DIFLUCAN IN SODIUM CHLORIDE 0.9% IN PLASTIC CONTAINER
Clinical safety rating
safeNo significant drug interactions Can cause hypernatremia and fluid overload.
Fluconazole is a triazole antifungal agent that inhibits fungal cytochrome P450 14α-demethylase, thereby blocking the conversion of lanosterol to ergosterol, a key component of the fungal cell membrane. This disrupts membrane integrity and function.
| Metabolism | Fluconazole is primarily metabolized by the liver, with approximately 11% of the dose metabolized; the unchanged drug is the major circulating entity. Hepatic metabolism involves N-oxidation and glucuronidation, but specific CYP enzymes are not significantly involved. It is a moderate inhibitor of CYP2C9 and CYP3A4. |
| Excretion | Primarily renal; approximately 80% of the dose is excreted unchanged in urine. Minor biliary/fecal elimination (<10%). |
| Half-life | Terminal elimination half-life is approximately 30 hours (range 20–50 hours) in adults; prolonged in renal impairment. In neonates, half-life is longer (up to 90 hours). |
| Protein binding | Approximately 11–12% bound to plasma proteins (mainly albumin). |
| Volume of Distribution | Approximately 0.7 L/kg, indicating extensive distribution into total body water; penetrates well into tissues and CSF. |
| Bioavailability | Oral bioavailability is >90% (virtually complete). IV administration is 100%. |
| Onset of Action | Oral: 1–2 hours to peak plasma concentrations. IV: immediate onset following infusion. Clinical response (e.g., fever resolution in candidemia) may take 24–72 hours. |
| Duration of Action | Duration of therapeutic effect correlates with half-life; single dose provides antifungal coverage for 2–3 days. Weekly dosing is effective for maintenance therapy. |
| Molecular Weight | 306.27 |
400 mg IV on day 1, then 200 mg IV once daily
| Dosage form | INJECTABLE |
| Renal impairment | For CrCl 50-90 mL/min: no adjustment; CrCl 10-49 mL/min: 50% dose or interval doubling; CrCl <10 mL/min (not on dialysis): 50% dose or interval doubling; on hemodialysis: one full dose after each dialysis session |
| Liver impairment | No specific dose adjustment for Child-Pugh A or B; caution in severe hepatic impairment (Child-Pugh C) with monitoring |
| Pediatric use | Loading dose: 12 mg/kg IV (max 400 mg) on day 1, then 6 mg/kg IV (max 200 mg) once daily; for weight <40 kg, adjust based on weight using these mg/kg doses |
| Geriatric use | Dose based on renal function; no specific age-related adjustment beyond renal considerations |
| 1st trimester | Avoid unless benefit outweighs risk. Associated with increased risk of miscarriage and congenital anomalies (e.g., craniosynostosis, heart defects) at high doses. |
| 2nd trimester | Use only if clearly needed. High doses associated with prolonged QT interval in fetus. |
| 3rd trimester | Use with caution near term; may increase risk of premature labor and low birth weight. |
Clinical note
No significant drug interactions Can cause hypernatremia and fluid overload.
| FDA category | Animal |
| Placental transfer | Fluconazole crosses the placenta; therapeutic concentrations in fetal plasma are similar to maternal levels. |
| Breastfeeding | Fluconazole is excreted into breast milk in low concentrations. The American Academy of Pediatrics considers it compatible with breastfeeding. However, monitor infant for potential adverse effects (e.g., diarrhea, rash). |
| Lactation Rating | L2 (Safer) |
| Teratogenic Risk | First trimester: Multiple case reports and epidemiological studies suggest an increased risk of spontaneous abortion and congenital anomalies, particularly craniofacial and skeletal malformations, with high-dose (400-800 mg/day) fluconazole exposure. Low-dose (150 mg single dose) exposure is not consistently associated with increased risk. Second and third trimesters: Standard doses are not associated with teratogenic risk, but prolonged high-dose therapy may increase risk of preterm birth and low birth weight. |
| Fetal Monitoring | Monitor liver function tests (AST, ALT, alkaline phosphatase, bilirubin) at baseline and periodically during therapy, especially with prolonged courses. Monitor renal function and electrolytes. In pregnant women with severe or recurrent vulvovaginal candidiasis, consider fungal cultures and sensitivity testing. Fetal ultrasound may be considered for anomalies if high-dose exposure occurs in first trimester. Monitor for signs of hepatic injury or renal impairment in the neonate if maternal therapy continues until delivery. |
| Fertility Effects | Limited data. In animal studies, high-dose fluconazole caused delayed parturition and impaired fertility. In humans, no conclusive evidence of adverse effects on fertility. Reversible oligospermia has been reported in males with prolonged high-dose therapy, but impact on female fertility is unknown. |
■ FDA Black Box Warning
No FDA black box warning.
| Common Effects | fluid replacement |
| Serious Effects |
Hypersensitivity to fluconazole or any excipientConcomitant use with terfenadine (multiple-dose fluconazole 400 mg/day)Concomitant use with cisaprideConcomitant use with pimozideConcomitant use with quinidine
| Precautions | Hepatic toxicity: severe liver injury including fatal cases; discontinue if signs of liver disease develop, Anaphylaxis and allergic reactions, QT prolongation and torsade de pointes; use with caution in patients with proarrhythmic conditions, Adrenal insufficiency: fluconazole may inhibit adrenal steroidogenesis, Fetal harm: use during pregnancy only if benefit outweighs risk; multiple congenital anomalies reported, Skin reactions: monitoring for exfoliative disorders |
| Food/Dietary | No significant food interactions with IV formulation. Oral fluconazole absorption is not affected by food. Avoid grapefruit juice? Not specifically contraindicated, but grapefruit juice may rarely affect CYP3A4 metabolism; no documented interaction with fluconazole. |
| Clinical Pearls | DIFLUCAN (fluconazole) in 0.9% sodium chloride is an IV formulation for patients unable to take oral. Monitor renal function and adjust dose if CrCl <50 mL/min. Caution with hepatotoxic drugs; check LFTs. QTc prolongation risk: avoid with other QTc-prolonging agents and electrolyte abnormalities. Transition to oral fluconazole when feasible. Incompatible with amphotericin B and other drugs; use separate lines. |
| Patient Advice | Do not mix with other medications in the same IV line. · Report any signs of liver problems (yellowing skin/eyes, dark urine, severe nausea) or irregular heartbeat. · Complete the full course even if feeling better. · May cause dizziness; avoid driving if affected. · Inform your doctor if you are pregnant, planning to become pregnant, or breastfeeding. |
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