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September 13, 1993

Ketoconazole and Fluconazole Drug Interactions

Author Affiliations

From the Department of Pharmacy Services, University Hospitals of Cleveland (Ohio) (Dr A. Baciewicz), and the Department of Surgery, Division of Cardiothoracic Surgery, Wayne State University, Detroit, Mich (Dr F. Baciewicz).

Arch Intern Med. 1993;153(17):1970-1976. doi:10.1001/archinte.1993.00410170042004

This article reviews potential drug interactions that exist between ketoconazole or fluconazole and other drugs. English-language data sources included human subjects' computerized databases and published indexes. Case reports and studies demonstrate decreased dosage requirements of cyclosporine sodium, methylprednisolone sodium succinate, and possibly anticoagulants and phenytoin after ketoconazole or fluconazole administration, suggesting hepatic enzyme inhibition. Increased dosage requirements of ketoconazole are necessary after rifampin administration, suggesting rifampin's induction of hepatic microsomal enzymes. Possibly a similar effect may occur with concomitant fluconazole and rifampin. The effect of ketoconazole administration on prednisolone sodium phosphate and theophylline warrants further study. Fluconazole, a more selective agent for fungal P-450, seems to be of less concern regarding the potential for drug interactions than ketoconazole.

(Arch Intern Med. 1993;153:1970-1976)