Capecitabine is a nucleoside metabolic inhibitor with antineoplastic activity used for the treatment of several types of cancer.

• Adjuvant treatment of colon cancer: For patients diagnosed with Dukes’ C colon cancer following surgical resection.
• Metastatic colorectal cancer: Used as first-line monotherapy in patients for whom treatment with fluoropyrimidine therapy alone is considered appropriate.
• Metastatic breast cancer: Used in combination with Docetaxel in patients whose disease has progressed after prior anthracycline-containing chemotherapy.
• Advanced breast cancer (monotherapy): Capecitabine may also be used alone in patients whose tumors are resistant to both paclitaxel and anthracycline-based chemotherapy regimens.

Capecitabine is an orally administered chemotherapeutic agent that functions as a prodrug. After administration, it is enzymatically converted within the body into Fluorouracil (5-FU), an antimetabolite that interferes with DNA synthesis and inhibits tumor growth.

Capecitabine is selectively activated within tumor tissue by the enzyme thymidine phosphorylase, which is present in higher concentrations in many tumor cells compared with normal tissues or plasma. This selective activation results in increased concentrations of the active drug within tumors. Fluorouracil is subsequently metabolized into two active cytotoxic metabolites: 5-fluoro-2′-deoxyuridine-5′-monophosphate (FdUMP), 5-fluorouridine triphosphate (FUTP) These metabolites damage cancer cells through two main mechanisms: Inhibition of DNA synthesis: FdUMP binds with the folate cofactor N5,N10-methylenetetrahydrofolate and the enzyme thymidylate synthase (TS) to form a stable ternary complex. This interaction blocks the conversion of deoxyuridylate to thymidylate, which is required for the formation of thymidine triphosphate, an essential component for DNA synthesis. As a result, DNA production is disrupted and cell division is inhibited. Interference with RNA and protein synthesis: FUTP may be mistakenly incorporated into RNA instead of uridine triphosphate (UTP) during RNA synthesis. This abnormal incorporation disrupts RNA processing and interferes with protein synthesis, ultimately leading to cancer cell damage and death.

Monotherapy: 1250 mg/m² twice daily orally for 2 weeks followed by a one-week rest period in 3-week cycles.

Adjuvant treatment: Is recommended for a total of 6 months (8 cycles).

In combination with docetaxel: The recommended dose of Capecitabine is 1250 mg/m² twice daily for 2 weeks followed by a 7-day rest period, combined with docetaxel at 75 mg/m² as a 1-hour IV infusion every 3 weeks. Capecitabine dosage may need to be individualized to optimize patient management. Capecitabine dosage has to be reduced by 25% in patients with moderate renal impairment.

Example: A person whose body weight is 64 kg and height is 1.64 m has a body surface area of 1.7 m² and should take 4 tablets of 500 mg and 1 tablet of 150 mg two times daily.

The tablets should be taken in morning and evening as prescribed by doctor. The tablets should be taken within 30 minutes after the end of a meal (breakfast and dinner) and swallowed whole with water. Tablets should not be cut or crushed. Capecitabine should only be prescribed by a doctor experienced in the use of anticancer medicines.

Capecitabine may interact with several medications that can influence its therapeutic effects or increase the risk of toxicity.

• Anticoagulants: Patients receiving anticoagulant therapy should have their INR or prothrombin time monitored frequently, as Capecitabine may enhance the anticoagulant effect. Dose adjustments of the anticoagulant may be required.
• Phenytoin: Concomitant use with Phenytoin may increase phenytoin levels in the blood. Regular monitoring of phenytoin concentrations is recommended, and dose adjustment may be necessary.
• Leucovorin: The presence of Leucovorin may increase the concentration of Fluorouracil, which can enhance both the effectiveness and toxicity of treatment.
• CYP2C9 substrates: Caution should be exercised when Capecitabine is administered together with drugs metabolized by the CYP2C9 enzyme.
• Food: Food may reduce both the rate and extent of Capecitabine absorption, although the medicine is usually recommended to be taken shortly after meals.

Capecitabine should not be used in patients with:

• Severe renal impairment
• Known hypersensitivity to Capecitabine or its components
• Severe leucopenia, neutropenia, or thrombocytopenia
• History of severe reactions to fluoropyrimidine therapy
• Complete dihydropyrimidine dehydrogenase (DPD) deficiency
• Pregnancy or breastfeeding

Common side effects associated with Capecitabine include:Abdominal pain, Rash, dry or itchy skin, Fatigue, Loss of appetite (anorexia), Diarrhea, Nausea and vomiting, Stomatitis, Hand-foot syndrome, Fever and infection, Chest pain. Severe skin reactions such as Stevens-Johnson Syndrome.

Capecitabine is classified as Pregnancy Category D and may cause harm to the developing fetus. Women should be informed about the potential risk during pregnancy. It is not known whether Capecitabine is excreted in human breast milk. Because of the potential risk to the nursing infant, breastfeeding should be discontinued during treatment and for at least 2 weeks after the final dose.

Coagulopathy: Capecitabine may increase the risk of bleeding in patients receiving anticoagulants. Monitoring of INR and appropriate dose adjustment are necessary.

Diarrhea: Severe diarrhea may occur. Treatment should be interrupted until symptoms improve to Grade 1 or resolve completely.

Cardiotoxicity: Patients with a history of coronary artery disease may be at increased risk of cardiac complications.

DPD deficiency: Patients with low or absent dihydropyrimidine dehydrogenase (DPD) activity may experience severe or fatal toxicity. Treatment should be discontinued if early severe toxicity occurs.

Dehydration and renal failure: Capecitabine therapy should be temporarily stopped if dehydration occurs to prevent kidney damage.

Dermatologic toxicity: Severe skin reactions such as Stevens–Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN) may occur. Treatment should be discontinued if these reactions develop.

Hand-foot syndrome: Therapy should be interrupted until symptoms improve.

Hyperbilirubinemia: Treatment should be paused until bilirubin levels return to normal.

Hematologic toxicity: Treatment should not be started if neutrophil count is <1.5 × 10⁹/L or platelet count is <100 × 10⁹/L.

Acute overdose may cause symptoms such as nausea, vomiting, diarrhea, mucositis, irritation of the gastrointestinal tract, bleeding, and suppression of bone marrow function. Treatment of overdose involves standard medical care and supportive measures to manage symptoms and reduce the risk of complications.

Cytotoxic Chemotherapy

Store in a dry place below 30°C, protected from light. Keep out of the reach of children.