Pronunciation:

floo-DAYR-a-been

Dosage Forms:

• Powder for Solution
• Solution

Warnings:

Fludarabine can severely suppress bone marrow function when used at high doses. In dose-ranging studies in patients with acute leukemia, fludarabine was associated with severe neurologic effects, including blindness, coma, and death. Life-threatening and sometimes fatal autoimmune hemolytic anemia, autoimmune thrombocytopenia/thrombocytopenic purpura (ITP), Evan's syndrome, and acquired hemophilia has been reported to occur after one or more cycles of treatment. Closely monitor patients for hemolysis. In a clinical investigation using fludarabine for injection in combination with pentostatin (deoxycoformycin) for the treatment of refractory CLL, there was an unacceptably high incidence of fatal pulmonary toxicity. Therefore, the use of fludarabine for injection in combination with pentostatin is not recommended .

Classifications:

Therapeutic—

Antineoplastic Agent

Pharmacologic—

Antimetabolite

Uses of This Medicine:

Fludarabine injection belongs to the group of medicines called antimetabolites. It is used to treat a type of cancer of the white blood cells called B-cell chronic lymphocytic leukemia (CLL). This medicine is used in patients with CLL who have already been treated with an alkylating agent (e.g., bendamustine) that did not work well. .

Fludarabine injection interferes with the growth of cancer cells, which are eventually destroyed. Since the growth of normal body cells may also be affected by fludarabine injection, other effects may 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 injection, you and your doctor should talk about the good this medicine will do as well as the risks of using it.

Fludarabine injection is to be administered only by or under the immediate supervision of your doctor.

Before Using This Medicine:

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 this medicine, the following should be considered:

Allergies—

Tell your doctor if you have ever had any unusual or allergic reaction to this medicine or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Children—

Appropriate studies have not been performed on the relationship of age to the effects of fludarabine injection in the pediatric population. Safety and efficacy have not been established.

Older adults—

No information is available on the relationship of age to the effects of fludarabine injection in geriatric patients.

Breast-feeding—

There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding.

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 you are receiving this medicine, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using this medicine with any of the following medicines is not recommended. Your doctor may decide not to treat you with this medication or change some of the other medicines you take.

• 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 required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• 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

Other interactions—

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. Discuss with your healthcare professional the use of your medicine with food, alcohol, or tobacco.

Other medical problems—

The presence of other medical problems may affect the use of this medicine. Make sure you tell your doctor if you have any other medical problems, 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 increase levels of uric acid in the body, which can cause gout or kidney stones.

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

• Kidney disease—Use with caution. Effects of fludarabine injection may be increased because of slower removal of the medicine from the body.

• Transfusions—Non-irradiated blood transfusion may increase the risk of side effects of fludarabine injection.

Proper Use of This Medicine:

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.

Precautions While Using This Medicine:

It is very important that your doctor check your progress at regular visits to make sure 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, 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 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 effect.

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; a 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 keep from getting pregnant. You should not become pregnant while you are 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 in thinking, or trouble in 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.

Side Effects of This Medicine:

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

stomach pain, severe

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

weakness in the arm 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

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.