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Fludarabine

 

Key Terms: Anemia, Chemotherapy, Deoxynucleic acid, Electrolytes, Food and Drug Administration, Gout, Intravenous, Neutropenia.

Definition

Fludarabine is a chemotherapy medicine used to treat certain types of cancer by destroying cancerous cells. It is known as the brand name Fludara. Fludarabine may also be referred to as Fludarabine phosphate, 2-fluoroadenine aribinoside 5-phosphate, and FAMP.

Purpose

Fludarabine is approved by the Food and Drug Administration (FDA) to treat refractory chronic lymphocytic leukemia (CLL). Patients must have a disease that did not respond to other treatment or a disease that became worse during other treatment. Fludarabine has also been used to treat Hodgkin's and non-Hodgkin's lymphoma, cutaneous T-cell lymphoma, macroglobulinemic lymphoma, mycosis fungoides, and hairy cell leukemia.

Description

Fludarabine has been available for use since the early 1990s, and is a member of the group of chemotherapy drugs known as antimetabolites. Antimetabolites interfere with the genetic material (DNA) inside the cancer cells and prevent them from further dividing and growing more cancer cells.

Recommended Dosage

Fludarabine is a clear solution that is administered through a vein.

A fludarabine dose can be determined using a mathematical calculation that measures a person's body surface area (BSA). This number is dependent upon a patient's height and weight. The larger the person, the greater the body surface area. BSA is measured in the units known as square meter (m2). The body surface area is calculated and then multiplied by the drug dosage in milligrams per square meter (mg/m2). This calculates the actual dose a patient is to receive.

The approved dose for chronic lymphocytic leukemia is 25 milligrams per square meter per day for 5 days in a row. The fludarabine is given intravenously into a vein over a 30-minute to 2-hour time period. This 5-day cycle is repeated every 4 weeks.

The dose of fludarabine may need to be decreased in patients who have kidney problems.

Precautions

Blood counts will be monitored regularly while on fludarabine therapy. During a certain time period after receiving fludarabine, there is an increased risk of getting infections. Caution should be taken to avoid unnecessary exposure to crowds and people with infections.

Patients with a known previous allergic reaction to chemotherapy drugs should tell their doctor.

Patients who may be pregnant or are trying to become pregnant should tell their doctor before receiving fludarabine. Chemotherapy can cause men and women to be sterile, or unable to have children. It is unknown if fludarabine has this effect on humans.

Patients should check with their doctors before receiving live virus vaccines while on chemotherapy.

Side Effects

The most common side effect expected from taking fludarabine is low blood counts (myelosuppression). When the white blood cell count is lower than normal (neutropenia), patients are at an increased risk of developing a fever and infections. Patients may need to be treated with antibiotics at this point. The platelet blood count can also be decreased due to fludarabine administration, but generally returns to normal within 2 weeks after the end of the infusion. Platelets are blood cells that cause clots to form to stop bleeding. When the platelet count is low, patients are at an increased risk for bruising and bleeding. Fludarabine causes low red blood cell counts (anemia). Low red counts make people feel tired and dizzy.

Fludarabine can cause the development of autoimmune hemolytic anemia, which occurs when the body begins to destroy its own red blood cells. It is an uncommon side effect, but very serious when it occurs.

Common side effects from fludarabine include nausea and vomiting. If nausea and vomiting are a problem, patients can be given antiemetics before receiving fludarabine. This medication helps prevent or decrease these side effects. Other common side effects include fever, chills, joint pain, fluid gain, fatigue, sleepiness, pain, muscle ache, weakness, and infection. Other less common side effects include loss of appetite (anorexia), diarrhea, abnormal touch sensation, cough, pneumonia, and shortness of breath.

Damage to the nerves and nervous system tissues can occur with fludarabine. Side effects due to this nerve damage include sleepiness, confusion, weakness, fatigue, irritability, numbness or tingling in the hands and feet, visual changes, and difficulty walking.

Infrequent side effects of fludarabine are skin rashes, pain, itching, fever, lung problems, insomnia, headache, muscle and joint aches, swelling, and decreased blood pressure.

Rare side effects of fludarabine include mouth sores, constipation and abdominal cramping, bleeding from the bladder, hair loss, hearing problems, and liver and kidney problems.

Fludarabine can cause the rapid breakdown of cancer cells. Patients who have large numbers of cancer cells in their bloodstream can develop a problem known as tumor lysis syndrome. The symptoms of this syndrome include pain in the lower back and blood in the urine. A patient can develop high or low levels of electrolytes and high levels of uric acid, which can lead to gout and kidney damage. The drug allopurinol may be given to patients prior to fludarabine treatment to prevent this from occurring. Drinking an increased amount of liquids also may help prevent the kidney damage.

All side effects a patient experiences should be reported to the doctor.

Interactions

Fludarabine should not be used in combination with the drug pentostatin. The combination causes severe lung damage.

—Nancy J. Beaulieu, R.Ph., B.C.O.P.

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Drug Info: Fludarabine
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Brand names: Fludara®

Chemical formula:



Fludarabine Phosphate Solution for injection

What is this medicine?

FLUDARABINE is a chemotherapy drug. It interferes with the growth of cancer cells. It is usually used to treat chronic lymphocytic leukemia (CLL).

This medicine may be used for other purposes; ask your health care provider or pharmacist if you have questions.

What should I tell my health care provider before I take this medicine?

They need to know if you have any of these conditions:
•infection (especially virus infection such as chickenpox or cold sores)
•kidney disease
•low blood counts like low platelets, red blood cells, white blood cells
•an unusual or allergic reaction to fludarabine, other chemotherapy, other medicines, foods, dyes, or preservatives
•pregnant or trying to get pregnant
•breast-feeding

How should I use this medicine?

This drug is given as an infusion into a vein. It is administered in a hospital or clinic by a specially trained health care professional.

Talk to your pediatrician regarding the use of this medicine in children. Special care may be needed.

Overdosage: If you think you have taken too much of this medicine contact a poison control center or emergency room at once.
NOTE: This medicine is only for you. Do not share this medicine with others.

What may interact with this medicine?

Do not take this medicine with any of the following medications:
•pentostatin

This medicine may also interact with the following medications:
•medicines to increase blood counts like filgrastim, pegfilgrastim, sargramostim
•vaccines

Talk to your doctor or health care professional before taking any of these medicines:
•acetaminophen
•aspirin
•ibuprofen
•naproxen
•ketoprofen

This list may not describe all possible interactions. Give your health care provider a list of all the medicines, herbs, non-prescription drugs, or dietary supplements you use. Also tell them if you smoke, drink alcohol, or use illegal drugs. Some items may interact with your medicine.

What should I watch for while using this medicine?

This drug may make you feel generally unwell. This is not uncommon, as chemotherapy can affect healthy cells as well as cancer cells. Report any side effects. Continue your course of treatment even though you feel ill unless your doctor tells you to stop.

Call your doctor or health care professional for advice if you get a fever, chills or sore throat, or other symptoms of a cold or flu. Do not treat yourself. This drug decreases your body's ability to fight infections. Try to avoid being around people who are sick.

This medicine may increase your risk to bruise or bleed. Call your doctor or health care professional if you notice any unusual bleeding.

Be careful brushing and flossing your teeth or using a toothpick because you may get an infection or bleed more easily. If you have any dental work done, tell your dentist you are receiving this medicine.

Avoid taking products that contain aspirin, acetaminophen, ibuprofen, naproxen, or ketoprofen unless instructed by your doctor. These medicines may hide a fever.

Do not become pregnant while taking this medicine. Women should inform their doctor if they wish to become pregnant or think they might be pregnant. There is a potential for serious side effects to an unborn child. Talk to your health care professional or pharmacist for more information. Do not breast-feed an infant while taking this medicine.

Men should inform their doctors if they wish to father a child. This medicine may lower sperm counts.

What side effects may I notice from receiving this medicine?

Side effects that you should report to your doctor or health care professional as soon as possible:
•allergic reactions like skin rash, itching or hives, swelling of the face, lips, or tongue
•low blood counts - this medicine may decrease the number of white blood cells, red blood cells and platelets. You may be at increased risk for infections and bleeding.
•signs of infection - fever or chills, cough, sore throat, pain or difficulty passing urine
•signs of decreased platelets or bleeding - bruising, pinpoint red spots on the skin, black, tarry stools, nosebleeds
•signs of decreased red blood cells - unusually weak or tired, fainting spells, lightheadedness
•breathing problems
•changes in hearing
•changes in vision
•confusion
•dry cough
•mouth sores
•muscle weakness
•pain, tingling, numbness in the hands or feet
•swelling of the ankles, feet, hands
•trouble passing urine or change in the amount of urine
•yellowing of the eyes or skin

Side effects that usually do not require medical attention (report to your doctor or health care professional if they continue or are bothersome):
•constipation
•diarrhea
•hair loss
•loss of appetite
•nausea, vomiting
•trouble sleeping

This list may not describe all possible side effects. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Where should I keep my medicine?

This drug is given in a hospital or clinic and will not be stored at home.

Last updated: 7/1/2002

Important Disclaimer: The drug information provided here is for educational purposes only. It is intended to supplement, not substitute for, the diagnosis, treatment and advice of a medical professional. This drug information does not cover all possible uses, precautions, side effects and interactions. It should not be construed to indicate that this or any drug is safe for you. Consult your medical professional for guidance before using any prescription or over the counter drugs.

Wikipedia: Fludarabine
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Fludarabine
Systematic (IUPAC) name
[(2R,3R,4S,5R)-5-(6-amino-2-fluoro-purin-9-yl)- 3,4-dihydroxy-oxolan-2-yl]methoxyphosphonic acid
Identifiers
CAS number 75607-67-9
ATC code L01BB05
PubChem 30751
DrugBank APRD00594
Chemical data
Formula C10H13FN5O7P 
Mol. mass 365.212 g/mol
Pharmacokinetic data
Bioavailability 55%
Protein binding 19 to 29%
Metabolism  ?
Half life 20 hours
Excretion Renal
Therapeutic considerations
Pregnancy cat.

D

Legal status

Prescription Only (S4)(AU) POM(UK)

Routes Intravenous, oral
 Yes check.svgY(what is this?)  (verify)

Fludarabine or fludarabine phosphate (Fludara) is a chemotherapy drug used in the treatment of hematological malignancies.

Contents

Indications

Fludarabine is highly effective in the treatment of chronic lymphocytic leukemia, producing higher response rates than alkylating agents such as chlorambucil alone.[1] Fludarabine is used in various combinations with cyclophosphamide, mitoxantrone, dexamethasone and rituximab in the treatment of indolent non-Hodgkins lymphomas. As part of the FLAG regimen, fludarabine is used together with cytarabine and granulocyte colony-stimulating factor in the treatment of acute myeloid leukaemia. Because of its immunosuppressive effects, fludarabine is also used in some conditioning regimens prior to non myeloablative allogeneic stem cell transplant.

Pharmacology

Fludarabine is a purine analog, and can be given both orally and intravenously. Fludarabine inhibits DNA synthesis by interfering with ribonucleotide reductase and DNA polymerase. It is active against both dividing and resting cells.

Side effects

Fludarabine is associated with profound lymphopenia, and as a consequence, increases the risk of opportunistic infections significantly. Patients who have been treated with fludarabine will usually be asked to take co-trimoxazole or to use monthly nebulised pentamidine to prevent Pneumocystis jiroveci pneumonia. The profound lymphopenia caused by fludarabine renders patients susceptible to transfusion-associated graft versus host disease, a fatal complication of blood transfusion. For this reason, all patients who have ever received fludarabine should only be given irradiated blood components.

Fludarabine causes anemia, thrombocytopenia and neutropenia, requiring regular blood count monitoring. Some patients require blood and platelet transfusion, or G-CSF injections to boost neutrophil counts.

Fludarabine is associated with the development of severe autoimmune hemolytic anemia in a proportion of patients.[2]

Difficulties are often encountered when harvesting peripheral blood stem cells from patients previously treated with fludarabine.[3]

References

  1. ^ Rai KR et al. Fludarabine compared with chlorambucil as primary therapy for chronic lymphocytic leukemia. N Engl J Med 2000;343:1750-7. PMID 11114313
  2. ^ Gonzalez H et al. Severe autoimmune hemolytic anemia in eight patients treated with fludarabine. Hematol Cell Ther. 1998;40:113-8. PMID 9698219
  3. ^ Tournilhac O et al. Impact of frontline fludarabine and cyclophosphamide combined treatment on peripheral blood stem cell mobilization in B-cell chronic lymphocytic leukemia. Blood 2004;103:363-5. PMID 12969985

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Oncology Encyclopedia. Gale Encyclopedia of Cancer. Copyright © 2006 by The Gale Group, Inc. All rights reserved.  Read more
Drug Info. Gold Standard. Copyright © 2008 by Gold Standard. All rights reserved.  Read more
Wikipedia. This article is licensed under the Creative Commons Attribution/Share-Alike License. It uses material from the Wikipedia article "Fludarabine" Read more