The azoles' mechanism of action is inhibition of ergosterol synthesis in the fungal cell wall, resulting in fungistatic activity. Azoles cause little or no nephrotoxicity and are available in oral preparations.

• Fluconazole: Fluconazole is available in both oral and IV formulations, has a long half-life, and penetrates into most body fluids, including ocular fluids and CSF.
  • - Toxicity is minimal but includes (usually reversible) hepatotoxicity and—at high doses—alopecia, muscle weakness, dry mouth, and metallic taste.
  • - Fluconazole is useful for coccidioidal and cryptococcal meningitis and for candidemia, but it is notably ineffective against aspergillosis or mucormycosis.
  • - It is effective as fungal prophylaxis in bone-marrow and high-risk liver transplant recipients.
• Voriconazole: Available in oral and IV formulations, voriconazole is considered the first-line agent against Aspergillus and has a broader spectrum than fluconazole against Candida species (including C. glabrata and C. krusei). It is also active against Scedosporium and Fusarium.
  • - Disadvantages of voriconazole (compared to fluconazole) include multiple drug interactions, hepatotoxicity, skin rashes (including photosensitivity), visual disturbances, and the need to monitor drug levels.
  • - As it is metabolized completely by the liver, dose adjustments are required in pts with liver failure. Dose adjustments for renal insufficiency are not required, but the parenteral formulation should be avoided in pts with severe renal insufficiency given the presence of cyclodextrin.
• Itraconazole: Available in oral and IV formulations, itraconazole is the drug of choice for mild to moderate blastomycosis and histoplasmosis. It is approved by the FDA for use in febrile neutropenic pts. Disadvantages of itraconazole include its poor penetration into CSF, the use of cyclodextrin in both the oral suspension and the IV preparation, the variable absorption of the drug in capsule form, and the need for monitoring of blood levels in pts taking capsules for disseminated mycoses.
• Posaconazole: Approved for prophylaxis of aspergillosis and candidiasis in high-risk immunocompromised pts, posaconazole is also effective against fluconazole-resistant Candida isolates and may be useful as salvage therapy for some other fungal infections.