What is the use of Metolazone (a thiazide-like diuretic)?

From the Guidelines

Metolazone is a thiazide-like diuretic that should be used to treat hypertension and edema associated with heart failure, liver disease, or kidney disease, with a typical dosage ranging from 2.5 to 10 mg once daily, as recommended by the most recent guidelines 1. The medication 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 initial daily dose of metolazone is 2.5 mg once, with a maximum total daily dose of 20 mg, and a duration of action of 12 to 24 hours, as outlined in the 2022 AHA/ACC/HFSA guideline for the management of heart failure 1.
• Metolazone is particularly effective when combined with loop diuretics like furosemide in patients with resistant edema or heart failure, as it works at a different site in the kidney, creating a synergistic effect, as noted in the 2013 ACCF/AHA guideline for the management of heart failure 1.
• Common side effects of metolazone include electrolyte imbalances (particularly potassium depletion), increased blood sugar, increased uric acid levels, and dehydration, highlighting the importance of regular monitoring of electrolytes, kidney function, and blood pressure during treatment, as recommended in the 2017 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 1.
• Patients should take metolazone in the morning to avoid nighttime urination and should maintain adequate fluid intake unless otherwise directed, and those with sulfa allergies should use caution as metolazone has a sulfonamide structure.

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 primary use of Metolazone 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 2

From the Research

Uses of Metolazone

• Metolazone is used to treat edema (fluid retention) in people with congestive heart failure, liver disease, or a kidney disorder such as nephrotic syndrome 3, 4, 5.
• It is also used to treat high blood pressure 6.
• Metolazone can be used in combination with other diuretics, such as loop diuretics, to manage volume overload in patients who are resistant to loop diuretic therapy alone 4, 5.
• The combination of metolazone and loop diuretics has been shown to be effective in improving blood pressure levels and reducing proteinuria in patients with type 2 diabetic kidney disease 7.

Benefits of Metolazone

• Metolazone has been shown to be safe and effective for long-term use in patients with chronic renal insufficiency and nephrotic syndrome 3.
• It can help to improve control of blood pressure and reduce edema in patients with congestive heart failure 3, 5.
• Metolazone can also help to reduce proteinuria in patients with type 2 diabetic kidney disease 7.

Administration of Metolazone

• Metolazone should be administered cautiously and with careful monitoring of the patient's weight to avoid excessive diuresis 4.
• If excessive diuresis occurs, both metolazone and the loop diuretic should be stopped temporarily, rather than simply reducing the dose of one or both drugs 4.