Capecitabine

From Wikipedia, the free encyclopedia
Jump to: navigation, search
Capecitabine
Capecitabine2DACS2.svg
Capecitabine3Dan.gif
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 cat. D (AU) D (US)
Legal status Prescription Only (S4) (AU) POM (UK) -only (US)
Routes Oral
Pharmacokinetic data
Bioavailability Extensive
Protein binding < 60%
Metabolism Hepatic, to 5'-DFCR, 5'-DFUR (inactive); neoplastic tissue, 5'-DFUR to active fluorouracil
Half-life 38–45 minutes
Excretion Renal (95.5%), faecal (2.6%)
Identifiers
CAS number 154361-50-9 YesY
ATC code L01BC06
PubChem CID 60953
DrugBank DB01101
ChemSpider 54916 YesY
UNII 6804DJ8Z9U YesY
KEGG D01223 YesY
ChEBI CHEBI:31348 YesY
ChEMBL CHEMBL1773 YesY
Chemical data
Formula C15H22FN3O6 
Mol. mass 359.35 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)
Common (1-10% frequency)
  • Herpes viral infection
  • Nasopharyngitis
  • Lower respiratory tract infection[Note 2]
  • Weight loss
  • Dehydration
  • Depression
  • Insomnia
  • Headache
  • Lethargy
  • Dizziness
  • Paraesthesia
  • Taste changes
  • Increased lacrimation
  • Conjunctivitis
  • Thrombophlebitis
  • Cough
  • Constipation
  • Epistaxis (nose bleed)
  • Rhinorrhoea
  • Gastrointestinal haemorrhage
  • Dyspepsia
  • Flatulence
  • Dry mouth
  • Hyperbilirubinaemia
  • LFT abnormalities
  • Erythema
  • Dry skin
  • Itchiness
  • Skin hyper-pigmentation
  • Macular rash
  • Skin desquamation
  • Dermatitis
  • Pigmentation disorder
  • Nail disorder
  • Pain in extremity
  • Back pain
  • Joint pain
  • Fever
  • Peripheral oedema
  • Malaise
  • Cardiotoxicity[Note 3]
Uncommon (0.1-1% frequency)
Rare (<0.1% frequency)
  • Lacrimal duct stenosis
  • Ventricular fibrillation
  • QT prolongation
  • Torsade de pointes
  • Bradycardia
  • Vasospasm
  • Liver failure
  • Cholestatic hepatitis

Notes on adverse effects:

  1. ^ Includes: anaemia, lymphopenia, neutropenia and thrombocytopenia
  2. ^ Includes pneumonia
  3. ^ Angina-like chest pain appears to be the most common symptom. Less common cardiac symptoms include (all of these side effects are uncommon, i.e. they occur in less than 1% of patients):
    • Tachycardia
    • Arrhythmias
    • Heart failure
    • Myocardial infarction (heart attack)
    • Cardiac arrest
    Usually occurs during the first 2-3 days of treatment is thought to be due to coronary vasospasm. Appears to resolve after capecitabine is stopped and to recur if it is restarted

Contraindications[edit]

Contraindications include:[6]

  • History of hypersensitivity to fluorouacil, capecitabine or any of its excipients.
  • Patients with DPD deficiency
  • Pregnancy and lactation
  • Patients with pre-existing blood dyscrasias
  • Patients with severe hepatic impairment or severe renal impairment
  • Treatment with sorivudine or its chemically related analogues, such as brivudine

Drug interactions[edit]

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

  • 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.[1]

Mechanism of action[edit]

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

[[File:
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
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
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]]
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. ^ "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

External links[edit]