|Trade names||Xeloda, others|
|Drug class||chemotherapy agent|
|Protein binding||< 60%|
|Metabolism||liver, to 5'-DFCR, 5'-DFUR (inactive); neoplastic tissue, 5'-DFUR to active fluorouracil|
|Elimination half-life||38–45 minutes|
|Excretion||kidney (95.5%), faecal (2.6%)|
|Chemical and physical data|
|Molar mass||359.35 g/mol|
|3D model (JSmol)|
Capecitabine, sold under the brand name Xeloda among others, is a chemotherapy medication used to treat breast cancer, gastric cancer and colorectal cancer. For breast cancer it is often used together with docetaxel. It is taken by mouth.
Common side effects include abdominal pain, vomiting, diarrhea, weakness, and rashes. Other severe side effects include blood clotting problems, allergic reactions, heart problems, and low blood cell counts. It is not recommended in people with kidney problems. Use during pregnancy may result in harm to the baby. Capecitabine, inside the body, is converted to 5-fluorouracil (5-FU) through which it acts. It belongs to the class of medications known as fluoropyrimidines, which also includes 5-fluorouracil and tegafur.
Capecitabine was patented in 1992 and approved for medical use in 1998. It is on the World Health Organization's List of Essential Medicines, the most effective and safe medicines needed in a health system. The wholesale cost in the developing world is about 122.64 to 195.66 USD per cycle of medication. In the United Kingdom it costs the NHS about £210.67 per cycle. In the United States it costs about 1,892.00 USD as of 2016.
- Colorectal cancer (either as neoadjuvant therapy with radiation, adjuvant therapy or for metastatic cases)
- Breast cancer (metastatic or as monotherapy/combotherapy; this is licensed as a second-line treatment in the UK)
- Gastric cancer (off-label in the US; this is a licensed indication in the UK)
- Oesophageal cancer (off-label in the US)
- Very common (>10% frequency)
Notes on adverse effects:
- History of hypersensitivity to fluorouracil, capecitabine or any of its excipients
- DPD deficiency (see Pharmacogenetics)
- Pregnancy and lactation
- Severe leucopenia, neutropenia, or thrombocytopenia
- Severe hepatic impairment or severe renal impairment
- Treatment with sorivudine or its chemically related analogues, such as brivudine
Drugs it is known to interact with include:
- Sorivudine or its analogues, such as, brivudine.
- CYP2C9 substrates, including, warfarin and other coumarin-derivatives anticoagulants
- Phenytoin, as it increases the plasma concentrations of phenytoin.
- Calcium folinate may enhance the therapeutic effects of capecitabine by means of synergising with its metabolite, 5-FU. It may also induce more severe diarrhoea by means of this synergy.
The dihydropyrimidine dehydrogenase (DPD) enzyme is responsible for the detoxifying metabolism of fluoropyrimidines, a class of drugs that includes capecitabine, 5-fluorouracil and tegafur. Genetic variations within the DPD gene (DPYD) can lead to reduced or absent DPD activity, and individuals who are heterozygous or homozygous for these variations may have partial or complete DPD deficiency; an estimated 0.2% of individuals have complete DPD deficiency. Those with partial or complete DPD deficiency have a significantly increased risk of severe or even fatal drug toxicities when treated with fluoropyrimidines; examples of toxicities include myelosuppression, neurotoxicity and hand-foot syndrome.
Mechanism of action
Click on genes, proteins and metabolites below to link to respective articles.[§ 1]
Capecitabine is metabolised to 5-FU which in turn is a thymidylate synthase inhibitor, hence inhibiting the synthesis of thymidine monophosphate (ThMP), the active form of thymidine which is required for the de novo synthesis of DNA.
Society and culture
One of the brandnames is Xeloda, marketed by Genentech.
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- Reddening, swelling, numbness and desquamation on palms and soles
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- Xeloda.com (patient information, tools, and resources)