15th Congress of the European Association for Clinical Pharmacology and Therapeutics (EACPT)
Abstract
Introduction: Apixaban and rivaroxaban, two oral direct factor Xa inhibitors (DOACs), have become an alternative to vitamin K antagonists because of their ease of use.However, safety and efficacy concerns have emerged with the availability of real-world data, particularly regarding their concomitant use with other drugs which may cause bleeding or with CYP3A and/or P-gp modulators.While age, weight and renal function are known factors for dose adjustment, CYP3A/P-gp genotypic and phenotypic activities are not routinely considered although they are involved in their metabolism and transport.Objectives: We aimed to determine whether CYP3A/P-gp genotypes and phenotypic activities could have a significant impact on apixaban and rivaroxaban blood exposure.Methods: This real-life observational study included 164 and 136 hospitalized patients treated with apixaban or rivaroxaban, respectively.CYP3A and P-gp phenotypic activities were assessed with the Geneva cocktail administered orally on the day of the study.Capillary blood samples were collected at t0 and 2h, 3h and 6h after cocktail administration to assess OH-midazolam/midazolam (CYP3A) metabolic ratios (MR) and fexofenadine (P-gp) AUC, and to assess apixaban and rivaroxaban blood concentrations.CYP3A and P-gp genetic polymorphisms were also measured.Results: Substantial interindividual variability was observed in dosenormalized blood concentrations and AUC of apixaban (117.4±55.9ng/ mL) and rivaroxaban (once a day:…
How strong is the evidence?
Evidence Hub reads this as a cohort study, done in people. Its evidence level is 3 of 5 (Moderate · trial / cohort / secondary analysis). Trials without a large randomized design, cohorts and secondary analyses give moderate evidence. Reported size: 136 participants or records.
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