiripentol. Coadministration may alter plasma concentrations of caffeine resulting in an increased risk of adverse reactions and/or decreased efficacy. Caffeine is a sensitive CYP1A2 substrate. In vitro data predicts inhibition or induction of CYP1A2 by stiripentol potentially resulting in clinically significant interactions.
Acetaminophen; Caffeine; Dihydrocodeine: (Moderate) Concomitant use of opioid agonists with stiripentol may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking stiripentol. Limit the use of opioid pain medications with stiripentol to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression. (Moderate) Consider a dose adjustment of caffeine when coadministered with stiripentol. Coadministration may alter plasma concentrations of caffeine resulting in an increased risk of adverse reactions and/or decreased efficacy. Caffeine is a sensitive CYP1A2 substrate. In vitro data predicts inhibition or induction of CYP1A2 by stiripentol potentially resulting in clinically significant interactions.
Acetaminophen; Caffeine; Pyrilamine: (Moderate) Consider a dose adjustment of caffeine when coadministered with stiripentol. Coadministration may alter plasma concentrations of caffeine resulting in an increased risk of adverse reactions and/or decreased efficacy. Caffeine is a sensitive CYP1A2 substrate. In vitro data predicts inhibition or induction of CYP1A2 by stiripentol potentially resulting in clinically significant interactions.
Acetaminophen; Chlorpheniramine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of stiripentol and chlorpheniramine. CNS depressants can potentiate the effects of stiripentol.
Acetaminophen; Chlorpheniramine; Dextromethorphan: (Moderate) Monitor for excessive sedation and somnolence during coadministration of stiripentol and chlorpheniramine. CNS depressants can potentiate the effects of stiripentol.
Acetaminophen; Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of stiripentol and chlorpheniramine. CNS depressants can potentiate the effects of stiripentol.
Acetaminophen; Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of stiripentol and chlorpheniramine. CNS depressants can potentiate the effects of stiripentol.
Acetaminophen; Chlorpheniramine; Phenylephrine : (Moderate) Monitor for excessive sedation and somnolence during coadministration of stiripentol and chlorpheniramine. CNS depressants can potentiate the effects of stiripentol.
Acetaminophen; Codeine: (Moderate) Concomitant use of opioid agonists with stiripentol may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking stiripentol. Limit the use of opioid pain medications with stiripentol to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression. Coadministration may alter plasma concentrations of codeine resulting in an increased risk of adverse reactions and/or decreased efficacy. Codeine is a CYP3A4 substrate. In vitro data predicts inhibition or induction of CYP3A4 by stiripentol potentially resulting in clinically significant interactions.
Acetaminophen; Dextromethorphan; Doxylamine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of stiripentol and doxylamine. CNS depressants can potentiate the effects of stiripentol.
Acetaminophen; Diphenhydramine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of stiripentol and diphenhydramine. CNS depressants can potentiate the effects of stiripentol.
Acetaminophen; Hydrocodone: (Major) Concomitant use of opioid agonists with stiripentol may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking stiripentol. Limit the use of opioid pain medications with stiripentol to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression. Coadministration may alter plasma concentrations of hydrocodone resulting in an increased risk of adverse reactions and/or decreased efficacy. Hydrocodone is a CYP3A4 substrate. In vitro data predicts inhibition or induction of CYP3A4 by stiripentol potentially resulting in clinically significant interactions.
Acetaminophen; Oxycodone: (Major) Concomitant use of opioid agonists with stiripentol may cause excessive sedation and somnolence. Limit the use of opioid pain medications with stiripentol to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression. Coadministration may alter plasma concentrations of oxycodone resulting in an increased risk of adverse reactions and/or decreased efficacy. Oxycodone is a CYP3A4 substrate. In vitro data predicts inhibition or induction of CYP3A4 by stiripentol potentially resulting in clinically significant interactions.
Albuterol; Budesonide: (Moderate) Consider a dose adjustment of budesonide when coadministered with stiripentol. Coadministration may alter plasma concentrations of budesonide resulting in an increased risk of adverse reactions and/or decreased efficacy. Budesonide is a sensitive CYP3A4 substrate. In vitro data predicts inhibition or induction of CYP3A4 by stiripentol potentially resulting in clinically significant interactions.
Alfentanil: (Moderate) Concomitant use of opioid agonists with stiripentol may cause excessive sedation and somnolence. Limit the use of opioid pain medications with stiripentol to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression. Coadministration may alter plasma concentrations of alfentanil resulting in an increased risk of adverse reactions and/or decreased efficacy. Alfentanil is a sensitive substrate of CYP3A4. In vitro data predicts inhibition or induction of CYP3A4 by stiripentol potentially resulting in clinically significant interactions.
Alosetron: (Moderate) Consider a dose adjustment of alosetron when coadministered with stiripentol. Coadministration may alter plasma concentrations of alosetron resulting in an increased risk of adverse reactions and/or decreased efficacy. Alosetron is a sensitive CYP1A2 substrate. In vitro data predicts inhibition or induction of CYP1A2 by stiripentol potentially resulting in clinically significant interactions.
Alpelisib: (Major) Avoid coadministration of alpelisib with stiripentol due to increased exposure to alpelisib and the risk of alpelisib-related toxicity. If concomitant use is unavoidable, closely monitor for alpelisib-related adverse reactions. Alpelisib is a BCRP substrate and stiripentol is a BCRP inhibitor.
Alprazolam: (Major) Avoid coadministration of alprazolam and stiripentol due to the potential for elevated alprazolam concentrations, which may cause prolonged sedation and respiratory depression. If coadministration is necessary, consider reducing the dose of alprazolam as clinically appropriate and monitor for an increase in alprazolam-related adverse reactions. Alprazolam is a CYP3A4 substrate and data show that stiripentol is both an inhibitor and inducer of CYP3A4. Coadministration with weak CYP3A4 inhibitors increased alprazolam maximum concentration by 82%, decreased clearance by 42%, and increased half-life by 16%.
Amitriptyline: (Moderate) Monitor for excessive sedation and somnolence during coadministration of stiripentol and tricyclic antidepressants. CNS depressants can potentiate the effects of stiripentol.
Amobarbital: (Moderate) Monitor for excessive sedation and somnolence during coadministration of stiripentol and amobarbital. CNS depressants can potentiate the effects of stiripentol.
Amoxapine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of stiripentol and amoxapine. CNS depressants can potentiate the effects of stiripentol.
Amoxicillin; Clarithromycin; Omeprazole: (Moderate) Consider a dose reduction of omeprazole when coadministered with stiripentol. Coadministration may increase plasma concentrations of omeprazole resulting in an increased risk of adverse reactions. Omeprazole is a sensitive CYP2C19 substrate. In vitro data predicts inhibition of CYP2C19 by stiripentol potentially resulting in clinically significant interactions.
Apalutamide: (Major) Avoid coadministration of stiripentol with apalutamide. If concurrent use is necessary, increase the dose of stiripentol. Coadministration may decrease stiripentol plasma concentrations resulting in a decrease in efficacy. Stiripentol is metabolized by CYP3A4 and CYP2C19; apalutamide is a strong inducer of CYP3A4 and CYP2C19.
Apomorphine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of stiripentol and apomorphine. CNS depressants can potentiate the effects of stiripentol.
Aprepitant, Fosaprepitant: (Moderate) Consider a dose adjustment of aprepitant when coadministered with stiripentol. Coadministration may alter plasma concentrations of aprepitant resulting in an increased risk of adverse reactions and/or decreased efficacy. Aprepitant is a sensitive CYP3A4 substrate. In vitro data predicts inhibition or induction of CYP3A4 by stiripentol potentially resulting in clinically significant interactions.
Aripiprazole: (Moderate) Monitor for excessive sedation and somnolence during coadministration of stiripentol and aripiprazole. CNS depressants can potentiate the effects of stiripentol.
Asenapine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of stiripentol and asenapine. CNS depressants can potentiate the effects of stiripentol.
Aspirin, ASA; Butalbital; Caffeine: (Moderate) Consider a dose adjustment of caffeine when coadministered with stiripentol. Coadministration may alter plasma concentrations of caffeine resulting in an increased risk of adverse reactions and/or decreased efficacy. Caffeine is a sensitive CYP1A2 substrate. In vitro data predicts inhibition or induction of CYP1A2 by stiripentol potentially resulting in clinically significant interactions. (Moderate) Monitor for excessive sedation and somnolence during coadministration of stiripentol and butalbital. CNS depressants can potentiate the effects of stiripentol.
Aspirin, ASA; Caffeine: (Moderate) Consider a dose adjustment of caffeine when coadministered with stiripentol. Coadministration may alter plasma concentrations of caffeine resulting in an increased risk of adverse reactions and/or decreased efficacy. Caffeine is a sensitive CYP1A2 substrate. In vitro data predicts inhibition or induction of CYP1A2 by stiripentol potentially resulting in clinically significant interactions.
Aspirin, ASA; Caffeine; Orphenadrine: (Moderate) Consider a dose adjustment of caffeine when coadministered with stiripentol. Coadministration may alter plasma concentrations of caffeine resulting in an increased risk of adverse reactions and/or decreased efficacy. Caffeine is a sensitive CYP1A2 substrate. In vitro data predicts inhibition or induction of CYP1A2 by stiripentol potentially resulting in clinically significant interactions. (Moderate) Monitor for excessive sedation and somnolence during coadministration of stiripentol and orphenadrine. CNS depressants can potentiate the effects of stiripentol.
Aspirin, ASA; Carisoprodol; Codeine: (Moderate) Concomitant use of opioid agonists with stiripentol may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking stiripentol. Limit the use of opioid pain medications with stiripentol to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression. Coadministration may alter plasma concentrations of codeine resulting in an increased risk of adverse reactions and/or decreased efficacy. Codeine is a CYP3A4 substrate. In vitro data predicts inhibition or induction of CYP3A4 by stiripentol potentially resulting in clinically significant interactions. (Moderate) Monitor for excessive sedation and somnolence during coadministration of stiripentol and carisoprodol. CNS depressants can potentiate the effects of stiripentol.
Aspirin, ASA; Omeprazole: (Moderate) Consider a dose reduction of omeprazole when coadministered with stiripentol. Coadministration may increase plasma concentrations of omeprazole resulting in an increased risk of adverse reactions. Omeprazole is a sensitive CYP2C19 substrate. In vitro data predicts inhibition of CYP2C19 by stiripentol potentially resulting in clinically significant interactions.
Aspirin, ASA; Oxycodone: (Major) Concomitant use of opioid agonists with stiripentol may cause excessive sedation and somnolence. Limit the use of opioid pain medications with stiripentol to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression. Coadministration may alter plasma concentrations of oxycodone resulting in an increased risk of adverse reactions and/or decreased efficacy. Oxycodone is a CYP3A4 substrate. In vitro data predicts inhibition or induction of CYP3A4 by stiripentol potentially resulting in clinically significant interactions.
Atogepant: (Major) Avoid use of atogepant and stiripentol when atogepant is used for chronic migraine. Use an atogepant dose of 30 or 60 mg PO once daily for episodic migraine if coadministered with stiripentol. Concurrent use may decrease atogepant exposure and reduce efficacy. Atogepant is a CYP3A substrate and stiripentol is a weak CYP3A inducer. Coadministration with a weak CYP3A inducer resulted in a 25% reduction in atogepant overall exposure and a 24% reduction in atogepant peak concentration.
Atracurium: (Moderate) Monitor for excessive sedation and somnolence during coadministration of stiripentol and atracurium. CNS depressants can potentiate the effects of stiripentol.
Atropine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of stiripentol and atropine. CNS depressants can potentiate the effects of stiripentol.
Atropine; Difenoxin: (Moderate) Monitor for excessive sedation and somnolence during coadministration of stiripentol and atropine. CNS depressants can potentiate the effects of stiripentol.
Avanafil: (Moderate) Consider a dose adjustment of avanafil when coadministered with stiripentol. Coadministration may alter plasma concentrations of avanafil resulting in an increased risk of adverse reactions and/or decreased efficacy. Avanafil is a sensitive CYP3A4 substrate. In vitro data predicts inhibition or induction of CYP3A4 by stiripentol potentially resulting in clinically significant interactions.
Azelastine: (Major) Avoid concomitant use of stiripentol with azelastine nasal solution. Concomitant use may cause somnolence, reductions in mental alertness, or additional CNS impairment. Educate patients about the signs and symptoms of CNS depression.
Azelastine; Fluticasone: (Major) Avoid concomitant use of stiripentol with azelastine nasal solution. Concomitant use may cause somnolence, reductions in mental alertness, or additional CNS impairment. Educate patients about the signs and symptoms of CNS depression.
Baclofen: (Moderate) Monitor for excessive sedation and somnolence during coadministration of stiripentol and baclofen. CNS depressants can potentiate the effects of stiripentol.
Belladonna; Opium: (Moderate) Concomitant use of opioid agonists with stiripentol may cause excessive sedation and somnolence. Limit the use of opioid pain medications with stiripentol to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression. (Moderate) Monitor for excessive sedation and somnolence during coadministration of stiripentol and belladona. CNS depressants can potentiate the effects of stiripentol.
Belzutifan: (Moderate) Monitor for anemia and hypoxia if concomitant use of stiripentol with belzutifan is necessary due to increased plasma exposure of belzutifan which may increase the incidence and severity of adverse reactions. Reduce the dose of belzutifan as recommended if anemia or hypoxia occur. Belzutifan is a CYP2C19 substrate and stiripentol is a CYP2C19 inhibitor.
Bendamustine: (Major) Consider the use of an alternative therapy if stiripentol treatment is needed in patients receiving bendamustine. Stiripentol may alter bendamustine exposure. Bendamustine is a CYP1A2 substrate and stiripentol is an inhibitor and inducer of CYP1A2 in vitro.
Benzhydrocodone; Acetaminophen: (Major) Concomitant use of opioid agonists with stiripentol may cause excessive sedation and somnolence. Limit the use of opioid pain medications with stiripentol to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression. Coadministration may alter plasma concentrations of hydrocodone resulting in an increased risk of adverse reactions and/or decreased efficacy. Benzhydrocodone is a prodrug of hydrocodone. Hydrocodone is a CYP3A4 substrate. In vitro data predicts inhibition or induction of CYP3A4 by stiripentol potentially resulting in clinically significant interactions.
Betrixaban: (Major) Avoid betrixaban use in patients with severe renal impairment receiving stiripentol. Reduce betrixaban dosage to 80 mg PO once followed by 40 mg PO once daily in all other patients receiving stiripentol. Bleeding risk may be increased; monitor patients closely for signs and symptoms of bleeding. Betrixaban is a substrate of P-gp; stiripentol inhibits P-gp.
Brexpiprazole: (Moderate) Monitor for excessive sedation and somnolence during coadministration of stiripentol and brexpiprazole. CNS depressants can potentiate the effects of stiripentol.
Brompheniramine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of stiripentol and brompheniramine. CNS depressants can potentiate the effects of stiripentol.
Brompheniramine; Dextromethorphan; Phenylephrine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of stiripentol and brompheniramine. CNS depressants can potentiate the effects of stiripentol.
Brompheniramine; Phenylephrine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of stiripentol and brompheniramine. CNS depressants can potentiate the effects of stiripentol.
Brompheniramine; Pseudoephedrine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of stiripentol and brompheniramine. CNS depressants can potentiate the effects of stiripentol.
Brompheniramine; Pseudoephedrine; Dextromethorphan: (Moderate) Monitor for excessive sedation and somnolence during coadministration of stiripentol and brompheniramine. CNS depressants can potentiate the effects of stiripentol.
Budesonide: (Moderate) Consider a dose adjustment of budesonide when coadministered with stiripentol. Coadministration may alter plasma concentrations of budesonide resulting in an increased risk of adverse reactions and/or decreased efficacy. Budesonide is a sensitive CYP3A4 substrate. In vitro data predicts inhibition or induction of CYP3A4 by stiripentol potentially resulting in clinically significant interactions.
Budesonide; Formoterol: (Moderate) Consider a dose adjustment of budesonide when coadministered with stiripentol. Coadministration may alter plasma concentrations of budesonide resulting in an increased risk of adverse reactions and/or decreased efficacy. Budesonide is a sensitive CYP3A4 substrate. In vitro data predicts inhibition or induction of CYP3A4 by stiripentol potentially resulting in clinically significant interactions.
Budesonide; Glycopyrrolate; Formoterol: (Moderate) Consider a dose adjustment of budesonide when coadministered with stiripentol. Coadministration may alter plasma concentrations of budesonide resulting in an increased risk of adverse reactions and/or decreased efficacy. Budesonide is a sensitive CYP3A4 substrate. In vitro data predicts inhibition or induction of CYP3A4 by stiripentol potentially resulting in clinically significant interactions.
Buprenorphine: (Major) Concomitant use of buprenorphine with stiripentol may cause excessive sedation and somnolence. Limit the use of buprenorphine with stiripentol to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. If buprenorphine is initiated in a patient taking stiripentol, reduce initial dosage and titrate to clinical response. If stiripentol is initiated a patient taking buprenorphine, use a lower initial dose of stiripentol and titrate to clinical response. Educate patients about the risks and symptoms of excessive CNS depression. Consider a dose adjustment of buprenorphine when coadministered with stiripentol. Coadministration may alter plasma concentrations of buprenorphine resulting in an increased risk of adverse reactions and/or decreased efficacy. Buprenorphine is a substrate of CYP3A4. In vitro data predicts inhibition or induction of CYP3A4 by stiripentol potentially resulting in clinically significant interactions.
Buprenorphine; Naloxone: (Major) Concomitant use of buprenorphine with stiripentol may cause excessive sedation and somnolence. Limit the use of buprenorphine with stiripentol to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. If buprenorphine is initiated in a patient taking stiripentol, reduce initial dosage and titrate to clinical response. If stiripentol is initiated a patient taking buprenorphine, use a lower initial dose of stiripentol and titrate to clinical response. Educate patients about the risks and symptoms of excessive CNS depression. Consider a dose adjustment of buprenorphine when coadministered with stiripentol. Coadministration may alter plasma concentrations of buprenorphine resulting in an increased risk of adverse reactions and/or decreased efficacy. Buprenorphine is a substrate of CYP3A4. In vitro data predicts inhibition or induction of CYP3A4 by stiripentol potentially resulting in clinically significant interactions.
Bupropion: (Moderate) Consider a dose adjustment of bupropion when coadministered with stiripentol. Coadministration may alter plasma concentrations of bupropion resulting in an increased risk of adverse reactions and/or decreased efficacy. Bupropion is a sensitive CYP2B6 substrate. In vitro data predicts inhibition or induction of CYP2B6 by stiripentol potentially resulting in clinically significant interactions.
Bupropion; Naltrexone: (Moderate) Consider a dose adjustment of bupropion when coadministered with stiripentol. Coadministration may alter plasma concentrations of bupropion resulting in an increased risk of adverse reactions and/or decreased efficacy. Bupropion is a sensitive CYP2B6 substrate. In vitro data predicts inhibition or induction of CYP2B6 by stiripentol potentially resulting in clinically significant interactions.
Buspirone: (Moderate) Consider a dose adjustment of buspirone when coadministered with stiripentol. Coadministration may alter plasma concentrations of buspirone resulting in an increased risk of adverse reactions and/or decreased efficacy. Buspirone is a sensitive CYP3A4 substrate. In vitro data predicts inhibition or induction of CYP3A4 by stiripentol potentially resulting in clinically significant interactions.
Butalbital; Acetaminophen: (Moderate) Monitor for excessive sedation and somnolence during coadministration of stiripentol and butalbital. CNS depressants can potentiate the effects of stiripentol.
Butalbital; Acetaminophen; Caffeine: (Moderate) Consider a dose adjustment of caffeine when coadministered with stiripentol. Coadministration may alter plasma concentrations of caffeine resulting in an increased risk of adverse reactions and/or decreased efficacy. Caffeine is a sensitive CYP1A2 substrate. In vitro data predicts inhibition or induction of CYP1A2 by stiripentol potentially resulting in clinically significant interactions. (Moderate) Monitor for excessive sedation and somnolence during coadministration of stiripentol and butalbital. CNS depressants can potentiate the effects of stiripentol.
Butalbital; Acetaminophen; Caffeine; Codeine: (Moderate) Concomitant use of opioid agonists with stiripentol may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking stiripentol. Limit the use of opioid pain medications with stiripentol to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression. Coadministration may alter plasma concentrations of codeine resulting in an increased risk of adverse reactions and/or decreased efficacy. Codeine is a CYP3A4 substrate. In vitro data predicts inhibition or induction of CYP3A4 by stiripentol potentially resulting in clinically significant interactions. (Moderate) Consider a dose adjustment of caffeine when coadministered with stiripentol. Coadministration may alter plasma concentrations of caffeine resulting in an increased risk of adverse reactions and/or decreased efficacy. Caffeine is a sensitive CYP1A2 substrate. In vitro data predicts inhibition or induction of CYP1A2 by stiripentol potentially resulting in clinically significant interactions. (Moderate) Monitor for excessive sedation and somnolence during coadministration of stiripentol and butalbital. CNS depressants can potentiate the effects of stiripentol.
Butalbital; Aspirin; Caffeine; Codeine: (Moderate) Concomitant use of opioid agonists with stiripentol may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking stiripentol. Limit the use of opioid pain medications with stiripentol to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression. Coadministration may alter plasma concentrations of codeine resulting in an increased risk of adverse reactions and/or decreased efficacy. Codeine is a CYP3A4 substrate. In vitro data predicts inhibition or induction of CYP3A4 by stiripentol potentially resulting in clinically significant interactions. (Moderate) Consider a dose adjustment of caffeine when coadministered with stiripentol. Coadministration may alter plasma concentrations of caffeine resulting in an increased risk of adverse reactions and/or decreased efficacy. Caffeine is a sensitive CYP1A2 substrate. In vitro data predicts inhibition or induction of CYP1A2 by stiripentol potentially resulting in clinically significant interactions. (Moderate) Monitor for excessive sedation and somnolence during coadministration of stiripentol and butalbital. CNS depressants can potentiate the effects of stiripentol.
Butorphanol: (Major) Concomitant use of mixed opioid agonists/antagonists like butorphanol with stiripentol may cause excessive sedation and somnolence. Limit the use of butorphanol with stiripentol to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. If butorphanol is initiated in a patient taking stiripentol, reduce initial dosage and titrate to clinical response. If stiripentol is initiated a patient taking butorphanol, use a lower initial dose of stiripentol and titrate to clinical response. Educate patients about the risks and symptoms of excessive CNS depression.
Caffeine: (Moderate) Consider a dose adjustment of caffeine when coadministered with stiripentol. Coadministration may alter plasma concentrations of caffeine resulting in an increased risk of adverse reactions and/or decreased efficacy. Caffeine is a sensitive CYP1A2 substrate. In vitro data predicts inhibition or induction of CYP1A2 by stiripentol potentially resulting in clinically significant interactions.
Caffeine; Sodium Benzoate: (Moderate) Consider a dose adjustment of caffeine when coadministered with stiripentol. Coadministration may alter plasma concentrations of caffeine resulting in an increased risk of adverse reactions and/or decreased efficacy. Caffeine is a sensitive CYP1A2 substrate. In vitro data predicts inhibition or induction of CYP1A2 by stiripentol potentially resulting in clinically significant interactions.
Calcium, Magnesium, Potassium, Sodium Oxybates: (Moderate) Monitor for excessive sedation and somnolence during coadministration of stiripentol and sodium oxybate. CNS depressants can potentiate the effects of stiripentol.
Cannabidiol: (Moderate) Monitor for stiripentol-related adverse reactions during coadministration with cannabidiol. Concomitant use causes an increase in stiripentol exposure. Coadministration increased stiripentol Cmax and AUC by 28% and 55%, respectively, in healthy volunteers and 17% and 30%, respectively, in patients with epilepsy. Also monitor for excessive sedation and somnolence during coadministration of cannabidiol and stiripentol; additive CNS depression may occur.
Capsaicin; Metaxalone: (Moderate) Monitor for excessive sedation and somnolence during coadministration of stiripentol and metaxalone. CNS depressants can potentiate the effects of stiripentol.
Carbamazepine: (Major) Avoid coadministration of stiripentol with carbamazepine. If concurrent use is necessary, increase the dose of stiripentol; consider a dose adjustment of carbamazepine. Coadministration may decrease stiripentol plasma concentrations resulting in a decrease in efficacy; carbamazepine exposure may be altered resulting in an increased risk of adverse reactions and/or decreased efficacy. Stiripentol is metabolized by CYP3A4, CYP1A2, and CYP2C19; carbamazepine is a strong inducer of CYP3A4, and an inducer of CYP1A2 and CYP2C19. Carbamazepine is a CYP1A2, CYP3A4, CYP2C8, and P-gp substrate. In vitro data predicts inhibition or induction of CYP1A2, CYP3A4, and CYP2C8 and inhibition of P-gp by stiripentol potentially resulting in clinically significant interactions.
Carbidopa; Levodopa; Entacapone: (Moderate) Monitor for excessive sedation and somnolence during coadministration of stiripentol and entacapone. CNS depressants can potentiate the effects of stiripentol.
Cariprazine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of stiripentol and cariprazine. CNS depressants can potentiate the effects of stiripentol.
Carisoprodol: (Moderate) Monitor for excessive sedation and somnolence during coadministration of stiripentol and carisoprodol. CNS depressants can potentiate the effects of stiripentol.
Celecoxib; Tramadol: (Moderate) Concomitant use of opioid agonists with stiripentol may cause excessive sedation and somnolence. Limit the use of opioid pain medications with stiripentol to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression. Coadministration may alter plasma concentrations of tramadol resulting in an increased risk of adverse reactions and/or decreased efficacy. Tramadol is a CYP3A4 substrate. In vitro data predicts inhibition or induction of CYP3A4 by stiripentol potentially resulting in clinically significant interactions.
Cenobamate: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cenobamate and stiripentol. Concurrent use may result in additive CNS depression.
Cetirizine: (Moderate) Concurrent use of cetirizine/levocetirizine with stiripentol should generally be avoided. Coadministration may increase the risk of CNS depressant-related side effects. If concurrent use is necessary, monitor for excessive sedation and somnolence.
Cetirizine; Pseudoephedrine: (Moderate) Concurrent use of cetirizine/levocetirizine with stiripentol should generally be avoided. Coadministration may increase the risk of CNS depressant-related side effects. If concurrent use is necessary, monitor for excessive sedation and somnolence.
Chlordiazepoxide: (Moderate) Monitor for excessive sedation and somnolence during coadministration of stiripentol and chlordiazepoxide. CNS depressants can potentiate the effects of stiripentol.
Chlordiazepoxide; Amitriptyline: (Moderate) Monitor for excessive sedation and somnolence during coadministration of stiripentol and chlordiazepoxide. CNS depressants can potentiate the effects of stiripentol. (Moderate) Monitor for excessive sedation and somnolence during coadministration of stiripentol and tricyclic antidepressants. CNS depressants can potentiate the effects of stiripentol.
Chlordiazepoxide; Clidinium: (Moderate) Monitor for excessive sedation and somnolence during coadministration of stiripentol and chlordiazepoxide. CNS depressants can potentiate the effects of stiripentol.
Chlorpheniramine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of stiripentol and chlorpheniramine. CNS depressants can potentiate the effects of stiripentol.
Chlorpheniramine; Codeine: (Moderate) Concomitant use of opioid agonists with stiripentol may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking stiripentol. Limit the use of opioid pain medications with stiripentol to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression. Coadministration may alter plasma concentrations of codeine resulting in an increased risk of adverse reactions and/or decreased efficacy. Codeine is a CYP3A4 substrate. In vitro data predicts inhibition or induction of CYP3A4 by stiripentol potentially resulting in clinically significant interactions. (Moderate) Monitor for excessive sedation and somnolence during coadministration of stiripentol and chlorpheniramine. CNS depressants can potentiate the effects of stiripentol.
Chlorpheniramine; Dextromethorphan: (Moderate) Monitor for excessive sedation and somnolence during coadministration of stiripentol and chlorpheniramine. CNS depressants can potentiate the effects of stiripentol.
Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of stiripentol and chlorpheniramine. CNS depressants can potentiate the effects of stiripentol.
Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of stiripentol and chlorpheniramine. CNS depressants can potentiate the effects of stiripentol.
Chlorpheniramine; Hydrocodone: (Major) Concomitant use of opioid agonists with stiripentol may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking stiripentol. Limit the use of opioid pain medications with stiripentol to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression. Coadministration may alter plasma concentrations of hydrocodone resulting in an increased risk of adverse reactions and/or decreased efficacy. Hydrocodone is a CYP3A4 substrate. In vitro data predicts inhibition or induction of CYP3A4 by stiripentol potentially resulting in clinically significant interactions. (Moderate) Monitor for excessive sedation and somnolence during coadministration of stiripentol and chlorpheniramine. CNS depressants can potentiate the effects of stiripentol.
Chlorpheniramine; Ibuprofen; Pseudoephedrine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of stiripentol and chlorpheniramine. CNS depressants can potentiate the effects of stiripentol.
Chlorpheniramine; Phenylephrine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of stiripentol and chlorpheniramine. CNS depressants can potentiate the effects of stiripentol.
Chlorpheniramine; Pseudoephedrine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of stiripentol and chlorpheniramine. CNS depressants can potentiate the effects of stiripentol.
Chlorpromazine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of stiripentol and chlorpromazine. CNS depressants can potentiate the effects of stiripentol.
Chlorzoxazone: (Moderate) Monitor for excessive sedation and somnolence during coadministration of stiripentol and chlorzoxazone. CNS depressants can potentiate the effects of stiripentol.
Cisapride: (Moderate) Consider a dose adjustment of cisapride when coadministered with stiripentol. Coadministration may alter plasma concentrations of cisapride resulting in an increased risk of adverse reactions and/or decreased efficacy. Cisapride is a CYP3A4 substrate. In vitro data predicts inhibition or induction of CYP3A4 by stiripentol potentially resulting in clinically significant interactions.
Cisatracurium: (Moderate) Monitor for excessive sedation and somnolence during coadministration of stiripentol and cisatracurium. CNS depressants can potentiate the effects of stiripentol.
Citalopram: (Moderate) Consider a dose reduction of citalopram when coadministered with stiripentol. Coadministration may increase plasma concentrations of citalopram resulting in an increased risk of adverse reactions. Citalopram is a substrate of CYP2C19; stiripentol may inhibit CYP2C19 at clinically relevant concentrations.
Clemastine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of stiripentol and clemastine. CNS depressants can potentiate the effects of stiripentol.
Clomipramine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of stiripentol and tricyclic antidepressants. CNS depressants can potentiate the effects of stiripentol.
Clonazepam: (Moderate) Monitor for excessive sedation and somnolence during coadministration of stiripentol and clonazepam. CNS depressants can potentiate the effects of stiripentol.
Clonidine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of stiripentol and clonidine. CNS depressants can potentiate the effects of stiripentol.
Clopidogrel: (Moderate) Consider a dose adjustment of clopidogrel when coadministered with stiripentol. Coadministration may result in reduced plasma concentrations of the active metabolite of clopidogrel and a reduction in platelet inhibition. Clopidogrel is metabolized to its active metabolite mainly by CYP2C19. In vitro data suggest stiripentol inhibits CYP2C19.
Clorazepate: (Moderate) Monitor for excessive sedation and somnolence during coadministration of stiripentol and clorazepate. CNS depressants can potentiate the effects of stiripentol.
Clozapine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of stiripentol and clozapine. CNS depressants can potentiate the effects of stiripentol.
Cobimetinib: (Moderate) Consider a dose adjustment of cobimetinib when coadministered with stiripentol. Coadministration may alter plasma concentrations of cobimetinib resulting in an increased risk of adverse reactions and/or decreased efficacy. Cobimetinib is a sensitive CYP3A4 substrate. In vitro data predicts inhibition or induction of CYP3A4 by stiripentol potentially resulting in clinically significant interactions.
Codeine: (Moderate) Concomitant use of opioid agonists with stiripentol may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking stiripentol. Limit the use of opioid pain medications with stiripentol to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression. Coadministration may alter plasma concentrations of codeine resulting in an increased risk of adverse reactions and/or decreased efficacy. Codeine is a CYP3A4 substrate. In vitro data predicts inhibition or induction of CYP3A4 by stiripentol potentially resulting in clinically significant interactions.
Codeine; Guaifenesin: (Moderate) Concomitant use of opioid agonists with stiripentol may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking stiripentol. Limit the use of opioid pain medications with stiripentol to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression. Coadministration may alter plasma concentrations of codeine resulting in an increased risk of adverse reactions and/or decreased efficacy. Codeine is a CYP3A4 substrate. In vitro data predicts inhibition or induction of CYP3A4 by stiripentol potentially resulting in clinically significant interactions.
Codeine; Guaifenesin; Pseudoephedrine: (Moderate) Concomitant use of opioid agonists with stiripentol may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking stiripentol. Limit the use of opioid pain medications with stiripentol to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression. Coadministration may alter plasma concentrations of codeine resulting in an increased risk of adverse reactions and/or decreased efficacy. Codeine is a CYP3A4 substrate. In vitro data predicts inhibition or induction of CYP3A4 by stiripentol potentially resulting in clinically significant interactions.
Codeine; Phenylephrine; Promethazine: (Moderate) Concomitant use of opioid agonists with stiripentol may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking stiripentol. Limit the use of opioid pain medications with stiripentol to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression. Coadministration may alter plasma concentrations of codeine resulting in an increased risk of adverse reactions and/or decreased efficacy. Codeine is a CYP3A4 substrate. In vitro data predicts inhibition or induction of CYP3A4 by stiripentol potentially resulting in clinically significant interactions. (Moderate) Monitor for excessive sedation and somnolence during coadministration of stiripentol and promethazine. CNS depressants can potentiate the effects of stiripentol.
Codeine; Promethazine: (Moderate) Concomitant use of opioid agonists with stiripentol may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking stiripentol. Limit the use of opioid pain medications with stiripentol to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression. Coadministration may alter plasma concentrations of codeine resulting in an increased risk of adverse reactions and/or decreased efficacy. Codeine is a CYP3A4 substrate. In vitro data predicts inhibition or induction of CYP3A4 by stiripentol potentially resulting in clinically significant interactions. (Moderate) Monitor for excessive sedation and somnolence during coadministration of stiripentol and promethazine. CNS depressants can potentiate the effects of stiripentol.
Colchicine: (Major) Avoid concomitant use of colchicine and stiripentol due to the risk for increased colchicine exposure which may increase the risk for adverse effects. Concomitant use is contraindicated in patients with renal or hepatic impairment. Additionally, this combination is contraindicated if colchicine is being used for cardiovascular risk reduction. If concomitant use is necessary outside of these scenarios, consider a colchicine dosage reduction. Specific dosage reduction recommendations are available for colchicine tablets for some indications; it is unclear if these dosage recommendations are appropriate for other products or indications. For colchicine tablets being used for gout prophylaxis, reduce the dose from 0.6 mg twice daily to 0.3 mg once daily or from 0.6 mg once daily to 0.3 mg once every other day. For colchicine tablets being used for gout treatment, reduce the dose from 1.2 mg followed by 0.6 mg to 0.6 mg without an additional dose. For colchicine tablets being used for Familial Mediterranean Fever, the maximum daily dose is 0.6 mg. Colchicine is a P-gp substrate and stiripentol is a P-gp inhibitor.
Conivaptan: (Moderate) Consider a dose adjustment of conivaptan when coadministered with stiripentol. Coadministration may alter plasma concentrations of conivaptan resulting in an increased risk of adverse reactions and/or decreased efficacy. Conivaptan is a sensitive CYP3A4 substrate. In vitro data predicts inhibition or induction of CYP3A4 by stiripentol potentially resulting in clinically significant interactions.
Cyclobenzaprine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of stiripentol and cyclobenzaprine. CNS depressants can potentiate the effects of stiripentol.
Cyclosporine: (Moderate) Consider a dose adjustment of cyclosporine when coadministered with stiripentol. Coadministration may alter plasma concentrations of cyclosporine resulting in an increased risk of adverse reactions and/or decreased efficacy. Cyclosporine is a CYP3A4 substrate. In vitro data predicts inhibition or induction of CYP3A4 by stiripentol potentially resulting in clinically significant interactions.
Cyproheptadine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of stiripentol and cyproheptadine. CNS depressants can potentiate the effects of stiripentol.
Dantrolene: (Moderate) Monitor for excessive sedation and somnolence during coadministration of stiripentol and dantrolene. CNS depressants can potentiate the effects of stiripentol.
Darifenacin: (Moderate) Consider a dose adjustment of darifenacin when coadministered with stiripentol. Coadministration may alter plasma concentrations of darifenacin resulting in an increased risk of adverse reactions and/or decreased efficacy. Darifenacin is a sensitive CYP3A4 substrate. In vitro data predicts inhibition or induction of CYP3A4 by stiripentol potentially resulting in clinically significant interactions.
Darunavir: (Moderate) Consider a dose adjustment of darunavir when coadministered with stiripentol. Coadministration may alter plasma concentrations of darunavir resulting in an increased risk of adverse reactions and/or decreased efficacy. Darunavir is a sensitive CYP3A4 substrate. In vitro data predicts inhibition or induction of CYP3A4 by stiripentol potentially resulting in clinically significant interactions.
Darunavir; Cobicistat: (Moderate) Consider a dose adjustment of darunavir when coadministered with stiripentol. Coadministration may alter plasma concentrations of darunavir resulting in an increased risk of adverse reactions and/or decreased efficacy. Darunavir is a sensitive CYP3A4 substrate. In vitro data predicts inhibition or induction of CYP3A4 by stiripentol potentially resulting in clinically significant interactions.
Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Moderate) Consider a dose adjustment of darunavir when coadministered with stiripentol. Coadministration may alter plasma concentrations of darunavir resulting in an increased risk of adverse reactions and/or decreased efficacy. Darunavir is a sensitive CYP3A4 substrate. In vitro data predicts inhibition or induction of CYP3A4 by stiripentol potentially resulting in clinically significant interactions.
Dasatinib: (Moderate) Consider a dose adjustment of dasatinib when coadministered with stiripentol. Coadministration may alter plasma concentrations of dasatinib resulting in an increased risk of adverse reactions and/or decreased efficacy. Dasatinib is a sensitive CYP3A4 substrate. In vitro data predicts inhibition or induction of CYP3A4 by stiripentol potentially resulting in clinically significant interactions.
Desflurane: (Moderate) Monitor for excessive sedation and somnolence during coadministration of stiripentol and desflurane. CNS depressants can potentiate the effects of stiripentol.
Desipramine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of stiripentol and tricyclic antidepressants. CNS depressants can potentiate the effects of stiripentol.
Deutetrabenazine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of stiripentol and deutetrabenazine. CNS depressants can potentiate the effects of stiripentol.
Dexmedetomidine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of stiripentol and dexmedetomidine. CNS depressants can potentiate the effects of stiripentol.
Dextromethorphan; Bupropion: (Moderate) Consider a dose adjustment of bupropion when coadministered with stiripentol. Coadministration may alter plasma concentrations of bupropion resulting in an increased risk of adverse reactions and/or decreased efficacy. Bupropion is a sensitive CYP2B6 substrate. In vitro data predicts inhibition or induction of CYP2B6 by stiripentol potentially resulting in clinically significant interactions.
Dextromethorphan; Diphenhydramine; Phenylephrine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of stiripentol and diphenhydramine. CNS depressants can potentiate the effects of stiripentol.
Dextromethorphan; Quinidine: (Moderate) Consider a dose adjustment of quinidine when coadministered with stiripentol. Coadministration may alter plasma concentrations of quinidine resulting in an increased risk of adverse reactions and/or decreased efficacy. Quinidine is a CYP3A4 substrate. In vitro data predicts inhibition or induction of CYP3A4 by stiripentol potentially resulting in clinically significant interactions.
Diazepam: (Moderate) Monitor for excessive sedation and somnolence during coadministration of stiripentol and diazepam. CNS depressants can potentiate the effects of stiripentol. Consider a dose adjustment of diazepam when coadministered with stiripentol. Coadministration may alter plasma concentrations of diazepam resulting in an increased risk of adverse reactions and/or decreased efficacy. Diazepam is a substrate of CYP3A4, CYP2B6, and CYP2C19. In vitro data predicts inhibition or induction of CYP3A4 and CYP2B6 and inhibition of CYP2C19 by stiripentol potentially resulting in clinically significant interactions.
Difelikefalin: (Moderate) Monitor for dizziness, somnolence, mental status changes, and gait disturbances if concomitant use of difelikefalin with CNS depressants is necessary. Concomitant use may increase the risk for these adverse reactions.
Dimenhydrinate: (Moderate) Monitor for excessive sedation and somnolence during coadministration of stiripentol and dimenhydrinate. CNS depressants can potentiate the effects of stiripentol.
Diphenhydramine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of stiripentol and diphenhydramine. CNS depressants can potentiate the effects of stiripentol.
Diphenhydramine; Ibuprofen: (Moderate) Monitor for excessive sedation and somnolence during coadministration of stiripentol and diphenhydramine. CNS depressants can potentiate the effects of stiripentol.
Diphenhydramine; Naproxen: (Moderate) Monitor for excessive sedation and somnolence during coadministration of stiripentol and diphenhydramine. CNS depressants can potentiate the effects of stiripentol.
Diphenhydramine; Phenylephrine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of stiripentol and diphenhydramine. CNS depressants can potentiate the effects of stiripentol.
Diphenoxylate; Atropine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of stiripentol and atropine. CNS depressants can potentiate the effects of stiripentol.
Dofetilide: (Moderate) Consider a dose adjustment of dofetilide when coadministered with stiripentol. Coadministration may alter plasma concentrations of dofetilide resulting in an increased risk of adverse reactions and/or decreased efficacy. Dofetilide is a CYP3A4 substrate. In vitro data predicts inhibition or induction of CYP3A4 by stiripentol potentially resulting in clinically significant interactions.
Doxepin: (Moderate) Monitor for excessive sedation and somnolence during coadministration of stiripentol and tricyclic antidepressants. CNS depressants can potentiate the effects of stiripentol.
Doxylamine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of stiripentol and doxylamine. CNS depressants can potentiate the effects of stiripentol.
Doxylamine; Pyridoxine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of stiripentol and doxylamine. CNS depressants can potentiate the effects of stiripentol.
Dronedarone: (Moderate) Consider a dose adjustment of dronedarone when coadministered with stiripentol. Coadministration may alter plasma concentrations of dronedarone resulting in an increased risk of adverse reactions and/or decreased efficacy. Dronedarone is a sensitive CYP3A4 substrate. In vitro data predicts inhibition or induction of CYP3A4 by stiripentol potentially resulting in clinically significant interactions.
Droperidol: (Moderate) Monitor for excessive sedation and somnolence during coadministration of stiripentol and droperidol. CNS depressants can potentiate the effects of stiripentol.
Duloxetine: (Moderate) Consider a dose adjustment of duloxetine when coadministered with stiripentol. Coadministration may alter plasma concentrations of duloxetine resulting in an increased risk of adverse reactions and/or decreased efficacy. Duloxetine is a sensitive CYP1A2 substrate. In vitro data predicts inhibition or induction of CYP1A2 by stiripentol potentially resulting in clinically significant interactions.
Efavirenz: (Moderate) Consider a dose adjustment of efavirenz when coadministered with stiripentol. Coadministration may alter plasma concentrations of efavirenz resulting in an increased risk of adverse reactions and/or decreased efficacy. Efavirenz is a CYP3A4 substrate. In vitro data predicts inhibition or induction of CYP3A4 by stiripentol potentially resulting in clinically significant interactions.
Efavirenz; Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) Consider a dose adjustment of efavirenz when coadministered with stiripentol. Coadministration may alter plasma concentrations of efavirenz resulting in an increased risk of adverse reactions and/or decreased efficacy. Efavirenz is a CYP3A4 substrate. In vitro data predicts inhibition or induction of CYP3A4 by stiripentol potentially resulting in clinically significant interactions.
Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate: (Moderate) Consider a dose adjustment of efavirenz when coadministered with stiripentol. Coadministration may alter plasma concentrations of efavirenz resulting in an increased risk of adverse reactions and/or decreased efficacy. Efavirenz is a CYP3A4 substrate. In vitro data predicts inhibition or induction of CYP3A4 by stiripentol potentially resulting in clinically significant interactions.
Eletriptan: (Moderate) Consider a dose adjustment of eletriptan when coadministered with stiripentol. Coadministration may alter plasma concentrations of eletriptan resulting in an increased risk of adverse reactions and/or decreased efficacy. Eletriptan is a sensitive CYP3A4 substrate. In vitro data predicts inhibition or induction of CYP3A4 by stiripentol potentially resulting in clinically significant interactions.
Eliglustat: (Moderate) Consider a dose adjustment of eliglustat when coadministered with stiripentol. Coadministration may alter plasma concentrations of eliglustat resulting in an increased risk of adverse reactions and/or decreased efficacy. Eliglustat is a CYP3A4 substrate. In vitro data predicts inhibition or induction of CYP3A4 by stiripentol potentially resulting in clinically significant interactions.
Encorafenib: (Major) Avoid coadministration of stiripentol with encorafenib. If concurrent use is necessary, consider a dose increase of stiripentol. Coadministration may decrease stiripentol plasma concentrations resulting in a decrease in efficacy. Stiripentol is a CYP3A substrate and encorafenib is a strong CYP3A inducer.
Entacapone: (Moderate) Monitor for excessive sedation and somnolence during coadministration of stiripentol and entacapone. CNS depressants can potentiate the effects of stiripentol.
Enzalutamide: (Major) Avoid coadministration of stiripentol with enzalutamide. If concurrent use is necessary, increase the dose of stiripentol. Coadministration may decrease stiripentol plasma concentrations resulting in a decrease in efficacy. Stiripentol is metabolized by CYP3A4 and CYP2C19; enzalutamide is a strong inducer of CYP3A4 and an inducer of CYP2C19.
Eplerenone: (Moderate) Consider a dose adjustment of eplerenone when coadministered with stiripentol. Coadministration may alter plasma concentrations of eplerenone resulting in an increased risk of adverse reactions and/or decreased efficacy. Eplerenone is a sensitive CYP3A4 substrate. In vitro data predicts inhibition or induction of CYP3A4 by stiripentol potentially resulting in clinically significant interactions.
Ergotamine; Caffeine: (Moderate) Consider a dose adjustment of caffeine when coadministered with stiripentol. Coadministration may alter plasma concentrations of caffeine resulting in an increased risk of adverse reactions and/or decreased efficacy. Caffeine is a sensitive CYP1A2 substrate. In vitro data predicts inhibition or induction of CYP1A2 by stiripentol potentially resulting in clinically significant interactions.
Esketamine: (Moderate) Closely monitor patients receiving esketamine and stiripentol for sedation and other CNS depressant effects. Instruct patients who receive a dose of esketamine not to drive or engage in other activities requiring alertness until the next day after a restful sleep.
Estazolam: (Moderate) Monitor for excessive sedation and somnolence during coadministration of stiripentol and estazolam. CNS depressants can potentiate the effects of stiripentol.
Eszopiclone: (Moderate) Monitor for excessive sedation and somnolence during coadministration of stiripentol and eszopiclone. CNS depressants can potentiate the effects of stiripentol.
Ethanol: (Major) Advise patients to avoid alcohol consumption while taking CNS depressants. Alcohol consumption may result in additive CNS depression.
Ethosuximide: (Moderate) Consider a dose adjustment of ethosuximide when coadministered with stiripentol. Coadministration may alter plasma concentrations of ethosuximide resulting in an increased risk of adverse reactions and/or decreased efficacy. Ethosuximide is a CYP3A4 substrate. In vitro data predicts inhibition or induction of CYP3A4 by stiripentol potentially resulting in clinically significant interactions.
Etomidate: (Moderate) Monitor for excessive sedation and somnolence during coadministration of stiripentol and general anesthetics. CNS depressants can potentiate the effects of stiripentol.
Everolimus: (Moderate) Monitor everolimus whole blood trough concentrations as appropriate and watch for everolimus-related adverse reactions if coadministration with stiripentol is necessary. The dose of everolimus may need to be reduced. Everolimus is a P-glycoprotein (P-gp) substrate and stiripentol is a P-gp inhibitor. Coadministration with P-gp inhibitors may decrease the efflux of everolimus from intestinal cells and increase everolimus blood concentrations.
Ezetimibe; Simvastatin: (Moderate) Consider a dose adjustment of simvastatin when coadministered with stiripentol. Coadministration may alter plasma concentrations of simvastatin resulting in an increased risk of adverse reactions and/or decreased efficacy. Simvastatin is a sensitive CYP3A4 substrate. In vitro data predicts inhibition or induction of CYP3A4 by stiripentol potentially resulting in clinically significant interactions.
Fedratinib: (Major) Avoid coadministration of fedratinib with stiripentol as concurrent use may increase fedratinib exposure. Fedratinib is a substrate of both CYP3A4 and CYP2C19; stiripentol is an inhibitor of both CYP3A4 and CYP2C19. The coadministration of fedratinib with agents that are both a CYP3A4 and CYP2C19 inhibitor has not been evaluated.
Felodipine: (Moderate) Consider a dose adjustment of felodipine when coadministered with stiripentol. Coadministration may alter plasma concentrations of felodipine resulting in an increased risk of adverse reactions and/or decreased efficacy. Felodipine is a sensitive CYP3A4 substrate. In vitro data predicts inhibition or induction of CYP3A4 by stiripentol potentially resulting in clinically significant interactions.
Fenfluramine: (Moderate) Limit fenfluramine dose increases to 0.05 mg/kg/dose every 7 days up to a maximum of 0.2 mg/kg/dose PO twice daily (Max: 17 mg/day) in patients also receiving stiripentol and clobazam. Monitor for excessive sedation and somnolence; additive CNS depression may occur. Coadministration increases fenfluramine plasma concentrations and decreases its metabolite, norfenfluramine, due to the inhibition of the metabolism of fenfluramine. The effect of stiripentol plus clobazam on fenfluramine exposure is greater when fenfluramine is at steady-state than for the first dose of fenfluramine. Coadministration of existing stiripentol plus clobazam is expected to increase the exposure of the first fenfluramine dose by up to 42%. At steady-state, coadministration is expected to result in a 166% increase in fenfluramine exposure and a 38% decrease in norfenfluramine exposure.
Fentanyl: (Moderate) Concomitant use of opioid agonists with stiripentol may cause excessive sedation and somnolence. Limit the use of opioid pain medications with stiripentol to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression. Coadministration may alter plasma concentrations of fentanyl resulting in an increased risk of adverse reactions and/or decreased efficacy. Fentanyl is a CYP3A4 substrate. In vitro data predicts inhibition or induction of CYP3A4 by stiripentol potentially resulting in clinically significant interactions.
Flibanserin: (Moderate) Monitor for excessive sedation and somnolence during coadministration of stiripentol and flibanserin. CNS depressants can potentiate the effects of stiripentol.
Fluphenazine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of stiripentol and fluphenazine. CNS depressants can potentiate the effects of stiripentol.
Flurazepam: (Moderate) Monitor for excessive sedation and somnolence during coadministration of stiripentol and flurazepam. CNS depressants can potentiate the effects of stiripentol.
Food: (Major) Advise patients to avoid cannabis use while taking CNS depressants due to the risk for additive CNS depression and potential for other cognitive adverse reactions.
Fosphenytoin: (Major) Avoid coadministration of stiripentol with fosphenytoin. If concurrent use is necessary, increase the dose of stiripentol. Coadministration may decrease stiripentol plasma concentrations resulting in a decrease in efficacy. Stiripentol is metabolized by CYP3A4, CYP1A2, and CYP2C19; phenytoin is a strong inducer of CYP3A4, and an inducer of CYP1A2 and CYP2C19. Fosphenytoin is a prodrug of phenytoin.
Gabapentin: (Moderate) Monitor for excessive sedation and somnolence during coadministration of stiripentol and gabapentin. Concurrent use may result in additive CNS depression.
General anesthetics: (Moderate) Monitor for excessive sedation and somnolence during coadministration of stiripentol and general anesthetics. CNS depressants can potentiate the effects of stiripentol.
Glyburide: (Moderate) Consider a dose reduction of glyburide when coadministered with stiripentol. Coadministration may increase plasma concentrations of glyburide resulting in an increased risk of adverse reactions. Glyburide is a substrate of BCRP and P-gp; stiripentol may inhibit BCRP and P-gp at clinically relevant concentrations.
Glyburide; Metformin: (Moderate) Consider a dose reduction of glyburide when coadministered with stiripentol. Coadministration may increase plasma concentrations of glyburide resulting in an increased risk of adverse reactions. Glyburide is a substrate of BCRP and P-gp; stiripentol may inhibit BCRP and P-gp at clinically relevant concentrations.
Haloperidol: (Moderate) Monitor for excessive sedation and somnolence during coadministration of stiripentol and haloperidol. CNS depressants can potentiate the effects of stiripentol.
Homatropine; Hydrocodone: (Major) Concomitant use of opioid agonists with stiripentol may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking stiripentol. Limit the use of opioid pain medications with stiripentol to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression. Coadministration may alter plasma concentrations of hydrocodone resulting in an increased risk of adverse reactions and/or decreased efficacy. Hydrocodone is a CYP3A4 substrate. In vitro data predicts inhibition or induction of CYP3A4 by stiripentol potentially resulting in clinically significant interactions.
Hydrocodone: (Major) Concomitant use of opioid agonists with stiripentol may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking stiripentol. Limit the use of opioid pain medications with stiripentol to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression. Coadministration may alter plasma concentrations of hydrocodone resulting in an increased risk of adverse reactions and/or decreased efficacy. Hydrocodone is a CYP3A4 substrate. In vitro data predicts inhibition or induction of CYP3A4 by stiripentol potentially resulting in clinically significant interactions.
Hydrocodone; Ibuprofen: (Major) Concomitant use of opioid agonists with stiripentol may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking stiripentol. Limit the use of opioid pain medications with stiripentol to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression. Coadministration may alter plasma concentrations of hydrocodone resulting in an increased risk of adverse reactions and/or decreased efficacy. Hydrocodone is a CYP3A4 substrate. In vitro data predicts inhibition or induction of CYP3A4 by stiripentol potentially resulting in clinically significant interactions.
Hydromorphone: (Moderate) Concomitant use of opioid agonists with stiripentol may cause excessive sedation and somnolence. Limit the use of opioid pain medications with stiripentol to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
Hydroxyzine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of stiripentol and hydroxyzine. CNS depressants can potentiate the effects of stiripentol.
Ibrutinib: (Moderate) Consider a dose adjustment of ibrutinib when coadministered with stiripentol. Coadministration may alter plasma concentrations of ibrutinib resulting in an increased risk of adverse reactions and/or decreased efficacy. Ibrutinib is a sensitive CYP3A4 substrate. In vitro data predicts inhibition or induction of CYP3A4 by stiripentol potentially resulting in clinically significant interactions.
Ibuprofen; Oxycodone: (Major) Concomitant use of opioid agonists with stiripentol may cause excessive sedation and somnolence. Limit the use of opioid pain medications with stiripentol to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression. Coadministration may alter plasma concentrations of oxycodone resulting in an increased risk of adverse reactions and/or decreased efficacy. Oxycodone is a CYP3A4 substrate. In vitro data predicts inhibition or induction of CYP3A4 by stiripentol potentially resulting in clinically significant interactions.
Iloperidone: (Moderate) Monitor for excessive sedation and somnolence during coadministration of stiripentol and iloperidone. CNS depressants can potentiate the effects of stiripentol.
Imipramine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of stiripentol and tricyclic antidepressants. CNS depressants can potentiate the effects of stiripentol.
Indinavir: (Moderate) Consider a dose adjustment of indinavir when coadministered with stiripentol. Coadministration may alter plasma concentrations of indinavir resulting in an increased risk of adverse reactions and/or decreased efficacy. Indinavir is a sensitive CYP3A4 substrate. In vitro data predicts inhibition or induction of CYP3A4 by stiripentol potentially resulting in clinically significant interactions.
Isavuconazonium: (Moderate) Consider a dose adjustment of isavuconazonium when coadministered with stiripentol. Coadministration may alter plasma concentrations of isavuconazonium resulting in an increased risk of adverse reactions and/or decreased efficacy. Isavuconazonium is a sensitive CYP3A4 substrate. In vitro data predicts inhibition or induction of CYP3A4 by stiripentol potentially resulting in clinically significant interactions.
Isocarboxazid: (Moderate) Monitor for excessive sedation and somnolence during coadministration of stiripentol and isocarboxazid. CNS depressants can potentiate the effects of stiripentol.
Isoflurane: (Moderate) Monitor for excessive sedation and somnolence during coadministration of stiripentol and general anesthetics. CNS depressants can potentiate the effects of stiripentol.
Isoniazid, INH; Pyrazinamide, PZA; Rifampin: (Major) Avoid coadministration of stiripentol with rifampin. If concurrent use is necessary, increase the dose of stiripentol. Coadministration may decrease stiripentol plasma concentrations resulting in a decrease in efficacy. Stiripentol is metabolized by CYP3A4, CYP1A2, and CYP2C19; rifampin is a strong inducer of CYP3A4, and an inducer of CYP1A2 and CYP2C19.
Isoniazid, INH; Rifampin: (Major) Avoid coadministration of stiripentol with rifampin. If concurrent use is necessary, increase the dose of stiripentol. Coadministration may decrease stiripentol plasma concentrations resulting in a decrease in efficacy. Stiripentol is metabolized by CYP3A4, CYP1A2, and CYP2C19; rifampin is a strong inducer of CYP3A4, and an inducer of CYP1A2 and CYP2C19.
Ketamine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of stiripentol and general anesthetics. CNS depressants can potentiate the effects of stiripentol.
Lansoprazole: (Moderate) Consider a dose reduction of lansoprazole when coadministered with stiripentol. Coadministration may increase plasma concentrations of lansoprazole resulting in an increased risk of adverse reactions. Lansoprazole is a sensitive CYP2C19 substrate. In vitro data predicts inhibition of CYP2C19 by stiripentol potentially resulting in clinically significant interactions.
Lansoprazole; Amoxicillin; Clarithromycin: (Moderate) Consider a dose reduction of lansoprazole when coadministered with stiripentol. Coadministration may increase plasma concentrations of lansoprazole resulting in an increased risk of adverse reactions. Lansoprazole is a sensitive CYP2C19 substrate. In vitro data predicts inhibition of CYP2C19 by stiripentol potentially resulting in clinically significant interactions.
Lapatinib: (Moderate) Monitor for an increase in lapatinib-related adverse reactions if coadministration with stiripentol is necessary. Lapatinib is a P-glycoprotein (P-gp) substrate and stiripentol is a P-gp inhibitor. Increased plasma concentrations of lapatinib are likely.
Lasmiditan: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lasmiditan and stiripentol. Concurrent use may result in additive CNS depression.
Lefamulin: (Moderate) Monitor for lefamulin-related adverse effects if oral lefamulin is administered with stiripentol as concurrent use may increase exposure from lefamulin tablets; an interaction is not expected with intravenous lefamulin. Lefamulin is a CYP3A4 and P-gp substrate and stiripentol is a P-gp inhibitor.
Lemborexant: (Major) Limit the dose of lemborexant to a maximum of 5 mg PO once daily if coadministered with stiripentol as concurrent use may increase lemborexant exposure and the risk of adverse effects. Additionally, monitor for excessive sedation and somnolence during coadministration as additive CNS effects are possible. The risk of next-day impairment, including impaired driving, is increased if lemborexant is taken with other CNS depressants. Lemborexant is a CYP3A4 substrate; stiripentol is a weak CYP3A4 inhibitor. Coadministration with a weak CYP3A4 inhibitor is predicted to increase lemborexant exposure by less than 2-fold.
Levocetirizine: (Moderate) Concurrent use of cetirizine/levocetirizine with stiripentol should generally be avoided. Coadministration may increase the risk of CNS depressant-related side effects. If concurrent use is necessary, monitor for excessive sedation and somnolence.
Levorphanol: (Moderate) Concomitant use of opioid agonists with stiripentol may cause excessive sedation and somnolence. Limit the use of opioid pain medications with stiripentol to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
Lofexidine: (Moderate) Monitor for excessive sedation and somnolence during coadministration. Stiripentol may potentiate the sedative effects of lofexidine.
Lomitapide: (Moderate) Consider a dose adjustment of lomitapide when coadministered with stiripentol. Coadministration may alter plasma concentrations of lomitapide resulting in an increased risk of adverse reactions and/or decreased efficacy. Lomitapide is a sensitive CYP3A4 substrate. In vitro data predicts inhibition or induction of CYP3A4 by stiripentol potentially resulting in clinically significant interactions.
Lonafarnib: (Major) Avoid coadministration of lonafarnib and stiripentol; concurrent use may increase the exposure of lonafarnib and the risk of adverse effects. If coadministration is unavoidable, reduce to or continue lonafarnib at a dosage of 115 mg/m2 and closely monitor patients for lonafarnib-related adverse reactions. Resume previous lonafarnib dosage 14 days after discontinuing stiripentol. Lonafarnib is a sensitive CYP3A4 substrate and stiripentol is a weak CYP3A4 inhibitor.
Loperamide: (Moderate) Monitor for loperamide-associated adverse reactions, such as CNS effects and cardiac toxicities (i.e., syncope, ventricular tachycardia, QT prolongation, torsade de pointes, cardiac arrest), if coadministered with stiripentol. Concurrent use may increase loperamide exposure. Loperamide is a P-gp substrate and stiripentol is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased loperamide plasma concentrations by 2- to 3-fold.
Loperamide; Simethicone: (Moderate) Monitor for loperamide-associated adverse reactions, such as CNS effects and cardiac toxicities (i.e., syncope, ventricular tachycardia, QT prolongation, torsade de pointes, cardiac arrest), if coadministered with stiripentol. Concurrent use may increase loperamide exposure. Loperamide is a P-gp substrate and stiripentol is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased loperamide plasma concentrations by 2- to 3-fold.
Lopinavir; Ritonavir: (Moderate) Monitor for decreased efficacy of ritonavir if coadministered with stiripentol. Concurrent use may decrease the plasma concentrations of ritonavir leading to a reduction of antiretroviral efficacy and the potential development of viral resistance. Ritonavir is a CYP3A substrate and stiripentol is a CYP3A inducer and inhibitor; the net effect of stiripentol on CYP3A is unknown.
Lorazepam: (Moderate) Monitor for excessive sedation and somnolence during coadministration of stiripentol and lorazepam. CNS depressants can potentiate the effects of stiripentol.
Lovastatin: (Moderate) Consider a dose adjustment of lovastatin when coadministered with stiripentol. Coadministration may alter plasma concentrations of lovastatin resulting in an increased risk of adverse reactions and/or decreased efficacy. Lovastatin is a sensitive CYP3A4 substrate. In vitro data predicts inhibition or induction of CYP3A4 by stiripentol potentially resulting in clinically significant interactions.
Loxapine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of stiripentol and loxapine. CNS depressants can potentiate the effects of stiripentol.
Lumacaftor; Ivacaftor: (Major) Avoid coadministration of stiripentol with lumacaftor; ivacaftor. If concurrent use is necessary, increase the dose of stiripentol. Coadministration may decrease stiripentol plasma concentrations resulting in a decrease in efficacy. Stiripentol is metabolized by CYP3A4; lumacaftor is a strong inducer of CYP3A4.
Lumacaftor; Ivacaftor: (Major) Avoid coadministration of stiripentol with lumacaftor; ivacaftor. If concurrent use is necessary, increase the dose of stiripentol. Coadministration may decrease stiripentol plasma concentrations resulting in a decrease in efficacy. Stiripentol is metabolized by CYP3A4; lumacaftor is a strong inducer of CYP3A4.
Lumateperone: (Major) Avoid coadministration of lumateperone and stiripentol as concurrent use may decrease lumateperone exposure which may reduce efficacy or there may be an increase in side effects from lumateperone. Lumateperone is a CYP3A4 substrate. In vitro data show that stiripentol is both an inducer and inhibitor of CYP3A4; therefore, the effect of coadministration is unpredictable and must be assessed on an individual basis.
Lurasidone: (Moderate) Consider a dose adjustment of lurasidone when coadministered with stiripentol. Coadministration may alter plasma concentrations of lurasidone resulting in an increased risk of adverse reactions and/or decreased efficacy. Additive somnolence and sedation may occur. Lurasidone is a sensitive CYP3A4 substrate. In vitro data predicts inhibition or induction of CYP3A4 by stiripentol potentially resulting in clinically significant interactions.
Maprotiline: (Moderate) Monitor for excessive sedation and somnolence during coadministration of stiripentol and maprotiline. CNS depressants can potentiate the effects of stiripentol.
Maraviroc: (Moderate) Consider a dose adjustment of maraviroc when coadministered with stiripentol. Coadministration may alter plasma concentrations of maraviroc resulting in an increased risk of adverse reactions and/or decreased efficacy. Maraviroc is a sensitive CYP3A4 substrate. In vitro data predicts inhibition or induction of CYP3A4 by stiripentol potentially resulting in clinically significant interactions.
Mavacamten: (Major) Reduce the mavacamten dose by 1 level (i.e., 15 to 10 mg, 10 to 5 mg, or 5 to 2.5 mg) in patients receiving mavacamten and starting stiripentol therapy. Avoid initiation of stiripentol in patients who are on stable treatment with mavacamten 2.5 mg per day because a lower dose of mavacamten is not available. Initiate mavacamten at the recommended starting dose of 5 mg PO once daily in patients who are on stable stiripentol therapy. Concomitant use increases mavacamten exposure, which may increase the risk of adverse drug reactions. Mavacamten is a CYP2C19 substrate and stiripentol is a weak CYP2C19 inhibitor. Concomitant use with another weak CYP2C19 inhibitor in CYP2C19 normal and rapid metabolizers increased overall mavacamten exposure by 48%.
Meclizine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of stiripentol and meclizine. CNS depressants can potentiate the effects of stiripentol.
Melatonin: (Moderate) Consider a dose adjustment of melatonin as clinically appropriate when administered with stiripentol. Coadministration may alter plasma concentrations of melatonin resulting in an increased risk of adverse reactions and/or decreased efficacy. Additive somnolence and sedation may occur. Melatonin is a sensitive CYP1A2 substrate. In vitro data predicts inhibition or induction of CYP1A2 by stiripentol potentially resulting in clinically significant interactions.
Meperidine: (Moderate) Concomitant use of opioid agonists with stiripentol may cause excessive sedation and somnolence. Limit the use of opioid pain medications with stiripentol to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
Meprobamate: (Moderate) Monitor for excessive sedation and somnolence during coadministration of stiripentol and meprobamate. CNS depressants can potentiate the effects of stiripentol.
Metaxalone: (Moderate) Monitor for excessive sedation and somnolence during coadministration of stiripentol and metaxalone. CNS depressants can potentiate the effects of stiripentol.
Metformin; Repaglinide: (Moderate) Consider a dose reduction of repaglinide when coadministered with stiripentol. Coadministration may increase plasma concentrations of repaglinide resulting in an increased risk of adverse reactions. Repaglinide is a sensitive CYP2C8 substrate. In vitro data predicts inhibition of CYP2C8 by stiripentol potentially resulting in clinically significant interactions.
Methadone: (Moderate) Concomitant use of opioid agonists with stiripentol may cause excessive sedation and somnolence. Limit the use of opioid pain medications with stiripentol to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression. Coadministration may alter plasma concentrations of methadone resulting in an increased risk of adverse reactions and/or decreased efficacy. Methadone is a CYP3A4 substrate. In vitro data predicts inhibition or induction of CYP3A4 by stiripentol potentially resulting in clinically significant interactions.
Methocarbamol: (Moderate) Monitor for excessive sedation and somnolence during coadministration of stiripentol and methocarbamol. CNS depressants can potentiate the effects of stiripentol.
Methohexital: (Moderate) Monitor for excessive sedation and somnolence during coadministration of stiripentol and methohexital. CNS depressants can potentiate the effects of stiripentol.
Methotrexate: (Moderate) Consider a dose reduction of methotrexate when coadministered with stiripentol. Coadministration may increase plasma concentrations of methotrexate resulting in an increased risk of adverse reactions. Methotrexate is a substrate of BCRP; stiripentol may inhibit BCRP at clinically relevant concentrations.
Methyldopa: (Moderate) Monitor for excessive sedation and somnolence during coadministration of stiripentol and methyldopa. CNS depressants can potentiate the effects of stiripentol.
Metoclopramide: (Moderate) Monitor for excessive sedation and somnolence during coadministration of stiripentol and metoclopramide. CNS depressants can potentiate the effects of stiripentol.
Midazolam: (Moderate) Consider a dose adjustment of midazolam when coadministered with stiripentol. Coadministration may alter plasma concentrations of midazolam resulting in an increased risk of adverse reactions and/or decreased efficacy. Additive somnolence and sedation may occur. Midazolam is a sensitive CYP3A4 substrate. In vitro data predicts inhibition or induction of CYP3A4 by stiripentol potentially resulting in clinically significant interactions.
Mirtazapine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of stiripentol and mirtazapine. CNS depressants can potentiate the effects of stiripentol.
Mitotane: (Major) Avoid coadministration of stiripentol with mitotane. If concurrent use is necessary, increase the dose of stiripentol. Coadministration may decrease stiripentol plasma concentrations resulting in a decrease in efficacy. Stiripentol is metabolized by CYP3A4; mitotane is a strong inducer of CYP3A4.
Molindone: (Moderate) Monitor for excessive sedation and somnolence during coadministration of stiripentol and molindone. CNS depressants can potentiate the effects of stiripentol.
Morphine: (Moderate) Concomitant use of opioid agonists with stiripentol may cause excessive sedation and somnolence. Limit the use of opioid pain medications with stiripentol to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
Morphine; Naltrexone: (Moderate) Concomitant use of opioid agonists with stiripentol may cause excessive sedation and somnolence. Limit the use of opioid pain medications with stiripentol to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
Nabilone: (Moderate) Monitor for excessive sedation and somnolence during coadministration of nabilone and stiripentol. Concurrent use may result in additive CNS depression.
Nalbuphine: (Major) Concomitant use of mixed opioid agonists/antagonists like nalbuphine with stiripentol may cause excessive sedation and somnolence. Limit the use of nalbuphine with stiripentol to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. If nalbuphine is initiated in a patient taking stiripentol, reduce initial dosage and titrate to clinical response. If stiripentol is initiated a patient taking nalbuphine, use a lower initial dose of stiripentol and titrate to clinical response. Educate patients about the risks and symptoms of excessive CNS depression.
Naloxegol: (Moderate) Consider a dose adjustment of naloxegol when coadministered with stiripentol. Coadministration may alter plasma concentrations of naloxegol resulting in an increased risk of adverse reactions and/or decreased efficacy. Naloxegol is a sensitive CYP3A4 substrate. In vitro data predicts inhibition or induction of CYP3A4 by stiripentol potentially resulting in clinically significant interactions.
Nanoparticle Albumin-Bound Paclitaxel: (Moderate) Monitor for an increase in paclitaxel-related adverse reactions or decreased efficacy of nab-paclitaxel if coadministration of nab-paclitaxel with stiripentol is necessary due to the risk of altered plasma concentrations of paclitaxel. Nab-paclitaxel is a CYP2C8 substrate. Stiripentol is a weak CYP2C8 inhibitor, as well as being both an inhibitor and inducer of CYP3A4. In vitro, the metabolism of paclitaxel to 6-alpha-hydroxypaclitaxel was inhibited by inhibitors of CYP3A4 and CYP2C8.
Nanoparticle Albumin-Bound Sirolimus: (Major) Avoid concomitant use of sirolimus and stiripentol. Concomitant use may alter sirolimus exposure resulting in decreased efficacy or increased risk for sirolimus-related adverse effects. Sirolimus is a CYP3A and P-gp substrate and stiripentol is a weak CYP3A inducer and P-gp inhibitor.
Nefazodone: (Moderate) Monitor for excessive sedation and somnolence during coadministration of stiripentol and nefazodone. CNS depressants can potentiate the effects of stiripentol.
Nirmatrelvir; Ritonavir: (Moderate) Monitor for a diminished response to nirmatrelvir if concomitant use of stiripentol is necessary. Concomitant use of nirmatrelvir and stiripentol may reduce the therapeutic effect of nirmatrelvir. Nirmatrelvir is a CYP3A substrate and stiripentol is a CYP3A inducer and inhibitor; the net effect of stiripentol on CYP3A is unknown. (Moderate) Monitor for decreased efficacy of ritonavir if coadministered with stiripentol. Concurrent use may decrease the plasma concentrations of ritonavir leading to a reduction of antiretroviral efficacy and the potential development of viral resistance. Ritonavir is a CYP3A substrate and stiripentol is a CYP3A inducer and inhibitor; the net effect of stiripentol on CYP3A is unknown.
Nisoldipine: (Moderate) Consider a dose adjustment of nisoldipine when coadministered with stiripentol. Coadministration may alter plasma concentrations of nisoldipine resulting in an increased risk of adverse reactions and/or decreased efficacy. Nisoldipine is a sensitive CYP3A4 substrate. In vitro data predicts inhibition or induction of CYP3A4 by stiripentol potentially resulting in clinically significant interactions.
Nortriptyline: (Moderate) Monitor for excessive sedation and somnolence during coadministration of stiripentol and tricyclic antidepressants. CNS depressants can potentiate the effects of stiripentol.
Olanzapine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of stiripentol and olanzapine. CNS depressants can potentiate the effects of stiripentol.
Olanzapine; Fluoxetine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of stiripentol and olanzapine. CNS depressants can potentiate the effects of stiripentol.
Olanzapine; Samidorphan: (Moderate) Monitor for excessive sedation and somnolence during coadministration of stiripentol and olanzapine. CNS depressants can potentiate the effects of stiripentol.
Oliceridine: (Moderate) Concomitant use of oliceridine with stiripentol may cause excessive sedation and somnolence. Limit the use of oliceridine with stiripentol to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Omeprazole: (Moderate) Consider a dose reduction of omeprazole when coadministered with stiripentol. Coadministration may increase plasma concentrations of omeprazole resulting in an increased risk of adverse reactions. Omeprazole is a sensitive CYP2C19 substrate. In vitro data predicts inhibition of CYP2C19 by stiripentol potentially resulting in clinically significant interactions.
Omeprazole; Amoxicillin; Rifabutin: (Moderate) Consider a dose reduction of omeprazole when coadministered with stiripentol. Coadministration may increase plasma concentrations of omeprazole resulting in an increased risk of adverse reactions. Omeprazole is a sensitive CYP2C19 substrate. In vitro data predicts inhibition of CYP2C19 by stiripentol potentially resulting in clinically significant interactions.
Omeprazole; Sodium Bicarbonate: (Moderate) Consider a dose reduction of omeprazole when coadministered with stiripentol. Coadministration may increase plasma concentrations of omeprazole resulting in an increased risk of adverse reactions. Omeprazole is a sensitive CYP2C19 substrate. In vitro data predicts inhibition of CYP2C19 by stiripentol potentially resulting in clinically significant interactions.
Opicapone: (Moderate) Opicapone should be given cautiously with other agents that cause CNS depression, including stiripentol, due to the possibility of additive sedation. COMT inhibitors, such as opicapone, have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Prescribers should re-assess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment. Patients should be advised to avoid driving or other tasks requiring mental alertness until they know how the combination affects them.
Orphenadrine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of stiripentol and orphenadrine. CNS depressants can potentiate the effects of stiripentol.
Oxazepam: (Moderate) Monitor for excessive sedation and somnolence during coadministration of stiripentol and oxazepam. CNS depressants can potentiate the effects of stiripentol.
Oxycodone: (Major) Concomitant use of opioid agonists with stiripentol may cause excessive sedation and somnolence. Limit the use of opioid pain medications with stiripentol to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression. Coadministration may alter plasma concentrations of oxycodone resulting in an increased risk of adverse reactions and/or decreased efficacy. Oxycodone is a CYP3A4 substrate. In vitro data predicts inhibition or induction of CYP3A4 by stiripentol potentially resulting in clinically significant interactions.
Oxymorphone: (Moderate) Concomitant use of opioid agonists with stiripentol may cause excessive sedation and somnolence. Limit the use of opioid pain medications with stiripentol to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
Ozanimod: (Major) Coadministration of ozanimod with stiripentol is not recommended. Coadministration may increase the exposure of the active metabolites of ozanimod, which may increase the risk of adverse reactions. Ozanimod is a BCRP substrate and stiripentol is a BCRP inhibitor. Coadministration with another BCRP inhibitor had no effect on ozanimod exposure, but doubled the exposure of the minor active metabolites, RP101988 and RP101075 (the direct precursor of the major active metabolite CC112273). Coadministration of ozanimod with BCRP inhibitors may also increase exposure of CC112273 and CC1084037.
Paclitaxel: (Moderate) Consider a dose reduction of paclitaxel when coadministered with stiripentol. Coadministration may increase plasma concentrations of paclitaxel resulting in an increased risk of adverse reactions. Paclitaxel is a substrate of CYP2C8; stiripentol may inhibit CYP2C8 at clinically relevant concentrations.
Paliperidone: (Moderate) Monitor for excessive sedation and somnolence during coadministration of stiripentol and paliperidone. Drugs with CNS depressant properties, such as paliperidone, can potentiate the effects of stiripentol.
Pancuronium: (Moderate) Monitor for excessive sedation and somnolence during coadministration of stiripentol and pancuronium. CNS depressants can potentiate the effects of stiripentol.
Pentazocine; Naloxone: (Major) Concomitant use of mixed opioid agonists/antagonists like pentazocine with stiripentol may cause excessive sedation and somnolence. Limit the use of pentazocine with stiripentol to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. If pentazocine is initiated in a patient taking stiripentol, reduce initial dosage and titrate to clinical response. If stiripentol is initiated a patient taking pentazocine, use a lower initial dose of stiripentol and titrate to clinical response. Educate patients about the risks and symptoms of excessive CNS depression.
Pentobarbital: (Moderate) Monitor for excessive sedation and somnolence during coadministration of stiripentol and pentobarbital. CNS depressants can potentiate the effects of stiripentol.
Perampanel: (Moderate) Monitor for excessive sedation and somnolence during coadministration of stiripentol and perampanel. CNS depressants can potentiate the effects of stiripentol.
Perphenazine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of stiripentol and perphenazine. CNS depressants can potentiate the effects of stiripentol.
Perphenazine; Amitriptyline: (Moderate) Monitor for excessive sedation and somnolence during coadministration of stiripentol and perphenazine. CNS depressants can potentiate the effects of stiripentol. (Moderate) Monitor for excessive sedation and somnolence during coadministration of stiripentol and tricyclic antidepressants. CNS depressants can potentiate the effects of stiripentol.
Phenelzine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of stiripentol and phenelzine. CNS depressants can potentiate the effects of stiripentol.
Phenobarbital: (Major) Avoid coadministration of stiripentol with phenobarbital. If concurrent use is necessary, increase the dose of stiripentol and monitor for excessive sedation and somnolence. Coadministration may decrease stiripentol plasma concentrations resulting in a decrease in efficacy; the CNS depressant effects of stiripentol may also be increased by phenobarbital. Stiripentol is metabolized by CYP3A4, CYP1A2, and CYP2C19; phenobarbital is a strong inducer of CYP3A4, and an inducer of CYP1A2 and CYP2C19.
Phenobarbital; Hyoscyamine; Atropine; Scopolamine: (Major) Avoid coadministration of stiripentol with phenobarbital. If concurrent use is necessary, increase the dose of stiripentol and monitor for excessive sedation and somnolence. Coadministration may decrease stiripentol plasma concentrations resulting in a decrease in efficacy; the CNS depressant effects of stiripentol may also be increased by phenobarbital. Stiripentol is metabolized by CYP3A4, CYP1A2, and CYP2C19; phenobarbital is a strong inducer of CYP3A4, and an inducer of CYP1A2 and CYP2C19. (Moderate) Monitor for excessive sedation and somnolence during coadministration of stiripentol and atropine. CNS depressants can potentiate the effects of stiripentol. (Moderate) Monitor for excessive sedation and somnolence during coadministration of stiripentol and scopolamine. CNS depressants can potentiate the effects of stiripentol.
Phenytoin: (Major) Avoid coadministration of stiripentol with phenytoin. If concurrent use is necessary, increase the dose of stiripentol. Coadministration may decrease stiripentol plasma concentrations resulting in a decrease in efficacy. Stiripentol is metabolized by CYP3A4, CYP1A2, and CYP2C19; phenytoin is a strong inducer of CYP3A4, and an inducer of CYP1A2 and CYP2C19.
Pimavanserin: (Moderate) Monitor for excessive sedation and somnolence during coadministration of stiripentol and pimavanserin. CNS depressants can potentiate the effects of stiripentol.
Pimozide: (Moderate) Monitor for excessive sedation and somnolence during coadministration of stiripentol and pimozide. CNS depressants can potentiate the effects of stiripentol. Consider a dose adjustment of pimozide when coadministered with stiripentol. Coadministration may alter plasma concentrations of pimozide resulting in an increased risk of adverse reactions and/or decreased efficacy. Pimozide is a CYP3A4 and CYP1A2 substrate. In vitro data predicts inhibition or induction of CYP3A4 and CYP1A2 by stiripentol potentially resulting in clinically significant interactions.
Pralsetinib: (Major) Avoid concomitant use of stiripentol with pralsetinib due to the risk of increased pralsetinib exposure which may increase the risk of adverse reactions. If concomitant use is necessary, reduce the daily dose of pralsetinib by 100 mg. Pralsetinib is a P-gp substrate and stiripentol is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased the overall exposure of pralsetinib by 81%.
Pramipexole: (Moderate) Monitor for excessive sedation and somnolence during coadministration of stiripentol and pramipexole. CNS depressants can potentiate the effects of stiripentol.
Prazosin: (Moderate) Consider a dose reduction of prazosin when coadministered with stiripentol. Coadministration may increase plasma concentrations of prazosin resulting in an increased risk of adverse reactions. Prazosin is a substrate of BCRP; stiripentol may inhibit BCRP at clinically relevant concentrations.
Pregabalin: (Moderate) Monitor for excessive sedation and somnolence during coadministration of stiripentol and pregabalin. Concurrent use may result in additive CNS depression.
Primidone: (Major) Avoid coadministration of stiripentol with primidone. If concurrent use is necessary, increase the dose of stiripentol and monitor for excessive sedation and somnolence. Coadministration may decrease stiripentol plasma concentrations resulting in a decrease in efficacy; the CNS depressant effects of stiripentol may also be increased by primidone. Stiripentol is metabolized by CYP3A4, CYP1A2, and CYP2C19; primidone is a strong inducer of CYP3A4, and an inducer of CYP1A2 and CYP2C19.
Probenecid; Colchicine: (Major) Avoid concomitant use of colchicine and stiripentol due to the risk for increased colchicine exposure which may increase the risk for adverse effects. Concomitant use is contraindicated in patients with renal or hepatic impairment. Additionally, this combination is contraindicated if colchicine is being used for cardiovascular risk reduction. If concomitant use is necessary outside of these scenarios, consider a colchicine dosage reduction. Specific dosage reduction recommendations are available for colchicine tablets for some indications; it is unclear if these dosage recommendations are appropriate for other products or indications. For colchicine tablets being used for gout prophylaxis, reduce the dose from 0.6 mg twice daily to 0.3 mg once daily or from 0.6 mg once daily to 0.3 mg once every other day. For colchicine tablets being used for gout treatment, reduce the dose from 1.2 mg followed by 0.6 mg to 0.6 mg without an additional dose. For colchicine tablets being used for Familial Mediterranean Fever, the maximum daily dose is 0.6 mg. Colchicine is a P-gp substrate and stiripentol is a P-gp inhibitor.
Prochlorperazine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of stiripentol and prochlorperazine. CNS depressants can potentiate the effects of stiripentol.
Promethazine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of stiripentol and promethazine. CNS depressants can potentiate the effects of stiripentol.
Promethazine; Dextromethorphan: (Moderate) Monitor for excessive sedation and somnolence during coadministration of stiripentol and promethazine. CNS depressants can potentiate the effects of stiripentol.
Promethazine; Phenylephrine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of stiripentol and promethazine. CNS depressants can potentiate the effects of stiripentol.
Propantheline: (Moderate) Monitor for excessive sedation and somnolence during coadministration of stiripentol and propantheline. CNS depressants can potentiate the effects of stiripentol.
Propofol: (Moderate) Monitor for excessive sedation and somnolence during coadministration of stiripentol and general anesthetics. CNS depressants can potentiate the effects of stiripentol.
Protriptyline: (Moderate) Monitor for excessive sedation and somnolence during coadministration of stiripentol and tricyclic antidepressants. CNS depressants can potentiate the effects of stiripentol.
Quazepam: (Moderate) Monitor for excessive sedation and somnolence during coadministration of stiripentol and quazepam. CNS depressants can potentiate the effects of stiripentol.
Quetiapine: (Moderate) Consider a dose adjustment of quetiapine when coadministered with stiripentol. Coadministration may alter plasma concentrations of quetiapine resulting in an increased risk of adverse reactions and/or decreased efficacy. Additive somnolence and sedation may occur. Quetiapine is a sensitive CYP3A4 substrate. In vitro data predicts inhibition or induction of CYP3A4 by stiripentol potentially resulting in clinically significant interactions.
Quinidine: (Moderate) Consider a dose adjustment of quinidine when coadministered with stiripentol. Coadministration may alter plasma concentrations of quinidine resulting in an increased risk of adverse reactions and/or decreased efficacy. Quinidine is a CYP3A4 substrate. In vitro data predicts inhibition or induction of CYP3A4 by stiripentol potentially resulting in clinically significant interactions.
Ramelteon: (Moderate) Consider a dose adjustment of ramelteon when coadministered with stiripentol. Coadministration may alter plasma concentrations of ramelteon resulting in an increased risk of adverse reactions and/or decreased efficacy. Additive somnolence and sedation may occur. Ramelteon is a sensitive CYP1A2 substrate. In vitro data predicts inhibition or induction of CYP1A2 by stiripentol potentially resulting in clinically significant interactions.
Rasagiline: (Moderate) Monitor for excessive sedation and somnolence during coadministration of stiripentol and rasagiline. CNS depressants can potentiate the effects of stiripentol.
Remifentanil: (Moderate) Concomitant use of opioid agonists with stiripentol may cause excessive sedation and somnolence. Limit the use of opioid pain medications with stiripentol to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
Repaglinide: (Moderate) Consider a dose reduction of repaglinide when coadministered with stiripentol. Coadministration may increase plasma concentrations of repaglinide resulting in an increased risk of adverse reactions. Repaglinide is a sensitive CYP2C8 substrate. In vitro data predicts inhibition of CYP2C8 by stiripentol potentially resulting in clinically significant interactions.
Repotrectinib: (Major) Avoid coadministration of repotrectinib with stiripentol due to increased repotrectinib exposure which may increase the risk for repotrectinib-related adverse effects. Repotrectinib is a P-gp substrate and stiripentol is a P-gp inhibitor.
Rifampin: (Major) Avoid coadministration of stiripentol with rifampin. If concurrent use is necessary, increase the dose of stiripentol. Coadministration may decrease stiripentol plasma concentrations resulting in a decrease in efficacy. Stiripentol is metabolized by CYP3A4, CYP1A2, and CYP2C19; rifampin is a strong inducer of CYP3A4, and an inducer of CYP1A2 and CYP2C19.
Rifapentine: (Major) Avoid coadministration of stiripentol with rifapentine. If concurrent use is necessary, consider a dose increase of stiripentol. Coadministration may decrease stiripentol plasma concentrations resulting in a decrease in efficacy. Stiripentol is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer.
Rifaximin: (Moderate) Monitor for an increase in rifaximin-related adverse reactions if coadministration with stiripentol is necessary. Concomitant use may increase rifaximin exposure. In patients with hepatic impairment, a potential additive effect of reduced metabolism may further increase systemic rifaximin exposure. Rifaximin is a P-gp substrate and stiripentol is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased rifaximin overall exposure by 124-fold.
Rimegepant: (Major) Avoid coadministration of rimegepant with stiripentol; concurrent use may increase rimegepant exposure. Rimegepant is a substrate of P-gp and BCRP and stiripentol is a P-gp and BCRP inhibitor.
Risperidone: (Major) Monitor for excessive sedation and somnolence during coadministration of stiripentol and risperidone. CNS depressants can potentiate the effects of stiripentol.
Ritonavir: (Moderate) Monitor for decreased efficacy of ritonavir if coadministered with stiripentol. Concurrent use may decrease the plasma concentrations of ritonavir leading to a reduction of antiretroviral efficacy and the potential development of viral resistance. Ritonavir is a CYP3A substrate and stiripentol is a CYP3A inducer and inhibitor; the net effect of stiripentol on CYP3A is unknown.
Rocuronium: (Moderate) Monitor for excessive sedation and somnolence during coadministration of stiripentol and rocuronium. CNS depressants can potentiate the effects of stiripentol.
Ropinirole: (Moderate) Monitor for excessive sedation and somnolence during coadministration of stiripentol and ropinirole. CNS depressants can potentiate the effects of stiripentol.
Rosiglitazone: (Moderate) Monitor for an increase in rosiglitazone-related adverse effects during concomitant use with stiripentol; adjust the dose of rosiglitazone based on clinical response. Coadministration may increase the exposure of rosiglitazone. Rosiglitazone is a CYP2C8 substrate and stiripentol is a weak CYP2C8 inhibitor.
Rotigotine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of stiripentol and rotigotine. CNS depressants can potentiate the effects of stiripentol.
Rufinamide: (Moderate) Monitor for excessive sedation and somnolence during coadministration of stiripentol and rufinamide. CNS depressants can potentiate the effects of stiripentol.
Safinamide: (Moderate) Monitor for excessive sedation and somnolence during coadministration of stiripentol and safinamide. CNS depressants can potentiate the effects of stiripentol.
Saquinavir: (Moderate) Consider a dose adjustment of saquinavir when coadministered with stiripentol. Coadministration may alter plasma concentrations of saquinavir resulting in an increased risk of adverse reactions and/or decreased efficacy. Saquinavir is a sensitive CYP3A4 substrate. In vitro data predicts inhibition or induction of CYP3A4 by stiripentol potentially resulting in clinically significant interactions.
Scopolamine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of stiripentol and scopolamine. CNS depressants can potentiate the effects of stiripentol.
Secobarbital: (Moderate) Monitor for excessive sedation and somnolence during coadministration of stiripentol and secobarbital. CNS depressants can potentiate the effects of stiripentol.
Sertraline: (Moderate) Consider a dose adjustment of sertraline when coadministered with stiripentol. Coadministration may alter plasma concentrations of sertraline resulting in an increased risk of adverse reactions and/or decreased efficacy. Sertraline is a CYP2B6 substrate. In vitro data predicts inhibition or induction of CYP2B6 by stiripentol potentially resulting in clinically significant interactions.
Sevoflurane: (Moderate) Monitor for excessive sedation and somnolence during coadministration of stiripentol and general anesthetics. CNS depressants can potentiate the effects of stiripentol.
Sildenafil: (Moderate) Consider a dose adjustment of sildenafil when coadministered with stiripentol. Coadministration may alter plasma concentrations of sildenafil resulting in an increased risk of adverse reactions and/or decreased efficacy. Sildenafil is a sensitive CYP3A4 substrate. In vitro data predicts inhibition or induction of CYP3A4 by stiripentol potentially resulting in clinically significant interactions.
Simvastatin: (Moderate) Consider a dose adjustment of simvastatin when coadministered with stiripentol. Coadministration may alter plasma concentrations of simvastatin resulting in an increased risk of adverse reactions and/or decreased efficacy. Simvastatin is a sensitive CYP3A4 substrate. In vitro data predicts inhibition or induction of CYP3A4 by stiripentol potentially resulting in clinically significant interactions.
Sirolimus: (Moderate) Monitor sirolimus concentrations and adjust sirolimus dosage as appropriate during concomitant use of stiripentol. Concomitant use may alter sirolimus exposure resulting in decreased efficacy or increased risk for sirolimus-related adverse effects. Sirolimus is a CYP3A and P-gp substrate and stiripentol is a weak CYP3A inducer and P-gp inhibitor.
Sodium Oxybate: (Moderate) Monitor for excessive sedation and somnolence during coadministration of stiripentol and sodium oxybate. CNS depressants can potentiate the effects of stiripentol.
St. John's Wort, Hypericum perforatum: (Major) Avoid coadministration of stiripentol with St. John's Wort. If concurrent use is necessary, increase the dose of stiripentol. Coadministration may decrease stiripentol plasma concentrations resulting in a decrease in efficacy. Stiripentol is metabolized by CYP3A4, CYP1A2, and CYP2C19; St. John's Wort is a strong inducer of CYP3A4, and an inducer of CYP2C19 and CYP1A2.
Succinylcholine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of stiripentol and succinylcholine. CNS depressants can potentiate the effects of stiripentol.
Sufentanil: (Moderate) Concomitant use of opioid agonists with stiripentol may cause excessive sedation and somnolence. Limit the use of opioid pain medications with stiripentol to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression. Coadministration may alter plasma concentrations of sufentanil resulting in an increased risk of adverse reactions and/or decreased efficacy. Sufentanil is a CYP3A4 substrate. In vitro data predicts inhibition or induction of CYP3A4 by stiripentol potentially resulting in clinically significant interactions.
Suvorexant: (Moderate) Monitor for excessive sedation and somnolence during coadministration of stiripentol and suvorexant. CNS depressants can potentiate the effects of stiripentol.
Tacrolimus: (Moderate) Consider a dose adjustment of tacrolimus when coadministered with stiripentol. Coadministration may alter plasma concentrations of tacrolimus resulting in an increased risk of adverse reactions and/or decreased efficacy. Tacrolimus is a sensitive CYP3A4 substrate. In vitro data predicts inhibition or induction of CYP3A4 by stiripentol potentially resulting in clinically significant interactions.
Talazoparib: (Moderate) Monitor for an increase in talazoparib-related adverse reactions if concomitant use of stiripentol is necessary. Concomitant use may increase talazoparib exposure. Talazoparib is a P-gp and BCRP substrate; stiripentol is a P-gp and BCRP inhibitor.
Tapentadol: (Moderate) Concomitant use of opioid agonists with stiripentol may cause excessive sedation and somnolence. Limit the use of opioid pain medications with stiripentol to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
Tasimelteon: (Moderate) Consider a dose adjustment of tasimelton when coadministered with stiripentol. Coadministration may alter plasma concentrations of tasimelton resulting in an increased risk of adverse reactions and/or decreased efficacy. Additive somnolence and sedation may occur. Tasimelton is a sensitive CYP1A2 substrate. In vitro data predicts inhibition or induction of CYP1A2 by stiripentol potentially resulting in clinically significant interactions.
Temazepam: (Moderate) Monitor for excessive sedation and somnolence during coadministration of stiripentol and temazepam. CNS depressants can potentiate the effects of stiripentol.
Tetrabenazine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of stiripentol and tetrabenazine. CNS depressants can potentiate the effects of stiripentol.
Thalidomide: (Moderate) Monitor for excessive sedation and somnolence during coadministration of stiripentol and thalidomide. CNS depressants can potentiate the effects of stiripentol.
Theophylline, Aminophylline: (Moderate) Consider a dose adjustment of aminophylline when coadministered with stiripentol. Coadministration may alter plasma concentrations of aminophylline resulting in an increased risk of adverse reactions and/or decreased efficacy. Aminophylline is a sensitive CYP1A2 substrate. In vitro data predicts inhibition or induction of CYP1A2 by stiripentol potentially resulting in clinically significant interactions. (Moderate) Consider a dose adjustment of theophylline when coadministered with stiripentol. Coadministration may alter plasma concentrations of theophylline resulting in an increased risk of adverse reactions and/or decreased efficacy. Theophylline is a sensitive CYP1A2 substrate. In vitro data predicts inhibition or induction of CYP1A2 by stiripentol potentially resulting in clinically significant interactions.
Thioridazine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of stiripentol and thioridazine. CNS depressants can potentiate the effects of stiripentol.
Thiotepa: (Moderate) Consider a dose adjustment of thiotepa when coadministered with stiripentol. Coadministration may alter plasma concentrations of thiotepa resulting in an increased risk of adverse reactions and/or decreased efficacy. Thiotepa is a CYP2B6 substrate. In vitro data predicts inhibition or induction of CYP2B6 by stiripentol potentially resulting in clinically significant interactions.
Thiothixene: (Moderate) Monitor for excessive sedation and somnolence during coadministration of stiripentol and thiothixene. CNS depressants can potentiate the effects of stiripentol.
Ticagrelor: (Moderate) Consider a dose adjustment of ticagrelor when coadministered with stiripentol. Coadministration may alter plasma concentrations of ticagrelor resulting in an increased risk of adverse reactions and/or decreased efficacy. Ticagrelor is a sensitive CYP3A4 substrate. In vitro data predicts inhibition or induction of CYP3A4 by stiripentol potentially resulting in clinically significant interactions.
Tipranavir: (Moderate) Consider a dose adjustment of tipranavir when coadministered with stiripentol. Coadministration may alter plasma concentrations of tipranavir resulting in an increased risk of adverse reactions and/or decreased efficacy. Tipranavir is a sensitive CYP3A4 substrate. In vitro data predicts inhibition or induction of CYP3A4 by stiripentol potentially resulting in clinically significant interactions.
Tizanidine: (Moderate) Consider a dose adjustment of tizanidine when coadministered with stiripentol. Coadministration may alter plasma concentrations of tizanidine resulting in an increased risk of adverse reactions and/or decreased efficacy. Additive somnolence and sedation may occur. Tizanidine is a sensitive CYP1A2 substrate. In vitro data predicts inhibition or induction of CYP1A2 by stiripentol potentially resulting in clinically significant interactions.
Tolcapone: (Moderate) Monitor for excessive sedation and somnolence during coadministration of stiripentol and tolcapone. CNS depressants can potentiate the effects of stiripentol.
Tolvaptan: (Moderate) Consider a dose adjustment of tolvaptan when coadministered with stiripentol. Coadministration may alter plasma concentrations of tolvaptan resulting in an increased risk of adverse reactions and/or decreased efficacy. Tolvaptan is a sensitive CYP3A4 substrate. In vitro data predicts inhibition or induction of CYP3A4 by stiripentol potentially resulting in clinically significant interactions.
Tramadol: (Moderate) Concomitant use of opioid agonists with stiripentol may cause excessive sedation and somnolence. Limit the use of opioid pain medications with stiripentol to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression. Coadministration may alter plasma concentrations of tramadol resulting in an increased risk of adverse reactions and/or decreased efficacy. Tramadol is a CYP3A4 substrate. In vitro data predicts inhibition or induction of CYP3A4 by stiripentol potentially resulting in clinically significant interactions.
Tramadol; Acetaminophen: (Moderate) Concomitant use of opioid agonists with stiripentol may cause excessive sedation and somnolence. Limit the use of opioid pain medications with stiripentol to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression. Coadministration may alter plasma concentrations of tramadol resulting in an increased risk of adverse reactions and/or decreased efficacy. Tramadol is a CYP3A4 substrate. In vitro data predicts inhibition or induction of CYP3A4 by stiripentol potentially resulting in clinically significant interactions.
Trazodone: (Moderate) Monitor for excessive sedation and somnolence during coadministration of stiripentol and trazodone. CNS depressants can potentiate the effects of stiripentol.
Triazolam: (Moderate) Consider a dose adjustment of triazolam when coadministered with stiripentol. Coadministration may alter plasma concentrations of triazolam resulting in an increased risk of adverse reactions and/or decreased efficacy. Additive somnolence and sedation may occur. Triazolam is a sensitive CYP3A4 substrate. In vitro data predicts inhibition or induction of CYP3A4 by stiripentol potentially resulting in clinically significant interactions.
Tricyclic antidepressants: (Moderate) Monitor for excessive sedation and somnolence during coadministration of stiripentol and tricyclic antidepressants. CNS depressants can potentiate the effects of stiripentol.
Trifluoperazine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of stiripentol and trifluoperazine. CNS depressants can potentiate the effects of stiripentol.
Trimipramine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of stiripentol and tricyclic antidepressants. CNS depressants can potentiate the effects of stiripentol.
Ubrogepant: (Major) Ubrogepant dose adjustment is necessary if coadministered with stiripentol as concurrent use may decrease ubrogepant exposure and efficacy or increase ubrogepant exposure and side effects. Ubrogepant is a CYP3A4, BCRP, and P-gp substrate and stiripentol is a weak CYP3A4 inhibitor and inducer and a BCRP and P-gp inhibitor.
Valbenazine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of stiripentol and valbenazine. CNS depressants can potentiate the effects of stiripentol.
Valerian, Valeriana officinalis: (Moderate) Monitor for excessive sedation and somnolence during coadministration of stiripentol and valerian. CNS depressants can potentiate the effects of stiripentol.
Valproic Acid, Divalproex Sodium: (Moderate) Monitor for excessive sedation and somnolence during coadministration of stiripentol and valproic acid. CNS depressants can potentiate the effects of stiripentol.
Vardenafil: (Moderate) Consider a dose adjustment of vardenafil when coadministered with stiripentol. Coadministration may alter plasma concentrations of vardenafil resulting in an increased risk of adverse reactions and/or decreased efficacy. Vardenafil is a sensitive CYP3A4 substrate. In vitro data predicts inhibition or induction of CYP3A4 by stiripentol potentially resulting in clinically significant interactions.
Vecuronium: (Moderate) Monitor for excessive sedation and somnolence during coadministration of stiripentol and vecuronium. CNS depressants can potentiate the effects of stiripentol.
Venetoclax: (Moderate) Consider a dose adjustment of venetoclax when coadministered with stiripentol. Coadministration may alter plasma concentrations of venetoclax resulting in an increased risk of adverse reactions and/or decreased efficacy. Venetoclax is a sensitive CYP3A4 substrate. In vitro data predicts inhibition or induction of CYP3A4 by stiripentol potentially resulting in clinically significant interactions.
Vigabatrin: (Moderate) Monitor for excessive sedation and somnolence during coadministration of stiripentol and vigabatrin. CNS depressants can potentiate the effects of stiripentol.
Warfarin: (Moderate) Closely monitor the INR if coadministration of warfarin with stiripentol is necessary as concurrent use may increase or decrease the exposure of warfarin leading to increased bleeding risk or reduced efficacy. Stiripentol is a CYP1A2 and weak CYP3A4 inhibitor and the R-enantiomer of warfarin is a CYP1A2/CYP3A4 substrate. Additionally, stiripentol is a CYP1A2 and weak CYP3A4 inducer, which may decrease the INR.
Zaleplon: (Moderate) Monitor for excessive sedation and somnolence during coadministration of stiripentol and zaleplon. CNS depressants can potentiate the effects of stiripentol.
Ziprasidone: (Moderate) Monitor for excessive sedation and somnolence during coadministration of stiripentol and ziprasidone. CNS depressants can potentiate the effects of stiripentol.
Zolpidem: (Moderate) Monitor for excessive sedation and somnolence during coadministration of stiripentol and zolpidem. CNS depressants can potentiate the effects of stiripentol.
Zuranolone: (Major) Avoid the use of multiple sedating agents due to the risk for additive CNS depression. If use is necessary, consider a downward dosage adjustment of either or both medications, especially in patients with additional risk factors for sedation-related harm.
Stiripentol is a structurally unique antiepileptic drug with several possible mechanisms of action including various effects on the gamma-aminobutyric acid (GABA)A receptor and novel inhibition of lactate dehydrogenase. Indirectly, stiripentol inhibits cytochrome P450 activity which increases blood concentrations of other antiepileptics including clobazam and its active metabolite.
Stiripentol is administered orally. Protein binding is 99%. The metabolic pathway for stiripentol has not been fully elucidated; in vitro studies suggest the main hepatic isoenzymes involved in metabolism are CYP1A2, CYP2C19, and CYP3A4. Elimination half-life ranges from 4.5 to 14 hours, increasing with increasing doses.
Affected cytochrome P450 isoenzymes and drug transporters: CYP1A2, CYP2C19, CYP3A4, CYP2B6, CYP2C8, P-gp, and BCRP
Stiripentol is a substrate of several CYP isoenzymes including CYP1A2, CYP2C19, and CYP3A4. Stiripentol inhibits and induces CYP1A2, CYP2B6, and CYP3A4. Stiripentol also inhibits CYP2C8, CYP2C19, P-glycoprotein (P-gp), and BCRP at clinically relevant concentrations.
-Route-Specific Pharmacokinetics
Oral Route
The median time to stiripentol peak plasma concentration is 2 to 3 hours. Systemic exposure increases in a greater than dose proportional manner from 500 to 2,000 mg.
-Special Populations
Hepatic Impairment
The effect of hepatic impairment on stiripentol pharmacokinetics is unknown; however, the drug is primarily metabolized by the liver.
Renal Impairment
The effect of renal impairment on stiripentol pharmacokinetics is unknown; however, stiripentol metabolites are primarily eliminated in the urine.
Pediatrics
The apparent clearance and Vd of stiripentol were related to body weight in a study of children (mean age: 7.3 years) with Dravet syndrome. Elimination half-life increased from 8.5 hours (for 10 kg) to 23.5 hours (for 60 kg).