From the Guidelines
Metolazone should be used at a starting dose of 2.5 to 5 mg once daily, with maintenance doses ranging from 2.5 to 20 mg daily, and considered for addition to loop diuretics in patients with refractory edema unresponsive to loop diuretics alone, as recommended by the 2022 AHA/ACC/HFSA guideline for the management of heart failure 1.
Key Considerations
- Metolazone is a thiazide-like diuretic medication used primarily to treat hypertension and edema associated with heart failure, liver disease, or kidney disease.
- The medication works by inhibiting sodium and chloride reabsorption in the distal convoluted tubule of the nephron, increasing water excretion and reducing blood volume and pressure.
- Patients taking metolazone should be monitored for electrolyte imbalances, particularly hypokalemia, hyponatremia, and hypercalcemia, with regular blood tests to check electrolytes and kidney function 1.
- Side effects may include dizziness, headache, increased urination, and electrolyte disturbances, and patients should maintain adequate hydration while taking this medication but avoid excessive fluid intake.
Clinical Use
- Metolazone may be considered for use in combination with loop diuretics like furosemide to achieve sequential nephron blockade, enhancing diuretic effect, with metolazone typically given 30 minutes before the loop diuretic 1.
- The 2018 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults also lists metolazone as a thiazide or thiazide-type diuretic option, with a usual dose range of 2.5–5 mg/d and daily frequency of 1 1.
Monitoring and Safety
- Regular monitoring of electrolyte levels and kidney function is necessary to minimize the risk of adverse effects, particularly in patients with pre-existing kidney disease or those taking other medications that may interact with metolazone 1.
- Patients should be educated on the importance of maintaining adequate hydration and avoiding excessive fluid intake while taking metolazone, as well as recognizing and reporting any signs of electrolyte imbalances or other adverse effects.
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. The increased delivery of sodium to the distal tubular exchange site results in increased potassium excretion.
The primary mechanism of action of metalazone is to inhibit sodium reabsorption at the cortical diluting site, leading to increased excretion of sodium and chloride ions and potassium excretion 2.
- Key effects include diuresis and saluresis, which usually begin within one hour and may persist for 24 hours or more.
- Therapeutic use is as a diuretic, with a potency approximately equal to thiazide diuretics, but with the added benefit of producing diuresis in patients with glomerular filtration rates below 20 mL/min.
From the Research
Metalazone Overview
- Metalazone, also known as metolazone, is a thiazide-type diuretic used to manage volume overload in patients with heart failure or hypertension.
- It is often administered in combination with a loop diuretic, such as furosemide, to enhance diuretic effects 3, 4, 5.
Clinical Effects
- The combination of metolazone and furosemide can lead to severe electrolyte disturbances, including hyponatremia, hypochloremia, alkalosis, and hypokalemia 3, 4.
- Metolazone has been associated with increased mortality, worsening renal function, and electrolyte imbalances in patients with acute decompensated heart failure 4.
- However, metolazone can also improve diuretic response, reduce congestion, and enhance clinical outcomes in patients with advanced heart failure 6.
Administration and Monitoring
- Metolazone should be administered cautiously, with careful monitoring of the patient's weight and electrolyte levels to avoid excessive diuresis 5.
- If excessive diuresis occurs, both metolazone and the loop diuretic should be stopped temporarily, rather than simply reducing the doses of either medication 5.