Abstract Details

Title Lack of Effect of Lacosamide on the Pharmacokinetic and Pharmacodynamic Profiles of Warfarin

Topic Epilepsy

Presentation(s) P04 - (-)

Poster/Presentation
Number 202

Objective

Background BACKGROUND: Warfarin is a widely used anticoagulant prescribed most often in the elderly and is prone to drug-drug interactions that can alter its anticoagulant activity. Warfarin is administered as a racemate but the anticoagulant effect is mostly due to the S enantiomer. Lacosamide is an antiepileptic drug approved for the adjunctive treatment of partial-onset seizures in adults. Co-administration of warfarin and lacosamide is expected, particularly in elderly populations.

Design/Methods DESIGN/METHODS: In this Phase I, open-label, randomized, 2-way crossover study, 16 healthy adult male volunteers received a single 25 mg dose of warfarin, either alone or co-administered with lacosamide following multiple doses of lacosamide 200 mg twice daily. Plasma concentrations of S- and R- warfarin, prothrombin time (PT) and international normalized ratio (INR) were determined serially over time. PK and PD parameters with and without lacosamide were statistically compared, using standard bioequivalence criteria. Tolerability and safety were monitored by recording vital signs, laboratory values, electrocardiograms (ECGs) and treatment-emergent adverse events (TEAEs).

Results RESULTS: All volunteers completed the study. Cmax and AUC of S- and R-warfarin, as well as peak value and AUC of PT and INR, following warfarin and lacosamide co-administration were equivalent to those after warfarin alone. In particular, the AUC ratio (90% confidence interval) was 0.97 (0.94-1.00) for S-warfarin, and 1.04 (1.01-1.06) for INR. There were no serious TEAEs or discontinuations due to TEAEs. No clinically relevant changes from baseline in laboratory, vital signs or ECG measurements were observed.

Conclusions CONCLUSIONS: Co-administration of lacosamide 400 mg/day did not alter the PK of warfarin or the anticoagulation level. These results suggest there is no need for dose adjustment of warfarin when co-administered with lacosamide.

Authors/Disclosures
PRESENTER	No disclosure on file
Matthew D. Cykowski, MD (Houston Methodist Hospital)	No disclosure on file
	No disclosure on file
	No disclosure on file
Thomas Kumke	No disclosure on file
Stefan M. Pulst, MD, FAAN (University of Utah)	Dr. Pulst has received personal compensation in the range of $500-$4,999 for serving as a Consultant for venrock. Dr. Pulst has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Arrowhead. Dr. Pulst has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Leverna. Dr. Pulst has received personal compensation in the range of $10,000-$49,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for AAN. Dr. Pulst has received personal compensation in the range of $500-$4,999 for serving as an Expert Witness for Leninthal LLC. The institution of Dr. Pulst has received research support from NINDS. Dr. Pulst has received intellectual property interests from a discovery or technology relating to health care.
	No disclosure on file

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