What is the recommended dosage and usage of Metolazone (thiazide-like diuretic) for treating hypertension or edema?

Metolazone Dosing and Usage

For heart failure with refractory edema, start metolazone at 2.5 mg once daily, administered 30 minutes before your loop diuretic, for a short burst of 2-3 days, then discontinue when target weight is achieved; for hypertension, start at 2.5-5 mg once daily as monotherapy. 1, 2, 3

Heart Failure with Refractory Edema

Indications for Use

• Metolazone is reserved for patients who fail to respond adequately to moderate or high-dose loop diuretics alone (Class 1, Level B-NR recommendation). 2
• Use when patients have persistent congestion despite optimized loop diuretic dosing, repeated hospitalizations, or NYHA class III-IV symptoms. 4
• Loop diuretics remain the preferred first-line agents; metolazone is not a first-line therapy. 2

Dosing Strategy

• Initial dose: 2.5 mg once daily 1, 2, 4, 3
• Maximum dose: 10-20 mg daily (though most patients respond to ≤5 mg) 1, 3, 5
• Timing: Administer 30 minutes before the loop diuretic to maximize sequential nephron blockade. 6, 4
• Duration: 2-5 days of burst therapy, then discontinue and return to maintenance loop diuretic when weight stabilizes. 6, 4
• Target weight loss of 0.5-1.0 kg per day during combination therapy. 6

Mechanism and Rationale

• Metolazone blocks sodium reabsorption at the distal convoluted tubule while loop diuretics act on the loop of Henle, creating synergistic sequential nephron blockade. 1, 6, 4
• This combination is superior to simply increasing loop diuretic doses. 1
• Metolazone maintains efficacy even when GFR <30 mL/min, unlike standard thiazides. 4, 5
• Duration of action is 12-24 hours, longer than most thiazides. 1, 4

Critical Monitoring Requirements

• Before starting: Check baseline electrolytes (sodium, potassium, chloride), creatinine, and blood pressure. 6, 4
• During therapy: Monitor weight daily, recheck electrolytes and renal function after 1-2 days. 6, 4
• Watch for: Severe hypokalemia (<2.5 mM), hyponatremia (<125 mM), hypochloremia, metabolic alkalosis, and worsening renal function. 2, 5, 7
• The greatest diuretic effect and electrolyte shifts occur within the first 3 days. 4

Safety Considerations and Pitfalls

• Severe electrolyte and volume depletion can occur rapidly when combining metolazone with loop diuretics. 6, 7
• If excessive diuresis occurs, stop both drugs temporarily—do not simply reduce doses. 8
• Consider hospital admission for high-risk patients: elderly, severe heart failure, baseline renal dysfunction, hypotension, azotemia, or oliguria. 6, 4
• Absorption may be reduced in heart failure due to gut wall edema. 4, 5
• Avoid potassium-sparing diuretics during initiation unless hypokalaemia persists despite ACE inhibition. 1

Hypertension

Dosing for Hypertension

• Initial dose: 2.5-5 mg once daily 1, 3
• Usual maintenance: 2.5-5 mg once daily 1
• Maximum dose: 20 mg daily (though rarely needed) 1
• Time to effect: 3-4 days to 3-6 weeks for blood pressure reduction. 3

Clinical Context

• Metolazone is not a first-line agent for hypertension; thiazides like chlorthalidone or hydrochlorothiazide are preferred based on trial evidence. 1
• Consider metolazone in hypertensive patients with concomitant mild fluid retention. 2
• Monitor for hypokalemia, hyponatremia, hyperuricemia, and glucose intolerance. 1

Contraindications and Special Populations

• Do not use as monotherapy if GFR <30 mL/min, except when combined synergistically with loop diuretics. 1, 4
• Avoid in patients with severe electrolyte depletion or anuria. 3
• Use with extreme caution in patients with hepatic cirrhosis and ascites due to risk of severe electrolyte disturbances. 7, 9

Key Takeaway

The most common error is using metolazone continuously rather than as short burst therapy in heart failure—this leads to excessive electrolyte depletion and renal dysfunction. 6, 4, 8 Always stop after 2-5 days when euvolemia is achieved, and never adjust doses during active diuresis. 8