adjuvant treatment of people with Stage III colon cancer as a single agent or as a component of a combination chemotherapy regimen;[8]
perioperative treatment of adults with locally advanced rectal cancer as a component of chemoradiotherapy;[8]
treatment of people with unresectable or metastatic colorectal cancer as a single agent or as a component of a combination chemotherapy regimen;[8]
treatment of people with advanced or metastatic breast cancer as a single agent if an anthracycline- or taxane-containing chemotherapy is not indicated;[8]
treatment of people with advanced or metastatic breast cancer in combination with docetaxel after disease progression on prior anthracycline-containing chemotherapy;[8]
treatment of adults with unresectable or metastatic gastric, esophageal, or gastroesophageal junction cancer as a component of a combination chemotherapy regimen;[8]
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;[8]
adjuvant treatment of adults with pancreatic adenocarcinoma as a component of a combination chemotherapy regimen.[8]
Severe hepatic impairment or severe renal impairment
Treatment with sorivudine or its chemically related analogues, such as brivudine
In 2020, the EU and UK license was updated to state that capecitabine was contra-indicated in patients that "have a known complete absence of dihydropyrimidine dehydrogenase (DPD) activity".[14] In US, as of 2024, there is no specific contraindication on the package inserts however, there is a cautionary warning: "Patients with certain homozygous or compound
heterozygous variants in the DPYD gene are at increased risk for acute
early-onset toxicity and serious, including fatal, adverse reactions due to
XELODA (e.g., mucositis, diarrhea, neutropenia, and neurotoxicity).
XELODA is not recommended for use in patients known to have certain
homozygous or compound heterozygous DPYD variants that result in
complete absence of DPD activity. Withhold or permanently discontinue
based on clinical assessment. No XELODA dose has been proven safe in
patients with complete absence of DPD activity. "[15]
Within the UK, DPYD testing to check for this contraindication is now routine practice,[16] this is not the case in the US.[17]
CYP2C9 substrates, including, warfarin and other coumarin-derivatives anticoagulants
Phenytoin, as it increases the plasma concentrations of phenytoin.
Calcium folinate may enhance the therapeutic effects of capecitabine by means of synergising with its metabolite, 5-FU. It may also induce more severe diarrhoea by means of this synergy.[18]
Capecitabine is metabolised to 5-FU which in turn is a thymidylate synthase inhibitor, hence inhibiting the synthesis of thymidine monophosphate (ThMP), the active form of thymidine which is required for the de novo synthesis of DNA.[20]
Drug synthesis
Overdose
Uridine Triacetate is a potential antidote for cases of suspected overdose.[21]
^World Health Organization (2019). World Health Organization model list of essential medicines: 21st list 2019. Geneva: World Health Organization. hdl:10665/325771. WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO.
^Rossi S, ed. (2013). Australian Medicines Handbook (2013 ed.). Adelaide: The Australian Medicines Handbook Unit Trust. ISBN978-0-9805790-9-3.
^ abAmstutz U, Froehlich TK, Largiadèr CR (September 2011). "Dihydropyrimidine dehydrogenase gene as a major predictor of severe 5-fluorouracil toxicity". Pharmacogenomics. 12 (9): 1321–1336. doi:10.2217/pgs.11.72. PMID21919607.
^Ma WW, Saif WM, Cartwright TH, Fakih M, El-Rayes BF, King T, et al. (20 May 2016). "Uridine triacetate as a lifesaving antidote for overdoses and severe early-onset 5-fluorouracil and capecitabine toxicities". Journal of Clinical Oncology. 34 (15_suppl): e21689 –e21689. doi:10.1200/JCO.2016.34.15_suppl.e21689. ISSN0732-183X.
