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

Clin Transplant. 2011 Mar-Apr;25(2):E163-7. doi: 10.1111/j.1399-0012.2010.01373.x. Epub 2010 Dec 16.

Abstract

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 voriconazole 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.

MeSH terms

  • Antifungal Agents / therapeutic use*
  • Drug Interactions
  • Female
  • Follow-Up Studies
  • Glomerular Filtration Rate
  • Graft Rejection / prevention & control*
  • Humans
  • Immunosuppressive Agents / therapeutic use
  • Itraconazole / therapeutic use*
  • Lung Transplantation*
  • Male
  • Middle Aged
  • Pyrimidines / therapeutic use*
  • Retrospective Studies
  • Tacrolimus / therapeutic use*
  • Treatment Outcome
  • Triazoles / therapeutic use*
  • Voriconazole

Substances

  • Antifungal Agents
  • Immunosuppressive Agents
  • Pyrimidines
  • Triazoles
  • Itraconazole
  • Voriconazole
  • Tacrolimus