Nivestim 12 MU/ 0.2 ml solution for injection/infusion

What Nivestim is

Nivestim contains the active substance filgrastim. 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 Nivestim is used for

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

• chemotherapy,
• bone marrow transplantation,
• severe chronic neutropenia (neutropenia is a condition of an abnormally low number of a particular type of white blood cell called a neutrophil),
• neutropenia in patients with HIV infection,
• peripheral blood stem cell mobilisation.

Do not use Nivestim

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

Take special care with Nivestim

• if you are suffering from any other illness (especially if you think you may have an infection),
• if you experience cough, fever and difficulty breathing. It could be due to a lung disorder (see section 4 ?POSSIBLE SIDE EFFECTS?),
• if you have sickle cell disease (an inherited blood disorder that affects red blood cells),
• 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 may need to have regular blood tests whilst being treated with Nivestim to count the number of neutrophils and other white blood cells in your blood. This will tell your doctor how the treatment is working and will also indicate if treatment needs to be continued.

Using other medicines
You should not receive Nivestim in the 24 hours before and the 24 hours after receiving chemotherapy. 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.
Filgrastim 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 your doctor may decide that you should not use this medicine. Filgrastim could affect your ability to become pregnant or stay pregnant.
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

Filgrastim has negligible influence on the ability to drive and use machines. If the patient is experiencing fatigue, caution is advised when driving a car or operating machinery.

Important information about some of the ingredients of Nivestim

This medicine contains sorbitol (E420). If you have been told by your doctor that you have an intolerance to some sugars (fructose), contact your doctor before taking this medicine. This medicine also contains sodium less than 1mmol sodium (23 mg) per dose, i.e. essentially ?sodium-free?.

Always use Nivestim exactly as your doctor tells you to.
This medicine is given by injection, either through an intravenous infusion (drip) or by a subcutaneous injection into the tissue just under the skin.
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 (see end of leaflet for self administration information). Do not attempt to self-administer without this training. Some of the information you require is given at the end of this leaflet, but proper treatment of your disease requires close and constant co-operation with your doctor. The amount of Nivestim you need, will depend on the condition you are taking Nivestim for and on your bodyweight.

Nivestim and neutropenia associated with chemotherapy

The usual dose for adults and children is 0.5 million units (5 micrograms) per kilogram of bodyweight each day. For example, if you weigh 60 kg your daily dose will be 30 million units (300 micrograms). 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.

Nivestim and bone marrow transplantation

The normal starting dose is 1 million units (10 micrograms) per kilogram of bodyweight each day given as an infusion. For example, if you weigh 60 kg your daily dose will be 60 million units (600 micrograms). You will normally receive your first dose of Nivestim at least 24 hours after your chemotherapy but within 24 hours of receiving your bone marrow transplantation. Your doctor may then test your blood to tell how well your treatment is working and how long it should last.

Nivestim and severe chronic neutropenia

The normal starting dose is between 0.5 million (5 micrograms) and 1.2 million (12 micrograms) units per kilogram bodyweight each day in a single or divided dose. Your doctor may 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 Nivestim is required for neutropenia.

Nivestim and neutropenia in patients with HIV infection

The normal starting dose is between 0.1 (1 micrograms) and 0.4 million units (4 micrograms) per kilogram bodyweight each day. Your doctor may test your blood at regular intervals to see how well the treatment is working and to decide on the dose necessary. 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. Long term treatment with Nivestim may be required to maintain a normal number of white cells in your blood.

Nivestim and peripheral blood stem cell transplantation

If you are donating stem cells for yourself, the usual dose is 0.5 million (5 micrograms) to 1 million units (10 micrograms) per kilogram bodyweight each day. Nivestim treatment will last for up to 2 weeks. 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 units per kilogram bodyweight each day. Nivestim treatment will last for 4 to 5 days.

If you use more Nivestim than you should

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

If you forget to use Nivestim

If you have forgotten to inject a dose, speak to your doctor or pharmacist to find out when you should inject the next dose. Do not use a double dose to make up for a forgotten injection.

If you stop using Nivestim

Your doctor will tell you when to stop using Nivestim. It is quite normal to have a number of courses of Nivestim treatment.

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

Like all medicines, Nivestim can cause side effects, although not everyone gets them.

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 Nivestim injection and get medical help immediately.

Increased spleen size and very rare cases of spleen ruptures have been reported. Some cases of rupture of the spleen 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 painsince 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 lung 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 Nivestim. Sickle cell crisis has happened in some patients with Sickle Cell Disease who have been given filgrastim.

The frequency of possible side effects listed below is defined using the following convention: Very common (affects more than 1 user in 10)
Common (affects 1 to 10 users in 100)
Uncommon (affects 1 to 10 users in 1,000)
Rare (affects 1 to 10 users in 10,000)
Very rare (affects less than 1 user in 10,000)

Very common side effects

• Feeling or being sick
• Bone and muscle pain
• Nose bleeds
• Decreased blood glucose levels
• Raised level of some liver enzymes or altered blood chemicals. Your doctor will take blood tests for these
• Raised uric acid level which may present as gout

Common side effects

• Fatigue
• Generalised weakness
• Headache
• Constipation or diarrhoea
• Loss of appetite
• Inflammation and ulceration of the mouth and lining of the gut
• Chest pain
• Cough
• Sore throat
• Hair loss
• Skin rash
• Enlarged liver
• Thinning of the bones
• Injection site pain
• Inflammation of the blood vessels
• Reduction in platelets (cells involved in clotting) ? which increases the risk of bleeding or bruising

Uncommon side effects

• Unspecified pain
• Blood or protein in your urine

Rare side effects

• Problems with your blood vessels

The side effects that may be experienced by you if you are acting as a stem cell donor for another person are:

Very common side effects

• Headache
• Bone or muscle pain
• Changes in your white cells or blood platelets (your doctor will monitor for this by blood tests)

Common side effects

• Raised levels of some liver enzymes (your doctor will monitor for this)

Uncommon side effects

• Severe allergic reaction
• Problems with your spleen
• Raised uric acid levels which may present as gout
• Worsening of existing rheumatoid arthritis

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 Nivestim 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 and transport refrigerated (2°C ? 8°C). Do not freeze. Keep the pre-filled syringe in the outer carton in order to protect from light.
The syringe can be removed from the refrigerator and left at room temperature for a single period of maximum 7 days (but not above 25°C).

Do not use Nivestim 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 Nivestim contains

• The active substance is filgrastim. Each ml contains 60 million units [MU] (600 micrograms) or 96 million units [MU] (960 micrograms) of filgrastim.
• Nivestim 12 MU/ 0.2 ml solution for injection/ infusion: each pre-filled syringe contains 12 million units (MU), 120 micrograms of filgrastim in 0.2 ml (corresponding to 0.6 mg/ml).
• Nivestim 30 MU/ 0.5 ml solution for injection/ infusion: each pre-filled syringe contains 30 million units (MU), 300 micrograms of filgrastim in 0.5 ml (corresponding to 0.6 mg/ml).
• Nivestim 48 MU/ 0.5 ml solution for injection/ infusion: each pre-filled syringe contains 48 million units (MU), 480 micrograms of filgrastim in 0.5 ml (corresponding to 0.96 mg/ml).
• The other ingredients are acetic acid (glacial), sodium hydroxide, sorbitol E420, polysorbate 80, and water for injections.

What Nivestim looks like and contents of the pack

Nivestim is a clear colourless solution for injection/ infusion in a glass pre-filled syringe with an injection needle (stainless steel) with a needle guard. There are 1, 5 or 10 syringes in each pack.

Marketing Authorisation Holder

Hospira UK Limited
Queensway
Royal Leamington Spa
Warwickshire
CV31 3RW
United Kingdom
Tel: +44 (0)1926 820 820
Fax: +44 (0)1926 821 041

Manufacturer

PLIVA Kraków, S.A.
ul. Mogilska 80
31-546 Kraków
Poland

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

BelgiëBelgiqueBelgien Hospira Benelux BVBA TélTel 32 2 332 03 15 LuxembourgLuxemburg Hospira Benelux BVBA TélTel 32 2 332 03 15

Hospira UK Limited Te. 44 0 1926 820820 Magyarország Pharmacenter Hungary Kft. Tel. 36-1-209-5927

eská republika Movianto eská republika s.r.o Tel 420 548 134 400 Malta Hospira UK Limited Tel 44 0 1926 820820

Danmark Hospira Nordic AB Tlf 46 08 672 85 00 Nederland Hospira Benelux BVBA Tel 32 2 332 03 15

Deutschland Hospira Deutschland GmbH Tel 49 0 89 43 77 77 0 Norge Hospira Nordic AB Tlf 46 08 672 85 00

Eesti Berren Medical, co Axellus OÜ Tel 372 662 3573 Österreich Astro-Pharma Vertrieb und Handel von pharmazeutischen Produkten GmbH Tel 43 01 961 93 13

Aenorasis S.A. 30 210 6136332 Polska Zaklady Farmaceutyczne S.A. Tel. 481 26178048

Portugal Hospira Portugal Lda España Hospira Productos Farmacéuticos y Hospitalarios S.L. Tel 34 914847100 Tel 351 214857434

France Hospira France Tél 33 0 826 30 03 02 România Hospira UK Limited Tel 44 0 1926 820820

Ireland Hospira Ireland Limited Tel 353 0 1 2962102 Slovenija Valentis Pharmaceuticals d.o.0 Tel 386 1 2000603

Ísland Hospira Nordic AB Sími 46 08 672 85 00 Slovenská republika Hospira UK Limited Tel 44 0 1926 820820

Italia Hospira Italia Srl Tel 39 0812405912 SuomiFinland Hospira Nordic AB PuhTel 46 08 672 85 00

Hospira UK Limited 44 0 1926 820820 Sverige Hospira Nordic AB Tel 46 08 672 85 00

Latvija Berren Medical, co Axellus SIA Tel 371 721 1629 United Kingdom Hospira UK Limited Tel 44 0 1926 820820

Lietuva
Berren Medical, c/o Axellus UAB
Tel: + 370 5 231 0654

This leaflet was last approved in

Information on self administration by the patient

This section contains information on how to give yourself an injection of Nivestim. 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 administer myNivestim?

Nivestim is usually given once a day by injection, usually into the tissue just under the skin. This is known as a subcutaneous injection.
Learning to give your own injections will mean that you will not have to wait at home for a nurse to call, nor will you have to go to the hospital or clinic every day to receive your injections.
You will need to have your injections at about the same time every day. The most suitable places for injection are:

• the front of the thighs,
• the abdomen, except for the area around the navel.

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

To give yourself a subcutaneous injection you will need the following items:

• A new pre-filled syringe of Nivestim.
• A sharps container (puncture proof container) for disposing of used syringes safely.
• Antiseptic wipes (if recommended by your doctor or nurse). How do I give my subcutaneous Nivestim injection?

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

2. Remove the Nivestim from the fridge and allow it to reach room temperature (approximately 25 °C). This will take 15?30 minutes. Check the date on the pack to make sure that the medicine has not passed the expiry date. Make sure you have your sharps bin nearby.

3. Find a comfortable well lit working place to give your injection and check the dose that you have been prescribed.

4. Wash your hands thoroughly with soap and water.

5. Remove the syringe from the blister pack and check that the solution is clear, colourless and practically free from visible particles. Do not use the Nivestim if the liquid has particles floating in it or any of the liquid has leaked out of the syringe.

6. Hold the syringe with the needle pointing upwards. Remove the protective cap from the injection needle and expel any air from the syringe and needle by gently pressing the plunger upwards. The syringe is now ready for use.

7. Decide where to inject Nivestim - find a place on the front of your abdomen or the front of your thigh. Choose a different injection site each time. Do not choose an area which is tender, red, bruised or scarred. If your nurse or doctor recommends it, clean the area of skin with an antiseptic wipe.

8. Pinch a large area of skin, taking care not to touch the area you have cleaned.

9. With your other hand, insert the needle at an approximate 45- angle.

10. Pull the plunger back slightly to check if any blood appears in the syringe. If you do see blood inside the syringe, remove the needle and re-insert it in a different site. Slowly push down the plunger until all the contents of the syringe have been emptied.

11. After injecting the solution remove the needle from the skin.

12. Ensure needle guard covers the needle according to instructions for active needle guard or passive needle guard below.

13. Place the syringe into the sharps container. Do not try to replace the protective cap.

Remember
Most people can learn to give themselves a subcutaneous injection, but if you are experiencing a lot of difficulty, please do not be afraid to ask for help and advice from your doctor or nurse.

Use of Active Ultrasafe Needle GuardforNivestim 12 MU/ 0.2 ml solution for injection/ infusion The pre-filled syringe has an UltraSafe Needle Guard attached in order to protect from needle stick injury. When handling the pre-filled syringe, keep hands behind the needle.

1. Perform the injection using the technique described above.

2. When you have completed the injection, slide the needle guard forward until the needle is completely covered (device ?clicks? into place).

Use of Ultrasafe Passive Needle Guard forNivestim 30 MU/ 0.5 ml solution for injection/ infusion and Nivestim 48 MU/ 0.5 ml solution for injection/ infusion

The pre-filled syringe has an UltraSafe Needle Guard attached in order to protect from needle stick injury. When handling the pre-filled syringe, keep hands behind the needle.

1. Perform the injection using the technique described above.

2. Depress the plunger while grasping the finger flange until the entire dose has been given. The passive needle guard will NOT activate unless the ENTIRE dose has been given.

3. Remove needle from your skin, then let go of the plunger and allow syringe to move up until the entire needle is guarded and locks into place.

• Keep used syringes out of the reach and sight of children
• NEVER put used syringes into your normal household waste bin.

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THE FOLLOWING INFORMATION IS INTENDED FOR MEDICAL OR HEALTHCARE PROFESSIONALS ONLY:

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

Accidental exposure to freezing temperatures for up to 24 hours does not affect the stability of Nivestim. The frozen pre-filled syringes can be thawed and then refrigerate for future use. If exposure has been greater then 24 hours or frozen more than once then Nivestim should NOT be used.

Nivestim 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, Nivestim may be diluted in glucose 50 mg/ml (5%) solution for infusion. Dilution to a final concentration less than 0.2 MU (2 micrograms) 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 MU (15 micrograms) 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 MU (300 micrograms) 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, Nivestim 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.