Capecitabine

Clinical data
Pronunciation	/kæpɪˈsaɪtəbiːn/
Trade names	Xeloda, Xitabin, Kapetral, others
AHFS/Drugs.com	Monograph
MedlinePlus	a699003
License data	EU EMA: by INN
Pregnancy category	AU: D
Routes of administration	By mouth
Drug class	chemotherapy agent
ATC code	L01BC06 (WHO)
Legal status
Legal status	AU: S4 (Prescription only) CA: ℞-only UK: POM (Prescription only) US: WARNING[1]Rx-only EU: Rx-only
Pharmacokinetic data
Bioavailability	Extensive
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%)
Identifiers
IUPAC name Pentyl [1-(3,4-dihydroxy-5-methyltetrahydrofuran-2-yl)-5-fluoro-2-oxo-1H-pyrimidin-4-yl]carbamate
CAS Number	154361-50-9 Y
PubChem CID	60953
IUPHAR/BPS	6799
DrugBank	DB01101 Y
ChemSpider	54916 Y
UNII	6804DJ8Z9U
KEGG	D01223 Y
ChEBI	CHEBI:31348 Y
ChEMBL	ChEMBL1773 Y
CompTox Dashboard (EPA)	DTXSID3046451
ECHA InfoCard	100.112.980
Chemical and physical data
Formula	C15H22FN3O6
Molar mass	359.354 g·mol−1
3D model (JSmol)	Interactive image
SMILES FC=1\C(=N/C(=O)N(C=1)[C@@H]2O[C@@H]([C@@H](O)[C@H]2O)C)\NC(=O)OCCCCC
InChI InChI=1S/C15H22FN3O6/c1-3-4-5-6-24-15(23)18-12-9(16)7-19(14(22)17-12)13-11(21)10(20)8(2)25-13/h7-8,10-11,13,20-21H,3-6H2,1-2H3,(H,17,18,22,23)/t8-,10-,11-,13-/m1/s1 Y Key:GAGWJHPBXLXJQN-UORFTKCHSA-N Y
(verify)

Capecitabine, sold under the brand name Xeloda among others, is a anticancer medication used to treat breast cancer, gastric cancer and colorectal cancer.^[2] For breast cancer it is often used together with docetaxel.^[3] It is taken by mouth.^[3]

Common side effects include abdominal pain, vomiting, diarrhea, weakness, and rashes.^[3] Other severe side effects include blood clotting problems, allergic reactions, heart problems such as cardiomyopathy, and low blood cell counts.^[3] Use during pregnancy may result in harm to the fetus.^[3] Capecitabine, inside the body, is converted to 5-fluorouracil (5-FU) through which it acts.^[3] It belongs to the class of medications known as fluoropyrimidines, which also includes 5-FU and tegafur.^[4]

Capecitabine was patented in 1992 and approved for medical use in 1998.^[5] It is on the World Health Organization's List of Essential Medicines.^[6]

Medical uses

Capecitabine is indicated for

• adjuvant treatment of people with Stage III colon cancer as a single agent or as a component of a combination chemotherapy regimen;^[7]
• perioperative treatment of adults with locally advanced rectal cancer as a component of chemoradiotherapy;^[7]
• treatment of people with unresectable or metastatic colorectal cancer as a single agent or as a component of a combination chemotherapy regimen;^[7]
• treatment of people with advanced or metastatic breast cancer as a single agent if an anthracycline- or taxane-containing chemotherapy is not indicated;^[7]
• treatment of people with advanced or metastatic breast cancer in combination with docetaxel after disease progression on prior anthracycline-containing chemotherapy;^[7]
• treatment of adults with unresectable or metastatic gastric, esophageal, or gastroesophageal junction cancer as a component of a combination chemotherapy regimen;^[7]
• treatment of adults with HER2-overexpressing metastatic gastric or gastroesophageal junction adenocarcinoma who have not received prior treatment for metastatic disease as a component of a combination regimen;^[7]
• adjuvant treatment of adults with pancreatic adenocarcinoma as a component of a combination chemotherapy regimen.^[7]

Adverse effects

Adverse effects by frequency:^{[8][9][10][11]}

Very common (>10% frequency)

Notes on adverse effects:

Contraindications

Contraindications include:^[10]

• 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

Drug interactions

Drugs it is known to interact with include:^[10]

• 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.^[13]

Pharmacogenetics

The dihydropyrimidine dehydrogenase (DPD) enzyme is responsible for the detoxifying metabolism of fluoropyrimidines, a class of drugs that includes capecitabine, 5-fluorouracil and tegafur.^[4] 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.^[4][14] 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.^[4][14]

Mechanism of action

Click on genes, proteins and metabolites below to link to respective articles.^{[§ 1]}

[[File:

[[

]]

[[

]]

[[

]]

[[

]]

[[

]]

[[

]]

[[

]]

[[

]]

[[

]]

[[

]]

[[

]]

[[

]]

[[

]]

[[

]]

[[

]]

[[

]]

[[

]]

[[

]]

[[

]]

[[

]]

[[

]]

[[

]]

[[

]]

[[

]]

[[

]]

[[

]]

[[

]]

[[

]]

[[

]]

[[

]]

[[

]]

[[

]]

[[

]]

[[

]]

[[

]]

[[

]]

[[

]]

[[

]]

[[

]]

[[

]]

[[

]]

[[

]]

[[

]]

[[

]]

[[

]]

[[

]]

[[

]]

|alt=Fluorouracil (5-FU) Activity edit]]

Fluorouracil (5-FU) Activity edit

1. ^ The interactive pathway map can be edited at WikiPathways: "FluoropyrimidineActivity_WP1601".

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.^[15]

Drug synthesis

Society and culture

Brand names

One of the brand names is Xeloda, marketed by Genentech.

Others include Xitabin, Capcibin, Kapetral and Pecaset by Eurolab.