Sublingual Administration of Tacrolimus is Safe and Provides Similar Drug Exposure to Per-oral Route in Liver Transplant Recipients During Early Postoperative Period–A Large, Retrospective, Observational Study

Background/Aims

Per-oral (PO) administration of tacrolimus (TAC) results in inadequate trough levels in the early postoperative period in liver-transplant (LT) recipients who undergo Roux-en-Y hepaticojejunostomy for biliary reconstruction. Sublingual administration (SL) of tacrolimus provides an alternative route in such patients.

The objectives of this study were to assess the feasibility and safety of SL tacrolimus in adult LT-recipients in the early postoperative period and to compare therapeutic efficacy of SL administration of tacrolimus versus PO route.

Methods

single-center, retrospective, observational study carried out in adult living donor liver transplant (LDLT) recipients between January 2022 and December 2022. Recipients who underwent Roux-en-Y hepaticojejunostomy for biliary reconstruction received tacrolimus through the SL route till postoperative day (POD) 5 as they were kept nil per oral constituted the study group while recipients who underwent duct-to-duct (D-D) anastomosis for biliary reconstruction were allowed orally from POD1 and received PO-tacrolimus were chosen as controls. The feasibility and safety of SL-tacrolimus were assessed in terms of patient acceptance, need to discontinue SL-tacrolimus, incidence of local adverse effects, and systemic adverse events like neurotoxicity and nephrotoxicity. Therapeutic efficacy was evaluated by comparing median trough levels (TAC level) achieved and incidence of graft rejection between two groups.

Results

Two hundred twelve patients underwent LT during the study period, of which 125 were included (58 in the SL-group and 67 in PO-group). Both groups had comparable baseline characteristics. In the SL-group, all patients tolerated SL-Tacrolimus well and no local adverse events were observed. Patients with SL-Tacrolimus administration achieved a higher median TAC level (ng/ml) vs. PO route (5.85 vs. 5 (P = 0.06)) despite receiving similar median cumulative tacrolimus dose before assessing TAC-level. Fifty percent of patients achieved TAC level ≥6 ng/ml in SL-group vs. 35.8% in PO-group (P = 0.14). The incidence of neurotoxicity, nephrotoxicity, and graft rejection during hospital stay were similar in both the groups (P = 0.56, 0.82, and 0.28, respectively).

Conclusion

SL-tacrolimus is safe and provides similar trough levels to PO-tacrolimus and may be considered as a viable alternative whenever inadequate TAC levels are anticipated through the per-oral route.