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XELODA (Capecitabine)

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XELODA (Capecitabine) HIGHLIGHTS OF PRESCRIBING INFORMATION ----------------------- WARNINGS AND PRECAUTIONS------------------------ These hig hlights do not include all the informatio n nee ded to use • Coagulopathy: May result in bleeding, death. Monitor anticoagulant XELODA safely and effectively. See full prescribing information for response (e.g., INR) and adjust anticoagulant dose accordingly. (5.1) XELODA . • Diarrhea: May be severe. Interrupt XELODA treatment immediately until diarrhea resolves or decreases to grade 1. Recommend standard XELODA (capecitabine) tablets, for oral use antidiarrheal treatments. (5.2) Initial U.S. Approval: 1998 • Cardiotoxicity: Common in patients with a prior history of coronary artery disease. (5.3) WARNING: XELODA-WARFARIN INTERACTION • Increased Risk of Severe or Fatal Adverse Reactions in Patients See full prescribing information for complete boxed warning. with Lo w or Absent Dihydropyrimidine Dehydrogenase (DPD) Patients receiving concomitant XELODA and oral coumarin-derivative Activity: Withhold or permanently discontinue XELODA in patients anticoagulants such as warfarin and phe nprocoumo n should have their with evidence of acute early-onset or unusually severe toxicity, which anticoagulant response (INR or prothrombin time) monitored frequently may indicate near complete or total absence of DPD activity. No in order to adjust the anticoagulant dose accordingly. Altered coagulation XELODA dose has been proven safe in patients with absent DPD parameters and/or bleeding, including de ath, have been re ported during activity. (5.4) concomitant use. • Dehydratio n and Renal Failure: Interrupt XELODA treatment until • Occurrence: Within several days and up to several mo nths after dehydration is corrected. Potential risk of acute renal failure secondary initiating XELODA therapy; may also be seen within 1 month after to dehydration. Monitor and correct dehydration. (5.5). stopping XELODA • Pregnancy: Can cause fetal harm. Advise women of the potential risk to • Predisposing factors: age>60 and diagnosis of cancer the fetus. (5.6, 8.1) • Mucocutaneous and Dermatologic Toxicity: Severe mucocutaneous reactions, Steven-Johnson Syndrome (SJS) and Toxic Epidermal --------------------------RECENT MAJOR CHANGES------------------------­ Necrolysis (TEN), have been reported. XELODA should be permanently Dosage and Administration (2.0) 10/2014 discontinued in patients who experience a severe mucocutaneous Contraindications (4.1) 02/2015 reaction during treatment. XELODA may induce hand-and-foot Warnings and Precautions (5.1, 5.2, 5.5, and 5.7) 10/2014 syndrome. Interrupt XELODA treatment until the hand-and-foot Warnings and Precautions (5.4) 02/2015 syndrome event resolves or decreases in intensity. (5.7) • Hyperbilirubinemia: Interrupt XELODA treatment immediately until --------------------------- INDICATIONS AND USAGE ---------------------------- the hyperbilirubinemia resolves or decreases in intensity. (5.8) XELODA (capecitabine) is a nucleoside metabolic inhibitor with • Hematologic: Do not treat patients with neutrophil counts <1.5 x 109/L antineoplastic activity indicated for: or thrombocyte counts <100 x 109/L. If grade 3-4 neutropenia or • Adjuv ant Colon Cancer (1.1) thrombocytopenia occurs, stop therapy until condition resolves. (5.9) – Patients with Dukes’ C colon cancer • Metastatic Colorectal Cancer (1.1) ------------------------------ ADVERSE REACTIONS ------------------------------ – First-line as monotherapy when treatment with fluoropyrimidine Most common adverse reactions (≥30%) were diarrhea, hand-and-foot therapy alone is preferred syndrome, nausea, vomiting, abdominal pain, fatigue/weakness, and • Metastatic Breast Cancer (1.2) hyperbilirubinemia. Other adverse reactions, including serious adverse – In combination with docetaxel after failure of prior anthracycline- reactions, have been reported. (6) containing therapy – As monotherapy in patients resistant to both paclitaxel and an To report SUSPECTED ADVERSE REACTIONS, contact Genentech at anthracycline-containing regimen 1-888-835-2555 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. ----------------------- DOSAGE AND ADMINISTRATION ----------------------- ------------------------------ DRUG INTERACTIONS------------------------------- • Take XELODA with water within 30 min after a meal (2) • Anticoagulants: Monitor anticoagulant response (INR or prothrombin • Monotherapy: 1250 mg/m2 twice daily orally for 2 weeks followed by a time) frequently in order to adjust the anticoagulant dose as needed. (5.2, one week rest period in 3-week cycles (2.1) 7.1) • Adjuvant treatment is recommended for a total of 6 months (8 cycles) • Phenytoin: Monitor phenytoin levels in patients taking XELODA (2.1) concomitantly with phenytoin. The phenytoin dose may need to be • In combination with docetaxel, the recommended dose of XELODA is reduced. (7.1) 1250 mg/m2 twice daily for 2 weeks followed by a 7-day rest period, • Leucovorin: The concentration of 5-fluorouracil is increased and its combined with docetaxel at 75 mg/m2 as a 1-hour IV infusion every 3 toxicity may be enhanced by leucovorin. (7.1) weeks (2.1) • CYP2C9 substrates: Care should be exercised when XELODA is • XELODA dosage may need to be individualized to optimize patient coadministered with CYP2C9 substrates. (7.1) management (2.2) • Food reduced both the rate and extent of absorption of capecitabine. (2, • Reduce the dose of XELODA by 25% in patients with moderate renal 7.1, 12.3) impairment (2.3) ----------------------- USE IN SPECIFIC POPULATIONS ----------------------- --------------------- DOSAGE FORMS AND STRENGTHS ---------------------- • Nursing Mothers: Discontinue nursing when receiving XELODA • Tablets: 150 mg and 500 mg (3) treatment. (8.3) • Geriatric: Greater incidence of adverse reactions. Monitoring required. ------------------------------ CONTRAINDICATIONS ------------------------------ (8.5) • Severe Renal Impairment (4.1) • Hepatic Impairment: Monitoring is recommended in patients with mild • Hypersensitivity (4.2) to moderate hepatic impairment. (8.6) • Renal Impairme nt: Reduce XELODA starting dose in patients with moderate renal impairment (2.3, 8.7, 12.3) See 17 for PATIENT COUNSELING INFORMATION and FDA- approved patient labeling Revised: 03/2015 ____________________________________________________________________________________________________________________________________ Reference1 ID: 3718670 FULL PRESCRIBING INFORMATION: CONTENTS* 6.3 Breast Cancer 6.4 Clinically Relevant Adverse Events in <5% of Patients WARNING: XELODA-WARFARIN INTERACTION 7 DRUG INTERACTIONS 1 INDICATIONS AND USAGE 7.1 Drug-Drug Interactions 1.1 Colorectal Cancer 7.2 Drug-Food Intera ction 1.2 Breast Cancer 8 USE IN SPECIFIC POPULATIONS 2 DOSAGE AND ADMINISTRATION 8.1 Pregnancy: Category D 2.1 Standard Starting Dose 8.3 Nursing Mothers 2.2 Dose Management Guidelines 8.4 Pediatric Use 2.3 Adjustment of Starting Dose in Special Populations 8.5 Geriatric Use 3 DOSAGE FORMS AND STRENGTHS 8.6 Hepatic Insufficiency 4 CONTRAINDICATIONS 8.7 Renal Insufficiency 4.1 Severe Renal Impairment 10 OVERDOSAGE 4.2 Hypersensitivity 11 DESCRIPTION 5 WARNINGS AND PRECAUTIONS 12 CLINICAL PHARMACOLOGY 5.1 Coagulopathy 12.1 Mechanism of Action 5.2 Diarrhea 12.3 Pharma cokinetics 5.3 Cardiotoxicity 13 NONCLINICAL TOXICOLOGY 5.4 Dihydropyrimidine Dehydrogenase Deficiency 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility 5.5 Dehydration and Renal Failure 14 CLINICAL STUDIES 5.6 Pregnancy 14.1 Adjuva nt Colon Ca ncer 5.7 Mucocutaneous and Dermatologic Toxicity 14.2 Metastatic Colorectal Cancer 5.8 Hyperbilirubinemia 14.3 Breast Cancer 5.9 Hematologic 15 REFERENCES 5.10 Geriatric Patients 16 HOW SUPPLIED/STORAGE AND HANDLING 5.11 Hepatic Insufficiency 17 PATIENT COUNSELING INFORMATION 5.12 Combination With Other Drugs 6 ADVERSE REACTIONS *Sections or subsections omitted from the full prescribing information are not 6.1 Adjuva nt Colon Ca ncer listed. 6.2 Metastatic Colorectal Cancer Reference2 ID: 3718670 FULL PRESCRIBING INFORMATION WARNING: XELODA-WARFARIN INTERACTION XELODA Warfarin Interaction: Patients receiving concomitant capecitabine and oral coumarin-derivative anticoagulant therapy should have their anticoagulant response (INR or prothrombin time) monitored frequently in order to adjust the anticoagulant dose accordingly. A clinically important XELODA-Warfarin drug interaction was demonstrated in a clinical pharmacology trial [see Warnings and Precautions (5.2) and Drug Interactions (7.1)]. Altered coagulation parameters and/or bleeding, including death, have been reported in patients taking XELODA concomitantly with coumarin-derivative anticoagulants such as warfarin and phenprocoumon. Postmarketing reports have shown clinically significant increases in prothrombin time (PT) and INR in patients who were stabilized on anticoagulants at the time XELODA was introduced. These events occurred within several days and up to several months after initiating XELODA therapy and, in a few cases, within 1 month after stopping XELODA. These events occurred in patients with and without liver metastases. Age greater than 60 and a diagnosis of cancer independently predispose patients to an increased risk of coagulopathy. 1 INDICATIONS AND USAGE 1.1 Colorectal Cancer • XELODA is indicated as a single agent for adjuvant treatment in patients with Dukes’ C colon cancer who have undergone complete resection of the primary tumor when treatment with fluoropyrimidine therapy alone is preferred. XELODA was non-inferior to
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