Drug Class Description

Generic Name

Drug Description

Presentation

Indications

Adult Dosage

Posology

The recommended dose regimen is two doses of 0.9 mg thyrotropin alfa administered at a 24-hour-interval by intramuscular injection only.

Therapy should be supervised by physicians with expertise in thyroid cancer.

Method of administration

After reconstitution with water for injection, 1.0 ml solution (0.9 mg thyrotropin alfa) is administered by intramuscular injection to the buttock. See section 6.6 for instructions for handling.

For radioiodine imaging or ablation, radioiodine administration should be given 24 hours following the final Thyrogen injection. Diagnostic scintigraphy should be performed 48 to 72 hours following radioiodine administration, whereas post-ablation scintigraphy may be delayed additional days to allow background activity to decline.

For diagnostic follow-up serum thyroglobulin (Tg) testing, the serum sample should be obtained 72 hours after the final injection of Thyrogen.

Paediatric population

Due to a lack of data on the use of Thyrogen in children, Thyrogen should be given to children only in exceptional circumstances.

Geriatric population

Results from controlled trials indicate no difference in the safety and efficacy of Thyrogen between adult patients less than 65 years and those greater than 65 years of age, when Thyrogen is used for diagnostic purposes.

No dose adjustment is necessary in the elderly population.

Special populations

The use of Thyrogen in patients with reduced liver function does not warrant special considerations.

Information from post marketing surveillance, as well as published information, suggests that elimination of Thyrogen is significantly slower in dialysis-dependent end stage renal disease (ESRD) patients, resulting in prolonged elevation of 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 Thyrogen 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.

Use of Thyrogen with Tg testing in follow up of post-thyroidectomy well differentiated thyroid cancer patients should be in accordance with official guidelines.

Contra Indications

· Hypersensitivity to bovine or human thyroid stimulating hormone or to any of the excipients.

· Pregnancy.

Special Precautions

Thyrogen should not be administered intravenously.

When used as an alternative to thyroid hormone withdrawal, the combination of the whole body scintigraphy (WBS) and Tg testing after Thyrogen administration assures the highest sensitivity for detection of thyroid remnants or cancer. False negative results may occur with Thyrogen. If a high index of suspicion for metastatic disease persists, a confirmatory withdrawal WBS and Tg testing should be considered.

The presence of Tg autoantibodies can be expected in 18-40% of patients with differentiated thyroid cancer and may cause false negative serum Tg measurements. Therefore, both TgAb and Tg assays are needed.

Careful eva luation of benefit-risk relationships should be assessed for Thyrogen administration in high risk elderly patients who have heart disease (e.g. valvular heart disease, cardiomyopathy, coronary artery disease, and prior or current tachyarrhythmia) and have not undergone thyroidectomy.

Effect on tumour growth and/or size:

In patients with thyroid cancer, several cases of stimulated tumour growth have been reported during withdrawal of thyroid hormones for diagnostic procedures which have been attributed to the associated prolonged elevation of thyroid stimulating hormone (TSH) levels.

There is a theoretical possibility that Thyrogen, like thyroid hormone withdrawal, may lead to stimulated tumour growth. In clinical trials with thyrotropin alfa, which produces a short-term increase in serum TSH levels, no case of tumour growth has been reported.

Due to elevation of TSH levels after Thyrogen administration patients with metastatic thyroid cancer particularly in confined spaces such as the brain, spinal cord and orbit or disease infiltrating the neck, may experience local oedema or focal haemorrhage at the site of these metastases resulting in increased tumour size. This may lead to acute symptoms, which depend on the anatomical location of the tissue e.g. hemiplegia, hemiparesis, loss of vision have occurred in patients with CNS metastases. It is recommended that pretreatment with corticosteroids be considered for patients in whom local tumour expansion may compromise vital anatomic structures.

Interactions

Formal interaction studies between Thyrogen and other medicinal products have not been performed. In clinical trials, no interactions were observed between Thyrogen and the thyroid hormones triiodothyronine (T3) and thyroxine (T4) when administered concurrently.

The use of Thyrogen allows for radioiodine imaging while patients are euthyroid on thyroid hormone suppression treatment. Data on radioiodine kinetics indicate that the clearance of radioiodine is approximately 50% greater while euthyroid than during the hypothyroid state when renal function is decreased, thus resulting in less radioiodine retention in the body at the time of imaging. This factor should be considered when selecting the activity of radioiodine for use in radioiodine imaging although only a 3.7 GBq131I activity have been tested in the trial of the pre-therapeutic stimulation.

Adverse Reactions

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

The undesirable effects mentioned in the first table, were those considered related to treatment with Thyrogen and occurring in 1/1,000 patients in three prospective clinical trials (N=442). The second table includes undesirable effects that have been reported to Genzyme after licensure of Thyrogen. The tables are followed by a description of certain other additional effects.

Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.

System Organ Class	Subject Incidence	Adverse Drug Reaction
Gastrointestinal disorders	Very common (>1/10):	Nausea
	Common (>1/100 to 1/10):	Vomiting
General disorders and administration site conditions	Common (>1/100 to 1/10):	Fatigue
	Uncommon (>1/1,000 to 1/100):	Influenza-like illness, Asthenia, Pyrexia, Rigors, Back pain
Nervous system disorders	Common (>1/100 to 1/10):	Dizziness Headache
	Uncommon (>1/1,000 to 1/100):	Paraesthesia
Skin and subcutaneous tissue disorders	Uncommon (>1/1,000 to 1/100):	Urticaria, Rash
Vascular disorders	Uncommon (>1/1,000 to 1/100):	Feeling hot

The following list of undesirable effects, considered related to treatment with Thyrogen have been reported in post-marketing experience: