Captabine

• Carcinoma of the colon or rectum

Capecitabine is a nucleoside metabolic inhibitor with antineoplastic activity indicated for: Adjuvant Colon Cancer: Patients with Dukes'C colon cancer. Metastatic Colorectal Cancer: First-line as monotherapy when treatment with fluoropyrimidine therapy alone is preferred. ... Read moreCapecitabine is a nucleoside metabolic inhibitor with antineoplastic activity indicated for: 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.

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Severe Renal Impairment Hypersensitivity leucopenia, neutropenia or thrombocytopenia Severe reactions to fluoropyrimidine therapy Complete DPD deficiency Pregnant or breast-feeding

Capecitabine is a preparation of Capecitabine, an orally-administered chemotherapeutic agent used in the treatment of cancers. Capecitabine is a prodrug, that is enzymatically converted to fluorouracil (antimetabolite) in the tumour, where it inhibits DNA synthesis and slows growth of tumour tissue.Capecitabine is a prodrug that is selectively tumour-activated to its cytotoxic moiety, fluorouracil, by thymidine phosphorylase, an enzyme found in higher concentrations in many tumours compared to normal tissues or plasma. Fluorouracil is further metabolized to two active metabolites, 5-fluoro-2'-deoxyuridine 5-monophosphate (FdUMP) and 5-fluorouridine triphosphate (FUTP), within normal and tumour cells. These metabolites cause cell injury by two different mechanisms. First, FdUMP and the folate cofactor, N5-10 methylenetetrahydrofolate, bind to thymidylate synthase (TS) to form a covalently bound ternary complex. This binding inhibits the formation of thymidylate from 2-deoxyuridylate. Thymidylate is the necessary precursor of thymidine triphosphate, which is essential for the synthesis of DNA, therefore a deficiency of this compound can inhibit cell division. Secondly, nuclear transcriptional enzymes can mistakenly incorporate FUTP in place of uridine triphosphate (UTP) during the synthesis of RNA. This metabolic error can interfere with RNA processing and protein synthesis through the production of fraudulent RNA.

Anticoagulants: Anticoagulant response (INR or prothrombin time) should be monitored frequently in order to adjust the anticoagulant dose as needed. Phenytoin: Phenytoin levels should be monitored 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. CYP2C9 substrates: Care should be exercised when Capecitabine is co-administered with CYP2C9 substrates. Food: Reduced both the rate and extent of absorption of Capecitabine.

Abdominal pain, Rash, dry or itchy skin, Tiredness, loss of appetite (anorexia), Diarrhea, Vomiting, Nausea, Stomatitis, Hand-and-foot skin-reaction, Fever, Infection, Chest pain, Steven-Johnson syndrome

The manifestations of acute overdose include nausea, vomiting, diarrhea, mucositis, gastrointestinal irritation and bleeding, and bone marrow depression. Medical management of overdose should include customary therapeutic and supportive medical interventions aimed at correcting the presenting clinical manifestations and preventing their possible complications.

Pregnancy category D. Capecitabine can cause fetal harm. Women are advised of the potential risk to the fetus. 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. 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.

Coagulopathy: Anticoagulant response should be monitored (e.g. INR) and anticoagulant dose must be adjusted accordingly. Otherwise may result in bleeding, death.Diarrhea: Capecitabine treatment should be stopped immediately until diarrhea resolves or decreases to grade 1. Standard antidiarrheal treatments recommended. Otherwise may get severe.Cardiotoxicity: Common in patients with a prior history of coronary artery disease.Increased Risk of Severe or Fatal Adverse Reactions in Patients with Low or Absent Dihydropyrimidine Dehydrogenase (DPD) Activity: Capecitabine should be withhold or permanently discontinued in patients with evidence of acute early-onset or unusually severe toxicity, which may indicate near complete or total absence of DPD activity.Dehydration and Renal Failure: Capecitabine treatment should be stopped until dehydration is corrected. Potential risk of acute renal failure secondary to dehydration.Mucocutaneous and Dermatologic Toxicity: Severe mucocutaneous reactions, Steven-Johnson Syndrome. (SJS) and Toxic Epidermal Necrolysis (TEN), have been reported. Capecitabine should be permanently discontinued in patients who experience a severe mucocutaneous reaction during treatment. Capecitabine may induce hand-and-foot syndrome. Capecitabine treatment should be interrupted until the hand-and-foot syndrome event resolves or decreases in intensity.Hyperbilirubinemia: Capecitabine treatment should be interrupted immediately until the hyperbilirubinemia resolves or decreases in intensity.Hematologic: Patients should not be treated with neutrophil counts <1.5x109/L or thrombocyte counts <100x109/L.