A Real-World Matched Cohort Study of the Effect of Concomitant Amiodarone or Diltiazem Administration on Apixaban Peak and Trough Concentrations.

Background: Apixaban is a substrate for p-glycoprotein and is extensively metabolized by cytochrome P450 (CYP) 3A4. There are minimal published data regarding the effect of amiodarone and diltiazem on apixaban serum concentrations.

Objective: The aim of this study was to determine the degree of elevation of apixaban concentrations resulting from amiodarone or diltiazem.

Methods: This was a matched cohort study approved by the Institutional Review Board. Patients receiving apixaban 5 mg twice daily with concomitant diltiazem or amiodarone were enrolled. Control groups were enrolled via matching characteristics of sex, age, weight, creatinine clearance, and statin therapy. Exclusions were an inappropriate dosage of apixaban or concomitant dronedarone, verapamil, ranolazine, naproxen, or both amiodarone and diltiazem. Blood samples were collected 3-4 h after and 0.5-2 h before an apixaban dose, corresponding to peak and trough concentrations, respectively. Results were compared using a t test.

Results: Thirty patients were enrolled in each of the four groups. The mean peak apixaban concentration was 239 ± 82 ng/mL in the amiodarone group and 208 ± 66 ng/mL in the corresponding control group (p = 0.068). Trough concentrations were 142 ± 71 ng/mL and 117 ± 41 ng/mL, respectively (p = 0.055). The mean peak apixaban concentration was 243 ± 99 ng/mL in the diltiazem group and 213 ± 82 ng/mL in the control group (p = 0.11). Trough concentrations were 130 ± 65 ng/mL and 108 ± 54 ng/mL, respectively (p = 0.09).

Conclusion: Coadministration of amiodarone and diltiazem resulted in a trend toward increased apixaban concentrations. The extent of elevation suggests that empiric dose changes are not necessary; however, individual patients may benefit from monitoring and dose adjustment.