Key result
In patients on maintenance hemodialysis, apixaban exposure was significantly lower when administered 30 minutes before dialysis, with a 5 mg pre-dialysis dose resulting in similar exposure to a 2.5 mg post-dialysis dose.
Why the study?
Patients on renal replacement therapy were excluded from randomized controlled trials of apixaban, leaving uncertainty regarding its benefits, dosing, and timing of intake in the haemodialysis population.
Does the timing of apixaban administration relative to hemodialysis affect drug exposure in patients with end-stage renal disease?
Does the timing of apixaban administration relative to hemodialysis affect drug exposure in patients with end-stage renal disease?
p-value: p=0.008
Exposure to apixaban in hemodialysis patients is significantly reduced when administered before dialysis compared to after, suggesting timing of intake is critical for dosing.
May support adjusted pre- or post-dialysis apixaban dosing in hemodialysis; extends PK data but leaves clinical outcomes open.
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 30 min before or immediately after dialysis on the mid-week dialysis day. RESULTS: Apixaban 5 mg resulted in higher area under the curve (AUC0-48) in comparison with 2.5 mg, although significance could only be reached for dosing pre-dialysis (2.5 mg versus 5 mg, P = 0.008). In line, peak concentrations (Cmax) after dosing pre-dialysis were significantly higher in the 5 mg than in the 2.5 mg groups (P = 0.02). In addition, dialysis resulted in significant reduction of drug exposure. AUC0-48 pre-dialysis were on average 48% (2.5 mg) and 26% (5 mg) lower than the AUC0-48 post-dialysis, in line with Cmax. As a result, a dose of 2.5 mg post-dialysis and a dose of 5 mg pre-dialysis resulted in similar AUC0-48. In contrast, significant differences were found between the 5 mg group post-dialysis and the 2.5 mg 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.
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Bosch et al. (2020) studied End-stage renal disease on maintenance hemodialysis (n=24). Apixaban vs. Different timing (30 minutes pre-dialysis vs immediately post-dialysis) and doses was evaluated on Area under the curve (AUC 0-48) (p=0.008). In patients on maintenance hemodialysis, apixaban exposure was significantly lower when administered 30 minutes before dialysis, with a 5 mg pre-dialysis dose resulting in similar exposure to a 2.5 mg post-dialysis dose.
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