THYROGEN

Illustrative leaflet: information for the user
THYROGEN 0.9 mg powder for injectable solution
Thyrotropin alfa
Please read this leaflet carefully before using this medicine
because it contains important information for you

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor or pharmacist.
• If you experience any side effects, including those not listed in this leaflet, contact your doctor or pharmacist. See section 4.

Contents of this leaflet:

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

1. What Thyrogen is and what it is used for

Thyrogen contains the active substance thyrotropin alfa, which is human thyroid-stimulating hormone (TSH) produced by biotechnological processes.
Thyrogen is used to detect the presence of certain types of thyroid cancer in patients who have undergone thyroidectomy and who are receiving thyroid hormone therapy. One of its effects is to stimulate any residual thyroid tissue to take up iodine, which is important for radioactive iodine imaging techniques. It also stimulates the production of thyroglobulin and thyroid hormones if residual thyroid tissue is present. These hormones can be measured in the blood.
Thyrogen is also used in conjunction with radioactive iodine treatment to destroy (ablate) residual thyroid tissue remaining after surgical removal of the thyroid gland (residual tissue), in patients without evidence of secondary tumour spread (metastases) who are receiving thyroid hormone replacement therapy.

2. What you need to know before using Thyrogen

Do not use Thyrogen
if you are allergic to bovine or human thyroid-stimulating hormone (TSH) or to any of the other
components of this medicine (listed in section 6).
if you are pregnant.

Warnings and precautions
Talk to your doctor or pharmacist before using Thyrogen:
if you have kidney disease requiring dialysis; your doctor will determine the appropriate dose of
Thyrogen for you, as you may be more susceptible to headache and nausea.
if your kidneys do not function properly; your doctor will decide how much radioactive iodine
should be administered to you.
if your liver does not function properly; you may still receive Thyrogen.

Effect on tumor growth
In patients with thyroid cancer, tumor growth has been reported following withdrawal of
thyroid hormones for diagnostic testing. This is believed to be due to prolonged exposure to high
levels of thyroid-stimulating hormone (TSH). Thyrogen might also cause tumor growth, although
this effect has not been observed in clinical studies.
Due to the increase in thyroid-stimulating hormone (TSH) levels after administration of Thyrogen,
patients with secondary tumor growths (metastases) may experience localized swelling or bleeding
at the metastatic sites, which could consequently increase in size. In cases of metastases located in
confined spaces, such as intracerebral (in the brain) or spinal cord metastases, patients may develop
symptoms that can appear rapidly, such as partial paralysis affecting one side of the body (hemiparesis),
respiratory problems, or vision loss.
Your doctor will determine whether you belong to a specific group of patients for whom pre-treatment
with corticosteroids should be considered (for example, if you have secondary tumors in the brain or
spinal cord). If you have any doubts, consult your doctor.

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

Elderly
No special precautions are required for elderly patients. However, if your 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.
There are no known interactions between Thyrogen and thyroid hormones you may be taking.
Your doctor will determine the exact activity of radioactive iodine to be used for diagnostic imaging
procedures, taking into account that you continue to use thyroid hormones.

Pregnancy and breastfeeding
Do not take Thyrogen if you are pregnant. If you are pregnant, suspect you may be pregnant, plan
to become pregnant, or are breastfeeding, consult your doctor or pharmacist before taking this
medicine.
Thyrogen must not be prescribed to women who are breastfeeding. Resume breastfeeding only
after consulting your doctor.

Driving and using machines
Some patients may experience dizziness or headache after administration of Thyrogen, which
could affect their ability to drive or operate machinery.

Thyrogen contains sodium
This medicine contains less than 1 mmol (23 mg) of sodium per vial, i.e., essentially ‘sodium-free’.

3. How to use Thyrogen

The medicine will be injected by a doctor or nurse.
Treatment must be supervised by a physician experienced in thyroid cancer. The Thyrogen powder must be reconstituted with water for injectable preparations. One vial of Thyrogen is required for each injection. Thyrogen must be administered only into the gluteal muscle. This solution must never be injected into a vein. Thyrogen must not be administered together with other medicines in the same injection.

The recommended dose of Thyrogen consists of two injections given 24 hours apart. The doctor or nurse will inject 1.0 ml of Thyrogen solution.

When undergoing radioactive iodine imaging procedures or ablation, your doctor will administer the radioactive iodine 24 hours after the final Thyrogen injection.

Diagnostic scans should be performed 48–72 hours after administration of radioactive iodine (i.e., 72–96 hours after the final Thyrogen injection).

The post-treatment scan may be delayed by a few days to allow background radioactivity to decrease.

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

Use in children
Your doctor will help determine whether Thyrogen should be given to the child.

If you use more Thyrogen than you should
Patients who have accidentally received too much Thyrogen have reported nausea, weakness, dizziness, headache, vomiting, and hot flashes.

Recommended treatment in case of overdose includes restoration of fluid balance, and administration of an antiemetic should also be considered.

If you have any doubts about how to use this medicine, consult your doctor.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone experiences 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):
hot flushes
urticaria
rash
influenza-like symptoms
fever
chills
back pain
diarrhoea
tingling or prickling sensation (paraesthesia)
neck pain
loss of taste sensation (ageusia)
impaired sense of taste (dysgeusia)
influenza
Not known (frequency cannot be estimated from the available data):
tumour swelling
pain (including pain at metastatic sites (secondary tumour growths))
tremor
stroke (brain damage)
palpitations
hot flushes
shortness of breath
itching
excessive sweating
muscle or joint pain
injection site reactions (including redness, discomfort, itching, localized pain or burning, and rash accompanied by itching)
low levels of thyroid-stimulating hormone (TSH)
hypersensitivity (allergic reactions), including urticaria, itching, hot flushes, breathing difficulties, and rash.
Very rare cases of hyperthyroidism (increased thyroid activity) or atrial fibrillation have been reported when Thyrogen was administered to patients who had not undergone total or partial thyroidectomy.

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

5. How to store Thyrogen

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the label, following “Exp.”.
The expiry date refers to the last day of the month.
Store in a refrigerator (2°C - 8°C).
Keep the vial in its outer packaging to protect it from light.
Thyrogen is recommended to be administered within 3 hours after reconstitution.
The reconstituted solution can be stored for up to 24 hours in a refrigerator (2°C - 8°C), protected
from light and avoiding microbial contamination.
Do not use this medicine if you notice foreign particles, cloudiness, or any change in colour.
Do not dispose of medicines via wastewater or household waste. Ask your pharmacist how to
dispose of medicines no longer required. This will help protect the environment.

6. Package contents and other information

What Thyrogen contains
The active substance is thyrotropin alfa.
After reconstitution with 1.2 ml of water for injections, each vial contains 0.9 mg/ml of thyrotropin alfa.
Withdraw only 1 ml, equivalent to 0.9 mg of thyrotropin alfa.
The excipients are:
Mannitol
Monobasic sodium phosphate monohydrate
Dibasic sodium phosphate heptahydrate
Sodium chloride
Thyrogen contains sodium; see section 2.

Description of the appearance of Thyrogen and contents of the pack
Powder for solution for injection.
White or almost white lyophilized powder.
Pack contents: one or two vials of Thyrogen per carton. 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

For further information on this medicinal product, contact the local representative of the Marketing Authorisation Holder:

België/Belgique/Belgien/ Magyarország
Luxembourg/Luxemburg SANOFI-AVENTIS Zrt.
Sanofi Belgium Tel: +36 1 505 0050
Tél/Tel: + 32 (0)2 710 54 00

България Malta
Swixx Biopharma EOOD Sanofi S.r.l.
Тел.: +359 (0)2 4942 480 Tel: +39 02 39394275

Česká republika Nederland
Sanofi s.r.o. Sanofi B.V.
Tel: +420 233 086 111 Tel: +31 20 245 4000

Danmark Norge
Sanofi Denmark A/S sanofi-aventis Norge AS
Tlf: +45 45 16 70 00 Tlf: + 47 67 10 71 00

Deutschland Österreich
Sanofi-Aventis Deutschland GmbH sanofi-aventis GmbH
Tel.: 0800 52 52 010 Tel: + 43 1 80 185 - 0
Tel: from abroad: +49 69 305 21 131

Eesti Polska
Swixx Biopharma OÜ Sanofi Sp. z o.o.
Tel: +372 640 10 30 Tel.: +48 22 280 00 00

Ελλάδα Portugal
Sanofi-Aventis Μονοπρόσωπη AEBE Sanofi – Produtos Farmacêuticos, Lda.
Τηλ: +30 210 900 16 00 Tel: +351 21 35 89 400

España România
sanofi-aventis, S.A. Sanofi Romania SRL
Tel: +34 93 485 94 00 Tel: +40 (0) 21 317 31 36

France Slovenija
Sanofi Winthrop Industrie Swixx Biopharma d.o.o.
Tél: 0 800 222 555 Tel: +386 1 235 51 00
Appel depuis l’étranger: +33 1 57 63 23 23

Hrvatska Slovenská republika
Swixx Biopharma d.o.o. Swixx Biopharma s.r.o.
Tel: +385 1 2078 500 Tel: +421 2 208 33 600

Ireland
sanofi-aventis Ireland Ltd. T/A SANOFI
Tel: +353 (0) 1 403 56 00

Ísland Suomi/Finland
Vistor hf. Sanofi Oy
Sími: +354 535 7000 Puh/Tel: + 358 (0) 201 200 300

Italia Sverige
Sanofi S.r.l. Sanofi AB
Tel: 800536389 Tel: +46 (0)8 634 50 00

Κύπρος
C.A. Papaellinas Ltd.
Τηλ: +357 22 741741

Latvija United Kingdom (Northern Ireland)
Swixx Biopharma SIA sanofi-aventis Ireland Ltd. T/A SANOFI
Tel: +371 6 616 47 50 Tel: +44 (0) 800 035 2525

Lietuva
Swixx Biopharma UAB
Tel: +370 5 236 91 40

More detailed information on this medicinal product is available on the European Medicines Agency website: http://www.ema.europa.eu

The following information is intended for healthcare professionals only:
The recommended dosage regimen for Thyrogen is two intramuscular injections of 0.9 mg thyrotropin alfa administered 24 hours apart.

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

Use aseptic technique.
Add 1.2 ml of water for injections to the powder in the vial. Gently swirl the vial until the powder is completely dissolved. Do not shake the solution. After complete dissolution, the total volume in the vial is 1.2 ml. The pH of the Thyrogen solution is approximately 7.0.

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

Withdraw 1.0 ml of the Thyrogen solution from the vial. This volume corresponds to 0.9 mg of thyrotropin alfa for injection.

Thyrogen does not contain preservatives. Immediately discard any unused solution. No special requirements for disposal.

After reconstitution, the solution must be injected within three hours. The reconstituted solution may be stored for up to 24 hours in a refrigerator (2°C - 8°C), protected from light and avoiding microbial contamination. It is important to remember that microbiological stability depends on the aseptic conditions maintained during preparation.