metolazone + spironolactone

Metolazone + spironolactone is a combination of two oral diuretic medications used together to manage fluid overload (edema) and related conditions, particularly in patients with hepatic cirrhosis, nephrotic syndrome, or heart failure who are refractory to single-agent therapy. Metolazone is a thiazide-like diuretic that inhibits sodium reabsorption at the cortical diluting site and proximal convoluted tubule, leading to increased excretion of sodium and water. Spironolactone is an aldosterone antagonist (potassium-sparing diuretic) that blocks mineralocorticoid receptors in the distal renal tubules, reducing sodium reabsorption while conserving potassium. The combination provides synergistic diuresis by targeting different sites along the nephron and helps prevent hypokalemia associated with thiazide-type agents[1][2][3][9]. This regimen is typically reserved for cases where monotherapy or loop diuretics are insufficient.