Mykrox

Serious side effects may occur. See "Drug Precautions" section.

Common side effects include:

• muscle weakness
• dizziness
• cramps
• thirst
• stomach pain
• stomach bloating
• upset stomach
• nausea or vomiting
• diarrhea or constipation
• headache
• hair loss
• dry mouth
• dizziness
• drowsiness
• fatigue
• insomnia
• tingling
• impotence
• blurred vision

This is not a complete list of metolazone side effects. Ask your doctor or pharmacist for more information.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

• Take metolazone exactly as prescribed.
• This medication comes in tablet form and is usually taken once daily.
• Metolazone can be taken with or without food.
• Because metolazone increases urination, it is best taken in the morning to avoid having to get up in the night to urinate.
• If you miss a dose, take it as soon as you remember. If it is almost time for your next dose, skip the missed dose.

Take metolazone exactly as prescribed by your doctor. Follow the directions on your prescription label carefully.

The metolazone dose your doctor recommends will be based on:

• the condition being treated
• other medical conditions you have
• other medications you are taking
• how you respond to this medication

To treat fluid retention caused by congestive heart failure the recommended dose range is metolazone 5 to 20 mg once daily.

To treat fluid retention caused by kidney disease the recommended dose range is metolazone 5 to 20 mg once daily.

For the treatment of mild to moderate high blood pressure the recommended dose range is metolazone 2½ to 5 mg once daily.

If you take too much metolazone call your doctor or Poison Contol Center, or seek emergency medical attention right away.

• Store at room temperature between 15° and 30°C (59° and 86°F).
• Keep this and all medications out of the reach of children.

This section provides information on the proper use of a number of products that contain metolazone. It may not be specific to Mykrox. Please read with care.

In addition to the use of this medicine, treatment for your high blood pressure may include weight control and changes in the types of foods you eat, especially foods high in sodium or potassium. Your doctor will tell you which of these are most important for you. You should check with your doctor before changing your diet .

Many patients who have high blood pressure will not notice any signs of the problem. In fact, many may feel normal. It is very important that you take your medicine exactly as directed and that you keep your appointments with your doctor even if you feel well .

Remember that this medicine will not cure your high blood pressure, but it does help control it. You must continue to take it as directed if you expect to lower your blood pressure and keep it down. You may have to take high blood pressure medicine for the rest of your life. If high blood pressure is not treated, it can cause serious problems such as heart failure, blood vessel disease, stroke, or kidney disease .

Use only the brand of this medicine that your doctor prescribed. Different brands may not work the same way .

Dosing

The dose of this medicine will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of this medicine. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

• For oral dosage form (tablets):
  • For fluid retention (edema):
    • Adults—At first, 5 to 20 milligrams (mg) once a day. Your doctor may adjust your dose if needed.
    • Children—Use and dose must be determined by your doctor .
  • For high blood pressure:
    • Adults—At first, 2.5 to 5 milligrams (mg) once a day. Your doctor may adjust your dose if needed.
    • Children—Use and dose must be determined by your doctor .

Missed Dose

If you miss a dose of this medicine, take it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not double doses.

Storage

Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light. Keep from freezing.

Keep out of the reach of children.

Do not keep outdated medicine or medicine no longer needed.

Ask your healthcare professional how you should dispose of any medicine you do not use.

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur:

• Black, tarry stools
• bleeding gums
• blistering, peeling, or loosening of skin
• bloating
• blood in urine or stools
• blurred vision
• bone pain
• chest pain
• chills
• clay-colored stools
• cold sweats
• coma
• confusion
• constipation
• convulsions
• cough
• dark urine
• decreased urine
• diarrhea
• dizziness, faintness, or lightheadedness when getting up from lying or sitting position
• drowsiness
• dry mouth
• fast, irregular, pounding, or racing heartbeat or pulse
• fever
• flushed, dry skin
• fruit-like breath odor
• general tiredness and weakness
• headache
• incoherent speech
• increased hunger
• increased thirst
• increased urination
• indigestion
• irritability
• itching
• joint or muscle pain
• light-colored stools
• loss of appetite
• lower back or side pain
• metallic taste
• mood changes
• muscle pain or cramps
• nausea and vomiting
• numbness or tingling in hands, feet, or lips
• pain in lower legs
• painful or difficult urination
• pinpoint red spots on skin
• rash
• red irritated eyes
• red skin lesions, often with a purple center
• redness or swelling of lower leg
• shortness of breath
• sore throat
• sores, ulcers, or white spots in mouth or on lips
• sugar in the urine
• sweating
• swelling of face, ankles, or hands
• swollen or painful glands
• tightness in chest
• trembling
• troubled breathing
• unexplained weight loss
• unpleasant breath odor
• unusual bleeding or bruising
• unusual tiredness or weakness
• upper right abdominal pain
• vomiting of blood
• weak pulse
• wheezing
• yellow eyes and skin

Get emergency help immediately if any of the following symptoms of overdose occur:

• Fainting
• irregular, fast or slow, or shallow breathing
• pale or blue lips, fingernails, or skin
• unusual drowsiness, dullness, tiredness, weakness, or feeling of sluggishness
• weakness and heaviness of legs

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

• Blue-green to black skin discoloration
• burning, tingling, numbness, or pain in the hands, arms, feet, or legs
• cracked, dry, or scaly skin
• decreased interest in sexual intercourse
• feeling of constant movement of self or surroundings
• hives or welts
• inability to have or keep an erection
• loss in sexual ability, desire, drive, or performance
• pain, redness, or sloughing of skin at place of injection
• restlessness
• sensation of pins and needles
• sensation of spinning
• stabbing pain

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

Adverse experience information is available from more than 14 years of accumulated marketing experience with other formulations of metolazone for which reliable quantitative information is lacking and from controlled clinical trials with Mykrox from which incidences can be calculated.

In controlled clinical trials with Mykrox, adverse experiences resulted in discontinuation of therapy in 6.7-6.8% of patients given ½ to 1 mg of Mykrox.

Adverse experiences occurring in controlled clinical trials with Mykrox with an incidence of >2%, whether or not considered drug-related, are summarized in the following table.

Some of the adverse effects reported in association with Mykrox also occur frequently in untreated hypertensive patients, such as headache and dizziness, which occurred in 14.8 and 7.4% of patients in a smaller parallel placebo group.

The following adverse effects were reported in less than 2% of the Mykrox treated patients.

Cardiovascular

Cold extremities, edema, orthostatic hypotension, palpitations.

Central and Peripheral Nervous System

Anxiety, depression, dry mouth, impotence, nervousness, neuropathy, weakness, “weird” feeling.

Dermatological

Pruritus, rash, skin dryness.

Eyes, Ears, Nose, Throat

Cough, epistaxis, eye itching, sinus congestion, sore throat, tinnitus.

Gastrointestinal

Abdominal discomfort (pain, bloating), bitter taste, constipation, diarrhea, nausea, vomiting.

Genitourinary

Nocturia.

Musculoskeletal

Back pain.

Other Adverse Experiences

Adverse experiences reported with other marketed metolazone formulations and most thiazide diuretics, for which quantitative data are not available, are listed in decreasing order of severity within body systems. Several are single or rare occurrences.

Cardiovascular

excessive volume depletion, hemoconcentration, venous thrombosis.

Central and Peripheral Nervous System

syncope, paresthesias, drowsiness, restlessness (sometimes resulting in insomnia).

Dermatologic/Hypersensitivity

toxic epidermal necrolysis (TEN), Stevens-Johnson Syndrome, necrotizing angiitis (cutaneous vasculitis), skin necrosis, purpura, petechiae, dermatitis, photosensitivity, urticaria, pruritus, skin rashes.

Gastrointestinal

hepatitis, intrahepatic cholestatic jaundice, pancreatitis, anorexia, nausea, diarrhea, abdominal pain.

Hematologic

aplastic (hypoplastic) anemia, agranulocytosis, leukopenia, thrombocytopenia.

Metabolic

hypokalemia (see WARNINGS, Hypokalemia), hyponatremia, hyperuricemia, hypochloremia, hypochloremic alkalosis, hyperglycemia, glycosuria, increase in serum urea nitrogen (BUN) or creatinine, hypophosphatemia, hypomagnesemia, hypercalcemia.

Musculoskeletal

acute gouty attacks.

Other

transient blurred vision, chills.

In addition, rare adverse experiences reported in association with similar antihypertensive-diuretics but not reported to date for metolazone include: sialadenitis, xanthopsia, respiratory distress (including pneumonitis), and anaphylactic reactions. These experiences could occur with clinical use of metolazone.

Intentional overdosage has been reported rarely with metolazone and similar diuretic drugs.

Signs and Symptoms

Orthostatic hypotension, dizziness, drowsiness, syncope, electrolyte abnormalities, hemoconcentration and hemodynamic changes due to plasma volume depletion may occur. In some instances depressed respiration may be observed. At high doses, lethargy of varying degree may progress to coma within a few hours. The mechanism of CNS depression with thiazide overdosage is unknown. Also, GI irritation and hypermotility may occur. Temporary elevation of BUN has been reported, especially in patients with impairment of renal function. Serum electrolyte changes and cardiovascular and renal function should be closely monitored.

Treatment

There is no specific antidote available but immediate evacuation of stomach contents is advised. Dialysis is not likely to be effective. Care should be taken when evacuating the gastric contents to prevent aspiration, especially in the stuporous or comatose patient. Supportive measures should be initiated as required to maintain hydration, electrolyte balance, respiration, and cardiovascular and renal function.

Mykrox Tablets (metolazone tablets, USP), ½ mg are white, flat-faced, round tablets, debossed “Mykrox” on one side, and “½” on reverse side.

NDC 53014-847-71        Bottle of 100’s

Store at 25°C (77°F); excursions permitted to 15°-30°C (59°-86°F) [See USP Controlled Room Temperature]. Protect from light. Keep out of the reach of children.

Celltech Pharmaceuticals, Inc.

Rochester, NY 14623 USA

® Celltech Manufacturing, Inc.

© 2003, Celltech Pharmaceuticals, Inc.

All rights reserved.

Rev. 2/03

R528B