Tacrolimus Dose Requirements In Lung Transplant Recipients On Systemic Azole Antifungals: The Influence Of Race

PurposeThe CYP3A5*1 polymorphism, predominant in African Americans (AAs), and drug interactions with CYP3A inhibitors/inducers significantly impact tacrolimus metabolism. Minimal data evaluating tacrolimus dose requirements (TDRs) in lung transplant recipients (LTRs) on concurrent strong CYP3A inhibitors exists. We sought to assess the effect of race on TDRs and transplantation outcomes in a cohort of LTRs initiated on a fixed tacrolimus dose and antifungal prophylaxis with a systemic azole after transplant.MethodsAll adult LTRs transplanted from 1/2015-10/2019 initiated on an equivalent tacrolimus dose posttransplant per institutional protocol were included and stratified by race. TDRs, tacrolimus levels, systemic azole use, biopsy proven acute rejection (BPAR), patient survival, and graft survival for the first year posttransplant were evaluated.Results68 LTRs were included (10 AA, 58 non-AA); the majority were on a systemic azole at 1 (90.8%) and 3 (90.3%) months posttransplant. TDRs were significantly higher in AAs at the first therapeutic level, discharge, and months 1, 3, 12 posttransplant (Figure 1); tacrolimus levels and time within therapeutic range (55% AA vs 40.5% non-AA, p=0.13) were similar. AAs had a similar time to first therapeutic level (11.2 days AA vs 7.8 days non-AA, p=0.10) and number of dose adjustments to achieve this level (4 vs 2.6, p=0.08). The majority of LTRs did not achieve a therapeutic tacrolimus level prior to discharge (80% AA vs 69% non-AA, p=0.48). No differences in BPAR (20% AA vs 25.9% non-AA, p=0.69), patient survival (100% AA vs 86.2% non-AA, p=0.21), or graft survival (100% for both) within 12 months posttransplant were observed.ConclusionWhile AA LTRs had significantly higher TDRs to maintain similar trough levels compared to non-AAs, this did not influence transplantation outcomes. Further research is needed to determine the optimal dosing strategy in LTRs immediately posttransplant. The CYP3A5*1 polymorphism, predominant in African Americans (AAs), and drug interactions with CYP3A inhibitors/inducers significantly impact tacrolimus metabolism. Minimal data evaluating tacrolimus dose requirements (TDRs) in lung transplant recipients (LTRs) on concurrent strong CYP3A inhibitors exists. We sought to assess the effect of race on TDRs and transplantation outcomes in a cohort of LTRs initiated on a fixed tacrolimus dose and antifungal prophylaxis with a systemic azole after transplant. All adult LTRs transplanted from 1/2015-10/2019 initiated on an equivalent tacrolimus dose posttransplant per institutional protocol were included and stratified by race. TDRs, tacrolimus levels, systemic azole use, biopsy proven acute rejection (BPAR), patient survival, and graft survival for the first year posttransplant were evaluated. 68 LTRs were included (10 AA, 58 non-AA); the majority were on a systemic azole at 1 (90.8%) and 3 (90.3%) months posttransplant. TDRs were significantly higher in AAs at the first therapeutic level, discharge, and months 1, 3, 12 posttransplant (Figure 1); tacrolimus levels and time within therapeutic range (55% AA vs 40.5% non-AA, p=0.13) were similar. AAs had a similar time to first therapeutic level (11.2 days AA vs 7.8 days non-AA, p=0.10) and number of dose adjustments to achieve this level (4 vs 2.6, p=0.08). The majority of LTRs did not achieve a therapeutic tacrolimus level prior to discharge (80% AA vs 69% non-AA, p=0.48). No differences in BPAR (20% AA vs 25.9% non-AA, p=0.69), patient survival (100% AA vs 86.2% non-AA, p=0.21), or graft survival (100% for both) within 12 months posttransplant were observed. While AA LTRs had significantly higher TDRs to maintain similar trough levels compared to non-AAs, this did not influence transplantation outcomes. Further research is needed to determine the optimal dosing strategy in LTRs immediately posttransplant.