Itraconazole
From IDWiki
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
Breakpoints
| Species | ECOFF (mg/L) | Breakpoints (μg/mL) | Breakpoints (mm) | ||||||
|---|---|---|---|---|---|---|---|---|---|
| S | I | SDD | R | S | I | SDD | R | ||
| Candida albicans | |||||||||
| Candida glabrata | |||||||||
| Candida krusei | |||||||||
| Candida parapsilosis | |||||||||
| Candida tropicalis | |||||||||
| Cryptococcus neoformans | |||||||||
| Cryptococcus gattii | |||||||||
| Aspergillus flavus | 1 | ≤1 | >1 | ||||||
| Aspergillus fumigatus | 1 | ≤1 | >1 | ||||||
| Aspergillus nidulans | 1 | ≤1 | >1 | ||||||
| Aspergillus niger | 4 | — | — | ||||||
| Aspergillus terreus | 0.5 | ≤1 | >1 | ||||||
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
