Sex and ethnicity may chiefly influence the interaction of fluconazole with calcineurin inhibitors

A. Scott Mathis, Teresa Direnzo, Gary S. Friedman, Bruce Kaplan, Robert Adamson

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Background. Calcineurin inhibitors (CNI) and azole antifungal agents have been reported to interact in a disparate manner. The azole dose and route and the level of involvement of the liver and intestines have been implicated, although data are limited. A significant interaction may result in CNI toxicity, and withdrawal of the azole may result in subtherapeutic CNI concentrations. Fluconazole, available in both intravenous and oral formulations, is commonly used in transplant recipients and is ideal for determining the presence of a disparate effect on CNI concentrations. We retrospectively investigated the interaction of CNIs with fluconazole, evaluating CNI blood troughs corrected for daily CNI dose, the factors influencing the interaction, and the effect on clinical outcomes in renal and simultaneous pancreas kidney transplant recipients. Methods. Twenty-eight patients received a CNI and fluconazole during the calendar year 1999, but only 19 patients had documented CNI blood troughs and out-patient follow-up. There were 25 episodes of use in the 19 included patients. CNI blood troughs were evaluated for changes induced by fluconazole, given by both routes, and clinical outcomes were tracked. Results. Data demonstrated both intravenous and oral fluconazole alter CNI blood concentrations. Two metabolic patterns were observed, and we termed these convergent and divergent. Divergent metabolizers did not have significant interaction (n=5), and convergent metabolizers did have a significant interaction (n=15). One patient had a divergent episode after a previous convergent episode. The main contributors to the lack of interaction appeared to be female sex and African American ethnicity. Additionally, tacrolimus levels were significantly more affected than cyclosporine, during and after fluconazole administration. No patient experienced nephrotoxicity or cellular rejection related to antifungal therapy. Conclusions. Oral and intravenous fluconazole appear to increase oral CNI trough concentrations to a similar extent even after adjusting for daily calcineurin dose. These interactions appear to be chiefly influenced by sex and ethnicity. Further prospective study is necessary to clarify this issue.

Original languageEnglish (US)
Pages (from-to)1069-1075
Number of pages7
JournalTransplantation
Volume71
Issue number8
StatePublished - 2001
Externally publishedYes

Fingerprint

Fluconazole
Azoles
Calcineurin Inhibitors
Kidney
Calcineurin
Antifungal Agents
Tacrolimus
African Americans
Cyclosporine
Intestines
Pancreas
Outpatients
Prospective Studies

ASJC Scopus subject areas

  • Transplantation
  • Immunology

Cite this

Scott Mathis, A., Direnzo, T., Friedman, G. S., Kaplan, B., & Adamson, R. (2001). Sex and ethnicity may chiefly influence the interaction of fluconazole with calcineurin inhibitors. Transplantation, 71(8), 1069-1075.

Sex and ethnicity may chiefly influence the interaction of fluconazole with calcineurin inhibitors. / Scott Mathis, A.; Direnzo, Teresa; Friedman, Gary S.; Kaplan, Bruce; Adamson, Robert.

In: Transplantation, Vol. 71, No. 8, 2001, p. 1069-1075.

Research output: Contribution to journalArticle

Scott Mathis, A, Direnzo, T, Friedman, GS, Kaplan, B & Adamson, R 2001, 'Sex and ethnicity may chiefly influence the interaction of fluconazole with calcineurin inhibitors', Transplantation, vol. 71, no. 8, pp. 1069-1075.
Scott Mathis A, Direnzo T, Friedman GS, Kaplan B, Adamson R. Sex and ethnicity may chiefly influence the interaction of fluconazole with calcineurin inhibitors. Transplantation. 2001;71(8):1069-1075.
Scott Mathis, A. ; Direnzo, Teresa ; Friedman, Gary S. ; Kaplan, Bruce ; Adamson, Robert. / Sex and ethnicity may chiefly influence the interaction of fluconazole with calcineurin inhibitors. In: Transplantation. 2001 ; Vol. 71, No. 8. pp. 1069-1075.
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AB - Background. Calcineurin inhibitors (CNI) and azole antifungal agents have been reported to interact in a disparate manner. The azole dose and route and the level of involvement of the liver and intestines have been implicated, although data are limited. A significant interaction may result in CNI toxicity, and withdrawal of the azole may result in subtherapeutic CNI concentrations. Fluconazole, available in both intravenous and oral formulations, is commonly used in transplant recipients and is ideal for determining the presence of a disparate effect on CNI concentrations. We retrospectively investigated the interaction of CNIs with fluconazole, evaluating CNI blood troughs corrected for daily CNI dose, the factors influencing the interaction, and the effect on clinical outcomes in renal and simultaneous pancreas kidney transplant recipients. Methods. Twenty-eight patients received a CNI and fluconazole during the calendar year 1999, but only 19 patients had documented CNI blood troughs and out-patient follow-up. There were 25 episodes of use in the 19 included patients. CNI blood troughs were evaluated for changes induced by fluconazole, given by both routes, and clinical outcomes were tracked. Results. Data demonstrated both intravenous and oral fluconazole alter CNI blood concentrations. Two metabolic patterns were observed, and we termed these convergent and divergent. Divergent metabolizers did not have significant interaction (n=5), and convergent metabolizers did have a significant interaction (n=15). One patient had a divergent episode after a previous convergent episode. The main contributors to the lack of interaction appeared to be female sex and African American ethnicity. Additionally, tacrolimus levels were significantly more affected than cyclosporine, during and after fluconazole administration. No patient experienced nephrotoxicity or cellular rejection related to antifungal therapy. Conclusions. Oral and intravenous fluconazole appear to increase oral CNI trough concentrations to a similar extent even after adjusting for daily calcineurin dose. These interactions appear to be chiefly influenced by sex and ethnicity. Further prospective study is necessary to clarify this issue.

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