Capecitabine
Capecitabine (Xeloda)
Capecitabine
(cap- SITE-ah-bean)
Pregnancy Category: D Xeloda (Rx)

Classification: Antineoplastic, antimetabolite

See Also: See also Antineoplastic Agents.

Action/Kinetics: An oral prodrug of 5'-deoxy-5-fluorouridine (5'DFUR) that is converted to 5-fluorouracil (5-FU). 5-FU is metabolized to 5-fluoro-2-deoxyuridine monophosphate (FdUMP) and 5-fluorouridine triphosphate (FUTP) which cause cell injury in two ways. First, FdUMP and the folate cofactor, N ^5-10-methylenetetrahydrofolate, bind to thymidylate synthase to form a covalently bound ternary complex which inhibits the formation of thymidylate from uracil. Thymidylate is essential for the synthesis of DNA so a deficiency inhibits cell division. Secondly, nuclear transcriptional enzymes can mistakenly incorporate FUTP in place of uridine triphosphate during RNA synthesis; this interferes with RNA processing and protein synthesis. Readily absorbed from the GI tract. Peak blood levels, capecitabine: 1.5 hr; peak blood levels, 5-FU: 2 hr. Food reduces the rate and extent of absorption. t 1/2, capecitabine and 5-FU: 45 min. Metabolites excreted in the urine.

Uses: Metastatic breast cancer in those resistant to both paclitaxel and an anthracycline-containing chemotherapy regimen or resistant to paclitaxel and for whom further anthracycline therapy is not indicated (e.g., those who have received cumulative doses of 400 mg/m ² of doxorubicin or doxorubicin equivalents).

Contraindications: Lactation.

Special Concerns: Use with caution in impaired renal function and in the elderly. Those over 80 years may experience a greater incidence of GI side effects. Safety and efficacy in children less than 18 years of age have not been determined. Use caution not to confuse Xeloda (capecitabine) with Xenical (orlistat).

Side Effects: GI: Diarrhea (may be severe), N&V;, stomatitis, abdominal pain, constipation, dyspepsia, intestinal obstruction, rectal bleeding, GI hemorrhage esophagitis, gastritis, colitis, duodenitis, haematemesis, necrotizing enterocolitis oral/ GI/esophageal candidiasis, gastroenteritis. CV: Cardiotoxicity ( MI angina, dysrhythmias, ECG changes, cardiogenic shock, sudden death), angina pectoris, cardiomyopathy hypotension, hypertension, venous phlebitis, thrombophlebitis, DVT, lymphedema, pulmonary embolism, CVA. Hematologic: Neutropenia (grade 3 or 4), thrombocytopenia, decreased hemoglobin, anemia, lymphopenia, coagulation disorder, idiopathic thrombocytopenia, pancytopenia, sepsis. Dermatologic: Hand-and-foot syndrome, dermatitis, nail disorder, increased sweating, photosensitivity, radiation recall syndrome. Neurological: Paresthesia, fatigue, headache, dizziness, insomnia. CNS: Ataxia, encephalopathy, decreased level of consciousness, loss of consciousness, confusion. Metabolic: Anorexia, dehydration, cachexia, hypertriglyceridemia. Respiratory: Dyspnea, epistaxis, bronchospasm, respiratory distress, URTI, bronchitis, pneumonia, bronchopneumonia, laryngitis. Musculoskeletal: Myalgia, pain in limb, bone pain, joint stiffness. GU: Nocturia, UTI. Hepatic: Hepatic fibrosis, cholestatic hepatitis, hepatitis. Miscellaneous: Hyperbilirubinemia (grade 3 or 4), eye irritation, pyrexia, edema, chest pain, drug hypersensitivity.

Overdose Management: Symptoms: N&V;, diarrhea, GI irritation and bleeding, bone marrow suppression. Treatment: Supportive medical interventions, dose interruption, adjust dose.

Drug Interactions: Antacids / Absorption of capecitabine Coumarin derivatives (warfarin) / Risk of bleeding and altered coagulation test results Leucovorin / 5-FU levels toxicity; deaths from severe enterocolitis, diarrhea, and dehydration seen in elderly clients receiving both drugs

How Supplied: Tablets: 150 mg, 500 mg

Dosage
?Tablets Metastatic breast cancer.
2,500 mg/m ²/day in two divided doses about 12 hr apart at the end of a meal for 2 weeks. Follow by a 1-week rest period (i.e., 3-week cycles).