Thyrotropin Other names: TSH Thyrotropin alfa Thyroid-stimulating hormone

Information from post marketing surveillance, as well as published information, suggests that elimination of thyrotropin alfa is significantly slower in dialysis-dependent end stage renal disease (ESRD) patients, resulting in prolonged elevation of thyroid stimulating hormone (TSH) levels for several days after treatment. This may lead to increased risk of headache and nausea. There are no studies of alternative dose schedules of thyrotropin alfa in patients with ESRD to guide dose reduction in this population.

In patients with significant renal impairment the activity of radioiodine should be carefully selected by the nuclear medicine physician.

Animal reproduction studies have not been conducted with thyrotropin alfa.

It is not known whether thyrotropin alfa can cause foetal harm when administered to a pregnant woman or whether thyrotropin alfa can affect reproductive capacity.

Thyrotropin alfa in combination with diagnostic radioiodine whole body scintigraphy is contra-indicated in pregnancy, because of the consequent exposure of the foetus to a high dose of radioactive material.

It is unknown whether thyrotropin alfa/metabolites are excreted in human milk. A risk to the suckling child cannot be excluded. Thyrotropin alfa should not be used during breast-feeding.

Fertility

It is not known whether thyrotropin alfa can affect fertility in humans.

Thyrotropin alfa may reduce the ability to drive or use machines, since dizziness and headaches have been reported.

Summary of the safety profile

The most commonly reported adverse reactions are nausea and headache, occurring in approximately 11%, and 6% of patients, respectively.

Tabulated list of adverse reactions

The adverse reactions mentioned in the table, combine adverse reactions in the six prospective clinical trials (N=481) and undesirable effects that have been reported after licensure of thyrotropin alfa.

Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness. The reporting rate is classified as very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1,000 to <1/100), rare (≥1/10,000 to <1/1,000), very rare (<1/10,000) and not known (cannot be estimated from the available data).

Description of selected adverse reactions

Very rare cases of hyperthyroidism or atrial fibrillation have been observed when thyrotropin alfa 0.9 mg has been administered in patients with presence of either partial or entire thyroid gland.

Manifestations of hypersensitivity have been reported uncommonly in both clinical and post-marketing settings. These reactions consisted of urticaria, rash, pruritus, flushing and respiratory signs and symptoms.

In clinical trials involving 481 patients, no patients have developed antibodies to thyrotropin alfa either after single or repeated limited (27 patients) use of the product. It is not recommended to perform TSH assays after thyrotropin alfa administration. The occurrence of antibodies which could interfere with endogenous TSH assays performed during regular follow-ups cannot be excluded.

Enlargement of residual thyroid tissue or metastases can occur following treatment with thyrotropin alfa. This may lead to acute symptoms, which depend on the anatomical location of the tissue. For example, hemiplegia, hemiparesis or loss of vision have occurred in patients with CNS metastases. Laryngeal oedema, respiratory distress requiring tracheotomy, and pain at the site of metastasis have also been reported after thyrotropin alfa administration. It is recommended that pre-treatment with corticosteroids be considered for patients in whom local tumour expansion may compromise vital anatomic structures.