DIFLUCAN
Clinical safety rating: caution
Comprehensive clinical and safety monograph for DIFLUCAN (DIFLUCAN).
Diflucan (fluconazole) is a triazole antifungal agent that inhibits fungal cytochrome P450 14-alpha-demethylase, thereby blocking the conversion of lanosterol to ergosterol, an essential component of the fungal cell membrane. This leads to increased membrane permeability and inhibition of fungal growth.
| Metabolism | Fluconazole is primarily metabolized by the liver, mainly via CYP2C9 and to a lesser extent CYP3A4. The major metabolite is a N-oxide metabolite. Approximately 80% of the drug is excreted unchanged in urine. |
| Excretion | Renal: 80% unchanged; fecal/biliary: 11% as metabolites |
| Half-life | 30 hours (range 20-50 hours); prolonged in renal impairment (up to 98 hours in CrCl <20 mL/min) |
| Protein binding | 11-12% primarily to albumin |
| Volume of Distribution | 0.7 L/kg (50 L in adults); extensive tissue penetration including CSF (50-90% of plasma concentrations) |
| Bioavailability | Oral: >90% (capsule); IV: 100% |
| Onset of Action | IV: immediate; oral: 1-2 hours to therapeutic plasma levels; topical: 2-3 days for clinical response |
| Duration of Action | 150 mg single dose: 72 hours for vaginal candidiasis; daily dosing: 24-48 hours; prolonged due to long half-life |
Oral or IV: 200-400 mg loading dose, then 100-200 mg once daily. Dose and duration depend on indication.
| Dosage form | FOR SUSPENSION |
| Renal impairment | GFR >50: no adjustment; GFR 10-50: 50% of dose or every 48 hours; GFR <10: 50% of dose every 48 hours. |
| Liver impairment | No specific Child-Pugh based adjustments; use with caution in severe hepatic impairment. |
| Pediatric use | Oral or IV: 6-12 mg/kg loading dose, then 3-6 mg/kg once daily, not to exceed 600 mg daily. |
| Geriatric use | Use standard dosing with caution for renal function; adjust dose based on creatinine clearance. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for DIFLUCAN (DIFLUCAN).
| Breastfeeding | Fluconazole excreted into breast milk; milk-to-plasma ratio approximately 0.9. With maternal doses up to 200 mg/day, infant dose is about 2-3 mg/kg/day (10-20% of maternal weight-adjusted dose), which is below the neonatal therapeutic dose. However, avoid high-dose therapy (>800 mg/day) during breastfeeding. Monitor infant for jaundice, diarrhea, or liver enzyme abnormalities. |
| Teratogenic Risk | First trimester: Single low dose (<150 mg) for vaginal candidiasis not associated with increased risk of malformations. Chronic high doses (≥400 mg/day) associated with major congenital malformations including craniosynostosis, congenital heart disease, and cleft palate (based on multiple case-control studies). Second/third trimesters: Low-dose short courses appear safe; prolonged high-dose exposure may cause oligohydramnios, joint contractures, and preterm delivery. |
■ FDA Black Box Warning
No FDA black box warning.
| Serious Effects |
["Hypersensitivity to fluconazole or any excipient","Concurrent use with terfenadine, cisapride, astemizole, or pimozide (due to risk of QT prolongation and torsades de pointes)","Concurrent use with quinidine or erythromycin (due to increased risk of cardiotoxicity)"]
| Precautions | ["Hepatic injury: Rare cases of serious hepatotoxicity, including hepatic necrosis and death. Discontinue if signs of liver injury occur.","Cardiovascular effects: Prolongs QT interval; caution in patients with risk factors such as electrolyte imbalance, concurrent QT-prolonging drugs, or pre-existing cardiac disease.","Exfoliative skin disorders: Rarely associated with Stevens-Johnson syndrome; discontinue if rash develops in patients with systemic fungal infections.","Fetal harm: Data suggest increased risk of spontaneous abortion and congenital anomalies; avoid use in pregnancy unless necessary.","CYP enzyme inhibition: Increases exposure to drugs metabolized by CYP2C9 and CYP3A4, including warfarin, phenytoin, and sulfonylureas.","Renal impairment: Dose adjustment required in renal insufficiency (CrCl <50 mL/min)."] |
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| Fetal Monitoring | Monitor maternal liver function tests (ALT, AST, alkaline phosphatase) at baseline and periodically, especially with prolonged treatment. In third trimester chronic high-dose use: fetal ultrasound for amniotic fluid volume, joint contractures, and cardiac anatomy. Assess neonatal bilirubin and liver enzymes if maternal high-dose fluconazole used near term. |
| Fertility Effects | No detrimental effects on female fertility in animal studies. In males, no human data; animal studies show no impairment of fertility at clinically relevant doses. |