{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,22]],"date-time":"2025-10-22T00:46:54Z","timestamp":1761094014914,"version":"build-2065373602"},"reference-count":12,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2014,11,25]],"date-time":"2014-11-25T00:00:00Z","timestamp":1416873600000},"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":[[2014,12]]},"abstract":"Study Objective<\/jats:title>To review quantitatively and qualitatively the U.S. Food and Drug Administration (FDA<\/jats:styled-content>) Adverse Event Reporting System (AERS<\/jats:styled-content>) database to provide clinicians with a general understanding of the comparative occurrence of clinically meaningful adverse events associated with 15 antimicrobial new molecular entities approved by the FDA<\/jats:styled-content> since 2006: anidulafungin, darunavir, maraviroc, raltegravir, doripenem, telavancin, ceftaroline, boceprevir, telaprevir, fidaxomicin, bedaquiline, dolutegravir, simeprevir, sofosbuvir, and dalbavancin.<\/jats:p><\/jats:sec>Design<\/jats:title>Retrospective analysis.<\/jats:p><\/jats:sec>Data Source<\/jats:title>FDA AERS<\/jats:styled-content> database.<\/jats:p><\/jats:sec>Measurements and Main Results<\/jats:title>Empirica Signal software was used to query the AERS<\/jats:styled-content> database from November 1968 to December 2012. Using disproportionality analyses, we calculated a relative reporting ratio (RRR<\/jats:styled-content>) estimate for reports of antimicrobial adverse events. The RRR<\/jats:styled-content> estimate compares the occurrence of a specific adverse event with an index drug of interest to the occurrence of the same adverse event with similar agents or with all other FDA<\/jats:styled-content>\u2010approved prescription drugs. Common industry practice considers an RRR<\/jats:styled-content> meaningful if the 5th percentile of the distribution is at least 2 (RRR<\/jats:styled-content>05<\/jats:sub> of 2.0 or higher). Antimicrobials were compared with agents within their respective antimicrobial therapeutic class as well as with all agents in the AERS<\/jats:styled-content> database. Seventeen adverse signals with an RRR<\/jats:styled-content>05<\/jats:sub> of 2.0 or higher were identified from the database for six agents. Ten of the 17 signals were not included in the most up\u2010to\u2010date manufacturers' package inserts for four of the six agents: doripenem\u2010associated hepatic dysfunction (RRR<\/jats:styled-content>05<\/jats:sub> 3.7) and hyperchloremia (RRR<\/jats:styled-content>05<\/jats:sub> 2.6); boceprevir\u2010associated weight loss (RRR<\/jats:styled-content>05<\/jats:sub> 2.2); darunavir\u2010associated premature labor (RRR<\/jats:styled-content>05<\/jats:sub> 3.1), sudden infant death syndrome (RRR<\/jats:styled-content>05<\/jats:sub> 2.9), ventricular hypertrophy (RRR<\/jats:styled-content>05<\/jats:sub> 2.7), acute coronary syndrome (RRR<\/jats:styled-content>05<\/jats:sub> 2.4), and congenital anomaly in offspring (RRR<\/jats:styled-content>05<\/jats:sub> 2.4); and raltegravir\u2010associated congenital heart valve disorders (RRR<\/jats:styled-content>05<\/jats:sub> 2.5) and SIDS<\/jats:styled-content> (RRR<\/jats:styled-content>05<\/jats:sub> 2.3).<\/jats:p><\/jats:sec>Conclusion<\/jats:title>Clinically meaningful adverse event signals appeared to be associated with antimicrobial new molecular entities approved since 2006 including many not yet identified in package inserts. Although a disproportionality analysis suggests a quantitative signal for these associations, causality cannot be inferred from the data. Due to several key limitations in this type of analysis, investigative studies are needed to further explore these adverse event signals and the potential mechanisms by which they occur.<\/jats:p><\/jats:sec>","DOI":"10.1002\/phar.1519","type":"journal-article","created":{"date-parts":[[2014,11,25]],"date-time":"2014-11-25T03:02:30Z","timestamp":1416884550000},"page":"1324-1329","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["How Safe Are Recently FDA<\/scp>\u2010Approved Antimicrobials? A Review of the FDA<\/scp> Adverse Event Reporting System Database"],"prefix":"10.1002","volume":"34","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9716-580X","authenticated-orcid":false,"given":"Tina M.","family":"Khadem","sequence":"first","affiliation":[{"name":"St. John Fisher College, Wegmans School of Pharmacy Rochester New York"},{"name":"University of Rochester Medical Center Department of Pharmacy Rochester New York"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robbert P.","family":"van Manen","sequence":"additional","affiliation":[{"name":"Oracle Health Sciences Global Business Unit Kattendijke The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jack","family":"Brown","sequence":"additional","affiliation":[{"name":"St. John Fisher College, Wegmans School of Pharmacy Rochester New York"},{"name":"University of Rochester Medical Center Department of Pharmacy Rochester New York"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2014,11,25]]},"reference":[{"key":"e_1_2_6_2_1","unstructured":"U.S. Food and Drug Administration.Drug Approval Reports. Available fromhttp:\/\/www.accessdata.fda.gov\/scripts\/cder\/drugsatfda\/index.cfm?fuseaction=Reports.ReportsMenu. Accessed June 12 2014."},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/9780470059876.ch9"},{"key":"e_1_2_6_4_1","unstructured":"U.S. Food and Drug Administration.FDA Adverse Event Reporting System. Available fromhttp:\/\/www.fda.gov\/Drugs\/GuidanceComplianceRegulatoryInformation\/Surveillance\/AdverseDrugEffects\/default.htm. Accessed June 28 2013."},{"key":"e_1_2_6_5_1","unstructured":"U.S. Department of Health and Human Services. Food and Drug Administration. Center for Drug Evaluation and Research (CDER). Center for Biologics Evaluation and Research (CBER).Guidance for Industry: Good Pharmacovigilance Practices and Pharmacoepidemiologic Assessment. Available fromhttp:\/\/www.fda.gov\/downloads\/regulatoryinformation\/guidances\/ucm126834.pdf. 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Acc\u2010essed October 29 2013."}],"container-title":["Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fphar.1519","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fphar.1519","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/accpjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/phar.1519","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,21]],"date-time":"2025-10-21T14:22:55Z","timestamp":1761056575000},"score":1,"resource":{"primary":{"URL":"https:\/\/accpjournals.onlinelibrary.wiley.com\/doi\/10.1002\/phar.1519"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,11,25]]},"references-count":12,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2014,12]]}},"alternative-id":["10.1002\/phar.1519"],"URL":"https:\/\/doi.org\/10.1002\/phar.1519","archive":["Portico"],"relation":{},"ISSN":["0277-0008","1875-9114"],"issn-type":[{"type":"print","value":"0277-0008"},{"type":"electronic","value":"1875-9114"}],"subject":[],"published":{"date-parts":[[2014,11,25]]},"assertion":[{"value":"2014-11-25","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}