THYROGEN 0.9 mg POWDER FOR INJECTABLE SOLUTION

Introduction

Package Leaflet: Information for the User

Thyrogen 0.9mg powder for solution for injection

Thyrotropin alfa

Read all of this leaflet carefully before you start using this medicine because it contains important information for you.

• Keep this leaflet, you may need to read it again.
• If you have any further questions, ask your doctor or pharmacist.
• If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the pack

1. What is Thyrogen and what is it used for
2. What you need to know before you use Thyrogen
3. How to use Thyrogen
4. Possible side effects
5. Storage of Thyrogen
6. Contents of the pack and other information

1. What is Thyrogen and what is it used for

Thyrogen contains the active substance thyrotropin alfa. Thyrogen is a human thyroid-stimulating hormone (TSH) produced by biotechnology processes.

Thyrogen is used for the detection of certain types of thyroid cancer in thyroidectomized patients maintained on thyroid hormones. One of the effects is that it stimulates any remaining thyroid tissue to take up iodine, which is important for imaging with radioactive iodine. It also stimulates the production of thyroglobulin and thyroid hormones if there is any residual thyroid tissue. These hormones can be measured in the blood.

Thyrogen is also used with radioactive iodine treatment to eliminate (ablate) remaining thyroid tissue after surgical removal of the thyroid gland (remnants) in patients who do not have secondary growths (metastases) and who are receiving thyroid hormone.

2. What you need to know before you start using Thyrogen

Do not use Thyrogen:

• if you are allergic to bovine or human thyroid-stimulating hormone (TSH) or to any of the other ingredients of this medicine (listed in section 6).
• if you are pregnant.

Warnings and precautions

Talk to your doctor or pharmacist before starting Thyrogen:

• if you have kidney disease that requires dialysis; your doctor will decide how much Thyrogen to give you, as you may be more likely to suffer from headache and nausea.
• if your kidney function is reduced; your doctor will decide the amount of radioactive iodine to be given.
• if your liver function is reduced; you can still receive Thyrogen.

Effect on tumor growth

In patients with thyroid cancer, cases of tumor growth have been reported during withdrawal of thyroid hormones for diagnostic procedures. This was thought to be related to elevated levels of thyroid-stimulating hormone (TSH) for a longer period. It is possible that Thyrogen may also cause tumor growth. This was not seen in clinical trials.

Due to the elevation of TSH levels after administration of Thyrogen, patients with secondary tumor growth (metastases) may experience local swelling or bleeding at the site of these metastases, which may increase in size. If metastases are present in confined spaces, e.g. intracerebral (in the brain) or in the spinal cord, patients may experience symptoms that can manifest rapidly, such as partial paralysis affecting one side of the body (hemiparesis), respiratory problems, or loss of vision.

Your doctor will decide if you belong to one of the specific patient groups where prior treatment with corticosteroids should be considered (e.g. if you have secondary tumor growth in the brain or spinal cord). If you have any doubts, consult your doctor.

Children

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

Elderly

No special precautions are necessary for elderly patients. However, if the thyroid gland has not been completely removed and you also suffer from heart disease, your doctor will help you decide whether you should receive Thyrogen.

Other medicines and Thyrogen

Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.

No drug interactions are known with Thyrogen and thyroid hormones that you may be taking.

Your doctor will determine the exact activity of radioactive iodine to be used for imaging, taking into account the fact that you continue to take thyroid hormones.

Pregnancy and breastfeeding

Do not take Thyrogen if you are pregnant. If you are pregnant or breastfeeding, think you may be pregnant, or plan to become pregnant, consult your doctor or pharmacist before using this medicine.

Thyrogen should not be administered to breastfeeding women. Breastfeeding should not be resumed until your doctor tells you to do so.

Driving and using machines

Some patients may feel dizzy or have headaches after administration of Thyrogen that may affect their ability to drive and use machines.

Thyrogen contains sodium

This medicine contains less than 23 mg of sodium (1mmol) per vial; this is essentially "sodium-free".

3. How to use Thyrogen

A doctor or nurse will inject your medicine.

Your treatment should be supervised by a doctor with experience in thyroid cancer. The Thyrogen powder must be dissolved in water for injectable preparations. Only one vial of Thyrogen is required per injection. Thyrogen should only be administered in the buttocks. This solution should never be injected into a vein. Thyrogen should not be mixed with other medicines in the same injection.

The recommended dose of Thyrogen consists of two doses administered with a 24-hour interval between them. Your doctor or nurse will inject 1.0 ml of the Thyrogen solution.

For ablation or imaging with radioactive iodine, your doctor will administer the radioactive iodine 24 hours after the last injection of Thyrogen.

The diagnostic scan should be performed 48 to 72 hours after administration of the radioactive iodine (72 to 96 hours after the last injection of Thyrogen).

The post-treatment scan may be postponed for a few days to allow the general radioactivity to decrease.

For thyroglobulin (Tg) analysis, your doctor or nurse will take a serum sample 72 hours after the last injection of Thyrogen.

Use in children

Your child's doctor will help decide whether Thyrogen should be given to your child.

If you use more Thyrogen than you should

Patient who received too much Thyrogen by accident have described nausea, weakness, dizziness, headache, vomiting, and flushing.

In case of overdose, treatment to restore fluid balance, as well as administration of an antiemetic, is recommended.

If you have any further questions on the use of this product, ask your doctor.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

The following effects have been reported with Thyrogen:

Very common(may affect more than 1 in 10 people):

• nausea

Common(may affect up to 1 in 10 people):

• vomiting
• fatigue
• dizziness
• headache
• weakness

Uncommon(may affect up to 1 in 100 people):

• feeling of heat
• hives (urticaria)
• skin rash
• flu-like symptoms
• fever
• chills
• back pain
• diarrhea
• tingling or prickling sensation (paresthesia)
• neck pain
• loss of taste (ageusia)
• distortion of the sense of taste (dysgeusia)
• flu

Not known(frequency cannot be estimated from the available data):

• tumor swelling
• pain (including pain at the site of metastases)
• tremor
• stroke
• palpitations

• flushing

• shortness of breath
• itching (pruritus)
• excessive sweating
• muscle or joint pain
• injection site reactions (including redness, discomfort, itching, pain, or stinging at the injection site, and skin rash with itching)
• low TSH
• hypersensitivity (allergic reactions), including hives (urticaria), itching, flushing, difficulty breathing, and skin rash.

In very rare cases, cases of hyperthyroidism(increased activity of the thyroid gland) or atrial fibrillationhave been reported when Thyrogen has been administered to patients who have not undergone total or partial removal of the thyroid gland.

Reporting of side effects

If you experience any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the national reporting system listed in Appendix V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of Thyrogen

Keep out of the sight and reach of children.

Do not use this medicine after the expiry date which is stated on the label after "EXP". The expiry date is the last day of the month shown.

Store in a refrigerator (2°C - 8°C).

Keep the vial in the outer packaging to protect it from light.

Thyrogen should be injected within 3 hours of reconstitution.

The reconstituted solution can be stored for up to 24 hours at a temperature between 2°C and 8°C, protected from light and avoiding bacterial contamination.

Do not use this medicine if you notice any visible signs of deterioration, such as particles, turbidity, or color change.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help protect the environment.

6. Contents of the pack and other information

Composition of Thyrogen

• The active substance is thyrotropin alfa.

Each vial contains 0.9 mg of thyrotropin alfa when reconstituted with 1.2 ml of water for injectable preparations.

Only 1 ml, equivalent to 0.9 mg of thyrotropin alfa, should be withdrawn.

• The other ingredients are:

Mannitol

Sodium phosphate monobasic monohydrate

Sodium phosphate dibasic heptahydrate

Sodium chloride.

Thyrogen contains sodium, see section 2.

Appearance and pack contents

Powder for solution for injection. White lyophilized powder.

Presentation: Packs of 1 or 2 vials of Thyrogen.

Not all pack sizes may be marketed.

Marketing authorisation holder and manufacturer

Marketing authorisation holder:

Sanofi Winthrop Industrie

82 Avenue Raspail

94250 Gentilly

France

Manufacturer:

Genzyme Ireland Limited

IDA Industrial Park

Old Kilmeaden Road

Waterford

Ireland

You can request more information about this medicine from the local representative of the marketing authorisation holder:

Date of last revision of this leaflet:

Detailed information on this medicine is available on the European Medicines Agency web site http://www.ema.europa.eu.

This information is intended only for healthcare professionals:

The recommended dose of Thyrogen is two intramuscular injections of 0.9 mg of thyrotropin alfa administered with a 24-hour interval between them.

Traceability

In order to improve the traceability of biological medicinal products, the name and batch number of the administered product should be clearly recorded.

Use of an aseptic technique.

Add 1.2 ml of water for injectable preparations to the vial containing the Thyrogen powder. Gently swirl the vial until all the contents are dissolved. Do not shake the solution. When the powder is dissolved, the total volume of the vial will be 1.2 ml. The pH of the Thyrogen solution is approximately 7.0.

Visually inspect the Thyrogen solution in each vial for particulate matter and color change. The Thyrogen solution should be clear and colorless. Do not use vials containing particulate matter, or that are turbid or discolored.

Withdraw 1.0 ml of the Thyrogen solution from the vial. This is equivalent to 0.9 mg of thyrotropin alfa.

Thyrogen does not contain preservatives. Discard unused solution immediately. No special requirements for disposal.

The solution should be injected within 3 hours of reconstitution. The reconstituted solution can be stored for up to 24 hours at a temperature between 2°C and 8°C, protected from light and avoiding bacterial contamination. It is important to note that microbiological safety will depend on the aseptic conditions used during preparation of the solution.