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Drug interactions and pharmacogenetic factors contribute to variation in apixaban concentration in atrial fibrillation patients in routine care
In this study, we assessed the impact of interacting medication and pharmacogenetic variation to better explain apixaban concentration differences among 358 Caucasian AF patients. Genotyping (ABCG2,ABCB1,CYP3A4*22,CYP3A5*3) was performed by TaqMan assays, and apixaban quantified by mass spectrometry. The typical patient was on average 77.2  years old, 85.5 kg, and had a serum creatinine of 103.1 µmol/L. Concomitant amiodarone, an antiarrhythmic agent and moderate CYP3A/ABCB1 inhibitor, the impaired-function variantABCG2 c.421C  >  A, and sex predicted higher apixaban concentrations when controlling for age, weig...
Source: Journal of Thrombosis and Thrombolysis - January 18, 2020 Category: Hematology Source Type: research

The real world use of combined P-glycoprotein and moderate CYP3A4 inhibitors with rivaroxaban or apixaban increases bleeding
AbstractThe use of direct oral anticoagulants for stroke prevention in atrial fibrillation continues to rise. Certain populations may be at higher risk for increased drug exposure and adverse events. Pharmacokinetic studies suggest increased exposure of rivaroxaban and apixaban with combined P-gp and moderate CYP3A4 inhibitors but the clinical relevance of this is unknown. This retrospective cohort study included patients receiving rivaroxaban or apixaban from January 1, 2012 to December 31, 2016 with a moderate inhibitor (amiodarone, dronedarone, diltiazem, verapamil) for at least 3 months in the drug –drug interaction ...
Source: Journal of Thrombosis and Thrombolysis - January 9, 2020 Category: Hematology Source Type: research