Does Trileptal (Oxcarbazepine) Induce Olanzapine Metabolism?
No, oxcarbazepine does not induce the metabolism of olanzapine and does not significantly affect olanzapine plasma concentrations. 1
Direct Evidence from Drug Interaction Studies
A prospective pharmacokinetic study specifically evaluated this interaction by administering oxcarbazepine (900-1,200 mg/day) for 5 consecutive weeks to patients stabilized on olanzapine (5-20 mg/day). 1 The results demonstrated:
- Olanzapine plasma levels remained essentially unchanged, increasing minimally from 26.5 ± 5.7 ng/ml at baseline to 27.8 ± 5.1 ng/ml after 5 weeks of oxcarbazepine coadministration 1
- This minimal change was not statistically significant 1
- The combination was well tolerated with no safety concerns 1
Mechanistic Explanation
The lack of interaction is explained by oxcarbazepine's distinct metabolic profile compared to its structural relative carbamazepine:
- Oxcarbazepine is only a weak inducer of cytochrome P450 enzymes, acting on a few specific isoforms (primarily CYP3A4 and CYP3A5) 2, 3, 4
- Oxcarbazepine undergoes nonoxidative metabolism via cytosolic hepatic reduction rather than CYP-mediated oxidation, resulting in a much lower enzyme-induction profile than carbamazepine 5, 3
- While oxcarbazepine can induce CYP3A4/3A5 and inhibit CYP2C19, these effects are insufficient to meaningfully alter olanzapine elimination 3, 4
Clinical Implications
No dose adjustment of olanzapine is required when initiating or discontinuing oxcarbazepine. 1 This represents a significant practical advantage over carbamazepine, which is a potent enzyme inducer that would be expected to substantially reduce olanzapine levels. 2
Common Pitfall to Avoid
Do not extrapolate carbamazepine's strong enzyme-inducing properties to oxcarbazepine—despite their structural similarity, their metabolic profiles differ substantially. 2, 5 Carbamazepine is a potent inducer of CYP450, epoxide hydrolase, and UDPGT enzyme systems, whereas oxcarbazepine has minimal inducing effects. 2