Interactions : אינטראקציות

4.5 Interaction with other medicinal products and other forms of interaction

Alcohol
Concomitant consumption of alcohol can increase the bioavailability of clobazam by 50% (see section 5.2) and therefore increase the effects of clobazam e.g. sedation (see section 4.4).
C entral nervous system depressant drugs
Especially when clobazam is administered at higher doses, an enhancement of the central depressive effect may occur in cases of concomitant use with antipsychotics, hypnotics, anxiolytics/sedatives, antidepressant agents, narcotic analgesics, anticonvulsant drugs, anaesthetics and sedative antihistamines. Special caution is also necessary when clobazam is administered in cases of intoxication with such substances or with lithium.
O pioids
The concomitant use of benzodiazepines, including clobazam, and opioids increases the risk of 5/8
sedation, respiratory depression, coma and death because of additive CNS depressant effect. Limit dosage and duration of concomitant use of benzodiazepines and opioids (see section 4.4).
Anticonvulsants
Addition of clobazam to established anticonvulsant medication (e.g. phenytoin, valproic acid) may cause a change in plasma levels of these drugs.
Phenytoin and carbamazepine 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 of clobazam and active metabolite is recommended, prior to initiation



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of stiripentol, and then once new steady-state concentration has been reached, i.e. after 2 weeks approximately. Clinical monitoring is recommended and dose adjustment may be necessary.
N arcotic analgesics
If clobazam is used concomitantly with narcotic analgesics, possible euphoria may be enhanced; this may lead to increased psychological dependence.
Muscle relaxants
The effects of muscle relaxants, analgesics and nitrous oxide may be enhanced.
CYP 2C19 inhibitors
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 (e.g. fluconazole, fluvoxamine, ticlopidine) or moderate (e.g. omeprazole) CYP2C19 inhibitors (see section 5.2).
Cannabidiol
When cannabidiol and clobazam are co-administered, bi-directional PK interactions occur. Based on a healthy volunteer study, elevated levels (3- to 4-fold) of N-desmethylclobazam (an active metabolite of clobazam) can occur when combined with cannabidiol, likely mediated by CYP2C19 inhibition. Increased systemic levels of these active substances may lead to enhanced pharmacological effects and to an increase in adverse drug reactions. Concomitant use of cannabidiol and clobazam increases the incidence of somnolence and sedation. Reduction in dose of clobazam should be considered if somnolence or sedation are experienced when clobazam is co-administered with cannabidiol.
CYP 2D6 substrates
Clobazam is a weak CYP2D6 inhibitor. Dose adjustment of drugs metabolized by CYP2D6 (e.g.
dextromethorphan, pimozide, paroxetine, nebivolol) may be necessary.