What is the use of metolazone (Zaroxolyn)?

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From the Guidelines

Metolazone (Zaroxolyn) is recommended for use in patients with heart failure who have fluid retention and do not respond to moderate- or high-dose loop diuretics, as an addition to treatment with a loop diuretic to relieve congestion, improve symptoms, and prevent worsening heart failure 1. The primary use of metolazone is to treat fluid retention associated with heart failure, kidney disease, or liver disease, by increasing urine output to reduce excess fluid in the body and lower blood pressure.

  • Key points to consider when using metolazone include:
    • Typical dosing ranges from 2.5 to 10 mg once daily
    • Lower doses are often used for hypertension, while higher doses are used for edema
    • Metolazone is particularly effective when combined with loop diuretics like furosemide in patients with resistant edema or severe heart failure
    • The medication achieves its effects by blocking sodium and chloride reabsorption in the distal tubules of the kidneys, which increases water excretion
  • Patients taking metolazone should monitor for side effects, including:
    • Electrolyte imbalances (particularly potassium depletion)
    • Increased blood sugar
    • Elevated uric acid levels
    • Regular blood tests are important to monitor kidney function and electrolyte levels while on this medication, as recommended by the 2022 AHA/ACC/HFSA guideline for the management of heart failure 1. According to the European Society of Cardiology, in cases of insufficient diuretic response or diuretic resistance, combining a loop diuretic with metolazone may be considered 1. However, the most recent and highest quality study, the 2022 AHA/ACC/HFSA guideline, recommends reserving the addition of metolazone to treatment with a loop diuretic for patients who do not respond to moderate- or high-dose loop diuretics, to minimize electrolyte abnormalities 1.

From the FDA Drug Label

INDICATIONS AND USAGE Metolazone tablets, USP, are indicated for the treatment of salt and water retention including: edema accompanying congestive heart failure; edema accompanying renal diseases, including the nephrotic syndrome and states of diminished renal function Metolazone tablets, USP, are also indicated for the treatment of hypertension, alone or in combination with other antihypertensive drugs of a different class.

The use of metolazone (Zaroxolyn) is for the treatment of:

  • Edema accompanying congestive heart failure
  • Edema accompanying renal diseases, including the nephrotic syndrome and states of diminished renal function
  • Hypertension, alone or in combination with other antihypertensive drugs of a different class 2

From the Research

Use of Metolazone (Zaroxolyn)

  • Metolazone is a thiazide-type diuretic used to manage volume overload in patients with conditions such as chronic renal failure, nephrotic syndrome, congestive heart failure (CHF), and cirrhosis 3, 4, 5, 6, 7.
  • It is often used in combination with a loop diuretic to produce a synergistic diuretic response in patients who are resistant to loop diuretic therapy alone 3, 5, 6.
  • The combination of metolazone and a loop diuretic, such as furosemide, has been shown to be highly effective in inducing diuresis and natriuresis in patients with severe fluid retention 6.
  • Metolazone can also be used to facilitate the use of sodium bicarbonate to treat acidosis in patients with renal insufficiency 7.
  • The use of metolazone requires careful monitoring of the patient's weight and serum electrolyte levels to avoid excessive diuresis and electrolyte imbalances 5, 6, 7.

Disease States Associated with Metolazone Use

  • Chronic renal failure: metolazone can be used to manage volume overload and edema in patients with chronic renal failure 3, 7.
  • Nephrotic syndrome: metolazone can be used to manage edema and proteinuria in patients with nephrotic syndrome 4, 7.
  • Congestive heart failure (CHF): metolazone can be used to manage volume overload and edema in patients with CHF 3, 5.
  • Cirrhosis: metolazone can be used to manage ascites and edema in patients with cirrhosis 4, 6.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Metolazone and spironolactone in cirrhosis and the nephrotic syndrome.

Clinical pharmacology and therapeutics, 1977

Research

Metolazone and its role in edema management.

Congestive heart failure (Greenwich, Conn.), 2003

Research

[Furosemide and metolazone: a highly effective diuretic combination].

Schweizerische medizinische Wochenschrift, 1980

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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