Package leaflet: Information for the user

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

1. What Ratiograstim is and what it is used for

What Ratiograstim is
Ratiograstim 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. Ratiograstim stimulates the bone marrow to produce a greater number of white blood cells.
What Ratiograstim 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. Ratiograstim stimulates the bone marrow to rapidly produce new white blood cells.
Ratiograstim 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 induce the bone marrow to produce more stem cells, which can be collected and reinfused after treatment. These cells may be taken 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 chronic severe 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 Ratiograstim

Do not use Ratiograstim

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 Ratiograstim.
Inform your doctor before starting treatment if you have:

sickle cell anemia, as Ratiograstim may trigger sickle cell crises.
osteoporosis (bone disease)

Contact your doctor immediately during treatment with Ratiograstim 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 are signs of a severe allergic reaction (hypersensitivity).
you develop swelling of the face or ankles, blood in the urine or brown-colored urine, or notice that you are urinating less than usual (glomerulonephritis).
you experience pain in the upper left part of the abdomen (abdominal pain), pain under the left side of the rib cage or 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), resulting in decreased blood clotting ability).
you develop symptoms of inflammation of the aorta (the large blood vessel carrying blood from the heart to the rest of the body), which has been rarely reported in cancer patients and healthy individuals. Symptoms may include fever, abdominal pain, malaise, back pain, and elevated 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 (leukemia, myelodysplastic syndrome [MDS]). You should discuss with your doctor the risks of developing blood cancers and which tests should be performed. If you have developed or are at risk of developing blood cancers, you must not use Ratiograstim unless prescribed by your doctor.
If you are a stem cell donor, you must be between 16 and 60 years of age.
Pay particular attention to other medicines that stimulate white blood cells
Ratiograstim 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 Ratiograstim
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.
Pregnancy and breastfeeding
Ratiograstim has not been studied in pregnant or breastfeeding women.
Ratiograstim 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 Ratiograstim, inform your doctor. Unless otherwise instructed by your doctor, you must stop breastfeeding while using Ratiograstim.

Driving and using machines
Ratiograstim may slightly affect the ability to drive or use machinery. This medicine may cause dizziness. It is recommended to wait and observe how you feel after taking this medicine before driving or operating machinery.
Ratiograstim 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 foods or drinks containing sugar because they feel unwell, vomit, or experience unpleasant effects such as bloating, stomach cramps, or diarrhea.
Ratiograstim 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 Ratiograstim

Use this medicine exactly as instructed by your doctor or pharmacist. If you have
any doubts, consult your doctor or pharmacist.
How is Ratiograstim administered and how much should I take?
Ratiograstim is generally administered 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-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 Ratiograstim to take.
Patients receiving bone marrow transplantation after chemotherapy:
You will usually receive the first dose of Ratiograstim 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 self-inject unless you have first received appropriate instruction from your doctor.
How long will I have to take Ratiograstim?
You will need to take Ratiograstim until your white blood cell count has returned to normal.
Blood tests will be performed to monitor the number of white blood cells in your blood.
Your doctor will tell you how long you need to take Ratiograstim.
Use in children
Ratiograstim is used to treat children undergoing chemotherapy or who suffer from a
severe reduction in the number of white blood cells in the blood (neutropenia). The dosage in children undergoing chemotherapy is the same as that used in adults.
If you use more Ratiograstim than you should
Do not increase the dose prescribed by your doctor. If you use more Ratiograstim than you should, contact your doctor or pharmacist as soon as possible.
If you forget to use Ratiograstim
If you have forgotten 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 missed 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 everybody gets them.

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

if you experience an allergic reaction including weakness, low 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, brown-coloured urine, or if you notice a reduction 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 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 life-threatening 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 (splenomegalia) 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 has been found in your urine (proteinuria).

A common side effect associated with the use of Ratiograstim 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 be observed. 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 (mucosal inflammation)
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 alteration)
Inflammation of blood vessels in the skin (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 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 Ratiograstim

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. Pre-filled 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. Pack contents and other information

What Ratiograstim contains

The active substance is filgrastim. Each mL of injection/infusion solution contains 60 million international units [IU] (600 micrograms) of filgrastim.
Ratiograstim 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.
Ratiograstim 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 Ratiograstim and contents of the pack
Ratiograstim is an injectable/infusion solution contained in a pre-filled syringe, with or without a safety device.
Ratiograstim is a clear, colourless solution. Each pre-filled syringe contains 0.5 mL or 0.8 mL of solution.
Ratiograstim is available in packs of 1, 5 or 10 pre-filled syringes, or multiple packs of 10 (2 packs of 5) pre-filled syringes.
Not all pack sizes may be marketed.

Marketing Authorisation Holder
ratiopharm 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:

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 ratiopharm GmbH
Teл.: +359 24899585 Allemagne/Deutschland
Tél/Tel: +49 73140202

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
ratiopharm GmbH Teva Nederland B.V.
Tel: +49 73140202 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
Laboratoires Biogaran ratiopharm - Comércio e Indústria de Produtos
Tél: +33 800970109 Farmacêuticos, Lda.
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 European Medicines Agency website: https://www.ema.europa.eu.

7. Instructions for performing self-injection

This section contains the information needed to perform a self-injection of Ratiograstim.
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-proof container.

How to perform a Ratiograstim self-injection
The injection must be administered into the tissue beneath the skin; this method is known as a subcutaneous injection. You should perform the injection at approximately the same time each day.

Equipment required
To administer a subcutaneous injection, you will need:

a pre-filled Ratiograstim syringe;
an alcohol swab or equivalent disinfectant;
a puncture-proof container (a plastic container provided by the hospital or pharmacy) for the safe disposal of used syringes.

What to do before performing a Ratiograstim self-injection

Try to inject the medicine at approximately the same time each day.
Remove the pre-filled Ratiograstim syringe from the refrigerator.
Check the expiry date (Exp.) printed on the label of the pre-filled syringe. Do not use the syringe if the date exceeds the last day of the month indicated.
Check the appearance of Ratiograstim. It should appear as a clear, transparent liquid. If you notice any particles, do not use the syringe.
To make the injection more comfortable, remove the pre-filled syringe from the refrigerator and allow it to warm to room temperature for 30 minutes, or gently hold it in your hand for several minutes. Do not heat Ratiograstim 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 Ratiograstim syringe, the alcohol swab, and the puncture-proof container).

How to prepare the Ratiograstim injection
Before administering the Ratiograstim injection, proceed as follows:

Hold the syringe with both hands and gently remove the needle cap straight off, without twisting. Pull horizontally, as shown in figures 1 and 2. Do not touch the needle or push the plunger.

Technical drawing showing two hands preparing a syringe and a human body with gray areas indicating injection sites on the body

Two hands holding a syringe horizontally with black arrows indicating a sliding or pressing motion towards the body

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 bubbles rise to the surface and move toward the top of the syringe. 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 Ratiograstim.
Double-check to ensure the syringe contains the correct dose of Ratiograstim.
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).

Linear diagram of the torso and arms of a man viewed from the back, with two gray areas indicating injection sites on the arms

3 4
If another person administers the injection, the medicine may also be injected into the back of the upper arms (see figure 4).
It is advisable to change the injection site each day to reduce the risk of hardening at the injection site.

How to perform the injection

Disinfect the skin 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 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 again in a different area.
Inject the liquid slowly and steadily, keeping 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 Ratiograstim remaining in the syringe.

A hand holding a syringe to inject medication into the body at an angle greater than or equal to 45 degrees

Black line drawing showing a hand pressing with the thumb on the skin of the abdomen

5 6

Remember
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-proof container and keep the container out of sight and reach of children.
To dispose of a full puncture-proof container, follow the instructions provided by your doctor, nurse, or pharmacist.
Never throw used syringes into regular household waste bins.

8. The following information is intended exclusively for healthcare professionals

Ratiograstim does not contain preservatives. To avoid potential risks of microbial contamination, Ratiograstim syringes are for single use only.
Accidental exposure to freezing temperatures does not have a negative effect on the stability of Ratiograstim.
Ratiograstim 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, Ratiograstim can be diluted in 50 mg/mL (5%) glucose solution for infusion.
Under no circumstances is dilution to a final concentration below 0.2 MIU (2 μg) per mL recommended. The solution should be inspected visually before use. Only clear solutions without visible particles should be used. In the case of patients treated with diluted filgrastim at concentrations below 1.5 MIU (15 μg) 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 filgrastim doses below 30 MIU (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, Ratiograstim 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 at temperatures between 2 °C and 8 °C, unless the solution has been prepared under controlled and validated aseptic conditions.

Package leaflet: Information for the user

Ratiograstim 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 side effects, including those not listed in this leaflet, tell your doctor, pharmacist, or nurse. See section 4.

Contents of this leaflet:

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

1. What Ratiograstim is and what it is used for

What Ratiograstim is used for
A reduced number of white blood cells (neutropenia) may occur for various reasons, decreasing the body's ability to defend itself against infections. Ratiograstim stimulates the bone marrow to rapidly produce new white blood cells.

Ratiograstim 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 in patients with 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 Ratiograstim

Do not use Ratiograstim

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 Ratiograstim.
Tell your doctor before starting treatment if you have:

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

Contact your doctor immediately during treatment with Ratiograstim 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 or 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 rib cage, 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 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 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 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 Ratiograstim 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
Ratiograstim 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 Ratiograstim
Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.

Pregnancy and breastfeeding
Ratiograstim has not been studied in pregnant or breastfeeding women.
Ratiograstim is not recommended during pregnancy.
It is important that you inform your doctor if:

you are pregnant or breastfeeding
you suspect you might be pregnant, or
you are planning a pregnancy. If you become pregnant while being treated with Ratiograstim, inform your doctor. Unless otherwise instructed by your doctor, you must stop breastfeeding if you are using Ratiograstim.

Driving and using machines
Ratiograstim may have a slight influence on the ability to drive vehicles and use machinery. 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.

Ratiograstim 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.

Ratiograstim contains sodium
This medicine contains less than 1 mmol (23 mg) of sodium per pre-filled syringe, i.e. it is essentially "sodium-free".