Itraconazole: Difference between revisions

From IDWiki
No edit summary
No edit summary
 
(One intermediate revision by the same user not shown)
Line 8: Line 8:
 
* Wide intersubject variability in levels
  
* Wide intersubject variability in levels
 
* Serum half-life is long
  
* Serum half-life is long
−
* Metabolized by [[Metabolized by::CYP3A4]] and inhibits [[Inhibits:CYP3A4]]
 +
* Metabolized by [[Metabolized by::CYP3A4]] and inhibits [[Inhibits::CYP3A4]]
 
* Excreted in urine and feces
  
* Excreted in urine and feces
   
  +
=== Breakpoints ===
  +
{| class="wikitable"
  +
! rowspan="2" |Species
  +
! rowspan="2" |ECOFF (mg/L)
  +
! colspan="4" |Breakpoints (μg/mL)
  +
! colspan="4" |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
  +
| colspan="2" rowspan="5" |
  +
|>1
  +
|
  +
|
  +
|
  +
|
  +
|-
  +
|[[Aspergillus fumigatus]]
  +
| 1
  +
|≤1
  +
|>1
  +
|
  +
|
  +
|
  +
|
  +
|-
  +
|[[Aspergillus nidulans]]
  +
|1
  +
|≤1
  +
|>1
  +
|
  +
|
  +
|
  +
|
  +
|-
  +
|[[Aspergillus niger]]
  +
|4
  +
|—
  +
|—
  +
|
  +
|
  +
|
  +
|
  +
|-
  +
|[[Aspergillus terreus]]
  +
|0.5
  +
|≤1
  +
|>1
  +
|
  +
|
  +
|
  +
|
  +
|}
 
== Dosing ==
  
== Dosing ==
   

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
Retrieved from "https://idwiki.org/index.php?title=Itraconazole&oldid=10909"
Powered by MediaWiki
Powered by Semantic MediaWiki