Pilot study on the probability of drug-drug interactions among direct oral anticoagulants (DOACs) and antiseizure medications (ASMs): a clinical perspective

Background: There is little and controversial information about changes in plasma concentrations (PCs) or clinical events during coadministration of antiseizure medications (ASMs) and direct oral anticoagulants (DOACs). We aimed to explore possible determinants of dosage class among DOACs trough PCs when ASMs are co-administered and the relative risks. We also provided some clinical examples of patients' management. Methods: Data on adult patients concomitantly treated with ASMs (grouped in enzyme-inducing [I-ASMs], non-inducing [nI-ASMs], and levetiracetam [LEV]) and DOACs with at least one measurement of DOACs' PC were retrospectively collected. The role of DOAC-ASM combinations in predicting PC class (ranging from I at ischemic/thromboembolic risk to IV at increased bleeding risk) was investigated by an ordered logit model, and the marginal probabilities of belonging to the four dosage classes were calculated. Results: We collected 46 DOACs' PCs out of 31 patients. There were 5 (10.9%) determinations in class I (4 out of 5 with concomitant I-ASMs) and 5 (10.9%) in class IV. The rivaroxaban/I-ASM combination was associated with lower DOAC dosages than rivaroxaban/LEV (OR: 0.00; 95% CI: 0.00-0.62). Furthermore, patient's probability of being in class I was approximately 50% with the rivaroxaban/I-ASM combination, while apixaban, dabigatran, and edoxaban had the highest cumulative probability of being in class II or III despite the ASM used. Conclusion: These preliminary results confirm the reduction of DOAC's PC by I-ASMs and suggest a better manageability of apixaban, dabigatran, and edoxaban independently from the concomitant ASM, whereas rivaroxaban seems the most liable to PC alterations with I-ASMs.