{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T10:29:34Z","timestamp":1785925774263,"version":"3.56.0"},"reference-count":18,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2020,1,20]],"date-time":"2020-01-20T00:00:00Z","timestamp":1579478400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["accpjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pharmacotherapy"],"published-print":{"date-parts":[[2020,2]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>There is a known drug interaction (DI) between xanthine oxidase (XO) inhibitors and the thiopurine immunosuppressants, azathioprine (AZA) and mercaptopurine (6\u2010MP). Xanthine oxidase inhibition increases concentrations of AZA and 6\u2010MP active metabolites, possibly resulting in myelosuppression. When allopurinol is used with AZA or 6\u2010MP, dose reduction of AZA or 6\u2010MP is recommended. Febuxostat is a newer XO inhibitor approved for the treatment of gout.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To determine the clinical impact of the febuxostat\u2010thiopurine DI.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design and Setting<\/jats:title>\n                    <jats:p>Case series derived from the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) and published medical literature.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Patients<\/jats:title>\n                    <jats:p>Nineteen patients who received concomitant febuxostat and either AZA or 6\u2010MP.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Measurements<\/jats:title>\n                    <jats:p>Laboratory and clinical data.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Nineteen cases reporting myelosuppressive events were identified in patients receiving febuxostat with AZA or 6\u2010MP. Eighteen cases were treated with the combination of AZA and febuxostat. A median of 1.6\u00a0months elapsed from initiation of the drug combination until discovery of the event. Sixteen cases required hospitalization; 15 reported administration of blood products. Thirteen cases reported resolution of the event with discontinuation of both drugs, two reported discontinuation of the thiopurine only, and one reported discontinuation of febuxostat only.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Limitations<\/jats:title>\n                    <jats:p>Thiopurine monotherapy may cause myelosuppression. Complications of immunosuppression that may contribute to the real\u2010world morbidity and mortality associated with the febuxostat\u2010thiopurine DI were not examined. Finally, FAERS data are limited by the voluntary nature of reporting.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Current febuxostat labeling contraindicates concomitant administration of febuxostat with either AZA or 6\u2010MP. This case series demonstrates that the DI can result in clinically significant adverse events and is supportive of current febuxostat labeling.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/phar.2362","type":"journal-article","created":{"date-parts":[[2019,12,30]],"date-time":"2019-12-30T01:32:32Z","timestamp":1577669552000},"page":"125-132","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Drug Interaction Between Febuxostat and Thiopurine Antimetabolites: A Review of the FDA Adverse Event Reporting System and Medical Literature"],"prefix":"10.1002","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3565-9441","authenticated-orcid":false,"given":"Jill K.","family":"Logan","sequence":"first","affiliation":[{"name":"Division of Pharmacovigilance Office of Surveillance and Epidemiology Center for Drug Evaluation and Research US Food and Drug Administration Silver Spring Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shalini","family":"Wickramaratne Senarath Yapa","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacology Office of Clinical Pharmacology Office of Translational Sciences Center for Drug Evaluation and Research US Food and Drug Administration Silver Spring Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa","family":"Harinstein","sequence":"additional","affiliation":[{"name":"Division of Pharmacovigilance Office of Surveillance and Epidemiology Center for Drug Evaluation and Research US Food and Drug Administration Silver Spring Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bhawana","family":"Saluja","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacology Office of Clinical Pharmacology Office of Translational Sciences Center for Drug Evaluation and Research US Food and Drug Administration Silver Spring Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9754-1986","authenticated-orcid":false,"given":"Monica","family":"Mu\u00f1oz","sequence":"additional","affiliation":[{"name":"Division of Pharmacovigilance Office of Surveillance and Epidemiology Center for Drug Evaluation and Research US Food and Drug Administration Silver Spring Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chandrahas","family":"Sahajwalla","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacology Office of Clinical Pharmacology Office of Translational Sciences Center for Drug Evaluation and Research US Food and Drug Administration Silver Spring Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosemarie","family":"Neuner","sequence":"additional","affiliation":[{"name":"Division of Pulmonary, Allergy, and Rheumatology Products Office of Drug Evaluation Office of New Drugs Center for Drug Evaluation and Research US Food and Drug Administration Silver Spring Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sally","family":"Seymour","sequence":"additional","affiliation":[{"name":"Division of Pulmonary, Allergy, and Rheumatology Products Office of Drug Evaluation Office of New Drugs Center for Drug Evaluation and Research US Food and Drug Administration Silver Spring Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,1,20]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinthera.2009.11.033"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.40807"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2004.10.031"},{"key":"e_1_2_6_5_1","unstructured":"U.S. Food and Drug Administration.Drugs@FDA: FDA Approved Drug Products. 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