{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T23:32:29Z","timestamp":1789083149719,"version":"build-2803163510"},"reference-count":14,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2025,10,25]],"date-time":"2025-10-25T00:00:00Z","timestamp":1761350400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pharmacoepidemiology and Drug"],"published-print":{"date-parts":[[2025,11]]},"abstract":"ABSTRACT<\/jats:title>\n \n Purpose<\/jats:title>\n Clozapine, a highly effective antipsychotic medication, is associated with rare but potentially life\u2010threatening neutropenia. In February 2025, the US Food and Drug Administration (FDA) eliminated its clozapine Risk Evaluation and Mitigation Strategies (REMS) program, which required documented absolute neutrophil count (ANC) lab results prior to clozapine dispensation. Considering the FDA decision, the purpose of this study was to examine the prevalence and patient\u2010level factors associated with clozapine\u2010associated neutropenia in a large, diverse, US\u2010based integrated health system.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n This was a retrospective cohort study of adult Kaiser Permanente Northern California members who initiated clozapine therapy between January 2021 and December 2022. Data were extracted from KPNC's electronic health record, including sociodemographic and clinical characteristics, medication fills, and ANC values. The main outcome was any neutropenic event within two years of clozapine initiation, classified as mild (ANC\u2009=\u20091000\u20131499\/\u03bcL) or severe (ANC\u2009<\u20091000\/\u03bcL).<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Among 402 patients, 10 (2.5%) experienced neutropenia within 24\u2009months of starting clozapine. Eight cases were mild, and two were severe, with one resulting in death. Race differed significantly between those who experienced neutropenia and those who did not (\n p<\/jats:italic>\n \u2009=\u20090.038). The mean clozapine dose at the time of neutropenia was 192.5\u2009mg, with significant differences between mild and severe cases (\n p<\/jats:italic>\n \u2009=\u20090.015). Logistic regression analyses showed no significant associations between neutropenia and patient\u2010level sociodemographic or clinical characteristics.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n Clozapine\u2010related neutropenia was rare and typically transient, but it can be life\u2010threatening. Continued adherence to the manufacturer's recommendations for ANC monitoring is warranted to ensure patient safety.<\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/pds.70249","type":"journal-article","created":{"date-parts":[[2025,10,25]],"date-time":"2025-10-25T13:54:02Z","timestamp":1761400442000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Clozapine\u2010Associated Neutropenia Prevalence in a Large, Integrated Healthcare System"],"prefix":"10.1002","volume":"34","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8264-1180","authenticated-orcid":false,"given":"Jill L.","family":"Nofziger","sequence":"first","affiliation":[{"name":"Regional Clinical Pharmacy Operations Kaiser Permanente Northern California Livermore California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea H.","family":"Kline\u2010Simon","sequence":"additional","affiliation":[{"name":"Division of Research Kaiser Permanente Northern California Pleasanton California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leah M.","family":"Arnbrecht","sequence":"additional","affiliation":[{"name":"Clinical Pharmacy Operations Kaiser Permanente Greater San Jose Area San Jose California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cimone","family":"Durojaiye","sequence":"additional","affiliation":[{"name":"Division of Research Kaiser Permanente Northern California Pleasanton California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew E.","family":"Hirschtritt","sequence":"additional","affiliation":[{"name":"Division of Research Kaiser Permanente Northern California Pleasanton California USA"},{"name":"Department of Psychiatry Kaiser Permanente Oakland Medical Center Oakland California USA"},{"name":"Department of Psychiatry and Behavioral Sciences University of California San Francisco California USA"},{"name":"Department of Health Systems Science Kaiser Permanente Bernard J. Tyson School of Medicine Pasadena California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,10,25]]},"reference":[{"key":"e_1_2_10_2_1","unstructured":"H. A.Duerr \u201cFDA Officially Removes REMS Requirement for Clozapine \u201dPsychiatric Times February 25 2025 https:\/\/www.psychiatrictimes.com\/view\/fda\u2010officially\u2010removes\u2010rems\u2010requirement\u2010for\u2010clozapine."},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12888\u2010016\u20101167\u20100"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1177\/0004867419833166"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1192\/bjb.2018.67"},{"key":"e_1_2_10_6_1","volume-title":"CLOZARIL [Package Insert]","author":"HLS Therapeutics (USA) Inc","year":"2023"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2215\u20100366(23)00343\u20107"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2215\u20100366(23)00366\u20108"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2215\u20100366(25)00001\u2010X"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2215\u20100366(24)00097\u2010X"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1017\/S0033291719000369"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1080\/17445647.2020.1750066"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.7812\/TPP\/20.010"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1176\/appi.prcp.20240056"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1176\/appi.ps.52.1.111"}],"container-title":["Pharmacoepidemiology and Drug Safety"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/pds.70249","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,21]],"date-time":"2025-11-21T08:53:34Z","timestamp":1763715214000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/pds.70249"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,25]]},"references-count":14,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2025,11]]}},"alternative-id":["10.1002\/pds.70249"],"URL":"https:\/\/doi.org\/10.1002\/pds.70249","archive":["Portico"],"relation":{},"ISSN":["1053-8569","1099-1557"],"issn-type":[{"value":"1053-8569","type":"print"},{"value":"1099-1557","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,25]]},"assertion":[{"value":"2025-05-07","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-10-15","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-10-25","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70249"}}