*The investigators stated that the true impact of Cobi is larger than measured in this study due to a limitation of the TT assy used (i.e., upper limit of detection was 120 seconds), and therefore the AUEC increases were underestimated. Further analyses of pharmacokinetic changes of DE and their impact on DE pharmacodymanics are needed to better inform dosing recommendations.*Coadministration of these agents is discouraged at this time due to insufficient data and increased risk of bleeding. Caution is advised if utilizing this combination is necessary. Close monitoring of thrombin time is warranted.
Dabigatran vs cobicistat
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Study Design
This was a single-center, open-label, fixed-sequence intra-subject study in healthy adults (n=18) to characterize separated and concomitant administration of cobicistat (Cobi) on the pharmacodynamics of dabigatran etexilate (DE).In Phase 1, DE 150mg was administered alone on Day 0, followed by a 4-day washout period.In Phase 2, Cobi 150mg was administered on Days 5-19, with co-administration of DE 150mg on Day 19, 2 hours prior to Cobi administration.In Phase 3, Cobi 150mg was administered on days 20-26, withconcomitant administration of DE 150mg on Day 26.
Study Results
16 participants completed the study. Cobi co-administration resulted in statistically significant increases in Phase 2 and Phase 3 of 30% and 33%, respectively, in thrombin timearea-under-the-effect-curve(TT AUEC) compared to DE alone.Using geometric mean ratios and 90% confidence intervals, the TT AUEC for DE 2 hours prior to Cobi / DE alone was 1.30 [1.21, 1.39], while that for DE + Cobi / DE alone was 1.33 [1.22, 1.44].No difference was observed when Cobi was administered separately or concomitantly with DE.
References
Brooks KM, C Hadigan, Gordon LA, et al. Cobicistat increases the effects of dabigatran on thrombin time in healthy volunteers. Conference On Retroviruses And Opportunistic Infections. Boston, MA. ; 2016.
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