Fludarabine (Fludara®)

Antimetabolites interfere with DNA production. This stops cell growth and division, resulting in the slowing or stopping of cancer growth. Since cancer cells, in general, divide faster and with less error-correcting than healthy cells, cancer cells are more sensitive to this damage.

Fludarabine exerts its anti-cancer effect by preventing DNA synthesis through inhibition of DNA polymerase (an enzyme that plays a major role in making DNA). Lack of functional DNA prevents the cancer cell from reproducing, which results in death of the cell. In this way, slowing or stopping the growth of cancer cells in your body.

How to Take Fludarabine

Fludarabine is given by intravenous (IV, into a vein) infusion, over about 30 minutes. The dosage and schedule is determined by the person's size and type of cancer. It can be given alone or with other drugs.

This medication can cause lung issues when co-administered with pentostatin.

You should also be careful when driving or operating heavy machinery as this drug can cause dizziness and seizures.

Possible Side Effects of Fludarabine

There are a number of things you can do to manage the side effects of fludarabine. Talk to your care team about these recommendations. They can help you decide what will work best for you. These are some of the most common or important side effects:

Low White Blood Cell Count (Leukopenia or Neutropenia)

White blood cells (WBC) are important for fighting infection. While receiving treatment, your WBC count can drop, putting you at a higher risk of getting an infection. You should let your doctor or nurse know right away if you have a fever (temperature greater than 100.4°F or 38°C), ), sore throat or cold, shortness of breath, cough, burning with urination, or a sore that doesn't heal.

Tips to preventing infection:

• Washing hands, both yours and your visitors, is the best way to prevent the spread of infection.
• Avoid large crowds and people who are sick (i.e.: those who have a cold, fever or cough or live with someone with these symptoms).
• When working in your yard, wear protective clothing including long pants and gloves.
• Do not handle pet waste.
• Keep all cuts or scratches clean.
• Shower or bathe daily and perform frequent mouth care.
• Do not cut cuticles or ingrown nails. You may wear nail polish, but not fake nails.
• Ask your oncology care team before scheduling dental appointments or procedures.
• Ask your oncology care team before you, or someone you live with has any vaccinations.

Low Red Blood Cell Count (Anemia)

Your red blood cells are responsible for carrying oxygen to the tissues in your body. When the red cell count is low, you may feel tired or weak. You should let your oncology care team know if you experience any shortness of breath, difficulty breathing or pain in your chest. If the count gets too low, you may receive a blood transfusion.

Low Platelet Count (Thrombocytopenia)

Platelets help your blood clot, so when the count is low you are at a higher risk of bleeding. Let your oncology care team know if you have any excess bruising or bleeding, including nose bleeds, bleeding gums or blood in your urine or stool. If the platelet count becomes too low, you may receive a transfusion of platelets.

• Do not use a razor (an electric razor is fine).
• Avoid contact sports and activities that can result in injury or bleeding.
• Do not take aspirin (salicylic acid), non-steroidal, anti-inflammatory medications (NSAIDs) such as Motrin/Advil (ibuprofen), Aleve (naproxen), Celebrex (celecoxib) etc. as these can all increase the risk of bleeding. Please consult with your healthcare team regarding use of these agents and all over the counter medications/supplements while on therapy.
• Do not floss or use toothpicks and use a soft-bristle toothbrush to brush your teeth.

Neurotoxicity and Neuropathy

Fludarabine can cause neurologic changes, including visual changes, blindness, seizure, agitation, and confusion. These side effects can be related to the dose of the medication received. If you experience any vision changes, seizures, mood changes or confusion, report these symptoms to your care team immediately.

Peripheral neuropathy is a toxicity that affects the nerves. It causes a numbness or tingling feeling in the hands and feet, often in the pattern of a stocking or glove. This can get progressively worse with additional doses of the medication. In some people, the symptoms slowly resolve after the medication is stopped, but for some it never goes away completely. You should let your healthcare provider know if you experience numbness or tingling in the hands and feet, as they may need to adjust the doses of your medication.

Nausea and/or Vomiting

Talk to your oncology care team so they can prescribe medications to help you manage nausea and vomiting. In addition, dietary changes may help. Avoid things that may worsen the symptoms, such as heavy or greasy/fatty, spicy or acidic foods (lemons, tomatoes, oranges). Try saltines, or ginger ale to lessen symptoms.

Call your oncology care team if you are unable to keep fluids down for more than 12 hours or if you feel lightheaded or dizzy at any time.

Fatigue

Fatigue is very common during cancer treatment and is an overwhelming feeling of exhaustion that is not usually relieved by rest. While on cancer treatment, and for a period after, you may need to adjust your schedule to manage fatigue. Plan times to rest during the day and conserve energy for more important activities. Exercise can help combat fatigue; a simple daily walk with a friend can help. Talk to your healthcare team for helpful tips on dealing with this side effect.

Decrease in Appetite or Taste Changes

Nutrition is an important part of your care. Cancer treatment can affect your appetite and, in some cases, the side effects of treatment can make eating difficult. Ask your oncology care team about nutritional counseling services at your treatment center to help with food choices.

• Try to eat five or six small meals or snacks throughout the day, instead of 3 larger meals.
• If you are not eating enough, nutritional supplements may help.
• You may experience a metallic taste or find that food has no taste at all. You may dislike foods or beverages that you liked before receiving cancer treatment. These symptoms can last for several months or longer after treatment ends.
• Avoid any food that you think smells or tastes bad. If red meat is a problem, eat chicken, turkey, eggs, dairy products and fish without a strong smell. Sometimes cold food has less of an odor.
• Add extra flavor to meat or fish by marinating it in sweet juices, sweet and sour sauce or dressings. Use seasonings like basil, oregano or rosemary to add flavor. Bacon, ham and onion can add flavor to vegetables.

Live Vaccines

You, or anyone you live with, should avoid having live or live-attenuated vaccines while receiving this medication. These include herpes zoster (Zostavax) for shingles prevention, oral polio, measles, nasal flu vaccine (FluMist®), rotovirus and yellow fever vaccines.

Important but Less Common Side Effects

• Progressive Multifocal Leukoencephalopathy (PML): Progressive Multifocal Leukoencephalopathy (PML) is a rare but very serious brain infection that has been reported with this medication. The signs of PML may develop over several weeks or months. They may include changes in mood or usual behavior, confusion, thinking problems, loss of memory, changes in vision, speech, or walking, and decreased strength or weakness on one side of the body. If you develop any of these signs, notify your oncology care team immediately.
• Secondary Skin Cancers: There is a very low risk of developing non melanoma skin cancer or a worsening/flare-up of pre-existing non-melanoma skin cancer with this medication, which can occur many years after treatment. Because this medication has been associated with the development of skin cancers, it is important to practice sun safety. Avoid the sun between 10-2pm, when it is strongest. Wear sunscreen (at least SPF 15) everyday; wear sunglasses, a hat and long sleeves/pants to protect your skin and seek out shade whenever possible.
• Blood Transfusions: Patients receiving fludarabine should only receive irradiated blood products due to the potential for transfusion-related GVHD.
• Tumor Lysis Syndrome: If there are a large amount of tumor cells in your body prior to treatment, you are at risk for tumor lysis syndrome. This happens when the tumor cells die too quickly and their waste overwhelms the body. You may be given a medication (allopurinol) and IV fluids to help prevent this. If you experience nausea, vomiting, diarrhea or become lethargic (drowsy, sluggish), notify your oncology team right away. TLS can affect your kidney function. Your provider will monitor your kidney function with blood work. Notify your provider if you have little or no urine output.
• Autoimmune Issues: In rare cases, this medication can cause autoimmune issues including hemolytic anemia, thrombocytopenic purpura, Evan’s Syndrome, and hemophilia. Your care team will carefully monitor you for any of these issues.

Sexual & Reproductive Concerns

This medication may affect your reproductive system, resulting in the menstrual cycle or sperm production becoming irregular or stopping permanently. Women may experience menopausal effects including hot flashes and vaginal dryness. In addition, the desire for sex may decrease during treatment. You may want to consider sperm banking or egg harvesting if you may wish to have a child in the future. Discuss these options with your oncology team.

Exposure of an unborn child to this medication could cause birth defects, so you should not become pregnant or father a child while on this medication. For women, effective birth control is necessary during treatment and for at least 6 months after treatment, even if your menstrual cycle stops. Men should not father a child while taking this medication or for 95 days after your last dose. You should not breastfeed while receiving this medication.