THYROGEN Powder for solution for injection Ref.[7880] Active ingredients: Thyrotropin

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

Posology

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

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.

Elderly

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 elderly (see section 4.4).

Patients with renal/hepatic impairment

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 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 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.

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

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. For instructions on reconstitution of the medicinal product before administration, see section 6.6.

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

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.

Unopened vials:

3 years.

Shelf-life after reconstitution:

It is recommended that the Thyrogen solution be injected within three hours. The reconstituted solution can be stored for up to 24 hours in a refrigerator (2°C-8°C) under protection from light, while avoiding microbial contamination.

Store in a refrigerator (2°C-8°C).

Keep the vial in the outer carton in order to protect from light.

For storage conditions after reconstitution of the medicinal product, see section 6.3.

Clear Type I glass 5 ml vials. The closure consists of a siliconised butyl stopper with a tamper proof flip-off cap. Each vial contains 1.1 mg thyrotropin alfa. After reconstitution with 1.2 ml water for injection, 1.0 ml of solution (equal to 0.9 mg Thyrogen) is withdrawn and administered to the patient.

To provide sufficient volume to allow accurate dispensing, each vial of Thyrogen is formulated to contain an overfill of 0.2 ml.

Package size: one or two vials per carton.

Not all pack sizes may be marketed.

The powder for solution for injection has to be reconstituted with water for injection. Only one vial of Thyrogen is required per injection. Each vial of Thyrogen is for single use only.

Use aseptic technique.

Add 1.2 ml water for injection to the Thyrogen powder in the vial. Swirl the contents of the vial gently until all material is dissolved. Do not shake the solution. When the powder is dissolved the total volume in the vial is 1.2 ml. The pH of the Thyrogen solution is approximately 7.0.

Visually inspect the Thyrogen solution in the vial for foreign particles and discoloration. The Thyrogen solution should be a clear, colourless solution. Do not use vials exhibiting foreign particles, cloudiness or discoloration.

Withdraw 1.0 ml of the Thyrogen solution from the product vial. This equals 0.9 mg thyrotropin alfa to be injected.

Thyrogen does not contain preservatives. Dispose of any unused solution immediately. No special requirements for disposal.

The Thyrogen solution should be injected within three hours, however the Thyrogen solution will stay chemically stable for up to 24 hours, if kept in a refrigerator (between 2°C and 8°C). It is important to note that the microbiological safety depends on the aseptic conditions during the preparation of the solution.