Capecitabine

External sites:	US NLM: Capecitabine;
Identifiers:	ATC code: L01BC06 (WHO) ; ; CAS Number: 154361-50-9 ; PubChem CID: 60953; IUPHAR/BPS: 6799; DrugBank: DB01101 ; ; ChemSpider: 54916 ; ; UNII: 6804DJ8Z9U; ; KEGG: D01223 ; ; ChEBI: CHEBI:31348; ; ChEMBL: ChEMBL1773 ; ;

Capecitabine
Names
Pronunciation	/kæpɪˈsaɪtəbiːn/
Trade names	Xeloda, Xitabin, Kapetral, others
	IUPAC name Pentyl [1-(3,4-dihydroxy-5-methyltetrahydrofuran-2-yl)-5-fluoro-2-oxo-1H-pyrimidin-4-yl]carbamate;
Clinical data
Drug class	Chemotherapy agent
Main uses	Breast cancer, gastric cancer, colorectal cancer
Side effects	Abdominal pain, vomiting, diarrhea, weakness, rashes
Pregnancy; category	AU: D; US: D (Evidence of risk); ;
Routes of; use	By mouth
Defined daily dose	Not established
External links
AHFS/Drugs.com	Monograph
MedlinePlus	a699003
Legal
License data	EU EMA: by INN;
Legal status	AU: S4 (Prescription only) ; CA: ℞-only ; UK: POM (Prescription only) ; US: ℞-only ;
Pharmacokinetics
Bioavailability	Extensive
Protein binding	< 60%
Metabolism	liver, to 5'-DFCR, 5'-DFUR (inactive); neoplastic tissue, 5'-DFUR to active fluorouracil
Elimination half-life	38–45 minutes
Excretion	Kidney (95.5%), faecal (2.6%)
Chemical and physical data
Formula	C15H22FN3O6
Molar mass	359.354 g·mol−1
3D model (JSmol)	Interactive image;
	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 ; Key:GAGWJHPBXLXJQN-UORFTKCHSA-N ;

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.^[2] It is taken by mouth.^[2]

Common side effects include abdominal pain, vomiting, diarrhea, weakness, and rashes.^[2] Other severe side effects include blood clotting problems, allergic reactions, heart problems such as cardiomyopathy, and low blood cell counts.^[2] It is not recommended in people with kidney problems.^[2] Use during pregnancy may result in harm to the baby.^[2] Capecitabine, inside the body, is converted to 5-fluorouracil (5-FU) through which it acts.^[2] It belongs to the class of medications known as fluoropyrimidines, which also includes 5-fluorouracil 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] The wholesale cost in the developing world is about US$122.64–195.66 per cycle of medication.^[7] In the United Kingdom it costs the NHS about £210.67 per cycle.^[1] In the United States it costs about $1,892.00 as of 2016.^[8]

Medical uses

It is used in the treatment of the following cancers:^[9]^[10]^[11]

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)

Dosage

The defined daily dose is not established^[3]

Side effects

Adverse effects by frequency:^[12]^[13]^[14]^[15]

Very common (>10% frequency)

Appetite loss
Diarrhea
Vomiting
Nausea
Stomatitis
Abdominal pain
Fatigue
Weakness
Hand-foot syndrome^[16]
Oedema
Fever
Pain
Headache
Hair loss
Dermatitis
Indigestion
Shortness of breath
Eye irritation
Myelosuppression^{[Note 1]}

Notes on adverse effects:

↑ Includes: anaemia, lymphopenia, neutropenia and thrombocytopenia

Contraindications

Contraindications include:^[14]

History of hypersensitivity to fluorouracil, 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:^[14]

Sorivudine or its analogues, such as, brivudine.
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.^[9]

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]^[17] 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]^[17]

Mechanism of action

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

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|alt=Fluorouracil (5-FU) Activity edit]]

Fluorouracil (5-FU) Activity edit

↑ 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.^[10]

Society and culture

One of the brandnames is Xeloda, marketed by Genentech.

Others include Xitabin, Capcibin, and Kapetral.

References

↑ ^1.0 ^1.1 ^1.2 British national formulary : BNF 69 (69 ed.). British Medical Association. 2015. pp. 585, 588. ISBN 9780857111562.
↑ ^2.0 ^2.1 ^2.2 ^2.3 ^2.4 ^2.5 ^2.6 ^2.7 "Capecitabine". The American Society of Health-System Pharmacists. Archived from the original on 15 April 2016. Retrieved 8 December 2016.
↑ ^3.0 ^3.1 "WHOCC - ATC/DDD Index". www.whocc.no. Archived from the original on 22 January 2021. Retrieved 18 September 2020.
↑ ^4.0 ^4.1 ^4.2 ^4.3 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. PMC 3831181. PMID 23988873.
↑ Fischer, Janos; Ganellin, C. Robin (2006). Analogue-based Drug Discovery. John Wiley & Sons. p. 511. ISBN 9783527607495. Archived from the original on 2020-12-06. Retrieved 2017-08-30.
↑ 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.
↑ "Capecitabine". International Drug Price Indicator Guide. Archived from the original on 22 January 2018. Retrieved 8 December 2016.
↑ "NADAC as of 2016-12-07 | Data.Medicaid.gov". Centers for Medicare and Medicaid Services. Archived from the original on 21 December 2016. Retrieved 19 December 2016.
↑ ^9.0 ^9.1 Rossi S, ed. (2013). Australian Medicines Handbook (2013 ed.). Adelaide: The Australian Medicines Handbook Unit Trust. ISBN 978-0-9805790-9-3.
↑ ^10.0 ^10.1 "Xeloda (capecitabine) dosing, indications, interactions, adverse effects, and more". Medscape Reference. WebMD. 25 January 2014. Archived from the original on 2 February 2014.
↑ Joint Formulary Committee (2013). British National Formulary (BNF) (65 ed.). London, UK: Pharmaceutical Press. ISBN 978-0-85711-084-8.
↑ "XELODA (capecitabine) tablet, film coated [Genentech, Inc.]". DailyMed. Genentech, Inc. December 2013. Archived from the original on 1 February 2014. Retrieved 25 January 2014.
↑ "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.
↑ ^14.0 ^14.1 ^14.2 "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.
↑ "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.
↑ Reddening, swelling, numbness and desquamation on palms and soles
↑ ^17.0 ^17.1 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

[17] Includes: anaemia, lymphopenia, neutropenia and thrombocytopenia

[WikiPathways-19] The interactive pathway map can be edited at WikiPathways: "FluoropyrimidineActivity_WP1601".

[BNF69-1] 1.0 ^1.1 ^1.2 British national formulary : BNF 69 (69 ed.). British Medical Association. 2015. pp. 585, 588. ISBN 9780857111562.

[AHFS2016-2] 2.0 ^2.1 ^2.2 ^2.3 ^2.4 ^2.5 ^2.6 ^2.7 "Capecitabine". The American Society of Health-System Pharmacists. Archived from the original on 15 April 2016. Retrieved 8 December 2016.

[who-3] 3.0 ^3.1 "WHOCC - ATC/DDD Index". www.whocc.no. Archived from the original on 22 January 2021. Retrieved 18 September 2020.

[pmid23988873-4] 4.0 ^4.1 ^4.2 ^4.3 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. PMC 3831181. PMID 23988873.

[Fis2006-5] Fischer, Janos; Ganellin, C. Robin (2006). Analogue-based Drug Discovery. John Wiley & Sons. p. 511. ISBN 9783527607495. Archived from the original on 2020-12-06. Retrieved 2017-08-30.

[WHO21st-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.

[ERC2014-7] "Capecitabine". International Drug Price Indicator Guide. Archived from the original on 22 January 2018. Retrieved 8 December 2016.

[8] "NADAC as of 2016-12-07 | Data.Medicaid.gov". Centers for Medicare and Medicaid Services. Archived from the original on 21 December 2016. Retrieved 19 December 2016.

[AMH-9] 9.0 ^9.1 Rossi S, ed. (2013). Australian Medicines Handbook (2013 ed.). Adelaide: The Australian Medicines Handbook Unit Trust. ISBN 978-0-9805790-9-3.

[MSR-10] 10.0 ^10.1 "Xeloda (capecitabine) dosing, indications, interactions, adverse effects, and more". Medscape Reference. WebMD. 25 January 2014. Archived from the original on 2 February 2014.

[BNF-11] Joint Formulary Committee (2013). British National Formulary (BNF) (65 ed.). London, UK: Pharmaceutical Press. ISBN 978-0-85711-084-8.

[DM-12] "XELODA (capecitabine) tablet, film coated [Genentech, Inc.]". DailyMed. Genentech, Inc. December 2013. Archived from the original on 1 February 2014. Retrieved 25 January 2014.

[EMA-13] "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.

[EMC-14] 14.0 ^14.1 ^14.2 "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.

[TGA-15] "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.

[Notes-16] Reddening, swelling, numbness and desquamation on palms and soles

[pmid21919607-18] 17.0 ^17.1 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.

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Capecitabine

Contents

Medical uses

Dosage

Side effects

Contraindications

Drug interactions

Pharmacogenetics

Mechanism of action

Society and culture

References

Further reading

External links

Navigation menu

External sites:	US NLM: Capecitabine
Identifiers:	ATC code: L01BC06 (WHO) CAS Number: 154361-50-9^Y PubChem CID: 60953 IUPHAR/BPS: 6799 DrugBank: DB01101^Y ChemSpider: 54916^Y UNII: 6804DJ8Z9U KEGG: D01223^Y ChEBI: CHEBI:31348 ChEMBL: ChEMBL1773^Y

Capecitabine

Medical uses

Dosage

Side effects

Contraindications

Drug interactions

Pharmacogenetics

Mechanism of action

Society and culture

References

Further reading

External links

Navigation menu

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