Tapazole^® (Methimazole Tablets, USP) (1-methylimidazole-2-thiol) is a white, crystalline substance that is freely soluble in water. It differs chemically from the drugs of the thiouracil series primarily because it has a 5- instead of a 6-membered ring. Each tablet contains 5 or 10 mg (43.8 or 87.6 µmol) methimazole, an orally administered antithyroid drug.

Each tablet also contains lactose monohydrate, magnesium stearate, starch (corn), pregelatinized starch and talc.

The molecular weight is 114.16, and the molecular formula is C₄H₆N₂S. The structural formula is as follows:

Tapazole is indicated in the medical treatment of hyperthyroidism. Long-term therapy may lead to remission of the disease. Tapazole may be used to ameliorate hyperthyroidism in preparation for subtotal thyroidectomy or radioactive iodine therapy. Tapazole is also used when thyroidectomy is contraindicated or not advisable.

Tapazole is administered orally. Tablets are usually given in 3 equal doses at approximately 8-hour intervals.

Adult † The initial daily dosage is 15 mg for mild hyperthyroidism, 30 to 40 mg for moderately severe hyperthyroidism, and 60 mg for severe hyperthyroidism, divided into 3 doses at 8-hour intervals. The maintenance dosage is 5 to 15 mg daily.

Pediatric † Initially, the daily dosage is 0.4 mg/kg of body weight divided into 3 doses and given at 8-hour intervals. The maintenance dosage is approximately 1/2 of the initial dose.

Tapazole Tablets are available in:

The 5-mg tablets are round, white to off-white, scored on one side and the other side debossed with "J94".

They are available as follows:

Bottles of 100 NDC 60793-104-01

The 10-mg tablets are round, white to off-white, scored on one side and the other side debossed with "J95".

They are available as follows: Bottles of 100 NDC 60793-105-01

Store at controlled room temperature, 15° to 30°C (59° to 86°F).

Distributed by: King Pharmaceuticals^®, Inc. Bristol, TN 37620 Manufactured by: AAI Development Services An aaiPharma Company 1726 North 23rd St. Wilmington, NC 28405, Prescribing Information as of February 2004.

Major adverse reactions (which occur with much less frequency than the minor adverse reactions) include inhibition of myelopoieses (agranulocytosis, granulocy-topenia, and thrombocytopenia), aplastic anemia, drug fever, a lupuslike syndrome, insulin autoimmune syndrome (which can result in hypoglycemic coma), hepatitis (jaundice may persist for several weeks after discontinuation of the drug), periar-teritis, and hypoprothrombinemia. Nephritis occurs very rarely.

Minor adverse reactions include skin rash, urticaria, nausea, vomiting, epigastric distress, arthralgia, paresthesia, loss of taste, abnormal loss of hair, myalgia, headache, pruritus, drowsiness, neuritis, edema, vertigo, skin pigmentation, jaundice, sialadenopathy, and lymphadenopathy.

It should be noted that about 10% of patients with untreated hyperthyroidism have leukopenia (white-blood-cell count of less than 4,000/mm³), often with relative granulopenia.

Anticoagulants (oral): The activity of oral anticoagulants may be potentiated by anti-vitamin-K activity attributed to methimazole.

ß-adrenergic blocking agents: Hyperthyroidism may cause an increased clearance of beta ratio. A dose reduction of beta-adrenergic blockers may be needed when a hyperthyroid patient becomes euthyroid.

Digitalis glycosides: Serum digitalis levels may be increased when hyperthyroid patients on a stable digitalis glycoside regimen become euthyroid; reduced dosage of digitalis glycosides may be required.

Theophylline: Theophylline clearance may decrease when hyperthyroid patients on a stable theophylline regimen become euthyroid; a reduced dose of theophylline may be needed.

Agranulocytosis is potentially a serious side effect. Patients should be instructed to report to their physicians any symptoms of agranulocytosis, such as fever or sore throat. Leukopenia, thrombocytopenia, and aplastic anemia (pancytopenia) may also occur. The drug should be discontinued in the presence of agranulocytosis, aplastic anemia (pancytopenia), hepatitis, or exfoliative dermatitis. The patient's bone marrow function should be monitored.

Due to the similar hepatic toxicity profiles of Tapazole and propylthiouracil, attention is drawn to the severe hepatic reactions which have occurred with both drugs. There have been rare reports of fulminant hepatitis, hepatic necrosis, encephalopathy, and death. Symptoms suggestive of hepatic dysfunction (anorexia, pruritis, right upper quadrant pain, etc) should prompt evaluation of liver function. Drug treatment should be discontinued promptly in the event of clinically significant evidence of liver abnormality including hepatic transaminase values exceeding 3 times the upper limit of normal.

Tapazole can cause fetal harm when administered to a pregnant woman. Tapazole readily crosses the placental membranes and can induce goiter and even cretinism in the developing fetus. In addition, rare instances of congenital defects: aplasia cutis, as manifested by scalp defects; esophageal atresia with tracheoesophageal fistula; and choanal atresia with absent/hypoplastic nipples, have occurred in infants born to mothers who received Tapazole during pregnancy. If Tapazole is used during pregnancy or if the patient becomes pregnant while taking this drug, the patient should be warned of the potential hazard to the fetus.

Since the above congenital defects have been reported in offspring of patients treated with Tapazole, it may be appropriate to use other agents in pregnant women requiring treatment for hyperthyroidism.

Postpartum patients receiving Tapazole should not nurse their babies.

Patients who receive Tapazole should be under close surveillance and should be cautioned to report immediately any evidence of illness, particularly sore throat, skin eruptions, fever, headache, or general malaise. In such cases, white-blood-cell and differential counts should be made to determine whether agranulocytosis has developed. Particular care should be exercised with patients who are receiving additional drugs known to cause agranulocytosis.

Because Tapazole may cause hypoprothrombinemia and bleeding, prothrombin time should be monitored during therapy with the drug, especially before surgical procedures (see General under PRECAUTIONS).

Periodic monitoring of thyroid function is warranted, and the finding of an elevated TSH warrants a decrease in the dosage of Tapazole.

In a 2 year study, rats were given methimazole at doses of 0.5, 3, and 18 mg/kg/day. These doses were 0.3, 2, and 12 times the 15 mg/day maximum human maintenance dose (when calculated on the basis of surface area). Thyroid hyperplasia, adenoma, and carcinoma developed in rats at the two higher doses. The clinical significance of these findings is unclear.

See WARNINGS † Tapazole^® used judiciously is an effective drug in hyperthyroidism complicated by pregnancy. In many pregnant women, the thyroid dysfunction diminishes as the pregnancy proceeds; consequently, a reduction in dosage may be possible. In some instances, use of Tapazole can be discontinued 2 or 3 weeks before delivery.

The drug appears in human breast milk and its use is contraindicated in nursing mothers (see WARNINGS).

See DOSAGE AND ADMINISTRATION.

Symptoms may include nausea, vomiting, epigastric distress, headache, fever, joint pain, pruritus, and edema. Aplastic anemia (pancy-topenia) or agranulocytosis may be manifested in hours to days. Less frequent events are hepatitis, nephrotic syndrome, exfoliative dermatitis, neuropathies, and CNS stimulation or depression. Although not well studied, methimazole-induced agranulocytosis is generally associated with doses of 40 mg or more in patients older than 40 years of age.

No information is available on the median lethal dose of the drug or the concentration of methimazole in biologic fluids associated with toxicity and/or death.

To obtain up-to-date information about the treatment of overdose, a good resource is your certified Regional Poison Control Center. Telephone numbers of certified poison control centers are listed in the Physicians Desk Reference (PDR). In managing overdosage, consider the possibility of multiple drug overdoses, interaction among drugs, and unusual drug kinetics in your patient. Protect the patients airway and support ventilation and perfusion. Meticulously monitor and maintain, within acceptable limits, the patient's vital signs, blood gases, serum electrolytes, etc. The patient's bone marrow function should be monitored. Absorption of drugs from the gastrointestinal tract may be decreased by giving activated charcoal, which, in many cases, is more effective than emesis or lavage; consider charcoal instead of or in addition to gastric emptying. Repeated doses of charcoal over time may hasten elimination of some drugs that have been absorbed. Safeguard the patient's airway when employing gastric emptying or charcoal.

Forced diuresis, peritoneal dialysis, hemodialysis, or charcoal hemoperfusion have not been established as beneficial for an overdose of methimazole.

Tapazole is contraindicated in the presence of hypersensitivity to the drug and in nursing mothers because the drug is excreted in milk.

Methimazole inhibits the synthesis of thyroid hormones and thus is effective in the treatment of hyperthyroidism. The drug does not inactivate existing thyroxine and triiodothyronine that are stored in the thyroid or circulating in the blood nor does it interfere with the effectiveness of thyroid hormones given by mouth or by injection.

The actions and use of methimazole are similar to those of propylthiouracil. On a weight basis, the drug is at least 10 times as potent as propylthiouracil, but methimazole may be less consistent in action.

Methimazole is readily absorbed from the gastrointestinal tract. It is metabolized rapidly and requires frequent administration. Methimazole is excreted in the urine. In laboratory animals, various regimens that continuously suppress thyroid function and thereby increase TSH secretion result in thyroid tissue hypertrophy. Under such conditions, the appearance of thyroid and pituitary neoplasms has also been reported. Regimens that have been studied in this regard include antithyroid agents as well as dietary iodine deficiency, subtotal thyroidectomy, implantation of autonomous thyrotropic hormone-secreting pituitary tumors, and administration of chemical goitrogens.

Patients should be instructed to report to their physicians any symptoms of agranulocytosis, such as fever or sore throat. Please also refer to the WARNINGS and PRECAUTIONS sections.

IMPORTANT NOTE: This is a summary and does not contain all possible information about this product. For complete information about this product or your specific health needs, ask your health care professional. Always seek the advice of your health care professional if you have any questions about this product or your medical condition. This information is not intended as individual medical advice and does not substitute for the knowledge and judgment of your health care professional. This information does not contain any assurances that this product is safe, effective, or appropriate for you.

METHIMAZOLE - ORAL

(meh-THIM-uh-zole)

COMMON BRAND NAME(S): Tapazole

USES: Methimazole is used to treat hyperthyroidism (overactive thyroid gland) or to prepare you for thyroid surgery or radioactive iodine therapy. It works by stopping the thyroid gland from making too much thyroid hormone.

HOW TO USE: Take this medication by mouth, usually 3 times a day (every 8 hours) or as directed by your doctor.

Dosage is based on your medical condition and response to therapy.

Take this medication exactly as prescribed. Do not increase your dose or take it more often than directed. Your condition will not improve faster, but side effects may be increased.

Use this medication regularly to get the most benefit from it. To help you remember, take it at the same times each day. Do not stop taking this medication without consulting your doctor. Inform your doctor if you develop new symptoms or if your condition worsens.

SIDE EFFECTS: Stomach upset, nausea, vomiting, loss of taste, headache, joint/muscle pain, abnormal hair loss, drowsiness, dizziness, or burning/tingling of hands/feet may occur. If any of these effects persist or worsen, contact your doctor or pharmacist promptly.

Remember that your doctor has prescribed this medication because he or she 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.

Tell your doctor immediately if any of these rare but very serious side effects occur: yellowing eyes/skin, dark urine, severe abdominal pain, loss of appetite, persistent nausea/vomiting, change in the amount of urine.

This medication may rarely cause a very serious decrease in the number of cells in your blood (blood counts), especially during the first few months after you start taking the medication. Tell your doctor immediately if you develop the following symptoms: fever, persistent sore throat, unusual tiredness, weakness, easy bruising/bleeding.

Be sure to keep all medical appointments so your doctor can closely monitor you.

A very serious allergic reaction to this drug is rare. However, seek immediate medical attention if you notice any of the following symptoms: rash, itching, swelling, 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.

Contact your doctor for medical advice about side effects. The following numbers do not provide medical advice, but in the US you may report side effects to the Food and Drug Administration (FDA) at 1-800-FDA-1088. In Canada, you may call Health Canada at 1-866-234-2345.

PRECAUTIONS: Before taking methimazole, tell your doctor or pharmacist if you are allergic to it; or if you have any other allergies.

Before using this medication, tell your doctor or pharmacist your medical history, especially of: liver disease, blood disorders (e.g., agranulocytosis, thrombocytopenia).

This drug may make you dizzy or drowsy. Use caution while driving, using machinery, or doing any activity that requires alertness. Limit alcoholic beverages.

Before you have surgery, tell your doctor or dentist that you take this medication.

This medication is not recommended for use during pregnancy. Discuss the risks and benefits with your doctor before taking methimazole. Tell your doctor immediately if you become pregnant or think you may be pregnant. Consult your doctor for more details.

This medication passes into breast milk and may have undesirable effects on a nursing infant. Consult your doctor before breast-feeding.

DRUG INTERACTIONS: Your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor or pharmacist first.

Before taking this medication, tell your doctor or pharmacist of all prescription and nonprescription/herbal products you may use, especially of: digoxin, beta blockers (e.g., metoprolol), theophylline, warfarin.

This document does not contain all possible interactions. Therefore, before using this product, tell your doctor or pharmacist of all the products you use. Keep a list of all your medications with you, and share the list with your doctor and pharmacist.

OVERDOSE: If overdose is suspected, contact your local poison control center or emergency room immediately. US residents can call the US National Poison Hotline at 1-800-222-1222. Canada residents can call a provincial poison control center. Symptoms of overdose may include: nausea, vomiting, stomach discomfort, fever, headache, joint pain, swelling.

NOTES: Do not share this medication with others.

Laboratory and/or medical tests (e.g., complete blood counts, liver and thyroid function tests, prothrombin time) should be performed periodically to monitor your progress or check for side effects. Consult your doctor for more details.

MISSED DOSE: If you miss a dose, take it as soon as you remember. If it is near the time of the next dose, skip the missed dose and resume your usual dosing schedule. Do not double the dose to catch up.

STORAGE: Store at room temperature between 59-86 degrees F (15-30 degrees C) 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 for more details about how to safely discard your product.

Information last revised July 2008 Copyright(c) 2008 First DataBank, Inc.