From the Guidelines
Eliquis (apixaban) can interact with certain seizure medications, potentially requiring dose adjustments or alternative treatments, with the most significant interactions occurring with enzyme-inducing antiepileptic drugs like carbamazepine, phenytoin, phenobarbital, and primidone, which can substantially reduce Eliquis levels in the blood by up to 50%. According to a recent study published in Circulation: Arrhythmia and Electrophysiology 1, apixaban is a substrate for P-gp and undergoes some metabolism via CYP3A4, which can create clinically relevant drug interactions. Some key points to consider when taking Eliquis with seizure medications include:
- Enzyme-inducing antiepileptic drugs like carbamazepine, phenytoin, phenobarbital, and primidone can substantially reduce Eliquis levels in the blood by up to 50%, making it less effective at preventing blood clots 1.
- Other seizure medications like lamotrigine, levetiracetam, and valproic acid generally have minimal interactions with Eliquis and are safer options.
- These interactions occur because enzyme-inducing seizure medications activate liver enzymes that speed up the breakdown of Eliquis, reducing its concentration in your bloodstream.
- Always inform all your healthcare providers about all medications you take, and never adjust doses without medical supervision, as improper anticoagulation can lead to serious bleeding risks or clotting events. It is essential to note that the study 1 provides a useful algorithm to quickly screen for clinically significant DOAC interactions, which can help healthcare providers make informed decisions about treatment. In certain clinical scenarios, when a combination is unavoidable, plasma level assessment of the DOAC is an option, but this should only be done at specialized centers with expertise in this area 1.
From the FDA Drug Label
- 2 Combined P-gp Strong CYP3A4 Inducers Avoid concomitant use of apixaban tablets with combined P-gp and strong CYP3A4 Inducers (e.g., rifampin, carbamazepine, phenytoin, St. John’s wort) because such drugs will decrease exposure to apixaban [see Clinical Pharmacology (12.3)].
Eliquis (apixaban) has interactions with certain seizure medications that are combined P-gp and strong CYP3A4 inducers, such as:
- Carbamazepine
- Phenytoin These medications may decrease exposure to apixaban and increase the risk of stroke and other thromboembolic events. Concomitant use of these medications with apixaban should be avoided 2.
From the Research
Eliquis Interaction with Seizure Medications
- Eliquis (apixaban) is a direct oral anticoagulant (DOAC) that may interact with seizure medications, also known as antiepileptic drugs (AEDs) 3, 4.
- The interaction between DOACs and AEDs can lead to an increased risk of bleeding or a reduced antithrombotic efficacy 3.
- Older AEDs, such as phenobarbital, phenytoin, and carbamazepine, are more likely to significantly reduce the anticoagulant effect of DOACs, including apixaban 3.
- Newer AEDs, such as lamotrigine, pregabalin, and levetiracetam, are less likely to affect DOACs efficacy, but their effects on P-glycoprotein are not well-known 3, 4.
- The concomitant use of DOACs and enzyme-inducing AEDs, such as carbamazepine and phenytoin, may lead to a reduced anticoagulant effect and an increased risk of thrombotic events 4, 5.
- Monitoring of DOAC plasma concentrations may be necessary in patients taking concomitant enzyme-inducing AEDs to guide dosing and minimize the risk of treatment failure 4.
- The European Society of Cardiology recommends avoiding the combination of DOACs with certain AEDs, such as levetiracetam and valproic acid, due to the risk of low DOAC concentrations 4.
- However, the clinical relevance of the interaction between DOACs and AEDs is not well-established, and further studies are needed to clarify their pharmacokinetic interactions and define the most appropriate clinical behavior 3, 5.