In the U.S.—

In Canada—

• Antineoplastic

Fludarabine ( floo-DARE-a-been) belongs to the group of medicines called antimetabolites. It is used to treat chronic lymphocytic leukemia (CLL), a type of cancer.

Fludarabine interferes with the growth of cancer cells, which are eventually destroyed. Since the growth of normal body cells may also be affected by fludarabine, other effects will also occur. Some of these may be serious and must be reported to your doctor. Other effects may not be serious but may cause concern. Some effects may not occur for months or years after the medicine is used.

Before you begin treatment with fludarabine, you and your doctor should talk about the good this medicine will do as well as the risks of using it.

Fludarabine is to be administered only by or under the immediate supervision of your doctor. It is available in the following dosage form:

Parenteral
• Injection (U.S. and Canada)

Oral
• Tablet (Canada)

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For fludarabine, the following should be considered:

Allergies—Tell your doctor if you have ever had any unusual or allergic reaction to fludarabine.

Pregnancy—There is a chance that this medicine may cause birth defects if either the male or female is taking it at the time of conception or if it is taken during pregnancy. Fludarabine has been shown to cause birth defects in rats and rabbits. In addition, many cancer medicines may cause sterility which could be permanent. Although sterility has not been reported with this medicine, it does occur in animals and the possibility should be kept in mind.

Be sure that you have discussed this with your doctor before taking this medicine. It is best to use some kind of birth control while you are receiving fludarabine and for at least 6 months after the last dose that you receive. Tell your doctor right away if you think you have become pregnant while receiving fludarabine.

Breast-feeding—It is not known whether fludarabine passes into breast milk. However, because this medicine may cause serious side effects, breast-feeding is not recommended while you are receiving it.

Children—There is no specific information comparing use of fludarabine in children with use in other age groups.

Older adults—Many medicines have not been studied specifically in older people. Therefore, it may not be known whether they work exactly the same way they do in younger adults. Although there is no specific information comparing use of fludarabine in the elderly with use in other age groups, it is not expected to cause different side effects or problems in older people than it does in younger adults.

Other medicines—Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When receiving fludarabine it is especially important that your health care professional know if you are taking any of the following:

• Amphotericin B by injection (e.g., Fungizone) or
• Antithyroid agents (medicine for overactive thyroid) or
• Azathioprine (e.g., Imuran) or
• Chloramphenicol (e.g., Chloromycetin) or
• Colchicine or
• Flucytosine (e.g., Ancobon) or
• Ganciclovir (e.g., Cytovene) or
• Interferon (e.g., Intron A, Roferon-A) or
• Plicamycin (e.g., Mithracin) or
• Zidovudine (e.g., AZT, Retrovir) or
• If you have ever been treated with radiation or cancer medicines—Fludarabine may increase the effects of these medicines or radiation therapy on the blood

• Probenecid (e.g., Benemid) or
• Sulfinpyrazone (e.g., Anturane)—Fludarabine may raise the amount of uric acid in the blood. Since these medicines are used to lower uric acid levels, they may not be as effective in patients receiving fludarabine

• Anemia or
• Immune deficiency condition—may increase the risk of side effects of fludarabine

• Chickenpox (including recent exposure) or
• Herpes zoster (shingles)—Risk of severe disease affecting other parts of the body

• Gout (history of) or
• Kidney stones (history of)—Fludarabine may increase levels of uric acid in the body, which can cause gout or kidney stones

• Infection—Fludarabine may decrease your body's ability to fight infection

• Kidney disease—Effects of fludarabine may be increased because of slower removal from the body

• Transfusions—non-irradiated blood transfusion may increase the risk of side effects of fludarabine

This medicine may cause nausea and vomiting. However, it is very important that you continue to receive the medicine even if you begin to feel ill. Ask your health care professional for ways to lessen these effects.

Dosing—

The dose of fludarabine will be different for different patients. The dose that is used may depend on a number of things, including what the medicine is being used for, the patient's size, and whether or not other medicines are also being taken. If you are receiving fludarabine at home, follow your doctor's orders or the directions on the label. If you have any questions about the proper dose of fludarabine, ask your doctor.

It is very important that your doctor check your progress at regular visits to make sure that this medicine is working properly and to check for unwanted effects.

While you are being treated with fludarabine, and after you stop treatment with it, do not have any immunizations (vaccinations) without your doctor's approval. Fludarabine may lower your body's resistance and there is a chance you might get the infection the immunization is meant to prevent. In addition, other persons living in your household should not take oral polio vaccine since there is a chance they could pass the polio virus on to you. Also, avoid persons who have recently taken oral polio vaccine. Do not get close to them and do not stay in the same room with them for very long. If you cannot take these precautions, you should consider wearing a protective face mask that covers the nose and mouth.

Fludarabine can temporarily lower the number of white blood cells in your blood, increasing the chance of getting an infection. It can also lower the number of platelets, which are necessary for proper blood clotting. If this occurs, there are certain precautions you can take, especially when your blood count is low, to reduce the risk of infection or bleeding:

• If you can, avoid people with infections. Check with your doctor immediately if you think you are getting an infection or if you get a fever or chills, cough or hoarseness, lower back or side pain, or painful or difficult urination.
• Check with your doctor immediately if you notice any unusual bleeding or bruising; black, tarry stools; blood in urine or stools; or pinpoint red spots on your skin.
• Be careful when using a regular toothbrush, dental floss, or toothpick. Your medical doctor, dentist, or nurse may recommend other ways to clean your teeth and gums. Check with your medical doctor before having any dental work done.
• Do not touch your eyes or the inside of your nose unless you have just washed your hands and have not touched anything else in the meantime.
• Be careful not to cut yourself when you are using sharp objects such as a safety razor or fingernail or toenail cutters.
• Avoid contact sports or other situations where bruising or injury could occur.

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Also, because of the way cancer medicines act on the body, there is a chance that they might cause other unwanted effects that may not occur until months or years after the medicine is used. These delayed effects may include certain types of cancer. Discuss these possible effects with your doctor.

Check with your doctor or nurseimmediately if any of the following side effects occur:

• More common
  • Arm, back or jaw pain;  black, tarry stools;  blood in urine or stools;  chest pain or discomfort;  chest tightness or heaviness ;  constipation;  cough or hoarseness;  coughing or spitting up blood;  fast or irregular heartbeat;  fever or chills;  general feeling of discomfort or illness ;  lower back or side pain;  nausea;  pain;  painful, burning, or difficult urination;  pale skin;  pinpoint red spots on skin;  shortness of breath;  sneezing;  sore throat;  sores, ulcers, or white spots on lips or in mouth;  stomach pain, severe;  sweating;  swelling;  tender, swollen glands in neck;  thickening of bronchial secretions ;  troubled breathing;  unusual bleeding or bruising;  unusual tiredness or weakness ;  vomiting of blood or material that looks like coffee grounds;  wheezing 
  
  

• Less common
  • Agitation;  aneurysm;  bleeding gums;  blurred vision;  confusion;  decreased urine output;  difficulty in breathing or swallowing;  dilated neck veins;  dizziness;  extreme fatigue;  fainting;  fast, pounding, or irregular heartbeat, or pulse;  headache ;  increased menstrual flow or vaginal bleeding;  irregular breathing;  loss of hearing ;  nosebleeds;  numbness or tingling in fingers, toes, or face;  pain, redness, or swelling in arm or leg;  paralysis;  prolonged bleeding from cuts;  seizures ;  slurred speech;  sudden and severe inability to speak;  temporary blindness ;  weakness in arm and/or leg on one side of the body, sudden and severe;  weight gain 
  
  

• Rare
  • Blindness;  continuing vomiting;  dark-colored urine;  drowsiness;  frequent urination;  hives;  itching; ;  light-colored stools;  loss of appetite;  loss of consciousness ;  lower abdominal cramping;  muscle tremors;  puffiness or swelling of the eyelids or around the eyes, face, lips or tongue;  rapid, deep breathing;  restlessness;  skin rash;  stomach pain;  trouble speaking, thinking or walking;  unusual tiredness or weakness;  yellow eyes or skin 
  
  

Other side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

• More common
  • Abdominal pain;  bladder pain;  body aches or pain;  burning, crawling, itching, numbness, prickling, “pins and needles”, or tingling feelings;  cloudy urine;  congestion;  diarrhea;  difficulty in moving;  dry mouth or throat;  flushed, dry skin;  frequent urge to urinate;  fruit-like breath odor;  increased hunger ;  increased thirst;  increased urination;  joint pain;  muscle aching or cramping;  muscle pains or stiffness ;  runny nose;  swollen joints ;  trouble in swallowing;  voice changes;  weight loss 
  
  

• Less common
  • Abdominal fullness;  bluish color of skin;  changes in skin color;  cracked lips;  dandruff;  decreased urination;  decrease in height;  difficulty in sleeping;  discouragement ;  feeling sad or empty;  gaseous abdominal pain;  heartburn;  irritability;  loss of interest or pleasure;  lightheadedness;  oily skin;  pain or tenderness around eyes and cheekbones;  rapid breathing;  recurrent fever;  stuffy nose;  sunken eye;  trouble concentrating;  wrinkled skin  
  
  

This medicine may rarely cause a temporary loss of hair in some people. After treatment with fludarabine has ended, normal hair growth should return.

After you stop treatment with fludarabine, it may still produce some side effects that need attention. During this period of time, check with your doctor if you notice the following:

• Rare
  • Cough or hoarseness;  fever or chills ;  loss of vision;  lower back or side pain;  painful or difficult urination  
  
  

Other side effects not listed above may also occur in some patients. If you notice any other effects, check with your doctor.