Starting Dose of Metolazone for Hypertension
For treating hypertension, start metolazone at 2.5 mg once daily. 1
FDA-Approved Dosing for Hypertension
The FDA label explicitly states that for mild to moderate essential hypertension, the initial dose is metolazone 2.5 to 5 mg once daily, with 2.5 mg representing the lower end of the therapeutic range 1. This dosing produces effects within 3-4 days to 3-6 weeks, and doses should be adjusted at appropriate intervals to achieve maximum therapeutic effect 1.
Evidence Supporting Lower Starting Doses
While the FDA label provides a range, clinical research demonstrates that even lower doses can be effective:
- A multicenter randomized trial found that 0.5 mg daily controlled blood pressure (diastolic BP <90 mmHg or ≥10 mmHg reduction) in 51-58% of patients with mild to moderate hypertension 2
- Another study showed that 2.5 mg daily achieved normotension in 48% of patients, though blood pressure response was somewhat inconsistent at this lower dose 3
Practical Dosing Algorithm
Start with 2.5 mg once daily as the standard initial dose for hypertension 1:
- If inadequate response after 3-6 weeks: Increase to 5 mg once daily before adding another antihypertensive agent 3
- Maximum dose for hypertension: 5 mg once daily (higher doses up to 20 mg are reserved for edematous states) 1
Important Caveats
Metolazone is NOT a first-line agent for hypertension 4. Current guidelines recommend thiazide-like diuretics as part of step 3-4 therapy, typically after ACE inhibitors/ARBs and calcium channel blockers have been tried 4. Metolazone specifically appears in guidelines primarily for:
- Resistant hypertension as part of combination therapy 4
- Heart failure with fluid retention where it's used for sequential nephron blockade with loop diuretics 4
Critical Monitoring Requirements
When starting metolazone, monitor closely for 1, 5:
- Hypokalemia: Dose-related potassium depletion occurs (mean decrease 0.5-0.6 mEq/L even at low doses) 2, 3
- Hyponatremia and hypochloremia: Can be severe, especially when combined with loop diuretics 6
- Renal function: Check creatinine and BUN, particularly in patients with baseline renal impairment 5, 7
- Electrolytes: Recheck within 1-2 weeks after initiation 4
Severe electrolyte disturbances (hypokalemia <2.5 mM, hyponatremia <125 mM) occurred in 10% of treatment episodes in contemporary heart failure patients, even with doses ≤5 mg 5.