(502) - Once-Daily Tacrolimus: A Valuable Option Post Lung Transplantation

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Prolonged-release once-daily tacrolimus (OD-TAC) can improve safety & efficacy by avoiding toxic peak levels as well improving adherence to immunosuppression (I/S) regime, compared with twice-daily tacrolimus (BID-TAC). Published data on use of OD-TAC post lung transplantation (LTx) has been minimal to date. This paper describes our centers experience using OD-TAC in 91 LTx recipients. OD-TAC was approved for use in LTx in Australia in 2010, and by our pharmacy in June 2011 for selected LTx recipients with a 1:1 dose conversion from BID-TAC to OD-TAC. Data including demographics, indication for conversion, mean TAC dose/trough drug levels, TAC level variability, rejection rates & adverse effects were recorded prospectively to audit efficacy & safety of OD-TAC in this cohort. 91 LTx recipients [mean age 47yrs (range 13-69), 57% male, 78% BLTx, median days post LTx = 395 (range 9-6915); LTx diagnosis:34% CF, 34%COPD, 27%ILD, 5% PAH ] were converted to OD-TAC. Main indications for conversion: 63% commenced antifungal therapy requiring very low doses of OD-TAC to prevent toxicity, 12% renal impairment (RI), 12% extreme TAC level variability & 13% poor BID-TAC adherence. Median (range) daily TAC dose and mean (±SD) trough level pre and 1 month post conversion were 2 mg(0.5-24), 8.5 ± 3.8ug/L* vs 1.5mg (0.5-24); 6.1±3.4ug/L* respectively (*p<0.01). No acute rejection occurred in patients switched to OD-TAC. 16/91(18%) patients are now deceased (primarily due to chronic rejection), 7(8%) patients ceased OD-TAC therapy due to adverse effects [n=3 rash & edema, n=4 with worsening RI ceased TAC completely] & 74% remain on OD-TAC with a median length of treatment of 358 days (range 18-722) despite 30% having now ceased antifungal therapy and requiring increased OD-TAC doses. An additional 4 CF LTx patients are now using OD-TAC twice daily to achieve therapeutic but non-toxic peak levels produced with BID-TAC. Overall variability of TAC levels was reduced & patients reported adherence in OD-TAC regime was superior to BID-TAC. OD-TAC has proven to be a valuable, safe and effective I/S option in the majority of selected LTx recipients, particularly in LTx recipients on antifungals requiring very low dose TAC, those with high TAC level variability, or with poor adherence to BID-TAC. Further comparison of overall level variability of OD-TAC cohort vs standard BID-TAC cohort is ongoing.