ine adverse reactions in the six prospective clinical trials (N=481) and undesirable effects that have been reported to Genzyme after licensure of Thyrogen.
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 events
Very rare cases of hyperthyroidism or atrial fibrillation have been observed when Thyrogen 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. The occurrence of antibodies which could interfere with endogenous TSH assays cannot be excluded.
Enlargement of residual thyroid tissue or metastases can occur following treatment with Thyrogen. 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 Thyrogen administration. It is recommended that pretreatment with corticosteroids be considered for patients in whom local tumour expansion may compromise vital anatomic structures.
Very rare cases of stroke have been reported from world-wide post marketing experience in female patients. The relationship to Thyrogen administration is unknown.
4.9 Overdose
Data on exposure above the recommended dose is limited to clinical studies and a special treatment program. Three patients in clinical trials and one patient in the special treatment program experienced symptoms after receiving Thyrogen doses higher than those recommended. Two patients had nausea after 2.7 mg IM dose, and in one of these patients nausea was also accompanied by weakness, dizziness and headache. The third patient experienced nausea, vomiting and hot flushes after 3.6 mg IM dose. In the special treatment program, a 77 year-old patient with metastatic thyroid cancer who had not been thyroidectomised received 4 doses of Thyrogen 0.9 mg over 6 days, developed atrial fibrillation, cardiac decompensation and terminal myocardial infarction 2 days later.
One additional patient enrolled in a clinical trial experienced symptoms after receiving Thyrogen intravenously. This patient received 0.3 mg of Thyrogen as a single intravenous (IV) bolus and, 15 minutes later experienced severe nausea, vomiting, diaphoresis, hypotension and tachycardia.
A suggested treatment in case of overdose would be the reestablishment of fluid balance and administration of an antiemetic may also be considered.
5. Pharmacological properties
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: Pituitary and Hypothalamic Hormones and Analogues, Anterior Pituitary Lobe Hormones and Analogues. ATC code for thyrotropin alfa: H01AB01
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