Last reviewed 2026-04-20 · How we verify

Xeloda (capecitabine)

Xeloda works by inhibiting the enzyme thymidylate synthase, which is necessary for DNA synthesis in cancer cells.

At a glance

Mechanism of action

Enzymes convert capecitabine to 5-fluorouracil (5-FU) in vivo. Both normal and tumor cells metabolize 5-FU to 5-fluoro-2-deoxyuridine monophosphate (FdUMP) and 5-fluorouridine triphosphate (FUTP). These metabolites cause cell injury by two different mechanisms. First, FdUMP and the folate cofactor, N5-10-methylenetetrahydrofolate, bind to thymidylate synthase (TS) to form covalently bound ternary complex. This binding inhibits the formation of thymidylate from 2-deoxyuridylate. Thymidylate is the necessary precursor of thymidine triphosphate, which is essential for the synthesis of DNA, so that deficiency of this compound can inhibit cell division. Second, nuclear transcriptional enzymes can mistakenly incorporate FUTP in place of uridine triphosphate (UTP) during the synthesis of RNA. This metabolic error can interfere with RNA processing and protein synthesis.

Approved indications

• Adjuvant treatment of Stage III colon cancer
• Perioperative treatment of locally advanced rectal cancer
• Treatment of unresectable or metastatic colorectal cancer
• Treatment of advanced or metastatic breast cancer (single agent)
• Treatment of advanced or metastatic breast cancer (with docetaxel)
• Treatment of unresectable or metastatic gastric, esophageal, or gastroesophageal junction cancer
• Treatment of HER2-overexpressing metastatic gastric or gastroesophageal junction adenocarcinoma
• Adjuvant treatment of pancreatic adenocarcinoma

Boxed warnings

• WARNING: SERIOUS ADVERSE REACTIONS OR DEATH IN PATIENTS WITH COMPLETE DPD DEFICIENCY and BLEEDING WITH CONCOMITANT USE OF VITAMIN K ANTAGONISTS Increased risk of serious adverse reactions or death in patients with complete DPD deficiency Test patients for genetic variants of DPYD prior to initiating capecitabine tablets unless immediate treatment is necessary. Avoid use of capecitabine tablets in patients with certain homozygous or compound heterozygous DPYD variants that result in complete DPD deficiency [see Warnings and Precautions ( 5.1 )]. 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 c apecitabine tablets concomitantly with oral vitamin K antagonists, such as warfarin [see Warnings and Precautions ( 5.2 ) , 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 tablets was introduced. 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 (7.2) ] . 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 capecitabine tablets unless immediate treatment is necessary. Avoid use of capecitabine tablets in patients with certain homozygous or compound heterozygous DPYD variants that result in complete DPD deficiency. ( 5.1 ) Altered coagulation parameters and/or bleeding, including death, have been reported in patients taking capecitabine tablets concomitantly with oral vitamin K antagonists. ( 5.2, 7.2 ) Monitor international normalized ratio (INR) more frequently and adjust the dose of the vitamin K antagonist as appropriate. ( 7.2 )

Common side effects

• palmar-plantar erythrodysesthesia syndrome
• diarrhea
• nausea
• stomatitis
• vomiting
• abdominal pain
• fatigue
• asthenia
• lethargy

Drug interactions

• Allopurinol
• Leucovorin
• CYP2C9 substrates
• Vitamin K antagonists
• Phenytoin
• Nephrotoxic drugs

Key clinical trials

• Therapy Adapted for High Risk and Low Risk HIV-Associated Anal Cancer (PHASE2)
• Durvalumab in Combination With Chemotherapy in Treating Patients With Advanced Solid Tumors, DURVA+ Trial (PHASE2)
• A Clinical Study of Sacituzumab Tirumotecan (Sac-TMT, MK-2870) in People With Breast Cancer (MK-2870-032) (PHASE3)
• Neoadjuvant mFolfirinox With or Without Preoperative Concomitant Chemoradiotherapy in Patients With Borderline Resectable Pancreatic Carcinoma (PANDAS-PRODIGE 44) (PHASE2)
• Testing the Addition of an Anti-Cancer Drug, ZEN003694, to the Usual Chemotherapy Treatment (Capecitabine) for Metastatic or Unresectable Cancers (PHASE1)
• A Study of Sacituzumab Tirumotecan (MK-2870) as a Single Agent and in Combination With Pembrolizumab (MK-3475) Versus Treatment of Physician's Choice in Participants With HR+/HER2- Unresectable Locally Advanced or Metastatic Breast Cancer (MK-2870-010) (PHASE3)
• Phase Ib/II Study of Zanidatamab Plus Tucatinib and Chemotherapy in HER2-Positive Advanced Breast Cancer (PHASE1,PHASE2)
• A Clinical Study of Patritumab Deruxtecan to Treat Breast Cancer (MK-1022-016) (PHASE3)

Primary sources

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