FLUCONAZOLE IN SODIUM CHLORIDE 0.9%
Clinical safety rating
safeNo 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. |
| Molecular Weight | 306.27 |
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 | Avoid unless essential; high doses associated with congenital anomalies. |
| 2nd trimester | Use only if clearly needed; monitor for hepatotoxicity. |
| 3rd trimester | Use only if clearly needed; monitor for neonatal toxicity. |
Clinical note
No significant drug interactions Can cause hypernatremia and fluid overload.
| FDA category | Animal |
| Placental transfer | Extensive placental transfer; achieves therapeutic levels in fetal plasma. |
| Breastfeeding | Fluconazole is excreted into breast milk in concentrations similar to plasma. Consider risk of infant exposure; monitor for adverse effects. |
| Lactation Rating | L2 (Safer if needed) |
| Teratogenic Risk | 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. |
■ FDA Black Box Warning
No FDA black box warning.
| Common Effects | fluid replacement |
| Serious Effects |
Hypersensitivity to fluconazole or any excipientConcomitant use with terfenadineConcomitant use with cisaprideConcomitant use with pimozideConcomitant use with quinidine
| 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. |
| Food/Dietary | No significant food interactions. However, avoid grapefruit and grapefruit juice as it may increase fluconazole levels. Maintain consistent intake of caffeine and alcohol as they may increase side effects like dizziness or liver strain. |
| Clinical Pearls | Fluconazole in 0.9% NaCl is an IV formulation; ensure compatibility before administration. May prolong QT interval, especially at high doses (≥400 mg/day); monitor ECG in patients with electrolyte disturbances or concurrent QT-prolonging drugs. Adjust dose in renal impairment (CrCl <50 mL/min: reduce by 50%). Maintain adequate hydration to prevent crystalluria. Do not mix with other medications in same IV line unless compatibility confirmed. |
| Patient Advice | Take this medication exactly as prescribed by your doctor. · Inform your doctor if you have liver disease, kidney problems, or heart rhythm disorders. · Avoid driving or operating machinery until you know how this medication affects you. · Report signs of liver toxicity: dark urine, pale stools, yellowing of skin or eyes, persistent nausea. · Contact your doctor if you experience fast or irregular heartbeat, dizziness, or fainting. |
Loading safety data…