Antithyroid preparations. Sulfur-containing imidazole derivatives
ATC code: H03BB02 (Thiamazole)
Brand names
Tapazole, Methimazole
Inhibits thyroid peroxidase – the key enzyme in thyroid hormone synthesis. This blocks tyrosine iodination and formation of thyroxine (T4) and triiodothyronine (T3) in the thyroid. Does not suppress release of previously synthesized hormones – the clinical effect develops as stores deplete, typically over 2–4 weeks. Does not affect peripheral T4-to-T3 conversion (unlike propylthiouracil).
First line
Thiamazole is first-line medical therapy for Graves disease in non-pregnant adults. 2016 recommends thiamazole as the preferred thionamide (exceptions: first trimester of pregnancy and life-threatening thyroid storm). Starting dose 10–40 mg daily depending on severity, course duration 12–18 months. Remission is achieved in 40–50% of patients. On relapse, radioiodine therapy or thyroidectomy is considered.
Sources
First line
Thiamazole is prescribed 4–8 weeks before elective thyroidectomy to achieve euthyroidism. Goal: reduce intra- and postoperative thyroid storm risk. 7–10 days before surgery, Lugol's solution or potassium iodide is added to reduce thyroid vascularity.
First line
Thiamazole is used to control thyrotoxicosis in toxic adenoma or toxic multinodular goiter before definitive treatment (radioiodine therapy or thyroidectomy). Long-term medical therapy alone does not provide durable remission in autonomously functioning nodules, so definitive treatment is discussed early.
Not recommended
In the first trimester, thiamazole is not used as first-line therapy. 2017 recommends switching to propylthiouracil at confirmation of pregnancy and continuing it through the first trimester. This is due to the risk of thiamazole embryopathy: aplasia cutis of the scalp, choanal and esophageal atresia, anterior abdominal wall defects. After the first trimester, a switch back to thiamazole is acceptable, as propylthiouracil carries higher hepatotoxicity risk.
Boxed warning
No formal FDA boxed warning in the US, but labels explicitly highlight the risk of fatal agranulocytosis and the need to stop the drug immediately on fever, sore throat or mouth ulcers.
FDA category D. Linked to embryopathy: aplasia cutis of the scalp, choanal and esophageal atresia, anterior abdominal wall defects. In the first trimester, replace with propylthiouracil; from the second trimester, a switch back to thiamazole is possible per endocrinologist decision. Minimum effective dose, regular free T4 monitoring at the upper half of the reference range.
Transfers into breast milk. ATA and LactMed allow breastfeeding at doses up to 20 mg daily, with dosing immediately after feeding. Infant TSH and free T4 are checked at 1 month.
Thiamazole is evaluated for the following indications with varying evidence strength: Graves disease (evidence tier A), Toxic adenoma (evidence tier A), Pre-thyroidectomy preparation (evidence tier A). See the full indication matrix with dosing and citations above on this page.
Common side effects of Thiamazole (≥ 1 in 100): Rash, pruritus, urticaria, Arthralgia, Nausea, epigastric discomfort, Metallic taste. See the Safety section for uncommon and serious reactions.
FDA category D. FDA category D. Linked to embryopathy: aplasia cutis of the scalp, choanal and esophageal atresia, anterior abdominal wall defects. In the first trimester, replace with propylthiouracil; from the second trimester, a switch back to thiamazole is possible per endocrinologist decision. Minimum effective dose, regular free T4 monitoring at the upper half of the reference range.
Transfers into breast milk. ATA and LactMed allow breastfeeding at doses up to 20 mg daily, with dosing immediately after feeding. Infant TSH and free T4 are checked at 1 month.
Thiamazole is contraindicated in: Severe leukopenia, history of agranulocytosis; Severe hepatic impairment; Hypersensitivity to thiamazole or imidazole derivatives; First trimester of pregnancy (propylthiouracil preferred); History of cholestatic jaundice on thionamides. Full list in the Safety section.
No formal FDA boxed warning in the US, but labels explicitly highlight the risk of fatal agranulocytosis and the need to stop the drug immediately on fever, sore throat or mouth ulcers.
the drug does not cause dependence. The 12–18-month course reflects the immune nature of Graves disease, not drug properties.
it suppresses synthesis but does not eliminate the autoimmune mechanism. Remission is achieved in only 40–50%.
in the first trimester it is replaced by propylthiouracil; later, switched back.