Capcitab

• Colorectal Cancer:
  Used as adjuvant treatment for Stage III colon cancer following surgery. Also indicated for metastatic colorectal cancer as monotherapy or in combination with other agents.
• Breast Cancer:
  Indicated for metastatic breast cancer after failure of anthracycline and taxane therapy or when these are contraindicated.
• Gastric Cancer:
  Used in advanced gastric cancer, often in combination with other chemotherapeutic agents.
• Off-label Uses:
  Occasionally used in other gastrointestinal cancers and head and neck cancers under investigational protocols.

• Adults (Colorectal & Breast Cancer):
  Typical dose: 1250 mg/m² orally twice daily (morning and evening) within 30 minutes after a meal, for 14 days followed by 7 days off (21-day cycle).
• Dose Adjustments:
  Modify dose based on toxicity severity, particularly hand-foot syndrome, diarrhea, or hematologic toxicity.
• Hepatic Impairment:
  Use with caution in moderate impairment; avoid in severe impairment.
• Renal Impairment:
  Reduce dose in moderate renal impairment (creatinine clearance 30–50 mL/min). Avoid in severe impairment (<30 mL/min).
• Elderly:
  No specific adjustment; monitor closely for toxicity.
• Pediatrics:
  Safety and efficacy not established.
• Administration Route:
  Oral tablets swallowed whole with water, twice daily after meals.

Capecitabine is an oral prodrug converted enzymatically to 5-fluorouracil (5-FU) preferentially in tumor tissue. 5-FU inhibits thymidylate synthase, disrupting DNA synthesis and repair, and incorporates into RNA, impairing RNA processing. This results in selective cytotoxicity towards rapidly proliferating cancer cells, leading to tumor cell death.

• Absorption:
  Well absorbed orally with peak plasma concentration in 1.5–2 hours.
• Bioavailability:
  Approximately 70%.
• Distribution:
  Widely distributed, crosses placenta; plasma protein binding ~54%.
• Metabolism:
  Sequentially converted by carboxylesterase, cytidine deaminase, and thymidine phosphorylase (higher in tumor tissue) to active 5-FU.
• Half-life:
  Capecitabine ~0.55–0.89 hours; active 5-FU metabolites have short half-life (~10–20 minutes).
• Elimination:
  Mainly renal elimination of metabolites.

• Pregnancy:
  Category D – Positive evidence of risk. Avoid use during pregnancy due to teratogenic and embryotoxic effects.
• Lactation:
  Unknown if excreted in human milk. Breastfeeding not recommended during treatment.

• Primary: Antimetabolite Antineoplastic Agent
• Subclass: Fluoropyrimidine derivative

• Hypersensitivity to capecitabine, 5-FU, or excipients.
• Severe renal impairment (creatinine clearance <30 mL/min).
• Pregnancy and lactation.
• Known DPD (dihydropyrimidine dehydrogenase) deficiency.
• Concurrent use with sorivudine or related compounds.

• Monitor for severe diarrhea, mucositis, hand-foot syndrome.
• Risk of myelosuppression requiring CBC monitoring.
• Caution in patients with renal or hepatic impairment.
• May cause cardiotoxicity (ischemia, arrhythmias).
• Monitor for signs of infection due to immunosuppression.
• Patients should be monitored for symptoms of DPD deficiency.

Common:

• Hand-foot syndrome (palmar-plantar erythrodysesthesia)
• Diarrhea, nausea, vomiting
• Fatigue
• Mucositis
• Anemia, neutropenia, thrombocytopenia

Serious/Rare:

• Severe myelosuppression
• Cardiotoxicity (angina, myocardial infarction)
• Severe dermatologic reactions (toxic epidermal necrolysis)
• Hepatotoxicity
• Cerebellar syndrome (rare)

• Sorivudine/Vidarabine: Contraindicated due to fatal toxicity.
• Warfarin: May increase anticoagulant effect; monitor INR closely.
• Phenytoin: Plasma levels may be altered; monitor accordingly.
• Live vaccines: Use with caution due to immunosuppression.
• No significant CYP450 involvement.

• Guidelines recommend capecitabine as an oral alternative to intravenous 5-FU in colorectal and breast cancer adjuvant settings.
• Recent FDA advisories highlight importance of DPD deficiency screening to avoid severe toxicity.
• Updated management protocols for hand-foot syndrome and diarrhea have been published to optimize tolerability.

• Store at 20°C to 25°C (68°F to 77°F).
• Protect from moisture and light.
• Keep tablets in original packaging until use.
• Keep out of reach of children.