What is the interaction between spironolactone and furosemide (Lasix) in patients with cirrhosis?

From the Guidelines

Spironolactone and furosemide can be used together in patients with cirrhosis, with a recommended starting regimen of spironolactone 100 mg daily and furosemide 40 mg daily, maintaining a 100:40 ratio as doses are adjusted, as stated in the 2021 practice guidance by the American Association for the Study of Liver Diseases 1.

Key Considerations

• The combination of spironolactone and furosemide works synergistically to increase sodium and water excretion, while minimizing electrolyte disturbances, as explained in the 2018 clinical practice guidelines for liver cirrhosis 2.
• Patients require regular monitoring of kidney function, electrolytes (particularly potassium), and blood pressure, as both medications can worsen renal function in advanced cirrhosis.
• The maximum recommended doses are spironolactone 400 mg and furosemide 160 mg daily, with careful monitoring to prevent complications such as hyperkalemia, gynecomastia, and ototoxicity.

Monitoring and Adjustments

• Body weight, serum creatinine, and sodium should be regularly monitored to assess response and detect adverse effects, as recommended in the 2021 practice guidance by the American Association for the Study of Liver Diseases 1.
• Diuretics should be tapered to the lowest dose necessary to maintain minimal or no ascites, to prevent the development of adverse effects.
• Fluid restriction is not necessary for ascites management unless there is concomitant moderate or severe hyponatremia (serum sodium ≤ 125 mmol/L), as stated in the 2021 practice guidance by the American Association for the Study of Liver Diseases 1.

From the FDA Drug Label

In patients with hepatic disease with cirrhosis and ascites. Clearance of spironolactone and its metabolites is reduced in patients with cirrhosis. In patients with cirrhosis, start with lowest initial dose and titrate slowly WARNINGS In patients with hepatic cirrhosis and ascites, Furosemide tablets therapy is best initiated in the hospital. In hepatic coma and in states of electrolyte depletion, therapy should not be instituted until the basic condition is improved

The interaction between spironolactone and furosemide in patients with cirrhosis is that both drugs can cause sudden alterations of fluid and electrolyte balance, which may precipitate impaired neurological function, worsening hepatic encephalopathy, and coma.

• Both drugs should be initiated in the hospital in patients with cirrhosis and ascites.
• Spironolactone should be started with the lowest initial dose and titrated slowly in patients with cirrhosis.
• Furosemide therapy should not be instituted until the basic condition is improved in patients with hepatic coma and electrolyte depletion.
• Supplemental potassium chloride and, if required, an aldosterone antagonist (such as spironolactone) are helpful in preventing hypokalemia and metabolic alkalosis [3] [4].

From the Research

Interaction between Spironolactone and Furosemide

• The interaction between spironolactone and furosemide in patients with cirrhosis is based on their synergistic effect in increasing natriuresis and reducing potassium loss 5, 6.
• Spironolactone is a potassium-sparing diuretic that acts as an aldosterone antagonist, while furosemide is a loop diuretic that inhibits sodium and chloride reabsorption in the ascending limb of the loop of Henle 7.
• The simultaneous administration of spironolactone and furosemide increases the natriuretic effect of each drug and diminishes their effects on potassium metabolism 6.

Efficacy and Safety

• Studies have shown that spironolactone alone or in combination with furosemide is effective in treating moderate ascites in nonazotemic cirrhosis 8, 9.
• The response rate, rapidity of ascites mobilization, and incidence of complications induced by diuretic therapy were similar in patients treated with spironolactone alone or in combination with furosemide 8.
• However, the need to reduce the diuretic dosage was significantly higher in patients treated with spironolactone and furosemide compared to those treated with spironolactone alone 8.

Dosage and Administration

• The recommended initial dose of spironolactone is 100-200 mg/d, and the usual maximum dose is 400 mg/d 5.
• The recommended initial dose of furosemide is 20-40 mg/d, and the usual maximum dose is 160 mg/d 5.
• The dosage of diuretics should be adjusted based on the patient's response and the presence of complications such as hypokalemia, hyponatremia, or renal impairment 5, 7.