FLUCONAZOLE IN DEXTROSE 5% IN PLASTIC CONTAINER
Clinical safety rating: safe
Inhibits CYP2C9 and CYP3A4 increasing levels of many drugs (eg warfarin phenytoin) Can cause QT prolongation and subsequent arrhythmias.
Fluconazole selectively inhibits fungal cytochrome P450-dependent enzyme lanosterol 14-α-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 via CYP2C9 and to a lesser extent by CYP3A4. Approximately 80% of an administered dose is excreted unchanged in urine; less than 11% is excreted as metabolites (primarily N-oxide and glucuronide conjugates). |
| Excretion | Renal: 80% unchanged drug; feces: 11%; biliary: minor. |
| Half-life | Terminal elimination half-life approximately 30 hours (range 20-50 hours). Prolonged in renal impairment (up to 98 hours in CrCl <20 mL/min). |
| Protein binding | 11-12% bound to albumin, primarily. |
| Volume of Distribution | Approximately 0.7 L/kg (50-70 L total), approaches total body water, indicating extensive tissue penetration, including CSF. |
| Bioavailability | Oral: >90%; IV: 100%. |
| Onset of Action | Oral: detectable plasma concentrations within 1-2 hours; IV: immediate. Clinical effect onset may be delayed until steady state (5-10 days without loading dose). |
| Duration of Action | Therapeutic concentrations persist for 2-5 days after single dose due to long half-life; once-daily dosing maintains steady state. |
200-400 mg IV once daily; for candidemia or invasive candidiasis, loading dose of 800 mg IV on day 1, then 400 mg IV once daily.
| Dosage form | INJECTABLE |
| Renal impairment | CrCl >50 mL/min: no adjustment; CrCl 10-50 mL/min: 50% of usual dose; CrCl <10 mL/min: 50% of usual dose after one full dose; hemodialysis: administer 100% of dose after each dialysis session. |
| Liver impairment | Child-Pugh A: no dose adjustment; Child-Pugh B or C: no specific guidelines, use with caution and monitor hepatotoxicity. |
| Pediatric use | Neonates (0-4 weeks): loading dose of 12 mg/kg IV, then 6 mg/kg IV every 72 hours; Infants and children (1 month-18 years): 6-12 mg/kg IV once daily (max 400 mg/day); for severe infections, up to 12 mg/kg IV every 12 hours. |
| Geriatric use | No specific dose adjustment beyond renal function monitoring; start at low end of dosing range and adjust based on CrCl. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Inhibits CYP2C9 and CYP3A4 increasing levels of many drugs (eg warfarin phenytoin) Can cause QT prolongation and subsequent arrhythmias.
| FDA category | Human |
| Breastfeeding | Fluconazole is excreted into human milk. M/P ratio is approximately 0.9. The dose received by a breastfed infant is less than 1% of the maternal weight-adjusted dose for standard maternal doses. No adverse effects reported in infants. Caution with high maternal doses. |
| Teratogenic Risk |
■ FDA Black Box Warning
None
| Common Effects | Headache |
| Serious Effects |
["Hypersensitivity to fluconazole, any component of the formulation, or other azole antifungals","Concurrent use of terfenadine (when fluconazole dose ≥400 mg/day), astemizole, cisapride, pimozide, or quinidine (due to risk of QT prolongation)","Concurrent use of HMG-CoA reductase inhibitors metabolized by CYP3A4 (e.g., simvastatin, atorvastatin) due to increased risk of myopathy/rhabdomyolysis"]
| Precautions | ["Hepatotoxicity: Cases of hepatic necrosis and fatal hepatic reactions have been reported; discontinue use if signs of hepatic injury occur.","QT prolongation and torsade de pointes: Risk increased in patients with electrolyte disturbances (hypokalemia, hypomagnesemia), bradycardia, or concurrent use of other QT-prolonging drugs.","Fetal harm: Avoid use during pregnancy unless clearly needed; fluconazole is associated with congenital anomalies (e.g., craniofacial, skeletal) with prolonged high-dose exposure in first trimester.","Adrenal insufficiency: Fluconazole inhibits CYP17A1 and CYP21A2, potentially causing adrenal suppression; monitor adrenal function in critically ill patients.","Drug interactions: Fluconazole is a potent inhibitor of CYP2C9 and moderate inhibitor of CYP3A4; monitor INR with warfarin, serum levels of phenytoin, cyclosporine, tacrolimus, and others.","Hypersensitivity: Serious allergic reactions including anaphylaxis and Stevens-Johnson syndrome have been reported."] |
Loading safety data…
| Fluconazole is teratogenic at high doses (≥400 mg/day) in the first trimester, causing a pattern of congenital anomalies including craniosynostosis, cardiac defects, and skeletal abnormalities. At standard doses (150 mg as single dose), risk is low. Second and third trimester: risk of spontaneous abortion and stillbirth may be increased with prolonged high doses; avoid continuous treatment in pregnancy unless essential. |
| Fetal Monitoring | Monitor maternal liver function tests, renal function, and serum fluconazole levels if high doses used. Ultrasound for fetal anatomy if first-trimester exposure to high-dose therapy. Monitor infant for jaundice and hepatotoxicity if maternal high-dose therapy continues during breastfeeding. |
| Fertility Effects | No direct evidence of impaired fertility in humans. In animal studies, high doses caused reversible female reproductive toxicity but no male effects. No clinically significant impact expected at therapeutic doses. |