25 mg / ml Concentrate for solution for injection / infusion
1. What Fludarabine Accord is and what it is used for
Fludarabine Accord contains the active substance fludarabine phosphate, which stops the growth of new cancer cells. All cells in the body form new cells of the same cell type through cell division. Fludarabine Accord is taken up by the cancer cells and counteracts cell division.
In cancers that affect the white blood cells (eg chronic lymphocytic leukemia ), the body produces a large number of abnormal white blood cells ( lymphocytes ), and the lymph nodes in different parts of the body begin to grow. The abnormal white blood cells are unable to perform the normal disease-fighting tasks and can displace the healthy blood cells. This can lead to infection, a decrease in the number of red blood cells ( anemia ), bruising, unusually extensive bleeding, or even organ failure.
Fludarabine Accord is used to treat chronic B-cell type (B- CLL ) lymphocytic leukemia in patients with a sufficient number of healthy blood cells in the bone marrow.
The first treatment of chronic lymphocytic leukemia with this medicine should only be started in patients with advanced disease who have disease-related symptoms or show signs of worsening of the disease.
Fludarabine phosphate contained in Fludarabine Accord may also be approved for the treatment of other conditions not mentioned in this product information. Ask your doctor, pharmacist, or another healthcare professional if you have any further questions, and always follow their instructions.
2. What you need to know before using Fludarabine Accord
Do not use Fludarabine Accord
Do not use Fludarabine Accord
- if you are allergic to fludarabine phosphate or any of the other ingredients of this medicine (listed in section 6)
- if you are breast-feeding
- if you have severe kidney problems
- if you have a lack of red blood cells (hemolytic anemia ). Your doctor will inform you if you have this disease.
→ Tell your doctor if any of the above apply to you.
Warnings and cautions
Talk to your doctor before using Fludarabine Accord :
If your bone marrow is not working properly or if you have a malfunctioning or weakened immune system or have had a serious infection in the past
→ Your doctor may decide not to give you this medicine or take precautions.
If you feel sick, notice unusual bruises, bleed more than usual after an injury, or if it seems like you are getting a lot of infection.
If you get red to brownish urine during treatment, or if you get a rash or blisters on the skin.
These symptoms may be signs of decreased blood cell count, which may be caused either by the disease itself or by the treatment. It can last for up to a year, regardless of whether you have been treated with this medicine before or not. During treatment with Fludarabine Accord, your immune system can also attack different parts of the body or the red blood cells (so-called “autoimmune diseases”). These conditions can be life-threatening. If this happens, the doctor will stop the treatment and you may receive other treatments, e.g. blood transfusion with irradiated blood (see below) and corticosteroids.
You will be given blood tests regularly during treatment and you will be closely monitored while you are being treated with this medicine.
If you notice unusual symptoms from the nervous system such as visual disturbances, headaches, confusion, seizures
If Fludarabine Accord is used for a long time, its long-term effects on the central nervous system are not known. However, patients treated with the recommended dose of one with up to 26 treatment regimens could tolerate it. When Fludarabine Accord is given at the recommended dose, after treatment with other medicines or at the same time as other medicines, the following side effects have been reported: neurological problems which manifest themselves as headache, nausea and vomiting, convulsions, visual disturbances including vision loss, altered state of mind (abnormal thoughts, confusion, altered consciousness) and sometimes neuromuscular disorders which manifest as muscle weakness in arms and legs (including persistent incomplete or complete paralysis) (symptoms of leukoencephalopathy, acute toxic leukoencephalopathy or reversible posterior leukoencephalopathy syndrome).
In patients who have received a dose four times the recommended dose, blindness, coma, and death have been reported. Some of these symptoms are delayed by about 60 days or more after stopping treatment. In some patients who have received a higher dose of Fludarabine Accord than the recommended dose, leukoencephalopathy, acute toxic leukoencephalopathy or reversible posterior leukoencephalopathy syndrome have also been reported. The same symptoms as described above for these diseases can occur.
Leukoencephalopathy, acute toxic leukoencephalopathy, or reversible posterior leukoencephalopathy syndrome can be persistent, life-threatening, or cause death.
If any of these diseases are suspected, treatment with Fludarabine Accord will be discontinued for further investigation.
If the diagnosis of leukoencephalopathy, acute toxic leukoencephalopathy, or reversible posterior leukoencephalopathy syndrome is confirmed, your doctor will stop your treatment with Fludarabine Accord permanently.
If you feel pain in the side, have blood in the urine, or if your urine volume decreases.
If your disease is very severe, your body may not be able to get rid of all the waste products from the cells destroyed by Fludarabine Accord. This is called tumor lysis syndrome and can cause kidney failure and heart problems from the first week of treatment. Your doctor is aware of this and may give you other medicines to prevent it.
If you are undergoing stem cell collection and you are being treated (or have been treated) with Fludarabine Accord,
If you need a blood transfusion and you are being treated (or have been treated) with Fludarabine Accord,
If you need a blood transfusion, your doctor will make sure that you only receive blood that has been treated with radiation. Serious complications, and even death, have occurred after transfusion of unirradiated blood.
If you notice any skin changes while you are taking this medicine or after stopping treatment,
If you have (or have had) skin cancer, it may worsen or flare up again during or after treatment with Fludarabine Accord. You may develop skin cancer during or after treatment with Fludarabine Accord.
What you should also keep in mind when you are treated with Fludarabine Accord:
Men and women of childbearing potential must use effective contraception during treatment and at least 6 months after stopping treatment. It cannot be ruled out that Fludarabine Accord may harm the unborn baby. Your doctor will carefully weigh the benefits of your treatment against the possible risks to the unborn baby. If you are pregnant, you will only be treated with Fludarabine Accord if necessary.
If you are considering breastfeeding or if you are breast-feeding, do not start or continue while you are being treated with Fludarabine Accord.
Discuss with your doctor if you need to be vaccinated. Live vaccines should be avoided during and after treatment with Fludarabine Accord.
- If you have kidney problems or are older than 65 years, you will regularly have to submit blood tests and/or other tests to check your kidney function. If your kidney problems are severe, you will not receive this medicine at all (see also sections 2 and 3).
Children and young people
The safety and efficacy of Fludarabine Accord in children under 18 years of age have not been established. Therefore, this medicine is not recommended for use in children.
Other medicines and Fludarabine Accord
Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines, including medicines obtained without a prescription.
You must tell your doctor about:
- pentostatin ( deoxicoformycin ), which is also used to treat B-type chronic lymphocytic leukemia, as concomitant use of these two drugs can lead to serious lung complications.
- dipyridamole, which is used to prevent coagulation of the blood or other similar drugs. They may reduce the effect of the Fludarabine Accord.
- cytarabine ( Ara-C ) is used in the treatment of chronic lymphocytic leukemia. If Fludarabine Accord is combined with cytarabine, the levels of the active form of Fludarabine Accord in leukemia cells may rise. However, the total levels in the blood and elimination from the blood have not been shown to change.
Elderly and Fludarabine Accord
People over the age of 65 will be given regular tests to check their kidney function (see also section 3. How to use Fludarabine Accord).
People older than 75 years will be followed very closely.
Pregnancy, breastfeeding, and fertility
Fludarabine Accord should not be given to pregnant women as animal studies and very limited human experience have shown a possible risk of abnormalities in the unborn baby as well as premature miscarriage or premature birth.
- If you are pregnant or breast-feeding, think you may be pregnant, or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine.
Your doctor will carefully weigh the benefits of your treatment against the possible risks to the unborn baby. If you are pregnant, you will only be treated with the medicine if necessary.
You should not start or continue breast-feeding during treatment with this medicine, as this medicine may interfere with the growth and development of your baby.
Consult a doctor before taking any medicine.
Men and women of childbearing potential must use effective contraception during treatment and for at least 6 months after stopping treatment.
Driving and using machines
Some people get tired, feel weak, have visual disturbances, become confused or anxious, or have seizures when treated with this medicine. Do not drive or use machines until you are sure you are not affected.
You are responsible for assessing whether you are fit to drive a motor vehicle or perform work that requires sharpened attention. One of the factors that can affect your ability in these respects is the use of drugs due to their effects and/or side effects. Descriptions of these effects and side effects can be found in other sections. Read all the information in this leaflet for guidance. If you are not sure, talk to your doctor or pharmacist.
Important information about some of the ingredients of Fludarabine Accord
This medicine contains less than 1 mmol sodium per dose, ie essentially ‘sodium-free’. almost “sodium-free”.
3. How to use Fludarabine Accord
Always use this medicine exactly as your doctor has told you. Consult a doctor if you are unsure.
Fludarabine Accord should be given under the supervision of a doctor who specializes in cancer treatment.
- For information on the preparation of the diluted solution, see section 6. Contents of the package and other information.
How much Fludarabine Accord is given:
The dose you receive depends on your body surface area. This is measured in square meters (m 2 ) and is calculated by your doctor based on your height and weight.
The recommended dose is 25 mg fludarabine phosphate per m 2 body surface area.
How Fludarabine Accord is given:
Fludarabine Accord is given as a solution as an injection or, for the most part, as an infusion.
An infusion means that the medicine is given directly into the bloodstream via a drip through a vein. An infusion takes about 30 minutes.
Your doctor will make sure that Fludarabine Accord is not given at the side of the vein (ravenously). No serious local reactions have been reported if this were to happen anyway.
How long Fludarabine Accord is given
Dose one is given once a day 5 days in a row.
The five-day regimen is repeated every 28 days until your doctor considers that the best effect has been achieved (usually after 6 rounds).
The duration of treatment depends on how successful the treatment is and how well you tolerate this medicine. The repeated rounds of treatment can be postponed if you experience problems in the form of side effects.
You will be given blood samples regularly during treatment. Your individual dose will be carefully adjusted depending on the number of blood cells and how you respond to the treatment.
The dose can also be reduced if you experience problems in the form of side effects.
If you have kidney problems or are older than 65 years, you will be regularly given samples to check your kidney function. If it is found that your kidneys are not working properly, you may be given a lower dose. If your kidney function is severely impaired, you will not receive this medicine at all (see also section 2).
If Fludarabine Accord is played
If any of the contents of Fludarabine Accord come in contact with your skin, nose, or lips, wash thoroughly with soap and water. If you get the solution in your eyes, rinse thoroughly with large amounts of water. Avoid inhaling vapors from the solution.
If you use more Fludarabine Accord then you should
In case of overdose, the doctor may discontinue treatment and treat any symptoms that may occur. High doses can cause a sharp decrease in the number of blood cells.
For Fludarabine Accord given intravenously, overdose has been reported to cause delayed blindness, coma, and even death.
If you have ingested too much medicine or if e.g. If a child has inadvertently ingested the medicine, contact a doctor, hospital, or the Poison Information Center for risk assessment and advice.
If a dose of Fludarabine Accord is missed
Your doctor will make a schedule for when you will receive the medicine. Contact a doctor immediately if you suspect a dose has been missed.
Do not take a double dose to make up for a forgotten dose.
If treatment with Fludarabine Accord is stopped
If the side effects become too severe, your doctor may, in consultation with you, decide to stop treatment with this medicine.
If you have any further questions on the use of this product, ask your doctor or pharmacist.
4. Possible side effects
Like all medicines, this medicine can cause side effects, although not everybody gets them. If you are not sure what the following side effects are, ask your doctor to explain them to you.
Some serious side effects can be life-threatening.
- If you have difficulty breathing, cough, or chest pain with or without fever. This may be a sign of infection in the lungs.
- If you notice unusual bruises bleed more than usual after injury, or if it seems like you are getting a lot of infection. This can be caused by a decreased number of blood cells. This can also lead to an increased risk of (serious) infections, caused by organisms that do not usually cause disease in healthy people (opportunistic infections ), including the recurrence of a virus, e.g. herpes zoster.
- If you feel pain in the side, have blood in the urine, or if your urine volume decreases. This may be a sign of tumor lysis syndrome (see section 2)
- If you notice any skin and/or mucous membrane reactions with redness, inflammation, blisters, or tissue breakdown. This may be a sign of a severe allergic reaction ( Lyell’s syndrome, Stevens-Johnson syndrome ).
- If you get palpitations (if you suddenly feel your heart beating) or chest pain. This may be a sign of heart problems.
- Contact a doctor immediately if you notice any of these side effects.
Listed below are possible side effects that are grouped by type. The rare side effects (less than 1 in 1000 patients) have been reported mainly after marketing authorization.
Very common (affects more than 1 in 10 people):
- The infection you (some serious)
- Infection is due to a weakened immune system (opportunistic infections ).
- Pneumonia ( CAP ) with symptoms such as breathing difficulties and/or cough with or without fever
- Decreased platelet count ( thrombocytopenia ) that can cause bruising and bleeding
- Decreased white blood cell count ( neutropenia )
- Reduced red blood cell count ( anemia )
- Vomiting, diarrhea, nausea
Common (affects up to 1 in 10 people)
- Other blood-related cancers ( myelodysplastic syndrome, acute myeloid leukemia ). Most patients with these conditions have previously, or concomitantly or later been treated with other cancer drugs (alkylating agents, topoisomerase inhibitors) or radiation
- Bone marrow suppression (myelosuppression).
- Severe loss of appetite leading to weight loss ( anorexia )
- Numbness or feeling of weakness in arms and legs ( peripheral neuropathy )
- Visual disturbances
- Inflammation of the mouth ( stomatitis )
- Swelling due to heavy fluid retention ( edema )
- Inflammation of the mucous membranes of the digestive tract from the mouth to the anal opening ( mucositis )
- Freezing breaks
- General malaise
Uncommon (affects up to 1 in 100 people)
- Autoimmune diseases (see section 2, Warnings and precautions)
- Tumor light syndrome (see section 2, Warnings and precautions)
- Adverse effects on the lungs, scarring of the lungs ( pulmonary fibrosis ), pneumonia ( pneumonitis ), shortness of breath ( dyspnoea )
- Bleeding in the stomach and intestines
- Abnormal levels of liver or pancreatic enzymes
Rare (affects up to 1 in 1,000 people)
- Diseases of the lymphatic system due to a viral infection ( EBV -associated lymphoproliferative disease)
- Strong concern
- Inflammation or damage to the optic nerve ( optic neuritis; optic neuropathy )
- Heart failure
- Irregular heartbeat ( arrhythmia )
- Skin cancer
- Reactions in the skin and/or mucous membranes with redness, inflammation, blistering, or tissue detachment ( Lyell’s syndrome, Stevens-Johnson syndrome ).
Has been reported (occurs in an unknown number of users)
- Inflammation of the bladder, which can cause pain to urinate and urine to become mixed with blood ( hemorrhagic cystitis ).
- Cerebral hemorrhage
- Bleeding in the lungs.
- Neurological problems which manifest themselves as headache, nausea and vomiting, convulsions, visual disturbances including vision loss, altered state of mind (abnormal thoughts, confusion, altered consciousness), and sometimes neuromuscular disorders which manifest as muscle weakness in arms and legs (including persistent incomplete or complete paralysis) (symptoms of leukoencephalopathy, acute toxic leukoencephalopathy or reversible posterior leukoencephalopathy syndrome).
5. How to store Fludarabine Accord
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 vial after EXP. The expiration date is the last day of the specified month.
Storage of Fludarabine Accord in unopened packaging
Store in a refrigerator (2 – 8 ° C). Do not freeze.
Storage of Fludarabine Accord after dilution
Chemical and physical in-use stability has been demonstrated at 0.2 mg/ml and 6.0 mg/ml after dilution with 0.9% sodium chloride and 5% glucose injection for 7 days at 2-8 ° C and 5 days at 20-25 ° C in non-PVC bags and glass bottles.
For microbiological reasons, the product should be used immediately. If not used immediately, in-use storage times and conditions before use are the responsibility of the user and should not be longer than 24 hours at 2 to 8 ° C, unless the solution has been diluted under controlled and approved aseptic conditions.
For information for healthcare professionals, see section 6. Contents of the package and other information.
Do not use this medicine if there are visible signs of injury.
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help to protect the environment.
6. Contents of the packaging and other information
- The active substance is fludarabine phosphate. Each ml contains 25 mg of fludarabine phosphate.
- The other ingredients are mannitol, disodium phosphate dihydrate, and water for injections.
Fludarabine Accord is packaged in 2 ml glass vials.
What the medicine looks like and the contents of the pack
Fludarabine Accord is a sterile, clear, colorless, or light brownish-yellow solution in a clear glass vial.
Fludarabine Accord is supplied in three pack sizes, containing 1, 5, or 10 vials.
Not all pack sizes may be marketed.
Marketing Authorization Holder and Manufacturer
Marketing Authorisation Holder
Accord Healthcare BV
3526 KV Utrecht
Accord Healthcare Limited
319 Pinner Road,
Middlesex, HA1 4HF,
Accord Healthcare Polska Sp.z oo,
ul. Lutomierska 50,95-200 Pabianice, Poland
Accord Healthcare BV
3526 KV Utrecht