Initial US Approval:
1998
Drug Class/Description:
Nucleoside metabolic inhibitor
WARNING: SERIOUS ADVERSE REACTIONS OR DEATH IN PATIENTS WITH COMPLETE DPD DEFICIENCY and BLEEDING WITH CONCOMITANT USE OF VITAMIN K ANTAGONISTS
See full prescribing information for complete boxed warning.
Serious adverse reactions or death may occur in patients with complete DPD deficiency. Test patients for genetic variants of DPYD prior to initiating XELODA unless immediate treatment is necessary. Avoid use of XELODA in patients with certain homozygous or compound heterozygous DPYD variants that result in complete DPD deficiency.
Altered coagulation parameters and/or bleeding, including death, have been reported in patients taking XELODA concomitantly with oral vitamin K antagonists. Monitor international normalized ratio (INR) more frequently and adjust the dose of the vitamin K antagonist as appropriate.
Recent Major Changes:
Boxed Warning 10/2025
Dosage and Administration 10/2025
Warnings and Precautions 10/2025
Indications and Usage:
XELODA (capecitabine) is a nucleoside metabolic inhibitor indicated for:
Colorectal Cancer
- 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.
Breast Cancer
- 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.
Gastric, Esophageal, or Gastroesophageal Junction Cancer
- 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.
Pancreatic Cancer
- adjuvant treatment of adults with pancreatic adenocarcinoma as a component of a combination chemotherapy regimen.
Dosage and Administration:
Adjuvant Treatment of Colon Cancer:
- 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. 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.
Perioperative Treatment of Rectal Cancer:
- With Concomitant Radiation Therapy: 825 mg/m2 orally twice daily
- Without Radiation Therapy: 1,250 mg/m2 orally twice daily
Unresectable or Metastatic Colorectal Cancer:
- 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.
- 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.
Advanced or Metastatic Breast Cancer:
- 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.
- 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.
Unresectable or Metastatic Gastric, Esophageal, or Gastroesophageal Junction Cancer:
- 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.
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.
HER2-overexpressing metastatic adenocarcinoma of the gastroesophageal junction or stomach:
- 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.
Pancreatic cancer:
- 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.
Refer to Sections 2.5 and 2.6 for information related to dosage modifications for adverse reactions and renal impairment.
Dosage Forms and Strengths:
Tablets: 150 mg and 500 mg
Contraindications:
History of severe hypersensitivity reactions to fluorouracil or capecitabine
Warnings and Precautions:
- Cardiotoxicity: May be more common in patients with a prior history of coronary artery disease. Withhold XELODA for cardiotoxicity as appropriate. The safety of resumption of XELODA in patients with cardiotoxicity that has resolved has not been established.
- Diarrhea: Withhold XELODA and then resume at same or reduced dose, or permanently discontinue, based on severity and occurrence.
- Dehydration: Optimize hydration before starting XELODA. Monitor hydration status and kidney function at baseline and as clinically indicated. Withhold XELODA and then resume at same or reduced dose or permanently discontinue, based on severity and occurrence.
- Renal Toxicity: Monitor renal function at baseline and as clinically indicated. Optimize hydration before starting XELODA. Withhold XELODA and then resume at same or reduced dose, or permanently discontinue, based on severity and occurrence.
- Serious Skin Toxicities: Monitor for new or worsening serious skin reactions. Permanently discontinue XELODA in patients who experience a severe cutaneous adverse reaction.
- Palmar-Plantar Erythrodysesthesia Syndrome: Withhold XELODA then resume at same or reduced dose, or permanently discontinue, based on severity and occurrence.
- Myelosuppression: Monitor complete blood count at baseline and before each cycle. XELODA is not recommended in patients with baseline neutrophil counts <1.5 x 109/L or platelet counts <100 x 109/L. For grade 3 or 4 myelosuppression, withhold XELODA and then resume at same or reduced dose, or permanently discontinue, based on occurrence.
- Hyperbilirubinemia: Patients with Grade 3-4 hyperbilirubinemia may resume treatment once the event is Grade 2 or less (<3 x ULN), using the percent of current dose as shown in column 3 of Table 1
- Embryo-Fetal Toxicity: Can cause fetal harm. Advise patients of the potential risk to a fetus and to use effective contraception.
Adverse Reactions:
- Most common adverse reactions in patients who received XELODA as a single agent for the adjuvant treatment for colon cancer (>30%) were palmar-plantar erythrodysesthesia syndrome, diarrhea, and nausea.
- Most common adverse reactions (>30%) in patients with metastatic colorectal cancer who received XELODA as a single agent were anemia, diarrhea, palmar-plantar erythrodysesthesia syndrome, hyperbilirubinemia, nausea, fatigue, and abdominal pain.
- Most common adverse reactions (>30%) in patients with metastatic breast cancer who received XELODA with docetaxel were diarrhea, stomatitis, palmar-plantar erythrodysesthesia syndrome, nausea, alopecia, vomiting, edema, and abdominal pain.
- Most common adverse reactions (>30%) in patients with metastatic breast cancer who received XELODA as a single agent were lymphopenia, anemia, diarrhea, hand-and-foot syndrome, nausea, fatigue, vomiting, and dermatitis.
Drug Interactions:
- Allopurinol: Avoid concomitant use of allopurinol with XELODA.
- Leucovorin: Closely monitor for toxicities when XELODA is coadministered with leucovorin.
- CYP2C9 substrates: Closely monitor for adverse reactions when CYP2C9 substrates are coadministered with XELODA.
- Vitamin K antagonists: Monitor INR more frequently and dose adjust oral vitamin K antagonist as appropriate
- Phenytoin: Closely monitor phenytoin levels in patients taking XELODA concomitantly with phenytoin and adjust the phenytoin dose as appropriate.
- Nephrotoxic drugs: Closely monitor for signs of renal toxicity when XELODA is used concomitantly with nephrotoxic drugs.
Use in Specific Populations:
- Lactation: Advise not to breastfeed.
- Hepatic Impairment: Monitor patients with hepatic impairment more frequently for adverse reactions.
Adapted From:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/020896s052lbl.pdf
Every health-care provider should make their own determination regarding specific safe and appropriate patient care practices, including drug dosages and indications. The provider should always consult the most recent prescribing/product information. FDA Focus information is not guaranteed to be accurate, complete, or current. JADPRO and its editors, authors, reviewers, and commentators cannot be held responsible for any liability incurred as a consequence of the application of any of the information listed within.
