FLUCONAZOLE IN SODIUM CHLORIDE 0.9%
Clinical safety rating: safe
No significant drug interactions Can cause hypernatremia and fluid overload.
Fluconazole is a triazole antifungal agent that inhibits fungal cytochrome P450-dependent 14α-demethylase, thereby blocking the conversion of lanosterol to ergosterol, an essential component of the fungal cell membrane. This leads to accumulation of toxic methylated sterols and depletion of ergosterol, disrupting membrane integrity and function.
| Metabolism | Fluconazole is primarily metabolized by the liver via the cytochrome P450 system, specifically CYP2C9 and CYP3A4. It also inhibits CYP2C9, CYP2C19, and CYP3A4. Approximately 80% of a dose is excreted unchanged in urine; the remainder is metabolized to inactive metabolites. |
| Excretion | Renal elimination of unchanged drug accounts for approximately 80% of the dose, with 11% as metabolites. Biliary/fecal excretion is minimal (<5%). |
| Half-life | Terminal elimination half-life is approximately 30 hours (range 20-50 hours) in adults with normal renal function. This long half-life allows once-daily dosing and achieves steady-state after 5-7 days. |
| Protein binding | 11-12% bound to plasma proteins (primarily albumin). |
| Volume of Distribution | Volume of distribution is approximately 0.7 L/kg (range 0.6-0.8 L/kg), indicating extensive distribution into total body water and tissues, including CSF, eyes, and urine. |
| Bioavailability | Bioavailability of oral fluconazole is >90% (oral solution and tablets). IV administration (as in this product) provides 100% bioavailability. |
| Onset of Action | IV infusion: Onset of antifungal activity occurs within hours, but clinical response may take days to weeks depending on infection site and severity. Oral: Peak plasma concentrations achieved in 1-2 hours; onset of clinical effect is similar to IV after first dose. |
| Duration of Action | Therapeutic concentrations persist for 24-48 hours after discontinuation due to long half-life. In patients with normal renal function, the duration of antifungal effect for a single dose extends beyond 24 hours, supporting once-daily dosing. |
400 mg IV loading dose on day 1, then 200 mg IV once daily; for invasive candidiasis or cryptococcal meningitis, 800 mg IV loading dose then 400 mg IV once daily
| Dosage form | INJECTABLE |
| Renal impairment | CrCl >50 mL/min: no adjustment; CrCl ≤50 mL/min (not on dialysis): administer 50% of recommended dose; hemodialysis: one full dose after each dialysis session |
| Liver impairment | Child-Pugh A and B: no adjustment required; Child-Pugh C: limited data, use with caution and monitor closely |
| Pediatric use | Loading dose: 12 mg/kg IV (max 800 mg) on day 1; maintenance: 6 mg/kg IV once daily (max 400 mg); for invasive candidiasis or cryptococcal meningitis: loading 12 mg/kg IV (max 800 mg), then 6-12 mg/kg IV once daily (max 800 mg) |
| Geriatric use | No specific dose adjustment; use based on renal function; age-related decline in renal function should be considered and CrCl calculated for dosing |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
No significant drug interactions Can cause hypernatremia and fluid overload.
| FDA category | Animal |
| Breastfeeding | Fluconazole is excreted into breast milk in concentrations similar to maternal plasma. The milk-to-plasma (M/P) ratio is approximately 1.0. In full-term infants with normal renal function, exposure is low and considered compatible with breastfeeding. However, caution is advised in preterm infants or those with renal impairment. Monitor infant for diarrhea, jaundice, or feeding difficulties. |
| Teratogenic Risk |
■ FDA Black Box Warning
No FDA black box warning.
| Common Effects | fluid replacement |
| Serious Effects |
["Hypersensitivity to fluconazole or any excipient","Coadministration with terfenadine, cisapride, or pimozide (risk of serious cardiac arrhythmias)","Coadministration with ergot alkaloids (risk of ergotism)","Use in pregnancy (especially high-dose therapy) unless potential benefit outweighs risk"]
| Precautions | ["Hepatotoxicity: Monitor liver function tests; risk of hepatic necrosis and death.","QT prolongation: Risk of torsades de pointes, especially in patients with electrolyte abnormalities or concurrent QT-prolonging drugs.","Fetal risk: Use in pregnancy only if clearly needed, especially during first trimester (potential for teratogenicity).","Drug interactions: Increased risk of bleeding with warfarin; increased risk of toxicity from cyclosporine, phenytoin, and oral hypoglycemics; avoid coadministration with terfenadine, cisapride, and pimozide due to risk of QT prolongation."] |
Loading safety data…
| First trimester: Fluconazole is associated with a dose-dependent risk of congenital malformations, including craniofacial, skeletal, and cardiac defects, particularly with prolonged use of high doses (≥400 mg/day). Epidemiological data suggest a small increased risk of spontaneous abortion and major malformations with low-dose exposure. Second and third trimesters: Limited evidence of fetal toxicity; however, risks include preterm delivery and low birth weight with high-dose therapy. FDA Pregnancy Category D. |
| Fetal Monitoring | Maternal: Hepatic function tests (ALT, AST) baseline and periodically, renal function, complete blood count, and serum potassium. Fetal: Ultrasound for congenital anomalies if exposed in first trimester, especially with high doses. Neonatal: Monitor for signs of hepatotoxicity, hypoglycemia, or electrolyte imbalances. |
| Fertility Effects | Fluconazole does not appear to adversely affect human fertility. In animal studies, high doses caused reversible impairment of spermatogenesis and ovulation, but no such effects have been reported in humans. Limited human data show no significant impact on conception rates. |