Itraconazole: Difference between revisions
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== Background == |
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* Azole antifungal |
* Azole antifungal |
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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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== Therapeutic Drug Monitoring == |
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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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| [[Candida albicans]] |
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|[[Candida glabrata]] |
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|[[Candida krusei]] |
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|[[Candida parapsilosis]] |
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|[[Candida tropicalis]] |
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|[[Cryptococcus neoformans]] |
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|[[Cryptococcus gattii]] |
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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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|[[Aspergillus fumigatus]] |
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| 1 |
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|≤1 |
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|>1 |
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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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|[[Aspergillus niger]] |
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|4 |
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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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== 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 |
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* May be used once daily for the treatment of some [[Candida|candidal]] or [[dermatophytes|dermatophytic]] infections |
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== Safety == |
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=== 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 |
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* 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 === |
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* [[Adverse drug reaction::Headache]] |
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* [[Adverse drug reaction::Relative adrenal insufficiency]] |
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* [[Adverse drug reaction::Hepatotoxicity]] |
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* [[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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== Adverse Effects == |
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* Headaches |
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* Relative adrenal insufficiency |
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* Hepatotoxicity |
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* QTc prolongation |
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[[Category: |
[[Category:Triazoles]] |
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Latest revision as of 13:03, 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
