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Capecitabine

 
Oncology Encyclopedia: Capecitabine

Key Terms: Colorectal cancer, Metastasis.

Definition

Capecitabine (brand name Xeloda) is a drug that interferes with the growth of cancer cells.

Purpose

Capecitabine is used to treat breast cancer and cancer of the colon and rectum (colorectal cancer) that have spread to other parts of the body (metastasized).

Description

Capecitabine is a recently developed drug. It is a type of medicine called an antimetabolite because it interferes with the metabolism and growth of cells. Capecitabine is an unusual anti-cancer drug in that it is most active in cancer cells; normal cells are exposed to far lower concentrations of the drug. Cancer cells convert capecitabine into another anti-cancer drug called 5-fluorouracil (fluorouracil). This substance prevents cells from growing and reproducing by interfering with the production of DNA and RNA. Eventually the cells die.

Capecitabine has been approved by the U.S. Food and Drug Administration for the treatment of metastasized breast cancer that is resistant to standard chemotherapy. Capecitabine may be used in combination with the drug docetaxel (Taxotere). A study completed in 2003 found that the combination of docetaxel and capecitabine improves survival in women with metastatic breast cancer without a significant increase in treatment-related side effects.

A study completed in 2001 found that capecitabine is as effective as 5-fluorouracil for treating metastasized colorectal cancer, and has fewer and less severe side effects. However, it does not increase the average survival time of approximately 13 months.

Recommended Dosage

The dosage of capecitabine depends on a number of factors including body size. The average dosage is 2500 mg per square meter of body surface area per day. Capecitabine is a pill that is taken with water within 30 minutes after a meal. It may be taken every 12 or 24 hours. For colorectal cancer, capecitabine may be administered for two weeks, followed by one week off, for a total of 30 weeks.

Precautions

Capecitabine can temporarily reduce the number of white blood cells, thus reducing the body's ability to fight infection. It is very important to avoid exposure to infections and to receive prompt medical treatment if exposed. Immunizations (vaccinations) should be avoided during or after treatment with capecitabine. It also is important to avoid contact with individuals who have recently taken an oral polio vaccine.

Capecitabine may temporarily reduce the number of blood platelets that are necessary for blood clotting. The risk of bleeding may be reduced by:

  • using caution when cleaning teeth
  • avoiding dental work
  • avoiding cuts, bruises, or other injuries

Capecitabine can cause birth defects and fetal death in animals. Therefore, this drug should not be taken by pregnant women or by either a man or woman at the time of conception. Because capecitabine may cause serious side effects, women usually are advised against breast-feeding while taking this drug.

Some individuals may have an allergic reaction to capecitabine. Allergies to foods, preservatives, or dyes, or to the drug 5-fluorouracil must be considered before this drug is prescribed.

Side Effects

Common side effects of capecitabine may include:

  • loss of appetite (anorexia
  • diarrhea
  • nausea and vomiting
  • stomach or abdominal pain
  • swelling, peeling, redness, or blistering of hands and feet
  • numbness, pain, itching, or tingling in hands and feet
  • pain, swelling, or sores in the mouth or on the lips
  • rashes or dry skin
  • fatigue or weakness due to reduced red blood cell count The treatment is stopped if side effects are severe enough to interfere with eating or other normal activities.

Less common or rare side effects of capecitabine may include:

  • constipation
  • cough or hoarseness
  • difficulty swallowing
  • shortness of breath
  • chest pain
  • blood pressure changes
  • fast or irregular heartbeat
  • pain or swelling of the ankles, legs, or stomach
  • poor coordination, dizziness
  • changes in fingernails or toenails
  • headache
  • heartburn
  • sensitivity to sunlight
  • muscle pain
  • eye irritation
  • insomnia
  • lower back or side pain
  • painful or difficult urination

Side effects of capecitabine may include symptoms of infection, such as fever, chills, sore throat, or swollen glands, or symptoms of liver malfunction. Side effects also may include unusual bleeding or bruising due to the reduction in blood platelets.

Other diseases or medical conditions may increase the side effects associated with capecitabine. Chicken pox or shingles (Herpes zoster) may become severe and spread to other parts of the body. If heart, kidney, or liver disease is present, the side effects related to these organs may be more severe. In addition, in the presence of liver disease, the amount of capecitabine in the body may be higher. Individuals over the age of 80 often experience more severe side effects with capecitabine.

Interactions

Other drugs that may interact with capecitabine include:

  • Amphotericin B (Fungizone)
  • Antithyroid drugs that are used to treat an overactive thyroid
  • Azathioprine (Imuran)
  • Chloramphenicol (Chloromycetin)
  • Colchicine
  • Flucytosine (Ancobon)
  • Ganciclovir (Cytovene)
  • Interferon (Intron A, Roferon-A)
  • Plicamycin (Mithracin)
  • Zidovudine (AZT, Retrovir)

Coumadin-type anticoagulants that are used to thin the blood and medicines containing aspirin can increase the chances of bleeding. Folic acid, alone or in a multi-vitamin, may increase the side effects of capecitabine. Finally, capecitabine can increase the effects on the blood of other cancer medicines or radiation therapy.

Resources

Periodicals

"Docetaxel and Capecitabine Improve Survival in Metastatic Breast Cancer." Drug Week October 10, 2003: 57.

—Margaret Alic, Ph.D.; Teresa G. Odle

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Drug Info: Capecitabine
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Brand names: Xeloda®

Chemical formula:



Capecitabine tablets

What are capecitabine tablets?

CAPECITABINE (Xeloda®) is a type of chemotherapy for treating cancer. Capecitabine interferes with the growth of cancer cells and decreases the size of the tumor. It is used for treating breast cancer, and colon or rectal cancer. Generic capecitabine tablets are not yet available.

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

They need to know if you have any of these conditions:
• bleeding or blood disorders
• decreased kidney function
• heart disease such as angina or coronary artery disease
• infection (especially virus infection such as chickenpox or herpes)
• irregular heart beat
• liver disease
• recent radiation therapy
• an unusual or allergic reaction to capecitabine, 5-fluorouracil, other medicines, foods, dyes, or preservatives
• pregnant or trying to get pregnant
• breast-feeding

How should I take this medicine?

Take capecitabine tablets by mouth within 30 minutes after the end of a meal (usually breakfast and dinner). Follow the directions on the prescription label. Swallow the tablets with a drink of water. Do not take your medicine more often than directed. Finish the full course prescribed by your doctor or health care professional, even if the tablets make you feel unwell. Do not stop taking except on your prescriber's advice.

Your prescriber or health care professional may want you to take a combination of 150 mg and 500 mg tablets for each dose. If a combination of tablets is prescribed, it is very important that you correctly identify the tablets. Taking the wrong tablets could result in an overdose (too much medication) or underdose (too little medication).

What if I miss a dose?

If you miss a dose, skip that dose and do not take double or extra doses. Instead, continue your regular dosing schedule and check with your prescriber or health care professional. If you vomit after taking a dose, call your prescriber or health care professional for advice.

What drug(s) may interact with capecitabine?

• aluminum hydroxide or magnesium hydroxide (Maalox®)
digoxin
• folic acid
leucovorin
phenytoin
warfarin

Tell your prescriber or health care professional about all other medicines you are taking, including nonprescription medicines, nutritional supplements, or herbal products. Also tell your prescriber or health care professional if you are a frequent user of drinks with caffeine or alcohol, if you smoke, or if you use illegal drugs. These may affect the way your medicine works. Check with your health care professional before stopping or starting any of your medicines.

What should I watch for while taking capecitabine?

Visit your prescriber or health care professional for checks on your progress. You will need to have regular blood checks. The side effects of capecitabine can continue after you finish your treatment; report side effects right away.

Capecitabine may make you feel generally unwell. This is not uncommon because capecitabine affects good cells as well as cancer cells. Report any side effects as above, but continue your course of medicine even though you feel ill, unless your prescriber or health care professional tells you to stop.

Capcitabine will decrease your body's ability to fight infections. Call your prescriber or health care professional if you have a fever, chills, sore throat or other symptoms of a cold or flu. Do not treat these symptoms yourself. Try to avoid being around people who are sick. Capecitabine may increase your risk to bruise or bleed. Call your prescriber or health care professional if you notice any unusual bleeding. Be careful not to cut, bruise or injure yourself because you may get an infection and bleed more than usual.

Capecitabine may harm your unborn baby. You should contact your prescriber immediately if you believe or suspect you or your partner have become pregnant while you are taking capecitabine.

If you are going to have surgery, tell your prescriber or health care professional that you are taking capecitabine.

What side effects may I notice from taking capecitabine?

The side effects you may experience with capecitabine therapy depend upon the dose, other types of chemotherapy or radiation therapy given, and the disease being treated. Not all of these effects occur in all patients. Discuss any concerns or questions with your prescriber or health care professional.

Side effects that you should report to your prescriber or health care professional as soon as possible:
• low blood counts - capecitabine 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 (100.5 degrees F or greater) 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, blood in the urine
• signs of decreased red blood cells - unusual weakness or tiredness, fainting spells, lightheadedness
• dehydration (excessive water loss from the body)
• hand-and-foot syndrome: pain, swelling, redness, or tingling of the hands and/or feet
• pain, redness, swelling, or sores in your mouth or throat
• severe diarrhea (more than 4 bowel movements a day or any diarrhea at night)
• severe nausea/vomiting (if you lose your appetite and eat much less than usual or vomit more than once in a 24 hour period)
• yellow color of skin or eyes

Side effects that usually do not require medical attention (report to your prescriber or health care professional if they continue or are bothersome):
• bone pain
• constipation
• difficulty sleeping
• dry or itchy skin
• eye irritation
• headache
• heart burn or indigestion
• loss of appetite or decreased appetite
• mild nausea or stomach upset
• mild diarrhea
• muslce aches
• tiredness
• weakness

Where can I keep my medicine?

Keep out of the reach of children in a container that small children cannot open.

Store at room temperature between 15—30 degrees C (59—86 degrees F). Protect from moisture. Keep container tightly closed. Throw away any unused medicine after the expiration date.

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: Capecitabine
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Capecitabine
Systematic (IUPAC) name
pentyl[1-(3,4-dihydroxy-5-methyl-tetrahydrofuran-2-yl)- 5-fluoro-2-oxo-1H-pyrimidin- 4-yl]aminomethanoate
Identifiers
CAS number 154361-50-9
ATC code L01BC06
PubChem 60953
DrugBank APRD00203
ChemSpider 54916
Chemical data
Formula C15H22FN3O6 
Mol. mass 359.35 g/mol
SMILES eMolecules & PubChem
Pharmacokinetic data
Bioavailability Extensive
Protein binding < 60%
Metabolism Hepatic, to 5'-DFCR, 5'-DFUR (inactive); neoplastic tissue, 5'-DFUR to active fluorouracil
Half life 38–45 minutes
Excretion Renal 95.5%, faecal 2.6%
Therapeutic considerations
Pregnancy cat.

D(AU) D(US)

Legal status

Prescription Only (S4)(AU) POM(UK) -only(US)

Routes Oral
 Yes check.svgY(what is this?)  (verify)

Capecitabine (INN) (pronounced /keɪpˈsaɪtəbiːn/) (Xeloda, Roche) is an orally-administered chemotherapeutic agent used in the treatment of metastatic breast and colorectal cancers. Capecitabine is a prodrug, that is enzymatically converted to 5-fluorouracil in the tumor, where it inhibits DNA synthesis and slows growth of tumor tissue. The activation of capecitabine follows a pathway with three enzymatic steps and two intermediary metabolites, 5'-deoxy-5-fluorocytidine (5'-DFCR) and 5'-deoxy-5-fluorouridine (5'-DFUR), to form 5-fluorouracil.

Contents

Indications

Capecitabine is FDA-approved for:

  • Adjuvant in colorectal cancer Stage III Dukes' C - used as first-line monotherapy.
  • Metastatic colorectal cancer - used as first-line monotherapy, if appropriate.
  • Metastatic breast cancer - used in combination with docetaxel, after failure of anthracycline-based treatment. Also as monotherapy, if the patient has failed paclitaxel-based treatment, and if anthracycline-based treatment has either failed or cannot be continued for other reasons (i.e., the patient has already received the maximum lifetime dose of an anthracycline).

In the UK, capecitabine is approved by the National Institute for Health and Clinical Excellence (NICE) for colon and colorectal cancer, and locally advanced or metastatic breast cancer.[1]

Dose

The usual starting dose is 2,500 mg/m2/day in two divided doses, 12 hours apart. One cycle includes two weeks of treatment followed by one week without treatment. Cycles can be repeated every three weeks.

Dose adjustments

  • For mild renal dysfunction (creatinine clearance 30-50 mL/min), it is recommended to reduce dose by 25%.
  • For severe renal dysfunction (creatinine clearance <30 mL/min), treatment is not recommended.
  • There is no recommendation for hepatic dysfunction.
  • For elderly patients, lower doses may be required due to higher incidences of serious adverse reactions.
  • Patients with Dihydropyrimidine dehydrogenase deficiency (a.k.a. DPD deficiency), a pharmacogenetic syndrome affecting capecitabine detoxification process in the liver, should have their dosage tailored.

Side effects

Potential major adverse reactions include:

Drug interactions

  • May interact with warfarin and increase bleeding risk.
  • May inhibit cytochrome CYP2C9 enzyme, and therefore increase levels of substrates such as phenytoin and other substrates of CYP2C9.
  • Much as fluorouracil, the concomitant use of leucovorin may increase both the efficacy while reducing the toxicity of capecitabine.
Xeloda Logo

Formulation

Capecitabine (as brand-name Xeloda) is available in light peach 150 mg tablets and peach 500 mg tablets.

References

  • Lacy, Charles F; Armstrong, Lora L; Goldman, Morton P; Lance, Leonard L (2004). Lexi-Comp's Drug Information Handbook (12th Edition). Lexi-Comp Inc. ISBN 1-59195-083-X
  • Fischer, David S; Knobf, M Tish; Durivage, Henry J; Beaulieu, Nancy J (2003). The Cancer Chemotherapy Handbook (6th Edition). Mosby. ISBN 0-323-01890-4
  • Thomson Centerwatch: Drugs Approved by the FDA (Xeloda) Retrieved 6/05
  • Mercier C, Ciccolini J (2007). "Severe or lethal toxicities upon capecitabine intake: is DPYD genetic polymorphism the ideal culprit?". Trends in pharmacological sciences 28 (12): 597–598. doi:10.1016/j.tips.2007.09.009. PMID 18001850.

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Copyrights:

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 "Capecitabine" Read more