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

From the Guidelines

Metolazone should be used at a starting dose of 2.5 to 5 mg once daily, and may be increased up to 20 mg daily for resistant edema, particularly when combined with loop diuretics like furosemide in patients with severe heart failure or refractory edema, as recommended by the 2022 AHA/ACC/HFSA guideline for the management of heart failure 1.

Key Considerations

• Metolazone is a thiazide-like diuretic that inhibits sodium and chloride reabsorption in the distal tubules of the kidneys, increasing water excretion and reducing blood volume and pressure.
• The medication is particularly effective in combination with loop diuretics for patients with resistant edema or severe heart failure, producing a synergistic diuretic effect.
• Common side effects include electrolyte imbalances, increased blood glucose, and elevated uric acid levels, emphasizing the need for regular monitoring of electrolytes, kidney function, and blood pressure during treatment.

Clinical Application

• Patients should take metolazone in the morning to prevent nighttime urination and maintain adequate hydration while avoiding excessive fluid intake if edema is being treated.
• 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 an option for hypertension management, with a usual dose range of 2.5–5 mg/daily 1.

Monitoring and Adjustments

• Regular monitoring of patient response and adjustment of the metolazone dose as necessary is crucial to achieve the treatment goal of eliminating clinical evidence of fluid retention while using the lowest dose possible to maintain euvolemia.
• As noted in the guidelines, diuretics should not be used in isolation but always combined with other guideline-directed medical therapy (GDMT) for heart failure that reduces hospitalizations and prolongs survival 1.

From the FDA Drug Label

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 uses of Metolazone are:

• Treatment of edema accompanying congestive heart failure
• Treatment of edema accompanying renal diseases
• Treatment of hypertension, alone or in combination with other antihypertensive drugs 2 Key mechanisms of action include:
• Inhibition of sodium reabsorption at the cortical diluting site
• Increased excretion of sodium, chloride, phosphate, and magnesium ions
• Increased potassium excretion 2

From the Research

Metolazone Overview

• Metolazone is a diuretic that has been used to treat various conditions, including chronic renal insufficiency, nephrotic syndrome, and heart failure 3, 4, 5, 6, 7
• The effects of metolazone have been studied in several patient populations, including those with renal failure, heart failure, and refractory fluid overload 3, 4, 5, 6, 7

Efficacy and Safety

• Metolazone has been shown to be effective in reducing edema and improving blood pressure control in patients with chronic renal insufficiency and nephrotic syndrome 3
• The combination of metolazone and furosemide has been used to treat refractory fluid overload in elderly renal failure patients under palliative care, with good tolerance and clinical improvement 5
• However, metolazone has also been associated with adverse effects, including serum electrolyte losses, hyperuricemia, and worsening renal function 3, 4, 6

Comparison with Other Diuretics

• Metolazone has been compared to high-dose loop diuretics in patients with acute decompensated heart failure, with metolazone being associated with increased mortality and adverse effects 6
• However, another study found that metolazone administration was associated with better decongestion and diuretic response in patients with advanced heart failure, with no differences in terms of worsening renal function or electrolyte unbalance 7

Clinical Applications

• Metolazone may be a useful addition to diuretic therapy in patients with refractory fluid overload or heart failure, particularly in those who are resistant to loop diuretics alone 5, 7
• However, the use of metolazone should be carefully considered, taking into account the potential risks and benefits, and the need for close monitoring of electrolytes and renal function 3, 4, 6