Interactions Between Direct Oral Anticoagulants (DOACs) and Antiseizure Medications: Potential Implications on DOAC Treatment

AbstractThe use of direct oral anticoagulants (DOACs) is increasing because of their superior efficacy and safety compared with vitamin K antagonists. Pharmacokinetic drug interactions, particularly those involving cytochrome P450- mediated metabolism and  P-glycoprotein transport, significantly affect the efficacy and safety of DOACs. In this article, we assess the effects of cytochrome P450- and P-glycoprotein-inducing antiseizure medications on DOAC pharmacokinetics in comparison to rifampicin. Rifampicin decreases to a varying extent the plasma exposure (area under the concentration–time curve) and peak concentration of each DOAC, consistent with its specific absorption and elimination pathways. For apixaban and rivaroxaban, rifampicin had a greater effect on the area under the concentration–time curve than on peak concentration. There fore, using peak concentration to monitor DOAC concentrations may underestimate the effect of rifampicin on DOAC exposure. Antiseizure medications that are cytochrome P450 and P-glycoprotein inducers are commonly used with DOACs. Several studies have observed a correlation between the concomitant us e of DOACs and enzyme-inducing antiseizure medications and DOAC treatment failure, for example, ischemic and thrombotic events. The European Society of Cardiology recommends avoiding this combination, as well as the combination of DOACs with levetiracetam and valproic acid, owing to a risk of low DO AC concentrations. However, levetiracetam...

Source: CNS Drugs - March 3, 2023 Category: Neurology Source Type: research