Xeloda 150mg - (fluoropyrimidine carbamate) with anti-tumor activity
Xeloda 150mg is a prodrug of 5’-deoxy-5-fluorouridine (5’-DFUR) which is changed to 5 fluoro uracil.
Xeloda 150mg is generally administered orally.
Xeloda 150mg is also have anti-metabolite activity
Colorectal cancer :
Adjuvant treatment in Duke’s colon cancer
First line therapy in colon-rectal cancer metastasis
In metastatic breast cancer: used in combination with docetaxel after failure of anthracycline containing chemotherapy
Mechanism of action
Capecitabine is a prodrug, it is metabolizing to 5-FU. In both non-cancer and cancer cells, 5-FU is metabolized in to 5-fluoro-2-deoxyuridine monophosphate (FdUMP) and 5-fluorouridine triphosphate (FUTP)
These two metabolites cause injury to the tumor cells by two major ways :
FdUMP and the folate cofactor (N5-10-methylenetetrahydrofolate), which binds to thymidylate synthase (TS) to form covalently bound ternary complex.
This binding prohibits the production of thymidylate from 2’-deaxyuridylate
Thymidylate an important messenger of thymidylate triphosphate.
It is essential for DNA synthesis; therefore, insufficiency of this compound leads to inhibit cell division
Nuclear transcriptional enzymes can falsely inserted FUTP alternative to uridine triphosphate during RNA synthesis. This metabolic failure can hinder with RNA conversion and protein synthesis via assembly of counterfeit RNA.
Capecitabine reaches the peak plasma level at about 1.5 hours
Food decreased both the rate and duration of absorption of Xeloda 150mg with mean Cmax and AUC0-∞ reduced by 60% and 35% respectively
The human plasma protein bound to Capecitabine is occurs in less than 60%
Capecitabine is largely metabolized to 5-FU enzymatically. In liver, 60 kDa carboxylesterase hydrolyses to 5’-deoxy-5-fluorocytidine.
Cytidine deaminase is an enzyme which converts 5’-DFCR to 5’-DFUR. Thymidine phosphorylase is also an enzyme which involved in the conversion of 5’-DFUR to 5-FU active drug
The route of elimination of Capecitabine is occurred through urine 95.5%
The mean terminal half-life period of Capecitabine is 0.75 hour
First line therapy of patients with advanced colorectal cancer:
The usual dose of Xeloda is 1250mg/m2 should be taken orally as twice daily (morning and evening dose 2500mg/m2); therapy continue for 2 weeks followed by 1-week rest period given as 3 weeks cycle
Adjuvant therapy for Duke’s colon cancer:
The usual dose of Xeloda is 1250mg/m2 orally as twice daily (morning and evening dose 2500mg/m2); for 2 weeks followed by 1 week given as 3 weeks for total 8 cycles (24 weeks)
Recommended dose: 1250mg/m2 should be taken as orally for twice daily
In combination with docetaxel;
1250mg/m2 of Xeloda 150mg with 75mg/m2 of docetaxel for 3 weeks
Xeloda should be administered within 30 minutes after a meal
The safety and efficacy of the Xeloda tablets in pediatric patients has not been established
Diarrhea, nausea, anemia, Lymphopenia, head and foot syndrome, edema, fatigue, fever, headache, pain, paresthesia, alopecia, dermatitis, abdominal pain, anorexia, loss of appetite, constipation, dyspepsia, stomatitis, vomiting, neutropenia, thrombocytopenia, dyspnea, bilirubin decreased, eye irritation
Chest pain, dermatitis, Pruritus, rash, dizziness, headache, weakness, dehydration, dry mouth, dyspepsia, taste disturbance, back pain
Post marketing reports:
Coagulopathy: concomitant with warfarin, anti-coagulant response should be monitored
Diarrhea: patients with severe diarrhea should be monitored
Cardio toxicity: while taking Xeloda 150mg, cardio toxicity occurs like; myocardial infarction, angina, dyshythmias,cardiac arrest sudden death, Cardiomyopathy
Dihydropyrimidine dehydrogenase deficiency
Dehydration and renal failure
Embryo fetal toxicity
Mucocutaneous and dermatologic toxicity
Care should be taken while using in geriatric patients