title: The Rise and Fall of Oral Ketoconazole.
abstract: BACKGROUND
  Ketoconazole was the first broad-spectrum oral antifungal agent available to treat systemic and superficial mycoses. Evidence of hepatotoxicity associated with its use emerged within the first few years of its approval. Growing evidence of serious side effects including endocrine dysregulation, several drug interactions, and death led to the review of oral ketoconazole in 2011.
  
  
  OBJECTIVE
  This article chronicles the use of oral ketoconazole from its introduction to its near replacement in medicine.
  
  
  CONCLUSIONS
  Due to its hepatotoxic side effects, oral ketoconazole was withdrawn from the European and Australian markets in 2013. The United States imposed strict relabeling requirements and restrictions for prescription, with Canada issuing a risk communication echoing these concerns. Today, oral ketoconazole is only indicated for endemic mycoses, where alternatives are not available or feasible. Meanwhile, topical ketoconazole is effective, safe, and widely prescribed for superficial mycoses, particularly as the first-line treatment for tinea versicolor.
authors.affiliation: Department of Medicine, University of Toronto, Toronto, Canada Mediprobe Research Inc., London, Ontario, Canada agupta@execulink.com.
authors.forename: Aditya K
authors.initials: AK
authors.lastname: Gupta
authors.affiliation: Mediprobe Research Inc., London, Ontario, Canada.
authors.forename: Danika C A
authors.initials: DC
authors.lastname: Lyons
mesh_terms: D000935:Antifungal Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000266:history*; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology; D049673:History, 20th Century; D049674:History, 21st Century; D006801:Humans; D007654:Ketoconazole / Q000008:administration & dosage / Q000009:adverse effects / Q000266:history*; D014481:United States
chemical_list: D000935:Antifungal Agents; D007654:Ketoconazole
keywords: azole antifungal; hepatotoxic; history; indication; ketoconazole