Metolazone Dosage and Usage for Hypertension and Edema
For hypertension, metolazone should be started at 2.5-5 mg once daily, while for edema (particularly in heart failure), the recommended dosage is 5-20 mg once daily. 1
Dosing for Hypertension
- Initial dose for mild to moderate essential hypertension: 2.5 to 5 mg once daily 1
- Lower starting doses (2.5 mg) are appropriate for elderly patients or those at risk for electrolyte disturbances 2
- Metolazone should be titrated to achieve the desired therapeutic response while using the minimal effective dose 1
- The antihypertensive effect may take 3-6 weeks to fully manifest 1
Dosing for Edema (Heart Failure)
- For edema of cardiac failure: 5 to 20 mg once daily 1
- For edema of renal disease: 5 to 20 mg once daily 1
- In patients with refractory heart failure, low-dose metolazone (≤5 mg) is effective and relatively safe when added to loop diuretics 3
- For resistant peripheral edema or ascites, metolazone can be combined with a loop diuretic for enhanced diuresis 4
Administration Timing
- When used in combination with loop diuretics, metolazone should be administered 30 minutes before the loop diuretic for optimal synergistic effect 5
- For patients with paroxysmal nocturnal dyspnea, a larger dose may be needed to ensure diuresis for a full 24-hour period 1
Combination Therapy
- For patients with refractory heart failure, adding metolazone to a loop diuretic creates a powerful synergistic effect through sequential nephron blockade 5
- When combining with loop diuretics, metolazone should be used for short durations (2-3 days) to avoid severe electrolyte disturbances 5, 6
- Target weight reduction of 0.5-1.0 kg per day during combined therapy 5
- The combination of metolazone and furosemide has been shown to significantly increase diuresis and natriuresis in patients with severe fluid retention 7
Monitoring
- Monitor serum electrolytes, renal function, and blood pressure before starting metolazone and periodically during treatment 5
- Daily monitoring of weight, electrolytes, and renal function is recommended during combination therapy with loop diuretics 5
- Watch for hypokalemia, hyponatremia, hypochloremia, and metabolic alkalosis, especially with combination diuretic therapy 6
- Clinically significant hypokalemia (<2.5 mM) or hyponatremia (<125 mM) may occur in approximately 10% of patients during treatment 3
Special Considerations
- Metolazone produces a diuretic response even in patients with low glomerular filtration rate 3
- Absorption of metolazone may be reduced in heart failure patients 3
- Consider hospital admission for initiation of combination therapy in high-risk patients (elderly, severe heart failure, baseline renal dysfunction) 5
- Concurrent administration of spironolactone with metolazone can help prevent decreases in serum potassium 8
- In patients with resistant hypertension, metolazone may be used as part of a step 4 treatment regimen 4
Cautions
- Severe electrolyte disturbances can occur, particularly when metolazone is combined with loop diuretics 6
- Initial treatment may produce small increases in serum creatinine in patients with renal insufficiency due to volume depletion 9
- Adverse effects include electrolyte imbalances, hyperuricemia, and potential worsening of renal function 9
- The combination of metolazone and furosemide should be used with caution due to potential severe electrolyte derangements 6