Methimazole

Methimazole (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, corn starch, and talc.

The molecular weight is 114.17, and the molecular formula is C₄H₆N₂S. The structural formula is as follows:

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.

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

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

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 methimazole 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, pruritus, 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.

Methimazole can cause fetal harm when administered to a pregnant woman. Methimazole 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 methimazole during pregnancy. If methimazole 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 methimazole, it may be appropriate to use other agents in pregnant women requiring treatment for hyperthyroidism.

Postpartum patients receiving methimazole should not nurse their babies.

Major adverse reactions (which occur with much less frequency than the minor adverse reactions) include inhibition of myelopoiesis (agranulocytosis, granulocytopenia, and thrombocytopenia), aplastic anemia, drug fever, a lupus like syndrome, insulin autoimmune syndrome (which can result in hypoglycemic coma), hepatitis (jaundice may persist for several weeks after discontinuation of the drug), periarteritis, 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.

Methimazole is administered orally. It is usually given in 3 equal doses at approximately 8-hour intervals.

Methimazole Tablets, USP 5 mg - white to off-white, round, flat-faced, bevelled-edged tablets, scored with “EM 5” on one side and plain on the other.

They are available in:

Bottles of 30 NDC 42254-008-30

Methimazole Tablets, USP 10 mg - white to off-white, round, flat-faced, bevelled-edged tablets, scored with “EM 10” on one side and plain on the other.

They are available in:

Bottles of 30 NDC 42254-009-30

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

Dispense in tight, light-resistant container.

Manufactured and Distributed by:
PAR PHARMACEUTICAL COMPANIES, INC.
Spring Valley, NY 10977

Revised: 11/09     OS640-01-1-09

Repackaged by:

REBEL DISTRIBUTORS CORP

Thousand Oaks, CA 91320

PRINCIPAL DISPLAY PANEL - 5 mg

NDC 42254-008-30

Methimazole
Tablets, USP
5 mg

Rx only

30 Tablets

Each tablet contains:
Methimazole ................................ 5 mg

USUAL DOSAGE:
See package insert for dosage information.

WARNING: This drug may cause toxic
reactions. If such reactions occur,
discontinue the drug. Constant
supervision of patient is essential.

KEEP THIS AND ALL DRUGS
OUT OF REACH OF CHILDREN.

Dispense in a tight, light-resistant
container. Keep tightly closed.

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

PRINCIPAL DISPLAY PANEL - 10 mg

NDC 42254-009-30

Methimazole
Tablets, USP
10 mg

Rx only

30 Tablets

Each tablet contains:
Methimazole ................................ 10 mg

USUAL DOSAGE:
See package insert for dosage information.

WARNING: This drug may cause toxic
reactions. If such reactions occur,
discontinue the drug. Constant
supervision of patient is essential.

KEEP THIS AND ALL DRUGS
OUT OF REACH OF CHILDREN.

Dispense in a tight, light-resistant
container. Keep tightly closed.

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