SIDE EFFECTS

Adverse reaction data were derived from post-marketing surveillance and clinical trials. The percentages in Table 4 below represent adverse reactions experienced by 481 thyroid cancer patients who participated in the clinical trials for Thyrogen. Most patients received 2 intramuscular injections, 0.9 mg of thyrotropin alfa per injection, 24 hours apart.

The safety profile of patients who received Thyrogen as an adjunctive treatment for radioiodine ablation of thyroid tissue remnants who have undergone a thyroidectomy for welldifferentiated thyroid cancer did not differ from that of patients who received Thyrogen for diagnostic purposes.

The most common adverse events ( > 5%) reported in clinical trials were nausea (11.9%) and headache (7.3%). Events reported in ≥ 1% of patients in the combined trials are summarized in Table 4. In some studies, an individual patient may have participated in both the Euthyroid phase (Thyrogen) and Hypothyroid phase (withdrawal).

Table 4: Summary of Adverse Events by Euthyroid Phase and Hypothyroid Phase in All Clinical Trials ( ≥ 1%)

Post-marketing experience indicates that Thyrogen administration may cause transient ( < 48 hours) influenza-like symptoms [also called flu-like symptoms (FLS)], which may include fever ( > 100°F/38°C), chills/shivering, myalgia/arthralgia, fatigue/asthenia/malaise, headache (non-focal), and chills.

Very rare manifestations of hypersensitivity to Thyrogen have been reported in clinical trials, post-marketing settings and in a special treatment program involving patients with advanced disease; these are urticaria, rash, pruritus, flushing and respiratory signs and symptoms.

In clinical trials no patients have developed antibodies to thyrotropin alfa, either after single or repeated (27 patients) use of the product.

Four patients out of 55 (7.3%) with CNS metastases who were followed in a special treatment protocol experienced acute hemiplegia, hemiparesis or pain one to three days after Thyrogen administration. The symptoms were attributed to local edema and/or focal hemorrhage at the site of the cerebral or spinal cord metastases. In addition, one case each of acute visual loss and of laryngeal edema with respiratory distress, requiring tracheotomy, with onset of symptoms within 24 hours after Thyrogen administration, have been reported in patients with metastases to the optic nerve and paratracheal areas, respectively. In addition, sudden, rapid and painful enlargement of locally recurring papillary carcinoma has been reported within 12-48 hours of Thyrogen administration. The enlargement was accompanied by dyspnea, stridor or dysphonia. Rapid clinical improvement occurred following glucocorticoid therapy. It is recommended that pretreatment with glucocorticoid be considered for patients in whom local tumor expansion may compromise vital anatomic structures.

There have been reports of deaths in which events leading to death occurred within 24 hours after administration of Thyrogen. A 77 year-old non-thyroidectomized patient with a history of heart disease and spinal metastases who received 4 Thyrogen injections over 6 days in a special treatment protocol experienced a fatal MI 24 hours after he received the last Thyrogen injection. The event was likely related to Thyrogen-induced hyperthyroidism. In post-marketing experience, there have been rare reports of events leading to death that occurred within 24 hours of administration of Thyrogen in patients with multiple serious medical problems. For patients for whom Thyrogen-induced hyperthyroidism could have serious consequences, hospitalization for administration of Thyrogen and post-administration observation should be considered. Such patients might include those with known heart disease, extensive metastatic disease, or other known serious underlying illness.

Information from post-marketing surveillance, as well as from the literature, suggests that elimination of Thyrogen is significantly slower in dialysis-dependent end stage renal disease (ESRD) patients, resulting in prolonged elevation of TSH levels. ESRD patients who receive Thyrogen may have markedly elevated TSH levels for several days after treatment, which may lead to increased risk of headache and nausea.

Post-marketing data include cases of atrial arrhythmias in elderly patients with pre-existing cardiac disease who received Thyrogen, and suggest that use of Thyrogen in this group should be considered carefully.

Read the entire FDA prescribing information for Thyrogen (Thyrotropin Alfa for Injection) »