From the Guidelines
Trileptal (oxcarbazepine) is a potent inducer of CYP3A4 and P-gp, and its use is contraindicated with certain medications that are strongly induced or inhibited by these enzymes, such as rifampicin, rifabutin, St John’s wort, carbamazepine, phenobarbital, or phenytoin, as it may lead to decreased exposure and potential loss of efficacy of these medications 1.
Important Interactions
- Trileptal can decrease the effectiveness of hormonal contraceptives, potentially leading to unplanned pregnancy, so additional contraceptive methods are recommended.
- It may also interact with other antiepileptic medications like carbamazepine, phenytoin, and phenobarbital, requiring dose adjustments.
- Trileptal can enhance the effects of CNS depressants such as alcohol, benzodiazepines, and opioids, causing excessive sedation.
- Additionally, it may interact with certain antidepressants, antipsychotics, and medications metabolized by the CYP3A4 enzyme system.
- Monoamine oxidase inhibitors (MAOIs) should be avoided with Trileptal due to potential serious reactions.
Mechanism of Interactions
These interactions occur because Trileptal affects liver enzymes that metabolize many medications, either inducing or inhibiting their activity.
Clinical Implications
Patients should always inform healthcare providers about all medications they're taking, including over-the-counter drugs and supplements, to prevent potentially harmful interactions with Trileptal.
Key Considerations
- Concomitant use with medicinal products that are strong P-gp and/or strong CYP inducers is contraindicated due to the decrease in exposure of certain medications with the potential loss in efficacy 1.
- Moderate P-gp or CYP inducers, such as modafinil, efavirenz, oxcarbazepine, and others, which can also reduce exposure of certain medications, are not currently recommended.
From the FDA Drug Label
Drug Interactions: In Vitro Oxcarbazepine can inhibit CYP2C19 and induce CYP3A4/5 with potentially important effects on plasma concentrations of other drugs. In addition, several AEDs that are cytochrome P450 inducers can decrease plasma concentrations of oxcarbazepine and MHD.
In Vivo Other Antiepileptic Drugs Potential interactions between oxcarbazepine and other AEDs were assessed in clinical studies. The effect of these interactions on mean AUCs and Cmin are summarized in Table 7 [see Drug Interactions (7. 1,7. 2)]
Hormonal Contraceptives Coadministration of oxcarbazepine with an oral contraceptive has been shown to influence the plasma concentrations of the two hormonal components, ethinylestradiol (EE) and levonorgestrel (LNG) [see Drug Interactions (7. 3)].
Other Drug Interactions Calcium Antagonists: After repeated coadministration of oxcarbazepine, the AUC of felodipine was lowered by 28% [90% CI: 20 to 33]. Verapamil produced a decrease of 20% [90% CI: 18 to 27] of the plasma levels of MHD.
Trileptal (Oxcarbazepine) Drug Interactions:
- Inhibition of CYP2C19: Oxcarbazepine can inhibit CYP2C19, potentially increasing plasma concentrations of drugs that are substrates of CYP2C19.
- Induction of CYP3A4/5: Oxcarbazepine can induce CYP3A4/5, potentially decreasing plasma concentrations of drugs that are substrates of CYP3A4/5.
- Interactions with other AEDs: Potential interactions between oxcarbazepine and other AEDs have been assessed in clinical studies.
- Hormonal Contraceptives: Coadministration of oxcarbazepine with oral contraceptives can decrease the plasma concentrations of ethinylestradiol and levonorgestrel.
- Calcium Antagonists: Repeated coadministration of oxcarbazepine can decrease the AUC of felodipine and the plasma levels of MHD with verapamil. 2 2
From the Research
Trileptal Drug Interactions
- Trileptal (oxcarbazepine) has a lower propensity for drug interactions compared to other antiepileptic drugs, such as carbamazepine, due to its unique metabolism pathway 3, 4.
- Oxcarbazepine undergoes reductive metabolism at its keto moiety to form the monohydroxy derivative (MHD), which is glucuronidated and excreted in the urine, with minimal involvement of the hepatic cytochrome P450-dependent enzymes 3, 4.
- This limited involvement in the cytochrome P450 system reduces the risk of interactions with other drugs that are metabolized by this system, such as oral contraceptives and certain antipsychotic drugs 3, 5.
- However, interactions can still occur with other antiepileptic drugs, such as valproic acid, and with certain chemotherapeutic regimens, which can affect the efficacy and toxicity of both the antiepileptic and the chemotherapeutic agents 5, 6.
- Clinicians should be vigilant when prescribing Trileptal concurrently with other medications, and serum drug concentrations should be closely monitored to avoid toxicity and ensure adequate therapeutic coverage 6.
Specific Interactions
- Trileptal may interact with certain antipsychotic drugs, such as risperidone, olanzapine, and quetiapine, although the evidence is limited and more studies are needed to fully understand these interactions 5.
- Trileptal may also interact with certain chemotherapeutic regimens, such as those used to treat breast, colorectal, lung, and renal cell cancers, which can affect the efficacy and toxicity of both the antiepileptic and the chemotherapeutic agents 6.
- The risk of interactions with other medications can be minimized by selecting alternative antiepileptic drugs that are less likely to interact, and by closely monitoring serum drug concentrations and adjusting the dosage as needed 6.