Metolazone Dosing
For adult patients with normal renal function requiring metolazone for diuretic-resistant edema, start with 2.5-5 mg orally once daily, with careful monitoring to avoid excessive diuresis. 1, 2
Standard Dosing Recommendations
- Initial dose: 2.5-5 mg orally once daily when used in combination with loop diuretics for refractory heart failure 1, 2
- The lower starting dose (≤5 mg) is supported by contemporary evidence and minimizes the risk of excessive fluid and electrolyte depletion 2
- Higher doses may occasionally be required (up to 10-20 mg daily), but should only be used with close monitoring 1, 3
Administration Strategy
- Metolazone should be administered cautiously with a means of surveillance allowing careful weight monitoring to avoid excessive diuresis 4
- When used for sequential nephron blockade in severe heart failure, give 2.5-5 mg orally once or twice daily in combination with a loop diuretic 1
- The drug is characterized by slow and sometimes erratic absorption, particularly with the Zaroxolyn formulation 4
Critical Monitoring Requirements
Electrolyte monitoring is essential due to high risk of complications:
- Hypokalemia occurs in up to 80% of patients when metolazone is used alone in liver disease, and remains a significant risk in heart failure 3, 2
- Clinically important hypokalemia (<2.5 mM) or hyponatremia (<125 mM) occur in approximately 10% of treatment episodes 2
- Monitor plasma sodium, potassium, BUN, and creatinine regularly during treatment 2
- Significant reductions in blood pressure and weight are expected 2
Important Clinical Pitfalls
If excessive diuresis occurs, stop both metolazone and the loop diuretic temporarily—do not simply reduce doses of either agent 4. This is a critical error to avoid, as dose reduction may not adequately control active diuresis.
Metolazone should be used with caution in patients with liver disease due to the high incidence of hypochloraemia (35%) and encephalopathy (35%) when used as monotherapy 3. Consider concurrent administration of amiloride or spironolactone to prevent hypokalemia 3.
Pharmacologic Considerations
- Metolazone has a large volume of distribution and high degree of renal clearance, providing the basis for favorable combination effects with loop diuretics 4
- The drug produces a diuretic response despite low glomerular filtration rate, making it useful when renal function is impaired 3
- Absorption may be reduced in heart failure patients 2
Clinical Outcomes
- NYHA functional class improvement is typically observed with combination therapy 2
- The low incidence of azotemia (5%) suggests particular utility when renal function is compromised 3
- Contemporary evidence supports metolazone ≤5 mg as effective and relatively safe in outpatients with refractory heart failure 2