Thyrogen 0.9 mg powder for solution for injection

Thyrogen is a human thyroid stimulating hormone (TSH) manufactured using biotechnology processes.

Thyrogen is used to detect certain types of thyroid cancer in patients who have had their thyroid gland removed and who are taking thyroid hormones. One of the effects is that it stimulates any remaining thyroid tissue to take up iodine which is important for radioiodine imaging. It also stimulates the production of thyroglobulin and thyroid hormones if there is any thyroid tissue left. These hormones can be measured in your blood.

Thyrogen is also used with radioiodine treatment to eliminate (ablate) the thyroid tissue left over after surgical removal of the thyroid gland (remnant) in patients who do not have secondaries (metastases) and who are taking thyroid hormone.

Do not use Thyrogen

Tell your doctor:

• if have ever had an allergic reaction (for example, rash or itchiness) to bovine or human thyroid stimulating hormone (TSH).
• if you are allergic to any of the other ingredients before you take this medicine (these are listed in Section 6; see also at the end of Section 2).
• if you are pregnant.

Take special care with Thyrogen

Thyrogen should never be injected into a vein.

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Tell your doctor if you have:

• kidney disease that require dialysis and he/she will decide how much Thyrogen to give to you as you may have more chance of experiencing headache and nausea.
• reduced kidney function and he/she will decide how much radioiodine to give you.
• reduced liver function; you should still be able to receive Thyrogen.

Elderly patients

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

Effect on tumour growth
In patients with thyroid cancer, tumour growth has been reported during withdrawal of thyroid hormones for diagnostic procedures. This was thought to be related to the elevated thyroid stimulating hormone (TSH) levels over a longer period. It is possible that Thyrogen may also cause tumour growth. In clinical trials this was not seen.

Due to elevation of TSH levels after Thyrogen, patients with secondary cancer growths (metastases) can experience local swelling or bleeding at the site of these metastases which may become bigger. If the metastases are present in narrow spaces e.g. intracerebral (in the brain) or in the spinal cord, patients could experience rapid symptoms such as partial paralysis affecting one side of the body (hemiparesis), breathing problems or loss of vision.

Your doctor will decide if you belong to a specific group of patients for which pre-treatment with corticosteroids is to be considered (for example, if you have secondary cancer growths in your brain or spinal cord ). Please talk to your doctor about this if you have concerns.

Using other medicines

There are no known drug interactions with Thyrogen and the thyroid hormones you may be taking.

Please tell you doctor if you are taking or have recently taken any other medicines including medicines obtained without prescription.

Your doctor will determine the exact activity of radioiodine to use for radioiodine imaging, taking into consideration the fact that you continue to take thyroid hormones.

Pregnancy and breast-feeding

Ask your doctor for advice before taking any medicine.

Do not take Thyrogen if you are pregnant. Please consult your doctor if you are pregnant or think you may be pregnant.

Thyrogen should not be given to breastfeeding women. Breast-feeding should only be resumed following advice from your doctor.

Driving and using machines

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

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Important information about some of the ingredients of Thyrogen

This medicinal product contains less than 1 mmol sodium (23 mg) per injection, i.e. essentially ?sodium- free?.

Your doctor, nurse or pharmacist will prepare the injection for you.

Your treatment should be supervised by a doctor who has expertise in thyroid cancer. Thyrogen powder must be dissolved in water for injection. Only one vial of Thyrogen is required per injection. The injection must be given intra-muscularly. Thyrogen must not be mixed with other medicines in the same injection

Use in children

Your child?s doctor will help you decide if Thyrogen should be given to your child.

Dosage:
The recommended dose of Thyrogen is two doses administered 24 hours apart. Your doctor or nurse will inject 1.0 ml of the Thyrogen solution.

Thyrogen should only be administered into the buttock muscle. Thyrogen solution should never be

injected into a vein.

If you have

• reduced liver function you should still be able to receive Thyrogen.
• kidney diseasethat require dialysis and your doctor will decide how much Thyrogen to give to you. You may have more chance of experiencing headache and nausea after receiving Thyrogen.
• reduced kidney function your doctor will decide how much radioiodine to give you.

When you undergo radioiodine imaging or elimination (ablation), your doctor will give you radioiodine 24 hours after your final Thyrogen injection.
Diagnostic scanning should be performed 48 to 72 hours after the radioiodine administration (72 to 96 hours after the final injection of Thyrogen).
Post-treatment scanning may be delayed a few days to allow background radioactivity to decline.

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

If you are given more Thyrogen than you should receive

Patients who accidentally received too much Thyrogen have reported nausea, weakness, dizziness, headache, vomiting and hot flashes.

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

Like all medicines, Thyrogen can cause side effects although not everybody gets them. The following effects have been reported with Thyrogen:

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Very common (affects more than 1 user in 10):

• nausea

Common (affects 1 to 10 users in 100):

• vomiting
• fatigue
• dizziness
• headache,
• diarrhoea,
• weakness,
• prickling or tingling sensation (paraesthesia).

Uncommon (affects 1 to 10 users in 1,000):

• feeling hot
• hives (urticaria)
• rash
• flu symptoms
• fever
• chills
• back pain

Frequency not known

(frequency cannot be estimated from the available data)

• swelling of the tumour
• pain (including pain at the site of metastases (secondary cancer growths))
• tremor
• palpitations
• flushing
• shortness of breath
• itching (pruritus)
• excessive sweating
• muscle or joint pain
• injection site reactions (including: redness, discomfort, itching, local pain or stinging, and an itchy rash)
• low TSH
• hypersensitivity (allergic reactions), these reactions include hives (urticaria), itching, flushing, difficulty in breathing and rash.

Very rare cases of hyperthyroidism (increased activity of the thyroid gland) or atrial fibrillation have been reported when Thyrogen was administered to patients who had not undergone total or partial removal of the thyroid gland.

If any of the side effects gets serious, or if any side effects not listed in this leaflet, please tell your doctor or pharmacist.

Keep out of the reach and sight of children.

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Do not use after the expiry date which is stated on the label after ?EXP?. The expiry date refers to the last day of that month.

Store in a refrigerator (2°C - 8°C).

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

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 to protect the environment.

What Thyrogen contains

The active substance in Thyrogen is thyrotropin alfa.
Each vial contains 0.9 mg/ml of thyrotropin alfa when reconstituted with 1.2 ml water for injection. Only 1 ml should be withdrawn equal to 0.9 mg of thyrotropin alfa.

The other ingredients are:

• mannitol
• sodium phosphate monobasic, monohydrate
• sodium phosphate dibasic, heptahydrate
• sodium chloride

(see at the endof Section 2 ?Important information about some of the ingredients of Thyrogen?)

What Thyrogen looks like and contents of the pack

Powder for solution for injection. White to off-white lyophilised powder.

Pack sizes: one or two vials of Thyrogen per carton.
Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer

Marketing authorisation holder:
Genzyme Europe B.V.,
Gooimeer 10,
1411 DD Naarden,
The Netherlands.

Manufacturing authorisation holder:
Genzyme Ltd.,
37 Hollands Road,
Haverhill, Suffolk CB9 8PU,
United Kingdom

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For any information about this medicine, please contact the local representative of the Marketing Authorisation Holder:

Ísland Genzyme AS, Tel 354 535 7000 BelgiëBelgiqueBelgien LuxemburgLuxembourg Genzyme Belgium N.V., TelTél 32 2 714 17 11

Magyarország Genzyme Genzyme Europe B.V. Képviselet CEE GmbH Tel 36 1 310 7440 . 359 2 971 1001

Nederland Genzyme Europe B.V., Tel 31 35 6991200 eská RepublikaSlovenská Republika Slovenija Genzyme Czech s.r.o., Tel 420 227 133 655

DanmarkNorgeSverigeSuomiFinland Genzyme AS, DanmarkTanska TlfPuh. 45 32712600 Österreich Genzyme Austria GmbH Tel 43 1 774 65 38

Deutschland Genzyme GmbH Tel 49 610236740 PolskaEestiLatvijaLietuva Genzyme Polska Sp. z o.o. PoolaPolijaLenkija, Tel 48 22 246 0900

Genzyme Hellas Ltd , 30 210 99 49 270 Portugal Genzyme Portugal S.A., Tel 351 21 422 0100

España Genzyme, S.L., Tel 34 91 6591670 România Genzyme CEE GmbH- Reprezentana pentru România Tel 40 21 243 4228

France Genzyme S.A.S., Tél 33 0 825 825 863 United KingdomIreland Genzyme Therapeutics United Kingdom Tel 44 1865 405200

Italia/Malta

Genzyme Srl (Italia/Italja),
Tel: +39 059 349811

This leaflet was last approved in

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The following information is intended for medicinal or healthcare professionals only:

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

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.

After reconstitution, the solution should be injected within three hours, however the Thyrogen solution will stay chemically stable for up to 24 hours, when stored between 2°C and 8°C protected from light. It is important to note that the microbiological safety depends on the aseptic conditions during the preparation of the solution.

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