Package leaflet: Information for the user

Tevagrastim 30 MUI/0.5 mL solution for injection/infusion, 48 MUI/0.8 mL solution for injection/infusion

filgrastim
Please read all of this leaflet carefully before you start using this medicine, as it contains important information for you.

Keep this leaflet. You may need to read it again.
If you have any questions, ask your doctor, pharmacist, or nurse.
This medicine has been prescribed for you only. Do not give it to other people, even if they have the same symptoms as yours, because it could be harmful.
If you experience any side effects, including those not listed in this leaflet, tell your doctor, pharmacist, or nurse. See section 4.

Contents of this leaflet:

What Tevagrastim is and what it is used for
What you need to know before using Tevagrastim
How to use Tevagrastim
Possible side effects
How to store Tevagrastim
Contents of the pack and other information
Instructions for self-injection
The following information is intended exclusively for healthcare professionals

1. What Tevagrastim is and what it is used for

What Tevagrastim is
Tevagrastim is a white blood cell growth factor (granulocyte colony-stimulating factor) and belongs to a group of medicines called cytokines. Growth factors are proteins naturally produced in the body, but they can also be manufactured using biotechnology for use as medicines. Tevagrastim stimulates the bone marrow to produce a greater number of white blood cells.

What Tevagrastim is used for
A reduction in the number of white blood cells (neutropenia) can occur for various reasons, reducing the body's ability to defend itself against infections. Tevagrastim stimulates the bone marrow to rapidly produce new white blood cells.

Tevagrastim may be used:

to increase the number of white blood cells after chemotherapy treatment, thereby helping to prevent infections;
to increase the number of white blood cells after a bone marrow transplant, thereby helping to prevent infections;
prior to high-dose chemotherapy to stimulate the bone marrow to produce more stem cells, which can be collected and reinfused after treatment. These cells may be collected from you or from a donor. The stem cells will then return to the bone marrow and produce blood cells;
to increase the number of white blood cells if you have severe chronic neutropenia, thereby helping to prevent infections;
in patients with advanced HIV infection, to help reduce the risk of infections.

2. What you need to know before using Tevagrastim

Do not use Tevagrastim

if you are allergic to filgrastim or to any of the other ingredients of this medicine (listed in section 6).

Warnings and precautions
Talk to your doctor, pharmacist or nurse before using Tevagrastim.
Tell your doctor before starting treatment if you have:

sickle cell anaemia, as Tevagrastim may trigger sickle cell crises.
osteoporosis (a bone disease)

Contact your doctor immediately during treatment with Tevagrastim if:

you develop sudden signs of allergy such as rash, itching or hives, swelling of the face, lips, tongue or other parts of the body, shortness of breath or difficulty breathing, as these may be signs of a serious allergic reaction (hypersensitivity).
you experience swelling of the face or ankles, blood in the urine or brown-coloured urine, or notice that you are urinating less than usual (glomerulonephritis).
you feel pain in the upper left side of your abdomen (abdominal pain), pain under the left side of your rib cage or at the tip of your left shoulder (these may be symptoms of an enlarged spleen (splenomegaly) or possible spleen rupture).
you notice unusual bleeding or bruising (these may be symptoms of a low platelet count (thrombocytopenia), resulting in reduced blood clotting ability).
you have symptoms of inflammation of the aorta (the large blood vessel carrying blood from the heart to the rest of the body), which has been reported rarely in cancer patients and healthy individuals. Symptoms may include fever, abdominal pain, malaise, back pain and elevated markers of inflammation. Inform your doctor if you experience such symptoms.

Loss of response to filgrastim
If you experience a decreased response or failure to maintain response to treatment with filgrastim, your doctor will investigate possible causes, including whether you have developed antibodies that neutralize the activity of filgrastim.
Your doctor may decide to monitor you closely; see section 4 of the package leaflet.
If you have severe chronic neutropenia, you may be at risk of developing blood cancer (leukaemia, myelodysplastic syndrome [MDS]). You should discuss with your doctor the risks of developing blood cancers and which tests should be performed. You must not use Tevagrastim if you have or are at risk of developing blood cancers, unless specifically prescribed by your doctor.
If you are a stem cell donor, you must be between 16 and 60 years of age.
Pay special attention to other medicines that stimulate white blood cells
Tevagrastim belongs to a group of medicines that stimulate the production of white blood cells.
Your healthcare provider must always record the exact medicine being used.
Other medicines and Tevagrastim
Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.
Pregnancy and breastfeeding
Tevagrastim has not been studied in pregnant or breastfeeding women.
Tevagrastim is not recommended during pregnancy.
It is important that you inform your doctor if:

you are pregnant or breastfeeding
you suspect you may be pregnant, or
you are planning a pregnancy. If you become pregnant while being treated with Tevagrastim, inform your doctor.

Unless otherwise directed by your doctor, you must stop breastfeeding while using Tevagrastim.
Driving and using machines
Tevagrastim may have a minor influence on the ability to drive and use machines.
This medicine may cause dizziness. It is recommended that you wait and observe how you feel after taking this medicine before driving or operating machinery.
Tevagrastim contains sorbitol
This medicine contains 50 mg of sorbitol per mL.
For intravenous use
Sorbitol is a source of fructose. If you (or your child) have hereditary fructose intolerance (HFI), a rare genetic disorder, you (or your child) must not take this medicine. Patients with HFI are unable to digest fructose, which may lead to serious adverse effects.
You must inform your doctor before taking this medicine if you (or your child) have HFI or if your child can no longer tolerate sugary foods or drinks because they feel unwell, vomit or experience unpleasant effects such as bloating, stomach cramps or diarrhoea.
Tevagrastim contains sodium
This medicine contains less than 1 mmol (23 mg) of sodium per pre-filled syringe, i.e. it is essentially “sodium-free”.

3. How to use Tevagrastim

Use this medicine exactly as directed by your doctor or pharmacist. If you have
any doubts, consult your doctor or pharmacist.
How is Tevagrastim administered and how much should I take?
Tevagrastim is usually given as a daily injection into the tissue just under the skin (known as a subcutaneous injection). It may also be given as a daily slow release injection into the vein (known as intravenous infusion). The usual dose depends on your condition and body weight. Your doctor will tell you how much Tevagrastim you should take.
Patients receiving bone marrow transplantation after chemotherapy:
You will normally receive the first dose of Tevagrastim at least 24 hours after chemotherapy and at least
24 hours after receiving the bone marrow transplant.
You or the people caring for you may be taught how to administer subcutaneous injections so that treatment can continue at home. However, you must not attempt to give yourself an injection unless you have first received appropriate instructions from your doctor.
How long should I take Tevagrastim?
You will need to take Tevagrastim until your white blood cell count has returned to normal. Blood tests will be performed to monitor your white blood cell count. Your doctor will tell you how long you need to take Tevagrastim.
Use in children
Tevagrastim is used to treat children undergoing chemotherapy or suffering from a severe reduction in white blood cells (neutropenia). The dosage in children undergoing chemotherapy is the same as that used in adults.
If you use more Tevagrastim than you should
Do not increase the dose prescribed by your doctor. If you use more Tevagrastim than you should, contact your doctor or pharmacist as soon as possible.
If you forget to use Tevagrastim
If you have missed an injection, or if the injected amount was too small, contact your doctor as soon as possible. Do not take a double dose to make up for a forgotten dose.
If you have any doubts about how to use this medicine, consult your doctor, pharmacist, or nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone gets them.
Important side effects
It is important that you contact your doctor immediately

if you experience an allergic reaction including weakness, drop in blood pressure, breathing difficulties, swelling of the face (anaphylaxis), skin rash, itchy rash (urticaria), swelling of the face, lips, mouth, tongue or throat (angioedema), or shortness of breath (dyspnoea).
if you develop cough, fever and difficulty breathing (dyspnoea), as these may be symptoms of acute respiratory distress syndrome (ARDS).
if kidney damage (glomerulonephritis) occurs. Kidney damage has been observed in patients receiving filgrastim. Contact your doctor immediately if you experience swelling of the face or ankles, blood in the urine, or brown-coloured urine, or if you notice a decrease in the frequency of urination.
if you experience any of the following side effects, or a combination of them:
- swelling or puffiness, which may be associated with less frequent urination, difficulty breathing, abdominal swelling and a feeling of fullness, and a general feeling of tiredness. These symptoms usually develop rapidly. These could be symptoms of a condition called "capillary leak syndrome", which causes blood to leak from small blood vessels into the body and requires urgent medical treatment.
if you experience a combination of the following symptoms:
- fever or chills, or a feeling of intense cold, rapid heart rate, confusion or disorientation, shortness of breath, severe pain or discomfort, and sweaty or clammy skin. These may be symptoms of a condition called "sepsis" (also known as "blood poisoning"), a serious infection with a systemic inflammatory response that can be potentially fatal and requires urgent medical treatment.
if you experience pain in the upper left part of the abdomen (abdominal pain), pain under the left side of the rib cage, or pain at the tip of the shoulder, as this may indicate a problem with the spleen (enlargement of the spleen (splenomegaly) or rupture of the spleen);
if you are being treated for severe chronic neutropenia and have blood in your urine (haematuria). Your doctor may regularly check your urine if this side effect occurs or if protein is found in your urine (proteinuria).

A common side effect associated with the use of Tevagrastim is muscle or bone pain (musculoskeletal pain), which can be relieved by taking common painkillers (analgesics). In patients undergoing stem cell or bone marrow transplantation, graft-versus-host disease (GvHD) may occur: this is a reaction of donor cells against the patient receiving the transplant; signs and symptoms include rash on the palms of the hands or soles of the feet, and ulcers or sores in the mouth, intestine, liver, skin, eyes, lungs, vagina and joints.
In healthy stem cell donors, an increase in white blood cells (leucocytosis) and a decrease in platelet count may occur. A decrease in platelet count reduces the blood's ability to clot (thrombocytopenia). These events will be monitored by your doctor.
The following side effects may occur:
Very common (may affect more than 1 in 10 people):

Decrease in platelets, which reduces the blood's ability to clot (thrombocytopenia)
Low red blood cell count (anaemia)
Headache
Diarrhoea
Vomiting
Nausea
Unusual hair loss or thinning (alopecia)
Tiredness (fatigue)
Pain and swelling of the lining of the digestive tract, from mouth to anus (mucositis)
Fever (pyrexia)

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

Inflammation of the lungs (bronchitis)
Inflammation of the upper respiratory tract
Urinary tract infection
Reduced appetite
Difficulty sleeping (insomnia)
Dizziness
Reduced sensation, particularly of the skin (hypoesthesia)
Tingling or numbness in hands or feet (paraesthesia)
Low blood pressure (hypotension)
High blood pressure (hypertension)
Cough
Coughing up blood (haemoptysis)
Pain in mouth and throat (oropharyngeal pain)
Nosebleeds (epistaxis)
Constipation
Mouth cavity pain
Enlargement of the liver (hepatomegaly)
Skin rash
Redness of the skin (erythema)
Muscle spasm
Pain during urination (dysuria)
Chest pain
Pain
Generalised weakness (asthenia)
General feeling of discomfort (malaise)
Swelling of hands and feet (peripheral oedema)
Increase in certain enzymes in the blood
Changes in blood test values
Transfusion reaction

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

Increase in white blood cells (leucocytosis)
Allergic reaction (hypersensitivity)
Rejection of transplanted bone marrow (graft-versus-host disease)
High levels of uric acid in the blood, which may cause gout (hyperuricaemia) (increased serum uric acid)
Liver damage caused by blockage of small veins within the liver (veno-occlusive disease)
Lungs not functioning properly, causing shortness of breath (respiratory failure)
Swelling and/or fluid in the lungs (pulmonary oedema)
Inflammation of the lungs (interstitial lung disease)
Abnormalities on chest X-ray (pulmonary infiltration)
Bleeding from the lungs (pulmonary haemorrhage)
Lack of oxygen absorption in the lung (hypoxia)
Irregular skin rash (maculopapular rash)
Condition that reduces bone density, making bones weaker, more fragile and prone to fractures (osteoporosis)
Reaction at the injection site

Rare (may affect up to 1 in 1,000 people):

Severe bone, chest, intestinal or joint pain (sickle cell crisis)
Sudden, life-threatening allergic reaction (anaphylactic reaction)
Pain and swelling in the joints, similar to gout (pseudogout)
A change in the regulation of body fluids that may cause swelling (fluid volume alteration)
Inflammation of the skin blood vessels (cutaneous vasculitis)
Purple, raised and painful lesions on limbs, and sometimes on the face and neck, associated with fever (Sweet's syndrome)
Worsening of rheumatoid arthritis
Unusual changes in urine
Reduced bone density
Inflammation of the aorta (the large blood vessel carrying blood from the heart to the rest of the body), see section 2
Formation of blood cells outside the bone marrow (extramedullary haematopoiesis)

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

5. How to store Tevagrastim

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date which is stated on the 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).
During the shelf life and for outpatient use, the medicine may be removed from the refrigerator (2 °C – 8 °C) and stored at a temperature below 25 °C for a single period of up to 4 days. If not used within 4 days, the medicine may be returned to the refrigerator (2 °C – 8 °C) until the expiry date. Syringes stored at temperatures above 8 °C for more than 4 days must be discarded.
Do not use this medicine if you notice that the liquid appears cloudy or contains visible particles.
Do not dispose of any medicine 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 Tevagrastim contains

The active substance is filgrastim. Each mL of injection/infusion solution contains 60 million International Units [IU] (600 micrograms) of filgrastim.
Tevagrastim 30 million IU/0.5 mL: Each pre-filled syringe contains 30 million International Units [IU] (300 micrograms) of filgrastim in 0.5 mL of solution.
Tevagrastim 48 million IU/0.8 mL: Each pre-filled syringe contains 48 million International Units [IU] (480 micrograms) of filgrastim in 0.8 mL of solution.
The other components are: Sodium hydroxide, glacial acetic acid, sorbitol, polysorbate 80, water for injections.

Description of the appearance of Tevagrastim and contents of the pack
Tevagrastim is an injectable/infusion solution contained in a pre-filled syringe.
Tevagrastim is a clear, colourless solution. Each pre-filled syringe contains 0.5 mL or 0.8 mL of solution.
Tevagrastim is available in packs of 1, 5 or 10 pre-filled syringes, or multiple packs of 10 (2 packs of 5) pre-filled syringes with injection needle, with or without needle safety device.
Not all pack sizes may be marketed.

Marketing Authorisation Holder
TEVA GmbH
Graf-Arco-Straße 3
89079 Ulm
Germany

Manufacturer
Merckle GmbH
Graf-Arco-Straße 3
89079 Ulm
Germany

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

België/Belgique/Belgien Lietuva
Teva Pharma Belgium N.V./S.A./AG UAB Teva Baltics
Tél/Tel: +32 38207373 Tel: +370 52660203

България Luxembourg/Luxemburg
Тева Фарма ЕАД Teva Pharma Belgium N.V./S.A./AG
Тел.: +359 24899585 Belgique/Belgien
Tél/Tel: +32 38207373

Česká republika Magyarország
Teva Pharmaceuticals CR, s.r.o. Teva Gyógyszergyár Zrt.
Tel: +420 251007111 Tel.: +36 12886400

Danmark Malta
Teva Denmark A/S Teva Pharmaceuticals Ireland
Tlf.: +45 44985511 L-Irlanda
Tel: +44 2075407117

Deutschland Nederland
TEVA GmbH Teva Nederland B.V.
Tel: +49 73140208 Tel: +31 8000228400

Eesti Norge
UAB Teva Baltics Eesti filiaal Teva Norway AS
Tel: +372 6610801 Tlf: +47 66775590

Ελλάδα Österreich
TEVA HELLAS Α.Ε. ratiopharm Arzneimittel Vertriebs-GmbH
Τηλ: +30 2118805000 Tel: +43 1970070

España Polska
Teva Pharma, S.L.U. Teva Pharmaceuticals Polska Sp. z o.o.
Tel: +34 913873280 Tel.: +48 223459300

France Portugal
Teva Santé Teva Pharma - Produtos Farmacêuticos, Lda.
Tél: +33 155917800 Tel: +351 214767550

Hrvatska România
Pliva Hrvatska d.o.o. Teva Pharmaceuticals S.R.L.
Tel: +385 13720000 Tel: +40 212306524

Ireland Slovenija
Teva Pharmaceuticals Ireland Pliva Ljubljana d.o.o.
Tel: +44 2075407117 Tel: +386 15890390

Ísland Slovenská republika
Teva Pharma Iceland ehf. TEVA Pharmaceuticals Slovakia s.r.o.
Sími: +354 5503300 Tel: +421 257267911

Italia Suomi/Finland
Teva Italia S.r.l. Teva Finland Oy
Tel: +39 028917981 Puh/Tel: +358 201805900

Κύπρος Sverige
TEVA HELLAS Α.Ε. Teva Sweden AB
Ελλάδα Tel: +46 42121100
Τηλ: +30 2118805000

Latvija United Kingdom (Northern Ireland)
UAB Teva Baltics filiāle Latvijā Teva Pharmaceuticals Ireland
Tel: +371 67323666 Ireland
Tel: +44 2075407117

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

7. Instructions for Performing Self-Injection

This section contains the information necessary to perform a self-injection of Tevagrastim.
It is important that you do not attempt to administer the injection yourself without first receiving proper instructions from your doctor or nurse. If you have any doubts about how to perform the injection or would like further information, please consult your doctor or pharmacist.
It is important that you dispose of used syringes in a special puncture-resistant container.
How to Perform a Self-Injection of Tevagrastim
The injection must be administered into the tissue beneath the skin; this method is known as a subcutaneous injection. You should administer the injection at approximately the same time each day.
Equipment Required
To perform a subcutaneous injection, you will need:

a pre-filled syringe of Tevagrastim;
an alcohol swab or equivalent disinfectant;
a puncture-resistant sharps container (a plastic container provided by the hospital or pharmacy) to safely dispose of the used syringe.

What to Do Before Performing a Subcutaneous Self-Injection of Tevagrastim

Try to inject the medication at approximately the same time each day.
Remove the pre-filled syringe of Tevagrastim from the refrigerator.
Check the expiration date (Exp.) printed on the label of the pre-filled syringe. Do not use the syringe if the date is beyond the last day of the month indicated.
Check the appearance of Tevagrastim. It should appear as a clear, transparent liquid. If you notice any particles in the solution, do not use the syringe.
To make the injection more comfortable, remove the pre-filled syringe from the refrigerator and allow it to sit at room temperature for 30 minutes, or gently hold it in your hands for several minutes. Do not heat Tevagrastim in any other way (e.g., using a microwave or hot water).
Do not remove the syringe cap until immediately before injection.
Wash your hands thoroughly.
Find a comfortable, well-lit place and arrange all necessary supplies within easy reach (the pre-filled syringe of Tevagrastim, the alcohol swab, and the puncture-resistant container).

How to Prepare the Tevagrastim Injection
Before administering the Tevagrastim injection, follow these steps:

Hold the syringe with both hands and gently remove the needle cap by pulling horizontally, without twisting, as shown in figures 1 and 2. Do not touch the needle and do not push the plunger.

Two hands hold a syringe horizontally with black arrows indicating a sliding motion to the right and to the left

Two hands holding a syringe and a cap for

1 2

You may notice a small air bubble in the pre-filled syringe. If air bubbles are present, gently tap the syringe with your fingers until the air bubbles rise to the top. With the syringe held upright, expel the air by pushing the plunger upward.
The syringe is marked with a graduated scale. Push the plunger to the number (mL) on the syringe that corresponds to the prescribed dose of Tevagrastim.
Double-check to ensure the syringe contains the correct dose of Tevagrastim.
The pre-filled syringe is now ready for use.

Where to Administer the Injection
The most suitable body areas for injection are:

the upper thighs; and
the abdomen, except the area around the navel (see figure 3).

Schematic human body highlighting in gray the abdominal areas and upper thighs for

Schematic drawing of a man's back with two gray areas indicating drug injection sites on the upper arms

3 4
If the injection is administered by another person, the medication may also be injected into the back of the upper arms (see figure 4).
It is advisable to change the injection site daily to reduce the risk of skin hardening at the injection site.
How to Administer the Injection

Disinfect the injection site using an alcohol swab and pinch the skin between your thumb and index finger, without compressing it (see figure 5).
Insert the needle completely into the skin, as demonstrated by your nurse or doctor (see figure 6).
Slowly pull back on the plunger to check whether a blood vessel has been punctured. If you see blood in the syringe, remove the needle from the skin and insert it into another area.
Inject the liquid slowly and steadily, continuing to hold the skin pinched.
Inject only the dose prescribed by your doctor.
After injecting the liquid, remove the needle and release the skin.
Use a new syringe for each injection. Do not reuse any remaining Tevagrastim in the syringe.

One hand holds a syringe and inserts the

Line drawing of a hand gently pressing on the skin of the

5 6
Reminder
If you have any doubts or problems, do not hesitate to contact your doctor or nurse for help or advice.
Disposal of Used Syringes

Do not recap used needles.
Place used syringes into the puncture-resistant sharps container and store the container out of sight and reach of children.
To dispose of a full puncture-resistant container, follow the instructions provided by your doctor, nurse, or pharmacist.
Never throw used syringes into regular household waste containers.

8. The following information is intended exclusively for healthcare professionals

Tevagrastim does not contain preservatives. To avoid potential risks of microbial contamination, Tevagrastim syringes are for single use only.
Accidental exposure to freezing temperatures does not have a negative effect on the stability of Tevagrastim.
Tevagrastim must 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 onto glass and plastic materials unless diluted as specified below.
If necessary, Tevagrastim may be diluted in 50 mg/mL (5%) glucose solution for infusion.
Final dilution concentrations below 0.2 MUI (2 μg) per mL are not recommended under any circumstances. The solution must be inspected visually before use. Only clear solutions without visible particles should be used. In patients treated with diluted filgrastim at concentrations below 1.5 MUI (15 μg) per mL, human serum albumin (HSA) must be added to a final concentration of 2 mg/mL. Example: In a final injection volume of 20 mL, total filgrastim doses below 30 MUI (300 μg) must be administered with the addition of 0.2 mL of human serum albumin at 200 mg/mL (20%). When diluted in 50 mg/mL (5%) glucose solution for infusion, Tevagrastim is compatible with glass and numerous plastic materials, including PVC, polyolefin (a copolymer of polypropylene and polyethylene), and polypropylene.
After dilution: The chemical and physical in-use stability of the diluted infusion solution has been demonstrated for 24 hours at temperatures between 2 °C and 8 °C. From a microbiological standpoint, the product should be used immediately. Otherwise, the duration and conditions of storage are the responsibility of the user and must not exceed 24 hours between 2 °C and 8 °C, unless the solution has been prepared under controlled and validated aseptic conditions.
Use of the pre-filled syringe without needle safety device
Administer the dose according to standard procedure.
Disposal
Unused medicinal product and waste materials derived from its use must be disposed of in accordance with local regulations.

Package leaflet: Information for the user

Tevagrastim 30 MUI/0.5 mL solution for injection/infusion, 48 MUI/0.8 mL solution for injection/infusion

filgrastim
Please read this leaflet carefully before using this medicine as it contains important information for you.

Keep this leaflet. You may need to read it again.
If you have any questions, ask your doctor, pharmacist, or nurse.
This medicine has been prescribed for you only. Do not give it to others, even if their symptoms are the same as yours, as it may be harmful.
If you experience any adverse reactions, including those not listed in this leaflet, contact your doctor, pharmacist, or nurse. See section 4.

Contents of this leaflet:

What Tevagrastim is and what it is used for
What you need to know before using Tevagrastim
How to use Tevagrastim
Possible side effects
How to store Tevagrastim
Contents of the pack and other information
Instructions for self-injection
The following information is intended exclusively for healthcare professionals

1. What Tevagrastim is and what it is used for

What Tevagrastim is
Tevagrastim is a white blood cell growth factor (granulocyte colony-stimulating factor) and belongs to a group of medicines called cytokines. Growth factors are proteins naturally produced in the body, but they can also be produced using biotechnology for use as medicines. Tevagrastim stimulates the bone marrow to produce a greater number of white blood cells.

Tevagrastim may be used:

to increase the number of white blood cells after chemotherapy treatment, thereby helping to prevent infections;
to increase the number of white blood cells after a bone marrow transplant, thereby helping to prevent infections;
prior to high-dose chemotherapy to stimulate the bone marrow to produce more stem cells, which can be collected and reinfused after treatment. These cells may be collected from you or from a donor. The stem cells will then return to the bone marrow and produce blood cells;
to increase the number of white blood cells if you have severe chronic neutropenia, thereby helping to prevent infections;
in patients with advanced HIV infection, to help reduce the risk of infections.

2. What you need to know before using Tevagrastim

Do not use Tevagrastim

if you are allergic to filgrastim or to any of the other ingredients of this medicine (listed in section 6).

Warnings and precautions
Talk to your doctor, pharmacist, or nurse before using Tevagrastim.
Inform your doctor before starting treatment if you have:

sickle cell anaemia, as Tevagrastim may trigger sickle cell crises.
osteoporosis (a bone disease).

Contact your doctor immediately during treatment with Tevagrastim if:

you experience sudden signs of allergy such as rash, itching or hives on the skin, swelling of the face, lips, tongue or other parts of the body, shortness of breath or difficulty breathing, as these may be signs of a serious allergic reaction (hypersensitivity).
you develop swelling of the face or ankles, blood in the urine, brown-coloured urine, or notice that you are urinating less than usual (glomerulonephritis).
you feel pain in the upper left part of the abdomen (abdominal pain), pain under the left side of the ribcage, or pain at the tip of the left shoulder (these may be symptoms of an enlarged spleen (splenomegaly) or possible spleen rupture).
you notice unusual bleeding or bruising (these may be symptoms of a reduced platelet count (thrombocytopenia), leading to decreased blood clotting ability).
you experience symptoms of inflammation of the aorta (the large blood vessel carrying blood from the heart to the rest of the body), which has been reported rarely in cancer patients and healthy individuals. Symptoms may include fever, abdominal pain, malaise, back pain, and increased markers of inflammation. Inform your doctor if such symptoms occur.

Loss of response to filgrastim
If you experience a decreased response or failure to maintain response to treatment with filgrastim, your doctor will investigate possible causes, including the possibility that you have developed antibodies that neutralize the activity of filgrastim.
Your doctor may decide to monitor you closely; see section 4 of the package leaflet.
If you are a patient with severe chronic neutropenia, you may be at risk of developing a blood cancer (leukaemia, myelodysplastic syndrome [MDS]). You should discuss with your doctor the risks of developing blood cancers and which tests should be performed. If you have or are at risk of developing blood cancers, you must not use Tevagrastim unless prescribed by your doctor.
If you are a stem cell donor, you must be between 16 and 60 years of age.
Pay special attention to other medicines that stimulate white blood cells
Tevagrastim belongs to a group of medicines that stimulate the production of white blood cells.
Healthcare professionals must always record the exact medicine being used.
Other medicines and Tevagrastim
Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.
Pregnancy and breastfeeding
Tevagrastim has not been studied in pregnant or breastfeeding women.
Tevagrastim is not recommended during pregnancy.
It is important that you inform your doctor if:

you are pregnant or breastfeeding,
you suspect you may be pregnant, or
you are planning a pregnancy. If you become pregnant while being treated with Tevagrastim, inform your doctor.

Unless otherwise instructed by your doctor, you must stop breastfeeding while using Tevagrastim.
Driving and using machines
Tevagrastim may have a minor effect on the ability to drive and use machines. This medicine may cause dizziness. It is recommended that you wait and observe how you feel after taking this medicine before driving or operating machinery.
Tevagrastim contains sorbitol
This medicine contains 50 mg of sorbitol per mL.
For intravenous use
Sorbitol is a source of fructose. If you (or your child) have hereditary fructose intolerance (HFI), a rare genetic disorder, you (or your child) must not take this medicine. Patients with HFI are unable to digest fructose, which may lead to serious adverse effects.
You must inform your doctor before taking this medicine if you (or your child) have HFI or if your child can no longer consume sugary foods or drinks because they feel unwell, vomit, or experience unpleasant effects such as bloating, stomach cramps, or diarrhoea.
Tevagrastim contains sodium
This medicine contains less than 1 mmol (23 mg) of sodium per pre-filled syringe, i.e. it is essentially "sodium-free".

3. How to use Tevagrastim

Use this medicine exactly as instructed by your doctor or pharmacist. If you have
any doubts, consult your doctor or pharmacist.
How is Tevagrastim administered and how much should I take?
Tevagrastim is usually given as a daily injection into the tissue just beneath the skin (known as a subcutaneous injection). It may also be given as a daily slow injection into the vein (known as intravenous infusion). The usual dose depends on your condition and body weight. Your doctor will tell you how much Tevagrastim you should take.
Patients receiving bone marrow transplantation after chemotherapy:
You will normally receive your first dose of Tevagrastim at least 24 hours after chemotherapy and at least
24 hours after receiving the bone marrow transplant.
You or the people caring for you may be taught how to administer the subcutaneous injections so that treatment can continue at home. However, you must not attempt to inject yourself unless you have first received appropriate instructions from your doctor.
How long should I take Tevagrastim?
You will need to take Tevagrastim until your white blood cell count has returned to normal. Blood tests will be performed to monitor your white blood cell count. Your doctor will tell you how long you need to continue taking Tevagrastim.
Use in children
Tevagrastim is used to treat children undergoing chemotherapy or suffering from a severe reduction in white blood cells (neutropenia). The dosage in children undergoing chemotherapy is the same as that used in adults.
If you use more Tevagrastim than you should
Do not increase the dose prescribed by your doctor. If you use more Tevagrastim than you should, contact your doctor or pharmacist as soon as possible.
If you forget to use Tevagrastim
If you have missed an injection, or if the injected amount was too low, contact your doctor as soon as possible. Do not take a double dose to make up for a forgotten dose.
If you have any questions about the use of this medicine, ask your doctor, pharmacist, or nurse.

4. Possible side effects

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

Important side effects
It is important that you contact your doctor immediately

if you experience an allergic reaction including weakness, drop in blood pressure, breathing difficulties, swelling of the face (anaphylaxis), rash, itchy skin rash (urticaria), swelling of the face, lips, mouth, tongue or throat (angioedema), and shortness of breath (dyspnoea).
if you develop cough, fever and difficulty breathing (dyspnoea), as these may be symptoms of acute respiratory distress syndrome (ARDS).
if kidney damage (glomerulonephritis) occurs. Kidney damage has been observed in patients receiving filgrastim. Contact your doctor immediately if you experience swelling of the face or ankles, blood in the urine, brown-coloured urine, or a decrease in the frequency of urination.
if you experience any of the following side effects, or a combination of them:
- swelling or puffiness, which may be associated with less frequent urination, difficulty breathing, abdominal swelling and a feeling of fullness, and a general feeling of tiredness. These symptoms usually develop rapidly. They could be symptoms of a condition called "capillary leak syndrome", which causes blood to leak from small blood vessels into the body and requires urgent medical treatment.
if you experience a combination of the following symptoms:
- fever or chills, or a feeling of intense cold, rapid heartbeat, confusion or disorientation, shortness of breath, severe pain or discomfort, and sweaty or clammy skin. These may be symptoms of a condition called "sepsis" (also known as "blood poisoning"), a serious infection with a systemic inflammatory response that can be potentially fatal and requires urgent medical treatment.
if you experience pain in the upper left part of the abdomen (abdominal pain), pain under the left side of the rib cage, or shoulder tip pain, as this may indicate a problem with the spleen (enlargement of the spleen (splenomegaly) or rupture of the spleen);
if you are being treated for severe chronic neutropenia and have blood in your urine (haematuria). Your doctor may regularly check your urine if this side effect occurs or if protein is found in your urine (proteinuria).

A common side effect associated with the use of Tevagrastim is muscle or bone pain (musculoskeletal pain), which can be relieved by taking common painkillers (analgesics). In patients undergoing stem cell or bone marrow transplantation, graft-versus-host disease (GvHD) may occur: this is a reaction of donor cells against the patient receiving the transplant; signs and symptoms include rash on the palms of the hands or soles of the feet and ulcers or sores in the mouth, intestines, liver, skin or eyes, lungs, vagina and joints.
In healthy stem cell donors, an increase in white blood cells (leucocytosis) and a decrease in platelet count may occur. A decrease in platelet count reduces the blood's ability to clot (thrombocytopenia). These events will be monitored by your doctor.

The following side effects may occur:

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

Decrease in platelets, reducing the blood's ability to clot (thrombocytopenia)
Low red blood cell count (anaemia)
Headache
Diarrhoea
Vomiting
Nausea
Unusual hair loss or thinning (alopecia)
Tiredness (fatigue)
Pain and swelling of the lining of the digestive tract, from mouth to anus (mucositis)
Fever (pyrexia)

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

Inflammation of the lungs (bronchitis)
Inflammation of the upper respiratory tract
Urinary tract infection
Reduced appetite
Difficulty sleeping (insomnia)
Dizziness
Reduced sensation, particularly of the skin (hypoesthesia)
Tingling or numbness of hands or feet (paraesthesia)
Low blood pressure (hypotension)
High blood pressure (hypertension)
Cough
Coughing up blood (haemoptysis)
Pain in mouth and throat (oropharyngeal pain)
Nosebleeds (epistaxis)
Constipation
Mouth pain
Enlargement of the liver (hepatomegaly)
Rash
Redness of the skin (erythema)
Muscle spasm
Pain during urination (dysuria)
Chest pain
Pain
Generalised weakness (asthenia)
Feeling of general discomfort (malaise)
Swelling of hands and feet (peripheral oedema)
Increase in certain enzymes in the blood
Changes in blood chemistry values
Transfusion reaction

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

Increase in white blood cells (leucocytosis)
Allergic reaction (hypersensitivity)
Rejection of transplanted bone marrow (graft-versus-host disease)
High levels of uric acid in the blood, which may cause gout (hyperuricaemia) (increased blood uric acid)
Liver damage caused by blockage of small veins within the liver (veno-occlusive disease)
Lungs not functioning properly, causing shortness of breath (respiratory failure)
Swelling and/or fluid in the lungs (pulmonary oedema)
Inflammation of the lungs (interstitial lung disease)
Abnormalities on chest X-ray (pulmonary infiltration)
Bleeding from the lungs (pulmonary haemorrhage)
Impaired oxygen uptake in the lungs (hypoxia)
Irregular skin rash (maculopapular rash)
Disease that reduces bone density, making bones weaker, more fragile and prone to fractures (osteoporosis)
Reaction at injection site

Rare (may affect up to 1 in 1,000 people):

Severe bone, chest, intestinal or joint pain (sickle cell crisis)
Sudden, life-threatening allergic reaction (anaphylactic reaction)
Pain and swelling of the joints, similar to gout (pseudogout)
A change in fluid regulation in the body that may cause swelling (fluid volume disturbance)
Inflammation of blood vessels in the skin (cutaneous vasculitis)
Purple, raised and painful lesions on limbs, and sometimes on face and neck, associated with fever (Sweet's syndrome)
Worsening of rheumatoid arthritis
Unusual changes in urine
Reduced bone density
Inflammation of the aorta (the large blood vessel carrying blood from the heart to the rest of the body), see section 2
Formation of blood cells outside the bone marrow (extramedullary haematopoiesis)

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor, pharmacist or nurse. 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 Tevagrastim

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the 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).
During the shelf life and for outpatient use, the medicine may be removed from the refrigerator (2 °C – 8 °C) and stored at temperatures below 25 °C for a single period of up to 4 days. If not used within 4 days, the medicine may be returned to the refrigerator (2 °C – 8 °C) and kept until the expiry date. Syringes stored at temperatures above 8 °C for more than 4 days must be discarded.
Do not use this medicine if you notice that the solution appears cloudy or contains visible particles.
Do not dispose of medicines via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What Tevagrastim contains

The active substance is filgrastim. Each mL of injection/infusion solution contains 60 million international units [IU] (600 micrograms) of filgrastim.
Tevagrastim 30 MIU/0.5 mL: Each pre-filled syringe contains 30 million international units [IU] (300 micrograms) of filgrastim in 0.5 mL of solution.
Tevagrastim 48 MIU/0.8 mL: Each pre-filled syringe contains 48 million international units [IU] (480 micrograms) of filgrastim in 0.8 mL of solution.
The other components are: Sodium hydroxide, glacial acetic acid, sorbitol, polysorbate 80, water for injections.

Description of the appearance of Tevagrastim and contents of the pack
Tevagrastim is an injectable/infusion solution contained in a pre-filled syringe.
Tevagrastim is a clear, colourless solution. Each pre-filled syringe contains 0.5 mL or 0.8 mL of solution.
Tevagrastim is available in packs of 1, 5 or 10 pre-filled syringes, or multiple packs of 10 (2 packs of 5) pre-filled syringes with injection needles, with or without needle safety devices.
Not all pack sizes may be marketed.

Marketing Authorisation Holder
TEVA GmbH
Graf-Arco-Straße 3
89079 Ulm
Germany

Manufacturer
Merckle GmbH
Graf-Arco-Straße 3
89079 Ulm
Germany

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