{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T05:24:40Z","timestamp":1789795480338,"version":"4.0.1"},"reference-count":27,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2020,4,22]],"date-time":"2020-04-22T00:00:00Z","timestamp":1587513600000},"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":[[2020,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Purpose<\/jats:title><jats:p>To identify and analyze postmarketing cases of complex sleep behaviors (CSBs) resulting in serious injuries, including death, associated with eszopiclone, zaleplon, or zolpidem (Z\u2010drugs).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Retrospective analysis of the U.S. Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) from 16 December 1992 through 27 February 2018 and medical literature using PubMed and EMBASE. We used random sampling and descriptive statistics.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We identified 66 cases that met inclusion and exclusion criteria, four of which were identified in the medical literature. Twenty cases reported death and 46 cases reported serious injuries in association with CSBs occurring after the use of a Z\u2010drug. Fatal cases described events, such as carbon monoxide poisoning, drowning, falls, hypothermia, motor vehicle collisions, and apparent completed suicide. Nonfatal cases resulting in serious injuries described events, such as accidental overdoses, falls, gunshot wounds, hypothermia, third\u2010degree burns, and self\u2010injuries or suicide attempts. Twenty\u2010two cases reported a previous episode of a CSB while taking a Z\u2010drug prior to the event reported in this case series.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The FAERS and medical literature cases support the need for increased awareness of the consequences that may occur because of CSBs associated with the use of Z\u2010drugs. Therefore, to protect public health, regulatory actions were taken, including adding a Boxed Warning, a Contraindication in patients who have experienced a prior episode of a CSB with a Z\u2010drug, and updating the existing Warnings and Precautions. An FDA Drug Safety Communication was also disseminated to alert healthcare professionals and the public of this potential risk.<\/jats:p><\/jats:sec>","DOI":"10.1002\/pds.5004","type":"journal-article","created":{"date-parts":[[2020,4,23]],"date-time":"2020-04-23T05:43:15Z","timestamp":1587620595000},"page":"684-691","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":46,"title":["Association of eszopiclone, zaleplon, or zolpidem with complex sleep behaviors resulting in serious injuries, including death"],"prefix":"10.1002","volume":"29","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0716-2673","authenticated-orcid":false,"given":"Kelly","family":"Harbourt","sequence":"first","affiliation":[{"name":"Division of Pharmacovigilance U.S. Food and Drug Administration, Center for Drug Evaluation and Research, Office of Surveillance and Epidemiology  Silver Spring Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ofir N.","family":"Nevo","sequence":"additional","affiliation":[{"name":"Division of Pharmacovigilance U.S. Food and Drug Administration, Center for Drug Evaluation and Research, Office of Surveillance and Epidemiology  Silver Spring Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rongmei","family":"Zhang","sequence":"additional","affiliation":[{"name":"Division of Biometrics VII U.S. Food and Drug Administration, Center for Drug Evaluation and Research, Office of Biostatistics  Silver Spring Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vicky","family":"Chan","sequence":"additional","affiliation":[{"name":"Division of Pharmacovigilance U.S. Food and Drug Administration, Center for Drug Evaluation and Research, Office of Surveillance and Epidemiology  Silver Spring Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Croteau","sequence":"additional","affiliation":[{"name":"Division of Pharmacovigilance U.S. Food and Drug Administration, Center for Drug Evaluation and Research, Office of Surveillance and Epidemiology  Silver Spring Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,4,22]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.1124\/pr.117.014449"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.1177\/0269881109106927"},{"key":"e_1_2_13_4_1","unstructured":"Ambien [Package Insert]. Bridgewater NJ: Sanofi\u2010Aventis U.S. LLC; 2019. Accessed April 23 2019."},{"key":"e_1_2_13_5_1","unstructured":"Lunesta [Package Insert]. Marlborough MA: Sunovion Pharmaceuticals Inc.; 2018. Accessed April 23 2019."},{"key":"e_1_2_13_6_1","unstructured":"Sonata [Package Insert]. Bristol TN: King Pharmaceuticals Inc.; 2013. Accessed April 23 2019."},{"key":"e_1_2_13_7_1","unstructured":"Southworth MR. Zaleplon Eszopiclone and Zolpidem and Sleep Driving. FDA ODS Postmarketing Safety Review: PID # D060196;2006."},{"key":"e_1_2_13_8_1","unstructured":"Symphony Health Solutions' Integrated Dataverse (IDV) Database. Nationally estimated number of patients with a prescription claim for a eszopiclone zaleplon or zolpidem from U.S. outpatient retail pharmacies. Years 2013\u20132016 Extracted August 2017."},{"key":"e_1_2_13_9_1","volume-title":"International Classification of Sleep Disorders","author":"American Academy of Sleep Medicine","year":"2014"},{"key":"e_1_2_13_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.smrv.2006.06.003"},{"issue":"111","key":"e_1_2_13_11_1","doi-asserted-by":"crossref","first-page":"e0164769","DOI":"10.1371\/journal.pone.0164769","article-title":"Prevalence of sleepwalking: a systematic review and meta\u2010analysis","volume":"11","author":"Stallman HM","year":"2016","journal-title":"PLoS One"},{"key":"e_1_2_13_12_1","unstructured":"U.S. Food and Drug Administration. Questions and Answers on FDA's Adverse Event Reporting System (FAERS).https:\/\/www.fda.gov\/drugs\/surveillance\/fda-adverse-event-reporting-system-faers. Updated June 4 2018. Accessed June 5 2019."},{"key":"e_1_2_13_13_1","unstructured":"U.S. Food and Drug Administration. FDA Adverse Event Reporting System (FAERS) [article online].http:\/\/www.fda.gov\/Drugs\/GuidanceComplianceRegulatoryInformation\/Surveillance\/AdverseDrugEffects\/default.htm. Accessed April 25 2019."},{"key":"e_1_2_13_14_1","unstructured":"Medical Dictionary for Regulatory Activities.https:\/\/www.meddra.org. Accessed May 22 2019."},{"key":"e_1_2_13_15_1","unstructured":"U.S. Food and Drug Administration. Code of Federal Regulations Title 21 Volume 5 Chapter 1 Section 314.80 Postmarketing reporting of adverse drug experiences. Revised as of April 1 2018."},{"key":"e_1_2_13_16_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.311.7005.619"},{"key":"e_1_2_13_17_1","unstructured":"U.S. Food and Drug Administration. 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