Dabigatran treatment simulation in patients undergoing maintenance haemodialysis

Karl-Heinz Liesenfeld; Andreas Clemens; Joerg Kreuzer; Martina Brueckmann; Friedrich Schulze

doi:10.1160/th15-07-0531

Thrombosis and Haemostasis, Inhaltsverzeichnis

Thromb Haemost 2016; 115(03): 562-569
DOI: 10.1160/th15-07-0531

Coagulation and Fibrinolysis

Schattauer GmbH

Dabigatran treatment simulation in patients undergoing maintenance haemodialysis

Karl-Heinz Liesenfeld^*

¹Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach an der Riß, Germany

,

Andreas Clemens^*

²Center for Thrombosis and Haemostasis, University Medical Centre, Mainz, Germany

,

Joerg Kreuzer

³Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim, Germany

,

Martina Brueckmann

³Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim, Germany

⁴Faculty of Medicine Mannheim of the University of Heidelberg, Mannheim, Germany

,

Friedrich Schulze

³Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim, Germany

› Institutsangaben

Abstract

Summary

Patients with atrial fibrillation requiring maintenance haemodialysis are at increased risk of ischaemic stroke and bleeds. Currently, vitamin K antagonists such as warfarin are predominantly used in these patients as limited data are available on the use of non-vitamin K oral anticoagulants, including dabigatran etexilate (dabigatran). Dabigatran is approximately 85 % renally eliminated, thus, its half-life is prolonged in renal impairment. This study simulated the dose-exposure relationship of dabigatran in patients undergoing haemodialysis. Dabigatran exposure was modelled at once- and twice-daily doses of 75 mg, 110 mg and 150 mg and at variations in non-renal clearance and dialysis settings. Resultant dose exposure (area under the curve [AUC]) was compared with values simulated from typical patients in the RE-LY^® trial (based on a previously characterised pharmacometric model). In this simulation, all twice-daily dosages resulted in exposures above those simulated from typical RE-LY patients (1.5- to 3.3-fold increase in AUC) and thus may not be optimal for use in haemodialysis patients. However, dabigatran doses of 75 mg or 110 mg once daily produced exposures comparable to those simulated in typical RE-LY patients (-13.3 and +4.4 %, respectively). Of patient and dialysis variables, non-renal clearance had the highest impact on exposure (≤30.8 % change). These data could potentially inform dose selection in patients undergoing maintenance haemodialysis and the findings warrant investigation in future clinical trials.

Keywords

Dabigatran - end-stage renal disease - maintenance haemodialysis - atrial fibrillation - pharmacokinetics

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Referenzen

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