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- Title
Management of Metabolic Cytochrome P450 3A4 Drug-Drug Interaction between Everolimus and Azole Antifungals in a Renal Transplant Patient.
- Authors
Billaud, E. M.; Antoine, C.; Berge, M.; Abboud, L.; Lefeuvre, S.; Benammar, M.; Glotz, D.
- Abstract
We report a case of a 54-year-old male renal transplant patient who received antifungal azole treatment in combination with the recently introduced immunosuppressant agent everolimus to prevent post-transplantation aspergillosis reactivation. Voriconazole was withdrawn after 1 month because of elevated concentrations (5mg/L trough plasma determination) and hepatotoxicity, and substituted by several months of treatment with posaconazole (observed concentration range 1-2 mg/L). We observed pharmaco- kinetic drug interactions between both voriconazole and posaconazole, and everolimus cytochrome P450 3A4 metabolism, resulting in 7.5- and 3.8-fold increase, respectively, in everolimus blood trough concentrations. Combined therapeutic drug monitoring (TDM) of both everolimus and azole inhibitors allowed for safe and convenient modification of everolimus dosage, which was tapered to maintain a target range of 5-15 ng/mL during and after anti- fungal treatments. While significant in their effects, these drug interactions were able to be managed safely through a careful approach to management and use of individual TDM.
- Subjects
CYTOCHROME P-450; DRUG interactions; AZOLES; IMMUNOSUPPRESSIVE agents; ANTIFUNGAL agents; KIDNEY transplant patients
- Publication
Clinical Drug Investigation, 2009, Vol 29, Issue 7, p481
- ISSN
1173-2563
- Publication type
Article
- DOI
10.2165/00044011-200929070-00006