Background and importance Potential interaction between tacrolimus and azole antifungals is often detected in transplanted patients with fungal colonisation or infection.
Aim and objectives To compare the influence of voriconazole and isavuconazole on maintenance of plasma levels of tacrolimus and to analyse their safety.
Material and methods A retrospective observational study was conducted according to cluster classification in all patients immunosuppressed with tacrolimus and receiving concomitant treatment with voriconazole or isavuconazole over a 2 year period in a class 5 hospital. The variables collected included age, plasma levels of tacrolimus for 10 days after the start of the combination, and toxicity associated with azole throughout treatment with it. The standard deviation of tacrolimus levels was calculated to determine which of the antifungals had generated more oscillation in plasma levels. For qualitative variables, absolute and relative frequencies were obtained, and for quantitative variables, the median (IQR) were used. For hypothesis contrast, Fisher’s exact test or the Mann–Whitney U test was performed according to the type of variable.
Results 45 patients were included, 23 received voriconazole and 22 isavuconazole. Median age was 62 years (56–67) for those receiving voriconazole versus 63 years (54–68) for those receiving isavuconazole (p=0.91). 34.8% (n=8) of patients treated with voriconazole achieved concentrations of tacrolimus >20 ng/mL (toxic concentration) within 10 days from the start of the combination compared with 14.3% (n=3) of patients treated with isavuconazole (p=0.1685). The median standard deviation of plasma concentrations was 3.76 ng/mL (2.89–4.5) with voriconazole versus 3.17 ng/mL (1.4–5) with isavuconazole (p=0.272). The proportion of patients who temporarily discontinued tacrolimus treatment due to high level concentrations and associated toxicity was 18.2% (n=4) with isavuconazole versus 34.8% (n=8) with voriconazole (p=0.318).
Regarding tolerance to treatment, 28.57% of patients treated with isavuconazole had side effects associated with azole, compared with 82.6% of those treated with voriconazole (p<0.005). Treatment had to be suspended due to these side effects in 47.82% (n=11) of patients treated with voriconazole and in no patient treated with isavuconazole (p<0.005).
Conclusion and relevance Treatment with isavuconazole resulted in fewer tacrolimus poisonings, although the difference was not statistically significant. In addition, treatment with isavuconazole was found to be safer, had fewer side effects and did not require antifungal discontinuation.
Conflict of interest No conflict of interest
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