Potential interactions between Trileptal and other AEDs were assessed in clinical studies. The effect of these interactions on mean AUCs and Cmin are summarized in Table3.
Table3: Summary of AED Interactions with Trileptal®
| AED |
| Dose of AED |
| Trileptal Dose |
| Influence of |
Trileptal on AED
| Influence of |
AED on MHD
|Carbamazepine||400-2000||900||nc1||40% decrease |
[CI: 17% decrease,
|Phenobarbital||100-150||600-1800||14% increase |
[CI: 2% increase,
|25% decrease |
[CI: 12% decrease,
up to 40%
[CI: 12% increase,
|30% decrease |
[CI: 3% decrease,
|Valproic acid||400-2800||600-1800||nc1||18% decrease |
[CI: 13% decrease,
1 nc denotes a mean change of less than 10%
3 Mean increase in adults at high Trileptal doses
In vivo, the plasma levels of phenytoin increased by up to 40% when Trileptal was given at doses above 1200 mg/day. Therefore, when using doses of Trileptal greater than 1200 mg/day during adjunctive therapy, a decrease in the dose of phenytoin may be required. The increase of phenobarbital level, however, is small (15%) when given with Trileptal.
Strong inducers of cytochrome P450 enzymes (i.e., carbamazepine, phenytoin and phenobarbital) have been shown to decrease the plasma levels of MHD (29%-40%).
No autoinduction has been observed with Trileptal.
Coadministration of Trileptal with an oral contraceptive has been shown to influence the plasma concentrations of the two hormonal components, ethinylestradiol (EE) and levonorgestrel (LNG). The mean AUC values of EE were decreased by 48% [90% CI: 22-65] in one study and 52% [90% CI: 38-52] in another study. The mean AUC values of LNG were decreased by 32% [90% CI: 20-45] in one study and 52% [90% CI: 42-52] in another study. Therefore, concurrent use of Trileptal with hormonal contraceptives may render these contraceptives less effective (see Drug Interactions subsection). Studies with other oral or implant contraceptives have not been conducted.
After repeated coadministration of Trileptal, the AUC of felodipine was lowered by 28% [90% CI: 20-33].
Verapamil produced a decrease of 20% [90% CI: 18-27] of the plasma levels of MHD.
Other Drug Interactions
Cimetidine, erythromycin and dextropropoxyphene had no effect on the pharmacokinetics of MHD. Results with warfarin show no evidence of interaction with either single or repeated doses of Trileptal.
Drug/Laboratory Test Interactions
There are no known interactions of Trileptal with commonly used laboratory tests.