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 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
