What is the recommended dosage and treatment protocol for metolazone in patients with hypertension and edema?

Metolazone Dosage and Treatment Protocol for Hypertension and Edema

For patients with hypertension, metolazone should be initiated at 2.5 mg once daily, with a maximum daily dose of 5 mg. For patients with edema, the recommended initial dose is 5 mg once daily, which can be titrated up to a maximum of 20 mg daily based on clinical response. 1, 2

Dosing for Hypertension

• Initial dose: 2.5 mg once daily 1
• Usual maintenance dose: 2.5-5 mg once daily 1, 3
• Maximum daily dose: 5 mg 1
• Administration: Single daily oral dose 1

Studies show that even low doses (0.5-2.0 mg) of metolazone can effectively reduce blood pressure, with 51-58% of patients achieving blood pressure control at the 0.5 mg dose 3. However, the FDA-approved labeling recommends starting with 2.5 mg for mild to moderate hypertension 1.

Dosing for Edema

• Edema of cardiac failure:

  • Initial dose: 5 mg once daily
  • Usual range: 5-20 mg once daily
  • Maximum daily dose: 20 mg 1, 2

• Edema of renal disease:

  • Initial dose: 5 mg once daily
  • Usual range: 5-20 mg once daily
  • Maximum daily dose: 20 mg 1

Treatment Protocol

For Hypertension:

1. Start with 2.5 mg once daily
2. Monitor blood pressure response after 3-6 weeks (may take this long to see full effect) 2
3. If target blood pressure not achieved, increase to 5 mg once daily
4. If inadequate response at maximum dose, add another antihypertensive agent

For Edema:

1. Start with 5 mg once daily
2. Assess response within 24 hours (diuresis typically begins within 1 hour and persists for 24+ hours) 1
3. Titrate dose based on clinical response (weight reduction, decreased edema)
4. For resistant edema, consider combination therapy with loop diuretics

Combination Therapy

For patients with resistant edema, particularly in heart failure:

• Metolazone (2.5-10 mg once daily) can be combined with a loop diuretic for sequential nephron blockade 4, 2
• This combination produces potent diuresis but requires careful monitoring 2, 5
• A common approach is to add 2.5 mg of metolazone for 2-3 days to the loop diuretic regimen, then return to the usual maintenance dose of loop diuretic when weight stabilizes 2

Monitoring Requirements

• Blood pressure: Regular monitoring to assess response
• Body weight: Daily measurements to evaluate fluid status 2
• Electrolytes: Check serum potassium, sodium, and renal function within 5-7 days after initiation and every 3-6 months thereafter 2
• Renal function: Monitor for worsening, especially with combination therapy 2, 6

Special Considerations

• Metolazone should be reserved for patients who do not respond to moderate or high-dose loop diuretics alone for edema management 4
• In elderly patients or those with renal impairment, start at the lower end of the dosing range
• Metolazone can cause significant electrolyte disturbances, particularly when combined with loop diuretics, including hypokalemia, hyponatremia, and metabolic alkalosis 6
• Potassium supplementation may be necessary, especially with combination diuretic therapy

Potential Adverse Effects

• Electrolyte abnormalities (hypokalemia, hyponatremia, hypochloremia)
• Hyperuricemia
• Glucose intolerance
• Worsening renal function 2

Metolazone remains effective even in patients with reduced renal function, making it valuable for patients with both hypertension and edema who have compromised kidney function 5.