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Metolazone vs. Thiazide Diuretics: Side Effects, Dosage, Drug Interactions

What are the differences between metolazone and thiazide diuretics?

What are metolazone and thiazide diuretics?

Metolazone is a diuretic ("water pill") used to treat high blood pressure and fluid accumulation. It works by blocking salt and fluid retention by the kidneys, thereby increasing urinary output of salt and water (diuresis). Although it is not a true thiazide, metolazone is chemically related to the thiazide class of diuretics which includes chlorthalidone (Hygroton) and hydrochlorothiazide, and works in a similar manner. Zaroxolyn is the original formulation of metolazone, and Diulo is similar. The absorption of these two drugs is relatively incomplete. Mykrox has more complete absorption and so less Mykrox needs to be given to have the same effects as a larger dose of Zaroxolyn or Diulo.

Thiazide diuretics (water pills) are used to treat high blood pressure (hypertension), congestive heart failure, and the accumulation of fluid and swelling (edema) of the body caused by conditions such as heart failure, chronic kidney failure, cirrhosis, corticosteroid medications, and nephrotic syndrome. Thiazides work by reducing the ability of the kidneys to reabsorb salt and water from the urine and into the body, thereby increasing the production and output of urine (diuresis). Examples of thiazide diuretics include chlorthalidone (Thalitone), hydrochlorothiazide (Microzide), and methyclothiazide.

What are the side effects of metolazone and thiazide diuretics?


Metolazone generally is well tolerated. Common side effects of metolazone are:

  • Hypokalemia (low blood potassium)
  • Hyponatremia (low blood sodium)
  • Hypomagnesemia (low blood magnesium)
  • Hypercalcemia (high blood calcium)

About 1 out of every 10 patients reports dizziness, lightheadedness, and headache. Fatigue has been reported in 1 out of every 25 patients. About 1 out of every 50 patients reports:

Thiazide diuretics, which are chemically related to metolazone, are known to increase the amount of uric acid in the blood. Precipitation of gout (which is associated with high uric acid) is rare. Metolazone can increase blood sugar in people with diabetes.

Thiazide diuretics

Side effects of thiazide diuretics are dose related and include:

  • Dizziness and lightheadedness
  • Blurred vision
  • Loss of appetite
  • Itching
  • Stomach upset
  • Headache
  • Weakness

Other side effects and adverse reactions include an increased sensitivity to sunlight, therefore avoid prolonged sun exposure.

Owing to their ability to increase the production of urine, these drugs may lower levels in the body of potassium and magnesium, which also are present in urine.

Thiazide diuretics may increase uric acid levels in blood.

Like other antihypertensive medications, thiazides cause sexual dysfunction.

What is the dosage of metolazone vs. thiazide diuretics?


The recommended dose is 2.5 to 5 mg for treating hypertension and 2.5 to 20 mg for treating edema.

Thiazide diuretics

Thiazide diuretics may come in oral tablet form. For example, Thalitone (chlorthalidone) is a common thiazide diuretic.

The optimal dose of Thalitone varies greatly from patient to patient. For high blood pressure, the recommended dose range is 25 to 100 mg daily. Most patients receive 12.5 to 25 mg daily.

Edema is treated with 50 to 100 mg daily or 100 mg every other day and the maximum dose is 200 mg daily.

Heart failure is treated with 12.5 to 100 mg daily.


Salt and sodium are the same.
See Answer

What drugs interact with metolazone and thiazide diuretics?


Metolazone can reduce blood potassium and magnesium levels. This is especially true in patients who also are taking "loop" diuretics such as furosemide (Lasix), bumetanide (Bumex), and torsemide (Demadex). Low potassium and magnesium levels can lead to heart rhythm abnormalities, especially in patients taking digoxin (Lanoxin).

Metolazone reduces excretion of lithium (Lithobid, Eskalith) by the kidneys and can lead to lithium toxicity in patients receiving lithium.

Steroids (for example, hydrocortisone) and nonsteroidal anti-inflammatory agents (NSAIDs) such as ibuprofen (Motrin), naproxen (Naprosyn), and nabumetone (Relafen) can reduce the effectiveness of metolazone by interfering with the excretion of salt and water.

Thiazide diuretics

Thiazide diuretics can lower potassium and magnesium blood levels since they are both eliminated in urine. Low levels of potassium and magnesium in the blood can result in abnormal heart rhythms, particularly in those who are also taking digoxin (Lanoxin) in addition to a thiazide. Thiazide diuretics can increase the risk of lithium (Eskalith, Lithobid) toxicity by reducing the kidney's ability to eliminate lithium in the urine.

Drugs known as nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen (Motrin), naproxen (Naprosyn), and nabumetone (Relafen) can reduce the effectiveness of thiazide diuretics in lowering blood pressure because they may reduce the ability of the kidneys to make urine, particularly in patients who have reduced kidney function.

People who have diabetes may have increased blood sugar levels when taking thiazide diuretics.

It is not recommended to use thiazide diuretics with dofetilide (Tikosyn), a drug used for treating abnormal heart rhythms, as this may increase the blood levels of dofetilide (Tikosyn) and cause abnormal heart rhythms. Thiazide diuretics can reduce how the body responds to norepinephrine and render norepinephrine less effective.

Are metolazone and thiazide diuretics safe to use while pregnant or breastfeeding?


Metolazone should not be used during pregnancy unless absolutely necessary.

Metolazone is excreted in breast-milk. Intense diuresis using metolazone may reduce the production of milk. Otherwise metolazone is considered safe to use during nursing if required by the mother.

Thiazide diuretics

Thiazide diuretics including Thalitone (chlorthalidone) cross the placenta and can cause jaundice in the fetus or newborn. Therefore, thiazide diuretics such as Thalitone should not be used during pregnancy unless absolutely necessary.

Large doses of thiazide diuretics may suppress milk production, but the American Academy of Pediatrics considers thiazides to be compatible with breastfeeding.


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