Capecitabine

Capecitabine

Systematic (IUPAC) name
Pentyl [1-(3,4-dihydroxy-5-methyltetrahydrofuran-2-yl)-5-fluoro-2-oxo-1H-pyrimidin-4-yl]carbamate
Clinical data
Trade names	Xeloda
AHFS/Drugs.com	monograph
MedlinePlus	a699003
Pregnancy category	AU: D US: D (Evidence of risk)
Legal status	AU: S4 (Prescription only) UK: POM (Prescription only) US: ℞-only
Routes of administration	Oral
Pharmacokinetic data
Bioavailability	Extensive
Protein binding	< 60%
Metabolism	Hepatic, to 5'-DFCR, 5'-DFUR (inactive); neoplastic tissue, 5'-DFUR to active fluorouracil
Biological half-life	38–45 minutes
Excretion	Renal (95.5%), faecal (2.6%)
Identifiers
CAS Number	154361-50-9 Y
ATC code	L01BC06 (WHO)
PubChem	CID: 60953
IUPHAR/BPS	6799
DrugBank	DB01101 Y
ChemSpider	54916 Y
UNII	6804DJ8Z9U Y
KEGG	D01223 Y
ChEBI	CHEBI:31348 Y
ChEMBL	CHEMBL1773 Y
Chemical data
Formula	C15H22FN3O6
Molecular mass	359.35 g/mol
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
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Capecitabine (INN) /keɪpˈsaɪtəbiːn/ (Xeloda, Roche) is an orally-administered chemotherapeutic agent used in the treatment of numerous cancers. Capecitabine is a prodrug that is enzymatically converted to 5-fluorouracil (5-FU) in the body.

It is on the World Health Organization's List of Essential Medicines, a list of the most important medications needed in a basic health system.

Medical uses

It is used in the treatment of the following cancers:

• 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)

It is often referred to as Xeloda, the name under which it is marketed by Genentech. It is available in 500-mg and 150-mg tablets.

Adverse effects

Adverse effects by frequency:

Very common (>10% frequency)

• Appetite loss
• Diarrhea
• Vomiting
• Nausea
• Stomatitis
• Abdominal pain
• Fatigue
• Weakness
• Hand-foot syndrome
• Oedema
• Fever
• Pain
• Headache
• Hair loss
• Dermatitis
• Indigestion
• Shortness of breath
• Eye irritation
• Myelosuppression

Notes on adverse effects:

Contraindications

Contraindications include:

• History of hypersensitivity to fluorouacil, 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:

• Sorivudine or its analogues, such as, brivudine.
• Allopurinol as it decreases the efficacy of 5-FU.
• 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.

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. 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.

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|{{{bSize}}}px|alt=Fluorouracil (5-FU) Activity edit]]

File:FluoropyrimidineActivity_WP1601.png

Fluorouracil (5-FU) Activity edit

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.

External links

• Xeloda.com (patient information, tools, and resources)
• OralChemo Advisor (patient information)