{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T09:33:46Z","timestamp":1787045626796,"version":"build-2736575974"},"reference-count":23,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T00:00:00Z","timestamp":1787011200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"European Union-NextGenerationEU","award":["BG-RRP-2.004-0003"],"award-info":[{"award-number":["BG-RRP-2.004-0003"]}]},{"award":["BG-RRP-2.004-0003"],"award-info":[{"award-number":["BG-RRP-2.004-0003"]}],"id":[{"id":"https:\/\/ror.org\/019w4f821","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Bulgarian National Scientific Fund","award":["BG-175467353-2024-11-0053\/KP-06-H83\/3"],"award-info":[{"award-number":["BG-175467353-2024-11-0053\/KP-06-H83\/3"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Clin. Med.","JCM"],"abstract":"<jats:p>Background\/Objectives: Ibrutinib is an established treatment for chronic lymphocytic leukemia\/small lymphocytic lymphoma (CLL\/SLL), but its use commonly occurs in older patients with polypharmacy, cardiovascular comorbidity and infection vulnerability. CYP3A-modifying drugs and antithrombotic agents are clinically actionable co-exposure domains because they may alter ibrutinib exposure, bleeding risk or the management of atrial arrhythmia. This study evaluated post-marketing reporting patterns for these co-exposures in FAERS. Methods: Adult FAERS reports through 25Q2 with ibrutinib exposure and CLL\/SLL-compatible indications were analyzed after false-positive indication captures were removed. Co-exposures were defined at report level using prespecified drug dictionaries, and grouped adverse-event reporting was evaluated using reporting odds ratio, proportional reporting ratio, chi-square and an information-component-style two-by-two metric. Results: The final cohort comprised 20,878 adult CLL\/SLL + ibrutinib reports. CYP3A modifier co-exposure was present in 1373 reports (6.6%), and antithrombotic co-exposure in 3701 reports (17.7%). Antithrombotic exposure increased with age, from 9.8% in reports aged 18\u201364 years to 23.2% in reports aged \u226575 years. CYP3A modifier exposure was associated with enriched reporting of infection and cytopenia phenotypes, particularly severe infection-like events with CYP3A inhibitors and inducers. Antithrombotic exposure showed consistent reporting enrichment for atrial arrhythmia, bleeding and major bleeding-like events, with the strongest grouped signals among anticoagulant-exposed reports. Overlap analyses showed that the co-exposure domains were not mutually exclusive. Conclusions: These findings should be interpreted as reporting disproportionality rather than incidence or causal risk, but they support prioritizing CYP3A-modifying drugs and antithrombotic therapy during medication reconciliation, interaction screening and risk mitigation in older patients receiving ibrutinib.<\/jats:p>","DOI":"10.3390\/jcm15166370","type":"journal-article","created":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T09:06:41Z","timestamp":1787044001000},"page":"6370","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Drug Safety and Polypharmacy Signals in Ibrutinib-Treated Chronic Lymphocytic Leukemia\/Small Lymphocytic Lymphoma: Age- and Sex-Specific FAERS Analysis of CYP3A Modifier and Antithrombotic Co-Exposure"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5362-7999","authenticated-orcid":false,"given":"Velizar","family":"Shivarov","sequence":"first","affiliation":[{"name":"Department of Experimental Research, Medical University Pleven, 5800 Pleven, Bulgaria"},{"name":"Department of Clinical Hematology, St. Sophia General Hospital, 1618 Sofia, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1056\/NEJMoa1400376","article-title":"Ibrutinib versus ofatumumab in previously treated chronic lymphoid leukemia","volume":"371","author":"Byrd","year":"2014","journal-title":"N. 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