The Impact of Rivaroxaban and Apixaban on Tacrolimus Trough Levels

Abstract

The solid organ transplant community is slow to adopt the routine practice of using direct oral anticoagulants. Rivaroxaban and apixaban share common metabolic pathways with tacrolimus. This study aimed to clarify the impact of rivaroxaban/apixaban on tacrolimus troughs. Fifty solid organ transplant recipients with concomitant use of tacrolimus and rivaroxaban/apixaban were retrospectively assessed for changes in tacrolimus troughs and dose. Average dose-adjusted tacrolimus troughs and average tacrolimus total daily doses prior to and after rivaroxaban/apixaban initiation were compared. Subgroup analyses evaluating rivaroxaban and apixaban individually were performed. Rivaroxaban was prescribed to 18 recipients, and apixaban was prescribed to 32 recipients. 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). The median doseadjusted tacrolimus trough and tacrolimus total daily dose prior to rivaroxaban/apixaban initiation was 2.15 ng/mL/mg (IQR 1.17, 3.37) and 4 mg (IQR 1.88, 6.25), respectively. The median dose-adjusted tacrolimus trough and tacrolimus total daily dose after rivaroxaban/apixaban initiation was 2.16 ng/mL/mg (IQR 1.24, 4.10) and 3.55 mg (IQR 1.5, 6.35), respectively. No significant difference was found between average dose-adjusted tacrolimus troughs or tacrolimus total daily doses before and after rivaroxaban/apixaban initiation or in the individual subgroup analyses for rivaroxaban/apixaban. It is unlikely that initiating rivaroxaban/apixaban affects tacrolimus troughs or requires tacrolimus dose adjustment. This study does not elucidate if tacrolimus affects rivaroxaban/apixaban pharmacokinetics or pharmacodynamics.

A Review of Direct-acting Oral Anticoagulants and Their Use in Solid Organ Transplantation

“…In a similar study, Scheibner et al 99 retrospectively evaluated 50 SOT recipients receiving TAC with either rivaroxaban (n = 18) or apixaban (n = 32) for changes in TAC trough levels and doses. The median dose-adjusted TAC trough and total daily dose were not statistically different pre-DOAC use and post-DOAC use.…”

“…The authors concluded that it was unlikely that rivaroxaban or apixaban have an impact on the exposure of TAC in SOT recipients. 99…”

“…This study demonstrated that the DOACs have a minor impact on raising calcineurin inhibitor trough concentrations and recommended that clinicians monitor levels after starting and stopping a DOAC but felt that preemptive calcineurin inhibitor dose reductions were not necessary. 98 In a similar study, Scheibner et al 99 retrospectively evaluated 50 SOT recipients receiving TAC with either rivaroxaban (n = 18) or apixaban (n = 32) for changes in TAC trough levels and doses. The median dose-adjusted TAC trough and total daily dose were not statistically different pre-DOAC use and post-DOAC use.…”

“…The authors concluded that it was unlikely that rivaroxaban or apixaban have an impact on the exposure of TAC in SOT recipients. 99 Triazole antifungals are commonly administered in SOT recipients for prophylaxis against or treatment of invasive fungal infections. Azoles are considered moderate (fluconcazole) to strong (ie, ketoconazole, itraconazole, posaconazole, and voriconazole) CYP3A4 inhibitors.…”