title: Drug safety assessment of oral formulations of ketoconazole.
abstract: BACKGROUND
  Ketoconazole was the first broad-spectrum oral antifungal approved by the FDA in 1981. Post-marketing reports of drug-related hepatotoxicity, endocrine dysregulation and drug interactions resulted in market withdrawal of the drug in some countries and strict product relabeling in others.
  
  
  METHODS
  This drug safety review summarizes reports of oral ketoconazole-related adverse events retrieved from a search of the PubMed database using the search strategy 'ketoconazole OR Nizoral AND hepat*', references from relevant publications, and data from the FDA Adverse Event Reporting System.
  
  
  CONCLUSIONS
  Although oral ketoconazole is effective in treating fungal infections, the potential for drug interactions, endocrine dysregulation, and hepatotoxicity may outweigh its benefits. Newer oral antifungals have similar or greater efficacy in treating dermatologic conditions and are associated with less risk. Likewise, newer agents with specific targets and fewer drug interactions have been developed to treat systemic fungal infections. Therefore, by the time ketoconazole prescribing guidelines were amended, its use had already largely been replaced with newer antifungals. Being that ketoconazole was the first broad-spectrum oral antifungal, experience with the drug made patient safety, and especially hepatic safety, an important consideration in future antifungal development.
authors.affiliation: University of Toronto, Department of Medicine , Toronto, Ontario , Canada agupta@execulink.com.
authors.forename: Aditya K
authors.initials: AK
authors.lastname: Gupta
authors.forename: Deanne
authors.initials: D
authors.lastname: Daigle
authors.forename: Kelly A
authors.initials: KA
authors.lastname: Foley
mesh_terms: D000284:Administration, Oral; D000935:Antifungal Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000494:pharmacology; D056486:Chemical and Drug Induced Liver Injury; D004347:Drug Interactions; D052244:Endocrine Disruptors / Q000008:administration & dosage / Q000009:adverse effects* / Q000494:pharmacology; D006801:Humans; D007654:Ketoconazole / Q000008:administration & dosage* / Q000009:adverse effects* / Q000494:pharmacology
chemical_list: D000935:Antifungal Agents; D052244:Endocrine Disruptors; D007654:Ketoconazole
keywords: antifungal; ergosterol synthesis inhibitor; hepatic injury; hepatotoxicity; imidazole; ketoconazole; liver injury; mycosis