What is Metolazone (a thiazide-like diuretic)?

From the Guidelines

Metolazone should be used at an initial daily dose of 2.5 mg once daily, with a maximum total daily dose of 20 mg, in patients with heart failure and refractory edema unresponsive to loop diuretics alone, as recommended by the 2022 AHA/ACC/HFSA guideline for the management of heart failure 1.

Key Points

• Metolazone is a thiazide-like diuretic that works by inhibiting sodium and chloride reabsorption in the distal convoluted tubule of the kidney, increasing urine output and reducing fluid retention in the body.
• The medication is particularly effective when combined with loop diuretics like furosemide in resistant edema cases, using a strategy called sequential nephron blockade.
• Common side effects of metolazone include electrolyte imbalances (particularly potassium depletion), increased blood glucose, elevated uric acid levels, and dehydration.
• Regular monitoring of electrolytes, kidney function, and blood pressure is essential during treatment with metolazone.
• Patients should take metolazone in the morning to avoid nighttime urination and maintain adequate fluid intake unless otherwise directed.
• Elderly patients typically require lower doses of metolazone due to decreased kidney function and increased sensitivity to the medication's effects.

Dosage and Administration

• Initial daily dose: 2.5 mg once daily
• Maximum total daily dose: 20 mg
• Duration of action: 12-24 hours
• The dose may be increased until urine output increases and weight decreases, generally by 0.5 to 1.0 kg daily, as needed and as tolerated by the patient 1.

From the FDA Drug Label

Metolazone is a quinazoline diuretic, with properties generally similar to the thiazide diuretics. The actions of metolazone result from interference with the renal tubular mechanism of electrolyte reabsorption. Metolazone acts primarily to inhibit sodium reabsorption at the cortical diluting site and to a lesser extent in the proximal convoluted tubule Sodium and chloride ions are excreted in approximately equivalent amounts.

Metolazone Mechanism of Action: Metolazone is a diuretic that acts by inhibiting sodium reabsorption in the renal tubules, resulting in increased excretion of sodium and chloride ions. Key Effects:

• Inhibits sodium reabsorption at the cortical diluting site
• Inhibits sodium reabsorption to a lesser extent in the proximal convoluted tubule
• Increases excretion of sodium and chloride ions in approximately equivalent amounts 2

From the Research

Metolazone Overview

• Metolazone is a thiazide-type diuretic used to treat hypertension and edema [(3,4)].
• It is often used in combination with loop diuretics to manage volume overload in patients with heart failure or renal insufficiency [(5,4,6,7)].

Efficacy and Safety

• Studies have shown that metolazone is effective in reducing blood pressure and improving edema in patients with hypertension and heart failure [(3,7)].
• However, metolazone has also been associated with adverse effects such as hyponatremia, hypokalemia, and worsening renal function [(5,6)].
• The combination of metolazone and loop diuretics can increase the risk of severe electrolyte disturbances 6.

Clinical Use

• Metolazone can be used as an alternative to high-dose loop diuretics in patients with acute decompensated heart failure 5.
• In elderly renal failure patients under palliative care, combination therapy with low-dose metolazone and furosemide may be effective in managing refractory fluid overload 7.
• Metolazone should be used with caution and under close monitoring to avoid excessive diuresis and electrolyte disturbances [(4,6)].