Absence of interaction between rivaroxaban, tacrolimus and everolimus in renal transplant recipients with deep vein thrombosis or atrial fibrillation

• Published in: Vascular pharmacology 2020-07, Vol.130, p.106682, Article 106682
• Main Authors: Camporese, G., Bernardi, D., Bernardi, E., Avruscio, G.P., Marchini, F., Bonfante, L., Furian, L., Neri, F., Villalta, S., Fabris, F., Simioni, P., Sartori, M.T.
• Format: Article
• Language: English
• Subjects: Anticoagulants; Bleeding; Complications; Creatinine; Fibrillation; Immunosuppressants; Immunosuppressive agents; Kidney transplantation; Pharmacokinetics; Renal function; Renal transplantation; Rivaroxaban; Tacrolimus; Thromboembolism; Thrombosis; Toxicity; Variability; Venous thromboembolism
• ISSN: 1537-1891; 1879-3649
• DOI: 10.1016/j.vph.2020.106682

No data are available on rivaroxaban use in renal transplant recipients and on its surmised interaction with immunosuppressants. The aim was to investigate potential interactions between rivaroxaban and immunosuppressants in this setting. Renal transplant recipients with a stable renal function treated with rivaroxaban and tacrolimus with or without everolimus were investigated. All drugs and creatinine concentrations were determined daily for 2 weeks after the start of anticoagulation. Blood samples were drawn at 8.00 am and 3–4 h later for trough and peak concentrations, respectively. Bleeding and thrombotic events were recorded during a minimum follow-up of 6 months. In 8 renal transplant patients, rivaroxaban levels showed a predictable pharmacokinetic trend, both at Ctrough (30–61 μg/L) and at Cpeak (143–449 μg/L), with limited variability in the 25th–75th percentile range. Tacrolimus (Ctrough 3–13 μg/L; Cpeak 3–16 μg/L), everolimus (Ctrough 3–11 μg/L; Cpeak 5–17 μg/L) and creatinine concentrations were stable as well. Immunosuppressors variability before and after rivaroxaban were 30% and 30% for tacrolimus, 27% and 29% for everolimus, respectively, as well as 14% and 3% for creatinine. For rivaroxaban monitoring, the reference change value better performed in identifying significant variations of its concentration. No patient had bleeding or thrombotic events, worsening of renal graft function, and signs of immunosuppressants toxicity during a mean follow-up of 23 (9–28) months. In conclusion, rivaroxaban does not seem to interact with tacrolimus and everolimus in renal transplant recipients. Both anticoagulant and immunosuppressive effects seem warranted, without major bleeding complications and effect on the graft function. [Display omitted]