DIFLUCAN IN DEXTROSE 5% IN PLASTIC CONTAINER
Clinical safety rating: caution
Comprehensive clinical and safety monograph for DIFLUCAN IN DEXTROSE 5% IN PLASTIC CONTAINER (DIFLUCAN IN DEXTROSE 5% IN PLASTIC CONTAINER).
Diflucan (fluconazole) inhibits fungal cytochrome P450 14α-demethylase (CYP51), blocking the conversion of lanosterol to ergosterol, a key component of the fungal cell membrane. This disrupts membrane integrity and function, leading to fungal cell death. At high concentrations, it may also directly damage fungal membranes.
| Metabolism | Fluconazole is primarily metabolized by the liver via CYP3A4 and CYP2C9 isoenzymes to inactive metabolites. Approximately 80% of an oral dose is excreted unchanged in urine. For intravenous (IV) formulation, the drug is available as fluconazole in 5% dextrose solution; the dextrose is metabolized via glycolysis and the citric acid cycle. |
| Excretion | Approximately 80% of the dose is excreted unchanged in urine via glomerular filtration and tubular secretion; about 11% is excreted as metabolites in urine; fecal excretion accounts for less than 5%. |
| Half-life | Terminal elimination half-life is approximately 30 hours (range 20-50 hours) in adults with normal renal function; prolonged to 98 hours in end-stage renal disease, requiring dose adjustment. |
| Protein binding | Low protein binding: 11-12% bound to plasma albumin; binding is independent of concentration. |
| Volume of Distribution | Volume of distribution approximates total body water: 0.7 L/kg (range 0.6-0.8 L/kg), indicating extensive tissue distribution, including CNS penetration (CSF concentrations ~50-90% of plasma). |
| Bioavailability | Oral bioavailability exceeds 90% (range 90-95%); not affected by food or gastric pH. Intravenous bioavailability is 100%. |
| Onset of Action | Oral: Peak plasma concentrations achieved in 1-2 hours; therapeutic effect for mucosal candidiasis begins within 24-48 hours. Intravenous: Immediate systemic availability; clinical effect for systemic infections may be seen within 24 hours. |
| Duration of Action | Single oral dose for vaginal candidiasis provides therapeutic concentrations for 72 hours; for systemic infections, daily dosing maintains steady state after 5-10 days due to long half-life. |
| Molecular Weight | 306.27 |
200 mg IV loading dose, then 100-200 mg IV once daily; for invasive candidiasis, 800 mg IV loading dose then 400 mg IV once daily.
| Dosage form | INJECTABLE |
| Renal impairment | For CrCl 10-50 mL/min: extend dosing interval to 24-48 hours; for CrCl <10 mL/min (not on dialysis): every 48-72 hours; hemodialysis: administer 50% of dose after each dialysis session. |
| Liver impairment | No adjustment recommended for mild to moderate hepatic impairment; for severe hepatic impairment (Child-Pugh Class C), consider dose reduction; specific guidelines not established. |
| Pediatric use | For candidemia: 12-25 mg/kg IV daily (based on adult equivalence); for prophylaxis: 3-12 mg/kg IV daily; for oropharyngeal candidiasis: 6 mg/kg IV on day 1 then 3 mg/kg IV daily. Maximum adult dose not to exceed 600 mg daily. |
| Geriatric use | Adjust dose based on renal function; no specific age-related adjustments other than renal; monitor for QT prolongation and hepatic toxicity. |
| 1st trimester | Avoid due to risk of congenital anomalies, particularly cardiac malformations, with high doses or prolonged use. |
| 2nd trimester | Use only if clearly needed; single dose therapy for vaginal candidiasis is unlikely to cause fetal harm. |
| 3rd trimester | Use only if clearly needed; prolonged use near term may increase risk of premature labor and fetal toxicity. |
Clinical note
Comprehensive clinical and safety monograph for DIFLUCAN IN DEXTROSE 5% IN PLASTIC CONTAINER (DIFLUCAN IN DEXTROSE 5% IN PLASTIC CONTAINER).
| Placental transfer | Extensive; fluconazole crosses the placenta readily reaching fetal plasma levels similar to maternal levels. |
| Breastfeeding | Fluconazole is excreted in human milk at concentrations similar to plasma. Single doses up to 200 mg are likely safe, but avoid high doses or repeated dosing due to potential infant accumulation. |
■ FDA Black Box Warning
None
| Serious Effects |
Known hypersensitivity to fluconazole or any excipientConcomitant use with CYP3A4 substrates that prolong QT interval (e.g., terfenadine, cisapride, pimozide, quinidine) due to risk of serious cardiovascular eventsCo-administration with drugs that are highly dependent on CYP3A4 and have a narrow therapeutic index (e.g., astemizole, erythromycin)
| Precautions | Hepatotoxicity: elevations in liver enzymes, rare cases of severe hepatic necrosis; monitor liver function., Anaphylaxis and severe skin reactions (Stevens-Johnson syndrome, toxic epidermal necrolysis)., QT prolongation and torsades de pointes: avoid in patients with hypokalemia, bradycardia, or concurrent QT-prolonging drugs., Fetal risk: use in pregnancy only if potential benefit outweighs risk; high doses associated with teratogenicity (contraindicated in first trimester for chronic, high-dose therapy)., Renal impairment: dosage adjustment required., Drug interactions: potent CYP2C9 and CYP3A4 inhibitor, affects warfarin, phenytoin, cyclosporine, tacrolimus, oral hypoglycemics, and other drugs. |
| Food/Dietary |
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| Lactation Rating | L2 (Safer) |
| Teratogenic Risk | Fluconazole is teratogenic in humans. First trimester exposure at doses ≥400 mg/day is associated with a distinct pattern of congenital anomalies including brachycephaly, abnormal facies, cleft palate, femoral bowing, and arthrogryposis. Second and third trimester exposure at high doses may increase risk of premature birth and low birth weight. Low doses (150 mg single dose) for vaginal candidiasis have not been consistently linked to major malformations but should be avoided in first trimester unless essential. |
| Fetal Monitoring | Monitor maternal liver function tests (LFTs) periodically due to potential hepatotoxicity. In pregnancy, perform fetal ultrasound for anomaly detection if high-dose exposure occurred in first trimester. Monitor maternal renal function and electrolytes (hypokalemia) during prolonged therapy. Monitor infant for adverse effects such as jaundice or liver enzyme elevation if maternal therapy continues during breastfeeding. |
| Fertility Effects | In animal studies, high doses of fluconazole caused prolonged estrus cycles, reduced fertility, and dystocia. Data in humans are limited; no specific adverse effects on fertility have been reported, but hormonal contraception efficacy may be reduced due to potential enzyme induction (though fluconazole is primarily an inhibitor). |
| No significant food interactions. Avoid grapefruit juice as it may alter drug metabolism. Take with or without food. |
| Clinical Pearls | Fluconazole in 5% dextrose is a triazole antifungal. Monitor renal function and adjust dose in CrCl <50 mL/min. Avoid rapid infusion; administer over 1-2 hours. Check for QT prolongation risk, especially with other QT-prolonging drugs. Use with caution in hepatic impairment. |
| Patient Advice | Do not stop taking this medication without consulting your doctor. · Finish the full course of therapy even if you feel better. · Report signs of liver problems (yellowing skin/eyes, dark urine, abdominal pain) or allergic reactions (rash, difficulty breathing) immediately. · Avoid alcohol as it may increase risk of liver injury. · Inform your doctor of all other medications, especially blood thinners, diabetes drugs, and drugs for irregular heartbeat. |