Capecitabine
Clinical data
Pronunciation/kæpɪˈstəbn/
Trade namesXeloda, Xitabin, Kapetral, others
AHFS/Drugs.comMonograph
MedlinePlusa699003
License data
Pregnancy
category
  • AU: D
Routes of
administration
By mouth
Drug classchemotherapy agent
ATC code
Legal status
Legal status
Pharmacokinetic data
BioavailabilityExtensive
Protein binding< 60%
Metabolismliver, to 5'-DFCR, 5'-DFUR (inactive); neoplastic tissue, 5'-DFUR to active fluorouracil
Elimination half-life38–45 minutes
Excretionkidney (95.5%), faecal (2.6%)
Identifiers
  • Pentyl [1-(3,4-dihydroxy-5-methyltetrahydrofuran-2-yl)-5-fluoro-2-oxo-1H-pyrimidin-4-yl]carbamate
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.112.980 Edit this at Wikidata
Chemical and physical data
FormulaC15H22FN3O6
Molar mass359.354 g·mol−1
3D model (JSmol)
  • 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=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 checkY
  • Key:GAGWJHPBXLXJQN-UORFTKCHSA-N checkY
  (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

Adverse effects

Adverse effects by frequency:[8][9][10][11]

Very common (>10% frequency)

Notes on adverse effects:

Contraindications

Contraindications include:[10]

Drug interactions

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

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:
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
|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

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

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

References

  1. ^ "FDA-sourced list of all drugs with black box warnings (Use Download Full Results and View Query links.)". nctr-crs.fda.gov. FDA. Retrieved 22 October 2023.
  2. ^ British national formulary : BNF 69 (69 ed.). British Medical Association. 2015. pp. 585, 588. ISBN 9780857111562.
  3. ^ a b c d e f "Capecitabine". The American Society of Health-System Pharmacists. Archived from the original on 15 April 2016. Retrieved 8 December 2016.
  4. ^ a b c d 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): 640–645. doi:10.1038/clpt.2013.172. PMC 3831181. PMID 23988873.
  5. ^ Fischer J, Ganellin CR (2006). Analogue-based Drug Discovery. John Wiley & Sons. p. 511. ISBN 9783527607495. Archived from the original on 12 January 2023. Retrieved 30 August 2017.
  6. ^ World Health Organization (2019). World Health Organization model list of essential medicines: 21st list 2019. Geneva: World Health Organization. hdl:10665/325771. WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO.
  7. ^ a b c d e f g h "FDA approves updated drug labeling including new indications and dosing regimens for capecitabine tablets under Project Renewal". U.S. Food and Drug Administration. 15 December 2022. Archived from the original on 27 January 2023. Retrieved 26 January 2023. Public Domain This article incorporates text from this source, which is in the public domain.
  8. ^ "XELODA (capecitabine) tablet, film coated [Genentech, Inc.]". DailyMed. Genentech, Inc. December 2013. Archived from the original on 1 February 2014. Retrieved 25 January 2014.
  9. ^ "Capecitabine Teva : EPAR – Product Information" (PDF). European Medicines Agency. Teva Pharma B.V. 10 January 2014. Archived (PDF) from the original on 4 February 2014. Retrieved 25 January 2014.
  10. ^ a b c "Capecitabine 150mg – Summary of Product Characteristics (SPC)". electronic Medicines Compendium. Zentiva. 23 December 2013. Archived from the original on 1 February 2014. Retrieved 25 January 2014.
  11. ^ "NAME OF THE MEDICINE XELODA® Capecitabine" (PDF). TGA eBusiness Services. Roche Products Pty Limited. 5 December 2013. Archived from the original on 11 September 2017. Retrieved 25 January 2014.
  12. ^ Reddening, swelling, numbness and desquamation on palms and soles
  13. ^ Rossi S, ed. (2013). Australian Medicines Handbook (2013 ed.). Adelaide: The Australian Medicines Handbook Unit Trust. ISBN 978-0-9805790-9-3.
  14. ^ 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): 1321–1336. doi:10.2217/pgs.11.72. PMID 21919607.
  15. ^ "Xeloda (capecitabine) dosing, indications, interactions, adverse effects, and more". Medscape Reference. WebMD. 25 January 2014. Archived from the original on 2 February 2014.

Further reading