Evaluation of a Weight-based Rabbit Anti-thymocyte Globulin Induction Dosing Regimen for Kidney Transplant Recipients.

STUDY OBJECTIVE: Although rabbit anti-thymocyte globulin (rATG) is commonly used as induction therapy for kidney transplantation, dosing is not standardized. Recently available findings suggest that even subtle differences in the cumulative dose of rATG induction may have an impact on acute rejection rates for patients receiving steroid-minimization maintenance immunosuppression. This investigation evaluated the potential consequences of rounding and capping rATG doses in patients receiving steroid-containing maintenance immunosuppression when calculating the dose based on actual body weight. DESIGN: Single-center retrospective cohort study. SETTING: A large academic medical center. PATIENTS: A total of 261 adult kidney transplant recipients between July 1, 2010, and December 31, 2012, who received rATG induction and were maintained on tacrolimus, mycophenolate, and prednisone. METHODS AND MEASUREMENTS: Incidences of biopsy-confirmed acute rejection, opportunistic infections and hematologic effects within 12 months posttransplant were assessed for patients receiving a cumulative rATG dose of 5 mg/kg or higher (5.2 ± 0.2 mg/kg, n=138) compared with those who received a cumulative rATG dose lower than  5 mg/kg (4.5 ± 0.6 mg/kg, n=123). The groups had similar baseline characteristics, immunologic risk, and indications for rATG induction. The incidence of clinically relevant biopsy-confirmed acute rejection was low and similar between the groups (8.7% for rATG of 5 mg/kg or higher vs 8.9% for rATG lower than  5 mg/kg, p=0.944). Patient survival, all-cause graft survival, and graft function did not differ between the groups. Incidences of cytomegalovirus and BK virus infection as well as the extent and duration of lymphopenia were also similar between the groups. CONCLUSIONS: In combination with triple maintenance immunosuppression consisting of tacrolimus, mycophenolate, and prednisone, modest differences in the cumulative rATG dose were not associated with increased risk of acute rejection. Measures to optimize rATG utilization present opportunities for cost-saving without sacrificing efficacy in this patient population.

Sublingual tacrolimus as an alternative to oral administration for solid organ transplant recipients.

PURPOSE: Available data regarding sublingual tacrolimus were analyzed to provide recommendations for solid organ transplant recipients. SUMMARY: Tacrolimus is an immunosuppressive agent with a narrow therapeutic range that is commonly used in solid organ transplantation. Achieving and maintaining appropriate tacrolimus exposure are critical for preventing rejection and minimizing toxicity. A variety of clinical situations requiring nonoral medication delivery arise, presenting the need for reliable alternative routes of tacrolimus administration. A review of the currently available literature revealed nine reports of sublingual tacrolimus use in human subjects. Seven reported that sublingual administration could achieve comparable tacrolimus trough concentrations to oral administration, but none investigated the correlation between tacrolimus trough concentration and exposure. One study of lung transplant recipients found that approximately 50% of the oral dose was needed to obtain therapeutic trough concentrations when converted to sublingual administration. Another study of patients with end-stage renal disease identified a similar sublingual:oral dosing ratio of 1:2. When converted from oral tacrolimus in combination with clotrimazole to sublingual administration, the sublingual:oral dosing ratio was 1:1. CONCLUSION: In addition to enteral tube and i.v. tacrolimus dosing, sublingual administration may be considered for short-term use in patients who are unable to receive medications orally. Based on the available data, it is reasonable to initiate sublingual tacrolimus at 50% of the current or anticipated oral dose in the absence of interacting medications. Dosing must be individualized, taking into consideration concomitant interacting medications, and adjusted to target levels based on therapeutic drug monitoring.