From the Guidelines
When starting carbamazepine in a patient already taking Eloquis (apixaban), you should be concerned about a significant drug interaction that reduces Eloquis effectiveness, substantially increasing the risk of thrombotic events. Carbamazepine is a strong inducer of CYP3A4 and P-glycoprotein, which can decrease apixaban plasma concentrations, as reported in a study on drug interactions affecting oral anticoagulant use 1. This interaction typically begins within 1-2 weeks of starting carbamazepine and may persist for 2-3 weeks after discontinuation. Some key points to consider include:
- The risk of reduced drug exposure leading to an increased risk of thrombotic outcomes and lower efficacy, as seen with rifampin, a combined P-gp and strong CYP3A4 inducer 1
- The potential for strong inducers of CYP3A4 or P-gp to decrease apixaban plasma concentrations, increasing the risk of thrombotic events 1
- The recommendation to avoid the combination of apixaban with a strong CYP3A4 and P-gp inhibitor, or to reduce the dose of apixaban by 50% if on a regimen of 5–10 mg by mouth twice daily 1 Consider alternative anticonvulsants with fewer interactions (such as levetiracetam or lamotrigine) if possible. If carbamazepine is necessary, the patient may need a different anticoagulant like warfarin with INR monitoring. At minimum, monitor the patient closely for signs of thrombosis such as stroke symptoms, deep vein thrombosis, or pulmonary embolism. The patient should be educated about these risks and instructed to report any concerning symptoms immediately. This interaction represents a serious clinical concern that could compromise the intended anticoagulant protection.
From the FDA Drug Label
Concomitant use of carbamazepine with rivaroxaban, apixaban, dabigatran, and edoxaban (direct acting oral anticoagulants) is expected to result in decreased plasma concentrations of these anticoagulants that may be insufficient to achieve the intended therapeutic effect. In general, coadministration of carbamazepine with rivaroxaban, apixaban, dabigatran, and edoxaban should be avoided
- Eloquis (apixaban) is a direct acting oral anticoagulant.
- Starting carbamazepine on a patient who is already on Eloquis may result in decreased plasma concentrations of Eloquis, which may be insufficient to achieve the intended therapeutic effect.
- Coadministration of carbamazepine with Eloquis should be avoided 2.
From the Research
Concerns with Concomitant Use of Carbamazepine and Eloquis
When starting carbamazepine on a patient who is already on Eloquis (apixaban), several concerns arise due to potential drug-drug interactions.
- The concomitant use of carbamazepine and apixaban may lead to subtherapeutic concentrations of apixaban, increasing the risk of treatment failure 3, 4.
- Carbamazepine is known to induce cytochrome P450 enzymes, which can affect the metabolism of apixaban, although apixaban's metabolic drug-drug interaction potential is considered low 5.
- Studies have shown that carbamazepine can significantly reduce apixaban concentrations, and this interaction may occur over 2-4 weeks 4.
- It is recommended to avoid the combination of carbamazepine and apixaban unless apixaban concentrations can be assessed using a calibrated assay 4.
- In some cases, switching to an alternative anticoagulant, such as edoxaban, may be considered, as it has shown no significant interaction with carbamazepine 3.
Monitoring and Management
- Close monitoring of the patient's international normalized ratio (INR) and apixaban concentrations is crucial when concomitantly using carbamazepine and apixaban.
- Dose adjustments of apixaban may be necessary to maintain therapeutic concentrations, and the patient's response to the medication should be closely monitored 4.
- Healthcare providers should be aware of the potential for drug-drug interactions and take steps to minimize the risks associated with concomitant use of carbamazepine and apixaban.