What is the recommended use and dosage of metolazone in patients with hypertension or edema?

Metolazone Use in Hypertension and Edema

Metolazone is recommended at a dose of 2.5-5 mg once daily for hypertension and 5-20 mg once daily for edema management, with careful monitoring of electrolytes and renal function due to its potent diuretic effects. 1

Dosing Recommendations

For Hypertension:

• Initial dose: 2.5-5 mg once daily 1
• Maximum daily dose: 20 mg 1
• Duration of action: 12-24 hours 2

For Edema (Heart Failure or Renal Disease):

• Initial dose: 5-20 mg once daily 1
• Maximum daily dose: 20 mg 2
• Duration of action: 12-24 hours 2

Mechanism and Clinical Use

Metolazone is a thiazide-like diuretic that acts at the distal convoluted tubule to inhibit sodium and chloride reabsorption. It has several important clinical applications:

1. Primary Hypertension Management: Effective as monotherapy in mild to moderate essential hypertension 1

2. Heart Failure: Used for volume control and to reverse fluid overload symptoms 2

   • Particularly effective when combined with loop diuretics in resistant edema
   • Can be used when loop diuretics alone are insufficient for volume control

3. Refractory Edema: Particularly valuable in combination therapy with loop diuretics 3

   • Synergistic effect when combined with furosemide due to sequential nephron blockade 2
   • Starting dose of 2.5 mg when used in combination therapy 3

Special Considerations

Combination Therapy with Loop Diuretics

• Metolazone-furosemide combination produces potent diuresis in resistant edema 4, 5
• Recommended approach for sequential nephron blockade:
  • Start with low dose metolazone (2.5 mg) 3
  • Use for 2-3 days to supplement loop diuretic 3
  • Monitor daily weights and electrolytes closely 3

Monitoring Requirements

• Regular monitoring of:
  • Electrolytes (especially potassium and sodium) 6, 5
  • Renal function 3
  • Daily weight measurements 3, 4
  • Signs of volume depletion 3

Potential Adverse Effects

• Severe electrolyte disturbances (hyponatremia, hypochloremia, hypokalemia) 6, 5
• Metabolic alkalosis 6
• Worsening renal function 5
• Hypotension 3

Precautions and Contraindications

• Use with caution in patients with:

  • Renal impairment (though still effective at lower GFR) 5
  • Liver disease (high risk of hypokalaemia and encephalopathy) 7
  • Elderly patients (increased sensitivity to volume depletion)

• Consider hospital admission when initiating metolazone-furosemide combination in high-risk patients (hypotension, azotemia, oliguria) 3

Clinical Pearls

1. Metolazone remains effective even with reduced renal function, making it valuable in cardiorenal syndrome 5

2. When using metolazone with furosemide, start with the lowest effective dose (2.5 mg) to minimize adverse effects 3, 5

3. The combination of metolazone and furosemide can produce dramatic diuresis - close monitoring is essential 4

4. In heart failure patients, metolazone should be used together with an ACE inhibitor or ARB and a β-blocker for optimal management 2

5. For patients with liver disease, consider adding potassium-sparing diuretics (spironolactone/amiloride) to prevent hypokalemia 7