*Purpose: To clarify the pharmacokinetic impact of rivaroxaban (RIVA) and apixaban (APIX) on tacrolimus (TAC) concentrations.

*Methods: Solid organ transplant recipients 18-years or older who were started on either RIVA or APIX while taking TAC between January 2014 and August 2018 were retrospectively reviewed. Recipients were excluded if they did not have a TAC trough within six months before and after RIVA/APIX initiation. The average dose-adjusted TAC trough and average TAC total daily dose prior to and after starting RIVA/APIX were compared using the sign test. The average dose-adjusted TAC trough was defined as an average of the TAC troughs divided by the TAC total daily doses. Baseline patient characteristics, incidence of acute kidney injury, and incidence of allograft rejection within six months after RIVA/APIX initiation were collected. Subgroup analyses evaluating RIVA and APIX individually were also performed.

*Results: A total of fifty solid organ transplant recipients met inclusion criteria (RIVA = 18, APIX = 32). Transplanted organs included kidney (n = 22), lung (n=18), liver (n = 7), simultaneous pancreas and kidney (n = 1), and simultaneous kidney and liver (n = 2). At the time of RIVA/APIX initiation, the median age was 64.5 years (IQR 58, 68.3), median time since transplant was 2.7 years (IQR 1.1, 7.3), and estimated creatinine clearance was 52.5 mL/min (IQR 39.9, 68.5). The mean body weight was 83.2 kg (SD ± 21.6), and the mean BMI was 29.7 kg/m² (SD ± 7.2). The median dose-adjusted TAC troughs prior to and after RIVA/APIX initiation were 2.15 ng/mL/mg (IQR 1.17, 3.37) and 2.16 ng/mL/mg (IQR 1.24, 4.10), respectively. The TAC total daily doses prior to and after RIVA/APIX initiation were 4 mg (IQR 1.88, 6.25) and 3.55 mg (IQR 1.5, 6.35), respectively. No significant difference was found between these outcomes or in individual subgroup analyses for RIVA and APIX. Of note, 28% (14/50) of patients developed an acute kidney injury within the first six months after RIVA/APIX initiation and one kidney transplant recipient was diagnosed with rejection. RIVA/APIX doses were inappropriate based on renal function per FDA guidelines in 28.5% (4/14) of patients diagnosed with an acute kidney injury.

*Conclusions: Based on these results, it is unlikely that initiating APIX or RIVA affects TAC pharmacokinetics or requires TAC dose adjustment. Additionally, kidney function should be carefully monitored for all patients taking these anticoagulants to guide the need for RIVA/APIX dose adjustment. To our knowledge, this was the largest study evaluating the pharmacokinetic impact of RIVA/APIX on TAC. This study does not elucidate if TAC affects RIVA or APIX pharmacokinetics or pharmacodynamics.

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