Capecitabine

Boxed Warning                                                                                                                                                           (12/2022)

Indications and Usage, Colorectal Cancer (

Capecitabine tablets are 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. (
  1.1 Colorectal Cancer

  Capecitabine tablets

  are

  indicated for the:

  • adjuvant treatment
    o
    f 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. (
  1.1 Colorectal Cancer

  Capecitabine tablets

  are

  indicated for the:

  • adjuvant treatment
    o
    f 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. (
  1.1 Colorectal Cancer

  Capecitabine tablets

  are

  indicated for the:

  • adjuvant treatment
    o
    f 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. (
  1.2 Breast Cancer

  Capecitabine tablets

  are

  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. (
  1.2 Breast Cancer

  Capecitabine tablets

  are

  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. (
  1.3 Gastric, Esophageal, or Gastroesophageal Junction Cancer

  Capecitabine tablets

  are

  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. (
  1.3 Gastric, Esophageal, or Gastroesophageal Junction Cancer

  Capecitabine tablets

  are

  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. (
  1.4 Pancreatic Cancer

  Capecitabine tablets are indicated for

  the

  adjuvant treatment of adults with pancreatic adenocarcinoma as a component of a combination chemotherapy regimen.
  )

• Single agent: 1,250 mg/m² twice daily orally for the first 14 days of each 21-day cycle for a maximum of 8 cycles. (
  2.1 Recommended Dosage for Colorectal Cancer

  Adjuvant Treatment of Colon Cancer

  Single Agent

  The recommended dosage of capecitabine tablets are 1,250 mg/m²orally twice daily

  for

  the first 14 days of each 21-day cycle for a maximum of 8 cycles.
  
  

  In Combination with Oxaliplatin-Containing Regimens
  
  
  
  

  The recommended dosage

  of

  capecitabine tablets are 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.
  
  
  
  

  Perioperative Treatment of Rectal Cancer
  
  

  The recommended dosage

  of

  capecitabine tablets are 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.
  
  

  Unresectable or Metastatic Colorectal Cancer
  
  

  Single Agent
  
  

  The recommended dosage

  of

  capecitabine tablets are 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 Oxaliplatin
  
  

  The recommended dosage of capecitabine tablets

  are

  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-Containing Regimens: 1,000 mg/m² orally twice daily for the first 14 days of each 21-day cycle for a maximum of 8 cycles in combination with oxaliplatin 130 mg/m² administered intravenously on day 1 of each cycle. (
  2.1 Recommended Dosage for Colorectal Cancer

  Adjuvant Treatment of Colon Cancer

  Single Agent

  The recommended dosage of capecitabine tablets are 1,250 mg/m²orally twice daily

  for

  the first 14 days of each 21-day cycle for a maximum of 8 cycles.
  
  

  In Combination with Oxaliplatin-Containing Regimens
  
  
  
  

  The recommended dosage

  of

  capecitabine tablets are 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.
  
  
  
  

  Perioperative Treatment of Rectal Cancer
  
  

  The recommended dosage

  of

  capecitabine tablets are 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.
  
  

  Unresectable or Metastatic Colorectal Cancer
  
  

  Single Agent
  
  

  The recommended dosage

  of

  capecitabine tablets are 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 Oxaliplatin
  
  

  The recommended dosage of capecitabine tablets

  are

  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/m² orally twice daily (
  2.1 Recommended Dosage for Colorectal Cancer

  Adjuvant Treatment of Colon Cancer

  Single Agent

  The recommended dosage of capecitabine tablets are 1,250 mg/m²orally twice daily

  for

  the first 14 days of each 21-day cycle for a maximum of 8 cycles.
  
  

  In Combination with Oxaliplatin-Containing Regimens
  
  
  
  

  The recommended dosage

  of

  capecitabine tablets are 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.
  
  
  
  

  Perioperative Treatment of Rectal Cancer
  
  

  The recommended dosage

  of

  capecitabine tablets are 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.
  
  

  Unresectable or Metastatic Colorectal Cancer
  
  

  Single Agent
  
  

  The recommended dosage

  of

  capecitabine tablets are 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 Oxaliplatin
  
  

  The recommended dosage of capecitabine tablets

  are

  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/m²orally twice daily (
  2.1 Recommended Dosage for Colorectal Cancer

  Adjuvant Treatment of Colon Cancer

  Single Agent

  The recommended dosage of capecitabine tablets are 1,250 mg/m²orally twice daily

  for

  the first 14 days of each 21-day cycle for a maximum of 8 cycles.
  
  

  In Combination with Oxaliplatin-Containing Regimens
  
  
  
  

  The recommended dosage

  of

  capecitabine tablets are 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.
  
  
  
  

  Perioperative Treatment of Rectal Cancer
  
  

  The recommended dosage

  of

  capecitabine tablets are 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.
  
  

  Unresectable or Metastatic Colorectal Cancer
  
  

  Single Agent
  
  

  The recommended dosage

  of

  capecitabine tablets are 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 Oxaliplatin
  
  

  The recommended dosage of capecitabine tablets

  are

  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/m² twice daily orally for the first 14 days of each 21-day cycle until disease progression or unacceptable toxicity. (
  2.1 Recommended Dosage for Colorectal Cancer

  Adjuvant Treatment of Colon Cancer

  Single Agent

  The recommended dosage of capecitabine tablets are 1,250 mg/m²orally twice daily

  for

  the first 14 days of each 21-day cycle for a maximum of 8 cycles.
  
  

  In Combination with Oxaliplatin-Containing Regimens
  
  
  
  

  The recommended dosage

  of

  capecitabine tablets are 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.
  
  
  
  

  Perioperative Treatment of Rectal Cancer
  
  

  The recommended dosage

  of

  capecitabine tablets are 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.
  
  

  Unresectable or Metastatic Colorectal Cancer
  
  

  Single Agent
  
  

  The recommended dosage

  of

  capecitabine tablets are 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 Oxaliplatin
  
  

  The recommended dosage of capecitabine tablets

  are

  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/m² orally twice daily for the first 14 days of each 21-day cycle until disease progression or unacceptable toxicity in combination with oxaliplatin 130 mg/m² administered intravenously on day 1 of each cycle. (
  2.1 Recommended Dosage for Colorectal Cancer

  Adjuvant Treatment of Colon Cancer

  Single Agent

  The recommended dosage of capecitabine tablets are 1,250 mg/m²orally twice daily

  for

  the first 14 days of each 21-day cycle for a maximum of 8 cycles.
  
  

  In Combination with Oxaliplatin-Containing Regimens
  
  
  
  

  The recommended dosage

  of

  capecitabine tablets are 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.
  
  
  
  

  Perioperative Treatment of Rectal Cancer
  
  

  The recommended dosage

  of

  capecitabine tablets are 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.
  
  

  Unresectable or Metastatic Colorectal Cancer
  
  

  Single Agent
  
  

  The recommended dosage

  of

  capecitabine tablets are 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 Oxaliplatin
  
  

  The recommended dosage of capecitabine tablets

  are

  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/m² or 1,250 mg/m² twice daily orally for the first 14 days of each 21-day cycle until disease progression or unacceptable toxicity. (
  2.2 Recommended Dosage for Breast Cancer

  Advanced or Metastatic Breast Cancer

  
  
  

  Single Agent

  The recommended dosage of capecitabine tablets

  are

  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 tablets are based on patient risk factors and adverse reactions.

  
  
  

  In Combination

  with

  Docetaxel

  The recommended dosage of capecitabine tablets

  are

  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

  fo

  r additional dosing information as appropriate.
  )
• In combination with docetaxel: 1,000 mg/m² or 1,250 mg/m² orally 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/m² administered intravenously on day 1 of each cycle (
  2.2 Recommended Dosage for Breast Cancer

  Advanced or Metastatic Breast Cancer

  
  
  

  Single Agent

  The recommended dosage of capecitabine tablets

  are

  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 tablets are based on patient risk factors and adverse reactions.

  
  
  

  In Combination

  with

  Docetaxel

  The recommended dosage of capecitabine tablets

  are

  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

  fo

  r additional dosing information as appropriate.
  )

• 625 mg/m² orally twice daily on days 1 to 21 of each 21-day cycle for a maximum of 8 cycles in combination with platinum-containing chemotherapy. (
  2.3 Recommended Dosage for Gastric, Esophageal, or Gastroesophageal Junction Cancer

  The recommended dosage of capecitabine tablets are

  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 tablets are based on patient risk factors and adverse reactions.

  The recommended dosage of capecitabine tablets are 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.
  )

 OR

• 850 mg/m² or 1,000 mg/m² orally twice daily for the first 14 days of each 21-day cycle until disease progression or unacceptable toxicity in combination with oxaliplatin 130 mg/m² administered intravenously on day 1 of each cycle. (
  2.3 Recommended Dosage for Gastric, Esophageal, or Gastroesophageal Junction Cancer

  The recommended dosage of capecitabine tablets are

  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 tablets are based on patient risk factors and adverse reactions.

  The recommended dosage of capecitabine tablets are 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/m² orally twice daily for the first 14 days of each 21-day cycle until disease progression or unacceptable toxicity in combination with cisplatin and trastuzumab. (
  2.3 Recommended Dosage for Gastric, Esophageal, or Gastroesophageal Junction Cancer

  The recommended dosage of capecitabine tablets are

  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 tablets are based on patient risk factors and adverse reactions.

  The recommended dosage of capecitabine tablets are 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/m² orally twice daily for the first 21 days of each 28-day cycle for maximum of 6 cycles in combination with gemcitabine 1,000 mg/m² administered intravenously on days 1, 8, and 15 of each cycle. (
  2.4 Recommended Dosage for Pancreatic Cancer

  The recommended dosage of capecitabine tablets are 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 (

Tablets, film-coated:

• 150 mg: Light-peach colored biconvex, oblong shaped film coated tablets, debossed with 150 on the one side and plain on  the other side.
•  500 mg: Peach colored biconvex, oblong shaped film coated tablets, debossed with 500 on the one side and plain on  the other side.

• Lactation:
  Advise not to breastfeed. (
  8.2 Lactation

  Risk Summary

  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

  (see Data)

  . Because of the potential for serious adverse reactions in a breastfed child, advise women not to breastfeed during treatment with capecitabine and for 1 week after the last dose.

  
  
  

  Data

  
  
  

  Lactating mice given a single oral dose of capecitabine excreted significant amounts of capecitabine metabolites into the milk.
  )
• Hepatic Impairment:
  Monitor patients with hepatic impairment more frequently for adverse reactions. (
  8.7 Hepatic Impairment

  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 (12.3)

  ]

  . Monitor patients with hepatic impairment more frequently for adverse reactions.
  )