Label: METHIMAZOLE tablet

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.
Methimazole tablet, USP contains 5 mg or 10 mg (43.8 or 87.6 μmol) methimazole, an orally administered antithyroid drug.
Each tablet also contains lactose monohydrate, pregelatinised starch, talc, and magnesium stearate.
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 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.

First Trimester Use of Methimazole and Congenital Malformations
Methimazole crosses the placental membranes and can cause fetal harm when administered in the first trimester of pregnancy. Rare instances of congenital defects, including aplasia cutis, craniofacial malformations (facial dysmorphism; choanal atresia), gastrointestinal malformations (esophageal atresia with or without tracheoesophageal fistula), omphalocele and abnormalities of the omphalomesenteric duct have occurred in infants born to mothers who received methimazole in the first trimester of pregnancy. If methimazole tablets are 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.
Because of the risk for congenital malformations associated with use of methimazole in the first trimester of pregnancy, it may be appropriate to use other agents in pregnant women requiring treatment for hyperthyroidism. If methimazole tablets is used, the lowest possible dose to control the maternal disease should be given.

Agranulocytosis
Agranulocytosis is a potentially 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 or aplastic anemia (pancytopenia), 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).

Vasculitis
Cases of vasculitis resulting in severe complications have been reported in patients receiving methimazole therapy. These cases of vasculitis include: leukocytoclastic cutaneous vasculitis, acute kidney injury and glomerulonephritis, alveolar/pulmonary hemorrhage, CNS vasculitis, and neuropathy.Most cases were associated with anti-neutrophilic cytoplasmic antibodies (ANCA)-positive vasculitis. In some cases, vasculitis resolved/improved with drug discontinuation; however, more severe cases required treatment with additional measures including corticosteroids, immunosuppressant therapy, and plasmapheresis. If vasculitis is suspected, discontinue therapy and initiate appropriate intervention

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. There have been postmarketing case reports of acute pancreatitis.

There are reports of a vasculitis, often associated with the presence of anti-neutrophilic cytoplasmic antibodies (ANCA), resulting in severe complications (see WARNINGS).

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.

To report SUSPECTED ADVERSE REACTIONS, contact Macleods Pharma USA, Inc. at 1-888-943-3210 or 1-855-926-3384 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

  
Signs and Symptoms
Symptoms may include nausea, vomiting, epigastric distress, headache, fever, joint pain, pruritus, and edema. Aplastic anemia (pancytopenia) or agranulocytosis may be manifested in hours to days. Less frequent events are hepatitis, nephrotic syndrome, exfoliative dermatitis, neuropathies, and CNS stimulation or depression.
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.
Treatment
To obtain up-to-date information about the treatment of overdose, a good resource is the certified RegionalPoison ControlCenter. In managing overdosage, consider the possibility of multiple drug overdoses, interaction among drugs, and unusual drug kinetics in the patient.
In the event of an overdose, appropriate supportive treatment should be initiated as dictated by the patient’s medical status.

Methimazole is administered orally. The total daily dosage is usually given in 3 divided doses at approximately 8-hour intervals.

Adults- The initial daily dosage is 15 mg for mild hyperthyroidism, 30 mg 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 mg 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.

Methimazole tablets, USP 5 mg - white to off-white, round, flat-faced, bevelled-edged tablets, debossed with “T and 80”separated by breakline on one side and plain on the other side.
They are available in:
               Bottles of 100             NDC 33342-335-11
               Bottles of 1000           NDC 33342-335-44
               Cartons of 100 (10 x 10 unit-dose blister) NDC 33342-335-12

Methimazole tablets, USP 10 mg - white to off-white, round, flat-faced, bevelled-edged tablets, debossed with “T and 81”separated by breakline on one side and plain on the other side.
They are available in:
               Bottles of 100             NDC 33342-336-11
               Bottles of 1000           NDC 33342-336-44
               Cartons of 100 (10 x 10 unit-dose blister)   NDC 33342-336-12

Store at 20° to 25°C (68° to 77°F); excursions permitted to 15° to 30°C (59° to 86°F) [See USP Controlled Room Temperature].
Dispense in tight, light-resistant container.

Manufactured for:
Macleods Pharma USA, Inc.
Princeton, NJ 08540

Manufactured by:
Macleods Pharmaceuticals Ltd.
At Oxalis Labs

Baddi, Himachal Pradesh, INDIA

Issue: June 2023

Rx only
Methimazole Tablets, USP 5 mg
NDC: 33342-335-11
container 100's Tablets

Rx only
Methimazole Tablets, USP 5 mg
NDC: 33342-335-44
container 1000's Tablets

Rx only
Methimazole Tablets, USP 5 mg
NDC: 33342-335-12
Carton 100's Tablets

Rx only
Methimazole Tablets, USP 10 mg
NDC: 33342-336-11
container 100's Tablets

Rx only
Methimazole Tablets, USP 10 mg
NDC: 33342-336-44
container 1000's Tablets

Rx only
Methimazole Tablets, USP 10 mg
NDC: 33342-336-12
Carton 100's Tablets