From the Guidelines
Metolazone combined with furosemide (Lasix) can be an effective strategy to facilitate diuresis in patients with acute CHF exacerbation, particularly in those with diuretic resistance, as supported by the 2016 ESC guidelines for the diagnosis and treatment of acute and chronic heart failure 1. When managing patients with acute heart failure (AHF) and signs of fluid overload, diuretics are a cornerstone treatment, and the combination of metolazone and furosemide can enhance diuresis by targeting different segments of the nephron.
- The initial approach to congestion management involves i.v. diuretics, with the addition of vasodilators for dyspnea relief if blood pressure allows, as stated in the 2016 ESC guidelines 1.
- To enhance diuresis or overcome diuretic resistance, options include dual nephron blockade by loop diuretics with thiazide diuretics, such as metolazone, which requires careful monitoring to avoid hypokalemia, renal dysfunction, and hypovolemia 1.
- The dose of furosemide should be limited to the smallest amount to provide adequate clinical effect and modified according to previous renal function and previous dose of diuretics, with the initial i.v. dose being at least equal to the pre-existing oral dose used at home 1.
- Close monitoring is essential when using the combination of metolazone and furosemide, as it can cause significant electrolyte abnormalities, dehydration, and acute kidney injury, and serum electrolytes, renal function, and fluid status should be checked frequently 1.
From the FDA Drug Label
Metolazone and furosemide administered concurrently have produced marked diuresis in some patients where edema or ascites was refractory to treatment with maximum recommended doses of these or other diuretics administered alone. The combination of metalazone with lasix (furosemide) can facilitate diuresis in patients with acute CHF exacerbation, as it has been shown to produce marked diuresis in some patients with refractory edema or ascites 2.
- Key points:
- The mechanism of this interaction is unknown
- This combination may cause unusually large or prolonged losses of fluid and electrolytes
- Patients should be monitored for signs of fluid and electrolyte imbalance, such as hyponatremia, hypochloremic alkalosis, and hypokalemia 2.
From the Research
Diuretic Therapy in Acute CHF Exacerbation
- The combination of metalazone with lasix (furosemide) can facilitate diuresis in patients with acute congestive heart failure (CHF) exacerbation, as shown in several studies 3, 4, 5, 6.
- A study from 1986 found that the combination of furosemide and metolazone induced greater natriuresis, urinary output, and weight loss than either agent alone 3.
- Another study from 2005 reported that the use of metolazone in combination with a loop diuretic improved NYHA functional class and reduced weight, blood pressure, and plasma sodium and potassium levels in patients with refractory systolic heart failure 4.
- A 2021 cohort study found that adding metolazone to furosemide was not associated with higher morbidity and mortality in patients with severe acute decompensated heart failure 5.
- A 2024 study compared the efficacy and safety of different diuretic regimens in ambulatory congested heart failure patients and found that the combination of furosemide and metolazone resulted in the highest sodium excretion and urinary volume 6.
Safety and Efficacy Considerations
- The use of metolazone in combination with furosemide may be associated with a higher incidence of worsening renal function, as reported in the 2024 study 6.
- However, the 2018 review of heart failure management in the emergency department setting emphasizes the importance of tailoring treatments to the underlying disease process and monitoring for potential complications 7.
- The combination of metalazone with lasix may be a useful strategy for facilitating diuresis in patients with acute CHF exacerbation, but its use should be carefully considered and monitored in individual patients 3, 4, 5, 6.