Metolazone in Hypertension and Edema Management
Metolazone is recommended for hypertension at doses of 2.5-5 mg once daily, and for edema management at 5-20 mg once daily, with careful monitoring of electrolytes due to risk of severe disturbances, especially when combined with loop diuretics. 1
Dosing Recommendations
For Hypertension:
- Initial dose of 2.5-5 mg once daily for mild to moderate essential hypertension 1
- Lower starting dose of 0.5 mg may be effective with minimal laboratory value changes in hypertensive patients 2
- Single daily dosing is recommended for all indications 1
For Edema:
- For edema of cardiac failure: 5-20 mg once daily 1
- For edema of renal disease: 5-20 mg once daily 1
- Diuresis and saluresis usually begin within one hour and persist for 24 hours or longer 1
Mechanism and Clinical Applications
- Metolazone is a thiazide-like diuretic that acts primarily on the distal convoluting tubule 3
- It can produce a diuretic response despite low glomerular filtration rate, making it effective in patients with renal insufficiency 4
- For patients with paroxysmal nocturnal dyspnea, a larger dose may ensure prolonged diuresis for a full 24-hour period 1
Sequential Nephron Blockade in Resistant Edema
- Metolazone works synergistically with loop diuretics through sequential nephron blockade, blocking sodium reabsorption at different sites in the nephron 3
- For resistant edema or heart failure, metolazone 2.5-10 mg once daily can be combined with a loop diuretic 5
- The American College of Cardiology recommends administering metolazone 30 minutes before loop diuretics for optimal synergistic effect 3
- Short-term use (2-3 days) is recommended when combining with loop diuretics 3
Monitoring and Safety Considerations
- Careful monitoring of electrolytes, renal function, and blood pressure is essential, especially when combined with loop diuretics 3
- Severe electrolyte disturbances can occur with metolazone, particularly when combined with furosemide, including hyponatremia, hypochloremia, alkalosis, and hypokalemia 6
- Target weight reduction of 0.5-1.0 kg per day during combination therapy 3
- Risk of adverse effects is higher in patients with severe renal insufficiency 3
Special Populations and Considerations
- In patients with liver disease and ascites, metolazone should be used with caution due to high incidence of hypokalaemia (80%), hypochloraemia (35%), and encephalopathy (35%) 7
- For patients with liver disease, an initial dose of 5 mg daily is suggested, though higher doses may eventually be required 7
- In patients with renal failure, metolazone has shown benefit in controlling edema and improving blood pressure control during long-term therapy 8
- Metolazone is not recommended as first-line therapy for hypertension in people ≥75 years or for ankle edema without signs of heart failure 5
Potential Complications and Pitfalls
- Avoid excessive diuresis in elderly patients with heart failure with preserved ejection fraction 5
- Consider hospital admission for initiation of combination therapy in high-risk patients (elderly, severe heart failure, baseline renal dysfunction) 3
- Diuretics should be used together with an ACE inhibitor or ARB and a β-blocker in heart failure patients 5
- Hypokalemia can usually be prevented by simultaneous administration of potassium-sparing diuretics like amiloride or spironolactone in patients with liver disease 7