Real-World Analysis of Potential Pharmacokinetic and Pharmacodynamic Drug Interactions with Apixaban in Patients with Non-Valvular Atrial Fibrillation.

Abstract

PurposeWe conducted this study to assess the real-world prevalence, nature, predictors, and clinical necessity of apixaban pharmacokinetic (PK) and pharmacodynamic (PD) drug interactions in patients with non-valvular atrial fibrillation (NVAF) at a tertiary medical institution in Saudi Arabia.Patients and MethodsAn observational retrospective cohort analysis was conducted in adult patients diagnosed with NVAF receiving apixaban for stroke prevention from the period of June 2015 to May 2019.ResultsOf the 1271 patients included in the analysis, 611 (48.1%) patients had potential PD– or PK–drug interactions with apixaban. Of those, 490 (38.6%) patients had potential PD drug–drug interactions (DDIs) and 121 (9.5%) patients had potential PK-DDIs. PD-DDIs with apixaban were mainly with antiplatelet therapy followed by non-steroidal anti-inflammatory drugs and antidepressants. PK-DDIs with apixaban were mainly with combined P-gp/CYP3A4 inhibitors or inducers. History of minor bleeding was positively correlated with PD-DDIs with apixaban, ß coefficient = 0.455 (OR 1.58; 95% CI 1.01–2.45); p<0.05. History of acute coronary syndrome was positively correlated with PD-DDIs with apixaban, ß coefficient = 0.515 (OR 1.60; 95% CI 1.36–1.99); p<0.05. History of heart failure was positively correlated with PK-DDIs with apixaban, ß coefficient = 0.459 (OR 1.58; 95% CI 1.07–2.35); p<0.05. Almost 15% of the included patients had no clinical indication to receive the potential interacting drug with apixaban and about 20% of them were assuming an inappropriate apixaban dose according to the product package insert.ConclusionPharmacodynamics and pharmacokinetics interactions are common in more than half of the patients with NVAF receiving apixaban for stroke prevention in this real-world analysis. Some of these interacting medications are not indicated. Drug–drug interactions should always be considered and monitored with apixaban with a regular assessment of the need for any interacting medication.