Apixaban in patients on haemodialysis: a single-dose pharmacokinetics study

Background. Apixaban, a direct oral anticoagulant inhibiting factor Xa, has been proven to reduce the risk of atrial fibrillation-related stroke and thromboembolism in patients with mild to moderate renal insufficiency. Patients on renal replacement therapy, however, were excluded from randomized controlled trials. Therefore, uncertainty remains concerning benefits, dosing and timing of intake in haemodialysis population. Methods. We conducted a Phase II pharmacokinetics study in which 24 patients on maintenance haemodialysis were given a single dose (2.5 mg or 5 mg) of apixaban, either 30min before or immediately after dialysis on the mid-week dialysis day. Results. Apixaban 5mg resulted in higher area under the curve (AUC(0-48)) in comparison with 2.5mg, although significance could only be reached for dosing pre-dialysis (2.5mg versus 5mg, P=0.008). In line, peak concentrations (C-max) after dosing pre-dialysis were significantly higher in the 5mg than in the 2.5mg groups (P=0.02). In addition, dialysis resulted in significant reduction of drug exposure. AUC(0-48) pre-dialysis were on average 48% (2.5mg) and 26% (5mg) lower than the AUC(0-48) post-dialysis, in line with C-max. As a result, a dose of 2.5mg post-dialysis and a dose of 5mg pre-dialysis resulted in similar AUC(0-48). In contrast, significant differences were found between the 5mg group post-dialysis and the 2.5mg group pre-dialysis (P=0.02). Conclusions. Our data suggest that exposure to apixaban in patients on maintenance haemodialysis is dependent not only on drug dose but also on timing of intake relative to the haemodialysis procedure.

Automated summary

The study findings suggest that exposure to apixaban in patients on maintenance haemodialysis is not only dependent on drug dose, but also on timing of intake relative to the haemodialysis procedure.