Fludarabine (Intravenous)

Fludarabine injection is a type of medicine known as an antimetabolite. It is used to treat a kind of cancer in the white blood cells called B-cell chronic lymphocytic leukemia (CLL). This medicine is for patients with CLL who have already received treatment with an alkylating agent (e.g., bendamustine) that was not effective.

Fludarabine injection works by interfering with the growth of cancer cells, leading to their eventual destruction. However, it can also affect the growth of normal body cells, which may lead to other effects. Some of these effects can be serious and should be reported to your doctor. There may also be effects that are not serious but could still cause concern. Some effects might not appear for months or even years after using the medicine.

Before starting treatment with fludarabine injection, you and your doctor should discuss the benefits of this medicine as well as the risks associated with it.

Fludarabine injection should only be given by or under the close supervision of your doctor.

It is very important that your doctor checks your progress at regular visits to ensure that this medicine is working properly. Blood tests may be needed to check for unwanted effects.

While you are being treated with fludarabine injection, and after you stop treatment with it, do not have any immunizations (vaccinations) without your doctor's approval. Fludarabine injection may lower your body's resistance, and there is a chance you might get the infection the immunization is meant to prevent. In addition, others in your household should not take oral polio vaccine since they could pass the polio virus on to you. Also, avoid people 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, consider wearing a protective face mask that covers your nose and mouth.

Fludarabine injection can temporarily lower the number of white blood cells in your blood, increasing the chance of getting an infection (e.g. pneumonia). 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 have fever or chills, cough or hoarseness, lower back or side pain, painful or difficult urination; shortness of breath; or unusual bleeding or bruising.
• Check with your doctor immediately if you notice any unusual bleeding or bruising; black, tarry stools; blood in the 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.

You should not use this medicine if you are also taking pentostatin (Nipent®). Taking it together with this medicine may increase the chance of serious side effects.

This medicine may cause a serious type of reaction called tumor lysis syndrome. Your doctor may give you a medicine to help prevent this. Call your doctor right away if you have a decrease or change in urine amount; joint pain, stiffness, or swelling; lower back, side, or stomach pain; rapid weight gain; swelling of the feet or lower legs; or unusual tiredness or weakness.

Using this medicine while you are pregnant can harm your unborn baby. Use an effective form of birth control to prevent getting pregnant. You should not become pregnant while taking this medicine and for 6 months after stopping it. If you think you have become pregnant while using the medicine, tell your doctor right away.

This medicine may cause unusual weakness, trouble thinking, or trouble seeing clearly. Make sure you know how you react to this medicine before you drive, use machines, or do other jobs that require you to be alert, well-coordinated, or able to think or see well.

In deciding to use a medicine, you and your doctor will weigh the risks against the benefits. Consider the following for this medicine:

Allergies

Inform your doctor if you have ever had an unusual or allergic reaction to this medicine or any other medicines. Also, let your health care professional know if you have any other allergies, such as to foods, dyes, preservatives, or animals. For over-the-counter products, read the label or package ingredients carefully.

Pediatric

Studies have not been done on how fludarabine injection affects children. Its safety and effectiveness in this age group have not been established.

Geriatric

There is no information available on how fludarabine injection affects older adults.

Breast Feeding

There are not enough studies in women to determine the risk to infants when using this medicine while breastfeeding. Consider the potential benefits and risks before using this medication during breastfeeding.

Interactions with Medicines

Some medicines should not be used together, while others may be combined even if an interaction could occur. In such cases, your doctor may adjust the dose or take other precautions. It is very important for your healthcare professional to know if you are taking any of the following medicines while receiving this medicine. The following interactions are significant but not all-inclusive.

Using this medicine with any of the following medicines is not recommended. Your doctor may choose not to treat you with this medication or adjust your other medicines.

• Measles Virus Vaccine, Live
• Mumps Virus Vaccine, Live
• Rotavirus Vaccine, Live
• Rubella Virus Vaccine, Live
• Varicella Virus Vaccine, Live
• Zoster Vaccine, Live

Using this medicine with any of the following medicines is usually not recommended, but may be necessary in some cases. If both medicines are prescribed, your doctor may change the dose or frequency of one or both.

• Adenovirus Vaccine
• Bacillus of Calmette and Guerin Vaccine, Live
• Cholera Vaccine, Live
• Dengue Tetravalent Vaccine, Live
• Influenza Virus Vaccine, Live
• Pentostatin
• Poliovirus Vaccine, Live
• Smallpox Vaccine
• Typhoid Vaccine, Live
• Yellow Fever Vaccine

Interactions with Food/Tobacco/Alcohol

Some medicines should not be taken around mealtimes or with certain foods due to possible interactions. Using alcohol or tobacco with some medicines may also lead to interactions. Discuss with your healthcare professional about using your medicine with food, alcohol, or tobacco.

Other Medical Problems

Other medical issues may affect how this medicine works. Make sure to tell your doctor if you have any other conditions, especially:

• Bone marrow problems (e.g., anemia, neutropenia, or thrombocytopenia)—Fludarabine injection may worsen these conditions.

• 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 raise uric acid levels, which can lead to gout or kidney stones.

• Infection—Fludarabine injection may lower your body's ability to fight infections.

• Kidney disease—Use with caution. The effects of fludarabine injection may be stronger due to slower removal from the body.

• Transfusions—Receiving non-irradiated blood transfusions may increase the risk of side effects from fludarabine injection.

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.

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

More common

• Arm, back, or jaw pain
• black, tarry stools
• blood in the 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 the skin
• shortness of breath
• sneezing
• sore throat
• sores, ulcers, or white spots on the lips or in the mouth
• severe stomach pain
• sweating
• swelling
• tender, swollen glands in the 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 the fingers, toes, or face
• pain, redness, or swelling in the arm or leg
• paralysis
• prolonged bleeding from cuts
• seizures
• slurred speech
• sudden and severe inability to speak
• temporary blindness
• sudden and severe weakness in the arm or leg on one side of the body
• 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
• yellow eyes or skin

Some 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
• decrease in height
• decreased urination
• 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 the eyes and cheekbones
• rapid breathing
• recurrent fever
• stuffy nose
• sunken eye
• trouble concentrating
• wrinkled skin

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

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

Available Dosage Forms:

• Powder for Solution
• Solution

Therapeutic Class: Antineoplastic Agent

Pharmacologic Class: Antimetabolite

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 doctor for ways to lessen these effects.

You will receive this medicine while you are in a hospital or cancer treatment center. A nurse or other trained health professional will give you this medicine.

This medicine is given through a needle placed in one of your veins. It is usually given every day for 5 days. This 5-day treatment is given again every 28 days until your body responds to the medicine. Each treatment usually takes about 30 minutes.