Time To Reach Therapeutic Tacrolimus Levels after Pediatric Heart Transplant

Abstract

Purpose Tacrolimus (TAC) is a mainstay immunosuppressive agent after pediatric heart transplantation (HT). TAC levels are affected in the post-op period by enteral feeding tolerance, renal and hepatic function. Published reports recommend a 0.2 mg/kg/day dose. Our aim was to determine the post-op day after HT when a consistent dose-response to TAC first occurs. Secondary objectives included TAC blood concentrations and mean dose (mg/kg/day) at hospital discharge. Methods and Materials A retrospective cohort design included patients ≤ 21 years receiving enteral TAC within 14 days after HT from 2006–2012. Patients with a BMI ≥ 85%, prior cyclosporine use, death prior to discharge, and retransplants were excluded. TAC dose and levels were collected for each post-op day. Levels and doses were used to determine when a consistent dose-response to TAC first occurs to obtain target concentrations, defined as the day in which dosing resulted in two consecutive levels in a therapeutic range of 10–12 mcg/dL. Levels > 15 mcg/dL were considered supratherapeutic. Results Of 89 patients, 46 met study criteria. The median age was 1.83 years (0.25–20 years), and 59% were female. By post-op day 2, 78% of patients were initiated on TAC at a mean dose of 0.12 + 0.05 mg/kg/day. Consistent dose-response to TAC was reached at day 4, and recommended dose was reached by day 11. [ figure 1 ] Approximately 80% of patients had ≥ 1 supratherapeutic TAC blood level prior to discharge at a median of 6.5 (3-26) days. At discharge, the mean TAC concentration was 11 + 2.9 mg/dL at a TAC dose of 0.18 + 0.12 mg/kg/day. Conclusions Stable TAC levels are achieved 4 days after HT in children. Lower initiation dose TAC early post-op may be warranted to prevent supratherapeutic levels which frequently occur.