Itraconazole: Difference between revisions
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* Indications include {{#ask: [[Is treated by::itraconazole]]}} |
* Indications include {{#ask: [[Is treated by::itraconazole]]}} |
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+ | === Pharmacokinetics === |
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+ | |||
+ | * Blood concentrations are about 30% higher with oral solution compared to oral capsules |
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+ | * Wide intersubject variability in levels |
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+ | * Serum half-life is long |
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+ | * Metabolized by [[Metabolized by::CYP3A4]] and inhibits [[Inhibits::CYP3A4]] |
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+ | * Excreted in urine and feces |
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+ | |||
+ | === Breakpoints === |
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+ | {| class="wikitable" |
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+ | ! rowspan="2" |Species |
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+ | ! rowspan="2" |ECOFF (mg/L) |
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+ | ! colspan="4" |Breakpoints (μg/mL) |
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+ | ! colspan="4" |Breakpoints (mm) |
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+ | |- |
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+ | ! S |
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+ | ! I |
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+ | !SDD |
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+ | !R |
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+ | !S |
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+ | !I |
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+ | ! SDD |
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+ | ! R |
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+ | |- |
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+ | | [[Candida albicans]] |
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+ | | |
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+ | | |
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+ | | |
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+ | | |
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+ | | |
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+ | | |
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+ | | |
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+ | | |
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+ | | |
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+ | |- |
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+ | |[[Candida glabrata]] |
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+ | | |
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+ | | |
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+ | | |
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+ | | |
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+ | | |
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+ | | |
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+ | | |
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+ | | |
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+ | | |
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+ | |- |
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+ | |[[Candida krusei]] |
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+ | | |
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+ | | |
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+ | | |
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+ | | |
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+ | | |
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+ | | |
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+ | | |
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+ | | |
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+ | | |
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+ | |- |
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+ | |[[Candida parapsilosis]] |
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+ | | |
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+ | | |
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+ | | |
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+ | | |
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+ | | |
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+ | | |
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+ | | |
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+ | | |
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+ | | |
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+ | |- |
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+ | |[[Candida tropicalis]] |
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+ | | |
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+ | | |
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+ | | |
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+ | | |
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+ | | |
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+ | | |
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+ | | |
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+ | | |
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+ | | |
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+ | |- |
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+ | |[[Cryptococcus neoformans]] |
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+ | | |
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+ | | |
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+ | | |
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+ | | |
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+ | | |
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+ | | |
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+ | | |
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+ | | |
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+ | | |
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+ | |- |
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+ | |[[Cryptococcus gattii]] |
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+ | | |
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+ | | |
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+ | | |
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+ | | |
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+ | | |
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+ | | |
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+ | | |
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+ | | |
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+ | | |
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+ | |- |
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+ | |[[Aspergillus flavus]] |
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+ | |1 |
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+ | |≤1 |
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+ | | colspan="2" rowspan="5" | |
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+ | |>1 |
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+ | | |
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+ | | |
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+ | | |
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+ | | |
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+ | |- |
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+ | |[[Aspergillus fumigatus]] |
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+ | | 1 |
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+ | |≤1 |
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+ | |>1 |
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+ | | |
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+ | | |
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+ | | |
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+ | | |
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+ | |- |
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+ | |[[Aspergillus nidulans]] |
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+ | |1 |
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+ | |≤1 |
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+ | |>1 |
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+ | | |
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+ | | |
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+ | | |
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+ | | |
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+ | |- |
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+ | |[[Aspergillus niger]] |
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+ | |4 |
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+ | |— |
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+ | |— |
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+ | | |
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+ | | |
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+ | | |
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+ | | |
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+ | |- |
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+ | |[[Aspergillus terreus]] |
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+ | |0.5 |
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+ | |≤1 |
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+ | |>1 |
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+ | | |
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+ | | |
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+ | | |
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+ | | |
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+ | |} |
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== Dosing == |
== Dosing == |
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+ | * Preference for oral solution rather than capsules in severe infections (see PK section above) |
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+ | * Can consider initial loading doses with IV or p.o |
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* Typical dose: 200 mg p.o. twice daily |
* Typical dose: 200 mg p.o. twice daily |
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− | * May be used once daily for the treatment of some [[dermatophytes]] |
+ | * May be used once daily for the treatment of some [[Candida|candidal]] or [[dermatophytes|dermatophytic]] infections |
== Safety == |
== Safety == |
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=== Therapeutic Drug Monitoring === |
=== Therapeutic Drug Monitoring === |
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+ | * Recommended in more serious or severe infections |
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* Should be measured 5 to 7 days after starting or changing the dose, or when interacting medications are changed |
* Should be measured 5 to 7 days after starting or changing the dose, or when interacting medications are changed |
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+ | ** Can likely be collected at any time after steady-state is reached, due to long halflife |
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− | * Target in prophylaxis is a trough ot 0.5 mg/L |
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− | * Target in |
+ | * 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]] |
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+ | * Toxicity likely increased at trough levels greated than 10 µg/mL |
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=== Adverse Drug Reactions === |
=== Adverse Drug Reactions === |
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* [[Adverse drug reaction::Hepatotoxicity]] |
* [[Adverse drug reaction::Hepatotoxicity]] |
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* [[Adverse drug reaction::QTc prolongation]] |
* [[Adverse drug reaction::QTc prolongation]] |
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+ | |||
+ | == Further Reading == |
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+ | |||
+ | * Therapeutic drug monitoring (TDM) of antifungal agents: guidelines from the British Society for Medical Mycology. ''J Antimicrob Chemother.'' 2014;69(5):1162-1176. doi: [https://doi.org/10.1093/jac/dkt508 10.1093/jac/dkt508] |
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[[Category:Triazoles]] |
[[Category:Triazoles]] |
Latest revision as of 09:03, 22 October 2024
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