30 MIU / 0.5 ml, 48 MIU / 0.8 ml solution for injection / infusion
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 that are produced naturally in the body, but they can also be produced through biotechnology for use as medicines. Ratiograstim works by stimulating the bone marrow to produce more white blood cells.
What Ratiograstim is used for
The number of white blood cells can be low ( neutropenia ) for various reasons and this makes it harder for the body to fight infection. Ratiograstim stimulates the bone marrow to rapidly produce new white blood cells.
Ratiograstim can be used for the following:
- To increase the number of white blood cells after treatment with chemotherapy to help prevent infection.
- To increase the number of white blood cells after bone marrow transplantation to help prevent infection.
- Before chemotherapy in high doses you to make so that the bone marrow produces more stem cells that can be collected and given back to you after the treatment. The stem cells can be taken from you or a donor. They are then returned to the bone marrow where they produce blood cells.
- To increase the number of white blood cells if you suffer from severe chronic neutropenia, to help prevent infection.
- To patients with advanced HIV infection, to help reduce the risk of infection.
What you need to know before you use Ratiograstim
Do not use Ratiograstim
- if you are allergic to filgrastim or any of the other ingredients of this medicine (listed in section 6).
Warnings and cautions
Talk to your doctor, pharmacist, or nurse before using Ratiograstim.
Tell your doctor before starting treatment if you have any
- sickle cell anemia, as this medicine may cause sickle cell crisis
- osteoporosis (osteoporosis).
Tell your doctor immediately during treatment with Ratiograstim, if you
- suffer from sudden signs of allergy, such as rash, itching or hives, swelling of the face, lips, tongue, or other body parts, shortness of breath, wheezing, or difficulty breathing as these may be signs of a severe allergic reaction (hypersensitivity).
- suffer from swelling of the face or ankles, blood in the urine or brown urine, or if you find that you urinate less than usual ( glomerulonephritis ).
- gets pain in the upper left part of the abdomen, below the ribs on the left side, or at the tip of the left shoulder blade (this may be a symptom of an enlarged spleen (so-called splenomegaly ) or possibly a broken spleen ).
- bleeds or bruises unusually easily (there may be symptoms of low platelet count ( thrombocytopenia ), which causes the blood not to coagulate properly).
- Inflammation of the aorta (the large blood vessel that transports blood from the heart to the body) has been reported with the frequency “rare” in cancer patients and healthy donors. Symptoms may include fever, abdominal pain, malaise, back pain, and increased inflammatory markers. Tell your doctor if you experience these symptoms.
Unsatisfactory treatment response
If you respond less or stop responding to filgrastim treatment, your doctor will investigate what is causing this. Among other things, your doctor will check if you have developed antibodies that neutralize the activity of filgrastim.
Your doctor may want to monitor you closely, see section 4 of this leaflet.
If you are a patient and have severe chronic neutropenia, there may be a risk of developing blood cancer ( leukemia, myelodysplastic syndrome (MDS)). Talk to your doctor about the risks of getting cancer in the blood and what tests should be done. If you get cancer or there is a chance that you may get blood cancer, do not use Ratiograstim unless your doctor tells you to.
If you are a stem cell donor, you must be between 16 and 60 years old.
Take special care with other medicines that stimulate the white blood cells
Ratiograstim belongs to a group of medicines that stimulate the production of white blood cells. The healthcare staff must always note in the medical record exactly which medicine you are using.
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 lactating women.
Ratiograstim is not recommended during pregnancy.
You must tell your doctor if you:
- is pregnant or breastfeeding
- think you may be pregnant, or
- plans to have children.
Tell your doctor if you become pregnant while you are being treated with Ratiograstim. Unless your doctor tells you otherwise, stop breastfeeding if you are using Ratiograstim.
Driving and using machines
Ratiograstim may have less effect on the ability to drive and use machines. This medicine may cause dizziness. You should wait and see how you feel after using this medicine, before driving or using machines.
Ratiograstim contains sorbitol and sodium
Ratiograstim contains sorbitol
This medicine contains 50 mg of sorbitol per ml.
Sorbitol is a source of fructose. If you (or your child) have hereditary fructose intolerance, a rare, inherited disease, you (or your child) should not use this medicine. Patients with hereditary fructose intolerance can not break down fructose, which can cause serious side effects. Talk to your doctor before using this medicine if you (or your child) have hereditary fructose intolerance, or if your child can no longer eat sweet food or drink without feeling sick, vomiting, or feeling uncomfortable such as bloating stomach cramps, or diarrhea.
Ratiograstim contains sodium
This medicine contains less than 1 mmol sodium (23 mg) per pre-filled syringe, ie essentially ‘sodium-free’.
How to use Ratiograstim
Always use this medicine exactly as your doctor or pharmacist has told you. Ask your doctor or pharmacist if you are unsure.
How do I get Ratiograstim and how big is dose one?
Ratiograstim is usually given as a daily injection into the tissue just under the skin (a so-called subcutaneous injection ). It can also be given as a daily, slow injection into a vein (a so-called intravenous infusion ). How much doget depends on your illness and your weight? Your doctor will tell you how much Ratiograstim to take.
Patients undergoing bone marrow transplantation after chemotherapy:
In normal cases, you will receive the first dose of Ratiograstim at least 24 hours after the chemotherapy treatment and at least 24 hours after receiving your bone marrow transplant.
You, or the people who take care of you, can teach you how to give your subcutaneous injection so that you can continue your treatment at home. However, you should not try this yourself if you have not received enough instruction first from your healthcare provider.
How long do I need to take Ratiograstim?
You will need to take Ratiograstim until your white blood cell count is normal. Blood samples will be taken regularly to check the number of white blood cells in your body. Your doctor will tell you how long you need to take Ratiograstim.
Use for children
Ratiograstim is used to treat children who are receiving chemotherapy or who have low white blood cell count ( neutropenia ). The dosage for children receiving chemotherapy is the same as for adults.
If you use more Ratiograstim than you should
Do not increase the dose as 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 missed an injection, or have injected too little, contact your doctor as soon as possible. Do not take a double dose to make up for a forgotten dose.
If you have any further questions on the use of this product, ask your doctor, pharmacist, or nurse.
Possible side effects
Like all medicines, this medicine can cause side effects, although not everybody gets them.
Important side effects are
You must tell your doctor immediately
- If you get an allergic reaction with weakness, drop in blood pressure, difficulty breathing, swelling of the face ( anaphylaxis ), skin rash, itchy rash ( hives ), swelling of the face, lips, mouth, tongue, or throat ( angioedema ) and shortness of breath ( dyspnoea ).
- If you get a cough, fever, and difficulty breathing ( dyspnoea ). This may be a sign of acute respiratory distress syndrome (ARDS).
- If you get kidney damage ( glomerulonephritis ). Kidney damage has been observed in patients receiving filgrastim. Contact your doctor immediately if you get swollen in the face or around the ankles, get blood in the urine or brown urine, or notice that you do not urinate as often as usual.
- If you get any of the following side effects: Swelling or fluid retention, which may be associated with urination more infrequently than usual, difficulty breathing, swollen abdomen and a feeling of satiety, and a general feeling of tiredness. These symptoms often develop at a rapid rate. These symptoms can be a sign of a side effect called “capillary leakage syndrome”, which causes fluid to leak from small blood vessels into the body. This condition must be treated immediately.
- If you experience two or more of any of the following symptoms at the same time: fever, frostbite, or freezing sharply, rapid heartbeat, confusion or disorientation, shortness of breath, severe pain or discomfort, and cold sweaty, or sweaty skin. This can be a symptom of a condition called “sepsis” (or “blood poisoning”), a serious infection with inflammation throughout the body, which can be life-threatening and requires immediate medical attention.
- If you get pain in the upper left part of the abdomen (abdomen), pain under the ribs on the left side, or at the tip of the shoulder blade, it may indicate problems with the spleen (enlarged spleen ( splenomegaly ) or ruptured spleen).
- If you are being treated for severe chronic neutropenia and have blood in your urine ( haematuria ). Your doctor may need to check your urine regularly if you experience this side effect or if you have protein (egg white) in your urine ( proteinuria ).
A common side effect of Ratiograstim is muscle and skeletal pain (musculoskeletal pain), which can be relieved with common painkillers ( analgesics ). Patients undergoing a stem cell or bone marrow transplant may suffer from so-called graft-versus-host disease (GvHD). This is a reaction of the donated cells directed at the patient receiving the transplant. Signs and symptoms of this condition are rashes on the palms or soles of the feet, sores in the oral cavity, intestines, liver, skin, or the eyes, lungs, vagina, and joints.
In healthy stem cell donors, an increase in the number of white blood cells ( leukocytosis ) and a decrease in the number of platelets may occur. This will be monitored by your doctor.
You may experience the following side effects:
Very common (may affect more than 1 in 10 people):
- decreased platelet count, which reduces the blood’s ability to coagulate ( thrombocytopenia )
- low red blood cell count ( anemia )
- headache
- diarrhea
- vomiting
- nausea
- abnormal hair loss or thinning ( alopecia )
- fatigue (exhaustion)
- soreness and swelling of the mucous membrane on the inside of the digestive tract, which runs from the mouth to the anus (mucositis)
- fever ( pyrexia ).
Common (may affect up to 1 in 10 people):
- inflammation of the lungs ( bronchitis )
- upper respiratory tract infection
- urinary tract infection
- decreased appetite
- difficult to sleep (insomnia)
- dizziness
- decreased sensitivity to touch, in particular, skin stimulation ( hypesthesia )
- tingling or numbness in the hands or feet ( paresthesia )
- low blood pressure ( hypotension )
- high blood pressure ( hypertension )
- cough
- bloody cough (hemoptysis)
- pain in the mouth and throat ( oropharyngeal pain)
- nosebleeds ( epistaxis )
- constipation
- pain in the mouth
- enlarged liver ( hepatomegaly )
- rash
- redness ( erythema )
- muscle spasms
- pain associated with urination ( dysuria )
- chest pain
- pain
- a general feeling of weakness ( asthenia )
- general malaise
- swelling of the hands and feet (peripheral edema )
- elevated levels of certain enzymes in the blood
- changes in blood chemistry
- transfusion reactions.
Uncommon (may affect up to 1 in 100 people):
- increased white blood cell count ( leukocytosis )
- allergic reaction (hypersensitivity)
- transplant bone marrow rejection ( graft-versus-host disease)
- high levels of uric acid in the blood, which can cause gout (hyperuricemia) (elevated level of uric acid in the blood)
- liver damage caused by blockage of the thin veins inside the liver (veno-occlusive disease)
- Impaired lung function leading to shortness of breath (respiratory failure)
- swelling and/or fluid accumulation in the lungs ( pulmonary edema )
- inflammation of the lungs (interstitial lung disease)
- abnormal X-ray of the lungs (lung infiltrate)
- hemorrhage from the lungs ( pulmonary hemorrhage)
- decreased oxygen uptake in the lungs ( hypoxia )
- elevated skin rash (maculopapular rash)
- a disease that makes the skeleton more fragile, which makes the skeleton weaker and easier to break ( osteoporosis )
- reaction at the injection site.
Rare (may affect up to 1 in 1,000 people):
- severe pain in the skeleton, chest, intestines, or joints ( sickle cell anemia with crisis)
- sudden life-threatening allergic reaction ( anaphylactic reaction )
- gout-like pain and swelling in joints (pseudoarthrosis)
- changes in fluid regulation in the body, which can lead to swelling (fluid volume disturbances)
- inflammation of the blood vessels of the skin ( cutaneous vasculitis )
- plum-colored, raised, painful sores on the arms and legs and sometimes on the face and neck, with fever (Sweets syndrome)
- aggravated rheumatoid arthritis
- unusual changes in the urine
- reduced bone density
- inflammation of the aorta (the large blood vessel that carries blood from the heart to the body), see section 2.
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 outer carton and prefilled syringe after EXP. The expiration date is the last day of the specified month.
Store in a refrigerator (2 ° C ‑ 8 ° C).
When used in environments without access to a refrigerator within the shelf life, the medicine can be taken out of the refrigerator (2 ° C ‑ 8 ° C) and stored at temperatures up to 25 ° C for a continuous period of up to 4 days. If not used within 4 days, it can be stored again in a refrigerator (2 ° C ‑ 8 ° C) until the expiration date. Syringes that have been stored above 8 ° C for more than 4 days should be discarded.
Do not use this medicine if it is cloudy or contains particles.
Medicines should not be disposed of via wastewater. Ask your pharmacist how to dispose of medicines no longer required. These measures will help to protect the environment.
Contents of the pack and other information
Content declaration
- The active substance is filgrastim. One ml solution for injection / infusion contains 60 million international units [MIU] (600 micrograms) filgrastimRatiograstim 30 MIU / 0.5 ml: A pre-filled syringe contains 30 million international units [MIU] (300 micrograms) filgrastim in 0.5 ml liquid.Ratiograstim 48 MIU / 0.8 ml: A pre-filled syringe contains 48 million international units [MIU] (480 micrograms) filgrastim in 0.8 ml liquid.
- The other ingredients are sodium hydrochloride, acetic acid, sorbitol, polysorbate 80, and water for injections.
What the medicine looks like and the contents of the pack
Ratiograstim is a solution for injection/infusion in a pre-filled syringe with or without a safety device. Ratiograstim is a clear and colorless solution. Each pre-filled syringe contains either 0.5 ml or 0.8 ml of liquid.
Ratiograstim is supplied 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 Authorization Holder and Manufacturer
Marketing Authorisation Holder
ratiopharm GmbH
Graf Arco Straße 3
89079 Ulm
Germany
Manufacturer
Teva Biotech GmbH
Dornierstraße 10
89079 Ulm
Germany
Merckle GmbH
Graf-Arco-Straße 3
89079 Ulm
Germany
Contact the representative of the marketing authorization holder to find out more about this medicine:
| Belgium / Belgique / BelgienTeva Pharma Belgium NV / SA / AGTel: +32 38207373 | LithuaniaUAB Teva BalticsTel: +370 52660203 |
| BulgariaTeva TV LADTel: +359 24899585 | Luxembourg / Luxemburgratiopharm GmbHGermany / GermanyTel: +49 73140202 |
| Czech RepublicTeva Pharmaceuticals CR, sroTel: +420 251007111 | HungaryTeva Gyógyszergyár Zrt.Tel: +36 12886400 |
| DenmarkTeva Denmark A / STel: +45 44985511 | MaltaTeva Pharmaceuticals IrelandL-IrelandTel: +44 2075407117 |
| Germanyratiopharm GmbHTel: +49 73140202 | The NetherlandsTeva Nederland BVTel: +31 8000228400 |
| EestiUAB Teva Baltics Eesti subsidiaryTel: +372 6610801 | NorwayTeva Norway ASTel: +47 66775590 |
| GreeceSpecifar Α.Β.Ε.Ε.:Ηλ: +30 2118805000 | Austriaratiopharm Arzneimittel Vertriebs-GmbHTel: +43 1970070 |
| SpainTeva Pharma, SLUTel: +34 913873280 | PolandTeva Pharmaceuticals Polska Sp. z ooTel: +48 223459300 |
| FranceTeva HealthTel: +33 155917800 | Portugalratiopharm – Commerce and Industry of Pharmaceutical Products, Lda.Tel: +351 214767550 |
| CroatiaPliva Hrvatska dooTel: +385 13720000 | RomaniaTeva Pharmaceuticals SRLTel: +40 212306524 |
| IrelandTeva Pharmaceuticals IrelandTel: +44 2075407117 | SloveniaPliva Ljubljana dooTel: +386 15890390 |
| IcelandTeva Pharma Iceland ehf.Phone: +354 5503300 | Slovak RepublicTEVA Pharmaceuticals Slovakia sroTel: +421 257267911 |
| ItalyTeva Italia SrlTel: +39 028917981 | Finland / FinlandTeva Finland OyPuh / Tel: +358 201805900 |
| .ΠροςSpecifar Α.Β.Ε.Ε.Greece:Ηλ: +30 2118805000 | SwedenTeva Sweden ABTel: +46 42121100 |
| LatviaUAB Teva Baltics subsidiary LatvijāTel: +371 67323666 | United Kingdom (Northern Ireland)Teva Pharmaceuticals IrelandIrelandTel: +44 2075407117 |