Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule, Oral:
Diacomit: 250 mg [contains fd&c blue #2 (indigotine)]
Diacomit: 500 mg
Packet, Oral:
Diacomit: 250 mg (60 ea); 500 mg (60 ea) [contains aspartame]
Pharmacology
Mechanism of Action
Precise mechanism behind anticonvulsant effects is unknown. May enhance GABAergic inhibitory neurotransmission by weak partial agonism and/or positive allosteric modulation of gamma-aminobutyric acid (GABA)-A receptors (Fisher 2009). Also inhibits multiple cytochrome P450 isoenzymes involved in the metabolism of other anticonvulsants; concurrent use may increase their systemic exposure and efficacy.
Pharmacokinetics/Pharmacodynamics
Absorption
Well absorbed; extensive first-pass metabolism (Walker 1995). Maximum concentration obtained with powder for suspension is slightly higher than that observed with capsules (Diacomit prescribing information [Canada 2012]).
Metabolism
Hepatic through demethylenation, primarily by CYP1A2, 2C19, 3A4, and glucuronidation (Moreland 1986)
Excretion
Urine (73%, primarily metabolites); feces (18% as unchanged drug) (Moreland 1986)
Time to Peak
Median: 2 to 3 hours
Half-Life Elimination
Adults: 4.5 to 13 hours (dose-dependent)
Protein Binding
~99% to plasma proteins
Use in Specific Populations
Special Populations: Children
In a pharmacokinetic study of children (n=35; median age: 7.3 years) with Dravet syndrome, clearance and volume of distribution were related to body weight and elimination half-life increased from 8.5 hours (10 kg) to 23.5 hours (60 kg). Adolescents may require lower dosing than younger children (May 2012).
Use: Labeled Indications
Dravet syndrome: Adjunctive treatment of refractory generalized tonic-clonic seizures in conjunction with clobazam and valproic acid (off-label) in patients ≥2 years with Dravet syndrome (previously known as severe myoclonic epilepsy in infancy) (Chiron 2000; Wirrell 2016).
Contraindications
There are no contraindications listed in the manufacturer's labeling.
Canadian labeling: Additional contraindications (not in US labeling): Hypersensitivity to stiripentol or any component of the formulation
Dosage and Administration
Dosing: Adult
Note: Not appropriate for monotherapy. The dosage of concomitant clobazam and valproate may need to be adjusted. Systemic exposure is slightly higher with the powder for suspension than that observed with capsules; patient monitoring is recommended when switching between dosage forms (Canadian labeling).
Dravet syndrome (adjunctive therapy): Oral: Usual: 50 mg/kg/day given in 2 or 3 divided doses. Maximum dose: 3 g/day (manufacturer's labeling). Some experts recommend initiating with 25 mg/kg/day and increasing by 10 mg/kg/day every 1 to 2 weeks up to 3 g/day (Andrade 2020).
Dosing: Geriatric
Refer to adult dosing.
Dosing: Pediatric
Note: FDA approved in combination with clobazam; international labeling (European Medicines Agency, Health Canada) recommends combination with clobazam and valproic acid. Other concomitant antiepileptic agents have also been studied (eg, topiramate) and efficacy data are evolving; although, experts suggest avoiding sodium channel blockers (eg, carbamazepine) which may exacerbate seizures (Wirrell 2016). The concomitant dosage of clobazam and/or valproate may need to be adjusted with initiation of stiripentol. Systemic exposure is slightly higher with the powder for suspension than that observed with capsules; patient monitoring is recommended when switching between dosage forms (Diacomit prescribing information [Canada 2012]). Two strengths of powder packets are available (250 mg and 500 mg); may combine the two strengths to achieve the appropriate dosage; ensure appropriate product selection.
Dravet syndrome (adjunctive therapy): Children and Adolescents: Limited data available in children <2 years of age: Oral: 50 mg/kg/day in 2 or 3 divided doses; round dose to nearest available dosage form; maximum daily dose: 3,000 mg/day. Some experts recommend initiating at a lower dosage of 10 to 15 mg/kg/day in divided doses and titrating to initial target dose of 50 mg/kg/day over a 2- to 4-week period (Wirrell 2016). Higher doses were reported in one open-label, multicenter trial of patients with Dravet syndrome (n=23; ages: 1 to 22 years); the initial dose was 50 mg/kg/day in divided doses in patients <20 kg and a fixed dose of 1,000 mg/day in divided doses in patients ≥20 kg; after 4 weeks, dosage was adjusted based on clinical response up to a maximum of 100 mg/kg/day (or 4,000 mg/day) in divided doses. In patients 1 to 8 years (n=15), mean daily dose was 59 mg/kg/day (range: 30 to 100 mg/kg/day) and in patients 13 to 22 years (n=8), mean daily dose was 1,469 mg/day (range: 500 to 3,000 mg/day) (Inoue 2009). Pharmacokinetic modeling studies indicate adolescents may require lower doses of 20 to 30 mg/kg/day (May 2012; Wirrell 2016).
Reconstitution
Mix powder for suspension with a glass of water.
Administration
Oral: Administer in 2 or 3 divided doses daily with a meal. Capsule should be swallowed whole with a glass of water. Do not crush, chew, or open capsule. Powder for suspension should be mixed with a glass of water and consumed immediately. After administering suspension, add a small amount of water (eg, 25 mL) to the dosing cup and drink the entire mixture to be sure there is no medication left in the cup.
Dietary Considerations
Some products may contain phenylalanine; use with caution in patient with phenylketonuria.
Storage
Store at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C and 30°C (59°F and 86°F). Store in original package. Protect from light. Powder for suspension should be consumed immediately after reconstitution and not stored.
Drug Interactions
Agomelatine: CYP1A2 Inhibitors (Moderate) may increase the serum concentration of Agomelatine. Monitor therapy
Alcohol (Ethyl): Stiripentol may enhance the sedative effect of Alcohol (Ethyl). Avoid combination
Alizapride: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy
Alosetron: CYP1A2 Inhibitors (Moderate) may increase the serum concentration of Alosetron. Management: Avoid concomitant use of alosetron and moderate CYP1A2 inhibitors whenever possible. If combined use is necessary, monitor for increased alosetron effects/toxicities. Consider therapy modification
Azelastine (Nasal): CNS Depressants may enhance the CNS depressant effect of Azelastine (Nasal). Avoid combination
Bendamustine: CYP1A2 Inhibitors (Moderate) may increase the serum concentration of Bendamustine. Management: Consider alternatives to moderate CYP1A2 inhibitors during therapy with bendamustine due to the potential for increased bendamustine plasma concentrations and increased bendamustine toxicity. Consider therapy modification
Blonanserin: CNS Depressants may enhance the CNS depressant effect of Blonanserin. Consider therapy modification
Bosentan: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy
Brexanolone: CNS Depressants may enhance the CNS depressant effect of Brexanolone. Monitor therapy
Brimonidine (Topical): May enhance the CNS depressant effect of CNS Depressants. Monitor therapy
Bromazepam: CYP1A2 Inhibitors (Moderate) may increase the serum concentration of Bromazepam. Monitor therapy
Bromopride: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy
Bromperidol: May enhance the CNS depressant effect of CNS Depressants. Avoid combination
Buprenorphine: CNS Depressants may enhance the CNS depressant effect of Buprenorphine. Management: Consider reduced doses of other CNS depressants, and avoiding such drugs in patients at high risk of buprenorphine overuse/self-injection. Initiate buprenorphine at lower doses in patients already receiving CNS depressants. Consider therapy modification
Caffeine and Caffeine Containing Products: Stiripentol may increase the serum concentration of Caffeine and Caffeine Containing Products. Avoid combination
Cannabidiol: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy
Cannabidiol: CYP2C19 Inhibitors (Moderate) may increase the serum concentration of Cannabidiol. Monitor therapy
Cannabis: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy
CarBAMazepine: Stiripentol may increase the serum concentration of CarBAMazepine. Avoid combination
Chlormethiazole: May enhance the CNS depressant effect of CNS Depressants. Management: Monitor closely for evidence of excessive CNS depression. The chlormethiazole labeling states that an appropriately reduced dose should be used if such a combination must be used. Consider therapy modification
Chlorphenesin Carbamate: May enhance the adverse/toxic effect of CNS Depressants. Monitor therapy
Cilostazol: CYP2C19 Inhibitors (Moderate) may increase serum concentrations of the active metabolite(s) of Cilostazol. CYP2C19 Inhibitors (Moderate) may increase the serum concentration of Cilostazol. Management: Reduce the cilostazol dose to 50 mg twice daily in patients who are also receiving moderate inhibitors of CYP2C19. Monitor clinical response to cilostazol closely. Consider therapy modification
Citalopram: CYP2C19 Inhibitors (Moderate) may increase the serum concentration of Citalopram. Management: Limit citalopram dose to a maximum of 20 mg/day if used with a moderate CYP2C19 inhibitor. Patients using this combination should be monitored closely for evidence of citalopram toxicity (eg, serotonin syndrome, QT prolongation). Consider therapy modification
CloBAZam: May increase the serum concentration of Stiripentol. Stiripentol may increase the serum concentration of CloBAZam. Monitor therapy
Clofazimine: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy
ClomiPRAMINE: CYP1A2 Inhibitors (Moderate) may increase the serum concentration of ClomiPRAMINE. Monitor therapy
Clopidogrel: CYP2C19 Inhibitors (Moderate) may decrease serum concentrations of the active metabolite(s) of Clopidogrel. Management: Due to a risk for impaired clopidogrel effectiveness with such a combination, carefully consider the need for a moderate CYP2C19 inhibitor in patients receiving clopidogrel. Monitor patients closely for evidence of a diminished response to clopidogrel. Consider therapy modification
CloZAPine: CYP1A2 Inhibitors (Moderate) may increase the serum concentration of CloZAPine. Monitor therapy
CNS Depressants: May enhance the adverse/toxic effect of other CNS Depressants. Monitor therapy
Conivaptan: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Avoid combination
CYP2C19 Inducers (Moderate): May decrease the serum concentration of CYP2C19 Substrates (High risk with Inducers). Monitor therapy
CYP2C19 Inducers (Strong): May increase the metabolism of CYP2C19 Substrates (High risk with Inducers). Management: Consider an alternative for one of the interacting drugs. Some combinations may be specifically contraindicated. Consult appropriate manufacturer labeling. Consider therapy modification
CYP2C19 Inhibitors (Moderate): May decrease the metabolism of CYP2C19 Substrates (High risk with Inhibitors). Monitor therapy
CYP2C19 Inhibitors (Strong): May decrease the metabolism of CYP2C19 Substrates (High risk with Inhibitors). Consider therapy modification
CYP2C19 Substrates (High risk with Inhibitors): CYP2C19 Inhibitors (Moderate) may decrease the metabolism of CYP2C19 Substrates (High risk with Inhibitors). Monitor therapy
CYP3A4 Inducers (Moderate): May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy
CYP3A4 Inducers (Strong): May increase the metabolism of CYP3A4 Substrates (High risk with Inducers). Management: Consider an alternative for one of the interacting drugs. Some combinations may be specifically contraindicated. Consult appropriate manufacturer labeling. Consider therapy modification
CYP3A4 Inhibitors (Moderate): May decrease the metabolism of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy
CYP3A4 Inhibitors (Strong): May decrease the metabolism of CYP3A4 Substrates (High risk with Inhibitors). Consider therapy modification
CYP3A4 Substrates (High risk with Inhibitors): Stiripentol may increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Management: Use of stiripentol with CYP3A4 substrates that are considered to have a narrow therapeutic index should be avoided due to the increased risk for adverse effects and toxicity. Any CYP3A4 substrate used with stiripentol requires closer monitoring. Consider therapy modification
Dabrafenib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Seek alternatives to the CYP3A4 substrate when possible. If concomitant therapy cannot be avoided, monitor clinical effects of the substrate closely (particularly therapeutic effects). Consider therapy modification
Dabrafenib: May decrease the serum concentration of CYP2C19 Substrates (High risk with Inducers). Management: Seek alternatives to the CYP2C19 substrate when possible. If concomitant therapy cannot be avoided, monitor clinical effects of the substrate closely (particularly therapeutic effects). Consider therapy modification
Deferasirox: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy
Dimethindene (Topical): May enhance the CNS depressant effect of CNS Depressants. Monitor therapy
Doxylamine: May enhance the CNS depressant effect of CNS Depressants. Management: The manufacturer of Diclegis (doxylamine/pyridoxine), intended for use in pregnancy, specifically states that use with other CNS depressants is not recommended. Monitor therapy
Dronabinol: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy
Droperidol: May enhance the CNS depressant effect of CNS Depressants. Management: Consider dose reductions of droperidol or of other CNS agents (eg, opioids, barbiturates) with concomitant use. Exceptions to this monograph are discussed in further detail in separate drug interaction monographs. Consider therapy modification
DULoxetine: CYP1A2 Inhibitors (Moderate) may increase the serum concentration of DULoxetine. Monitor therapy
Enzalutamide: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Concurrent use of enzalutamide with CYP3A4 substrates that have a narrow therapeutic index should be avoided. Use of enzalutamide and any other CYP3A4 substrate should be performed with caution and close monitoring. Consider therapy modification
Enzalutamide: May decrease the serum concentration of CYP2C19 Substrates (High risk with Inducers). Conversely, concentrations of active metabolites may be increased for those drugs activated by CYP2C19. Management: Concurrent use of enzalutamide with CYP2C19 substrates that have a narrow therapeutic index should be avoided. Use of enzalutamide and any other CYP2C19 substrate should be performed with caution and close monitoring. Consider therapy modification
Esketamine: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy
Flunitrazepam: CNS Depressants may enhance the CNS depressant effect of Flunitrazepam. Consider therapy modification
Fosnetupitant: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy
Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Avoid combination
HYDROcodone: CNS Depressants may enhance the CNS depressant effect of HYDROcodone. Management: Avoid concomitant use of hydrocodone and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Consider therapy modification
HydrOXYzine: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy
Idelalisib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Avoid combination
Kava Kava: May enhance the adverse/toxic effect of CNS Depressants. Monitor therapy
Lemborexant: May enhance the CNS depressant effect of CNS Depressants. Management: Dosage adjustments of lemborexant and of concomitant CNS depressants may be necessary when administered together because of potentially additive CNS depressant effects. Close monitoring for CNS depressant effects is necessary. Consider therapy modification
Lofexidine: May enhance the CNS depressant effect of CNS Depressants. Management: Drugs listed as exceptions to this monograph are discussed in further detail in separate drug interaction monographs. Monitor therapy
Lorlatinib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Avoid concurrent use of lorlatinib with any CYP3A4 substrates for which a minimal decrease in serum concentrations of the CYP3A4 substrate could lead to therapeutic failure and serious clinical consequences. Consider therapy modification
Magnesium Sulfate: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy
Mefloquine: May diminish the therapeutic effect of Anticonvulsants. Mefloquine may decrease the serum concentration of Anticonvulsants. Management: Mefloquine is contraindicated for malaria prophylaxis in persons with a history of convulsions. Monitor anticonvulsant concentrations and treatment response closely with concurrent use. Consider therapy modification
Melatonin: CYP1A2 Inhibitors (Moderate) may increase the serum concentration of Melatonin. Monitor therapy
Methotrimeprazine: CNS Depressants may enhance the CNS depressant effect of Methotrimeprazine. Methotrimeprazine may enhance the CNS depressant effect of CNS Depressants. Management: Reduce adult dose of CNS depressant agents by 50% with initiation of concomitant methotrimeprazine therapy. Further CNS depressant dosage adjustments should be initiated only after clinically effective methotrimeprazine dose is established. Consider therapy modification
MetyroSINE: CNS Depressants may enhance the sedative effect of MetyroSINE. Monitor therapy
Mianserin: May diminish the therapeutic effect of Anticonvulsants. Monitor therapy
MiFEPRIStone: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Management: Minimize doses of CYP3A4 substrates, and monitor for increased concentrations/toxicity, during and 2 weeks following treatment with mifepristone. Avoid cyclosporine, dihydroergotamine, ergotamine, fentanyl, pimozide, quinidine, sirolimus, and tacrolimus. Consider therapy modification
Minocycline (Systemic): May enhance the CNS depressant effect of CNS Depressants. Monitor therapy
Mitotane: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Doses of CYP3A4 substrates may need to be adjusted substantially when used in patients being treated with mitotane. Consider therapy modification
Nabilone: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy
Netupitant: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy
OLANZapine: CYP1A2 Inhibitors (Moderate) may increase the serum concentration of OLANZapine. Monitor therapy
Opioid Agonists: CNS Depressants may enhance the CNS depressant effect of Opioid Agonists. Management: Avoid concomitant use of opioid agonists and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Consider therapy modification
Orlistat: May decrease the serum concentration of Anticonvulsants. Monitor therapy
Orphenadrine: CNS Depressants may enhance the CNS depressant effect of Orphenadrine. Avoid combination
Oxomemazine: May enhance the CNS depressant effect of CNS Depressants. Avoid combination
OxyCODONE: CNS Depressants may enhance the CNS depressant effect of OxyCODONE. Management: Avoid concomitant use of oxycodone and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Consider therapy modification
Paraldehyde: CNS Depressants may enhance the CNS depressant effect of Paraldehyde. Avoid combination
Pentoxifylline: CYP1A2 Inhibitors (Moderate) may increase the serum concentration of Pentoxifylline. Monitor therapy
Perampanel: May enhance the CNS depressant effect of CNS Depressants. Management: Patients taking perampanel with any other drug that has CNS depressant activities should avoid complex and high-risk activities, particularly those such as driving that require alertness and coordination, until they have experience using the combination. Consider therapy modification
PHENobarbital: May decrease the serum concentration of Stiripentol. Avoid combination
Phenytoin: Stiripentol may decrease the serum concentration of Phenytoin. Avoid combination
Pirfenidone: CYP1A2 Inhibitors (Moderate) may increase the serum concentration of Pirfenidone. Management: Avoid concomitant use of pirfenidone and moderate CYP1A2 inhibitors whenever possible. If combined, decrease the pirfenidone dose to 1,602 mg per day (534 mg three times daily) and monitor for increased pirfenidone toxicities. Consider therapy modification
Piribedil: CNS Depressants may enhance the CNS depressant effect of Piribedil. Monitor therapy
Pomalidomide: CYP1A2 Inhibitors (Moderate) may increase the serum concentration of Pomalidomide. Monitor therapy
Pramipexole: CNS Depressants may enhance the sedative effect of Pramipexole. Monitor therapy
Propranolol: CYP1A2 Inhibitors (Moderate) may increase the serum concentration of Propranolol. Monitor therapy
Ramelteon: CYP1A2 Inhibitors (Moderate) may increase the serum concentration of Ramelteon. Monitor therapy
Ramosetron: CYP1A2 Inhibitors (Moderate) may increase the serum concentration of Ramosetron. Monitor therapy
Rasagiline: CYP1A2 Inhibitors (Moderate) may increase the serum concentration of Rasagiline. Management: Limit rasagiline dose to 0.5 mg once daily in patients taking moderate CYP1A2 inhibitors. Consider therapy modification
ROPINIRole: CNS Depressants may enhance the sedative effect of ROPINIRole. Monitor therapy
ROPINIRole: CYP1A2 Inhibitors (Moderate) may increase the serum concentration of ROPINIRole. Monitor therapy
Ropivacaine: CYP1A2 Inhibitors (Moderate) may increase the serum concentration of Ropivacaine. Monitor therapy
Rotigotine: CNS Depressants may enhance the sedative effect of Rotigotine. Monitor therapy
Rufinamide: May enhance the adverse/toxic effect of CNS Depressants. Specifically, sleepiness and dizziness may be enhanced. Monitor therapy
Sarilumab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy
Selective Serotonin Reuptake Inhibitors: CNS Depressants may enhance the adverse/toxic effect of Selective Serotonin Reuptake Inhibitors. Specifically, the risk of psychomotor impairment may be enhanced. Monitor therapy
Siltuximab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy
Sodium Oxybate: May enhance the CNS depressant effect of CNS Depressants. Management: Consider alternatives to combined use. When combined use is needed, consider minimizing doses of one or more drugs. Use of sodium oxybate with alcohol or sedative hypnotics is contraindicated. Consider therapy modification
Suvorexant: CNS Depressants may enhance the CNS depressant effect of Suvorexant. Management: Dose reduction of suvorexant and/or any other CNS depressant may be necessary. Use of suvorexant with alcohol is not recommended, and the use of suvorexant with any other drug to treat insomnia is not recommended. Consider therapy modification
Tapentadol: May enhance the CNS depressant effect of CNS Depressants. Management: Avoid concomitant use of tapentadol and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Consider therapy modification
Tasimelteon: CYP1A2 Inhibitors (Moderate) may increase the serum concentration of Tasimelteon. Monitor therapy
Tetrahydrocannabinol: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy
Tetrahydrocannabinol and Cannabidiol: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy
Thalidomide: CNS Depressants may enhance the CNS depressant effect of Thalidomide. Avoid combination
Theophylline Derivatives: CYP1A2 Inhibitors (Moderate) may increase the serum concentration of Theophylline Derivatives. Management: Consider avoidance of this combination. If coadministration is necessary, monitor for increased theophylline serum concentrations and toxicities when combined. Theophylline dose reductions will likely be required. Exceptions: Dyphylline. Consider therapy modification
TiZANidine: CYP1A2 Inhibitors (Moderate) may increase the serum concentration of TiZANidine. Management: If combined use cannot be avoided, initiate tizanidine in adults at 2 mg and increase in 2 to 4 mg increments based on patient response. Monitor for increased effects of tizanidine, including adverse reactions. Consider therapy modification
Tocilizumab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy
Trimeprazine: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy
Zolpidem: CNS Depressants may enhance the CNS depressant effect of Zolpidem. Management: Reduce the Intermezzo brand sublingual zolpidem adult dose to 1.75 mg for men who are also receiving other CNS depressants. No such dose change is recommended for women. Avoid use with other CNS depressants at bedtime; avoid use with alcohol. Consider therapy modification
Adverse Reactions
Note: Adverse reactions reported with combination (clobazam) therapy.
>10%:
Central nervous system: Drowsiness (67%), agitation (27%), ataxia (27%), hypotonia (18% to 24%), dysarthria (12%), insomnia (12%)
Endocrine & metabolic: Weight loss (27%)
Gastrointestinal: Decreased appetite (45% to 46%), nausea (15%)
Hematologic & oncologic: Decreased platelet count (13%), neutropenia (13%)
Neuromuscular & skeletal: Tremor (15%)
1% to 10%:
Central nervous system: Aggressive behavior (9%), fatigue (9%)
Endocrine & metabolic: Weight gain (6%)
Gastrointestinal: Vomiting (9%), sialorrhea (6%)
Respiratory: Bronchitis (6%), nasopharyngitis (6%)
Miscellaneous: Fever (6%)
Warnings/Precautions
Concerns related to adverse effects:
- Appetite/weight loss: Loss of appetite and weight loss have been observed in 46% and 27% of patients (mean age: 9.2 years), respectively, during clinical trials; monitor the growth rate of pediatric patients closely. Valproate dose reduction by 30% may help minimize appetite and weight loss.
- Blood dyscrasias: Neutropenia and thrombocytopenia have been observed in clinical trials; monitor CBC during therapy.
- CNS depression: May cause CNS depression (eg, drowsiness, sleepiness) and impair physical or mental abilities; patients must be cautioned about performing tasks that require mental alertness (eg, operating machinery or driving). If CNS depression occurs during co-administration with clobazam, consider dosage adjustment of clobazam and/or other concomitant antiseizure drugs.
- Suicidal ideation: Pooled analysis of trials involving various antiepileptics (regardless of indication) showed an increased risk of suicidal thoughts/behavior (incidence rate: 0.43% treated patients compared to 0.24% of patients receiving placebo); risk observed as early as 1 week after initiation and continued through duration of trials (most trials ≤24 weeks). Monitor all patients for notable changes in behavior that might indicate suicidal thoughts or depression; notify health care provider immediately if symptoms occur.
Disease-related concerns:
- Hepatic impairment: Use with caution in patients with mild impairment; primarily undergoes hepatic metabolism. Avoid use in patients with moderate to severe hepatic impairment.
- Renal impairment: Use with caution in patients with mild impairment; elimination of metabolites is primarily renal. Avoid use in patients with moderate to severe renal impairment.
Concurrent drug therapy issues:
- Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.
Dosage form specific issues:
- Powder for suspension: Systemic exposure is slightly higher with the powder for suspension than that observed with capsules; may consider patient monitoring when switching between dosage forms. Powder for suspension contains phenylalanine; use caution in patients with phenylketonuria.
Other warnings:
- Appropriate use: Must be used in conjunction with clobazam (labeled use) and valproate (off-label use) (Chiron 2000; Wirrell 2016); not approved for use as monotherapy.
- Withdrawal: Anticonvulsants should not be discontinued abruptly because of the possibility of increasing seizure frequency; therapy should be withdrawn gradually (over at least 1 month) to minimize the potential of increased seizure frequency, unless safety concerns require a more rapid withdrawal.
Monitoring Parameters
CBC (prior to initiation and every 6 months or as clinically indicated thereafter); weight; growth rate in children.
Pregnancy
Pregnancy Considerations
Adverse events have been observed in animal reproduction studies. Information related to the use of stiripentol in pregnancy has not been located (de Jong 2016).
Stiripentol is used in combination with clobazam or valproic acid (off-label); refer to individual monographs for additional information.
Data collection to monitor pregnancy and infant outcomes following exposure to stiripentol is ongoing. Patients may enroll themselves in the North American Antiepileptic Drug (NAAED) Pregnancy Registry (1-888-233-2334 or http://www.aedpregnancyregistry.org).
Patient Education
- Discuss specific use of vaccine and side effects with caregiver as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
- Patient may experience dizziness, fatigue, lack of appetite, weight gain, weight loss, nausea, vomiting, trouble sleeping, increased saliva, stuffy nose, or sore throat. Have patient report immediately to prescriber agitation, sensing things that seem real but are not, tremors, decreased muscle tone, difficulty controlling movements, twitching, change in balance, difficulty swallowing, difficulty speaking, severe loss of strength and energy, bruising, bleeding, irritability, panic attacks, mood changes, signs of depression (thoughts of suicide, anxiety, emotional instability, or confusion), or signs of infection (HCAHPS).
- Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.
Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.
