Each vial contains 50 mg fludarabine phosphate as a powder for injection or infusion. The powder will be made up into a solution before it is given. 1 ml of reconstituted solution contains 25 mg fludarabine phosphate.
Excipients/Inactive Ingredients: Mannitol and sodium hydroxide.
Important information about some of the ingredients of Fludalym: This medicine contains less than 1 mmol sodium (23 mg) per ml, i.e. essentially 'sodium-free'.
Pharmacotherapeutic Group: Cytotoxic Chemotherapy.
All cells of the body produce new cells like themselves by dividing. For this purpose, the cell' genetic material (DNA) must be copied and reproduced. Fludalym works by hindering the production of new DNA. Therefore, when Fludalym is taken up by the cancer cells, it stops the growth of new cancer cells.
In cancers of the white blood cells (as chronic lymphocytic leukaemia) many abnormal lymphocytes are produced. The abnormal lymphocytes either do not work properly or are too young (immature) to carry out the normal disease fighting functions of white blood cells. If there are too many of these abnormal lymphocytes, they push aside healthy blood cells in the bone marrow where most of the new blood cells are formed. Without enough healthy blood cells, infections, anaemia, bruising, excessive bleeding or even organ failure can result.
Fludalym is an anti-cancer drug.
Fludalym is used to treat chronic B-cell lymphocytic leukaemia (B-CLL) in patients with sufficient healthy blood cell production. This is a type of cancer of white blood cells (the cells are called lymphocytes).
First treatment for chronic lymphocytic leukaemia with Fludalym should only be started in patients with advanced disease having disease related symptoms or evidence of disease progression.
Fludalym should be administered under the supervision of a qualified doctor experienced in cancer therapy.
The dose given depends on the size of the patient's body. It varies with body surface area. Technically this is measured in square metres (m2), but actually is worked out from the height and weight. The recommended dose is 25 mg/m2 body surface. This will be given either as an injection or as an infusion (with a drip) into a vein once a day for 5 consecutive days every 28 days.
This five day course of treatment will be repeated every 28 days until the doctor has decided that the best effect has been achieved.
The dosage may be decreased or the repeat course delayed if side effects are a problem. If the patient has kidney problems, he/she will receive a reduced dose and will have regular blood tests.
The safety of this drug in children and adolescents below age 18 has not been established and treatment is not recommended.
If any of the Fludalym solution comes into contact with the skin or skin lining of the nose or mouth, wash the area thoroughly with soap and water. If the solution gets into the eyes, rinse them thoroughly with lots of water. Try not to breathe in any fumes coming from the solution.
If the patient forgets to use Fludalym: The doctor will set the times at which the patient is to receive this medicine. If the patient thinks that he/she may have missed a dose, contact the doctor as soon as possible.
If the patient has any further questions on the use of this product, ask the doctor or pharmacist.
In case of an overdose, the doctor will stop the therapy and treat the symptoms.
Symptoms of an overdose can be blindness which may not appear until later, coma and death due to irreversible toxicity to the central nervous system. High doses can also lead to a severely reduced number of blood cells.
Do not use Fludalym: If the patient is allergic (hypersensitive) to fludarabine phosphate or any of the other ingredients of Fludalym.
If the patient is breast feeding.
If the kidney function is severely impaired.
If the patient has a low number of red blood cells (haemolytic anaemia).
If the patient is not feeling very well, the doctor may decide not to give this medicine, or may give this medicine with caution. This is very important if the bone marrow is not working properly or if the patient is susceptible to infections.
If there is any unusual bruising, excessive bleeding after injury or if the patient seems to be catching a lot of infections, tell the doctor. The number of normal blood cells may be reduced, the patient must have a regular blood tests during treatment.
The disease itself and the therapy may cause a reduction of the number of blood cells and the immune system may attack different parts of the patient's body (autoimmune disorder). It may also be directed against the red blood cells (called 'autoimmune haemolysis'). This condition can be life threatening. If this condition occurs, the patient may receive further medication such as transfusion of blood (irradiated, see as follows) and corticosteroides.
If in need of blood transfusion and being (or have been) treated with this medicine, mention this to the doctor. The doctor will ensure that the only blood the patient will receive has gone through a special treatment (irradiation). There have been severe complications and even death reported when non-irradiated blood has been given.
If the patient needs to have stem cells collected and being (or have been) treated with this medicine, mention this to the doctor.
If the liver does not work properly, the doctor may give this medicine with caution.
If the patient has any form of kidney disease, the kidney function should be checked regularly. If it is found that the kidneys do not work properly, the patient may be given this medicine at a reduced dose. If the kidneys work at only a very low level, do not give this medicine at all. Patients aged 65 years or older should have their kidney function checked before start of treatment.
There is little information on the effects of Fludalym in patients aged 75 years and older. The doctor will use it with caution in this age group.
If the patient has very severe chronic lymphocytic leukaemia, the body may not be able to get rid of all the waste products from the cells destroyed by Fludalym. This is called tumour lysis syndrome and may cause dehydration, kidney failure and heart problems. The doctor will be aware of this and may give the patient other medicines to stop this happening.
If the patient experiences any unusual symptoms from the nervous system, mention it to the doctor. This is because when used in patients at doses four times greater than the recommended dose, severe central nervous system (brain and spinal cord) effects including blindness, coma and death have been reported.
Tell the doctor if there are any changes to the patient's skin either while receiving this medicine or after having finished the course of therapy. The doctor should check the seriousness of the skin changes. If the patient has skin cancer, the damaged areas of the skin may become worse when using this medicine.
Men and women who may still be fertile, must use a reliable form of contraception during, and for at least 6 months after stopping treatment.
Check with a doctor about any vaccinations the patient may need, because live vaccinations should be avoided during and after treatment with Fludalym.
Driving and Using Machines: The effect of treatment with Fludalym on the ability to drive or use machines has not been evaluated. Fludalym may although influence the ability to drive and use machineries since side effects like tiredness, weakness, agitation, seizures and visual disturbances have been observed.
Ask the doctor or pharmacist for advice before taking any medicine.
Fludarabine treatment has the potential to harm the unborn child. The patient must not be given Fludalym if pregnant unless clearly necessary and when the potential benefits justify the potential risks to the unborn child. If the patient is a woman who may still be fertile, must avoid becoming pregnant during treatment and for at least 6 months after stopping treatment. However, if the patient does become pregnant inform the doctor immediately.
Men who are treated with Fludalym and can father a child must use a reliable form of contraception during, and for at least 6 months after stopping treatment.
It is not known if this medicine appears in the breast milk of women treated with Fludalym. However, in animal studies the medicinal product was found in breast milk. Therefore, the patient must not breast feed during treatment with this medicine.
Like all medicines, Fludalym can cause side effects, although not everybody gets them. If the patient is not sure what the adverse reactions as follows are, ask the doctor to explain them to the patient.
Some side effects can be life-threatening. If the patient has difficulty breathing, has a cough, or has chest pain with or without fever. These may be signs of an infection of the lungs.
If the patient notices any unusual bruising, more bleeding than usual after injury or if the patient seems to be catching a lot of infections. These may be caused by a reduced number of blood cells. This may also lead to an increased risk of (serious) infections, caused by organisms, that usually do not cause disease in healthy persons (opportunistic infections) including a late reactivation of viruses, for example herpes zoster.
If the patient notices any pain in the side, blood in the urine, or reduced amount of urine. These may be signs of tumour lysis syndrome (see Precautions).
If the patient notices any skin and/or mucous coat reaction with redness, inflammation, blistering and tissue break down. These may be signs of a severe allergic reaction (Lyell's syndrome, Stevens-Johnson syndrome).
If the patient has palpitations (if the patient suddenly becomes aware of his/her heartbeat) or chest pain. These may be signs of heart problems.
Tell the doctor immediately, if the patient notices any of these effects.
As follows are the list of possible side effects by how common they are. The rare side effects (less than 1 in every 1000 patients) were mainly identified from post-marketing experience.
Very common means 1 or more in every 10 patients are likely to get these: infections (some serious); infections due to depressed immune system (opportunistic infections); infection of the lungs (pneumonia) with possible symptoms like breathing difficulties and/or cough with or without fever; reduction in the number of blood platelets (thrombocytopenia) with the possibility of bruising and bleeding; lowered white blood cell count (neutropenia); lowered red blood cell count (anaemia); cough; vomiting, diarrhea, feeling sick (nausea); fever; feeling tired (fatigue); weakness.
Common means between 1 and 10 in every 100 patients are likely to get these: other blood related cancers (myelodysplastic syndrome, acute myeloid leukaemia). Most patients with these conditions were previously, or at the same time or later treated with other cancer drugs (alkylating agents, topoisomerase inhibitors) or radiation therapy; bone marrow depression (myelosuppression); severe loss of appetite leading to weight loss (anorexia); numbness or weakness in limbs (peripheral neuropathy); disturbed vision; inflammation inside of the mouth (stomatitis); skin rash; swelling due to excessive fluid retention (oedema); inflammation of the mucous coat of the digestive system from the mouth to the anus (mucositis); chills; generally feeling unwell.
Uncommon means between 1 and 10 in every 1,000 patients are likely to get these: autoimmune disorder (see Precautions); tumour lysis syndrome (see Precautions); confusion; lung toxicity; scaring through out the lungs (pulmonary fibrosis), inflammation of the lungs (pneumonitis), shortness of breath (dyspnoea); bleeding in the stomach or intestines; abnormal levels of the liver or pancreas enzymes.
Rare means less than 10 in every 10,000 patients are likely to get these: disorders of the lymph system due to a viral infection (EBV-associated lymphoproliferative disorder); coma; seizures; agitation; blindness; inflammation or damage of the nerve of the eyes (optic neuritis; optic neuropathy); heart failure; irregular heart beat (arrhythmia); skin cancer; skin and/or mucous coat reaction with redness, inflammation, blistering and tissue break down (Lyell's syndrome, Stevens-Johnson syndrome).
Frequency not known: inflammation of the bladder, which can cause pain when passing urine, and can lead to blood in the urine (haemorrhagic cystitis); bleeding in the brain; bleeding in the lungs.
If any side effects get serious, or if the patient notices any side effects not listed, please tell the doctor.
Using other medicines: Please tell the doctor if the patient is taking or has recently taken any other medicines, including medicines obtained without a prescription. This is especially important if the patient is taking a drug called pentostatin or deoxycoformycin (also used to treat chronic lymphocytic leukaemia) as a combination with Fludalym is not recommended. Some drugs, e.g. dipyridamole (used to prevent excessive blood clotting) may reduce the effectiveness of Fludalym.
Instructions for Use, Handling and Disposal: ANTINEOPLASTIC AGENT: A crossover from initial treatment with fludarabine phosphate to chlorambucil for non responders to fludarabine phosphate should be avoided because most patients who have been resistant to fludarabine phosphate have shown resistance to chlorambucil.
Instructions for use: Reconstitution: Fludalym should be prepared for parenteral use by aseptically adding sterile water for injection. When reconstituted with 2 ml of sterile water for injection, the powder should fully dissolve in 15 seconds or less. Each ml of the resulting solution will contain 25 mg of fludarabine phosphate, 25 mg of mannitol, and sodium hydroxide to adjust the pH to 7.7. The pH range for the final product is 7.2-8.2.
Dilution: The required dose (calculated on the basis of the patient's body surface) is drawn up into a syringe. For intravenous bolus injection this dose is further diluted in 10 ml of 0.9% sodium chloride. Alternatively, for infusion, the required dose may be diluted in 100 ml of 0.9% sodium chloride and infused over approximately 30 minutes.
Fludarabine phosphate must not be mixed with other drugs.
Storage after reconstitution: The physicochemical stability of the drug product after reconstitution in water for injections has been demonstrated for 8 hours at 25°C ± 2°C/ 60% ± 5% RH and for 7 days at 5°C ± 3°C.
From a microbiological point of view, the product should be used immediately. If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user.
Inspection prior to use: The reconstituted solution is clear and colourless. It should be visually inspected before use. Only clear and colourless solutions without particles should be used. Fludalym should not be used in case of a defective container.
Handling and disposal: Fludalym should not be handled by pregnant staff.
Procedures for proper handling should be followed according to local requirements for cytotoxic drugs. Caution should be exercised in the handling and preparation of the Fludalym solution. The use of latex gloves and safety
glasses is recommended to avoid exposure in case of breakage of the vial or other accidental spillage.
If the solution comes into contact with the skin or mucous membranes, the area should be washed thoroughly with soap and water. In the event of contact with the eyes, rinse them thoroughly with copious amounts of water. Exposure by inhalation should be avoided.
The medicinal product is for single use only.
Any unused product or waste material should be disposed of in accordance with local requirements for cytotoxic agents.
L01BB05 - fludarabine ; Belongs to the class of antimetabolites, purine analogues. Used in the treatment of cancer.
Lyophilisate for soln for inj/infusion (vial) 50 mg x 1's.