Fluconazole: Difference between revisions
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*Fungistatic |
*Fungistatic |
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*Efficacy predicted by AUC/MIC ratio |
*Efficacy predicted by AUC/MIC ratio |
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− | *Susceptibility breakpoints for [[Candida albicans]] are: |
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− | **Susceptible MIC ≤2 |
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− | **Susceptible dose-dependent MIC 4 |
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− | **Resistant MIC ≥8 |
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+ | ===Clinical Breakpoints=== |
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− | ==Monitoring== |
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+ | {| class="wikitable" |
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+ | ! rowspan="2" |Species |
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+ | ! rowspan="2" |ECV (μg/mL) |
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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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+ | !SDD |
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+ | !I |
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+ | !R |
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+ | !S |
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+ | !SDD |
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+ | !I |
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+ | !R |
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+ | |- |
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+ | |[[Candida albicans]] |
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+ | |0.5 |
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+ | |≤2 |
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+ | |4 |
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+ | |— |
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+ | |≥8 |
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+ | |≥17 |
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+ | |14-16 |
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+ | |— |
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+ | |≤13 |
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+ | |- |
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+ | |[[Candida dubliniensis]] |
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+ | |0.5 |
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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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+ | |8 |
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+ | |— |
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+ | |≤32 |
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+ | |— |
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+ | |≥64 |
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+ | |— |
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+ | |≥15 |
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+ | |— |
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+ | |≤14 |
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+ | |- |
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+ | |[[Candida guilliermondii]] |
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+ | |8 |
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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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+ | | colspan="4" |intrinsically resistant |
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+ | | colspan="4" |intrinsically resistant |
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+ | |- |
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+ | |[[Candida lusitaniae]] |
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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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+ | | |
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+ | | |
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+ | | |
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+ | |- |
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+ | |[[Candida parapsilosis]] |
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+ | |1 |
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+ | |≤2 |
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+ | |4 |
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+ | |— |
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+ | |≥8 |
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+ | |≥17 |
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+ | |14-16 |
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+ | |— |
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+ | |≤13 |
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+ | |- |
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+ | |[[Candida tropicalis]] |
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+ | |1 |
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+ | |≤2 |
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+ | |4 |
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+ | |— |
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+ | |≥8 |
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+ | |≥17 |
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+ | |14-16 |
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+ | |— |
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+ | |≤13 |
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+ | |- |
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+ | |[[Cryptococcus neoformans]] |
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+ | |8 |
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+ | | colspan="8" rowspan="2" | |
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+ | |- |
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+ | |[[Cryptococcus gattii]] |
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+ | |16-32 |
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+ | |} |
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+ | |||
+ | == Dosing == |
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+ | |||
+ | * Invasive candidiasis: fluconazole 6 to 12 mg/kg PO/IV q24h |
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+ | *[[Candidemia]]: 12 mg/kg IV load followed by 6 mg/kg PO/IV daily |
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+ | **Can use 800 mg daily for isolates that show dose-dependent susceptibility |
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+ | *[[Vaginal candidiasis]]: 150 mg PO once, with or without intravaginal [[clotrimazole]] |
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+ | *[[Oral thrush]]: 100 mg po daily for 7 to 14 days |
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+ | *[[Esophageal candidiasis]]: 200 mg PO daily for 14 to 21 days |
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+ | *[[Urinary tract infection]]: 200 mg po daily for 7 to 14 days |
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+ | *[[Intra-abdominal infections|Intraabdominal infection]]: 400 mg PO daily |
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+ | |||
+ | ===Monitoring=== |
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*ECG for QT prolongation |
*ECG for QT prolongation |
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*Beware [[Adverse drug reaction::drug-drug interactions]], especially with new DOACs |
*Beware [[Adverse drug reaction::drug-drug interactions]], especially with new DOACs |
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− | [[Category: |
+ | [[Category:Triazoles]] |
Latest revision as of 19:25, 12 November 2021
Background
- Antifungal in the triazole family with excellent bioavadilability but limited efficacy outside of Candida
Pharmacokinetics and Pharmacodynamics
- Good oral bioavailability
- Good CNS penetration
- Fungistatic
- Efficacy predicted by AUC/MIC ratio
Clinical Breakpoints
Species | ECV (μg/mL) | Breakpoints (μg/mL) | Breakpoints (mm) | ||||||
---|---|---|---|---|---|---|---|---|---|
S | SDD | I | R | S | SDD | I | R | ||
Candida albicans | 0.5 | ≤2 | 4 | — | ≥8 | ≥17 | 14-16 | — | ≤13 |
Candida dubliniensis | 0.5 | ||||||||
Candida glabrata | 8 | — | ≤32 | — | ≥64 | — | ≥15 | — | ≤14 |
Candida guilliermondii | 8 | ||||||||
Candida krusei | intrinsically resistant | intrinsically resistant | |||||||
Candida lusitaniae | 1 | ||||||||
Candida parapsilosis | 1 | ≤2 | 4 | — | ≥8 | ≥17 | 14-16 | — | ≤13 |
Candida tropicalis | 1 | ≤2 | 4 | — | ≥8 | ≥17 | 14-16 | — | ≤13 |
Cryptococcus neoformans | 8 | ||||||||
Cryptococcus gattii | 16-32 |
Dosing
- Invasive candidiasis: fluconazole 6 to 12 mg/kg PO/IV q24h
- Candidemia: 12 mg/kg IV load followed by 6 mg/kg PO/IV daily
- Can use 800 mg daily for isolates that show dose-dependent susceptibility
- Vaginal candidiasis: 150 mg PO once, with or without intravaginal clotrimazole
- Oral thrush: 100 mg po daily for 7 to 14 days
- Esophageal candidiasis: 200 mg PO daily for 14 to 21 days
- Urinary tract infection: 200 mg po daily for 7 to 14 days
- Intraabdominal infection: 400 mg PO daily
Monitoring
- ECG for QT prolongation
- Liver enzymes for hepatitis
Adverse Drug Reactions
- Best side effect profiles of the antifungals
- Before starting, check:
- Liver enzymes as baseline (hepatitis)
- Creatinine (requires renal dosing)
- EKG (QTc prolongation)
- Beware drug-drug interactions, especially with new DOACs