What is the recommended dosing frequency for metolazone (thiazide-like diuretic)?

From the Guidelines

Metolazone should be administered once daily, with a typical starting dose of 2.5 mg, as indicated in the 2013 ACCF/AHA guideline for the management of heart failure 1. The recommended dosing frequency for metolazone, a thiazide-like diuretic, is based on its duration of action, which is 12 to 24 hours, allowing for once-daily administration.

• The initial daily dose of metolazone is 2.5 mg, which can be adjusted based on the patient's response, with a maximum total daily dose of 20 mg, as outlined in the guideline 1.
• Morning administration is preferred to minimize the risk of nocturia and disrupt sleep.
• In patients with heart failure, metolazone can be used in combination with a loop diuretic, with metolazone given 30 minutes before the loop diuretic to enhance diuretic efficacy through sequential nephron blockade, as suggested by the guideline 1.
• Patients on metolazone should be monitored for potential side effects, including electrolyte imbalances, such as hypokalemia and hyponatremia, and hypotension, especially when initiating therapy.
• The guideline recommends the use of diuretics, including metolazone, in patients with heart failure, unless contraindicated, to reduce morbidity and mortality 1.

From the FDA Drug Label

A single daily dose is recommended The recommended dosing frequency for metolazone is once daily.

• The duration of effect can be varied by adjusting the daily dose.
• High doses may prolong the effect.
• When a desired therapeutic effect has been obtained, it may be possible to reduce dosage to a lower maintenance level 2

From the Research

Dosing Frequency of Metolazone

The recommended dosing frequency for metolazone, a thiazide-like diuretic, varies depending on the patient's condition and response to treatment.

• In patients with hypertension, a daily dose of 0.5 mg to 2.0 mg is commonly used, as shown in a study published in 1986 3.
• For patients with severe refractory congestive cardiac failure, a dose of 1.25-10 mg daily is recommended, with some patients requiring doses as high as 200 mg, as reported in a study from 1990 4 and a review of the literature from 2005 5.
• In outpatients with refractory heart failure, a low starting dose of metolazone (< or =5 mg) is often used in combination with a loop diuretic, as observed in an observational study from 2005 5.
• The dosing frequency may need to be adjusted based on the patient's response to treatment and the presence of any adverse effects, such as hypokalemia or hyponatremia, as noted in several studies 6, 4, 5.

Factors Influencing Dosing Frequency

Several factors can influence the dosing frequency of metolazone, including:

• The patient's renal function, as metolazone is effective even in patients with low glomerular filtration rates, as reported in a study from 2005 5.
• The presence of other medical conditions, such as hypertension or heart failure, which may require adjustments to the dosing frequency, as shown in studies from 1985 7 and 1986 3.
• The patient's response to treatment, including the presence of any adverse effects, which may require adjustments to the dosing frequency, as noted in several studies 6, 4, 5.