Fluconazole: Difference between revisions
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*Antifungal in the triazole family with excellent bioavadilability but limited efficacy outside of ''Candida'' |
*Antifungal in the triazole family with excellent bioavadilability but limited efficacy outside of ''Candida'' |
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===Pharmacokinetics and Pharmacodynamics=== |
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* |
*Good oral bioavailability |
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* |
*Good CNS penetration |
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* |
*Fungistatic |
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*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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|[[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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|[[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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|[[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]] |
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Latest revision as of 23:25, 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
