Mechanism of Action: Enzymes convert Capecitabine to 5-fluorouracil (5-FU) in vivo. Both normal and tumor cells metabolize 5-FU to 5-fluoro-2'-deoxyuridine monophosphate (FdUMP) and 5-fluorouridine triphosphate (FUTP). These metabolites cause cell injury.
Absorption: Following oral administration of 1255 mg/m² BID to cancer patients, Capecitabine reaches peak blood levels in about 1.5 hours (Tmax).
Distribution: Plasma protein binding of Capecitabine and its metabolites is less than 60% and is not concentration-dependent.
Bioactivation and Metabolism: Capecitabine is extensively metabolized enzymatically to 5-FU. In the liver, a 60 kDa carboxylesterase hydrolyzes much of the compound to 5-deoxy-5-fluorocytidine (5'-DFCR). Cytidine deaminase, an enzyme found in most tissues, including tumors, subsequently converts 5'-DFCR to 5'-DFUR. The enzyme thymidine phosphorylase (ThPase) then hydrolyzes 5'-DFUR to the active drug 5-FU.
Excretion: Capecitabine and its metabolites are predominantly excreted in urine; 95.5% of the administered Capecitabine dose is recovered in urine.
Adjuvant Colon Cancer
Patients with Dukes' C colon cancer.
Metastatic Colorectal Cancer
First-line as monotherapy when treatment with fluoropyrimidine therapy alone is preferred.
Metastatic Breast Cancer
In combination with docetaxel after failure of prior anthracycline-containing therapy.
As monotherapy in patients resistant to both paclitaxel and an anthracycline-containing regimen.
Monotherapy (Metastatic Colorectal Cancer, Adjuvant Colorectal Cancer, Metastatic Breast Cancer)
The recommended dose of Capecitabine is 1250 mg/m² administered orally twice daily (morning and evening; equivalent to 2500 mg/m² total daily dose) for 2 weeks, followed by a 1-week rest period, given as 3-week cycles.
Adjuvant treatment in patients with Dukes' C colon cancer is recommended for a total of 6 months, i.e., Capecitabine 1250 mg/m² orally twice daily for 2 weeks, followed by a 1-week rest period, given as 3-week cycles for a total of 8 cycles (24 weeks).
In Combination with Docetaxel (Metastatic Breast Cancer)
In combination with docetaxel, the recommended dose of Capecitabine is 1250 mg/m² twice daily for 2 weeks, followed by a 1-week rest period, combined with docetaxel at 75 mg/m² as a 1-hour intravenous infusion every 3 weeks.
Pregnancy: Pregnancy Category D. Can cause fetal harm. Advise women of the potential risk to the fetus.
Nursing Mothers: Discontinue nursing when receiving Capecitabine treatment.
Geriatric Patients: Greater incidence of adverse reactions. Monitoring required.
Capecitabine is contraindicated in patients with known hypersensitivity to Capecitabine or any of its components and in patients with severe renal impairment.
Coagulopathy
May result in bleeding or death. Monitor anticoagulant response (e.g., INR) and adjust anticoagulant dose accordingly.
Diarrhea
May be severe. Interrupt Capecitabine treatment immediately until diarrhea resolves or decreases to Grade 1. Standard antidiarrheal treatments are recommended.
Cardiotoxicity
Common in patients with a prior history of coronary artery disease.
Dehydration and Renal Failure
Interrupt Capecitabine treatment until dehydration is corrected. There is a potential risk of acute renal failure secondary to dehydration. Monitor and correct dehydration.
Mucocutaneous and Dermatologic Toxicity
Severe mucocutaneous reactions, including Stevens-Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN), have been reported.
Hyperbilirubinemia
Interrupt Capecitabine treatment immediately until hyperbilirubinemia resolves or decreases in intensity.
Hematologic Toxicity
Do not treat patients with neutrophil counts <1.5 × 10⁹/L or thrombocyte counts <100 × 10⁹/L. If Grade 3-4 neutropenia or thrombocytopenia occurs, stop therapy until the condition resolves.
The most common adverse reactions (≥30%) include diarrhea, hand-and-foot syndrome, nausea, vomiting, abdominal pain, fatigue/weakness, and hyperbilirubinemia.
Anticoagulants: Monitor anticoagulant response (INR or prothrombin time) frequently to adjust the anticoagulant dose as needed.
Phenytoin: Monitor phenytoin levels in patients taking Capecitabine concomitantly with phenytoin. The phenytoin dose may need to be reduced.
Leucovorin: The concentration of 5-fluorouracil is increased, and its toxicity may be enhanced by leucovorin
The manifestations of acute overdose may include nausea, vomiting, diarrhea, gastrointestinal irritation and bleeding, and bone marrow depression. Medical management of overdose should include customary supportive medical interventions aimed at correcting the presenting clinical manifestations.
Although no clinical experience using dialysis as a treatment for Capecitabine overdose has been reported, dialysis may be beneficial in reducing circulating concentrations of 5-DFUR, a low molecular-weight metabolite of the parent compound. Single doses of Capecitabine were not lethal to mice, rats, and monkeys at doses up to 2000 mg/kg.
Store at a temperature not exceeding 30°C in a dry place. Protect from light and moisture.
Keep out of reach of children.
