Capecitabine

Capecitabine (INN) (Xeloda, Roche) is an orally-administered chemotherapeutic agent used in the treatment of numerous cancers. Capecitabine is a prodrug, that is enzymatically converted to 5-fluorouracil (5-FU) in the body.

Medical uses
It is used in the treatment of the following cancers:
 * 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
Adverse effects by frequency:


 * Very common (>10% frequency):


 * Appetite loss
 * Diarrhoea
 * Vomiting
 * Nausea
 * Stomatitis
 * Abdominal pain
 * Fatigue
 * Weakness
 * Hand-foot syndrome
 * Oedema
 * Fever
 * Pain
 * Headache
 * Hair loss
 * Dermatitis
 * Indigestion
 * Shortness of breath
 * Eye irritation
 * Myelosuppression


 * Common (1-10% frequency):


 * Herpes viral infection
 * Nasopharyngitis
 * Lower respiratory tract infection
 * 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


 * 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:

Contraindications
Contraindications include:
 * 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:
 * 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.

Mechanism of action
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.