Is there a drug interaction between Furosemide (Lasix) and Fluconazole (Diflucan)?

Drug Interaction Between Furosemide (Lasix) and Fluconazole (Diflucan)

There is no significant direct drug interaction between furosemide (Lasix) and fluconazole (Diflucan), but caution is warranted in patients with renal impairment as both medications can affect kidney function.

Evaluation of Evidence

The available guidelines do not specifically identify a direct pharmacokinetic or pharmacodynamic interaction between furosemide and fluconazole. However, several important considerations emerge from the evidence:

Fluconazole Interactions

• Fluconazole can be used with rifamycins, though the dose of fluconazole may need to be increased 1.
• Unlike some other azole antifungals (ketoconazole, itraconazole, voriconazole), fluconazole does not appear on lists of medications with significant interactions with furosemide 1.
• Fluconazole is primarily eliminated through renal excretion via glomerular filtration and tubular secretion 1.

Furosemide Considerations

• Furosemide is listed as potentially interacting with other medications through the anionic pathway in the kidneys 1.
• Furosemide has been identified as a risk factor for nephrotoxicity when used concomitantly with vancomycin 2.

Clinical Implications

Renal Function Concerns

1. Renal Clearance Impact:

   • Fluconazole clearance is positively correlated with glomerular filtration rate (GFR) 3.
   • In patients with impaired renal function, fluconazole elimination half-life can be approximately three times longer than in patients with normal renal function 3.
   • Furosemide can cause transient worsening of renal function, particularly in patients with compromised renal status 4.

2. Potential Additive Nephrotoxicity:

   • Research has identified furosemide as a risk factor for nephrotoxicity when combined with certain medications 2, 5.
   • While not directly studied together, both medications can impact renal function, potentially creating an additive effect.

Dosing Considerations

For patients receiving both medications:

• Monitor renal function closely, especially at initiation of therapy and with any dose changes.
• Adjust fluconazole dosing based on renal function:
  • GFR >50 mL/min: Standard dosing
  • GFR 21-50 mL/min: Consider 50% dose reduction 6
  • GFR 11-20 mL/min: Consider 75% dose reduction 6
  • Hemodialysis: Dose after dialysis sessions as approximately 38% of fluconazole is removed during a 3-hour hemodialysis session 3

Monitoring Recommendations

When administering furosemide and fluconazole concurrently:

1. Baseline Assessment:

   • Measure serum creatinine and electrolytes before starting therapy
   • Calculate estimated GFR

2. Ongoing Monitoring:

   • Monitor renal function regularly (every 2-3 days initially, then weekly)
   • Monitor electrolytes, particularly potassium levels
   • Watch for signs of fluid/electrolyte imbalance

3. Clinical Vigilance:

   • Be alert for symptoms of acute kidney injury
   • Monitor for enhanced diuretic effect or reduced response
   • Assess for signs of fluconazole toxicity if renal function declines

Special Populations

• Elderly patients: Use additional caution as they are more susceptible to drug effects and have age-related decline in renal function 1.
• Patients with heart failure: Increased risk of acute kidney injury with furosemide 4.
• Patients on multiple medications: Higher risk of drug interactions and adverse effects 5.

Conclusion

While there is no documented direct pharmacokinetic interaction between furosemide and fluconazole, their combined effects on renal function warrant careful monitoring, especially in patients with baseline renal impairment, the elderly, or those with conditions that may compromise kidney function.