T Kim1, T Jancel2, P Kumar1, A F Freeman3. 1. Pharmacy Department, National Institutes of Health Clinical Center, Bethesda, MD, USA. 2. Office of Safety and Epidemiology, US Food and Drug Administration, Silver Spring, MD, USA. 3. Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, Bethesda, MD, USA.
Abstract
WHAT IS KNOWN AND OBJECTIVE: Despite the known significant drug-drug interaction between isavuconazole and tacrolimus, there are no recommendations on dose adjustment when these drugs are given concomitantly. We report on a patient with a mediastinal Aspergillus fumigatus infection resistant to posaconazole and describe how she was successfully managed with tacrolimus therapeutic drug-level monitoring. CASE SUMMARY: Our patient presented with a mediastial Aspergillus fumigatus infection, 2 years after lung transplantation. A. fumigatus was resistant to posaconazole, and the patient had intolerance to voriconazole shown by elevated transaminases. The patient was given isavuconazole with drug-level monitoring. She was managed successfully with no adverse events. Tacrolimus concentration continued to increase after more than 2 weeks of therapy and required a further reduction to 72% of the usual dose to maintain the target concentrations over a 8-week period. WHAT IS NEW AND CONCLUSION: When isavuconazole is given to patients on tacrolimus, the dose of the latter will need considerable reduction. We would suggest an initial 50% reduction and recommend close weekly monitoring of tacrolimus concentration. Further dose decreases of 25-50% may be required. Published 2015. This article is a U.S. Government work and is in the public domain in the USA.
WHAT IS KNOWN AND OBJECTIVE: Despite the known significant drug-drug interaction between isavuconazole and tacrolimus, there are no recommendations on dose adjustment when these drugs are given concomitantly. We report on a patient with a mediastinal Aspergillus fumigatus infection resistant to posaconazole and describe how she was successfully managed with tacrolimus therapeutic drug-level monitoring. CASE SUMMARY: Our patient presented with a mediastial Aspergillus fumigatus infection, 2 years after lung transplantation. A. fumigatus was resistant to posaconazole, and the patient had intolerance to voriconazole shown by elevated transaminases. The patient was given isavuconazole with drug-level monitoring. She was managed successfully with no adverse events. Tacrolimus concentration continued to increase after more than 2 weeks of therapy and required a further reduction to 72% of the usual dose to maintain the target concentrations over a 8-week period. WHAT IS NEW AND CONCLUSION: When isavuconazole is given to patients on tacrolimus, the dose of the latter will need considerable reduction. We would suggest an initial 50% reduction and recommend close weekly monitoring of tacrolimus concentration. Further dose decreases of 25-50% may be required. Published 2015. This article is a U.S. Government work and is in the public domain in the USA.
Entities:
Keywords:
drug-drug interaction; new antifungal agent; therapeutic drug monitoring
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