Thiamazole Other names: Tapazole Methimazole

Thiamazole inhibits dose-dependently the incorporation of iodine into tyrosine and thereby the neosynthesis of thyroid hormones. This property permits symptomatic therapy of hyperthyroidism regardless of its cause. Whether thiamazole furthermore affects the ‘natural course’ taken by the immunologically induced type of hyperthyroidism (Graves' disease), i.e. whether it suppresses the underlying immunopathogenitic process, can presently not be decided with certainty.

The release of previously synthesised thyroid hormones from the thyroid is not affected. This explains why the length of the latency period until normalisation of the serum concentrations of thyroxine and triiodothyronine, and thus to clinical improvement, differs in individual cases. Hyperthyroidism due to the release of hormones after destruction of thyroid cells, e.g. after radioiodine therapy or in thyroiditis, is also not affected.

Thiamazole is absorbed rapidly and completely. After administration, maximum serum levels are reached within 0.4 to 1.2 hours. Protein binding is negligibly low. Thiamazole accumulates in the thyroid where it is metabolised only slowly. In spite of fluctuating serum levels, the accumulation of thiamazole in the thyroid gland still leads to a concentration plateau. This results in a duration of action of nearly 24 hours for the single dose. According to present knowledge, the kinetics of thiamazole is independent of thyroid function. The elimination half-life is about 3 to 6 hours and is prolonged in hepatic insufficiency).

Thiamazole undergoes renal and biliary elimination; excretion with the faeces is slight, suggesting enterohepatic circulation. 70% of the substance are excreted by the kidneys within 24 hours. Only a small amount is excreted in unchanged form. At present, no experience is available on the pharmacological activity of the metabolites. Limited data of pharmacokinetics in patients with renal and hepatic impairment are available (see section 4.2). No data are available following repeated dose administration (see section 4.2).

Preclinical safety studies are limited.

Single-dose toxicity data show that the acute toxic potential of thiamazole is low.

In repeat-dose studies, bone marrow depression was seen at dose levels, which were considerably higher than the therapeutic dose levels.

Genotoxicity studies did not reveal any evidence of mutagenic or clastogenic effects.

In a two-year chronic toxicity study in rats no relevant findings other than pharmacologically mediated effects on the thyroid were observed. In a chronic two-year study in mice a higher incidence of hepatomas, which did not reach the level of statistical significance, was seen when thiamazole was administered at a concentration of 500 mg/l in drinking water. The relevance of the latter finding is questionable and thiamazole is not classified as a carcinogen by IARC (International Agency for Research of Cancer) or NTP (National Toxicology Program) criteria.