Fluconazole

 

KEY POINTS

• Fluconazole (Diflucan) is an Azole derivative antifungal drug that works by interfering with ergosterol synthesis, which is the principal sterol in the fungal cell membrane
  • Exhibits fungistatic activity versus mosts yeasts, but has fungicidal activity versus many moulds
• Is a corner-stone in the management of Candida infections
  • Beware resistance in Candida glabrata, which may be sensitive, d0se-dependent sensitive (DDS), or resistant
  • Candida krusei is inherently resistant to fluconazole
  • Other Candida species can have fluconazole resistance. Beware this in particular with patients who have a prolonged history of fluconazole exposure or who are being treated at institutions with a history of fluconazole-resistant Candida.
• Available oral or injectable – a good drug to watch for IV to PO transition
  • Due to excellent bioavailability, fluconazole oral has been used to treat candidemia (i.e., a Candida bloodstream infection) – most oral drugs are not suitable for oral use with a bloodstream infection
• Doses vary greatly depending on indication, from 150mg once to 800mg or more daily
  • Adjust doses for renal dysfunction
• Beware drug-drug interactions via inhibition of CYP: 1A2, 2C19, 2C9 and 3A4
• Beware hepatotoxicity and increases in AST/ALT

RESOURCES

• Fluconazole Package Insert (oral and injectable)
• IDSA Candidemia Guideline (2016)
  • Other IDSA Guidelines For Fungi
• Guidelines For Opportunistic Infections From AIDSinfo
• 2015 CDC Sexually Transmitted Diseases Guideline (2015)
• Pharmacology Of Systemic Antifungal Agents (2006)
• Current Concepts In Antifungal Pharmacology (2011)