Trileptal

Trileptal Drug Interactions

oxcarbazepine

Manufacturer:

Novartis

Distributor:

DKSH
Full Prescribing Info
Drug Interactions
Enzyme inhibition: Oxcarbazepine was evaluated in human liver microsomes to determine its capacity to inhibit the major cytochrome P450 enzymes responsible for the metabolism of other drugs. The results demonstrate that oxcarbazepine and its pharmacologically active metabolite (the monohydroxy derivative, MHD) inhibit CYP2C19. Therefore, interactions could arise when co-administering high doses of Trileptal with drugs that are metabolized by CYP2C19 (e.g. phenobarbital, phenytoin, see as follows). In some patients treated with Trileptal and drugs metabolized via CYP2C19 dose reduction of the co-administered drugs might be necessary. In human liver microsomes, oxcarbazepine and MHD have little or no capacity to function as inhibitors for the following enzymes: CYP1A2, CYP2A6, CYP2C9, CYP2D6, CYP2E1, CYP4A9 and CYP4A11.
Enzyme induction: Oxcarbazepine and MHD induce, in vitro and in vivo, cytochromes CYP3A4 and CYP3A5 responsible for the metabolism of dihydropyridine calcium antagonists, oral contraceptives, and antiepileptic drugs (e.g. carbamazepine), resulting in a lower plasma concentration of these drugs (see as follows). A decrease in plasma concentrations may also be observed for other drugs mainly metabolized by CYP3A4 and CYP3A5, for example immunosuppressants (e.g. ciclosporin).
In vitro, oxcarbazepine and MHD are weak inducers of UDP-glucuronyl transferase. Therefore, in vivo they are unlikely to have an effect on drugs which are mainly eliminated by conjugation through the UDP-glucuronyl transferases (e.g. valproic acid, lamotrigine). Even in view of the weak induction potential of oxcarbazepine and MHD, a higher dose of concomitantly used drugs which are metabolized via CYP3A4 or via conjugation (UDPGT) may be necessary. In the case of discontinuation of Trileptal therapy, a dose reduction of the concomitant medication may be necessary.
Induction studies conducted with human hepatocytes confirmed oxcarbazepine and MHD as weak inducers of isoenzymes of the 2B and 3A4 CYP sub-family. The induction potential of oxcarbazepine/MHD on other CYP isoenzymes is not known.
Antiepileptic drugs and enzyme inducing drugs: Potential interactions between Trileptal and other antiepileptic drugs were assessed in clinical studies. The effect of these interactions on mean AUCs and Cmin are summarized in the following Table 2. (See Table 2.)

Click on icon to see table/diagram/image

In vivo, plasma levels of phenytoin increased by up to 40% when Trileptal was given at doses above 1,200 mg/day. Therefore, when using doses of Trileptal greater than 1,200 mg/day during adjunctive therapy, a decrease in the dose of phenytoin may be required (see DOSAGE & ADMINISTRATION). The increase in the phenobarbital level, however, is small (15%) when given with Trileptal.
Strong inducers of cytochrome P450 enzymes and/or UGT (e.g. rifampicin, carbamazepine, phenytoin and phenobarbital) have been shown to decrease the plasma/serum levels of MHD (29-49%).
No autoinduction has been observed with Trileptal.
Hormonal contraceptives: Trileptal was shown to have an influence on the two components, ethinylestradiol (EE) and levonorgestrel (LNG), of an oral contraceptive. The mean AUC values of EE and LNG were decreased by 48-52% and 32-52%, respectively. Studies with other oral or implant contraceptives have not been conducted. Therefore, concurrent use of Trileptal with hormonal contraceptives may render these contraceptives ineffective (see USE IN PREGNANCY & LACTATION).
Calcium antagonists: After repeated co-administration of Trileptal, the AUC values of felodipine were lowered by 28%. However, the plasma levels remained in the recommended therapeutic range.
On the other hand, verapamil produced a decrease of 20% in the plasma levels of MHD. This decrease in MHD plasma levels is not considered to be of clinical relevance.
Other drug interactions: Cimetidine, erythromycin and dextropropoxyphene had no effect on the pharmacokinetics of MHD, whereas viloxazine produced minor changes in the MHD plasma levels (about 10% higher after repeated co-administration). Results with warfarin show no evidence of interaction with either single or repeated doses of Trileptal.
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