Capecitabine

Registered South African indications:

• Metastatic breast cancer
• Colorectal cancer
• Gastric cancer

Contraindications

• Hypersensitivity to the active ingredient or any of its excipients 
• History of severe and unexpected reactions to fluoropyrimidine therapy
• Hypersensitivity to fluorouracil
• Pregnancy 
• Breastfeeding
• Severe renal impairment 
• Severe hepatic impairment 
• Complete absence of dihydropyrimidine dehydrogenase (DPD) activity
• Severe leukopenia, neutropenia, or thrombocytopenia
• Coadministration with sorivudine or its chemically related analogues 

Cautions 

• Mild to moderate renal impairment 
• Mild to moderate hepatic impairment 
• Elderly
• Dehydration 
• Coronary artery disease
• Cardiac disease or history thereof
• Arrhythmias or history thereof
• Angina pectoris or history thereof 
• Central nervous system disease
• Peripheral nervous system disease
• Diabetes mellitus
• History of eye disorders
• Galactose intolerance
• Lapp lactase deficiency 
• Glucose-galactose malabsorption 

Forms avail. in SA and covered in this monograph: tab

Used for the treatment of

• Colon cancer
• Colorectal cancer
• Breast cancer

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Consult specialist for dosages and regimens

Not established for use in children

Pregnancy 

• Contraindicated
• There are no studies in pregnant women using capecitabine; however, it should be assumed that capecitabine may cause foetal harm if administered to pregnant women
• In reproductive toxicity studies in animals, capecitabine administration caused embryolethality and teratogenicity. These findings are expected effects of fluoropyrimidine derivatives
• Women of childbearing potential should be advised to avoid becoming pregnant while receiving treatment with capecitabine

Breastfeeding 

• Contraindicated
• It is not known whether capecitabine is excreted in human breast milk. No studies have been conducted to assess the impact of capecitabine on milk production or its presence in human breast milk
• In lactating mice, considerable amounts of capecitabine and its metabolites were found in milk. As the potential for harm to the nursing infant is unknown, breast-feeding should be discontinued while receiving treatment with capecitabine and for 2 weeks after the final dose

Fertility

• There is no data on capecitabine and impact on fertility. The capecitabine pivotal studies included females of childbearing potential and males only if they agreed to use an acceptable method of birth control to avoid pregnancy for the duration of the study and for a reasonable period thereafter
• In animal standard fertility studies, impairment of fertility was observed in female mice receiving capecitabine; however, this effect was reversible after a drug-free period. In addition, during a 13-week study, atrophic and degenerative changes occurred in the reproductive organs of male mice; however, these effects were reversible after a drug-free period

Renal Impairment 

• Mild to moderate: Caution, no dose adjustment recommended
• Severe: Contraindicated

Hepatic Impairment

• Mild to moderate: Caution; no information available
• Severe: Contraindicated

Elderly

• Caution; dose adjustment recommended 

Porphyria Information

• Not porphyrinogenic (NP)

Drugs in Sport

• Permitted - No warning

Central Nervous System Disorders

• Insomnia
• Depression
• Confusional state
• Panic attack
• Depressed mood
• Decreased libido
• Headache
• Lethargy
• Dizziness
• Parasthesia
• Dysgeusia 
• Aphasia
• Memory impairment
• Ataxia
• Syncope
• Balance disorder
• Sensory disorder
• Neuropathy peripheral
• Toxic leukoencephalopathy
• Sleep disorder (when used in combination treatment)
• Anxiety (when used in combination treatment)
• Dysaesthesia (when used in combination treatment)
• Peripheral neuropathy (when used in combination treatment)
• Peripheral sensory neuropathy (when used in combination treatment)
• Neurotoxicity (when used in combination treatment)
• Tremor (when used in combination treatment)
• Neuralgia (when used in combination treatment)
• Hypoaesthesia (when used in combination treatment) 

Cardiovascular Disorders

• Angina unstable
• Angina pectoris
• Myocardial ischaemia
• Atrial fibrillation
• Arrhythmia
• Tachycardia
• Sinus tachycardia
• Palpitations 
• Ventricular fibrillation
• QT prolongation
• Torsade de pointes
• Bradycardia
• Vasospasm 
• Thrombophlebitis
• Deep vein thrombosis
• Hypertension
• Petechiae
• Hypotension
• Hot flush
• Peripheral coldness
• Cardiac ischaemia / infarction (when used in combination treatment) 
• Lower limb oedema (when used in combination treatment)
• Hypertension(when used in combination treatment)
• Embolism (when used in combination treatment)
• Flushing (when used in combination treatment)
• Hypertensive crisis (when used in combination treatment)
• Phlebitis (when used in combination treatment) 

Respiratory Disorders

• Dyspnoea
• Epistaxis
• Cough
• Rhinorrhoea
• Pulmonary embolism
• Pneumothorax
• Haemoptysis
• Asthma
• Dyspnoea exertional
• Sore throat (when used in combination treatment)
• Dysaesthesia of pharynx (when used in combination treatment)
• Hiccups (when used in combination treatment)
• Pharyngolaryngeal pain (when used in combination treatment)
• Dysphonia (when used in combination treatment) 

Gastrointestinal Disorders

• Diarrhoea
• Nausea and vomiting
• Stomatitis
• Abdominal pain
• Gastrointestinal haemorrhage
• Constipation
• Dyspepsia 
• Flatulence
• Dry mouth
• Intestinal obstruction
• Ascites
• Enteritis
• Gastritis
• Dysphagia
• Oesophagitis
• Gastro-oesophageal reflux disease
• Colitis
• Blood in stool
• Mouth ulceration (when used in combination treatment)
• Oral pain (when used in combination treatment)
• Rectal haemorrhage (when used in combination treatment)
• Lower abdominal pain (when used in combination treatment)
• Oral dysaesthesia (when used in combination treatment) 
• Paraesthesia oral (when used in combination treatment) 
• Hypoaesthesia oral (when used in combination treatment) 
• Abdominal distention (when used in combination treatment)  

Hepatobiliary Disorders

• Hyperbilirubinemia
• Abnormalities in hepatic function test 
• Jaundice 
• Hepatic failure 
• Cholestatic hepatitis 

Genitourinary Disorders

• Hydronephrosis
• Urinary incontinence
• Haematuria
• Nocturia
• Vaginal haemorrhage
• Proteinuria (when used in combination treatment)  
• Decreased creatinine renal clearance (when used in combination treatment)  
• Dysuria (when used in combination treatment)  
• Acute renal failure secondary to dehydration (when used in combination treatment)  

Endocrine and Metabolic Disorders

• Anorexia
• Dehydration
• Decreased weight
• Diabetes
• Hypokalaemia
• Appetite disorder
• Malnutrition
• Hypertriglyceridaemia 
• Hyponatraemia (when used in combination treatment)
• Hypomagnesaemia (when used in combination treatment)
• Hypocalcaemia (when used in combination treatment)
• Hyperglycaemia (when used in combination treatment) 

Musculoskeletal Disorders

• Pain in extremity
• Back pain
• Arthralgia 
• Joint swelling
• Bone pain
• Facial pain
• Musculoskeletal stiffness
• Muscular weakness
• Myalgia (when used in combination treatment) 
• Muscle spasms (when used in combination treatment) 
• Trismus (when used in combination treatment) 

Skin and Subcutaneous Tissue Disorders

• Palmar-plantar erythrodysaesthesia syndrome
• Rash
• Alopecia
• Erythema
• Dry skin
• Pruritus
• Skin hyper-pigmentation
• Skin desquamation
• Dermatitis
• Pigmentation disorder
• Nail disorder
• Blister
• Skin ulcer
• Urticaria
• Photosensitivity reaction
• Palmar erythema
• Swelling face
• Purpura
• Radiation recall syndrome 
• Cutaneous lupus erythematosus 
• Stevens-Johnson Syndrome 
• Toxic Epidermal Necrolysis 
• Infusion related reaction (when used in combination treatment) 
• Injection site reaction (when used in combination treatment) 
• Infusion site pain (when used in combination treatment) 
• Injection site pain (when used in combination treatment) 
• Hyperhidrosis (when used in combination treatment) 
• Night sweats (when used in combination treatment) 

Immune, Blood and Lymphatic System Disorders

• Herpes viral infection
• Nasopharyngitis
• Lower respiratory tract infection
• Sepsis
• Urinary tract infection
• Cellulitis
• Tonsillitis
• Pharyngitis
• Oral candidiasis
• Influenza
• Gastroenteritis
• Fungal infection
• Infection
• Tooth abscess
• Lipoma
• Neutropenia
• Anaemia 
• Pancytopenia
• Granulocytopenia
• Thrombocytopenia
• Leukopenia
• Haemolytic anaemia
• Prolonged International Normalised Ratio (INR) increased/Prothrombin time 
• Hypersensitivity 
• Upper respiratory tract infection (when used in combination treatment)
• Rhinitis (when used in combination treatment)
• Oral herpes (when used in combination treatment) 
• Bone marrow depression (when used in combination treatment)
• Neutropenic fever (when used in combination treatment)
• Influenza like illness
• Rigors
• Pyrexia

Sensory Disorders

• Increased lacrimation
• Conjunctivitis
• Eye irritation
• Reduced visual acuity 
• Diplopia
• Lacrimal duct stenosis
• Corneal disorders
• Keratitis 
• Punctate keratitis 
• Vertigo 
• Ear pain 
• Dry eye (when used in combination treatment)
• Eye pain (when used in combination treatment)
• Visual  impairment (when used in combination treatment)
• Vision blurred (when used in combination treatment)
• Tinnitus (when used in combination treatment)
• Hypoacusis (when used in combination treatment) 

Others

• Chest pain
• Oedema
• Weakness (when used in combination treatment) 
• Lethargy (when used in combination treatment) 
• Temperature intolerance (when used in combination treatment) 
• Mucosal inflammation (when used in combination treatment) 
• Fever (when used in combination treatment) 

• CYP2C9 substrates  
• Coumarin-derivative anticoagulants
• Phenytoin
• Folinic acid/folic acid
• Sorivudine and analogues  
• Antacids
• Radiotherapy
• Allopurinol
• Interferon alpha

• Renal function
• Hepatic function 
• Full blood count

Specific cases may require

• International Normalised Ratio (INR)

Capecitabine is a prodrug of 5-fluorouracil (5-FU). The enzyme involved in the final conversion to 5-FU, thymidine phosphorylase (ThyPase), is found in tumour tissues, but also in normal tissues. Capecitabine demonstrates a synergistic effect in combination with docetaxel, which may be related to the upregulation of thymidine phosphorylase by docetaxel.  Fluorouracil is a fluorinated pyrimidine antimetabolite that inhibits thymidylate synthetase, blocking the methylation of deoxyuridylic acid to thymidylic acid, interfering with DNA, and to a lesser degree, RNA synthesis. Since DNA and RNA are essential for cell division and growth, the effect of 5-FU may be to create a thymidine deficiency that provokes unbalanced growth and death of a cell. The effects of DNA and RNA deprivation are most marked on those cells which proliferate more rapidly and which metabolise 5-FU at a more rapid rate.

Tablet 150mg

• Capecitabine Specpharm (Specpharm)
• Capeloda 150 (Cipla)
• Capexa (Ingwe)
• Caxeta 150 (Ranbaxy Pharmaceuticals)
• Pecaset (Eurolab)
• Xeloda (Roche) originator

Tablet 500mg

• Capecitabine Specpharm (Specpharm)
• Capeloda 500 (Cipla)
• Capexa (Ingwe)
• Caxeta 500 (Ranbaxy Pharmaceuticals)
• Pecaset (Eurolab)
• Xeloda (Roche) originator