Itraconazole

Background

• Azole antifungal
• Indications include Alternaria, Blastomyces dermatitidis, Chromoblastomycosis, Coccidioides immitis, Cryptococcus, Entomophthoromycotina, Exophiala, Exserohilum, Fonsecaea, Histoplasma capsulatum, Mycetoma, Paracoccidioides brasiliensis, Sappinia diploidea, Sporothrix schenckii

Pharmacokinetics

• Blood concentrations are about 30% higher with oral solution compared to oral capsules
• Wide intersubject variability in levels
• Serum half-life is long
• Metabolized by CYP3A4 and inhibits CYP3A4
• Excreted in urine and feces

Dosing

• Preference for oral solution rather than capsules in severe infections (see PK section above)
• Can consider initial loading doses with IV or p.o
• Typical dose: 200 mg p.o. twice daily
• May be used once daily for the treatment of some candidal or dermatophytic infections

Safety

Therapeutic Drug Monitoring

• Recommended in more serious or severe infections
• Should be measured 5 to 7 days after starting or changing the dose, or when interacting medications are changed
  • Can likely be collected at any time after steady-state is reached, due to long halflife
• Target in prophylaxis is a trough level of 0.5 µg/mL
• Target in treatment is a trough level greater than 0.5 µg/mL, or greater than 0.5 to 1 µg/mL for blastomycosis
• Toxicity likely increased at trough levels greated than 10 µg/mL

Adverse Drug Reactions

• Headache
• Relative adrenal insufficiency
• Hepatotoxicity
• QTc prolongation

Further Reading

• Therapeutic drug monitoring (TDM) of antifungal agents: guidelines from the British Society for Medical Mycology. J Antimicrob Chemother. 2014;69(5):1162-1176. doi: 10.1093/jac/dkt508