Capecitabine

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Capecitabine
Capecitabine.svg
Capecitabine-from-xtal-2009-3D-balls.png
Systematic (IUPAC) name
Pentyl [1-(3,4-dihydroxy-5-methyltetrahydrofuran-2-yl)-5-fluoro-2-oxo-1H-pyrimidin-4-yl]carbamate
Clinical data
Trade namesXeloda
AHFS/Drugs.commonograph
MedlinePlusa699003
Legal status
RoutesOral
Pharmacokinetic data
BioavailabilityExtensive
Protein binding< 60%
MetabolismHepatic, to 5'-DFCR, 5'-DFUR (inactive); neoplastic tissue, 5'-DFUR to active fluorouracil
Half-life38–45 minutes
ExcretionRenal (95.5%), faecal (2.6%)
Identifiers
CAS number154361-50-9 YesY
ATC codeL01BC06
PubChemCID 60953
DrugBankDB01101
ChemSpider54916 YesY
UNII6804DJ8Z9U YesY
KEGGD01223 YesY
ChEBICHEBI:31348 YesY
ChEMBLCHEMBL1773 YesY
Chemical data
FormulaC15H22FN3O6 
Molecular mass359.35 g/mol
 YesY (what is this?)  (verify)
 
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Capecitabine
Capecitabine.svg
Capecitabine-from-xtal-2009-3D-balls.png
Systematic (IUPAC) name
Pentyl [1-(3,4-dihydroxy-5-methyltetrahydrofuran-2-yl)-5-fluoro-2-oxo-1H-pyrimidin-4-yl]carbamate
Clinical data
Trade namesXeloda
AHFS/Drugs.commonograph
MedlinePlusa699003
Legal status
RoutesOral
Pharmacokinetic data
BioavailabilityExtensive
Protein binding< 60%
MetabolismHepatic, to 5'-DFCR, 5'-DFUR (inactive); neoplastic tissue, 5'-DFUR to active fluorouracil
Half-life38–45 minutes
ExcretionRenal (95.5%), faecal (2.6%)
Identifiers
CAS number154361-50-9 YesY
ATC codeL01BC06
PubChemCID 60953
DrugBankDB01101
ChemSpider54916 YesY
UNII6804DJ8Z9U YesY
KEGGD01223 YesY
ChEBICHEBI:31348 YesY
ChEMBLCHEMBL1773 YesY
Chemical data
FormulaC15H22FN3O6 
Molecular mass359.35 g/mol
 YesY (what is this?)  (verify)

Capecitabine (INN) /kpˈstəbn/ (Xeloda, Roche) is an orally-administered chemotherapeutic agent used in the treatment of numerous cancers.[1] Capecitabine is a prodrug, that is enzymatically converted to 5-fluorouracil (5-FU) in the body.[2]

Medical uses[edit]

It is used in the treatment of the following cancers:[1][2][3]

Adverse effects[edit]

Adverse effects by frequency:[4][5][6][7]

Very common (>10% frequency)

Notes on adverse effects:

Contraindications[edit]

Contraindications include:[6]

Drug interactions[edit]

Drugs it is known to interact with includes:[6]

Pharmacogenetics[edit]

The dihydropyrimidine dehydrogenase (DPD) enzyme is responsible for the detoxifying metabolism of fluoropyrimidines, a class of drugs that includes capecitabine, 5-fluorouracil and tegafur.[9] 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.[9][10] 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.[9][10] The FDA-approved drug label for capecitabine states that the drug is contraindicated in patients with known DPD deficiency.[4]

Mechanism of action[edit]

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

[[File:
FluoropyrimidineActivity_WP1601go to articlego to articlego to articlego to pathway articlego to pathway articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to PubChem Compoundgo to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to pathway articlego to pathway articlego to articlego to articlego to articlego to articlego to articlego to WikiPathwaysgo to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to article
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FluoropyrimidineActivity_WP1601go to articlego to articlego to articlego to pathway articlego to pathway articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to PubChem Compoundgo to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to pathway articlego to pathway articlego to articlego to articlego to articlego to articlego to articlego to WikiPathwaysgo to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to article
|{{{bSize}}}px|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 and RNA during gene expression.[2]

References[edit]

  1. ^ a b c Rossi, S, ed. (2013). Australian Medicines Handbook (2013 ed.). Adelaide: The Australian Medicines Handbook Unit Trust. ISBN 978-0-9805790-9-3.  edit
  2. ^ a b c "Xeloda (capecitabine) dosing, indications, interactions, adverse effects, and more". Medscape Reference. WebMD. 25 January 2014. 
  3. ^ Joint Formulary Committee (2013). British National Formulary (BNF) (65 ed.). London, UK: Pharmaceutical Press. ISBN 978-0-85711-084-8.  edit
  4. ^ a b "XELODA (capecitabine) tablet, film coated [Genentech, Inc.]". DailyMed. Genentech, Inc. December 2013. Retrieved 25 January 2014. 
  5. ^ "Capecitabine Teva : EPAR - Product Information" (PDF). European Medicines Agency. Teva Pharma B.V. 10 January 2014. Retrieved 25 January 2014. 
  6. ^ a b c "Capecitabine 150mg - Summary of Product Characteristics (SPC)". electronic Medicines Compendium. Zentiva. 23 December 2013. Retrieved 25 January 2014. 
  7. ^ "NAME OF THE MEDICINE XELODA® Capecitabine" (PDF). TGA eBusiness Services. Roche Products Pty Limited. 5 December 2013. Retrieved 25 January 2014. 
  8. ^ Reddening, swelling, numbness and desquamation on palms and soles
  9. ^ a b c Caudle, KE; Thorn, CF; Klein, TE; Swen, JJ; McLeod, HL; Diasio, RB; Schwab, M (December 2013). "Clinical Pharmacogenetics Implementation Consortium guidelines for dihydropyrimidine dehydrogenase genotype and fluoropyrimidine dosing.". Clinical pharmacology and therapeutics 94 (6): 640–5. doi:10.1038/clpt.2013.172. PMID 23988873. 
  10. ^ a b Amstutz, U; Froehlich, TK; Largiadèr, CR (September 2011). "Dihydropyrimidine dehydrogenase gene as a major predictor of severe 5-fluorouracil toxicity.". Pharmacogenomics 12 (9): 1321–36. PMID 21919607. 

External links[edit]