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Ketoconazole and Fluconazole Drug Interactions

Peter K. Honig, MD; Louis R. Cantilena, MD, PhD
Arch Intern Med. 1994;154(9):1038-1041. doi:10.1001/archinte.1994.00420090130018.
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We read with interest the article on ketoconazole and fluconazole drug interactions by Baciewicz and Baciewicz,1 which appeared in the Archives. We agree that the azole antifungals have the capability to influence the metabolism of a wide variety of concurrently administered drugs and the Food and Drug Administration is increasingly aware of such potential interactions.2

The authors fail to cite recent information regarding interactions between the popular nonsedating antihistamines and these antifungal agents. A prospective study3 conducted by our group has shown ketoconazole to influence the biotransformation of terfenadine, allowing the accumulation of the cardiotoxic parent compound. The concomitant administration of these drugs is contraindicated. A similar interaction study of terfenadine and fluconazole did not demonstrate any clinically significant cardiac repolarization abnormalities.4

We also feel that it is important to mention that concomitant administration of ketoconazole and astemizole is contraindicated (as indicated on Hismanal [Janssen Pharmaceutica,


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