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The cardiotoxicity observed with XELODA includes myocardial infarction/ischemiaanginadysrhythmiascardiac arrestcardiac failuresudden deathelectrocardiographic changesand cardiomyopathyThese adverse reactions may be more common in patients with a prior history of coronary artery disease.
Other than warfarinno formal drug-drug interaction studies between XELODA and other CYP2C9 substrates have been conductedCare should be exercised when XELODA is coadministered with CYP2C9 substrates.
Enzymes convert capecitabine to 5-fluorouracil5-FUin vivoBoth normal and tumor cells metabolize 5-FU to 5-fluoro-2deoxyuridine monophosphateFdUMPand 5-fluorouridine triphosphateFUTPThese metabolites cause cell injury by two different mechanismsFirstFdUMP and the folate cofactorNmethylenetetrahydrofolatebind to thymidylate synthaseTSto form a covalently bound ternary complexThis binding inhibits the formation of thymidylate from 2deoxyuridylateThymidylate is the necessary precursor of thymidine triphosphatewhich is essential for the synthesis of DNAso that a deficiency of this compound can inhibit cell divisionSecondnuclear transcriptional enzymes can mistakenly incorporate FUTP in place of uridine triphosphateUTPduring the synthesis of RNAThis metabolic error can interfere with RNA processing and protein synthesis.
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