{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T14:28:19Z","timestamp":1788964099332,"version":"build-2803163510"},"reference-count":45,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2022,11,10]],"date-time":"2022-11-10T00:00:00Z","timestamp":1668038400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"PROGETTI DI FARMACOVIGILANZA ATTIVA FINANZIABILI ATTRAVERSO I FONDI FV 2012, 2013 e 2014"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Hand-Foot syndrome (HFS) and diarrhoea are dose-limiting Adverse Drug Reactions (ADRs) of capecitabine-based chemotherapy. Four polymorphisms in the dihydropyrimidine dehydrogenase (DPYD) gene, encoding the DPD enzyme responsible for the metabolism of fluoropyrimidines, such as capecitabine, are strongly associated with severe ADRs, and their screening should be performed before starting treatment. Moreover, capecitabine-related toxicity may worsen due to drug-drug and drug-supplement interactions. Here we investigated factors responsible for severe HFS and diarrhoea presented by two patients, non-carriers of the recommended DPYD single nucleotide polymorphisms (SNPs) but carriers of other genetic variants suggested to increase the risk of capecitabine-related ADRs. Through careful therapy recognition, we demonstrated that, unbeknownst to the oncologists, the patients were taking folic acid during the treatment with capecitabine at a dosage higher than 2000 mg\/m2, which is the maximum tolerated dose when folate is administered. To resolve the ADRs, the therapy had to be drastically changed. In one case, dose reduction of capecitabine and discontinuation of lipid-lowering agents were carried out. In the other case, discontinuation of capecitabine and folic acid and capecitabine re-administration were performed after a month. Genetic and environmental factors should be considered good predictors of severe capecitabine-related toxicity. Medication reconciliation should be encouraged to avoid the harmful consequences of inappropriate treatments.<\/jats:p>","DOI":"10.3390\/ph15111388","type":"journal-article","created":{"date-parts":[[2022,11,10]],"date-time":"2022-11-10T19:16:23Z","timestamp":1668107783000},"page":"1388","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Concomitant Administration of Capecitabine and Folate Supplements: Need to Encourage Medication Reconciliation"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7986-8704","authenticated-orcid":false,"given":"Berenice","family":"Stefanelli","sequence":"first","affiliation":[{"name":"Postgraduate School of Clinical Pharmacology and Toxicology, University of Salerno, Via S. Allende, 84081 Baronissi, Italy"},{"name":"Clinical Pharmacology Unit, San Giovanni di Dio e Ruggi d\u2019Aragona University Hospital, Via San Leonardo 1, 84131 Salerno, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5595-7841","authenticated-orcid":false,"given":"Carmine","family":"Sellitto","sequence":"additional","affiliation":[{"name":"Department of Medicine, Surgery and Dentistry \u201cScuola Medica Salernitana\u201d, University of Salerno, Via S. Allende, 84081 Baronissi, Italy"},{"name":"PhD School \u201cMedicina Traslazionale dello Sviluppo e dell\u2019Invecchiamento Attivo\u201d, Department of Medicine, Surgery and Dentistry \u201cScuola Medica Salernitana\u201d, University of Salerno, Via S. Allende, 84081 Baronissi, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8543-5462","authenticated-orcid":false,"given":"Emanuela","family":"De Bellis","sequence":"additional","affiliation":[{"name":"Postgraduate School of Clinical Pharmacology and Toxicology, University of Salerno, Via S. Allende, 84081 Baronissi, Italy"},{"name":"Clinical Pharmacology Unit, San Giovanni di Dio e Ruggi d\u2019Aragona University Hospital, Via San Leonardo 1, 84131 Salerno, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martina","family":"Torsiello","sequence":"additional","affiliation":[{"name":"PhD School \u201cScienze Biochimiche e Biotecnologiche\u201d, Department of Precision Medicine, University of Campania \u201cLuigi Vanvitelli\u201d, Piazza Luigi Miraglia, 80138 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicola","family":"Bertini","sequence":"additional","affiliation":[{"name":"Postgraduate School of Clinical Pharmacology and Toxicology, University of Salerno, Via S. Allende, 84081 Baronissi, Italy"},{"name":"Clinical Pharmacology Unit, San Giovanni di Dio e Ruggi d\u2019Aragona University Hospital, Via San Leonardo 1, 84131 Salerno, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angelo Maria","family":"Pezzullo","sequence":"additional","affiliation":[{"name":"Public Health Department, Catholic University, Largo Francesco Vito, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3441-889X","authenticated-orcid":false,"given":"Graziamaria","family":"Corbi","sequence":"additional","affiliation":[{"name":"Department of Medicine and Health Sciences, University of Molise, 86100 Campobasso, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6431-8278","authenticated-orcid":false,"given":"Francesco","family":"Sabbatino","sequence":"additional","affiliation":[{"name":"Department of Medicine, Surgery and Dentistry \u201cScuola Medica Salernitana\u201d, University of Salerno, Via S. Allende, 84081 Baronissi, Italy"},{"name":"Oncology Unit, University Hospital \u201cSan Giovanni di Dio e Ruggi d\u2019Aragona\u201d, Via San Leonardo 1, 84131 Salerno, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefano","family":"Pepe","sequence":"additional","affiliation":[{"name":"Department of Medicine, Surgery and Dentistry \u201cScuola Medica Salernitana\u201d, University of Salerno, Via S. Allende, 84081 Baronissi, Italy"},{"name":"Oncology Unit, University Hospital \u201cSan Giovanni di Dio e Ruggi d\u2019Aragona\u201d, Via San Leonardo 1, 84131 Salerno, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2153-4357","authenticated-orcid":false,"given":"Angela","family":"Tesse","sequence":"additional","affiliation":[{"name":"Nantes Universit\u00e9, CNRS, INSERM, l\u2019institut du thorax, F-44000 Nantes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6964-2739","authenticated-orcid":false,"given":"Valeria","family":"Conti","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology Unit, San Giovanni di Dio e Ruggi d\u2019Aragona University Hospital, Via San Leonardo 1, 84131 Salerno, Italy"},{"name":"Department of Medicine, Surgery and Dentistry \u201cScuola Medica Salernitana\u201d, University of Salerno, Via S. Allende, 84081 Baronissi, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8235-9118","authenticated-orcid":false,"given":"Amelia","family":"Filippelli","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology Unit, San Giovanni di Dio e Ruggi d\u2019Aragona University Hospital, Via San Leonardo 1, 84131 Salerno, Italy"},{"name":"Department of Medicine, Surgery and Dentistry \u201cScuola Medica Salernitana\u201d, University of Salerno, Via S. Allende, 84081 Baronissi, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,11,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2147","DOI":"10.1056\/NEJMoa1612645","article-title":"Adjuvant Capecitabine for Breast Cancer after Preoperative Chemotherapy","volume":"376","author":"Masuda","year":"2017","journal-title":"N. Engl. J. 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