Extended-Release Tacrolimus Versus LifeCycle Pharma Tacrolimus in Kidney Transplant Recipients: A Switch Study

BACKGROUND: Tacrolimus is a first-line immunosuppressant used in kidney transplantation. However, its narrow therapeutic window and variable exposure present challenges. Extended- and prolonged-release formulations, ER-tacrolimus (Advagraf) and LCP-tacrolimus (Envarsus), respectively, improve adherence, and LCP-tacrolimus provides higher bioavailability. The safety and benefits of switching from ER-tacrolimus to LCP-tacrolimus were evaluated. METHODS: In this open-label switch study, first-time, adult, kidney transplant recipients with stable graft function, therapeutic ER-tacrolimus levels, and rapid metabolizer status (C/D ratio <1.05) were switched to LCP-tacrolimus, followed by reconversion to ER-tacrolimus after 3 weeks. The primary outcome was the dose required to maintain therapeutic trough levels; secondary outcomes included differences in adverse effects, pill burden, patient preference, and pharmacokinetics (tacrolimus trough concentration, C0; peak blood levels, Cmax; area under the concentration-time curve, AUC). RESULTS: Twelve patients were included. The dose to achieve therapeutic C0 (5-8 µg/L) was 30% lower with LCP-tacrolimus than with ER-tacrolimus (6.0 mg versus 8.5 mg, P = 0.004), with similar pill burden and adverse effects. AUC or Cmax were similar [LCP-tac: 14.75 (11.68-16.27); ER-tac: 17.15 (13.53-20.93)]. For CYP3A5 expressors (n = 7; 58%), there was a stronger correlation between C0 and AUC for LCP-tacrolimus (0.85, P = 0.016; 0.43, P = 0.34, respectively). No serious adverse events were observed. CONCLUSIONS: Conversion to LCP-tacrolimus with a 30% dose reduction achieved therapeutic C0 without differences in pill burden or overall exposure. In the CYP3A5 expressors, C0 was more strongly correlated with exposure to LCP-tacrolimus, suggesting more reliable trough monitoring. The small sample size, short follow-up period, and selection bias limit interpretation.