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 |
| Molecular Weight | 306.27 |
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 | Avoid unless essential; associated with increased risk of miscarriage and congenital anomalies (e.g., craniofacial, skeletal) at high doses in animal studies. Single oral dose for vaginal candidiasis may be considered. |
| 2nd trimester | Use if clearly needed; no evidence of significant human teratogenicity in standard doses, but high or prolonged doses should be avoided. |
| 3rd trimester | Use if clearly needed; high doses near term have been associated with oligohydramnios and neonatal abnormalities (e.g., craniosynostosis, congenital heart disease). |
Clinical note
Comprehensive clinical and safety monograph for DIFLUCAN (DIFLUCAN).
| Placental transfer | Fluconazole crosses the placenta extensively; fetal plasma concentrations reach approximately 50-90% of maternal levels after oral administration. |
| Breastfeeding | Fluconazole is excreted into breast milk in low concentrations; after a single 150 mg oral dose, the infant dose is approximately 2-3% of the maternal weight-adjusted dose. Considered compatible with breastfeeding by the AAP; however, prolonged high-dose therapy should be used with caution. |
■ FDA Black Box Warning
No FDA black box warning.
| Serious Effects |
Hypersensitivity to fluconazole or any azole antifungalCoadministration with terfenadine (when fluconazole dose is 400 mg/day or higher)Coadministration with astemizole, cisapride, pimozide, quinidine, erythromycin, or other drugs known to prolong QT interval
| 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). |
| Food/Dietary |
Loading safety data…
| Lactation Rating | L2 (Safer) |
| 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. |
| 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. |
| No significant food interactions. Absorption unaffected by food. Avoid grapefruit juice as it may increase fluconazole levels. Reduce caffeine intake to prevent increased stimulant effects. |
| Clinical Pearls | DIFLUCAN (fluconazole) is a triazole antifungal with excellent oral bioavailability and CSF penetration. Use loading dose (e.g., 800 mg) for serious infections like cryptococcal meningitis. Monitor liver function; QT prolongation risk, especially with concurrent CYP3A4 inhibitors. Adjust dose for renal impairment (CrCl <50 mL/min). |
| Patient Advice | Take exactly as prescribed; do not skip doses. · Complete the full course even if you feel better. · Report signs of liver problems: dark urine, yellow skin/eyes, abdominal pain. · Avoid alcohol during treatment and for 3 days after last dose. · Use effective contraception if of childbearing age; fluconazole may cause fetal harm. · Notify your doctor if you have heart conditions or take other medications. · Take with or without food; if nausea occurs, take with food. |