METHIMAZOLE TABLETS, USP

Methimazole, 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, potato starch and talc.

The molecular weight is 114.16, and the molecular formula is C ₄H ₆N ₂S. 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 tri-iodothyronine 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.

Methimazole is readily absorbed in the gastrointestinal tract, metabolized in the liver, and excreted in the urine.

Methimazole is indicated:

• In patients with Graves’ disease with hyperthyroidism or toxic multinodular goiter for whom surgery or radioactive iodine therapy is not an appropriate treatment option.
• To ameliorate symptoms of hyperthyroidism in preparation for thyroidectomy or radioactive iodine therapy

Methimazole is contraindicated in the presence of hypersensitivity to the drug or any of the other product components.

Congenital Malformations

Methimazole readily crosses placental membranes and can cause fetal harm, particularly when administered in the first trimester of pregnancy. Rare instances of congenital defects, including aplasia cutis, craniofacial malformations (facial dysmorphism; choanal atresia) and gastrointestinal malformations (esophageal atresia with or without tracheoesophageal fistula; umbilical abnormalities) 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, particularly during organogenesis, in the first trimester of pregnancy. If methimazole is used, the lowest possible dose to control the maternal disease should be given.

Agranulocytosis

Agranulocytosis is a potentially a life-threatening adverse reaction of methimazole therapy. Patients should be instructed to immediately report to their physicians any symptoms suggestive 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), ANCA-positive vasculitis, hepatitis, or exfoliative dermatitis, and the patient’s bone marrow indices should be monitored.

Liver Toxicity

Although there have been reports of hepatotoxicity (including acute liver failure) associated with methimazole, the risk of hepatotoxicity appears to be less with methimazole than with propylthiouracil, especially in the pediatric population. Symptoms suggestive of hepatic dysfunction (anorexia, pruritus, right upper quadrant pain, etc.) should prompt evaluation of liver function (bilirubin, alkaline phosphatase) and hepatocellular integrity (ALT, AST). 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.

Hypothyroidism

Methimazole can cause hypothyroidism necessitating routine monitoring of TSH and free T4 levels with adjustments in dosing to maintain a euthyroid state. Because the drug readily crosses placental membranes, methimazole can cause fetal goiter and cretinism when administered to a pregnant woman. For this reason, it is important that a sufficient, but not excessive, dose be given during pregnancy (see Precautions, Pregnancy).

Major adverse reactions (which occur with much less frequency than the minor adverse reactions) include inhibition of myelopoieses (agranulocytosis, granulocytopenia, thrombocytopenia, and 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.

NDC: 70934-622-30

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