Itraconazole: Difference between revisions

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== Background ==
 
* Azole antifungal
  
* Azole antifungal
 
* Indications include {{#ask: [[Is treated by::itraconazole]]}}
  
* Indications include {{#ask: [[Is treated by::itraconazole]]}}
   
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=== Pharmacokinetics ===
−
== 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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|-
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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 ==
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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
  +
* 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
  +
  +
== Safety ==
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=== Therapeutic Drug Monitoring ===
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* 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
  
* 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 ot 0.5 mg/L
  
−
* Target in treatment is a trough >0.5 mg/L
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* 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
  +
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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 ==
  
−
* [[Has adverse drug reaction::Headache]]
  
−
* [[Has adverse drug reaction::Relative adrenal insufficiency]]
  
−
* [[Has adverse drug reaction::Hepatotoxicity]]
  
−
* [[Has adverse drug reaction::QTc prolongation]]
  
   
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[[Category:Antifungals]]
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[[Category:Triazoles]]

Latest revision as of 09:03, 22 October 2024

Background

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
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