Enzyme Inhibition: Oxcarbazepine and its pharmacologically active metabolite (MHD) inhibits CYP2C19. Interactions are thus possible if high doses of Trileptal are administered together with drugs metabolized by CYP2C19 (eg, phenytoin). Plasma levels of phenytoin increased by up to 40% when Trileptal was given at doses exceeding 1200 mg/day (see table). In such cases, it may be necessary to reduce the concomitantly administered dose of phenytoin (see Dosage & Administration).
Enzyme Induction: In vitro and in vivo, oxcarbazepine and MHD are weak inducers of cytochrome CYP3A4 and CYP3A5, which are primarily responsible for the metabolism of eg, dihydropyridine calcium channel blockers (eg, felodipine), immunosuppressants (eg, ciclosporin, tacrolimus), oral contraceptives (see as follows) and some other antiepileptics (eg, carbamazepine). This results in lower serum levels of these drugs (see table).
In vitro, oxcarbazepine and MHD are weak inducers of UDP-glucuronyl transferase (nonspecific UGT enzyme study). They therefore seem unlikely to have a clinically relevant effect in vivo on drugs that are mainly eliminated by conjugation via UDP glucuronyl transferases.
Even in view of the weak induction potential of oxcarbazepine and MHD, dose reduction of the concurrently administered drug may be necessary on discontinuation of Trileptal; this should be decided on the basis of clinical monitoring and determination of plasma levels.
Hormonal Contraceptives: Trileptal has been shown to affect ethinyloestradiol and levonorgestrel, the 2 components of a hormonal contraceptive. Mean AUC for ethinyloestradiol and levonorgestrel was lowered by 48-52% and 32-52%, respectively. Concurrent use with Trileptal may therefore render hormonal contraceptives ineffective (see Precautions). An alternative reliable method of contraception should therefore be used.
Other Antiepileptics: Possible interactions between Trileptal and other antiepileptics were investigated in clinical trials.
It was possible to show that strong inducers of cytochrome P450 (eg, carbamazepine, phenytoin and phenobarbital) lower plasma concentrations of MHD (29-40%).
In the event of concomitant administration of >1 antiepileptics with oxcarbazepine, careful dose adjustment and/or monitoring of plasma levels should be considered on an individual basis.
Effects on mean AUC and Cmin are summarized in the table.
Click on icon to see table/diagram/image
No autoinduction has been observed with Trileptal.
Other Drug Interactions: Cimetidine, erythromycin, viloxazine and dextropropoxyphene had no effect on the pharmacokinetics of MHD.
Patients treated with tricyclic antidepressants were included in the clinical trials; no clinically relevant interactions were observed.
Combining lithium with oxcarbazepine may lead to increased neurotoxicity.