indication

For the treatment of hyperthyroidism, goiter, Graves disease and psoriasis.

pharmacology

Used in the treatment of hyperthyroidism or an overactive thyroid gland, methimazole inhibits the synthesis of thyroid hormones and thus is effective in the treatment of hyperthyroidism. It may also be used to ameliorate hyperthyroidism in preparation for subtotal thyroidectomy or radioactive iodine therapy.

mechanism of action

Methimazole binds to thyroid peroxidase and thereby inhibits the conversion of iodide to iodine. Thyroid peroxidase normally converts iodide to iodine (via hydrogen peroxide as a cofactor) and also catalyzes the incorporation of the resulting iodide molecule onto both the 3 and/or 5 positions of the phenol rings of tyrosines found in thyroglobulin. Thyroglobulin is degraded to produce thyroxine (T4) and tri-iodothyronine (T3), which are the main hormones produced by the thyroid gland. So methimazole effectively inhibits the production of new thyroid hormones.

toxicity

Oral LD₅₀ in rats is 2250 mg/kg. Symptoms of overdose 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.

biotransformation

Primarily hepatic. Metabolized rapidly, requiring frequent administration.

absorption

Rapid with an oral bioavailability of 93%.

half life

5-6 hours

route of elimination

Methimazole is excreted in the urine.

drug interactions

Acenocoumarol: The antithyroid agent, methimazole, may decrease the anticoagulant effect of acenocoumarol.

Anisindione: The antithyroid agent, methimazole, may decrease the anticoagulant effect of anisindione.

Dicumarol: The antithyroid agent, methimazole, may decrease the anticoagulant effect of dicumarol.

Digoxin: The antithyroid agent increases the effect of digoxin

Tamoxifen: Methimazole may decrease the therapeutic effect of Tamoxifen by decreasing the production of active metabolites. Consider alternate therapy.

Tamsulosin: Methimazole, a CYP2D6 inhibitor, may decrease the metabolism and clearance of Tamsulosin, a CYP2D6 substrate. Monitor for changes in therapeutic/adverse effects of Tamsulosin if Methimazole is initiated, discontinued, or dose changed.

Warfarin: Methimazole may decrease the anticoagulant effect of warfarin. Monitor for changes in the therapeutic and adverse effects of warfarin if methimazole is initiated, discontinued or dose changed.