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

From the Guidelines

Metolazone is a thiazide-like diuretic medication primarily used to treat high blood pressure and fluid retention associated with heart failure, kidney disease, or liver cirrhosis, with a typical starting dose of 2.5 mg once daily and a maximum total daily dose of 20 mg. The medication works by inhibiting sodium and chloride reabsorption in the distal convoluted tubule of the kidney, increasing urine output and reducing blood pressure 1. It's particularly effective when combined with loop diuretics like furosemide in resistant edema cases, a strategy called sequential nephron blockade 1. When taking metolazone, patients should monitor for side effects including electrolyte imbalances (particularly potassium depletion), increased blood sugar, elevated uric acid levels, and dehydration. Regular blood tests to check electrolytes, kidney function, and blood sugar are important during treatment, as recommended in the 2018 guideline for the prevention, detection, evaluation, and management of high blood pressure in adults 1. Some key points to consider when using metolazone include:

• Starting with a low dose and titrating up as needed to minimize side effects
• Monitoring for signs of dehydration, such as dry mouth, dark urine, and decreased urine output
• Avoiding use in patients with severe kidney disease or those taking certain medications, such as lithium or digoxin
• Being aware of potential interactions with other medications, including other antihypertensives and diuretics. Overall, metolazone is a valuable medication for managing fluid retention and high blood pressure in certain patient populations, but its use requires careful consideration of potential side effects and interactions.

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

Use of Metolazone

• Metolazone is a potent thiazide-like diuretic used in the treatment of severe congestive heart failure (HF) 3
• It is often used in combination with a loop diuretic to manage volume overload in patients resistant to loop diuretic therapy alone 4
• Metolazone is also used in the treatment of hypertension, with low dosages (0.5-2.5 mg/day) shown to be effective in reducing blood pressure 5, 6

Dosage and Administration

• A wide dose range of metolazone has been investigated, but a low starting dose (<5 mg) is often recommended 3
• Metolazone should be administered cautiously, with careful monitoring of the patient's weight to avoid excessive diuresis 4
• The absorption of metolazone may be reduced in heart failure patients, and its diuretic response may be affected by the patient's glomerular filtration rate 3

Adverse Effects

• Metolazone has been associated with hypokalemia, hyponatremia, and worsening renal function, particularly when used in high doses or in combination with loop diuretics 7
• The risk of these adverse effects may be minimized by using low doses of metolazone and carefully monitoring the patient's laboratory values 5, 6

Clinical Outcomes

• The use of metolazone in acute decompensated heart failure has been associated with increased mortality, as well as adverse effects such as hypokalemia, hyponatremia, and worsening renal function 7
• In contrast, high-dose loop diuretics may be a preferred strategy over the routine early addition of thiazide-type diuretics when diuresis is inadequate, as they are not associated with reduced survival or increased adverse effects 7