Apixaban Concentration with and without Coadministration of Carbamazepine: A Case with No Apparent Interaction

The direct-acting oral anticoagulants (DOACs) have many advantages over warfarin. In particular, apixaban has rapid onset (1–3 h) and offset (half-life 8–15 h) of action, with predictable dosing, which precludes the need for routine coagulation monitoring.1 In contrast to warfarin, which has numerous drug–drug interactions, apixaban has fewer reported drug–drug interactions.2,3 Apixaban is primarily metabolized by the cytochrome P450 isozymes CYP3A4 and CYP3A5 and is a substrate for the P-glycoprotein (P-gp) transport protein.4 Drugs that are strong inhibitors or inducers of both CYP3A4 and P-gp are reported to increase and decrease apixaban concentrations, respectively. The manufacturer’s product monograph states that strong inhibitors of both these pathways are contraindicated in combination with apixaban, whereas those that are strong inducers (such as carbamazepine) should “generally be avoided” given the likelihood of reduced apixaban concentrations4; however, there are no specific data describing this interaction.