The recommended dose of Capecitabine is 1250 mg/m 2 administered twice a day orally . The tablet must be swallowed whole with water within 30 minutes after a meal (morning and evening; equivalent to total daily dose of 2500 mg/m 2 ) for 2-weeks followed by a 1-week rest period given as 3-week cycles. Avoid crushing or cutting the Capecite tablets.

• General: Chest pain
• Psychiatric: Confusion
• Skin: Increased sweating, photosensitivity, radiation recall syndrome
• Respiratory: Dyspnea, epistaxis, bronchospasm, respiratory distress
• Gastrointestinal: Intestinal obstruction, rectal bleeding, GI hemorrhage, esophagitis, gastritis, colitis, duodenitis, haematemesis, necrotizing enterocolitis
• Hepatobiliary: Hepatic fibrosis, cholestatic hepatitis, hepatitis
• Infections: Oral candidiasis, upper respiratory tract infection, urinary tract infection, bronchitis, pneumonia, sepsis, bronchopneumonia, gastroenteritis, gastrointestinal candidiasis, laryngitis, esophageal candidiasis
• Neurological: Ataxia, encephalopathy, depressed level of consciousness, loss of consciousness
• Cardiac: Angina pectoris , cardiomyopathy
• Vascular: Hypotension, hypertension, venous phlebitis and thrombophlebitis,deep venous thrombosis, lymphoedema, pulmonary embolism, cerebrovascular
Accident
• Renal and Urinary: Nocturia
• Metabolism: Cachexia, hypertriglyceridemia
• Musculoskeletal: Bone pain, joint stiffness
• Blood: Coagulation disorder, idiopathic thrombocytopenic purpura, pancytopenia

The manifestations of acute overdose would include gastrointestinal irritation, vomiting, bone marrow depression, diarrhea, nausea and bleeding.

Treatment: Management of overdose is supportive treatment aimed at correcting the presenting clinical manifestations. Dialysis may be of benefit in reducing circulating concentrations of 5’-DFUR which is low–molecular-weight metabolite of the parent compound

Contraindicated in patients with

• Known hypersensitivity to Capecitabine or to any excipients of product.
• Severe renal impairment (creatinine clearance below 30 mL/min [Cockroft and Gault])
• Known hypersensitivity to 5-fluorouracil.

1. Diarrhea: Diarrhea can be induced by Capecitabine, which can be severe. Fluid and electrolyte replacement must be given to patients with severe diarrhea if they become dehydrated. Administration of Capecitabine should be immediately interrupted if grade 2, 3 and 4 diarrhea occurs until the diarrhea resolves or decreases in intensity to grade 1. Standard antidiarrheal treatments such as loperamide are recommended.

2. Renal Insufficiency: In patients with moderate renal impairment a dose reduction to 75% of the Capecitabine starting dose is recommended. No adjustment in starting dose is required in patients with mild renal impairment.

3. Coagulopathy: Bleeding and/or altered coagulation parameters have been reported in patients co administered with coumarin-derivative anticoagulants such as warfarin and phenprocoumon.

4. Geriatric Patients: Patients ≥80 years old may have an increased incidence of gastrointestinal grade 3 or 4 adverse events
5. Pregnancy: In pregnant women , Capecitabine may cause fetal harm. 198 mg/kg/day dose of Capecitabine given during organogenesis caused teratogenic malformations and embryo death in mice.
6. Hand-and-Foot Syndrome: Hand-and-foot syndrome is characterized by the following: dysesthesia/paresthesia, numbness, painless or painful swelling, tingling, erythema, blistering, desquamation, blistering and severe pain. If grade 2 or 3 hand-and-foot syndrome occurs, administration of Capecitabine should be interrupted until the event resolves or decreases in intensity to grade 1.

7. Cardiac: Cardiotoxicity has been reported including angina, myocardial infarction, dysrhythmias, electrocardiograph changes , cardiogenic shock, and sudden death especially in patients with a prior history of coronary artery disease

8. Hepatic Insufficiency: When Capecitabine is administered to patients with mild to moderate hepatic dysfunction due to liver metastases they must be carefully monitored. The effect of severe hepatic dysfunction on the disposition of Capecitabine is currently not known.

9. Nausea: Patients with grade 2 nausea (food intake significantly decreased but able to eat intermittently) or greater must stop taking Capecitabine immediately. Initiation of symptomatic treatment is recommended.

10. Vomiting: Patients with grade 2 vomiting (2 to 5 episodes in a 24-hour period) or greater should stop taking Capecitabine.

11. Carcinogenesis, Mutagenesis and Impairment of Fertility: Long-term studies in animals to evaluate the carcinogenic potential of capecitabine have not been performed. Capecitabine was not mutagenic in vitro to bacteria or mammalian cells.Capecitabine was clastogenic in vitro to human peripheral blood lymphocytes but not clastogenic in vivo to mouse bone marrow. Fluorouracil causes mutations in bacteria and yeast and chromosomal abnormalities in the mouse micronucleus test in vivo.
Impairment of Fertility: General reproductive performance in mice demonstrated that oral capecitabine doses of 760 mg/kg/day disturbed estrus and caused a decrease in fertility. In mice that became pregnant, no fetuses survived this dose. The disturbance in estrus was reversible. In males, this dose caused degenerative changes in the testes, and decreases in the number of spermatocytes and spermatids.

12. Nursing Women: It is not known if the drug is excreted in human milk. Since many drugs are excreted in human milk and due to the potential for serious adverse events in nursing infants, it is recommended that nursing be discontinued when receiving Capecitabine.

13. Pediatric Use: In patients<18 years, safety and effectiveness of capecitabine is not established.

Store at temperature not exceeding 30°C.

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