Details

Autor(en) / Beteiligte

• De Vriese, An S., MD, PhD
• Caluwé, Rogier, MD
• Bailleul, Els, MD
• De Bacquer, Dirk, PhD
• Borrey, Daniëlle, PhD
• Van Vlem, Bruno, MD, PhD
• Vandecasteele, Stefaan J., MD, PhD
• Emmerechts, Jan, MD, PhD

Titel

Dose-Finding Study of Rivaroxaban in Hemodialysis Patients

Ist Teil von

• American journal of kidney diseases, 2015-07, Vol.66 (1), p.91-98

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2015

Quelle

MEDLINE

Beschreibungen/Notizen

• Background Use of vitamin K antagonists for the prevention of stroke and systemic embolism in dialysis patients with nonvalvular atrial fibrillation is controversial. However, no good alternatives presently are available. The anti−factor Xa antagonist rivaroxaban is contraindicated for lack of pharmacokinetic, pharmacodynamic, and clinical data. This study aims to characterize the pharmacokinetics/pharmacodynamics of rivaroxaban in maintenance hemodialysis patients. Study Design Pharmacokinetic and pharmacodynamic study. Setting & Participants 18 maintenance hemodialysis patients without residual kidney function at 2 centers. Drug Administration, Outcomes, & Measurements (1) A single dose of 10 mg of rivaroxaban was administered at the end of each of 3 consecutive dialysis sessions and area under the curve (AUC) and the effect on coagulation parameters were measured for 44 hours thereafter. (2) A single dose of 10 mg of rivaroxaban was given 6 to 8 hours before a dialysis session and the effect of dialysis on rivaroxaban concentrations was evaluated. (3) To assess potential accumulation, 10 mg of rivaroxaban was given once daily and AUC was measured during 24 hours on days 1 and 7. Results Mean AUC0-44 of rivaroxaban plasma concentrations after a single dose of 10 mg was 2,072 μg/L/h, mean maximum concentration was 172.6 μg/L, and mean terminal elimination half-life was 8.6 hours. Dialysis had no appreciable effect on rivaroxaban plasma concentrations. Mean trough concentration after multiple daily doses of 10 mg was 20.2 μg/L. Limitations Higher rivaroxaban doses and patients with substantial residual kidney function were not studied. Conclusions A 10-mg dose of rivaroxaban in hemodialysis patients without residual kidney function results in drug exposure similar as published for 20 mg in healthy volunteers. Rivaroxaban is not eliminated by dialysis. There is no accumulation after multiple daily dosing. The efficacy and safety of rivaroxaban in hemodialysis patients should be the subject of a large randomized trial.