Tevagrastim 48 MIU/0.8 ml solution for injection or infusion

What Tevagrastim is

Tevagrastim contains the active substance filgrastim. Filgrastim is a protein produced by biotechnology in bacteria called Escherichia coli. It belongs to a group of proteins called cytokines and is very similar to a natural protein (granulocyte-colony stimulating factor [G-CSF]) produced by your own body. Filgrastim stimulates the bone marrow (the tissue where new blood cells are made) to produce more blood cells, especially certain types of white cells. White cells are important as they help your body fight infection.

What Tevagrastim is used for

Your doctor has prescribed Tevagrastim for you to help your body make more white blood cells. Your doctor will tell you why you are being treated with Tevagrastim. Tevagrastim is useful in several different conditions which are:

• chemotherapy,
• bone marrow transplantation,
• severe chronic neutropenia,
• neutropenia in patients with HIV infection,
• peripheral blood stem cell mobilisation.

Do not use Tevagrastim

• if you are allergic (hypersensitive) to filgrastim or to any of the other ingredients of Tevagrastim.

Take special care with Tevagrastim

• if you experience a cough, fever and difficulty breathing. It could be a consequence of a pulmonary disorder (see section ?4. POSSIBLE SIDE EFFECTS?).
• if you have sickle cell disease; or
• if you get left upper abdominal pain or pain at the tip of your shoulder. It could be a consequence of a spleen disorder (see section -4. POSSIBLE SIDE EFFECTS-).

You will need to have regular blood tests whilst being treated with Tevagrastim to count the number of neutrophils and other white blood cells in your blood. This will tell your doctor how well the treatment is working and will also indicate if treatment needs to be continued.

Using other medicines
Please tell your doctor or pharmacist if you are taking or have recently taken any other medicines, including medicines obtained without a prescription.

Pregnancy and breast-feeding

Ask your doctor or pharmacist for advice before taking any medicine.
Tevagrastim has not been tested in pregnant women. It is important to tell your doctor if you are pregnant, think you may be pregnant or plan to get pregnant, as the doctor may decide that you should not use this medicine.

It is unknown whether filgrastim passes over to the breast milk. Therefore, your doctor may decide that you should not use this medicine if you are breast-feeding.

Driving and using machines
If you experience fatigue, do not drive or use any tools or machines.

Important information about some of the ingredients of Tevagrastim

This medicine contains sorbitol (a type of sugar). If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicine.

Always use Tevagrastim exactly as your doctor has told you. You should check with your doctor or pharmacist if you are not sure.

The usual dose is...

The amount of Tevagrastim you need will depend on the condition you are taking Tevagrastim for and on your bodyweight. Your doctor will tell you when to stop using Tevagrastim. It is quite normal to have a number of courses of Tevagrastim treatment.

Tevagrastim and chemotherapy
The usual dose is 0.5 million international units (MIU) per kilogram of bodyweight each day. For example, if you weigh 60 kg your daily dose will be 30 million international units (MIU). Your treatment will usually last for about 14 days. In some disease types however, longer treatment lasting up to about one month may be required.

Tevagrastim and bone marrow transplantation
The usual starting dose is 1 million international units (MIU) per kilogram of bodyweight each day. For example, if you weigh 60 kg your daily dose will be 60 million international units (MIU). You will normally receive your first dose of Tevagrastim at least 24 hours after your chemotherapy but within 24 hours of receiving your bone marrow transfusion. Your doctor will test your blood daily to see how well the treatment is working and to find the dose that is best for you. The treatment will be discontinued when white cells in your blood reach a certain number.

Tevagrastim and severe chronic neutropenia
The usual starting dose is between 0.5 million and 1.2 million international units (MIU) per kilogram bodyweight each day in a single or divided dose. Your doctor will then test your blood to see how well your treatment is working and to find the dose that is best for you. Long-term treatment with Tevagrastim is required for neutropenia.

Tevagrastim and neutropenia in patients with HIV infection
The usual starting dose is between 0.1 and 0.4 million international units (MIU) per kilogram bodyweight each day. Your doctor will test your blood at regular intervals to see how well the treatment is working. Once the number of white cells in your blood have returned to normal it may be possible to reduce the dose frequency to less than once per day. Your doctor will continue to test your blood regularly and will recommend the best dose for you. Long term treatment with Tevagrastim may be required to maintain a normal number of white cells in your blood.

Tevagrastim and peripheral blood stem cell mobilisation
If you are donating stem cells for yourself, the usual dose is 0.5 million to 1 million international units (MIU) per kilogram bodyweight each day. Tevagrastim treatment will last for up to 2 weeks and in exceptional cases longer. Your doctor will monitor your blood to determine the best time to collect the stem cells.

If you are acting as a stem cell donor for another person, the usual dose is 1 million international units (MIU) per kilogram bodyweight each day. Tevagrastim treatment will last for 4 to 5 days.

Method of administration

This medicine is given by injection, either through an intravenous infusion (drip) or into the tissue just under the skin. This is known as a subcutaneous (SC) injection. If you are receiving this medicine by subcutaneous injection, your doctor may suggest that you learn how to give yourself the injections. Your doctor or nurse will give you instructions on how to do this. Do not attempt to self-administer without this training. Some of the information you require is given at the end of this package leaflet, but proper treatment of your disease requires close and constant co-operation with your doctor.

Each pre-filled syringe is for single use only.

If you use more Tevagrastim than you should
If you use more Tevagrastim than you should, contact your doctor or pharmacist as soon as possible.

If you forget to use Tevagrastim

Do not use a double dose to make up for a forgotten injection.

If you stop using Tevagrastim

Before you stop using Tevagrastim, talk to your doctor.

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

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

The following frequency conventions are used in the evaluation of side effects Very common Common Uncommon Rare Very rare Not known more than 1 user in 10 1 to 10 users in 100 1 to 10 users in 1,000 1 to 10 users in 10,000 less than 1 user in 10,000 frequency cannot be estimated from the available data.

Allergic-type reactions to filgrastim, including skin rash, raised areas of the skin that itch and anaphylaxis (weakness, drop in blood pressure, difficulty breathing and swelling of the face) have been reported. If you think you are having this type of reaction, stop your Tevagrastim injection and get medical help immediately.

Increased spleen size and very rare cases of spleen ruptures have been reported. Some cases of splenic rupture were fatal.

It is important that you contact your doctor immediately if you experience pain in the upper left side of the abdomen or left shoulder pain since this may relate to a problem with your spleen.

It is also very important that you call your doctor if you think you may have an infection. There are many ways an infection may show itself. You should watch for a temperature of 37.8 °C or above, chills or other signs of infection, such as a rash, sore throat, diarrhoea, ear-ache, difficult or painful breathing or problems such as cough or wheezing. These symptoms could be signs of severe pulmonary side effects, like pneumonia and respiratory distress syndrome in adults, which may be fatal. If you have a fever or any of these symptoms, contact your doctor immediately and go straight to your hospital.

If you have Sickle Cell Disease, make sure that you tell your doctor before you start taking Tevagrastim. Sickle cell crisis has happened in some patients with Sickle Cell Disease who have been given filgrastim.

As a very common side effect, filgrastim may cause bone and muscle pain. Ask your doctor which medicine you can take to help with this.

You may experience the following additional side effects:

• reduction in red blood cells which can make the skin pale and cause weakness or breathlessness, reduction in blood platelets, which increases risk of bleeding or bruising, rise in white blood cells
• rejection of transplanted bone marrow (frequency unknown)
• elevated levels of some liver or blood enzymes, high blood levels of uric acid, low blood levels of glucose
• headache
• transient low blood pressure, vascular disorders (which can cause pain, redness and swelling in the limbs)
• nosebleed, cough, sore throat
• cough, fever and difficulty breathing or coughing up blood (frequency unknown)
• feeling sick, vomiting, constipation, diarrhoea, loss of appetite, mucositis (painful inflammation and ulceration of the mucous membranes lining the digestive tract)
• pains or difficulties in passing urine (very rare), blood in the urine, protein in the urine
• enlarged liver
• inflammation of blood vessels, often with skin rash (very rare); the appearance of plum-coloured, raised, painful lesions on the limbs (sometimes the face and neck) with fever (Sweet's syndrome, very rare); hair loss; pain at the site of injection; rash
• joint pain; chest pain; worsening of rheumatic conditions; loss of calcium from the bones; pain and swelling of the joints, similar to gout (frequency unknown)
• fatigue, generalised weakness, unspecified pain.

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

Keep out of the reach and sight of children.

Do not use Tevagrastim after the expiry date which is stated on the outer carton and on the pre-filled syringe after EXP. The expiry date refers to the last day of that month.

Store in a refrigerator (2 °C ? 8 °C).

Do not use Tevagrastim if you notice it is cloudy or there are particles in it.

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 Tevagrastim contains

• The active substance is filgrastim. Each ml of solution for injection or infusion contains 60 million international units [MIU] (600 µicrogram) of filgrastim.Tevagrastim 30 MIU/0.5 ml: Each pre-filled syringe contains 30 million international units [MIU] (300 microgram) of filgrastim in 0.5 ml solution. Tevagrastim 48 MIU/0.8 ml: Each pre-filled syringe contains 48 million international units [MIU] (480 microgram) of filgrastim in 0.8 ml solution.
• The other ingredients are: Sodium hydroxide, glacial acetic acid, sorbitol, polysorbate 80, water for injections. You will find detailed information about the ingredient sorbitol (a sugar) in section 2. under the heading ?Important information about some of the ingredients of Tevagrastim?.

What Tevagrastim looks like and contents of the pack

Tevagrastim is a solution for injection or infusion in a pre-filled syringe. Tevagrastim is a clear and colourless solution. Each pre-filled syringe contains 0.5 ml or 0.8 ml of solution.

Tevagrastim are supplied in packs of 1, 5 or 10 pre-filled syringes or multipacks of 10 (2 packs of 5) pre-filled syringes with injection needle and with or without a needle safety guard. Not all pack sizes may be marketed.

Marketing Authorisation HolderTeva GmbH
Wasastraße 50
D-01445 Radebeul
Germany

Manufacturer

Teva Pharma B.V.
Swensweg 5
2031 GA Haarlem
The Netherlands

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

BelgiëBelgiqueBelgien Teva Pharma Belgium NVSA TélTel 32 38 20 73 73 LuxembourgLuxemburg Teva Pharma Belgium NVSA TélTel 32 38 20 73 73

Teva Pharmaceuticals Bulgaria EOOD Te 359 2 489 95 82 Magyarország Teva Magyarország Zrt Tel 36 1 288 64 00

eská republika Teva Pharmaceuticals CR, s.r.o. Tel 420 251 007 111 Malta Drugsales Ltd. Tel 356 21 419 07012

Danmark Teva Denmark A.S. Tlf 45 0 44 98 55 11 Nederland Pharmachemie B.V. Tel 31 23 5 147 147

Deutschland Teva GmbH Tel 49 351 8340 Norge Teva Sweden AB Tlf 46 42 12 11 00

Eesti UAB Sicor Biotech Eesti Filiaal TEVA Grupi Tel 372 611 24 07 Österreich ARAC Tel 43 1 524 05 89 10

Teva .. 30 210 72 79 099 Polska Teva Pharmaceuticals Polska Sp. z o.o. Tel 48 22 345 93 00

España Teva Genéricos Española, S.L.U. Tel 34 91 387 32 80 Portugal Teva Pharma Produtos Farmacêuticos, Lda. Tel 351 21 423 59 10

France Teva Santé SAS Tél 33 1 55 91 78 00 România Teva Pharmaceuticals S.R.L. Tel 40 21 212 08 90

Ireland IVAX Pharmaceuticals Ireland Tel 353 42 939 58 92 Slovenija Pliva Ljubljana d.o.o. Tel. 38615890390

Ísland Teva Sweden AB Sími 46 42 12 11 00 Slovenská republika TEVA Pharmaceuticals Slovakia s.r.o. Tel 421 2 57 26 79 12

Italia Teva Italia S.r.l. Tel 39 02 89 17 98 05 SuomiFinland Teva Sweden AB PuhTel 46 42 12 11 00

Teva .. 30 210 72 79 099 Sverige Teva Sweden AB Tel 46 42 12 11 00

Latvija UAB Sicor Biotech filiale Latvija TEVA Tel 371 6 77 84 980 United Kingdom Teva UK Limited Tel 44 1323 501 111

Lietuva
UAB SICOR Biotech / TEVA grup-s nar-
Tel: +370 5 266 02 03

This leaflet was last approved in {MM/YYYY}

INFORMATION FOR INJECTING YOURSELF

This section contains information on how to give yourself an injection of Tevagrastim. It is important that you do not try to give yourself the injection unless you have received special training from your doctor or nurse. It is also important that you dispose of the syringe in a puncture-proof container. If you are not sure about giving yourself the injection or you have any questions, please ask your doctor or nurse for help.

How do I inject Tevagrastim myself?

You will need to give yourself the injection into the tissue just under the skin. This is known as a subcutaneous injection. You will need to have your injections at about the same time every day.

Equipment that you need

To give yourself a subcutaneous injection you will need:

• a pre-filled syringe of Tevagrastim,
• alcohol wipes or similar,
• a puncture-proof container (plastic container provided by the hospital or pharmacy) so you can dispose of used syringes safely.

What should I do before I give myself a subcutaneous injection of Tevagrastim?

1. Try to self-inject at approximately the same time every day.

2. Take your Tevagrastim pre-filled syringe out of the refrigerator.

3. Check the expiry date on the pre-filled syringe label (EXP). Do not use it if the date has passed the last day of the month shown.

4. Check the appearance of Tevagrastim. It must be a clear and colourless liquid. If there are particles in it, you must not use it.

5. For a more comfortable injection, let the pre-filled syringe stand for 30 minutes to reach room temperature or hold the pre-filled syringe gently in your hand for a few minutes. Do not warm Tevagrastim in any other way (for example, do not warm it in a microwave or in hot water).

6. Do not remove the cover from the syringe until you are ready to inject.

7. Wash your hands thoroughly.

8. Find a comfortable, well-lit place and put everything you need where you can reach them (the Tevagrastim pre-filled syringe, alcohol wipes and the puncture-proof container).

How do I prepare my Tevagrastim injection Before you inject Tevagrastim you must do the following 1. Hold the syringe barrel and gently take the cover from the needle without twisting. Pull straight as shown in pictures 1 and 2. Do not touch the needle or push the plunger. 1

2 2. You may notice a small air bubble in the pre-filled syringe. If there are air bubbles present, gently tap the syringe with your fingers until the air bubbles rise to the top of the syringe. With the syringe pointing upwards, expel all air from the syringe by pushing the plunger upwards. 3. The syringe has a scale on the syringe barrel. Push the plunger up to the number ml on the syringe that matches the dose of Tevagrastim that your doctor prescribed. 4. Check again to make sure the correct dose of Tevagrastim is in the syringe. 5. You can now use the pre-filled syringe.

Where should I give my injection?

The most suitable places to inject yourself are:

• the top of your thighs; and
• the abdomen, except for the area around the navel (see picture 3).

If someone else is injecting you, they can also use the back of your arms (see picture 4).

It is better to change the injection site every day to avoid the risk of soreness at any one site.

How do I give my injection?

1. Disinfect your skin by using an alcohol wipe and pinch the skin between your thumb and forefinger, without squeezing it (see picture 5).

2. Put the needle fully into the skin as shown by your nurse or doctor (see picture 6).

3. Pull slightly on the plunger to check that a blood vessel has not been punctured. If you see blood in the syringe, remove the needle and re-insert it in another place.

Pre-filled syringe without a needle safety guard

4. Inject the liquid slowly and evenly, always keeping your skin pinched. 5. Inject only the dose your doctor has told you. 6. After injecting the liquid, remove the needle and let go of your skin. 7. Only use each syringe for one injection. Do not use any Tevagrastim that is left in the syringe. 5 6 Pre-filled syringe with a needle safety guard

4. Always keeping your skin pinched, depress the plunger slowly and evenly until the entire dose has been given and the plunger cannot be depressed any further. Do not release the pressure on the plunger!

5. Inject only the dose your doctor has told you.

6. After injecting the liquid, remove the needle while maintaining pressure on the plunger and then let go of your skin.

7. Let go of the plunger. The needle safety guard will rapidly move to cover the needle.

8. Only use each syringe for one injection. Do not use any Tevagrastim that is left in the syringe.

7

8

Remember

If you have any problems, please do not be afraid to ask your doctor or nurse for help and advice.

Disposing of used syringes

The used syringes should be disposed of in accordance with local requirements.

Pre-filled syringe without needle safety guard

• Do not put the cover back on used needles.
• Put used syringes into the puncture-proof container and keep this container out of the reach and sight of children.
• Dispose of the full puncture-proof container as instructed by your doctor, nurse or pharmacist.
• Never put the syringes that you have used into your normal household rubbish bin.

Pre-filled syringe with needle guard

• The needle safety guard prevents needle stick injuries after use, so no special disposal precautions are required. Dispose of the syringe as instructed by your doctor, nurse or pharmacist.

THE FOLLOWING INFORMATION IS INTENDED FOR MEDICAL OR HEALTHCARE PROFESSIONALS ONLY

Tevagrastim does not contain any preservative. In view of the possible risk of microbial contamination, Tevagrastim syringes are for single use only.

Accidental exposure to freezing temperatures does not adversely affect the stability of Tevagrastim.

Tevagrastim should not be diluted with sodium chloride solution. This medicinal product must not be mixed with other medicinal products except those mentioned below. Diluted filgrastim may be adsorbed to glass and plastic materials except diluted, as mentioned below.

If required, Tevagrastim may be diluted in glucose 50 mg/ml (5%) solution for infusion. Dilution to a final concentration less than 0.2 MIU (2 ?g) per ml is not recommended at any time. The solution should be visually inspected prior to use. Only clear solutions without particles should be used. For patients treated with filgrastim diluted to concentrations below 1.5 MIU (15 ?g) per ml, human serum albumin (HSA) should be added to a final concentration of 2 mg/ml. Example: In a final injection volume of 20 ml, total doses of filgrastim less than 30 MIU (300 ?g) should be given with 0.2 ml of 200 mg/ml (20%) human albumin solution added. When diluted in glucose 50 mg/ml (5%) solution for infusion, Tevagrastim is compatible with glass and a variety of plastics including PVC, polyolefin (a co-polymer of polypropylene and polyethylene) and polypropylene.

After dilution: Chemical and physical in-use stability of the diluted solution for infusion has been demonstrated for 24 hours at 2 °C to 8 °C. From a microbiological point of view, the product should be used immediately. If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user and would normally not be longer than 24 hours at 2 °C to 8 °C, unless dilution has taken place in controlled and validated aseptic conditions.

Using the pre-filled syringe with a needle safety guard

The needle safety guard covers the needle after injection to prevent needle stick injury. This does not affect normal operation of the syringe. Depress the plunger slowly and evenly until the entire dose has been given and the plunger cannot be depressed any further. While maintaining pressure on the plunger, remove the syringe from the patient. The needle safety guard will cover the needle when releasing the plunger.

Using the pre-filled syringe without a needle safety guard

Administer the dose as per standard protocol.

Disposal

Any unused product or waste material should be disposed of in accordance with local requirements.