DIFLUCAN IN SODIUM CHLORIDE 0.9%
Clinical safety rating
safeNo significant drug interactions Can cause hypernatremia and fluid overload.
Fluconazole, a bis-triazole antifungal, selectively inhibits fungal cytochrome P450 14α-demethylase (CYP51), blocking the conversion of lanosterol to ergosterol, a critical component of the fungal cell membrane. This disrupts membrane integrity and function, leading to fungal cell death.
| Metabolism | Primarily hepatic metabolism via cytochrome P450 isoenzymes (CYP2C9, CYP3A4, and to a lesser extent CYP2C19). Fluconazole is a moderate inhibitor of CYP2C9 and CYP3A4 and a weak inhibitor of CYP2C19. Approximately 80% of an administered dose is excreted unchanged in urine; the remainder is excreted as metabolites. |
| Excretion | Primarily renal excretion of unchanged drug (~80% of dose). Approximately 11% excreted as metabolites. Biliary/fecal excretion accounts for <5%. |
| Half-life | Terminal elimination half-life is approximately 30 hours (range 20-50 hours) in adults with normal renal function. Prolonged in renal impairment (up to 98 hours in creatinine clearance <20 mL/min). |
| Protein binding | Plasma protein binding is 11-12%, primarily to albumin. The low binding results in extensive free drug distribution. |
| Volume of Distribution | Volume of distribution (Vd) is approximately 0.7 L/kg (range 0.5-0.9 L/kg), indicating extensive distribution into total body water and tissues, including penetration into cerebrospinal fluid (CSF), vitreous humor, and peritoneal fluid. |
| Bioavailability | Oral bioavailability is >90%, essentially complete. Absorption is unaffected by gastric pH or food. Intravenous bioavailability is 100%. |
| Onset of Action | Intravenous: onset of antifungal activity occurs within 1-2 hours after start of infusion. Oral: onset within 2-4 hours after ingestion. |
| Duration of Action | Duration of therapeutic effect is approximately 24 hours due to once-daily dosing. Clinical response in fungal infections (e.g., candidemia) typically observed within days to weeks; maintenance therapy often continues for 2-4 weeks after resolution of symptoms. |
| Molecular Weight | 306.27 |
400 mg IV on day 1, then 200 mg IV once daily; for esophageal candidiasis: 200 mg IV on day 1, then 100 mg IV once daily
| Dosage form | INJECTABLE |
| Renal impairment | CrCl >50 mL/min: no adjustment; CrCl 21-50 mL/min: administer 50% of usual dose; CrCl 11-20 mL/min: administer 25% of usual dose; intermittent hemodialysis: administer full dose after each dialysis session |
| Liver impairment | Child-Pugh Class A and B: no adjustment; Child-Pugh Class C: insufficient data, use with caution |
| Pediatric use | Neonates (0-14 days): 6-12 mg/kg IV every 72 hours; Infants/Children (15 days-1 year): 6-12 mg/kg IV every 24 hours; Children >1 year: 6-12 mg/kg IV every 24 hours; maximum 400 mg/day |
| Geriatric use | No specific dose adjustment recommended; monitor renal function and adjust dose based on creatinine clearance due to age-related renal impairment |
| 1st trimester | Avoid in first trimester unless essential; associated with increased risk of spontaneous abortion and musculoskeletal malformations with high doses. |
| 2nd trimester | Use only if clearly needed; caution with prolonged use due to potential fetal harm. |
| 3rd trimester | Use only if clearly needed; caution near term due to risk of neonatal jaundice from bilirubin displacement. |
Clinical note
No significant drug interactions Can cause hypernatremia and fluid overload.
| FDA category | Animal |
| Placental transfer | Fluconazole crosses the placenta extensively; fetal plasma concentrations reach approximately 80-90% of maternal levels. |
| Breastfeeding | Fluconazole is excreted into breast milk in concentrations similar to plasma. Caution in breastfeeding due to potential for adverse effects in breastfed infants, especially with high maternal doses. Consider discontinuing drug or nursing. |
| Lactation Rating | L3 (Moderately Safe) - use with caution |
| Teratogenic Risk | Fluconazole is contraindicated in the first trimester except for treatment of serious fungal infections where benefit outweighs risk. First trimester: increased risk of spontaneous abortion and congenital anomalies (e.g., craniosynostosis, cardiac defects, cleft lip/palate) with prolonged high-dose therapy (≥400 mg/day). Second and third trimesters: low risk at single 150 mg dose; high-dose prolonged use may cause fetal toxicity. Category D for first trimester; Category C for later trimesters. |
| Fetal Monitoring | Monitor liver function tests (AST, ALT, bilirubin), renal function (serum creatinine, BUN), and complete blood count (CBC) periodically during therapy. In high-dose regimens, monitor for signs of hepatotoxicity, QT prolongation (ECG), and fetal surveillance if used in pregnancy (ultrasound for early detection of anomalies). |
| Fertility Effects | In animal studies, high-dose fluconazole impaired fertility in male and female rats (reduced spermatogenesis, prolonged estrous cycles). Human data are limited; no significant impact on fertility is expected at standard doses, but high-dose long-term use may potentially affect reproductive function. Clinical significance in humans is unknown. |
■ FDA Black Box Warning
None
| Common Effects | fluid replacement |
| Serious Effects |
Known hypersensitivity to fluconazole or any excipientConcomitant use with cisapride or ergotamine (risk of prolonged QT interval and serious arrhythmias)
| Precautions | Hepatotoxicity: Elevations in liver enzymes have been observed; rare cases of severe hepatic necrosis and fatal hepatic failure have occurred. Discontinue if signs of hepatic injury develop., QT prolongation: Fluconazole may prolong the QT interval, potentially leading to torsade de pointes. Caution in patients with electrolyte disturbances, bradyarrhythmias, or concurrent use of other QT-prolonging drugs., Adrenal insufficiency: Cases of reversible adrenal insufficiency have been reported, particularly in patients receiving corticosteroids or those with stress., Dermatologic reactions: Exfoliative skin disorders (e.g., Stevens-Johnson syndrome) may occur. Discontinue if rash progresses., Renal impairment: Dose adjustment required in patients with renal dysfunction (CrCl <50 mL/min) due to extensive renal elimination., Pregnancy: Use only if benefit outweighs risk; single-dose therapy for vulvovaginal candidiasis is not recommended during pregnancy., Lactation: Fluconazole is excreted in human milk; caution in nursing mothers. |
| Food/Dietary | No significant food interactions. Avoid alcohol due to potential hepatotoxicity. |
| Clinical Pearls | Do not use with other fluconazole formulations to avoid dose errors. Monitor renal function and adjust dose in creatinine clearance <50 mL/min. Infuse over 1-2 hours; avoid rapid infusion due to risk of QT prolongation. Check for drug interactions with warfarin, sulfonylureas, phenytoin, and CYP2C9 substrates. |
| Patient Advice | This medication is used to treat fungal infections and is given intravenously. · Report any signs of liver problems (dark urine, yellowing eyes/skin, abdominal pain) or irregular heartbeat immediately. · Avoid alcohol consumption during treatment and for several days after completion. · Inform your doctor if you are pregnant, plan to become pregnant, or are breastfeeding. · Do not stop treatment early even if you feel better; complete the full course. |
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