Capecitabine
From Wikipedia, the free encyclopedia
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|---|---|
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| 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  |
| ATC code | L01BC06 |
| PubChem | CID 60953 |
| DrugBank | DB01101 |
| ChemSpider | 54916 |
| UNII | 6804DJ8Z9U |
| KEGG | D01223 |
| ChEBI | CHEBI:31348 |
| ChEMBL | CHEMBL1773 |
| Chemical data | |
| Formula | C15H22FN3O6 |
| Mol. mass | 359.35 g/mol |
| SMILES
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| (what is this?) (verify) | |
Capecitabine (INN) /keɪpˈsaɪtəbiːn/ (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 in the body.[2]
Medical uses
It is used in the treatment of the following cancers:[1][2][3]
- Colorectal cancer (either 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
Adverse effects by frequency:[4][5][6][7]
Very common (>10% frequency):
- Appetite loss
- Diarrhoea
- Vomiting
- Nausea
- Stomatitis
- Abdominal pain
- Fatigue
- Weakness
- Hand-foot syndrome[8]
- Oedema
- Fever
- Pain
- Headache
- Hair loss
- Dermatitis
- Indigestion
- Shortness of breath
- Eye irritation
- Myelosuppression[Note 1]
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):
- Lipoma
- Sepsis
- Urinary tract infection
- Cellulitis
- Tonsillitis
- Pharyngitis
- Oral candidiasis
- Influenza
- Gastroenteritis
- Fungal infection
- Infection
- Tooth abscess
- Febrile neutropenia
- Haemolytic anaemia
- INR increased
- Prothrombin time prolonged
- Hypersensitivity
- Diabetes
- Hypokalaemia
- Appetite disorder
- Malnutrition
- Hypertriglyceridaemia
- Confusional state
- Panic attack
- Depressed mood
- Libido decreased
- Difficulty coming up with words
- Memory impairment
- Incoordination
- Syncope
- Balance disorder
- Sensory disorder
- Peripheral neuropathy
- Visual acuity reduced
- Seeing double
- Ear pain
- Vertigo
- Deep vein thrombosis
- Hypertension
- Petechiae
- Hypotension
- Hot flush
- Peripheral coldness
- Blood clot in the lung
- Pneumothorax
- Coughing up blood
- Asthma
- Exertional dyspnoea
- Jaundice
- Intestinal obstruction
- Ascites
- Enteritis
- Gastritis
- Difficulty swallowing
- Oesophagitis
- Abdominal discomfort
- Gastro-oesophageal reflux disease
- Colitis
- Blood in the stool
- Blister
- Skin ulcer
- Rash
- Urticaria (hives)
- Photosensitivity reaction
- Palmar erythema
- Swelling face
- Purpura
- Radiation recall syndrome
- Vaginal bleeding
- Joint swelling
- Bone pain
- Facial pain
- Musculoskeletal stiffness
- Muscular weakness
- Hydronephrosis
- Urinary incontinence
- Blood in the urine
- Urination during one's sleep
- Increased blood creatinine
- Chills
- Influenza-like illness
- Rigors
- Body temperature increased
Rare (<0.1% frequency):
- Lacrimal duct stenosis
- Ventricular fibrillation
- QT prolongation
- Torsade de pointes
- Bradycardia
- Vasospasm
- Liver failure
- Cholestatic hepatitis
Notes on adverse effects:
- ↑ Includes: anaemia, lymphopenia, neutropenia and thrombocytopenia
- ↑ Includes pneumonia
- ↑ 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
Contraindications
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
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
Click on genes, proteins and metabolites below to link to respective articles. [§ 1]
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 and RNA during gene expression.[2]
References
- ↑ 1.0 1.1 1.2 Rossi, S, ed. (2013). Australian Medicines Handbook (2013 ed.). Adelaide: The Australian Medicines Handbook Unit Trust. ISBN 978-0-9805790-9-3.
- ↑ 2.0 2.1 2.2 "Xeloda (capecitabine) dosing, indications, interactions, adverse effects, and more". Medscape Reference. WebMD. 25 January 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. Retrieved 25 January 2014.
- ↑ "Capecitabine Teva : EPAR - Product Information" (PDF). European Medicines Agency. Teva Pharma B.V. 10 January 2014. Retrieved 25 January 2014.
- ↑ 6.0 6.1 6.2 "Capecitabine 150mg - Summary of Product Characteristics (SPC)". electronic Medicines Compendium. Zentiva. 23 December 2013. Retrieved 25 January 2014.
- ↑ "NAME OF THE MEDICINE XELODA® Capecitabine" (PDF). TGA eBusiness Services. Roche Products Pty Limited. 5 December 2013. Retrieved 25 January 2014.
- ↑ Reddening, swelling, numbness and desquamation on palms and soles
External links
- Xeloda.com (patient information, tools, and resources)
- OralChemo Advisor (patient information)
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