P3.44: Sublingual tacrolimus use in intestinal transplant recipients

Abstract

Introduction: Therapeutic tacrolimus concentrations are essential to prevent rejection in intestinal transplant patients. Traditional administration of liquid tacrolimus via jejunal tube (JT) immediately post-transplant may require high doses and result in delays in achieving therapeutic concentrations, likely due to decreased enteral bioavailability. Tacrolimus may be administered via the sublingual (SL) route, with passive diffusion of drug across oral mucosa. Administration via the sublingual route avoids enteral metabolism and bypasses the liver first-pass effect, and may result in faster onset of action. There is a paucity of data regarding SL tacrolimus use in intestinal transplant patients. Methods: This was a retrospective, single center review of adult intestinal or multivisceral transplant patients transplanted between 06/2017 and 12/2018 who were converted from JT to SL tacrolimus within the first 30 days after transplant due to subtherapeutic tacrolimus troughs (less than 20 ng/mL). Daily tacrolimus doses, routes, drug levels, and incidence of rejection were recorded. Results: Sixteen patients met inclusion criteria: 12 intestine, 2 multivisceral, 1 intestine+ liver, and 1 intestine+ kidney. Subjects were initiated on JT tacrolimus immediately postoperatively, and were transitioned to SL tacrolimus at an average of 6 ± 3.4 days postoperatively. The mean daily JT dose was 12.2 ± 3.9 mg and the mean JT tacrolimus trough was 9.6 ± 5 .4 ng/mL prior to transition. After changing to SL, the mean daily SL dose was 10.4 mg ± 3.8 and the mean tacrolimus trough was 21.8 ± 3.8 ng/mL. Subjects reached therapeutic levels (greater than 20 ng/mL) 1.9 ± 0.8 days after transition and stayed on SL dosing 13.7 ± 8.1 days during the first month. The conversion ratio of JT to SL tacrolimus was 0.4 ± 0.3. No adverse effects as a result of administering the drug via the sublingual route were noted, and 2 patients were treated for rejection during the first month. Conclusion: The use of sublingual tacrolimus allowed for rapid achievement of target tacrolimus troughs in intestinal transplant patients with the use of lower doses than jejunal tube tacrolimus administration, and may provide a viable option for immunosuppression immediately post-transplant. Limitations include the retrospective nature of the study, as well as conversion of doses prior to reaching steady state. Further prospective dose conversion studies in intestinal transplant patients are warranted.