Real-World Impact of Amiodarone on Apixaban Population Pharmacokinetics in Hospitalized Patients

Despite common coadministration in nonvalvular atrial fibrillation (NVAF), there is minimal evidence regarding the impact of concomitant amiodarone use on apixaban pharmacokinetics (PK). We described the population PK of apixaban (2.5 and 5 mg twice daily) in 106 hospitalized patients with and without concomitant amiodarone administration at steady state. Apixaban PK was reasonably described by a one-compartment model with first-order absorption and linear elimination. Aside from the receipt of amiodarone, age was retained as a statistically significant covariate on apparent clearance. Model-based simulations depicted concomitant amiodarone use increasing AUC_T for both 2.5 mg (1.58, 90% CI [1.28, 1.87]) and 5 mg (1.12, 90% CI [0.91, 1.34]) dosing groups based on geometric mean ratios relative to the apixaban only groups. Similarly, C_max was also increased for both 2.5 mg (1.48, 90% CI [1.21, 1.75]) and 5 mg (1.09, 90% CI [0.92, 1.27]) dose groups. Lastly, concomitant amiodarone increased C_min for both 2.5 mg (1.68, 90% CI [1.35, 2]) and 5 mg (1.11, 90% CI [0.85, 1.37]) dose groups. Overall differences in apixaban exposures do not appear to be clinically significant across both dosing regimens, but amiodarone coadministration was found to decrease apixaban clearance by 33% (ranging from 12% to 48%). The results support the current practice of no empiric dose adjustment for apixaban when concurrently administered with amiodarone.