<p><strong>Alcohol</strong>: Concomitant consumption of alcohol can increase the bioavailability of clobazam by 50% and therefore lead to increased clobazam effects.<br />
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<strong>Central nervous system depressant drugs</strong>: Especially when clobazam is administered in higher doses, a mutually potentiating effect is to be expected if other central nervous system depressant drugs (such as antipsychotics, anxiolytics, certain antidepressant agents, anticonvulsant drugs, sedative antihistamines, anaesthetics, hypnotics or narcotic analgesics, or other sedatives) are taken at the same time. Special caution is also necessary when clobazam is administered in cases of intoxication with such substances or with lithium.<br />
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<strong>Opioids</strong>: The concomitant use of benzodiazepines, including clobazam, and opioids increases the risk of sedation, respiratory depression, coma, and death because of the additive CNS depressant effect. Limit dosage and duration of concomitant use of benzodiazepines and opioids.<br />
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<strong>Anticonvulsants</strong>: If clobazam is administered simultaneously with anticonvulsants in the treatment of epilepsy, the dosage must be adjusted under regular medical supervision (EEG monitoring), as there may be interactions with the patient&#39;s basic anticonvulsant medication. In patients receiving concomitant treatment with valproic acid, there may be a slight to moderate rise in plasma valproic acid concentration. Phenytoin plasma levels may rise if patients receive concomitant treatment with clobazam. Where possible, it is recommended that blood levels of concomitantly administered valproic acid or phenytoin be monitored. Carbamazepine and phenytoin may cause an increase in the metabolic conversion of clobazam to the active metabolite N-desmethyl clobazam. Stiripentol increases plasma levels of clobazam and its active metabolite N-desmethylclobazam, through inhibition of CYP3A and CYP2C19. Monitoring of blood levels is recommended, prior to initiation of stiripentol, and then once new steady-state concentration has been reached, i.e. after 2 weeks approximately.<br />
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<strong>Narcotic analgesics</strong>: If clobazam is used concomitantly with narcotic analgesics, possible euphoria may be enhanced; this may lead to increased psychological dependence.<br />
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<strong>Muscle relaxants</strong>: The effects of muscle relaxants and nitrous oxide may be enhanced.<br />
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<strong>CYP 2C19 inhibitors</strong>: Strong and moderate inhibitors of CYP2C19 may result in increased exposure to N-desmethylclobazam (N-CLB), the active metabolite of clobazam. Dosage adjustment of clobazam may be necessary when co-administered with strong CYP2C19 inhibitors (e.g., cannabidiol containing medicinal products, fuconazole, fuvoxamine, ticlopidine) or moderate CYP2C19 inhibitors (e.g. omeprazole).<br />
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<strong>CYP 2D6 substrates</strong>: Clobazam is a weak CYP2D6 inhibitor. Dose adjustment of drugs metabolized by CYP2D6 (e.g. dextromethorphan, pimozide, paroxetine, nebivolol) may be necessary.</p>