Capecitabine
Antimetabolites
AntimetabolitesHigh alert
An error with this medicine can cause serious harm: double checks and protocols are used.
An oral prodrug that tumours convert to fluorouracil. Hand–foot syndrome, diarrhoea and DPD deficiency are what to watch.
Quick facts
- Group
- Antimetabolites
- Target
- Thymidylate synthase (inhibited by FdUMP made from fluorouracil)
- Used for
- Colon and rectal cancer · Pancreatic cancer
- Key effects
- Hand–foot syndrome · Diarrhoea · Fatigue
- Monitor
- DPYD genotype · Blood counts · Hands and feet
- ATC
- L01BC06
No doses: the clinician sets them by the current guideline.
Mechanism of action
The crystal holds FdUMP, the active nucleotide that cells make from the fluorouracil released by capecitabine, bound to human thymidylate synthase.
Capecitabine is absorbed intact and converted to fluorouracil in three steps: carboxylesterase (liver), cytidine deaminase, and finally thymidine phosphorylase, which is especially active in many tumours. Fluorouracil then becomes FdUMP, which locks thymidylate synthase with the folate cofactor and stops thymidine production, and other metabolites are built into RNA and DNA. Dihydropyrimidine dehydrogenase (DPD) breaks down most of the fluorouracil formed.
- Carboxylesterase and cytidine deaminase process the prodrug
- Thymidine phosphorylase releases fluorouracil, much of it in the tumour
- FdUMP locks thymidylate synthase: no thymidine for DNA
- DPD breaks down the fluorouracil
Indications
- Colon and rectal cancer: adjuvant, with chemoradiotherapy, and in advanced disease. Colorectal cancer →
- Advanced or metastatic breast cancer. Breast cancer →
- Pancreatic cancer, as adjuvant combination treatment. Pancreatic cancer →
Adverse effects
Common
- Hand–foot syndrome (palmar-plantar erythrodysaesthesia): red, painful, peeling palms and soles
- Diarrhoea, nausea, mouth sores
- Fatigue
- Raised bilirubin
Contraindications
- History of severe hypersensitivity to capecitabine or fluorouracil
Key interactions
- Warfarin and other vitamin K antagonists
- Raised INR and bleeding, sometimes fatal: INR is monitored closely.
- Phenytoin
- Higher phenytoin levels: levels are monitored.
- Allopurinol
- May lower the active metabolites and reduce efficacy; avoided.
- Leucovorin, folic acid and folate analogues
- Strengthen fluorouracil and its toxicity.
What is monitored
- DPYD genotype or DPD status before starting, where available
- Blood counts, kidney and liver function
- Hands and feet, stool frequency, hydration
- INR if on a vitamin K antagonist
Administration and safety
- Tablets are swallowed whole with water after a meal; they are not chewed, cut or crushed (if unavoidable, only by trained staff).
- Hazardous drug at home: handled with gloves or clean hands, stored away from children.
- Treatment is interrupted for moderate diarrhoea, hand–foot syndrome or mouth sores, as the regimen specifies.
Pregnancy and breastfeeding
Can cause fetal harm; effective contraception is advised for women and men.
Nursing care
- Teach the patient to recognise and report early hand–foot syndrome, diarrhoea, mouth sores and chest pain, and to stop and call rather than continue.
- Check hydration and kidney function, especially in older patients.
- Review all medicines for warfarin, phenytoin, allopurinol or folic acid supplements.
- Moisturising creams and avoiding friction and heat on hands and feet.
Pharmacokinetics
- Absorption
- Oral tablets, taken with water after a meal.
- Metabolism
- Three-step activation to fluorouracil; DPD then inactivates fluorouracil.
- Elimination
- Mainly in the urine as metabolites.
Test yourself
Think of the answer, then tap the question to see it.
Which enzyme performs the last step that releases fluorouracil from capecitabine?
Thymidine phosphorylase, which is especially active in many tumours.
What test can prevent fatal toxicity before starting capecitabine?
DPYD (DPD) testing: complete DPD deficiency causes severe or fatal toxicity.
What is the typical dose-limiting skin effect of capecitabine?
Hand–foot syndrome (palmar-plantar erythrodysaesthesia).
Which anticoagulant interaction carries a boxed warning?
Vitamin K antagonists such as warfarin: raised INR and bleeding.
Connections
← Back to the class: Antimetabolites
Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.
Sources: DailyMed - CAPECITABINE tablet (DailyMed (U.S. National Library of Medicine), 2026); Capecitabine: MedlinePlus Drug Information (MedlinePlus (U.S. National Library of Medicine), 2026); RCSB PDB - 6QXG: Crystal structure of His-tag human thymidylate synthase (HT-hTS) in complex with FdUMP (RCSB Protein Data Bank, 2026); ATCDDD - ATC/DDD Index (WHO Collaborating Centre for Drug Statistics Methodology, 2026).
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Representative model, for educational purposes only.