Capecitabine Prescribing Information
Altered coagulation parameters and/or bleeding, including death, have been reported in patients taking capecitabine concomitantly with vitamin K antagonists, such as warfarin.
Clinically significant increases in PT and INR have been reported in patients who were on stable doses of oral vitamin K antagonists 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
Capecitabine increased exposure of CYP2C9 substrates
Capecitabine increases exposure of vitamin K antagonist
Monitor INR more frequently and refer to the prescribing information of oral vitamin K antagonist for dosage adjustment, as appropriate, when capecitabine is used concomitantly with vitamin K antagonist.
Capecitabine may increases exposure of phenytoin, which may increase the risk of adverse reactions related to phenytoin. Closely monitor phenytoin levels and refer to the prescribing information of phenytoin for dosage adjustment, as appropriate, when capecitabine is used concomitantly with phenytoin.
Capecitabine increased exposure of CYP2C9 substrates
Capecitabine increases exposure of vitamin K antagonist
Monitor INR more frequently and refer to the prescribing information of oral vitamin K antagonist for dosage adjustment, as appropriate, when capecitabine is used concomitantly with vitamin K antagonist.
Capecitabine may increases exposure of phenytoin, which may increase the risk of adverse reactions related to phenytoin. Closely monitor phenytoin levels and refer to the prescribing information of phenytoin for dosage adjustment, as appropriate, when capecitabine is used concomitantly with phenytoin.
Capecitabine is a nucleoside metabolic inhibitor indicated for:
• adjuvant treatment of patients with Stage III colon cancer as a single agent or as a component of a combination chemotherapy regimen. (
Capecitabine tablet is indicated for the:
• adjuvant treatment of patients with Stage III colon cancer as a single agent or as a component of a combination chemotherapy regimen.
• perioperative treatment of adults with locally advanced rectal cancer as a component of chemoradiotherapy.
• treatment of patients with unresectable or metastatic colorectal cancer as a single agent or as a component of a combination chemotherapy regimen.
• perioperative treatment of adults with locally advanced rectal cancer as a component of chemoradiotherapy. (
Capecitabine tablet is indicated for the:
• adjuvant treatment of patients with Stage III colon cancer as a single agent or as a component of a combination chemotherapy regimen.
• perioperative treatment of adults with locally advanced rectal cancer as a component of chemoradiotherapy.
• treatment of patients with unresectable or metastatic colorectal cancer as a single agent or as a component of a combination chemotherapy regimen.
• treatment of patients with unresectable or metastatic colorectal cancer as a single agent or as a component of a combination chemotherapy regimen. (
Capecitabine tablet is indicated for the:
• adjuvant treatment of patients with Stage III colon cancer as a single agent or as a component of a combination chemotherapy regimen.
• perioperative treatment of adults with locally advanced rectal cancer as a component of chemoradiotherapy.
• treatment of patients with unresectable or metastatic colorectal cancer as a single agent or as a component of a combination chemotherapy regimen.
• treatment of patients with advanced or metastatic breast cancer as a single agent if an anthracycline-or taxane-containing chemotherapy is not indicated. (
Capecitabine tablet is indicated for the:
• treatment of patients with advanced or metastatic breast cancer as a single agent if an anthracycline-or taxane-containing chemotherapy is not indicated.
• treatment of patients with advanced or metastatic breast cancer in combination with docetaxel after disease progression on prior anthracycline-containing chemotherapy.
• treatment of patients with advanced or metastatic breast cancer in combination with docetaxel after disease progression on prior anthracycline-containing chemotherapy. (
Capecitabine tablet is indicated for the:
• treatment of patients with advanced or metastatic breast cancer as a single agent if an anthracycline-or taxane-containing chemotherapy is not indicated.
• treatment of patients with advanced or metastatic breast cancer in combination with docetaxel after disease progression on prior anthracycline-containing chemotherapy.
• treatment of adults with unresectable or metastatic gastric, esophageal, or gastroesophageal junction cancer as a component of a combination chemotherapy regimen. (
Capecitabine tablet is indicated for the:
• treatment of adults with unresectable or metastatic gastric, esophageal, or gastroesophageal junction cancer as a component of a combination chemotherapy regimen.
• treatment of adults with HER2-overexpressing metastatic gastric or gastroesophageal junction adenocarcinoma who have not received prior treatment for metastatic disease as a component of a combination regimen.
• treatment of adults with HER2-overexpressing metastatic gastric or gastroesophageal junction adenocarcinoma who have not received prior treatment for metastatic disease as a component of a combination regimen. (
Capecitabine tablet is indicated for the:
• treatment of adults with unresectable or metastatic gastric, esophageal, or gastroesophageal junction cancer as a component of a combination chemotherapy regimen.
• treatment of adults with HER2-overexpressing metastatic gastric or gastroesophageal junction adenocarcinoma who have not received prior treatment for metastatic disease as a component of a combination regimen.
• adjuvant treatment of adults with pancreatic adenocarcinoma as a component of a combination chemotherapy regimen. (
Capecitabine tablet is indicated for the adjuvant treatment of adults with pancreatic adenocarcinoma as a component of a combination chemotherapy regimen.
• Single agent: 1,250 mg/m
2twice daily orally for the first 14 days of each 21-day cycle for a maximum of 8 cycles. (
The recommended dosage of capecitabine tablet is 1,250 mg/m2orally twice daily for the first 14 days of each 21-day cycle for a maximum of 8 cycles.
The recommended dosage of capecitabine tablet is 1,000 mg/m2orally twice daily for the first 14 days of each 21-day cycle for a maximum of 8 cycles in combination with oxaliplatin 130 mg/m2administered intravenously on day 1 of each cycle.
Refer to the oxaliplatin prescribing information for additional dosing information as appropriate.
The recommended dosage of capecitabine is 825 mg/m2orally twice daily when administered with concomitant radiation therapy and 1,250 mg/m2orally twice daily when administered without radiation therapy as part of a peri-operative combination regimen.
The recommended dosage of capecitabine tablet is 1,250 mg/m2orally twice daily for the first 14 days of a 21-day cycle until disease progression or unacceptable toxicity.
The recommended dosage of capecitabine tablet is 1,000 mg/m2orally twice daily for the first 14 days of each 21-day cycle until disease progression or unacceptable toxicity in combination with oxaliplatin 130 mg/m2administered intravenously on day 1 of each cycle.
Refer to the Prescribing Information for oxaliplatin for additional dosing information as appropriate.
2orally twice daily for the first 14 days of each 21-day cycle for a maximum of 8 cycles in combination with oxaliplatin 130 mg/m
2administered intravenously on day 1 of each cycle. (
The recommended dosage of capecitabine tablet is 1,250 mg/m2orally twice daily for the first 14 days of each 21-day cycle for a maximum of 8 cycles.
The recommended dosage of capecitabine tablet is 1,000 mg/m2orally twice daily for the first 14 days of each 21-day cycle for a maximum of 8 cycles in combination with oxaliplatin 130 mg/m2administered intravenously on day 1 of each cycle.
Refer to the oxaliplatin prescribing information for additional dosing information as appropriate.
The recommended dosage of capecitabine is 825 mg/m2orally twice daily when administered with concomitant radiation therapy and 1,250 mg/m2orally twice daily when administered without radiation therapy as part of a peri-operative combination regimen.
The recommended dosage of capecitabine tablet is 1,250 mg/m2orally twice daily for the first 14 days of a 21-day cycle until disease progression or unacceptable toxicity.
The recommended dosage of capecitabine tablet is 1,000 mg/m2orally twice daily for the first 14 days of each 21-day cycle until disease progression or unacceptable toxicity in combination with oxaliplatin 130 mg/m2administered intravenously on day 1 of each cycle.
Refer to the Prescribing Information for oxaliplatin for additional dosing information as appropriate.
• With Concomitant Radiation Therapy: 825 mg/m
2orally twice daily (
The recommended dosage of capecitabine tablet is 1,250 mg/m2orally twice daily for the first 14 days of each 21-day cycle for a maximum of 8 cycles.
The recommended dosage of capecitabine tablet is 1,000 mg/m2orally twice daily for the first 14 days of each 21-day cycle for a maximum of 8 cycles in combination with oxaliplatin 130 mg/m2administered intravenously on day 1 of each cycle.
Refer to the oxaliplatin prescribing information for additional dosing information as appropriate.
The recommended dosage of capecitabine is 825 mg/m2orally twice daily when administered with concomitant radiation therapy and 1,250 mg/m2orally twice daily when administered without radiation therapy as part of a peri-operative combination regimen.
The recommended dosage of capecitabine tablet is 1,250 mg/m2orally twice daily for the first 14 days of a 21-day cycle until disease progression or unacceptable toxicity.
The recommended dosage of capecitabine tablet is 1,000 mg/m2orally twice daily for the first 14 days of each 21-day cycle until disease progression or unacceptable toxicity in combination with oxaliplatin 130 mg/m2administered intravenously on day 1 of each cycle.
Refer to the Prescribing Information for oxaliplatin for additional dosing information as appropriate.
• Without Radiation Therapy: 1,250 mg/m
2orally twice daily (
The recommended dosage of capecitabine tablet is 1,250 mg/m2orally twice daily for the first 14 days of each 21-day cycle for a maximum of 8 cycles.
The recommended dosage of capecitabine tablet is 1,000 mg/m2orally twice daily for the first 14 days of each 21-day cycle for a maximum of 8 cycles in combination with oxaliplatin 130 mg/m2administered intravenously on day 1 of each cycle.
Refer to the oxaliplatin prescribing information for additional dosing information as appropriate.
The recommended dosage of capecitabine is 825 mg/m2orally twice daily when administered with concomitant radiation therapy and 1,250 mg/m2orally twice daily when administered without radiation therapy as part of a peri-operative combination regimen.
The recommended dosage of capecitabine tablet is 1,250 mg/m2orally twice daily for the first 14 days of a 21-day cycle until disease progression or unacceptable toxicity.
The recommended dosage of capecitabine tablet is 1,000 mg/m2orally twice daily for the first 14 days of each 21-day cycle until disease progression or unacceptable toxicity in combination with oxaliplatin 130 mg/m2administered intravenously on day 1 of each cycle.
Refer to the Prescribing Information for oxaliplatin for additional dosing information as appropriate.
• Single agent: 1,250 mg/m
2twice daily orally for the first 14 days of each 21-day cycle until disease progression or unacceptable toxicity. (
The recommended dosage of capecitabine tablet is 1,250 mg/m2orally twice daily for the first 14 days of each 21-day cycle for a maximum of 8 cycles.
The recommended dosage of capecitabine tablet is 1,000 mg/m2orally twice daily for the first 14 days of each 21-day cycle for a maximum of 8 cycles in combination with oxaliplatin 130 mg/m2administered intravenously on day 1 of each cycle.
Refer to the oxaliplatin prescribing information for additional dosing information as appropriate.
The recommended dosage of capecitabine is 825 mg/m2orally twice daily when administered with concomitant radiation therapy and 1,250 mg/m2orally twice daily when administered without radiation therapy as part of a peri-operative combination regimen.
The recommended dosage of capecitabine tablet is 1,250 mg/m2orally twice daily for the first 14 days of a 21-day cycle until disease progression or unacceptable toxicity.
The recommended dosage of capecitabine tablet is 1,000 mg/m2orally twice daily for the first 14 days of each 21-day cycle until disease progression or unacceptable toxicity in combination with oxaliplatin 130 mg/m2administered intravenously on day 1 of each cycle.
Refer to the Prescribing Information for oxaliplatin for additional dosing information as appropriate.
• In Combination with Oxaliplatin: 1,000 mg/m
2orally twice daily for the first 14 days of each 21-day cycle until disease progression or unacceptable toxicity in combination with oxaliplatin 130 mg/m
2administered intravenously on day 1 of each cycle. (
The recommended dosage of capecitabine tablet is 1,250 mg/m2orally twice daily for the first 14 days of each 21-day cycle for a maximum of 8 cycles.
The recommended dosage of capecitabine tablet is 1,000 mg/m2orally twice daily for the first 14 days of each 21-day cycle for a maximum of 8 cycles in combination with oxaliplatin 130 mg/m2administered intravenously on day 1 of each cycle.
Refer to the oxaliplatin prescribing information for additional dosing information as appropriate.
The recommended dosage of capecitabine is 825 mg/m2orally twice daily when administered with concomitant radiation therapy and 1,250 mg/m2orally twice daily when administered without radiation therapy as part of a peri-operative combination regimen.
The recommended dosage of capecitabine tablet is 1,250 mg/m2orally twice daily for the first 14 days of a 21-day cycle until disease progression or unacceptable toxicity.
The recommended dosage of capecitabine tablet is 1,000 mg/m2orally twice daily for the first 14 days of each 21-day cycle until disease progression or unacceptable toxicity in combination with oxaliplatin 130 mg/m2administered intravenously on day 1 of each cycle.
Refer to the Prescribing Information for oxaliplatin for additional dosing information as appropriate.
• Single agent: 1,000 mg/m
2or 1,250 mg/m
2twice daily orally for the first 14 days of each 21-day cycle until disease progression or unacceptable toxicity. (
The recommended dosage of capecitabine tablet is 1,000 mg/m2or 1,250 mg/m2orally twice daily for the first 14 days of a 21-day cycle until disease progression or unacceptable toxicity. Individualize the dose and dosing schedule of capecitabine tablet based on patient risk factors and adverse reactions.
The recommended dosage of capecitabine tablet is 1,000 mg/m2or 1,250 mg/m2orally twice daily for the first 14 days of a 21-day cycle until disease progression or unacceptable toxicity in combination with docetaxel 75 mg/m2administered intravenously on day 1 of each cycle.
Refer to the Prescribing Information for docetaxel for additional dosing information as appropriate.
• In combination with docetaxel: 1,000 mg/m
2or 1,250 mg/m
2orally twice daily for the first 14 days of a 21-day cycle, until disease progression or unacceptable toxicity in combination with docetaxel at 75 mg/m
2administered intravenously on day 1 of each cycle (
The recommended dosage of capecitabine tablet is 1,000 mg/m2or 1,250 mg/m2orally twice daily for the first 14 days of a 21-day cycle until disease progression or unacceptable toxicity. Individualize the dose and dosing schedule of capecitabine tablet based on patient risk factors and adverse reactions.
The recommended dosage of capecitabine tablet is 1,000 mg/m2or 1,250 mg/m2orally twice daily for the first 14 days of a 21-day cycle until disease progression or unacceptable toxicity in combination with docetaxel 75 mg/m2administered intravenously on day 1 of each cycle.
Refer to the Prescribing Information for docetaxel for additional dosing information as appropriate.
• 625 mg/m
2orally twice daily on days 1 to 21 of each 21-day cycle for a maximum of 8 cycles in combination with platinum-containing chemotherapy. (
The recommended dosage of capecitabine tablet for unresectable or metastatic gastric, esophageal, or gastroesophageal junction cancer is:
• 625 mg/m2orally twice daily on days 1 to 21 of each 21-day cycle for a maximum of 8 cycles in combination with platinum-containing chemotherapy.
OR
• 850 mg/m2or 1,000 mg/m2orally twice daily for the first 14 days of each 21-day cycle until disease progression or unacceptable toxicity in combination with oxaliplatin 130 mg/m2administered intravenously on day 1 of each cycle. Individualize the dose and dosing schedule of capecitabine tablet based on patient risk factors and adverse reactions.
The recommended dosage of capecitabine tablet for HER2-overexpressing metastatic gastric or gastroesophageal junction adenocarcinoma is 1,000 mg/m2orally twice daily for the first 14 days of each 21-day cycle until disease progression or unacceptable toxicity in combination with cisplatin and trastuzumab.
Refer to the Prescribing Information for agents used in combination for additional dosing information as appropriate.
• 850 mg/m
2or 1,000 mg/m
2orally twice daily for the first 14 days of each 21-day cycle until disease progression or unacceptable toxicity in combination with oxaliplatin 130 mg/m
2administered intravenously on day 1 of each cycle. (
The recommended dosage of capecitabine tablet for unresectable or metastatic gastric, esophageal, or gastroesophageal junction cancer is:
• 625 mg/m2orally twice daily on days 1 to 21 of each 21-day cycle for a maximum of 8 cycles in combination with platinum-containing chemotherapy.
OR
• 850 mg/m2or 1,000 mg/m2orally twice daily for the first 14 days of each 21-day cycle until disease progression or unacceptable toxicity in combination with oxaliplatin 130 mg/m2administered intravenously on day 1 of each cycle. Individualize the dose and dosing schedule of capecitabine tablet based on patient risk factors and adverse reactions.
The recommended dosage of capecitabine tablet for HER2-overexpressing metastatic gastric or gastroesophageal junction adenocarcinoma is 1,000 mg/m2orally twice daily for the first 14 days of each 21-day cycle until disease progression or unacceptable toxicity in combination with cisplatin and trastuzumab.
Refer to the Prescribing Information for agents used in combination for additional dosing information as appropriate.
• 1,000 mg/m
2orally twice daily for the first 14 days of each 21-day cycle until disease progression or unacceptable toxicity in combination with cisplatin and trastuzumab. (
The recommended dosage of capecitabine tablet for unresectable or metastatic gastric, esophageal, or gastroesophageal junction cancer is:
• 625 mg/m2orally twice daily on days 1 to 21 of each 21-day cycle for a maximum of 8 cycles in combination with platinum-containing chemotherapy.
OR
• 850 mg/m2or 1,000 mg/m2orally twice daily for the first 14 days of each 21-day cycle until disease progression or unacceptable toxicity in combination with oxaliplatin 130 mg/m2administered intravenously on day 1 of each cycle. Individualize the dose and dosing schedule of capecitabine tablet based on patient risk factors and adverse reactions.
The recommended dosage of capecitabine tablet for HER2-overexpressing metastatic gastric or gastroesophageal junction adenocarcinoma is 1,000 mg/m2orally twice daily for the first 14 days of each 21-day cycle until disease progression or unacceptable toxicity in combination with cisplatin and trastuzumab.
Refer to the Prescribing Information for agents used in combination for additional dosing information as appropriate.
• 830 mg/m
2orally twice daily for the first 21 days of each 28-day cycle for maximum of 6 cycles in combination with gemcitabine 1,000 mg/m
2administered intravenously on days 1, 8, and 15 of each cycle. (
The recommended dosage of capecitabine tablet is 830 mg/m2orally twice daily for the first 21 days of each 28-day cycle until disease progression, unacceptable toxicity, or for a maximum 6 cycles in combination with gemcitabine 1,000 mg/m2administered intravenously on days 1, 8, and 15 of each cycle.
Refer to Prescribing Information for gemcitabine for additional dosing information as appropriate.
Refer to Sections 2.5 and 2.6 for information related to dosage modifications for adverse reactions and renal impairment (
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.
When capecitabine tablet is administered with docetaxel, withhold capecitabine tablet and docetaxel until the requirements for resuming both capecitabine tablet and docetaxel are met. Refer to the Prescribing Information for docetaxel for additional dosing information as appropriate.
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% | |
Patients with Grade 3-4 hyperbilirubinemia may resume treatment once the event is Grade 2 or less (less than three times the upper limit of normal), using the percent of current dose as shown in column 3 of Table 1
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)
Tablets, film-coated:
• Capecitabine tablets, USP 150 mg are light peach colored, capsule shaped, biconvex, film coated tablets debossed with ‘6’ on one side and ‘H’ on the other side.
• Capecitabine tablets, USP 500 mg are peach colored, oval shaped, biconvex, film coated tablets debossed with ‘3’ on one side and ‘H’ on the other side.
•
There is no information regarding the presence of capecitabine or its metabolites in human milk, or on its effects on milk production or the breastfed child. Capecitabine metabolites were present in the milk of lactating mice
Lactating mice given a single oral dose of capecitabine excreted significant amounts of capecitabine metabolites into the milk.
•
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
Capecitabine is contraindicated in patients with history of severe hypersensitivity reaction to fluorouracil or capecitabine
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.
The safety of capecitabine as a single agent was evaluated in patients with Stage III colon cancer in X-ACT
Deaths due to all causes occurred in 0.8% of patients who received capecitabine on study or within 28 days of receiving study drug. Permanent discontinuation due to an adverse reaction occurred in 11% of patients who received capecitabine.
Most common adverse reactions (>30%) were palmar-plantar erythrodysesthesia syndrome, diarrhea, and nausea.
Tables 2 and 3 summarize the adverse reactions and laboratory abnormalities in X-ACT.
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:
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 | 2.3 | 2.2 |
Neutrophils decreased | 2.2 | 26 |
ALT increased | 1.6 | 0.6 |
Calcium increased | 1.1 | 0.7 |
Hemoglobin decreased | 1 | 1.2 |
Platelets decreased | 1 | 0.7 |
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
The safety of capecitabine for the perioperative treatment of adults with locally advanced rectal cancer as a component of chemoradiotherapy was derived from published literature
The safety of capecitabine as a single agent was evaluated in a pooled metastatic colorectal cancer population (Study SO14695 and Study SO14796)
Deaths due to all causes occurred in 8% of patients who received capecitabine on study or within 28 days of receiving study drug. Permanent discontinuation due to an adverse reaction or intercurrent illness occurred in 13% of patients who received capecitabine.
Most common adverse reactions (>30%) were anemia, diarrhea, palmar-plantar erythrodysesthesia syndrome, hyperbilirubinemia, nausea, fatigue, and abdominal pain.
Table 4 shows the adverse reactions occurring in this pooled colorectal cancer population.
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 | – | 51 | 3 | <1 |
Abdominal pain | 35 | 9 | <1 | 31 | 5 | – |
Vomiting | 27 | 4 | <1 | 30 | 4 | <1 |
Stomatitis | 25 | 2 | <1 | 62 | 14 | 1 |
Constipation | 14 | 1 | <1 | 17 | 1 | – |
Gastrointestinal motility disorder | 10 | <1 | – | 7 | <1 | – |
Oral discomfort | 10 | – | – | 10 | – | – |
Skin and Subcutaneous Tissue | ||||||
Palmar-plantar erythrodysesthesia syndrome | 54 | 17 | NA | 6 | 1 | NA |
Dermatitis | 27 | 1 | – | 26 | 1 | – |
Hepatobiliary | ||||||
Hyperbilirubinemia | 48 | 18 | 5 | 17 | 3 | 3 |
General | ||||||
Fatigue* | 42 | 4 | – | 46 | 4 | – |
Pyrexia | 18 | 1 | – | 21 | 2 | – |
Edema | 15 | 1 | – | 9 | 1 | – |
Pain | 12 | 1 | – | 10 | 1 | – |
Metabolism and Nutrition | ||||||
Decreased appetite | 26 | 3 | <1 | 31 | 2 | <1 |
Respiratory Thoracic and Mediastinal | ||||||
Dyspnea | 14 | 1 | – | 10 | <1 | 1 |
Eye | ||||||
Eye irritation | 13 | – | – | 10 | <1 | – |
Nervous System | ||||||
Peripheral sensory neuropathy | 10 | – | – | 4 | – | – |
Headache | 10 | 1 | – | 7 | – | – |
Musculoskeletal | ||||||
Back pain | 10 | 2 | – | 9 | <1 | – |
– Not observed
* Includes weakness NA = Not Applicable
Clinically relevant adverse reactions in <10% of patients are presented below:
The safety of capecitabine for the treatment of patients with unresectable or metastatic colorectal cancer as a component of a combination chemotherapy regimen was derived from published literature
The safety of capecitabine in combination with docetaxel was evaluated in patients with metastatic breast cancer in Study SO14999
Permanent discontinuation due to an adverse reaction occurred in 26% of patients who received capecitabine. Dosage interruptions due to an adverse reaction occurred in 79% of patients who received capecitabine and dosage reductions due to an adverse reaction occurred in 65%.
Most common adverse reactions (>30%) were diarrhea, stomatitis, palmar-plantar erythrodysesthesia syndrome, nausea, alopecia, vomiting, edema, and abdominal pain.
Table 5 summarizes the adverse reactions 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 | – |
Nausea | 45 | 7 | – | 36 | 2 | – |
Vomiting | 35 | 4 | 1 | 24 | 2 | – |
Abdominal pain | 30 | 3 | <1 | 24 | 2 | – |
Constipation | 20 | 2 | – | 18 | – | – |
Dyspepsia | 14 | – | – | 8 | 1 | – |
Skin and Subcutaneous Tissue | ||||||
Palmar-plantar erythrodysesthesia syndrome | 63 | 24 | NA | 8 | 1 | NA |
Alopecia | 41 | 6 | – | 42 | 7 | – |
Nail disorder | 14 | 2 | – | 15 | – | – |
Cardiac | ||||||
Edema | 33 | <2 | – | 34 | <3 | 1 |
General | ||||||
Pyrexia | 28 | 2 | – | 34 | 2 | – |
Asthenia | 26 | 4 | <1 | 25 | 6 | – |
Fatigue | 22 | 4 | – | 27 | 6 | – |
Weakness | 16 | 2 | – | 11 | 2 | – |
Pain in Limb | 13 | <1 | – | 13 | 2 | – |
Blood and Lymphatic System | ||||||
Neutropenic fever | 16 | 3 | 13 | 21 | 5 | 16 |
Nervous System | ||||||
Taste disturbance | 16 | <1 | – | 14 | <1 | – |
Headache | 15 | 3 | – | 15 | 2 | – |
Paresthesia | 12 | <1 | – | 16 | 1 | – |
Dizziness | 12 | – | – | 8 | <1 | – |
Musculoskeletal and Connective Tissue | ||||||
Arthralgia | 15 | 2 | – | 24 | 3 | – |
Myalgia | 15 | 2 | – | 25 | 2 | – |
Back Pain | 12 | <1 | – | 11 | 3 | – |
Respiratory, Thoracic and Mediastinal | ||||||
Dyspnea | 14 | 2 | <1 | 16 | 2 | – |
Cough | 13 | 1 | – | 22 | <1 | – |
Sore Throat | 12 | 2 | – | 11 | <1 | – |
Metabolism and Nutrition | ||||||
Anorexia | 13 | <1 | – | 11 | <1 | – |
Appetite decreased | 10 | – | – | 5 | – | – |
Dehydration | 10 | 2 | – | 7 | <1 | <1 |
Eye | ||||||
Lacrimation increased | 12 | - | - | 7 | <1 | - |
– Not observed
NA = Not Applicable
Clinically relevant adverse reactions in <10% of patients are presented below:
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 |
The safety of capecitabine as a single agent was evaluated in patients with metastatic breast cancer in Study SO14697
Permanent discontinuation due to an adverse reaction or intercurrent illness occurred in 8% of patients.
Most common adverse reactions (>30%) were lymphopenia, anemia, diarrhea, hand-and-foot syndrome, nausea, fatigue, vomiting, and dermatitis.
Table 7 summarizes the adverse reactions 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 | – |
Vomiting | 37 | 4 | – |
Stomatitis | 24 | 7 | – |
Abdominal pain | 20 | 4 | – |
Constipation | 15 | 1 | – |
Skin and Subcutaneous Tissue | |||
Hand-and-foot syndrome | 57 | 11 | NA |
Dermatitis | 37 | 1 | – |
General | |||
Fatigue | 41 | 8 | – |
Pyrexia | 12 | 1 | – |
Metabolism and Nutrition | |||
Anorexia | 23 | 3 | – |
Hepatobiliary | |||
Hyperbilirubinemia | 22 | 9 | 2 |
Nervous System | |||
Paresthesia | 21 | 1 | – |
Eye | |||
Eye irritation | 15 | – | – |
– = Not observed
NA = Not Applicable
Clinically relevant adverse reactions in <10% of patients who received capecitabine as a single agent are presented below.
The safety of capecitabine for the treatment of adults with unresectable or metastatic gastric, esophageal, or gastroesophageal junction cancer as a component of a combination chemotherapy regimen was derived from published literature
The safety of capecitabine for the treatment of patients with HER2-overexpressing metastatic gastric or gastroesophageal junction adenocarcinoma who have not received prior treatment for metastatic disease as a component of a combination regimen was derived from the published literature
The safety of capecitabine for the adjuvant treatment of adults with pancreatic adenocarcinoma as a component of a combination chemotherapy regimen was derived from the published literature