Is Zaroxolyn (metolazone) a diuretic?

Zaroxolyn (Metolazone) is a Thiazide-Like Diuretic

Yes, Zaroxolyn (metolazone) is a thiazide-like diuretic that acts primarily by inhibiting sodium reabsorption at the cortical diluting site in the renal tubules. 1

Pharmacological Classification and Mechanism of Action

• Metolazone is classified as a quinazoline diuretic with properties similar to thiazide diuretics, though with some distinct characteristics 1
• It acts by inhibiting sodium and chloride reabsorption primarily at the cortical diluting site in the distal tubule and to a lesser extent in the proximal convoluted tubule 1
• Unlike traditional thiazide diuretics, metolazone can produce diuresis even in patients with severely compromised renal function (glomerular filtration rates below 20 mL/min) 1

Clinical Applications in Heart Failure Management

• Metolazone is commonly used in heart failure management, particularly in combination with loop diuretics for patients with refractory fluid retention 2
• It is specifically listed in heart failure guidelines as an option for sequential nephron blockade in patients not responding adequately to loop diuretics alone 2
• The 2022 AHA/ACC/HFSA guideline for heart failure management specifically mentions metolazone as an agent that may be added to loop diuretics in patients with refractory edema 2

Dosing and Administration

• The typical initial daily dose of metolazone is 2.5 mg once daily, with a maximum total daily dose of 20 mg 2
• When used for sequential nephron blockade in combination with loop diuretics, the recommended dose is 2.5 to 5 mg once or twice daily 2
• The duration of action is approximately 12 to 24 hours 2
• For optimal synergistic effect when combined with loop diuretics, metolazone is often administered 30 minutes before the loop diuretic 3

Synergistic Effects with Loop Diuretics

• Metolazone works synergistically with loop diuretics through sequential nephron blockade, blocking sodium reabsorption at different sites in the nephron 3
• This combination has been shown to produce marked diuresis in patients with edema or ascites refractory to maximum recommended doses of loop diuretics alone 1, 4
• The combination of metolazone and loop diuretics has been demonstrated to be effective even in patients with advanced heart failure and poor response to high-dose loop diuretics 5

Monitoring and Precautions

• When using metolazone, especially in combination with loop diuretics, close monitoring is essential for:
  • Electrolyte abnormalities, particularly hypokalemia and hyponatremia 6
  • Renal function, as combination therapy can cause deterioration 7
  • Fluid status and blood pressure to avoid excessive diuresis 4
• The risk of electrolyte depletion is significant and can predispose patients to serious cardiac arrhythmias, particularly in the presence of digitalis therapy 2

Historical Context

• Metolazone has been recognized for its synergistic effects with loop diuretics since at least the early 1970s, when it was found to be of "great value in patients whose fluid retention was refractory to other diuretics" 8
• It has maintained its place in heart failure management guidelines due to its unique properties and efficacy in diuretic-resistant cases 2

In conclusion, Zaroxolyn (metolazone) is definitively classified as a thiazide-like diuretic with unique properties that make it particularly valuable in heart failure management, especially in combination with loop diuretics for patients with refractory fluid retention.