Xeloda-500mg

Class: Pyrimidine Antimetabolite Actions Capecitabine is an oral systemic prodrug that is enzymatically converted to 5-fluorouracil (5-FU). Healthy and tumor cells metabolize 5-FU to 5-fluoro-2-deoxyuridine monophosphate (FdUMP) and 5-fluorouridine triphosphate (FUTP). These metabolites cause cell injury by 2 different mechanisms. By inhibiting the formation of thymidine triphosphate, which is essential for the synthesis of DNA. Second, nuclear transcriptional enzymes can mistakenly incorporate FUTP during the synthesis of RNA. This metabolic error can intefere with RNA processing and protein synthesis. Capecitabine is readily absorbed from the GI tract. Capecitabine reaches peak blood levels in » 1.5 hr (Tmax) with peak 5-FU levels occurring slightly later, at 2 hr. Food reduces both the rate and extent of absorption. Plasma protein binding of capecitabine and its metabolites is < 60%. Capecitabine is primarily bound to human albumin (» 35%). The elimination half-life of parent capecitabine and 5-FU was » 45 min. Greater than 70% of the administered capecitabine dose is recovered in urine as drug-related species. Indications Treatment of resistant metastatic breast cancer. Colorectal cancer. Contraindications Hypersensitivity to 5-FU. Route/Dosage Breast Cancer ADULTS: PO 2500 mg/m2/day in 2 divided doses, » 12 hr apart, for 2 wk. After a 1-wk rest period, this 3-wk cycle is repeated. Round to the nearest dose that gives a whole tablet size, rather than cutting tablets in half. Dosing adjustments for all toxicities except palmar-plantar erythrodysesthesia are needed. Once the capecitabine dose is reduced, it should not be increased. Please see manufacturer's recommendations. Interactions Antacids May increase capecitabine levels. Cimetidine or metronidazole May increase serum concentrations of fluorouracil and potentially increase toxicity Fluorouracil Drug interactions have been reported with fluorouracil, the principal active metabolite of capecitabine. Levamisole Risk of hepatotoxicity may be increased by concomitant administration with fluorouracil. Leucovorin May enhance GI toxicity of fluorouracil. Warfarin May alter warfarin's effects Lab Test Interferences None well documented. Adverse Reactions CARDIOVASCULAR: Edema. CNS: Fatigue; paresthesia; headache; dizziness; insomnia. DERMATOLOGIC: Hand-and-foot syndrome; dermatitis; nail disorder. GI: Nausea; vomiting; anorexia; diarrhea; stomatitis; abdominal pain; constipation; dyspepsia; hyperbilirubinemia. HEMATOLOGIC: Neutropenia; thrombocytopenia; anemia; lymphopenia. METABOLIC: Dehydration. MUSCULOSKELETAL: Myalgia. SPECIALSENSES: Eye irritation. Precautions Pregnancy: Category D. Lactation: Undetermined. Children: Safety and efficacy not established. Elderly: Patients ³ 80 yr may experience a greater incidence of GI grade 3 or 4 adverse events. CAD: Use cautiously in patients with previous history of CAD. Cardiac effects: Cardiotoxicity has been associated with fluorinated pyrimidine therapy. Diarrhea: Capecitabine can induce diarrhea, sometimes severe. If grade 2, 3, or 4 diarrhea occurs, immediately interrupt administration until the diarrhea resolves or decreases in intensity to grade 1. Following grade 3 or 4 diarrhea, decrease subsequent doses of capecitabine. Fertility impairment: In mice, oral capecitabine doses of 760 mg/kg/day caused a decrease in fertility. Hand-and-foot syndrome: If grade 2 or 3 hand-and-foot syndrome occurs, interrupt administration of capecitabine until the event resolves or decreases in intensity to grade 1. Following grade 3 hand-and-foot syndrome, decrease subsequent doses of capecitabine. Hepatic function impairment: Carefully monitor patients with mild to moderate hepatic dysfunction caused by liver metastases. Hyperbilirubinemia: If grade 2 to 4 elevations in bilirubin occur, immediately interrupt administration until the hyperbilirubinemia resolves or decreases in intensity to grade 1. PATIENT CARE CONSIDERATIONS Administration/Storage Store at room temperature. Adminster orally and take at the end of a meal with water. Follow procedures for proper handling and disposal of anticancer drugs. Wear gloves and avoid skin exposure and inhalation of fumes. Assessment/Interventions Provide close monitoring for the development of diarrhea, nausea, vomiting, hand-and-foot syndrome, and stomatitis. Adjust dose based on NCIC toxicity grade and manufacturer recommendations. OVERDOSAGE: SIGNS & SYMPTOMS Nausea, vomiting, diarrhea, GI irritation and bleeding, bone marrow depression Patient/Family Education Inform patients of the expected adverse effects, particularly nausea, vomiting, diarrhea, and hand-and-foot syndrome. Instruct patients experiencing grade 2 or greater diarrhea (an increase of 4 to 6 stools/day or nocturnal stools) to stop taking capecitabine immediately. Standard antidiarrheal treatments (eg, loperamide) are recommended. Instruct patients experiencing grade 2 or greater nausea (food intake significantly decreased but able to eat intermittently) to stop taking capecitabine immediately. Instruct patients experiencing grade 2 or greater vomiting (2 to 5 episodes in a 24-hr period) to stop taking capecitabine immediately. Instruct patients experiencing grade 2 or greater hand-and-foot syndrome (eg, painful erythema, swelling of the hands or feet that results in discomfort affecting the patients' activities of daily living) to stop taking capecitabine immediately. Instruct patients experiencing grade 2 or greater stomatitis (eg, painful erythema, edema, or ulcers of the mouth or tongue, but able to eat) to stop taking capecitabine immediately. Instruct patients who develop a fever of ³ 100.5°F (38°C) or other evidence of potential infection to call health care provider. Books@Ovid