Methima

Each tablet contains Methimazole 5 mg (INN: Thiamazole).

Pharmacology: Pharmacodynamics: Methimazole inhibits the synthesis of thyroid hormones by blocking the oxidation of iodine in the thyroid gland. As a result, methimazole inhibits the ability of iodine to combine with tyrosine to form thyroxine (T₄) and triiodothyronine (T₃). It is effective in the treatment of hyperthyroidism. It does not inactivate existing thyroxine (T₄) and triiodothyronine (T₃), which are stored in the thyroid or which circulate in the blood.
Pharmacokinetics: Methimazole is rapidly absorbed from GI tract following oral administration with peak plasma concentrations occurring within about 1-2 hours. Onset of action is 12-18 hours. Methimazole readily crosses the placenta and is distributed into milk in concentrations approximately equal to those in maternal serum. This drug concentrated in thyroid gland. Protein binding of methimazole is 0%. Methimazole metabolized in the liver. The elimination half-life of methimazole reportedly ranges from about 5-13 hours. The drug is excreted in urine. In one study, about 12% of a dose was excreted in urine within 24 hours. Bioavailability of this drug is 80-95%.

For treatment of hyperthyroidism.

Children: Initial dosage: 0.4 mg/kg/day in 3 equally divided doses at approximately 8 hour intervals.
Maintenance dosage: 0.2 mg/kg/day in 3 equally divided doses at approximately 8 hour intervals.
Adults: Initial dosage: 15 mg/day in 3 divided doses for mild hyperthyroidism, 30-40 mg/day in 3 divided doses for moderately-severe hyperthyroidism, 60 mg/day in 3 divided doses for severe hyperthyroidism. Total daily dosage is usually given in 3 equally divided doses at approximately 8 hour intervals.
Maintenance dosage: 5-15 mg/day (may be given as a single daily dose in many cases).
Mode of Administration: Methimazole is administered orally. Total daily dosage is usually given in 3 equally divided doses at approximately 8-hour intervals. Alternatively, methimazole may be administered as a single daily dose.

Overdosage: In general, overdosage of methimazole may be expected to produce effects that are extensions of common adverse reactions. 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. Agranulocytosis is the most serious effect associated with methimazole overdosage. Less frequent adverse effects include exfoliative dermatitis, hepatitis, nephrotic syndrome, neuropathies and CNS stimulation or depression. No data are available on the median lethal dose of methimazole or the concentration of drug in biologic fluids associated with toxicity and/or death.
Treatments: Treatment of methimazole overdosage generally involves appropriate supportive care as dictated by the patient's medical status.

Methimazole is contraindicated in patients who are hypersensitive to the drug or any ingredient in the formulation. Cross-sensitivity between thioamides may occur (i.e. in approximately 50% of patients switched from one thioamide agent to the other). In patients who develop agranulocytosis or other serious adverse effects while receiving methimazole, some clinicians state that use of the other drug also is contraindicated because of the risk to cross-sensitivity between the two drugs. In patients experiencing serious allergic reactions to methimazole, some clinicians state that using the alternative antithyroid drug (i.e. propylthiouracil) is not recommended.

Hematologic effects: Antithyroid agents have been associated (rarely) with significant bone marrow depression. The most severe manifestation is agranulocytosis. Agranulocytosis is a potentially life-threatening adverse effect of methimazole therapy. Baseline complete blood count, include white count differential, be performed prior to initiating antithyroid drug therapy in patients. Patients receiving methimazole should be closely monitored and should be instructed to contact their clinician immediately if signs or symptoms of illness, particularly sore throat, skin eruptions, fever, chills, headache, or general malaise occur. Aplastic anemia, thrombocytopenia, and leukopenia may also occur. Use with extreme caution in patients receiving other drugs known to cause myelosuppression (particularly agranulocytosis) and in patients >40 years of age; avoid doses ≥40 mg/day.
Hemorrhagic effects: Because antithyroid agents may cause hypoprothrombinemia and bleeding. Monitor prothrombin time during therapy, especially before surgical procedures.
Hepatic effects: Liver function test, including alkaline phosphatase, aminotransferase, and bilirubin, be performed prior to initiating antithyroid drug therapy. Advised to immediately discontinue the drug and promptly contact their clinician if pruritic rash, jaundice, alcoholic stools, dark urine, arthralgias, abdominal pain, or fatigue occurs. Discontinue in the presence of hepatitis (transaminase >3 times upper limit of normal).
Thyroid function: Methimazole can cause hypothyroidism. When methimazole is discontinued, thyroid function should be monitored every 1-3 months for 6-12 months to diagnose relapse early, and patients should be advised to contact clinicians if symptoms of hyperthyroidism occur.

Pregnancy: Pregnancy category: D.
Methimazole has been found to readily cross the placenta and may cause fetal harm, particularly when administered in the first trimester of pregnancy. The drug can also cause fetal goiter and hypothyroidism (cretinism) when administered to a pregnant woman. There was a distinct and consistent pattern of congenital malformations associated with the use of methimazole. Approximately 90% of the congenital malformations with methimazole were craniofacial malformations (e.g., scalp epidermal aplasia, facial dysmorphism, choanal atresia). Congenital anomalies, including esophageal atresia, choanal atresia, aplasia cutis, and iridic and retinal coloboma, have been observed in neonates born to mother taking methimazole during pregnancy. Nonteratogenic adverse effects, including fetal and neonatal hypothyroidism, have been observed following maternal methimazole use. Uncontrolled maternal hyperthyroidism may result in adverse neonatal outcomes (e.g. prematurity, low birth weight) and adverse maternal outcomes (e.g. preeclampsia, congestive heart failure, stillbirth, abortion). Antithyroid treatment is recommended for the control of hyperthyroidism during pregnancy. Due to an increased risk of congenital anomalies with methimazole, propylthiouracil is considered first-line therapy, especially during the first trimester. Patients receiving methimazole should be switched to propylthiouracil if pregnancy is confirmed in first trimester. Due to an increased risk of hepatotoxicity, use of methimazole may be preferred during the second and third trimester. If drug therapy is changed, maternal thyroid function should be monitored after 2 weeks and then every 2 to 4 weeks.
Lactation: Methimazole is distributed into milk. However, several studies found no effect on clinical status in nursing infants of women receiving methimazole. The American Thyroid Association considers doses of methimazole less than 30 mg/day to be safe during breast-feeding. Methimazole should be administered after breast-feeding and in divided doses.

Cardiovascular: ANCA-positive vasculitis, edema.
Central nervous system: Drowsiness, fever, headache, neuritis, vertigo.
Dermatologic: Alopecia, exfoliative dermatitis, pruritus, skin pigmentation, skin rash, urticarial.
Endocrine & metabolic: Goiter, hypoglycemic coma.
Gastrointestinal: Constipation, epigastric distress, loss of taste perception, nausea, salivary gland swelling, vomiting, weight gain.
Hematologic: Agranulocytosis, aplastic anemia, granulocytopenia, hypoprothrombinemia, leukopenia, thrombocytopenia.
Hepatic: Hepatic necrosis, hepatitis, jaundice.
Neuromuscular & skeletal: Arthralgia, myalgia, paresthesia.
Renal: Nephritis.
Miscellaneous: Insulin autoimmune syndrome, lymphadenopathy, SLE-like syndrome.

Avoid concomitant use: Avoid concomitant use of methimazole with any of clozapine, pimozide, sodium iodide I131.
Increased Effect/Toxicity: Methimazole may increase the levels/effects of aripiprazole, cardiac glycosides, clozapine, lomitapide, pimozide, theophylline derivatives.
Decreased Effect: Methimazole may decrease the levels/effects of sodium iodide I131; vitamin K antagonists.

Store below 30°C.

Antithyroid Agents

H03BB02 - thiamazole ; Belongs to the class of sulfur-containing imidazole derivative agents. Used in the management of thyroid diseases.

D