Voriconazole and itraconazole in lung transplant recipients receiving tacrolimus (FK 506): efficacy and drug interaction

Background: The aim of this study was to compare the extent of interaction between tacrolimus and itraconazole vs. voriconazole. Patients and methods: This retrospective study included 60 lung transplant recipients who were treated with a tacrolimus-based regimen; 40 received prophylactic itraconazole for the first six months following lung transplantation (LTX), and 20 were treated with voriconazole. All patients had at least 12 months of follow-up. Tacrolimus levels and dosage requirements were compared during and after azole therapy. We assessed the rejection rate, fungal infection rate, and renal function during the study period. Results: The mean tacrolimus dose during itraconazole treatment was 3.26 +/- 2.1 mg/d compared with 5.74 +/- 2.9 mg/d after itraconazole was stopped, p < 0.0001. Similarly, the mean tacrolimus dose during voricnoazole treatment was 1.75 +/- 0.9 mg/d compared with 4.85 +/- 0.38 mg/d after voriconazole was stopped (p = 0.002). Thus, the mean increase in the total daily dose of tacrolimus after itraconazole and voriconazole withdrawal was 76% and 64%, respectively. No differences in the rejection or fungal infection rates or renal toxicity were observed during the study period, although an increase in positive fungal isolates was noted during itraconazole therapy. Conclusion: The tacrolimus dose was reduced more with itraconazole than with voriconazole, without an increase in the rejection rate and with renal function preservation.