How to achieve optimal trough levels when switching calcineurin inhibitors (CNI) to everolimus (EVER): the 50%-per-week rule

Scanty data are available on the best schedule for switching calcineurin-inhibitors (CNI) to everolimus (EVER) in liver transplant (LT) patients. We explored prospectively introduction of EVER at a dosage of 0.75 mg b.i.d.with overnight withdrawal of antimetabolites and reduction of CNI by 50% per week to a complete stop after 4 weeks (the 50%-per-week rule). Adult, consenting recipients of LT from a deceased donor with a minimum follow-up of 12 months were included if they had a C0 ≤150ng/mL, and/or C2 ≤650ng/mL or a TAC trough level ≤8ng/mL. EVER trough levels were obtained 7, 14, 21, 28 days after switch and each month thereafte for 6 months. Target EVER trough levels were 3-8ng/mL. Twenty-seven patients were enrolled (mean age 56.4 ± 9.6 years; M/F=18/9) at a mean follow-up of 42.9 ± 29.3 months from LT. Twenty-one patients (77.8%) were on CsA; 6 patients (22.2%) were on TAC. At baseline, mean CsA dose was 131.6 ± 41.4mg/day and mean TAC dose was 2.8 ± 1.4 mg/day. Mean baseline C0 was 86.8 ± 70.9 ng/mL and mean baseline TAC trough level 6.7 ± 1 ng/mL. Seven days after switch, mean EVER trough level was 6.5 ± 3.2 ng/mL (2.2/14 ng/mL) and 21 patients (77.7%) were within the target range. In 2 patients (7.4%) EVER trough level was < 3 ng/mL (1 CsA; 1 TAC), while in 4 (11.1%) EVER trough level was > 8 ng/mL (3 CsA; 1 TAC). EVER at a dosage of 0.75 mg b.i.d. with 50% reduction of CNI allows to achieve trough levels between 3 and 8 ng/mL in 77.7% of cases, provided that patients have C0 ≤ 150ng/mL and/or C2 ≤ 650 ng/mL, or a TAC trough level ≤8 ng/mL at the time of switch.