CAPECITABINE- capecitabine_tablet, film coated

Capecitabine is metabolized to fluorouracil in vivo 5-10 Population-based exposure-effect analyses demonstrated a positive association between AUC of fluorouracil and grade 3-4 hyperbilirubinemia. The AUC of capecitabine and its metabolite 5’-DFCR increases proportionally over a dosage range of 500 mg/m 2 2 max Absorption 2 max Effect of Food max 0-INF max 0-INF max Distribution Elimination Metabolism 2 Excretion Specific Populations Racial or Ethnic Groups 2 max max Patients with Renal Impairment Table 8 Effect of Renal Impairment on the Pharmacokinetics of Capecitabine, 5’-DFUR, and FBAL Renal Impairment a Changes in AUC b Capecitabine 5’-DFUR c FBAL c 5-FU CLcr 30 to 50 mL/min Increased by 25% Increased by 42% Increased by 85% No relevant change CLcr <30 mL/min Increased by 25% Increased by 71% Increased by 258% Increased by 24% a b 2 c Patients with Hepatic Impairment 0-INF max 0-INF max Drug Interaction Studies Clinical Studies Effect of Capecitabine on Warfarin: 2 Effect of Capecitabine on Celecoxib: 2 max trough Effect of Antacids on Capecitabine: 2 max Effect of Allopurinol on Capecitabine: Effect of Capecitabine on Docetaxel and Effect of Docetaxel on Capecitabine: max In Vitro Cytochrome P450 (CYP) Enzymes: in vitro The DPYD DPYD DPYD DPYD DPYD DPYD DPYD DPYD DPYD DPYD DPYD DPYD DPYD DPYD DPYD [see Warnings and Precautions (5.

Capecitabine is a nucleoside metabolic inhibitor indicated for: Colorectal Cancer 1. 1 Breast Cancer 1. 2 Gastric, Esophageal, or Gastroesophageal Junction Cancer 1. 3 Pancreatic Cancer 1. 4 Capecitabine tablet is indicated for the: Capecitabine tablet is indicated for the: Capecitabine tablet is indicated for the: Capecitabine tablet is indicated for the adjuvant treatment of adults with pancreatic adenocarcinoma as a component of a combination chemotherapy regimen.

Adjuvant Treatment of Colon Cancer 2 2. 1 Perioperative Treatment of Rectal Cancer 2 2. 1 Unresectable or Metastatic Colorectal Cancer: 2 2. 1 Advanced or Metastatic Breast Cancer: 2 2 2. 2 Unresectable or Metastatic Gastric, Esophageal, or Gastroesophageal Junction Cancer 2 2. 3 HER2-overexpressing metastatic adenocarcinoma of the gastroesophageal junction or stomach 2 2. 3 Pancreatic cancer 2 2 2. 6 Adjuvant Treatment of Colon Cancer Single Agent 2 In Combination with Oxaliplatin-Containing Regimens 2 2 Perioperative Treatment of Rectal Cancer 2 2 Unresectable or Metastatic Colorectal Cancer Single Agent 2 In Combination with Oxaliplatin 2 2 Advanced or Metastatic Breast Cancer Single Agent 2 2 In Combination with Docetaxel 2 2 2 The recommended dosage of capecitabine tablet for unresectable or metastatic gastric, esophageal, or gastroesophageal junction cancer is: 2 2 2 2 2 The recommended dosage of capecitabine tablet is 830 mg/m 2 2 Monitor patients for adverse reactions and modify dosages of capecitabine tablet as described in Table 1. Do not replace missed doses of capecitabine tablet; instead resume capecitabine tablet with the next planned dosage. Table 1 Recommended Dosage Modifications for Adverse Reactions Severity Dosage Modification Resume at Same or Reduced Dose (Percent of Current Dose) Grade 2 1st appearance Withhold until resolved to grade 0-1. 100% 2nd appearance 75% 3rd appearance 50% 4th appearance Permanently discontinue. - Grade 3 1st appearance Withhold until resolved to grade 0-1. 75% 2nd appearance 50% 3rd appearance Permanently discontinue. - Grade 4 1st appearance Permanently discontinue OR Withhold until resolved to grade 0-1. 50% Hyperbilirubinemia [see Warnings and Precautions (5. 10) Reduce the dose of capecitabine tablet by 25% for patients with creatinine clearance (CLcr) of 30 to 50 mL/min as determined by Cockcroft-Gault equation. A dosage has not been established in patients with severe renal impairment (CLcr <30 mL/min) [see Use in Specific Populations (8. 6) Round the recommended dosage for patients to the nearest 150 mg dose to provide whole capecitabine tablets. [see Warnings and Precautions (5.

The following clinically significant adverse reactions are described elsewhere in the labeling: [see Warnings and Precautions (5. 3) [see Warnings and Precautions (5. 4) [see Warnings and Precautions (5. 5) [see Warnings and Precautions (5. 6) [see Warnings and Precautions (5. 7) [see Warnings and Precautions (5. 8) [see Warnings and Precautions (5. 9) [see Warnings and Precautions (5. 10) Most common adverse reactions in patients who received capecitabine as a single agent for the adjuvant treatment for colon cancer (>30%) were palmar-plantar erythrodysesthesia syndrome, diarrhea, and nausea. 1 Most common adverse reactions (>30%) in patients with metastatic colorectal cancer who received capecitabine as a single agent were anemia, diarrhea, palmar-plantar erythrodysesthesia syndrome, hyperbilirubinemia, nausea, fatigue, and abdominal pain. 1 Most common adverse reactions ( >30%) in patients with metastatic breast cancer who received capecitabine with docetaxel were diarrhea, stomatitis, palmar-plantar erythrodysesthesia syndrome, nausea, alopecia, vomiting, edema, and abdominal pain. 1 Most common adverse reactions (>30%) in patients with metastatic breast cancer who received capecitabine as a single agent were lymphopenia, anemia, diarrhea, hand-and-foot syndrome, nausea, fatigue, vomiting, and dermatitis. 1 To report SUSPECTED ADVERSE REACTIONS, contact Hetero Labs limited at 1-866-495-1995 or FDA at 1-800-FDA-1088 or www. gov/medwatch. Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Adjuvant Treatment of Colon Cancer Single Agent [see Clinical Studies (14. 1) 2 2 2 Table 2 Adverse Reactions ( > Adverse Reaction Capecitabine (N=995) Fluorouracil + Leucovorin (N=974) All Grades (%) Grade 3 or 4 (%) All Grades (%) Grade 3 or 4 (%) Skin and Subcutaneous Tissue Palmar-plantar erythrodysesthesia syndrome 60 17 9 <1 Gastrointestinal Diarrhea 47 12 65 14 Nausea 34 2 47 2 Stomatitis 22 2 60 14 Vomiting 15 2 21 2 Abdominal pain 14 3 16 2 General Fatigue 16 <1 16 1 Asthenia 10 <1 10 1 Lethargy 10 <1 9 <1 Clinically relevant adverse reactions in <10% of patients are presented below: Eye: Gastrointestinal: General: Metabolism and Nutrition: Nervous System: Skin & Subcutaneous Tissue: Table 3 Grade 3 or 4 Laboratory Abnormalities (>1%) in Patients Who Received Capecitabine as a Single Agent for Adjuvant Treatment of Colon Cancer in X-ACT Laboratory Abnormality Capecitabine (N=995) Fluorouracil + Leucovorin (N=974) Grade 3 or 4 (%) Grade 3 or 4 (%) Bilirubin increased 20 6 Lymphocytes decreased 13 13 Neutrophils/granulocytes decreased 2. 4 26 Calcium decreased 2. 2 Neutrophils decreased 2. 2 26 ALT increased 1. 6 Calcium increased 1. 7 Hemoglobin decreased 1 1. 2 Platelets decreased 1 0. 7 In Combination with Oxaliplatin-Containing Regimens The safety of capecitabine for the perioperative treatment of adults with Stage III colon cancer as a component of a combination chemotherapy regimen was derived from published literature [see Clinical Studies (14. 1) Perioperative Treatment of Rectal Cancer [see Clinical Studies (14. 1) Metastatic Colorectal Cancer Single Agent [see Clinical Studies (14. 1) 2 2 2 Table 4 Adverse Reactions ( > Adverse Reaction Capecitabine (N=596) Fluorouracil + Leucovorin (N=593) All Grades (%) Grade 3 (%) Grade 4 (%) All Grades (%) Grade 3 (%) Grade 4 (%) Blood and Lymphatic System Anemia 80 2 <1 79 1 <1 Neutropenia 13 1 2 46 8 13 Gastrointestinal Diarrhea 55 13 2 61 10 2 Nausea 43 4 en dash 51 3 <1 Abdominal pain 35 9 <1 31 5 en dash Vomiting 27 4 <1 30 4 <1 Stomatitis 25 2 <1 62 14 1 Constipation 14 1 <1 17 1 en dash Gastrointestinal motility disorder 10 <1 en dash 7 <1 en dash Oral discomfort 10 en dash en dash 10 en dash en dash Skin and Subcutaneous Tissue Palmar-plantar erythrodysesthesia syndrome 54 17 NA 6 1 NA Dermatitis 27 1 en dash 26 1 en dash Hepatobiliary Hyperbilirubinemia 48 18 5 17 3 3 General Fatigue* 42 4 en dash 46 4 en dash Pyrexia 18 1 en dash 21 2 en dash Edema 15 1 en dash 9 1 en dash Pain 12 1 en dash 10 1 en dash Metabolism and Nutrition Decreased appetite 26 3 <1 31 2 <1 Respiratory Thoracic and Mediastinal Dyspnea 14 1 en dash 10 <1 1 Eye Eye irritation 13 en dash en dash 10 <1 en dash Nervous System Peripheral sensory neuropathy 10 en dash en dash 4 en dash en dash Headache 10 1 en dash 7 en dash en dash Musculoskeletal Back pain 10 2 en dash 9 <1 en dash en dash Not observed * Includes weakness NA = Not Applicable Eye: Gastrointestinal: General: Infections: Metabolism and Nutrition: Musculoskeletal: Nervous System: Psychiatric: Respiratory, Thoracic, and Mediastinal: Skin and Subcutaneous Tissue: Vascular: In Combination with Oxaliplatin [see Clinical Studies (14. 1) Metastatic Breast Cancer In Combination with Docetaxel [see Clinical Studies (14. 2) 2 2 2 Table 5 Adverse Reactions (>=10%) in Patients Who Received Capecitabine with Docetaxel for Metastatic Breast Cancer in Study SO14999 Adverse Reaction Capecitabine with Docetaxel (N=251) Docetaxel (N=255) All Grades (%) Grade 3 (%) Grade 4 (%) All Grades (%) Grade 3 (%) Grade 4 (%) Gastrointestinal Diarrhea 67 14 <1 48 5 <1 Stomatitis 67 17 <1 43 5 en dash Nausea 45 7 en dash 36 2 en dash Vomiting 35 4 1 24 2 en dash Abdominal pain 30 3 <1 24 2 en dash Constipation 20 2 en dash 18 en dash en dash Dyspepsia 14 en dash en dash 8 1 en dash Skin and Subcutaneous Tissue Palmar-plantar erythrodysesthesia syndrome 63 24 NA 8 1 NA Alopecia 41 6 en dash 42 7 en dash Nail disorder 14 2 en dash 15 en dash en dash Cardiac Edema 33 <2 en dash 34 <3 1 General Pyrexia 28 2 en dash 34 2 en dash Asthenia 26 4 <1 25 6 en dash Fatigue 22 4 en dash 27 6 en dash Weakness 16 2 en dash 11 2 en dash Pain in Limb 13 <1 en dash 13 2 en dash Blood and Lymphatic System Neutropenic fever 16 3 13 21 5 16 Nervous System Taste disturbance 16 <1 en dash 14 <1 en dash Headache 15 3 en dash 15 2 en dash Paresthesia 12 <1 en dash 16 1 en dash Dizziness 12 en dash en dash 8 <1 en dash Musculoskeletal and Connective Tissue Arthralgia 15 2 en dash 24 3 en dash Myalgia 15 2 en dash 25 2 en dash Back Pain 12 <1 en dash 11 3 en dash Respiratory, Thoracic and Mediastinal Dyspnea 14 2 <1 16 2 en dash Cough 13 1 en dash 22 <1 en dash Sore Throat 12 2 en dash 11 <1 en dash Metabolism and Nutrition Anorexia 13 <1 en dash 11 <1 en dash Appetite decreased 10 en dash en dash 5 en dash en dash Dehydration 10 2 en dash 7 <1 <1 Eye Lacrimation increased 12 - - 7 <1 - en dash Not observed NA = Not Applicable Blood and Lymphatic System: Cardiac: Eye: Gastrointestinal: General: Hepatobiliary: Immune System: Infection: Metabolism and Nutrition: Musculoskeletal and Connective Tissue: Nervous System: Psychiatric: Renal and Urinary: Respiratory, Thoracic and Mediastinal: Skin and Subcutaneous Tissue: Vascular: Table 6 Laboratory Abnormalities (>=20%) in Patients Who Received Capecitabine with Docetaxel for Metastatic Breast Cancer in Study SO14999 Laboratory Abnormality Capecitabine with Docetaxel (N=251) Docetaxel (N=255) All Grades (%) Grade 3 (%) Grade 4 (%) All Grades (%) Grade 3 (%) Grade 4 (%) Hematologic Lymphocytopenia 99 48 41 98 44 40 Leukopenia 91 37 24 88 42 33 Neutropenia 86 20 49 87 10 66 Anemia 80 7 3 83 5 <1 Thrombocytopenia 41 2 1 23 1 2 Hepatobiliary Hyperbilirubinemia 20 7 2 6 2 2 Single Agent The safety of capecitabine as a single agent was evaluated in patients with metastatic breast cancer in Study SO14697 [see Clinical Studies (14. 2) 2 Table 7 Adverse Reactions (>10%) in Patients Who Received Capecitabine for Metastatic Breast Cancer in Study SO14697 Adverse Reaction Capecitabine (n=162) All Grades (%) Grade 3 (%) Grade 4 (%) Blood and Lymphatic System Lymphopenia 94 44 15 Anemia 72 3 1 Neutropenia 26 2 2 Thrombocytopenia 24 3 1 Gastrointestinal Diarrhea 57 12 3 Nausea 53 4 en dash Vomiting 37 4 en dash Stomatitis 24 7 en dash Abdominal pain 20 4 en dash Constipation 15 1 en dash Skin and Subcutaneous Tissue Hand-and-foot syndrome 57 11 NA Dermatitis 37 1 en dash General Fatigue 41 8 en dash Pyrexia 12 1 en dash Metabolism and Nutrition Anorexia 23 3 en dash Hepatobiliary Hyperbilirubinemia 22 9 2 Nervous System Paresthesia 21 1 en dash Eye Eye irritation 15 en dash en dash en dash = Not observed NA = Not Applicable Pooled Safety Population Blood & Lymphatic System: Cardiac: Ear: Eye: Gastrointestinal: General: Hepatobiliary: Immune System: Infections: Metabolism and Nutrition: Musculoskeletal and Connective Tissue: Nervous System: Psychiatric: Renal and Urinary: Respiratory, Mediastinal and Thoracic: Skin and Subcutaneous Tissue: Vascular: Unresectable or Metastatic Gastric, Esophageal, or Gastroesophageal Junction Cancer [see Clinical Studies (14. 3) [see Clinical Studies (14. 3) Pancreatic Cancer [see Clinical Studies (14. 4) The following adverse reactions have been identified during post-approval use of capecitabine. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Eye: Hepatobiliary: Immune System Disorders: Nervous System: Renal & Urinary: Skin & Subcutaneous Tissue:.

Capecitabine is contraindicated in patients with history of severe hypersensitivity reaction to fluorouracil or capecitabine [see Adverse Reactions (6. 1) History of severe hypersensitivity reactions to fluorouracil or capecitabine ( 4.

Lactation 8. 2 Hepatic Impairment 8. 7 Risk Summary [see Clinical Pharmacology (12. 1) 2 (see Data) Data Animal Data Risk Summary (see Data) Data Capecitabine can cause fetal harm when administered to a pregnant woman [see Use in Specific Populations (8. 1) Pregnancy Testing Contraception Females Males [see Nonclinical Toxicology (13. Infertility [see Nonclinical Toxicology (13. 1) The safety and effectiveness of capecitabine in pediatric patients have not been established. Of 7938 patients with colorectal cancer who were treated with capecitabine, 33% were older than 65 years. Of the 4536 patients with metastatic breast cancer who were treated with capecitabine, 18% were older than 65 years. [see Drug Interactions (7. 1) The exposure of capecitabine and its inactive metabolites (5-DFUR and FBAL) increases in patients with CLcr <50 mL/min as determined by Cockcroft-Gault [see Clinical Pharmacology (12. 3) [see Dosage and Administration (2. 6) The exposure of capecitabine increases in patients with mild to moderate hepatic impairment. The effect of severe hepatic impairment on the safety and pharmacokinetics of capecitabine is unknown [see Clinical Pharmacology (12.

WARNING: INCREASED RISK OF BLEEDING WITH CONCOMITANT USE OF VITAMIN K ANTAGONISTS
Altered coagulation parameters and/or bleeding, including death, have been reported in patients taking capecitabine concomitantly with oral vitamin K antagonists, such as warfarin [see Warnings and Precautions (5. 1) Drug Interactions (7. 2) Clinically significant increases in prothrombin time (PT) and international normalized ratio (INR) have been reported in patients who were on stable doses of a vitamin K antagonist at the time capecitabine was introduced. These events occurred within several days and up to several months after initiating capecitabine and, in a few cases, within 1 month after stopping capecitabine. These events occurred in patients with and without liver metastases. Monitor INR more frequently and adjust the dose of the vitamin K antagonist as appropriate [see Drug Interactions (7.
DRUG INTERACTIONS
Allopurinol: 7. 1 Leucovorin: 7. 1 CYP2C9 substrates 7. 2 Vitamin K antagonists Phenytoin: 7. 2 Nephrotoxic drugs: 7. 3 Allopurinol [see Clinical Pharmacology (12. 3) Leucovorin CYP2C9 Substrates [see Clinical Pharmacology (12. 3) Vitamin K Antagonists [see Clinical Pharmacology (12. 3) [see Warning and Precautions (5. 1) Phenytoin Due of the additive pharmacologic effect, concomitant use of capecitabine with other drugs known to cause renal toxicity may increase the risk of renal toxicity [see Warnings and Precautions (5.

OVERDOSAGE
Administer uridine triacetate within 96 hours for management of capecitabine overdose.
NONCLINICAL TOXICOLOGY
Adequate studies investigating the carcinogenic potential of capecitabine have not been conducted. Capecitabine was not mutagenic in vitro in vitro in vivo in vivo. 2
CLINICAL STUDIES
Adjuvant Treatment of Colon Cancer Single Agent > > 9 > 9 < < < 2 2 2 Table 9 Baseline Demographics in X-ACT Capecitabine (N=1004) Fluorouracil + Leucovorin (N=983) Age (median, years) 62 63 Range (25-80) (22-82) Sex Male, % 54 54 Female, % 46 46 ECOG Performance Status 0, % 85 85 1, % 15 15 Staging en dash Primary Tumor PT1, % 1 0. 6 PT2, % 9 9 PT3, % 76 76 PT4, % 14 0 Other, % 0. 1 14 Staging en dash Lymph Node pN1, % 69 71 pN2, % 30 29 Other, % 0. 1 Efficacy results are summarized in Table 10 and Figures 1 and 2. The median follow-up at the time of the analysis was 6. Because the upper 2-sided 95% confidence limit of hazard ratio for DFS was less than 1. 20, capecitabine was non-inferior to fluorouracil + leucovorin. The choice of the non-inferiority margin of 1. 20 corresponds to the retention of approximately 75% of the fluorouracil + leucovorin effect on DFS. The hazard ratio for capecitabine compared to fluorouracil + leucovorin with respect to overall survival was 0. 86 (95% CI 0. The 5-year overall survival rates were 71% for capecitabine and 68% for fluorouracil + leucovorin. Table 10 Efficacy Results in X-ACTa (All Randomized Population) Efficacy Parameters Capecitabine (N=1004) Fluorouracil + Leucovorin (N=983) 5-year Disease-free Survival Rate b 59% 55% Hazard Ratio 0. 88 (95% CI) (0. 01) p-value c p = 0. 068 a b c Figure 1 Kaplan-Meier Estimates of Disease-Free Survival in X-ACT (All Randomized Population) Figure 2 Kaplan-Meier Estimates of Overall Survival in X-ACT (All Randomized Population) In Combination with Oxaliplatin-Containing Regimens Perioperative Treatment of Rectal Cancer Metastatic Colorectal Cancer 2 2 2 Table 11 Baseline Demographics for Study SO14695 and Study SO14796 Study SO14695 Study SO14796 Capecitabine (N=302) Fluorouracil + Leucovorin (N=303) Capecitabine (N=301) Fluorouracil + Leucovorin (N=301) Age (median, years) 64 63 64 64 Range (23-86) (24-87) (29-84) (36-86) Sex Male, % 60 65 57 57 Female, % 40 35 43 43 Karnofsky PS (median) 90 90 90 90 Range (70-100) (70-100) (70-100) (70-100) Colon, % 74 77 66 65 Rectum, % 26 23 34 35 Prior radiation therapy, % 17 21 14 14 Prior adjuvant fluorouracil, % 28 36 19 14 Efficacy results for Study SO14695 and Study SO14796 are shown in Table 12 and Table 13. Table 12 Efficacy Results for First-Line Treatment of Metastatic Colorectal Cancer (Study SO14695) Capecitabine (N=302) Fluorouracil + Leucovorin (N=303) Overall Response Rate % (95% CI) 21 (16, 26) 11 (8, 15) p - 0. 0014 Time to Progression Median, months (95% CI) 4. 0) Hazard Ratio 0. 99 95% CI (0. 17) Overall Survival Median, months (95% CI) 12. 7) Hazard Ratio 1. 00 95% CI (0. 18) Table 13 Efficacy Results for First-Line Treatment of Metastatic Colorectal Cancer (Study SO14796) Capecitabine (N=301) Fluorouracil + Leucovorin (N=301) Overall Response Rate % (95% CI) 21 (16, 26) 14 (10, 18) p-value 0. 027 Time to Progression Median, months (95% CI) 4. 1) Hazard Ratio 0. 97 95% CI (0. 14) Overall Survival Median, months (95% CI) 13. 92 95% CI (0. 09) Efficacy results of the pooled population from Study SO14695 and Study SO14796 are shown in Figure 3. Statistical analyses were performed to determine the percent of the survival effect of fluorouracil + leucovorin that was retained by capecitabine. The estimate of the survival effect of fluorouracil + leucovorin was derived from a meta-analysis of ten randomized studies from the published literature comparing fluorouracil to regimens of fluorouracil + leucovorin that were similar to the control arms used in these Studies SO14695 and SO14796. The method for comparing the treatments was to examine the worst case (95% confidence upper bound) for the difference between fluorouracil + leucovorin and capecitabine, and to show that loss of more than 50% of the fluorouracil + leucovorin survival effect was ruled out. It was demonstrated that the percent of the survival effect of fluorouracil + leucovorin maintained was at least 61% for Study SO14796 and 10% for Study SO14695. The pooled result is consistent with a retention of at least 50% of the effect of fluorouracil + leucovorin. It should be noted that these values for preserved effect are based on the upper bound of the fluorouracil + leucovorin vs capecitabine difference. Figure 3 Kaplan-Meier Curve for Overall Survival of Pooled Data (Studies SO14695 and SO14796) In Combination with Oxaliplatin capecitabinefigure1 capecitabinefigure2 capecitabinefigure3 In Combination With Docetaxel 2 2 2 Table 14 Baseline Demographics in Metastatic Breast Cancer (Study SO14999) Capecitabine + Docetaxel (N=255) Docetaxel (N=256) Age (median, years) 52 51 Karnofsky Performance Status (median) 90 90 Site of Disease Lymph nodes, % 47 49 Liver, % 45 48 Bone, % 42 46 Lung, % 37 39 Skin, % 29 29 Prior Chemotherapy Anthracycline 1 100 100 Fluorouracil, % 77 74 Paclitaxel, % 10 9 Resistance to an Anthracycline No resistance, % 7 7 Progression on anthracycline therapy, % 26 29 Stable disease after 4 cycles of anthracycline therapy, % 16 16 Relapsed within 2 years of completion of anthracycline-adjuvant therapy, % 31 29 Experienced a brief response to anthracycline therapy, with subsequent progression while on therapy or within 12 months after last dose, % 20 20 No. of Prior Chemotherapy Regimens for Treatment of Metastatic Disease 0, % 35 31 1, % 48 53 2, % 17 15 3, % 0 1 1 Table 15 Efficacy Results in Metastatic Breast Cancer (Study SO14999) Efficacy Parameter Capecitabine + Docetaxel (N=255) Docetaxel (N=256) Time to Disease Progression Median, months 6. 2 95% CI (5. 5) Hazard Ratio 0. 643 p-value 0. 0001 Overall Survival Median, months 14. 6 95% CI (12. 7) Hazard Ratio 0. 775 p-value 0. 0126 Response Rate 1 32% 22% 1 Figure 4 Kaplan-Meier Estimates for Time to Disease Progression in Metastatic Breast Cancer (Study SO14999) Figure 5 Kaplan-Meier Estimates of Survival in Metastatic Breast Cancer (Study SO14999) Single Agent 2 2 Table 16 Baseline Demographics in Metastatic Breast Cancer (Study SO14697) Patients With Measurable Disease (N=135) All Patients (N=162) Age (median, years) 55 56 Karnofsky Performance Status 90 90 No. Disease Sites 1-2, % 32 37 3-4, % 46 43 >5, % 22 21 Dominant Site of Disease Visceral 1 75 68 Soft Tissue, % 22 22 Bone, % 3 10 Prior Chemotherapy Paclitaxel, % 100 100 Anthracycline 2 90 91 Fluorouracil, % 81 82 Resistance to Paclitaxel, % 76 77 Resistance to an Anthracycline 2 41 41 Resistance to both Paclitaxel and an Anthracycline 2 32 31 1 2 Table 17 Efficacy Results in Metastatic Breast Cancer (Study SO14697) Efficacy Parameter Resistance to Both Paclitaxel and an Anthracycline (N=43) Response Rate 1 25. 6% Complete Response 0% Partial Response 1 11% Duration of Response 1 2 5. 7) 1 2 capecitabinefigure4 capecitabinefigure5 The efficacy of capecitabine for treatment of adults with unresectable or metastatic gastric, esophageal, or gastroesophageal junction cancer as a component of a combination chemotherapy regimen was derived from studies in the published literature. Capecitabine was evaluated in REAL-2, a randomized non-inferiority, 2x2 factorial trial, where the major efficacy outcome measure was overall survival, and an additional randomized trial conducted by the North Central Cancer Treatment Group, where the major efficacy outcome measure was objective response rate. The efficacy of capecitabine for the adjuvant treatment of adults with pancreatic adenocarcinoma as a component of a combination chemotherapy regimen was derived from a study in the published literature. Capecitabine was evaluated in ESPAC-4 trial, a two-group, open-label, multicenter, randomized trial, where the major efficacy outcome measure was overall survival.
REFERENCES
1. “OSHA Hazardous Drugs.” OSHA. http://www.osha.gov/SLTC/hazardousdrugs/index.html.
Patient Information
Capecitabine (kap″ e sye′ ta been) tablets What is the most important information I should know about capecitabine tablets? Capecitabine tablets can cause serious side effects, including: Increased risk of bleeding when taking capecitabine tablets with blood thinner medicines, such as warfarin. Taking capecitabine tablets with these medicines can cause changes in how fast your blood clots and can cause bleeding that can lead to death. and Tell your healthcare provider right away if you develop any signs or symptoms of bleeding. “What are the possible side effects of capecitabine tablets?” What are capecitabine tablets? and: and Do not take capecitabine tablets if you: Before taking capecitabine tablets, tell your healthcare provider about all your medical conditions, including if you: “What is the most important information I should know about capecitabine tablets?” Females Males How should I take capecitabine tablets? Do not “What are the possible side effects of capecitabine tablets?” Do not What are the possible side effects of capecitabine tablets? Capecitabine tablets can cause serious side effects including: See “What is the most important information I should know about capecitabine tablets?” Serious side effects in people with dihydropyrimidine dehydrogenase (DPD) enzyme deficiency. all your healthcare provider right away if you develop any of the following symptoms and they are severe, Heart problems. Stop taking capecitabine tablets and call your healthcare provider or go to the nearest hospital emergency room right away if you get any new symptoms of a heart problem including: Diarrhea. Loss of too much body fluid (dehydration) and kidney failure. Severe skin and mouth reactions. Decreased white blood cells, platelets, and red blood cell counts. Decreased white blood cells, platelets, and red blood cell counts can happen with capecitabine tablets and can sometimes be severe. Increased level of bilirubin in your blood and liver problems. Eye irritation, skin rash and other side effects with exposure to crushed capecitabine tablets. Do not chew, cut, or crush capecitabine tablets. “How should I take capecitabine tablets.” Severe allergic reactions can happen with capecitabine tablets. See “Do not take capecitabine tablets if you:” Stop taking capecitabine tablets and call your healthcare provider right away or go to an emergency room if you have any of the following symptoms of a severe allergic reaction to capecitabine tablets: How should I store capecitabine tablets? Keep capecitabine tablets and all medicines out of the reach of children. General information about the safe and effective use of capecitabine tablets. What are the ingredients in capecitabine tablets? Active ingredient: Inactive ingredients: Hetero Labs Limited, Unit V, Polepally, Jadcherla, Mahabubnagar - 509 301, India. For: BluePoint Laboratories Revised: 12/2024 This Patient Information has been approved by the U.S. Food and Drug Administration. Revised: 12/2024

BluePoint Laboratories

CAPECITABINE- capecitabine_tablet, film coated Product manual source documgent