Capecitabine

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Capecitabine
Capecitabine.svg
Capecitabine-from-xtal-2009-3D-balls.png
Clinical data
Pronunciation /kæpˈstəbin/
Trade names Xeloda, others
AHFS/Drugs.com Monograph
MedlinePlus a699003
Pregnancy
category
  • AU: D
  • US: D (Evidence of risk)
Routes of
administration
by mouth
Drug class chemotherapy agent
ATC code L01BC06 (WHO)
Legal status
Legal status
  • AU: S4 (Prescription only)
  • UK: POM (Prescription only)
  • US: ℞-only
Pharmacokinetic data
Bioavailability Extensive
Protein binding < 60%
Metabolism lilver, to 5'-DFCR, 5'-DFUR (inactive); neoplastic tissue, 5'-DFUR to active fluorouracil
Biological half-life 38–45 minutes
Excretion kidney (95.5%), faecal (2.6%)
Identifiers
CAS Number 154361-50-9 YesY
PubChem (CID) 60953
IUPHAR/BPS 6799
DrugBank DB01101 YesY
ChemSpider 54916 YesY
UNII 6804DJ8Z9U YesY
KEGG D01223 YesY
ChEBI CHEBI:31348 YesY
ChEMBL CHEMBL1773 YesY
ECHA InfoCard 100.112.980
Chemical and physical data
Formula C15H22FN3O6
Molar mass 359.35 g/mol
3D model (Jmol) Interactive image
  (verify)

Capecitabine, sold under the brand name Xeloda among others, is a chemotherapy medication used to treat breast cancer, gastric cancer and colorectal cancer.[1] For breast cancer it is often used together with docetaxel. It is taken by mouth.[2]

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.[2]

Capecitabine was patented in 1992 and approved for medical use in 1998.[3] It is on the World Health Organization's List of Essential Medicines, the most effective and safe medicines needed in a health system.[4] The wholesale cost in the developing world is about 122.64 to 195.66 USD per cycle of medication.[5] In the United Kingdom it costs the NHS about £210.67 per cycle.[1] In the United States it costs about 1,892.00 USD as of 2016.[6]

Medical uses[edit]

It is used in the treatment of the following cancers:[7][8][9]

  • 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)

Adverse effects[edit]

Adverse effects by frequency:[10][11][12][13]

Very common (>10% frequency)

Notes on adverse effects:

Contraindications[edit]

Contraindications include:[12]

Drug interactions[edit]

Drugs it is known to interact with include:[12]

  • 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.[7]

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.[15] 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.[15][16] 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.[15][16]

Mechanism of action[edit]

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

[[File:
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FluoropyrimidineActivity_WP1601 go to article go to article go to article go to pathway article go to pathway article go to article go to article go to article go to article go to article go to article go to article go to article go to article go to PubChem Compound go to article go to article go to article go to article go to article go to article go to article go to article go to article go to article go to article go to article go to article go to article go to article go to article go to article go to article go to pathway article go to pathway article go to article go to article go to article go to article go to article go to WikiPathways go to article go to article go to article go to article go to article go to article go to article go to article go 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.[8]

Society and culture[edit]

One of the brandnames is Xeloda, marketed by Genentech.

References[edit]

  1. ^ a b British national formulary : BNF 69 (69 ed.). British Medical Association. 2015. p. 585, 588. ISBN 9780857111562. 
  2. ^ a b "Capecitabine". The American Society of Health-System Pharmacists. Retrieved 8 December 2016. 
  3. ^ Fischer, Janos; Ganellin, C. Robin (2006). Analogue-based Drug Discovery. John Wiley & Sons. p. 511. ISBN 9783527607495. 
  4. ^ "WHO Model List of Essential Medicines (19th List)" (PDF). World Health Organization. April 2015. Retrieved 8 December 2016. 
  5. ^ "Capecitabine". International Drug Price Indicator Guide. Retrieved 8 December 2016. 
  6. ^ "NADAC as of 2016-12-07 | Data.Medicaid.gov". Centers for Medicare and Medicaid Services. Retrieved 19 December 2016. 
  7. ^ a b Rossi, S, ed. (2013). Australian Medicines Handbook (2013 ed.). Adelaide: The Australian Medicines Handbook Unit Trust. ISBN 978-0-9805790-9-3. 
  8. ^ a b "Xeloda (capecitabine) dosing, indications, interactions, adverse effects, and more". Medscape Reference. WebMD. 25 January 2014. 
  9. ^ Joint Formulary Committee (2013). British National Formulary (BNF) (65 ed.). London, UK: Pharmaceutical Press. ISBN 978-0-85711-084-8. 
  10. ^ "XELODA (capecitabine) tablet, film coated [Genentech, Inc.]". DailyMed. Genentech, Inc. December 2013. Retrieved 25 January 2014. 
  11. ^ "Capecitabine Teva : EPAR - Product Information" (PDF). European Medicines Agency. Teva Pharma B.V. 10 January 2014. Retrieved 25 January 2014. 
  12. ^ a b c "Capecitabine 150mg - Summary of Product Characteristics (SPC)". electronic Medicines Compendium. Zentiva. 23 December 2013. Retrieved 25 January 2014. 
  13. ^ "NAME OF THE MEDICINE XELODA® Capecitabine" (PDF). TGA eBusiness Services. Roche Products Pty Limited. 5 December 2013. Retrieved 25 January 2014. 
  14. ^ Reddening, swelling, numbness and desquamation on palms and soles
  15. ^ 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. 
  16. ^ 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. doi:10.2217/pgs.11.72. PMID 21919607. 

External links[edit]