Metolazone Oral: Uses, Side Effects, Interactions, Pictures, Warnings & Dosing

Uses

How to use Metolazone

Take this medication by mouth with or without food, usually once daily, or as directed by your doctor. The dosage is based on your medical condition and response to therapy.

If you take this drug too close to bedtime, you may need to wake up to urinate. It is best to take this medication at least 4 hours before your bedtime.

Use this medication regularly in order to get the most benefit from it. Remember to use it at the same time each day as directed. Keep taking this medication even if you feel well. Most people with high blood pressure do not feel sick. Do not stop taking this medication without consulting your doctor. It may take up to 3-6 weeks to see a lowering of your blood pressure.

Cholestyramine and colestipol can decrease the absorption of metolazone. If you are taking either of these drugs, separate metolazone from cholestyramine by at least 4 hours and from colestipol by at least 2 hours.

If your condition lasts or gets worse, tell your doctor or pharmacist.

Side Effects

Dizziness, lightheadedness, headache, blurred vision, loss of appetite, stomach upset, diarrhea, or constipation may occur as your body adjusts to the medication. If any of these effects last or get worse, tell your doctor or pharmacist promptly.

Remember that this medication has been prescribed because your doctor has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.

This medication may lead to dehydration and electrolyte imbalance. Tell your doctor right away if you have any of these unlikely but serious symptoms of dehydration or electrolyte imbalance: muscle cramps or weakness, confusion, severe dizziness, unusual dry mouth or thirst, nausea or vomiting, fast/irregular heartbeat, fainting, seizures.

Tell your doctor right away if you have any serious side effects, including: nausea/vomiting that doesn’t stop, sore throat or fever that doesn’t go away, numbness/tingling of the arms/legs, decreased sexual ability, easy bleeding or bruising, stomach/abdominal pain, yellowing of eyes/skin, signs of kidney problems (such as change in the amount of urine), decrease in vision, eye pain.

A very serious allergic reaction to this drug is rare. However, get medical help right away if you notice any symptoms of a serious allergic reaction, including: rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing.

This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.

In the US – Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088 or at www.fda.gov/medwatch.

In Canada – Call your doctor for medical advice about side effects. You may report side effects to Health Canada at 1-866-234-2345.

Precautions

Before taking metolazone, tell your doctor or pharmacist if you are allergic to it; or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.

Before using this medication, tell your doctor or pharmacist your medical history, especially of: kidney disease, liver disease, untreated mineral imbalance (such as sodium, potassium), gout, lupus.

If you have diabetes, metolazone may affect your blood sugar. Check your blood sugar regularly as directed and share the results with your doctor. Tell your doctor right away if you have symptoms of high blood sugar such as increased thirst/urination. Your doctor may need to adjust your diabetes medication, exercise program, or diet.

This drug may reduce the potassium levels in your blood. Ask your doctor about adding potassium to your diet. A potassium supplement may be prescribed by your doctor.

This medication may make you more sensitive to the sun. Limit your time in the sun. Avoid tanning booths and sunlamps. Use sunscreen and wear protective clothing when outdoors. Tell your doctor right away if you get sunburned or have skin blisters/redness.

Before having surgery, tell your doctor or dentist that you are taking this medication.

This drug may make you dizzy or blur your vision. Alcohol or marijuana (cannabis) can make you more dizzy. Do not drive, use machinery, or do anything that needs alertness or clear vision until you can do it safely. Limit alcoholic beverages. Talk to your doctor if you are using marijuana (cannabis).

To minimize dizziness and lightheadedness, get up slowly when rising from a seated or lying position.

Older adults may be more sensitive to the side effects of this drug, especially dizziness.

During pregnancy, metolazone should be used only when clearly needed. Discuss the risks and benefits with your doctor.

This drug passes into breast milk. Consult your doctor before breast-feeding.

Interactions

See also the How to Use section.

Drug interactions may change how your medications work or increase your risk for serious side effects. This document does not contain all possible drug interactions. Keep a list of all the products you use (including prescription/nonprescription drugs and herbal products) and share it with your doctor and pharmacist. Do not start, stop, or change the dosage of any medicines without your doctor’s approval.

Some products that may interact with this drug include: cholestyramine, colestipol, diazoxide, digoxin, dofetilide, lithium.

Some products have ingredients that could raise your blood pressure or worsen your swelling. Tell your pharmacist what products you are using, and ask how to use them safely (especially cough-and-cold products, diet aids, or NSAIDs such as ibuprofen/naproxen).

This product can affect the results of certain lab tests (such as parathyroid function tests). Make sure laboratory personnel and your doctors know you use this drug.

Does Metolazone interact with other drugs you are taking?

Enter your medication into the WebMD interaction checker

Overdose

If someone has overdosed and has serious symptoms such as passing out or trouble breathing, call 911. Otherwise, call a poison control center right away. US residents can call their local poison control center at 1-800-222-1222. Canada residents can call a provincial poison control center. Symptoms of overdose may include fainting, severe weakness, a severe decrease in amount of urine, or slow or shallow breathing.

Do not share this medication with others.

Lifestyle changes such as stress reduction programs, exercise, and dietary changes may increase the effectiveness of this medicine. Talk to your doctor or pharmacist about lifestyle changes that might benefit you.

Lab and/or medical tests (such as blood mineral levels such as potassium, kidney/liver function) should be done while you are taking this medication. Keep all medical and lab appointments. Consult your doctor for more details.

Have your blood pressure checked regularly while taking this medication. Discuss with your doctor how to monitor your own blood pressure.

If you miss a dose, use it as soon as you remember. If it is near the time of the next dose, skip the missed dose. Use your next dose at the regular time. Do not double the dose to catch up.

Store at room temperature away from light and moisture. Do not store in the bathroom. Keep all medications away from children and pets.

Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company.

Images

metolazone 5 mg tablet

Color: whiteShape: roundImprint: 25 logo

This medicine is a white, round, tablet imprinted with “25” and “logo”.

metolazone 10 mg tablet

Color: yellowShape: roundImprint: 27 logo

This medicine is a white, round, tablet imprinted with “25” and “logo”.

metolazone 2.5 mg tablet

Color: whiteShape: roundImprint: 17 logo

This medicine is a white, round, tablet imprinted with “25” and “logo”.

metolazone 5 mg tablet

Color: blueShape: ovalImprint: logo and 55

This medicine is a white, round, tablet imprinted with “25” and “logo”.

metolazone 2.5 mg tablet

Color: pinkShape: ovalImprint: Logo and 50

This medicine is a white, round, tablet imprinted with “25” and “logo”.

metolazone 2.5 mg tablet

Color: pinkShape: roundImprint: 643 2 1/2

This medicine is a white, round, tablet imprinted with “25” and “logo”.

metolazone 5 mg tablet

Color: blueShape: roundImprint: M 5

This medicine is a white, round, tablet imprinted with “25” and “logo”.

metolazone 5 mg tablet

Color: blueShape: roundImprint: 644 5

This medicine is a white, round, tablet imprinted with “25” and “logo”.

metolazone 2.5 mg tablet

Color: pinkShape: roundImprint: M 2 1/2

This medicine is a white, round, tablet imprinted with “25” and “logo”.

metolazone 10 mg tablet

Color: yellowShape: roundImprint: 645 10

This medicine is a white, round, tablet imprinted with “25” and “logo”.

metolazone 10 mg tablet

Color: yellowShape: ovalImprint: E 56

This medicine is a white, round, tablet imprinted with “25” and “logo”.

metolazone 10 mg tablet

Color: yellowShape: roundImprint: M 10

This medicine is a white, round, tablet imprinted with “25” and “logo”.

metolazone 5 mg tablet

Color: orangeShape: roundImprint: M 173

This medicine is a white, round, tablet imprinted with “25” and “logo”.

metolazone 2.5 mg tablet

Color: peachShape: roundImprint: M 172

This medicine is a white, round, tablet imprinted with “25” and “logo”.

metolazone 10 mg tablet

Color: light greenShape: roundImprint: M 174

This medicine is a white, round, tablet imprinted with “25” and “logo”.

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Drug Survey

Are you currently using Metolazone?

This survey is being conducted by the WebMD marketing sciences department.

Selected from data included with permission and copyrighted by First Databank, Inc. This copyrighted material has been downloaded from a licensed data provider and is not for distribution, except as may be authorized by the applicable terms of use.

CONDITIONS OF USE: The information in this database is intended to supplement, not substitute for, the expertise and judgment of healthcare professionals. The information is not intended to cover all possible uses, directions, precautions, drug interactions or adverse effects, nor should it be construed to indicate that use of a particular drug is safe, appropriate or effective for you or anyone else. A healthcare professional should be consulted before taking any drug, changing any diet or commencing or discontinuing any course of treatment.

Side Effects, Dosage, Uses & More

Highlights for metolazone

1. Metolazone oral tablet is available as both a generic and brand-name drug. Brand name: Zaroxolyn.
2. The most common side effects of metolazone are constipation, dry mouth, diarrhea, headache, stomach pain, and blurred vision.
3. Metolazone is used to treat high blood pressure (hypertension) and the buildup of excess fluid and salt in your body (edema).

• Low sodium and potassium levels warning: In rare cases, taking metolazone has suddenly led to low sodium levels (hyponatremia) or low potassium levels (hypokalemia) or both. If this occurs, your doctor may have you stop using metolazone.
• High nitrogen levels warning: Metolazone can cause high levels of nitrogen in your body (azotemia). If you have kidney disease, and experience high levels of nitrogen in your body or you’re having trouble urinating (or are not urinating as often), then your doctor will stop treatment with metolazone.
• Low blood pressure when standing warning: Metolazone can cause low blood pressure when you stand up (orthostatic hypotension).

Metolazone oral tablet is a prescription drug that’s available as the brand-name drug Zaroxolyn. It’s also available as a generic drug. Generic drugs usually cost less. In some cases, they may not be available in every strength or form as the brand.

Why it’s used

Metolazone is used to treat high blood pressure. It’s also used to treat the buildup of excess fluid and salt in your body. Metolazone may be taken as part of a combination therapy with other medications.

How it works

Metolazone belongs to a class of drugs called diuretics. A class of drugs is a group of medications that work in a similar way. They’re often used to treat similar conditions. Diuretics work by causing you to urinate more. This helps remove excess fluid and salt from your body. Removing this excess fluid and salt also helps to lower your blood pressure.

Metolazone oral tablet doesn’t cause drowsiness. However, it can cause other side effects. Mild side effects may go away within a few days or a couple of weeks. If they’re more severe or don’t go away, talk to your doctor or pharmacist.

More common side effects

The most common side effects that occur with metolazone include:

• abdominal pain
• blurred vision
• constipation
• diarrhea
• dry mouth
• headache

Serious side effects

Call your doctor right away if you have any of these serious side effects. Call 911 if your symptoms feel life-threatening or if you think you’re having a medical emergency.

• Allergic reactions. Symptoms can include:
  • rash
  • hives
  • itching
  • raised welts
  • facial swelling
  • fever
  • difficulty breathing
  • peeling or blistering skin
• Heart problems. Symptoms can include:
  • irregular heartbeat
  • chest pain
• Liver problems. Symptoms can include:
  • yellowing of the whites of your eyes or your skin
  • weakness or tiredness
  • abdominal pain
  • nausea
  • vomiting
• Nerve problems. Symptoms can include:
  • muscle pain or cramps
  • numbness in your hands or feet

Disclaimer: Our goal is to provide you with the most relevant and current information. However, because drugs affect each person differently, we cannot guarantee that this information includes all possible side effects. This information is not a substitute for medical advice. Always discuss possible side effects with a healthcare provider who knows your medical history.

Metolazone oral tablet can interact with other medications, herbs, or vitamins you might be taking. An interaction is when a substance changes the way a drug works. This can be harmful or cause the drugs that you take to not work as well. To help prevent interactions, your doctor should manage all of your medications carefully. To find out how this drug might interact with something else you’re taking, talk to your doctor or pharmacist.

Examples of drugs that can cause interactions with metolazone are listed below.

Antibiotics

Taking certain antibiotics with metolazone can make metolazone not work as well. These include:

• methenamine

Other blood pressure drugs

These drugs can lower your blood pressure too much if taken with metolazone. They include:

• angiotensin-converting enzyme (ACE) inhibitors, such as:
  • benazepril
  • captopril
  • enalapril
  • enalaprilat
  • fosinopril
  • moexipril
  • perindopril
  • quinapril
  • ramipril
  • trandolapril
• angiotensin II receptor blockers (ARBs), such as:
  • irbesartan
  • losartan
  • olmesartan
  • telmisartan
  • valsartan
• beta-blockers, such as:
  • acebutolol
  • atenolol
  • betaxolol
  • bisoprolol
  • esmolol
  • metoprolol
  • nadolol
  • nebivolol
  • penbutolol
  • pindolol
  • propranolol
  • timolol (systemic)
• calcium channel blockers, such as:
  • amlodipine
  • felodipine
  • nicardipine
  • nifedipine
• direct renin inhibitors, such as:
  • aliskiren
• loop diuretics, such as:
  • bumetanide
  • furosemide
  • indapamide
  • torsemide
• potassium-sparing diuretics, such as:
  • eplerenone
  • spironolactone
  • triamterene

Blood thinners (anticoagulants)

Your dose of these drugs may need to be increased if you’re taking them with metolazone. When you take them with metolazone, they may not work as well. These drugs include:

• warfarin

Corticosteroids

Taking these medications with metolazone may increase your risk for hypokalemia (low sodium). These include:

• prednisone
• prednisolone
• methylprednisolone

Diabetes drugs

Your dose of these drugs may need to be increased if you’re taking them with metolazone. When you take them with metolazone, they may not work as well. These drugs include:

• insulin

Diuretics

Taking these drugs with metolazone may increase your risk for low sodium levels (hypokalemia). These include:

• furosemide

Heart drugs

Metolazone may increase the effects of these drugs. These drugs include:

• digoxin

Mood stabilizers

Metolazone may increase the effects of these drugs. These drugs include:

• lithium

Pain drugs

Taking the following pain drugs with metolazone can make metolazone not work as well:

• aspirin
• nonsteroidal anti-inflammatory drugs (NSAIDs), such as:
  • diclofenac
  • ibuprofen
  • indomethacin
  • ketoprofen
  • ketorolac
  • meloxicam
  • nabumetone
  • naproxen
  • piroxicam
• COX-2 Inhibitors
  • celecoxib

Taking the following pain drugs with metolazone can lower your blood pressure too much:

• barbiturates, such as:
  • butabarbital
  • butalbital
  • methohextal
  • pentobarbital
  • phenobarbital
  • secobarbital
  • thiopental
• narcotics, such as:
  • codeine
  • dihydrocodeine
  • fentanyl
  • hydrocodone
  • hydromorphone
  • levorphanol
  • mepiridine
  • methadone
  • morphine
  • opium
  • oxycodone
  • oxymorphone
  • tramadol

Disclaimer: Our goal is to provide you with the most relevant and current information. However, because drugs interact differently in each person, we cannot guarantee that this information includes all possible interactions. This information is not a substitute for medical advice. Always speak with your healthcare provider about possible interactions with all prescription drugs, vitamins, herbs and supplements, and over-the-counter drugs that you are taking.

Metolazone oral tablet comes with several warnings.

Allergy warning

Metolazone can cause a severe allergic reaction. Symptoms can include:

• trouble breathing
• swelling of your throat or tongue
• hives

Don’t take this drug again if you’ve ever had an allergic reaction to it. Taking it again could be fatal (cause death).

Alcohol interaction

Drinking alcohol while you take this drug can increase your risk for low blood pressure when you stand up (orthostatic hypotension).

Warnings for people with certain health conditions

For people with anuria: If your body isn’t able to make urine (anuria), you shouldn’t take metolazone. Metolazone is removed from your body by your kidneys. If your kidneys aren’t working well, this will make it harder for your body to get rid of the drug.

For people with liver failure: You shouldn’t take metolazone if you have advanced stages of liver failure. Metolazone can cause changes to your electrolyte levels, which may bring on a hepatic coma in people with liver disease.

For people with diabetes: Metolazone can increase your blood sugar level. Talk to your doctor before using this drug if you have diabetes.

For people with gout: Metolazone can increase the amount of acid in your body. This can cause gouty attacks.

For people with kidney disease: Metolazone is eliminated from your body through your kidneys and can build up in your body if your kidneys aren’t working as well as they should. This can lead to toxicity. Tell your doctor if you have kidney disease or kidney damage.

For people with systemic lupus erythematosus: Taking metolazone may make your systemic lupus erythematosus worse.

Warnings for other groups

For pregnant women: Metolazone is a category B pregnancy drug. That means two things:

1. Studies of the drug in pregnant animals haven’t shown risk to the fetus.
2. There aren’t enough studies done in pregnant women to show the drug poses a risk to the fetus.

Speak with your doctor if you’re pregnant or planning to become pregnant. Metolazone should only be used during pregnancy if the potential benefit justifies the potential risk to the fetus.

Women who are breastfeeding: Metolazone may pass into breast milk and can cause serious adverse effects. Talk to your doctor before taking metolazone if you’re breast-feeding or plan to breastfeed.

For children: This medicine shouldn’t be used in people younger than 18 years.

This dosage information is for metolazone oral tablet. All possible dosages and forms may not be included here. Your doctor will tell you what dosage is right for you. Your dose, form, and how often you take it will depend on:

• your age
• the condition being treated
• how severe your condition is
• other medical conditions you have
• how you react to the first dose

Forms and strengths

Generic: metolazone

• Form: Oral tablet
• Strengths: 2.5 mg, 5 mg, 10 mg

Brand: Zaroxolyn

• Form: Oral tablet
• Strengths: 2.5 mg, 5 mg, 10 mg

Dosage for hypertension

Adult dosage (ages 18 years and older)

The usual dose for mild to moderate hypertension is 2.5–5 mg by mouth, once per day.

Child dosage (ages 0–17 years)

This medicine hasn’t been studied in children and shouldn’t be used in people younger than 18 years.

Dosage for edema

Adult dosage (ages 18 years and older)

The usual dose for edema is 5–20 mg by mouth, once per day.

Child dosage (ages 0–17 years)

This medicine hasn’t been studied in children and shouldn’t be used in people younger than 18 years.

Special considerations

People with kidney disease: If you have kidney disease, you may need a lower dose or you may need a different dosing schedule. Metolazone is removed from your body by your kidneys. It can build up in your body if your kidneys aren’t working as well as they should. This can lead to toxicity.

People with heart disease: If you have heart disease or decreased heart function you may need a lower dose or you may need a different dosing schedule.

Disclaimer: Our goal is to provide you with the most relevant and current information. However, because drugs affect each person differently, we cannot guarantee that this list includes all possible dosages. This information is not a substitute for medical advice. Always speak with your doctor or pharmacist about dosages that are right for you.

Metolazone oral tablet is used for short-term or long-term therapy. For swelling and water retention in your legs and arms, metolazone is used as short-term therapy. For high blood pressure, it’s used as long-term therapy. It comes with serious risks if you don’t take it as prescribed.

If you don’t take it at all: If you don’t take metolazone at all, your blood pressure or edema, or both, might not be controlled. This may lead to a heart attack, stroke, pain, or infection.

If you stop taking it suddenly: If you’re taking metolazone for high blood pressure and suddenly stop taking it, you may experience rebound high blood pressure. This is a sudden increase in your blood pressure after you stop taking your blood pressure medication. Symptoms of rebound hypertension include headache, confusion, chest pain, sweating, nausea, and vomiting.

If you don’t take it on schedule: If you don’t take metolazone according to the schedule for your doses, it may not work as well. In order for this drug to work, you need a consistent amount of it in your body at all times.

If you take too much: Taking too much metolazone can cause dizziness, drowsiness, fainting spells, low blood pressure when you stand up, changes in your electrolytes, and trouble breathing. If you think you have taken too much metolazone, you should go to the nearest emergency room or contact poison control right away.

What to do if you miss a dose: If you forget to take your dose, take it as soon as you remember, unless you remember just a few hours before the time for your next dose. Then only take one dose. Never try to catch up by taking two doses at once. This could result in toxic side effects.

How to tell if the drug is working: You may or may not be able to tell if metolazone is working; however, your doctor will check your blood pressure and fluid volume regularly to see if they’re at normal levels and controlled. You also may purchase a blood pressure monitor from your local pharmacy so that you can check your blood pressure yourself.

Keep these considerations in mind if your doctor prescribes metolazone oral tablet for you.

General

• Metolazone can be taken with or without food.
• Metolazone should be taken early in the day. This helps to avoid frequent urination throughout the night.
• Not every pharmacy stocks this drug. When filling your prescription, be sure to call ahead.

Storage

• Keep it between 68°F (20ºC) and 77°F (25°C).
• Don’t freeze metolazone.
• Keep it away from light and high temperature.
• Keep your drugs away from areas where they could get wet, such as bathrooms. Store these drugs away from moisture and damp locations.

Refills

A prescription for this medication is refillable.You should not need a new prescription for this medication to be refilled. Your doctor will write the number of refills authorized on your prescription.

Travel

When traveling with your medication:

• Always carry your medication with you, such as in your carry-on bag.
• Don’t worry about airport X-ray machines. They can’t hurt your medication.
• You may need to show airport staff the pharmacy label for your medication. Always carry the original prescription-labeled box with you.
• Don’t put this medication in your car’s glove compartment or leave it in the car. Be sure to avoid doing this when the weather is very hot or very cold.

Self-management

You may need to buy a blood pressure monitor. These can be purchased at most pharmacies.

Clinical monitoring

While you’re taking metolazone, your doctor will regularly monitor your electrolyte levels, blood sugar level, blood acid levels, calcium levels, heart function, liver function, and kidney function.

Sun sensitivity

Metolazone can make your skin more sensitive to the sun. This increases your risk of sunburn. Avoid the sun if you can. If you can’t, be sure to wear protective clothing and apply sunscreen.

Insurance

Many insurance companies require a prior authorization for this drug. This means your doctor will need to get approval from your insurance company before your insurance company will pay for the prescription.

There are other drugs available. Some may be better for you than others. Talk to your doctor about other options that may work for you.

Disclaimer: Healthline has made every effort to make certain that all information is factually correct, comprehensive, and up-to-date. However, this article should not be used as a substitute for the knowledge and expertise of a licensed healthcare professional. You should always consult your doctor or other healthcare professional before taking any medication. The drug information contained herein is subject to change and is not intended to cover all possible uses, directions, precautions, warnings, drug interactions, allergic reactions, or adverse effects. The absence of warnings or other information for a given drug does not indicate that the drug or drug combination is safe, effective, or appropriate for all patients or all specific uses.

Metolazone – instructions for use

metolazone

Instruction:

• Pharmacological action
• Pharmacokinetics
• Readings
• Contraindications
• With care
• Pregnancy and breastfeeding
• Dosage and Administration
• Side effects
• Overdose
• Interaction
• Transport management
• Sports medicine
• Classification

Pharmacological action

Metolazone is a thiazide diuretic. Suppresses sodium reabsorption in the distal tubules, causing increased excretion of water and sodium, potassium and hydrogen ions.

Pharmacokinetics

Absorption and distribution

Bioavailability is about 40-65%. Onset of action: diuresis, ~60 minutes. Duration of action: ≥24 hours.

Time to reach maximum plasma concentration (TC _max ) – 8 hours.

Communication with plasma proteins – 95%.

Biotransformation and excretion

Metolazone is slightly metabolized. 70-95% is excreted unchanged in the urine due to glomerular filtration and active tubular secretion.

Half-life (T _½ ) – 20 hours.

Elimination – with urine (80%), with bile (10%).

Indications

Mild to moderate hypertension, edema in heart failure, nephrotic syndrome and conditions of reduced kidney function.

Contraindications

• Hypersensitivity to metolazone;
• anuria;
• hepatic coma or precoma.

With caution

• Diabetes,
• hypercholesterolemia,
• hyperuricemia,
• gout,
• hypotension,
• systemic lupus erythematosus,
• sympathectomy,
• liver diseases.

Pregnancy and breastfeeding

Use in pregnancy

FDA fetal category B.

Adequate and strictly controlled studies on the safety of metolazone during pregnancy in humans have not been conducted. Metolazone crosses the placental barrier.

Animal studies have not shown evidence of teratogenicity.

In the event of pregnancy, absence of menstruation or suspected possible pregnancy, the patient should inform her doctor.

The use of metolazone in pregnant women is contraindicated unless the potential benefit to the mother outweighs the possible risk to the fetus.

Use during breastfeeding

Special studies on the safety of the use of metolazone during breastfeeding have not been conducted.

Metolazone is excreted in breast milk. A risk to the infant cannot be ruled out.

Should stop breast-feeding if necessary to use the drug.

Dosage and administration

Orally (by mouth).

Children

200-400 mcg/kg/day in 1-2 divided doses.

Adults

Edema: 5-20 mg once daily.

Arterial hypertension: 2.5-5 mg once a day.

Side effects

Generally well tolerated, most adverse reactions reported were mild and transient.

Frequency not determined: chest pain, depression, dizziness, drowsiness, electrolyte disturbances, glucosuria, gout attacks, headache, hemoconcentration, hepatotoxicity, hyperuricemia, hypochloremic alkalosis, hypokalemia, hypomagnesemia, hyponatremia, hypophosphatemia, hyperglycemia, hypercalcemia, decreased libido, increased blood urea nitrogen, joint pain, leukopenia, necrotizing angiitis, neuropathy, nocturia, orthostatic hypotension, palpitations, pancreatitis, anxiety, Stevens-Johnson syndrome, syncope, toxic epidermal necrolysis, urticaria, venous thrombosis.

Overdose

Symptoms: labored breathing, dizziness, drowsiness, fainting, gastrointestinal irritation, lethargy leading to coma.

Interaction

The combined use of metolazone with aymaline increases the risk of cholestasis.

Alfuzosin may increase the hypotensive effect of drugs that lower blood pressure.

When used concomitantly, thiazide diuretics may increase the likelihood of allergic or hypersensitivity reactions to allopurinol and may increase the serum concentration of oxypurinol, the active metabolite of allopurinol.

Blood pressure lowering drugs may increase the hypotensive effect of amifostine.

Co-administration of metolazone with aminolevulinic acid may enhance the photosensitizing effect of aminolevulinic acid.

When used in combination with amphetamines, the antihypertensive effect of metolazone may be reduced.

Thiazide diuretics may increase the hypotensive and nephrotoxic effects of angiotensin-converting enzyme inhibitors.

Anticholinergics may increase the serum concentration of thiazide diuretics.

When used concomitantly, thiazide diuretics may reduce the therapeutic effect of antidiabetic agents.

Barbiturates may enhance the hypotensive effect of drugs that lower blood pressure.

With the simultaneous use of benperidol with antihypertensive drugs, the effect of antihypertensive drugs is enhanced.

Beta ₂ -agonists may enhance the hypokalemic effect of thiazide diuretics.

Brigatinib may reduce the antihypertensive effect and increase the bradycardia effect of antihypertensive agents.

Metolazone may increase the bradycardial effect of drugs that cause bradycardia.

Brimonidine may enhance the hypotensive effect of antihypertensive drugs.

Blood pressure lowering drugs may enhance the hypotensive effect of bromperidol. Bromperidol may reduce the antihypertensive effect of blood pressure lowering agents.

Photosensitizing agents may enhance the photosensitizing effect of verteporfin.

Thiazide diuretics may increase the hypercalcemic effect of vitamin D analogues.

Thiazide diuretics may reduce the excretion of calcium salts. Simultaneous intake with calcium salts can lead to metabolic alkalosis.

Co-administration of carbamazepine with diuretics may lead to symptomatic hyponatremia.

Due to the hypokalemic and hypomagnesemic action, thiazide diuretics can enhance the adverse / toxic effects of cardiac glycosides.

Corticosteroids may enhance the hypokalemic effect of thiazide diuretics.

Thiazide diuretics may increase the adverse/toxic effects of cyclophosphamide (potentiation of granulocytopenia is possible).

Dexketoprofen may increase the toxic effects of sulfonamides.

Co-administration of dexmethylphenidate may reduce the therapeutic effect of antihypertensive agents.

Co-administration of diacerein may enhance the therapeutic effect of diuretics and may increase the risk of dehydration or hypokalemia.

Diazoxide may enhance the antihypertensive effect of blood pressure lowering agents.

Thiazide diuretics may increase the adverse/toxic effects of diazoxide.

Thiazide diuretics may enhance the hypokalemic effect of dichlorphenamide.

Thiazide diuretics may increase the plasma concentration of dofetilide and increase its QT prolongation effect.

Antihypertensive agents may increase the hypotensive effect of duloxetine.

Thiazide diuretics may increase the arrhythmogenic effect of fexinidazole.

Herbal medicines with hypertensive properties may reduce the antihypertensive effect of antihypertensive drugs.

Herbal medicines with antihypertensive properties may enhance the hypotensive effect of blood pressure lowering agents.

Ipragliflozin may enhance the effects of diuretics and also increase the risks associated with their use, such as the risk of dehydration and hypotension.

Yohimbine may reduce the antihypertensive effect of antihypertensive drugs.

Bile acid sequestrants may reduce the absorption of thiazide diuretics and reduce the diuretic response.

Thiazide diuretics may increase the arrhythmogenic effect of ivabradine.

Antihypertensive agents may enhance the hypotensive effect of levodopa.

Thiazide diuretics may increase the adverse/toxic effects of levosulpiride.

The simultaneous use of thiazide diuretics with licorice is not recommended due to the risk of hypokalemia.

Thiazide diuretics may reduce lithium excretion.

Co-administration of lormetazepam may enhance the hypotensive effect of antihypertensive agents.

Thiazide diuretics may increase the severity of adverse reactions of mecamylamine.

Thiazide diuretics reduce the effectiveness of methenamine.

Methylphenidate may reduce the hypotensive effect of antihypertensive drugs.

With the simultaneous administration of molsidomine with antihypertensive drugs, the hypotensive effect is enhanced.

Thiazide diuretics may enhance the hypotensive effect and QTc effect of arsenic trioxide.

Naftopidil may enhance the hypotensive effect of antihypertensive drugs.

Nicergoline enhances the effect of antihypertensive drugs.

Co-administration of nicorandil may potentiate the effects of antihypertensive agents.

Antihypertensive drugs may enhance the hypotensive effect of nitroprusside.

Thiazide diuretics may increase the nephrotoxic effect of NSAIDs. NSAIDs may reduce the therapeutic effect of thiazide diuretics.

Co-administration of obinutuzumab may enhance the effects of antihypertensive agents.

Opioid agonists may increase the severity of adverse reactions and reduce the therapeutic effect of diuretics.

Thiazide diuretics may increase the risk of hyponatremia when used concomitantly with oxcarbazepine.

Prostacyclin analogues may increase the effect of antihypertensive drugs.

Photosensitizing agents may increase the photosensitizing effect of the porfimer.

Co-administration with pentoxifylline may enhance the effect of antihypertensive drugs.

Thiazide diuretics may increase plasma concentrations and enhance the hypokalemic effect of topiramate.

Thiazide diuretics may increase the hypercalcemic effect of toremifene.

Phosphodiesterase 5 inhibitors may potentiate the effects of antihypertensives.

The combination of promazine with antihypertensive drugs can lead to severe orthostatic hypotension.

Reboxetine may enhance the hypokalemic effect of thiazide diuretics.

Antihypertensive drugs may enhance the hypotensive effect of folcodine.

Quinagolide may enhance the effect of antihypertensive drugs.

Selective serotonin reuptake inhibitors may enhance the hyponatremic effect of thiazide diuretics.

Diuretics may increase the nephrotoxic effect of sodium phosphates and increase the risk of acute phosphate nephropathy.

Ethanol may enhance the orthostatic hypotensive effect of thiazide diuretics.

Influence on the ability to drive vehicles and control mechanisms

It is necessary to refrain from driving vehicles and engaging in activities that require increased concentration of attention and speed of psychomotor reactions.

Sports medicine

Metolazone may cause anti-doping rule violations and positive results in doping controls.

Metolazone belongs to class S5 “Diuretics and masking agents” of the WADA Prohibited List.

NOTE: Detection in an athlete’s sample at any time or in-competition, as the case may be, of any number of substances that are authorized for use while meeting the threshold concentration level, for example: formoterol, salbutamol, cathine, ephedrine, methylephedrine and pseudoephedrine, in combination with a diuretic or masking agent will be considered an Adverse Analytical Finding (AAF) unless the Athlete has an approved Therapeutic Use Exemption (TUE) for that substance in addition to a Therapeutic Use Exemption for the diuretic.

Glossary

9030 5

Classification

• ATX

  C03BA08

• Pharmacological group

  Diuretics

• ICD codes 10

  I10 Essential (primary) hypertension

  I15 Secondary hypertension

  I50.0 Congestive heart failure

  N04 Nephrotic syndrome

• FDA pregnancy category

  B
  (no risk in non-human studies)

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Learn more about the active substance Metolazone:

• INN
• Reviews
• Questions
• Latin name
• Chemical formula

Information about the active substance Metolazone is intended for medical and pharmaceutical professionals, for reference purposes only. The instructions are not intended to replace professional medical advice, diagnosis or treatment. The information contained here may change over time. The most accurate information on the use of drugs containing the active substance Metolazone is contained in the manufacturer’s instructions attached to the package.

Metolazone (Metolazone Tablets): Uses, Dosage, Side Effects, Interactions, Warning

• Generic Name: Metolazone Tablets
• Brand Name: Metolazone

• Concomitant Drugs Bumex Microzide Active

90 005

• Product description
• Indications
• Dosage
• Side effects
• Drug interactions
• Warnings
• Precautions
• Overdose and Contraindications
• Clinical Pharmacology
• Medication Guide

Product Description

900 35 METOLAZONE (Mykrox)
(metolazone) Tablet

DO NOT EXCHANGE: DO NOT EXCHANGE ZAROXOLINE TABLETS AND OTHERS FORMS OF METOLAZONE THAT HAVE A SLOW AND INCOMPLETE BIODEPENDENCE AND ARE NOT THERAPEUTICALLY EQUIVALENT IN THE SAME DOSES OF THE METAL PRODUCT OF THE MICROX TABLET AND THE AVAILABLE PRODUCT OF BIOLAZONE. ZAROXOLIN BIOEQUIVALENTS AND MICROX BIOEQUIVALENTS SHOULD NOT BE REPLACED BY ANOTHER.

DESCRIPTION

Metolazone, USP oral tablets contain 2.5 mg, 5 mg, or 10 mg of metolazone, USP, a diuretic/saluretic/hypotensive of the quinazoline class.

Metolazone has the molecular formula C ₁₆ H ₁₆ Boat ₃ OR ₃ S, chemical name 7-chloro-1,2,3,4 -tetrahydro-2-methyl-3-( 2-methylphenyl)-4-oxo-6-quinazolinesulfonamide, and molecular weight 365.83. Structural formula:

Metolazone is poorly soluble in water, but is more soluble in plasma, blood, alkalis and organic solvents. Inactive Ingredients: Colloidal silica, FD&C Yellow #6 Lake HT, magnesium stearate and microcrystalline cellulose. In addition, the 10mg dose contains D&C Yellow #10 Lake HT and FD&C Blue #2 Lake HT.

Indications

INDICATIONS

Metolazone tablets are indicated for the treatment of salt and water retention including:

• edema accompanying congestive heart failure;
• edema associated with kidney disease, including nephrotic syndrome and conditions of reduced kidney function.

Metolazone tablets are also indicated for the treatment of hypertension, alone or in combination with other antihypertensive drugs of another class. Mykrox tablets, a more rapidly available form of metolazone, are intended for the treatment of new patients with mild to moderate hypertension. Dose titration is necessary if Mykrox tablets replace Zaroxolyn tablets and other metolazone preparations, which have slow and incomplete bioavailability, in the treatment of hypertension.

Use in pregnancy

The usual use of diuretics for healthy women is inappropriate and exposes mother and fetus to unnecessary danger. Diuretics do not prevent the development of toxemia of pregnancy, and there is no evidence of their usefulness in the treatment of advanced toxemia.

Edema during pregnancy may occur due to pathological causes or due to the physiological and mechanical consequences of pregnancy. Metolazone tablets are indicated in pregnancy when edema is caused by pathological causes, as well as in the absence of pregnancy (see PRECAUTIONS ). Dependent edema during pregnancy due to restricted venous return by the dilated uterus is properly treated by elevating the lower extremities and using a support hose; the use of diuretics to reduce intravascular volume in this case is illogical and unnecessary. During normal pregnancy, hypervolemia is observed, which is not harmful to either the fetus or the mother (in the absence of cardiovascular disease), but in most pregnant women it is associated with edema, including generalized edema. If this swelling causes discomfort, strengthening the supine position often helps. In rare cases, this swelling can cause severe discomfort that does not go away with rest. In these cases, a short course of diuretics may be appropriate.

Dosage

DOSAGE AND ADMINISTRATION

The effective dosage of metolazone tablets must be individualized according to the indication and the patient’s response. A single daily dose is recommended. Therapy with metolazone tablets should be titrated to obtain an initial therapeutic response and to determine the lowest possible dose to maintain the desired therapeutic response.

Usual one-day dosing regimens

Suitable starting dosages usually fall within the indicated ranges.

Edema of heart failure

Metolazone tablets 5 to 20 mg once daily.

Edema of renal failure

Metolazone tablets 5 to 20 mg once daily.

Mild to moderate essential hypertension

Metolazone tablets 2.5 to 5 mg once daily.

New patients – if it is currently considered desirable to switch patients to Zaroxoline tablets and other metolazone preparations that share its slow and incomplete bioavailability with Mykrox, the dose should be determined by titration, starting with one tablet (0. 5 mg) once a day and increasing to two tablets. (1 mg) once daily as needed.

Treatment of edematous conditions

The time interval required to achieve the effect of the initial dosage may vary. Diuresis and saluresis usually begin within one hour and persist for 24 hours or longer. When the desired therapeutic effect is achieved, it is recommended to reduce the dose, if possible. The daily dose depends on the severity of the patient’s condition, sodium intake and body response. The decision to change the daily dose should be based on the results of careful clinical and laboratory studies. If antihypertensive drugs or diuretics are prescribed concomitantly with metolazone tablets, a more careful dosage adjustment may be required. For patients who are prone to experience paroxysmal nocturnal dyspnoea, a higher dose may be recommended to prolong diuresis and saluresis for a full 24 hours.

Treatment of hypertension

The time interval required for the initial drug regimen to show an effect can vary from three to four days to three to six weeks in the treatment of high blood pressure. Doses should be adjusted at appropriate intervals to achieve the maximum therapeutic effect.

HOW SUPPLIED

Metolazone tablets, USP are available containing 2.5 mg, 5 mg and 10 mg metolazone.

B 2.5 mg Peach colored tablets, round, biconvex, unlabeled, embossed with M on one side of the tablet and 172 on the other side. They are available in the following versions:

NDC 0378-6172-01 vials of 100 tablets
NDC 0378-6172-10 vials of 1000 tablets

B 5mg 90 036 Tablets orange, round, biconvex, unlabeled , embossed with M on one side of the tablet and 173 on the other side. They are available in the following variants:

NDC 0378-6173-01 vials of 100 tablets
NDC 0378-6173-10 vials of 1000 tablets

B 10 mg Light tablets – green, round, biconvex, unmarked, embossed M on one side of the tablet and 174 on the other side. They are available in the following versions:

NDC 0378-6174-01 vials of 100 tablets
NDC 0378-6174-10 vials of 1000 tablets 20 to 25°C (68 to 77 °F). [Cm. USP for controlled room temperature.]

Keep away from light.

Dispense in a tight, lightfast container as defined by USP using a child-proof cap.

Mylan Pharmaceuticals Inc. Morgantown, WV 26505. Revised: October 2004

Side effects

SIDE EFFECTS

Metolazone is generally well tolerated and most of the reported adverse reactions were mild and transient. Many of the adverse reactions associated with metolazone represent a continuation of its expected pharmacological activity and may be due to either its antihypertensive action or its renal/metabolic action. The following adverse reactions have been reported. Some of them are found singly or relatively rarely. Adverse reactions are listed in descending order of severity by body system.

Cardiovascular

Chest pain/discomfort, orthostatic hypotension, excessive volume depletion, hemoconcentration, venous thrombosis, palpitations.

Central and peripheral nervous system

Syncope, neuropathy, dizziness, paresthesia, psychotic depression, impotence, dizziness/lightheadedness, drowsiness, fatigue, weakness, agitation (sometimes leading to insomnia), headache.

Dermatological diseases / hypersensitivity

Toxic epidermal necrolysis (TEN), Stevens-Johnson syndrome, necrotizing angiitis (skin vasculitis), skin necrosis, purpura, petechiae, dermatitis (photosensitivity), urticaria, pruritus, skin rash.

Gastrointestinal tract

Hepatitis, intrahepatic cholestatic jaundice, pancreatitis, vomiting, nausea, epigastric upset, diarrhea, constipation, anorexia, bloating, abdominal pain.

Hematological

Aplastic/hypoplastic anemia, agranulocytosis, leukopenia, thrombocytopenia.

Metabolic

Hypokalemia, hyponatremia, hyperuricemia, hypochloremia, hypochloremic alkalosis, hyperglycemia, glucosuria, elevated serum urea nitrogen (BUN) or creatinine, hypophosphatemia, hypomagnesemia, hypercalcemia.

Musculoskeletal

Joint pain, acute attacks of gout, muscle cramps or spasms.

Other

Transient blurred vision, chills, dry mouth.

In addition, adverse reactions have been reported with similar antihypertensive drugs. diuretics, but which have not been reported on metolazone to date: bitterness, sialadenitis, xanthopsia, respiratory distress (including pneumonitis), and anaphylactic reactions. These reactions should be considered as possible cases in the clinical use of metolazone.

If adverse reactions are moderate or severe, the dose of metolazone should be reduced or therapy discontinued.

Drug interactions

DRUG INTERACTIONS

Diuretics

Furosemide and possibly other loop diuretics given concomitantly with metolazone may cause unusually large or prolonged fluid and electrolyte losses (see WARNING). ).

Other antihypertensives

When metolazone tablets are used with other antihypertensive drugs, care must be taken, especially during initial therapy. It may be necessary to adjust the dosage of other antihypertensive drugs.

Alcohol, barbiturates and narcotics

The hypotensive effects of these drugs may be enhanced by volume reduction which may be associated with metolazone therapy.

Digitalis glycosides

Diuretic-induced hypokalemia may increase myocardial sensitivity to digitalis. This can lead to serious arrhythmias.

Corticosteroids or ACTH

May increase the risk of hypokalemia and increase salt and water retention.

Lithium

Serum lithium levels may increase (see WARNINGS ).

Curariforms

Diuretic-induced hypokalemia may potentiate the neuromuscular blocking effect of curariforms (such as tubocurarine) – the most serious effect may be respiratory depression, which may progress to apnea. Accordingly, it is recommended to cancel metolazone three days before a planned operation.

Salicylates and other non-steroidal anti-inflammatory drugs

May reduce the antihypertensive effect of metolazone tablets.

Sympathomimetics

Metolazone may desensitize arteries to norepinephrine, but this reduction is not sufficient to rule out the effectiveness of a pressor agent for therapeutic use.

Insulin and oral antidiabetics

See PRECAUTIONS : General : Glucose tolerance .

Methenamine

Efficacy may be reduced due to the alkalinizing effect of metolazone in the urine.

Anticoagulants

Metolazone and other thiazide-like diuretics may interfere with the hypoprothrombinemic response to anticoagulants; dosage adjustment may be required.

Drug interactions/lab tests

None reported.

Warnings

WARNINGS

Rapid onset of hyponatremia and/or hypokalemia

In rare cases, rapid onset of severe hyponatremia and/or hypokalemia has been reported after initial doses of thiazides and nethiazides. diuretics. With the rapid onset of symptoms of severe electrolyte imbalance, the drug should be discontinued and supportive measures should be started immediately. Parenteral electrolytes may be required. The feasibility of therapy with this class of drugs should be carefully reassessed.

Hypokalemia

Hypokalemia may be accompanied by weakness, convulsions and cardiac arrhythmias. Serum potassium should be measured at regular and appropriate intervals, and dose reduction, potassium supplementation, or the addition of a potassium-sparing diuretic should be considered as indicated. Hypokalemia is of particular concern in patients with digitization or ventricular arrhythmias; dangerous or fatal arrhythmias may occur. Hypokalemia is dose dependent.

Concomitant therapy

Lithium

In general, diuretics should not be given concomitantly with lithium as they reduce its renal clearance and increase the risk of lithium toxicity. Please read the prescribing information for lithium before using this concomitant therapy.

Furosemide

Unusually large or prolonged fluid and electrolyte losses may occur if metolazone is administered concomitantly with patients receiving furosemide (see DRUG INTERACTIONS ).

Other antihypertensive drugs

When metolazone is used with other antihypertensive drugs, special care must be taken to avoid excessive lowering of blood pressure, especially during initial therapy.

Cross-allergy

Cross-allergy may occur when metolazone is administered to patients who are allergic to sulfonamide derivatives, thiazides or quinetasone.

Sensitivity reactions

Sensitivity reactions (eg, angioedema, bronchospasm) may occur with or without a history of allergies or asthma and may occur with the first dose of metolazone.

Precautions

PRECAUTIONS

DO NOT EXCHANGE: DO NOT EXCHANGE ZAROXOLINE TABLETS AND OTHER FORMS OF METOLAZONE THAT AFFECT SLOW AND INCOMPLETE BIODEPENDENCE AND ARE NOT THERAPEUTICALLY EQUIVALENT IN THE SAME DOSES OF THE METAL PRODUCT OF MICROX TABLETS AND THE AVAILABLE PRODUCT OF BIOLAZONE. ZAROXOLIN BIOEQUIVALENTS AND MICROX BIOEQUIVALENTS SHOULD NOT BE REPLACED BY ANOTHER.

General

Fluid and electrolytes

All patients receiving metolazone tablet therapy should have their serum electrolytes measured at appropriate intervals and watch for clinical signs of fluid and/or electrolyte imbalance, namely hyponatremia, hypochloremic alkalosis and hypokalemia ai . Patients with severe edema associated with heart failure or kidney disease may develop low-salt syndrome, especially when exposed to hot weather and a low-salt diet. Determination of electrolytes in serum and urine is especially important when the patient has prolonged vomiting, severe diarrhea, or when the patient is administered parenteral fluids. The warning signs of imbalance are: dry mouth, thirst, weakness, lethargy, drowsiness, restlessness, muscle pain or cramps, muscle fatigue, hypotension, oliguria, tachycardia, and gastrointestinal disturbances such as nausea and vomiting. Hyponatremia can occur at any time during long-term therapy and in rare cases can be life-threatening.

The risk of hypokalemia increases with high doses, with rapid diuresis, with severe liver disease, with concomitant use of corticosteroids, with insufficient oral intake, or with excessive extrarenal potassium loss, such as vomiting or diarrhea. .

Thiazide-like diuretics have been shown to increase urinary excretion of magnesium; this can lead to hypomagnesemia.

how often can promethazine be taken

Glucose tolerance

Metolazone may increase blood glucose levels, which may cause hyperglycemia and glucosuria in patients with diabetes or latent diabetes.

Hyperuricemia

Metolazone regularly causes an increase in serum uric acid levels and can sometimes cause attacks of gout even in patients who have not previously had a history of gout.

Azotemia

Azotemia, presumably prerenal azotemia, may develop while taking metolazone. If azotemia and oliguria worsen during treatment in patients with severe kidney disease, metolazone should be discontinued.

Renal failure

Use caution when administering metolazone tablets to patients with severely impaired renal function. Since most of the drug is excreted through the kidneys, accumulation may occur.

Orthostatic hypotension

Orthostatic hypotension possible; this may be exacerbated by alcohol, barbiturates, narcotics, or concomitant therapy with other antihypertensive drugs.

Hypercalcemia

Hypercalcemia may occur infrequently with metolazone, especially in patients taking high doses of vitamin D or in patients with high bone turnover, and may indicate latent hyperparathyroidism. Metolazone should be discontinued before testing for parathyroid function.

Systemic lupus erythematosus

Thiazide diuretics cause exacerbation or activation of systemic lupus erythematosus, and this possibility should be considered when taking metolazone tablets.

Carcinogenesis, Mutagenesis, Impairment of Fertility

Mice and rats treated with metolazone 5 days a week for up to 18 and 24 months, respectively, at daily doses of 2, 10 and 50 mg/kg, showed no evidence of a carcinogenic effect of the drug. The small number of animals studied histologically and the poor survival of mice limit the conclusions that can be drawn from these studies.

Metolazone is not mutagenic. in vitro in the Ames test using Salmonella typhimurium strains TA-97, TA-98, TA-100, TA-102 and TA-1535.

Reproductive capacity has been evaluated in mice and rats. There is no evidence that metolazone can alter the reproductive performance of mice. In a rat study in which males were orally administered metolazone at doses of 2, 10, and 50 mg/kg for 127 days prior to mating with untreated females, males mated with tribal males showed an increased number of resorption sites. Group 50 mg/kg. In addition, there was a decrease in offspring birth weight and a decrease in pregnancy rates in females mated with males from the 10 and 50 mg/kg groups.

Pregnancy

Teratogenic effects

Pregnancy category B

for metolazone. However, there are no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, metolazone tablets should only be used during pregnancy if absolutely necessary. Metolazone crosses the placental barrier and enters the cord blood.

Non-teratogenic effects

The use of metolazone tablets in pregnant women requires that the expected benefits be weighed against possible hazards to the fetus. These hazards include fetal or neonatal jaundice, thrombocytopenia, and possibly other adverse reactions that have occurred in adults. It is not known what effect the use of the drug during pregnancy has on the later growth, development and functional maturation of the child. No such effects of metolazone have been reported.

Operation and delivery

Based on clinical studies in which women received metolazone in late pregnancy until the time of delivery, there is no evidence that the drug has any adverse effect on the normal course of labor or delivery.

Nursing mothers

Metolazone passes into breast milk. Because of the potential for serious adverse reactions to metolazone in nursing infants, a decision should be made to discontinue breastfeeding or discontinue the drug, taking into account the importance of the drug to the mother.

Pediatric use

Safety and efficacy in pediatric patients have not been established in controlled clinical trials. There is limited experience with metolazone in pediatric patients with congestive heart failure, hypertension, bronchopulmonary dysplasia, nephrotic syndrome, and nephrogenic diabetes insipidus. The doses used typically ranged from 0.05 to 0.1 mg/kg given once daily and typically resulted in a weight loss of 1 to 2.8 kg and an increase in urine output of 150-300 cm3. Not all patients responded to treatment. and some put on weight. Those patients who did respond did so in the first few days of treatment. Prolonged use (more than a few days) has generally not been associated with further benefit or a return to baseline and is not recommended.

There is limited experience with the combination of metolazone and furosemide in pediatric patients with furosemide-resistant edema. Some were positive, while others did not or had an exaggerated response with hypovolemia, tachycardia, and orthostatic hypotension requiring fluid replacement. Severe hypokalemia and a tendency to maintain diuresis up to 24 hours after discontinuation of metolazone have been reported. Hyperbilirubinemia has been reported in 1 newborn. Careful clinical and laboratory monitoring of all children receiving diuretics is shown. see CONTRAINDICATIONS , WARNINGS and PRECAUTIONS .

Geriatric Use

Clinical studies of metolazone did not include sufficient numbers of subjects aged 65 years and over to determine if they differed from younger subjects. Other reported clinical experience has found no difference in response between older and younger patients. In general, dose selection for the elderly patient should be cautious, usually starting at the lower end of the dosing range, reflecting a greater incidence of decreased hepatic, renal, or cardiac function, as well as concomitant disease or other drug therapy.

This drug is known to be largely excreted by the kidneys and the risk of toxic reactions to this drug may be higher in patients with impaired renal function. Because older patients are more likely to have decreased renal function, care should be taken in dose selection and it may be beneficial to monitor renal function.

Overdose and contraindications

OVERDOSAGE

Deliberate overdose of metolazone and similar diuretics has been rarely reported.

Signs and symptoms

Orthostatic hypotension, dizziness, drowsiness, syncope, electrolyte disturbances, hemoconcentration and hemodynamic changes due to plasma volume depletion may occur. In some cases, there may be oppressed breathing. In high doses, lethargy of varying degrees can progress to a coma within a few hours. The mechanism of CNS depression in thiazide overdose is unknown. Gastrointestinal irritation and increased motility may also occur. Transient increases in BUN have been reported, especially in patients with impaired renal function. Serum electrolyte changes, as well as cardiovascular and renal function, should be closely monitored.

Care

There is no specific antidote, but immediate gastric evacuation is recommended. Dialysis is unlikely to be effective. When evacuating the contents of the stomach, care should be taken to prevent its aspiration, especially in patients who are in stupor or coma. If necessary, supportive measures should be initiated to maintain hydration, electrolyte balance, respiration, and cardiovascular and renal function.

CONTRAINDICATIONS

Anuria, hepatic coma or precoma, known allergy or hypersensitivity to metolazone.

Clinical pharmacology

CLINICAL PHARMACOLOGY

Metolazone is a quinazoline diuretic, its properties are generally similar to thiazide. diuretics. The action of metolazone is the result of interference with the renal tubular mechanism of electrolyte reabsorption. Metolazone acts primarily by inhibiting sodium reabsorption in the cortical dilution site and, to a lesser extent, in the proximal convoluted tubule. Sodium and chloride ions are excreted from the body in approximately equivalent amounts. Increased delivery of sodium to the site of exchange of the distal tubules leads to an increase in potassium excretion. Metolazone does not inhibit carbonic anhydrase. The proximal action of metolazone has been demonstrated in humans by increased excretion of phosphate and magnesium ions and by a markedly increased fractional excretion of sodium in patients with severely impaired glomerular filtration. This action has been demonstrated in animals using micropuncture studies.

With metolazone tablets, diuresis and saluresis usually begin within one hour and may persist for 24 hours or more. For most patients, the duration of the effect can be varied by adjusting the daily dose.

High doses may prolong the effect. A single daily dose is recommended. When the desired therapeutic effect is achieved, it will be possible to reduce the dosage to a lower maintenance level.

The diuretic activity of metolazone at the maximum therapeutic dosage is approximately equal to thiazide diuretics. However, unlike thiazides, metolazone can cause diuresis in patients with a glomerular filtration rate below 20 ml/min.

Co-administration of metolazone and furosemide has produced marked diuresis in some patients whose edema or ascites has not responded to the maximum recommended doses of either diuretic administered alone. The mechanism of this interaction is unknown (see WARNINGS and DRUG INTERACTIONS ).