How does it work?
Fludara tablets and injection contain the active ingredient fludarabine phosphate, which is a type of chemotherapy medicine for cancer known as a 'cytotoxic antimetabolite'.
Fludarabine is used to treat a type of cancer of the white blood cells called chronic lymphocytic leukaemia (CLL). It works by killing the abnormal blood cells that cause this disease.
The bone marrow produces cells called stem cells. These normally develop into the different types of blood cells (white blood cells, red blood cells and platelets) and when these are mature they leave the bone marrow and enter the bloodstream. In leukaemia the bone marrow produces too many immature white blood cells. These abnormal cells take up space in the bone marrow and result in less room for production of normal healthy blood cells.
Fludarabine works by stopping the abnormal blood cells from multiplying. It does this by inhibiting the production of the cells' genetic material, DNA and RNA. Both DNA and RNA are needed for growth and multiplication of cells. Fludarabine causes a deficiency of DNA and RNA in the cancerous cells, and this causes them to grow in an unbalanced way, resulting in the death of the cells.
Unfortunately, fludarabine can also affect normal, healthy cells, particularly those that multiply quickly, such as healthy blood cells. Although the aim of treating leukaemia with fludarabine is to kill the cancerous blood cells, the most important side effect is on the bone marrow, where blood cells are made. Fludarabine also decreases the production of normal blood cells, which can leave people susceptible to infection. Fludarabine is, therefore, only used to treat chronic lymphocytic leukaemia in people who have enough healthy cells remaining in their bone marrow. Regular blood tests are needed to monitor the levels of blood cells.
In most chemotherapy regimens, doses are administered in courses at various intervals to allow normal cells to recover from the adverse effects of the anticancer medicines between doses. However, during this period, cancer cells will also recover and start to replicate again. Successful treatment depends on the administration of the next course of therapy before the cancer cells reach their previous numbers and the net effect is to decrease the amount of cancer with each successive course.
What is it used for?
- Chronic lymphocytic leukaemia.
How is this treatment given?
- Fludarabine can be given by mouth as tablets, or by slow injection or infusion (drip) into a vein (intravenously). The drip is given over about 30 minutes.
- The treatment is usually given for five days every 28 days. This is one cycle of treatment. The number of cycles given depends on how well the treatment is tolerated and how the leukaemia responds.
- Fludara tablets can be taken either with or without food. The tablets should be swallowed whole with water; they must not be broken, crushed or chewed. The tablets should not be handled by pregnant women.
- The number of tablets to take will vary from person to person and may change with each treatment cycle. It is important to follow the instructions given by your doctor and printed on the dispensing label. This medicine must only be taken under specialist medical supervision.
- If you vomit after taking a dose or forget to take a dose you should ask your doctor for advice. Don't take a double dose to make up for a missed dose.
- This medicine (as well as the disease itself) can decrease the number of healthy blood cells in your blood. A low white blood cell count can increase your susceptibility to infections; a low red blood cell count causes anaemia and a low platelet count can cause problems with blood clotting. For this reason, you will need regular blood tests to monitor your blood cells during treatment with this medicine. Tell your doctor immediately if you experience any of the following symptoms during your treatment, as they may indicate problems with your blood cells: unexplained bruising or bleeding, purple spots, sore mouth or throat, mouth ulcers, high temperature (fever) or other signs of infection, or suddenly feeling tired, breathless, or generally unwell.
- Fludarabine kills the leukaemic cells quickly and this can sometimes cause a condition called tumour lysis syndrome, where the body cannot cope with all the waste products of the killed cancer cells. This may cause symptoms such as a rapid heartbeat, rapid breathing, breathlessness, dizziness or fainting, together with a rise in uric acid levels in the blood. You may be given a medicine called allopurinol to avoid problems with raised uric acid levels. You may be asked to drink plenty of fluid while having treatment with fludarabine to help avoid these problems.
- Tell your doctor if you get any of the following problems while having treatment with this medicine, as they could be signs of other potentially serious side effects: cough, feeling breathless or wheezy, chest pain, disturbance in your vision, feeling confused or agitated, blood in your urine, pain on passing urine, red/brownish urine, reduced amount of urine, pain in your side, a rash or blisters on your skin.
- You should tell all healthcare professionals that treat you that you are taking this medicine. This is because if you need treatment with any blood products these must be irradiated before they are given to you. There have been cases of severe complications and even death when transfusions of non-irradiated blood have been given to people treated with this medicine.
- This medicine may be harmful to an unborn baby, and for this reason you should use effective contraception to avoid getting pregnant or fathering a child during treatment. You should continue to use contraception to prevent pregnancy for at least six months after treatment with this medicine is stopped. Women should consult their doctor immediately if they get pregnant during treatment.
- Your ability to become pregnant or father a child may be affected by taking this drug. It is important to discuss fertility with your doctor before starting treatment.
Use with caution in
- People aged over 75 years.
- People with decreased kidney function.
- People with decreased liver function.
- People with a severe reduction in blood cell production in the bone marrow, resulting in low levels of white blood cells, red blood cells or platelets in the blood (for example due to radiotherapy or previous courses of chemotherapy).
- People with a poorly functioning immune system or a history of serious infections.
- People with a history of skin cancer.
Not to be used in
- People with moderate to severely decreased kidney function.
- People with a condition called haemolytic anaemia, where there are decreased numbers of red blood cells in the bloodstream due to an increase in their breakdown by the body.
- There is insufficient information regarding the safety and effectiveness of this medicine in children. It is not recommended for children.
This medicine should not be used if you are allergic to any of its ingredients. Please inform your doctor or pharmacist if you have previously experienced such an allergy.
If you feel you have experienced an allergic reaction, stop using this medicine and inform your doctor or pharmacist immediately.
Pregnancy and breastfeeding
Certain medicines should not be used during pregnancy or breastfeeding. However, other medicines may be safely used in pregnancy or breastfeeding providing the benefits to the mother outweigh the risks to the unborn baby. Always inform your doctor if you are pregnant or planning a pregnancy, before using any medicine.
- This medicine is likely to be harmful to a developing baby. It must not be used during pregnancy unless considered essential by your doctor for treating life-threatening illness. In addition, pregnant women should not handle this medicine.
- Women who could get pregnant should use effective contraception to prevent pregnancy, and men should use effective contraception to prevent fathering a child, both during treatment, and for at least six months after treatment is finished. Seek medical advice from your doctor. Consult your doctor immediately if you become pregnant.
- This medicine may pass into breast milk. Mothers who need treatment with this medicine should not breastfeed. Seek further medical advice from your doctor.
Medicines and their possible side effects can affect individual people in different ways. The following are some of the side effects that are known to be associated with this medicine. Just because a side effect is stated here, it does not mean that all people using this medicine will experience that or any side effect.
Very common (affect more than 1 in 10 people)
- Decrease in the number of healthy white blood cells, red blood cells or platelets in the blood (neutropenia, anaemia and thrombocytopenia) - see warning section above.
- Feeling or being sick. You will be given medicines to help with this.
Common (affect between 1 in 10 and 1 in 100 people)
- Inflammation of the lining of the mouth, causing a sore mouth or mouth ulcers.
- Loss of appetite.
- Disorder of the peripheral nerves causing weakness and numbness (peripheral neuropathy).
- Visual disturbances.
- Excessive fluid retention in the body tissues, resulting in swelling (oedema).
- Feeling generally unwell.
- Inflammation of the mucous membranes in the intestinal tract (mucositis).
Uncommon (affect between 1 in 100 and 1 in 1000 people)
- Changes to the lungs, such as inflammation or stiffening.
- Tumour lysis syndrome, where the body is unable to cope with all the waste products of the cancer cells killed by this medicine. This may lead to abnormal levels of salts in your blood and possibly kidney failure.
- Abnormal results in liver function tests.
- Bleeding in the gut.
Rare (affect between 1 in 1000 and 1 in 10,000 people)
- Inability of the heart to pump blood efficiently (heart failure).
- Abnormal heart beats (arrhythmias).
- Severe allergic blistering skin reaction (Stevens-Johnson syndrome).
- Severe flaking of the surface layer of the skin (toxic epidermal necrolysis).
- Skin cancer.
- Inflammation of the bladder and blood in the urine.
- Bleeding in the brain or lungs.
The side effects listed above may not include all of the side effects reported by the medicine's manufacturer.
For more information about any other possible risks associated with this medicine, please read the information provided with the medicine or consult your doctor or pharmacist.
How can this medicine affect other medicines?
It is important to tell your doctor or pharmacist what medicines you are already taking, including those bought without a prescription and herbal medicines, before you start treatment with this medicine. Similarly, check with your doctor or pharmacist before taking any new medicines during treatment this one, to ensure that the combination is safe.
Vaccines may be less effective in people receiving chemotherapy. This is because chemotherapy medicines reduce the activity of the immune system and can prevent the body forming adequate antibodies. Live vaccines should be postponed until at least six months after finishing chemotherapy because they may cause infection. Live vaccines include the following: oral polio; rubella; measles, mumps and rubella (MMR); BCG; chickenpox; yellow fever and oral typhoid vaccines.
There may be an increased risk of side effects if this medicine is used in combination with other medicines that can affect blood cell counts, for example other chemotherapy medicines, or the antipsychotic clozapine.
The effectiveness of fludarabine may be reduced by dipyridamole.
Pentostatin is not recommended for use in combination with fludarabine, as this combination carries an increased risk of potentially fatal lung damage.
Other medicines containing the same active ingredient
Fludarabine injection is also available without a brand name, ie as the generic medicine.