Lack of effect of lacosamide on the pharmacokinetic and pharmacodynamic profiles of warfarin. Issue 7 (24th April 2013)

• Record Type: Journal Article
• Authors: Stockis, Armel; van Lier, Jan Jaap; Cawello, Willi; Kumke, Thomas; Eckhardt, Klaus
• Is Part Of: Epilepsia. Volume 54:Issue 7(2013:Jul.)
• Page Start: 1161
• Page End: 1166
• Publication Date: 2013-04-24
• Subjects: Epilepsy -- Periodicals; 616.853
• DOI: 10.1111/epi.12192
• Languages: English
• ISSNs: 0013-9580

Abstract

<abstract abstract-type="main" id="epi12192-abs-0001"> <title>Summary</title> <sec id="epi12192-sec-0001" sec-type="section"> <title>Purpose</title> <p>The aim of this study was to evaluate the effect of the antiepileptic drug lacosamide on the pharmacokinetics and pharmacodynamics of the anticoagulant warfarin.</p> </sec> <sec id="epi12192-sec-0002" sec-type="section"> <title>Methods</title> <p>In this open‐label, two‐treatment crossover study, 16 healthy adult male volunteers were randomized to receive a single 25‐mg dose of warfarin alone in one period and lacosamide 200 mg twice daily on days 1–9 with a single 25 mg dose of warfarin coadministered on day 3 in the other period. There was a 2‐week washout between treatments. Pharmacokinetic end points were area under the plasma concentration–time curve (AUC<sub>(0, last)</sub> and AUC<sub>(0, ∞)</sub>) and maximum plasma concentration (C<sub>max</sub>) for S‐ and R‐warfarin. Pharmacodynamic end points were area under the international normalized ratio (INR)–time curve (AUC<sub>INR</sub>), maximum INR (INR<sub>max</sub>), maximum prothrombin time (PT<sub>max</sub>) and area under the PT‐time curve (AUC<sub>PT</sub>).</p> </sec> <sec id="epi12192-sec-0003" sec-type="section"> <title>Key Findings</title> <p>Following warfarin and lacosamide coadministration, C<sub>max</sub> and AUC of S‐ and R‐warfarin, as well as peak value and AUC of PT and INR, were equivalent to those after warfarin alone. In particular, the AUC<sub>(0, ∞)</sub> ratio (90% confidence interval) for coadministration of warfarin and lacosamide versus warfarin alone was 0.97 (0.94–1.00) for S‐warfarin and 1.05 (1.02–1.09) for R‐warfarin, and the AUC<sub>INR</sub> ratio was 1.04 (1.01–1.06). All participants completed the study.</p> </sec> <sec id="epi12192-sec-0004" sec-type="section"> <title>Significance</title> <p>Coadministration of lacosamide 400 mg/day did not alter the pharmacokinetics of warfarin 25 mg or the anticoagulation level. These results suggest that there is no need for dose adjustment of warfarin when coadministered with lacosamide.</p> </sec> </abstract>