Name: Metolazone

Metolazone Dosage

Your dose of metolazone will depend on your doctor's orders. The following is an average dosing schedule:

For fluid retention (edema):

  • Adults: Start with 5 to 20 milligrams (mg), once daily. Your doctor may adjust your dose if needed.
  • Children: Usage and dose will be determined by doctor.

For high blood pressure:

  • Adults: Start with 2.5 to 5 mg, once daily. Your doctor may adjust your dose if needed.
  • Children: Usage and dose will be determined by doctor.

Metolazone Overdose

If you suspect an overdose, call 911 or contact your doctor immediately. You can get in touch with a poison control center at 800-222-1222.

Missed Dose of Metolazone

If you miss a dose of metolazone, take it as soon as you remember. However, if it is almost time for the next dose, skip the missed dose and continue on your regular dosing schedule. Do not double up on doses to make up for a missed one.

Metolazone Overview

Metolazone is a prescription medication used to treat high blood pressure and fluid retention caused by congestive heart failure or kidney disease. This medication belongs to a group of drugs called diuretics ("water pills"), which help the body get rid of excess fluid by increasing the amount of salt and water the kidneys remove from the blood.

This medication comes in tablet form and is usually taken once daily. Metolazone can be taken with or without food.

Common side effects of metolazone include headache, stomach pain, and dry mouth. Metolazone may cause drowsiness. Do not drive or operate heavy machinery until you know how it affects you.

Metolazone Food Interactions

Medications can interact with certain foods. In some cases, this may be harmful and your doctor may advise you to avoid certain foods. In the case of metolazone, there are no specific foods that you must exclude from your diet when receiving this medication.

Metolazone and Pregnancy

Tell your doctor if you are pregnant or plan to become pregnant.

The FDA categorizes medications based on safety for use during pregnancy. Five categories - A, B, C, D, and X, are used to classify the possible risks to an unborn baby when a medication is taken during pregnancy.

Metolazone falls into category B. There are no good studies that have been done in humans with metolazone. But in animal studies, pregnant animals were given this medication, and the babies did not show any medical issues related to this medication.

What is the most important information I should know about metolazone?

You should not use metolazone if you are unable to urinate, or if you have severe liver disease.

What happens if I miss a dose?

Take the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up the missed dose.


Diuretic and antihypertensive agent; structurally and pharmacologically similar to thiazide diuretics.a e

Uses of Metolazone

  • It is used to treat high blood pressure.
  • It is used to get rid of extra fluid.

What do I need to tell my doctor BEFORE I take Metolazone?

  • If you have an allergy to metolazone or any other part of metolazone.
  • If you are allergic to any drugs like this one, any other drugs, foods, or other substances. Tell your doctor about the allergy and what signs you had, like rash; hives; itching; shortness of breath; wheezing; cough; swelling of face, lips, tongue, or throat; or any other signs.
  • If you are not able to pass urine.

This is not a list of all drugs or health problems that interact with this medicine.

Tell your doctor and pharmacist about all of your drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for you to take metolazone with all of your drugs and health problems. Do not start, stop, or change the dose of any drug without checking with your doctor.

How is this medicine (Metolazone) best taken?

Use this medicine as ordered by your doctor. Read all information given to you. Follow all instructions closely.

  • Take with or without food.
  • This medicine may cause you to pass urine more often. To keep from having sleep problems, try to take before 6 pm.
  • Keep taking metolazone as you have been told by your doctor or other health care provider, even if you feel well.
  • To gain the most benefit, do not miss doses.

What do I do if I miss a dose?

  • Take a missed dose as soon as you think about it.
  • If it is close to the time for your next dose, skip the missed dose and go back to your normal time.
  • Do not take 2 doses at the same time or extra doses.

What are some side effects that I need to call my doctor about right away?

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

  • Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
  • Signs of fluid and electrolyte problems like mood changes, confusion, muscle pain or weakness, a heartbeat that does not feel normal, very bad dizziness or passing out, fast heartbeat, more thirst, seizures, feeling very tired or weak, not hungry, unable to pass urine or change in the amount of urine produced, dry mouth, dry eyes, or very bad upset stomach or throwing up.
  • Signs of kidney problems like unable to pass urine, change in how much urine is passed, blood in the urine, or a big weight gain.
  • Signs of high blood sugar like confusion, feeling sleepy, more thirst, more hungry, passing urine more often, flushing, fast breathing, or breath that smells like fruit.
  • Signs of liver problems like dark urine, feeling tired, not hungry, upset stomach or stomach pain, light-colored stools, throwing up, or yellow skin or eyes.
  • Signs of a pancreas problem (pancreatitis) like very bad stomach pain, very bad back pain, or very bad upset stomach or throwing up.
  • Very bad dizziness or passing out.
  • A burning, numbness, or tingling feeling that is not normal.
  • Chest pain or pressure.
  • Change in sex ability.
  • Any unexplained bruising or bleeding.
  • Feeling very tired or weak.
  • Fever or chills.
  • Sore throat.
  • Restlessness.
  • Low mood (depression).

Consumer Information Use and Disclaimer

  • If your symptoms or health problems do not get better or if they become worse, call your doctor.
  • Do not share your drugs with others and do not take anyone else's drugs.
  • Keep a list of all your drugs (prescription, natural products, vitamins, OTC) with you. Give this list to your doctor.
  • Talk with the doctor before starting any new drug, including prescription or OTC, natural products, or vitamins.
  • Some drugs may have another patient information leaflet. Check with your pharmacist. If you have any questions about this medicine, please talk with your doctor, nurse, pharmacist, or other health care provider.
  • If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

This information should not be used to decide whether or not to take metolazone or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to metolazone. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.

Review Date: October 4, 2017

Metolazone - Clinical Pharmacology

Metolazone is a quinazoline diuretic, with properties generally similar to the thiazide diuretics. The actions of Metolazone result from interference with the renal tubular mechanism of electrolyte reabsorption. Metolazone acts primarily to inhibit sodium reabsorption at the cortical diluting site and to a lesser extent in the proximal convoluted tubule. Sodium and chloride ions are excreted in approximately equivalent amounts. The increased delivery of sodium to the distal tubular exchange site results in increased potassium excretion. Metolazone does not inhibit carbonic anhydrase. A proximal action of Metolazone has been shown in humans by increased excretion of phosphate and magnesium ions and by a markedly increased fractional excretion of sodium in patients with severely compromised glomerular filtration. This action has been demonstrated in animals by micropuncture studies.

When Upstate's Metolazone tablets, USP, are given, diuresis and saluresis usually begin within one hour and may persist for 24 hours or more. For most patients, the duration of effect can be varied by adjusting the daily dose. High doses may prolong the effect. A single daily dose is recommended. When a desired therapeutic effect has been obtained, it may be possible to reduce dosage to a lower maintenance level.

The diuretic potency of Metolazone tablets, USP, at maximum therapeutic dosage is approximately equal to thiazide diuretics. However, unlike thiazides, Metolazone tablets, USP, may produce diuresis in patients with glomerular filtration rates below 20 mL/min.

Metolazone tablets, USP, and furosemide administered concurrently have produced marked diuresis in some patients where edema or ascites was refractory to treatment with maximum recommended doses of these or other diuretics administered alone. The mechanism of this interaction is unknown (see WARNINGS and PRECAUTIONS, Drug Interactions).

Maximum blood levels of Metolazone are found approximately eight hours after dosing. A small fraction of Metolazone is metabolized. Most of the drug is excreted in the unconverted form in the urine.

Indications and Usage for Metolazone

Upstate's Metolazone tablets, USP, are indicated for the treatment of salt and water retention including:

  • edema accompanying congestive heart failure;
  • edema accompanying renal diseases, including the nephrotic syndrome and states of diminished renal function.

Metolazone tablets, USP, are also indicated for the treatment of hypertension, alone or in combination with other antihypertensive drugs of a different class. MYKROX Tablets, a more rapidly available form of Metolazone, are intended for the treatment of new patients with mild to moderate hypertension. A dose titration is necessary if MYKROX Tablets are to be substituted for Upstate's Metolazone tablets, USP, in the treatment of hypertension. See package circular for MYKROX Tablets (UCB).

Usage In Pregnancy

The routine use of diuretics in an otherwise healthy woman is inappropriate and exposes mother and fetus to unnecessary hazard. Diuretics do not prevent development of toxemia of pregnancy, and there is no evidence that they are useful in the treatment of developed toxemia.

Edema during pregnancy may arise from pathologic causes or from the physiologic and mechanical consequences of pregnancy. Metolazone tablets, USP, are indicated in pregnancy when edema is due to pathologic causes, just as it is in the absence of pregnancy (see PRECAUTIONS). Dependent edema in pregnancy resulting from restriction of venous return by the expanded uterus is properly treated through elevation of the lower extremities and use of support hose; use of diuretics to lower intravascular volume in this case is illogical and unnecessary. There is hypervolemia during normal pregnancy which is harmful to neither the fetus nor the mother (in the absence of cardiovascular disease), but which is associated with edema, including generalized edema, in the majority of pregnant women. If this edema produces discomfort, increased recumbency will often provide relief. In rare instances, this edema may cause extreme discomfort which is not relieved by rest. In these cases, a short course of diuretics may be appropriate.


(me TOLE a zone)

Pharmacologic Category

  • Diuretic, Thiazide-Related

Dosing Adult

Edema (renal disease): Oral: Initial: 5-20 mg once daily.

Edema (heart failure) (off-label dose): Oral: Initial: 2.5 mg once daily; maximum daily dose: 20 mg (ACCF/AHA [Yancy, 2013]); Note: Dosing frequency may be adjusted based on patient-specific diuretic needs (eg, administration every other day or weekly) (HFSA [Lindenfeld, 2010]).

Hypertension: Oral: Initial: 2.5-5 mg once daily; adjust dose as necessary to achieve maximum therapeutic effect.

For Healthcare Professionals

Applies to metolazone: oral tablet


A rare case of hyperosmolar nonketotic hyperglycemia is associated with metolazone.[Ref]

Metabolic side effects are the most common and profound. The rapid onset of hyponatremia or hypokalemia is often sudden and may be profound, particularly if metolazone is given with a loop diuretic. Hypokalemia may be important in patients with underlying cardiac arrhythmias. Metolazone may increase serum calcium and uric acid levels and lower serum magnesium and phosphate levels. Glucose intolerance is reported in rare cases.[Ref]


Cardiovascular side effects are uncommon. Postural hypotension is reported in less than 5% of patients. Rare cases of venous thrombosis are reported, thought to be due to metolazone-induced hypovolemia and increased serum concentrations of clotting factors. Rare cardiovascular side effects also include palpitations, hypovolemia, and chest pain.[Ref]


Renal insufficiency, manifest as a rise in serum creatinine and BUN, may occur, although, in most cases, creatinine clearance increases as a result of metolazone therapy.[Ref]

Nervous system

Nervous system side effects include headache, dizziness, and fatigue. Two cases of syncope and seizures are reported. Metolazone-induced hypovolemia and electrolyte changes may induce hepatic encephalopathy in some patients.[Ref]

It is not clear whether the patients who developed syncope and seizure activity were hypotensive or hypovolemic at the time of the seizures or that metolazone can definitively be implicated. In one case the patient was also taking theophylline and had hypomagnesemia, which may be a complication of metolazone therapy.[Ref]


Hypersensitivity reactions include rare case reports of necrotizing vasculitis, angiitis, and pruritic rashes.[Ref]

A case of cutaneous hypersensitivity angiitis has been reported in a patient who had previously tolerated thiazide diuretics, indicating that, despite the chemical similarity between thiazides and metolazone, there is not necessarily cross-reactivity.[Ref]


Hematologic abnormalities are rare. Cases of reversible hypoplastic anemia, aplastic anemia, agranulocytosis, and mild leukopenia are reported.[Ref]


Gastrointestinal side effects are rare, and include a case of acute pancreatitis. Nausea, vomiting, anorexia, and abdominal bloating are also rare.[Ref]


Hepatic side effects include a rare case of cholestatic jaundice.[Ref]


Musculoskeletal cramps are associated with metolazone therapy, as with other diuretics, and may be associated with electrolyte disorders and rapid intravascular volume shifts.[Ref]

Some side effects of metolazone may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.

Usual Adult Dose for Edema

Initial dose: 5 mg orally once a day (Zaroxolyn) or
0.5 mg orally once a day (Mykrox).

Liver Dose Adjustments

Data not available

Dose Adjustments

Data not available


Metolazone is contraindicated in patients who are anuric, comatose, or severely obtunded.

Be cognizant of the possibility of the rapid onset of significant hyponatremia or hypokalemia, particularly if metolazone is given with a loop diuretic. This may be especially important in patients with underlying cardiac arrhythmias.

All patients receiving therapy with metolazone should have serum electrolyte measurements done at appropriate intervals and be observed for clinical signs of fluid and/or electrolyte imbalance: namely, hyponatremia, hypochloremic alkalosis, and hypokalemia. In individuals with severe edema accompanying cardiac failure or renal disease, a low-salt syndrome may be produced, especially with hot weather and a low-salt diet. Serum and urine electrolyte determinations are particularly important when the patient has protracted vomiting, severe diarrhea, or is receiving parenteral fluids. Warning signs of imbalance are dryness of mouth, thirst, weakness, lethargy, drowsiness, restlessness, muscle pains or cramps, muscle fatigue, hypotension, oliguria, tachycardia, and gastrointestinal disturbances such as nausea and vomiting. Hyponatremia may occur at any time during long term treatment and, on rare occasions, may be life threatening.

The risk of hypokalemia is increased when larger doses are administered, when diuresis is rapid, when severe liver disease is present, when corticosteroids are given concomitantly, when oral intake is inadequate or when excess potassium is being lost extrarenally, such as with vomiting or diarrhea.

Thiazide-like diuretics have been shown to increase the urinary excretion of magnesium; this may result in hypomagnesemia.

Metolazone therapy may raise blood glucose concentrations possibly causing hyperglycemia and glycosuria in individuals with diabetes or latent diabetes.

Metolazone therapy regularly causes an increase in serum uric acid and can occasionally precipitate gouty attacks even in patients without a prior history of them.

Azotemia, presumably prerenal azotemia, may be precipitated during the use of metolazone. If azotemia and oliguria worsen during therapy of patients with severe renal disease, metolazone should be discontinued.

Cautions should be used when administering metolazone tablets to patients with severely impaired renal function. As most of the drug is excreted by the renal route, accumulation may be observed.

Orthostatic hypotension has been observed in some patients.

Hypercalcemia may infrequently occur with metolazone therapy, especially in patients taking high doses of vitamin D or with high bone turnover states, and may signify hidden hyperparathyroidism. Metolazone therapy should be discontinued before tests for parathyroid function are performed.

Thiazide diuretics have exacerbated or activated systemic lupus erythematosus and this possibility should be considered with metolazone therapy.