Background
Lung transplant recipients (LTR) are at high risk for opportunistic fungal infections (FI). Yet, treatment with azoles results in drug-drug interactions with tacrolimus, requiring dose adjustment (voriconazole: 67%, fluconazole: 40%). We assessed the interaction magnitude, defined by change in tacrolimus dose-corrected trough concentration (C/D) and its influencing factors.

Methods  
In this retrospective study, LTR using tacrolimus p.o. and azoles for FI in 2018-2022 were included. Demographics, drug formulation, doses, concentrations, and blood tests (albumin, ALAT, CRP, eGFR, Hct) were extracted from patient records. Change in C/D before, during and after azole treatment were calculated. Spearman?s correlations of C/D during treatment with demographics and lab parameters were assessed using SPSS.  

Results 
In total, 33 LTR were included with 523 tacrolimus concentrations. C/D increased after azole start, median [IQR] 4 times [2.7-6.1] for voriconazole (n=22), and 2 times [1.4-3.7] for fluconazole (n=11), suggesting median dose reductions of 75% and 50% respectively. Median first tacrolimus concentrations after azole start were 13.8 µg/L (range: 5.7-46.1 µg/L) for voriconazole and 11.1 µg/L (2.8-28.9) for fluconazole, compared to 9.2 µg/L (5.2-14.9) before start. C/D during treatment was correlated with C/D before treatment (r=0.60, p<.001), BMI (r=.36, p<.05), and Hct (r=-.46, p<.01). After the 3rd sample after azole discontinuation, median C/D was comparable with before treatment. 

Conclusion
The drug-drug interaction magnitude between tacrolimus and azoles is variable, and current guidelines for precautionary dose adjustment may not be sufficient.