How Safe Are Recently FDA‐Approved Antimicrobials? A Review of the FDA Adverse Event Reporting System Database. Issue 12 (25th November 2014)

• Record Type: Journal Article
• Authors: Khadem, Tina M.; van Manen, Robbert P.; Brown, Jack
• Is Part Of: Pharmacotherapy. Volume 34:Issue 12(2014)
• Page Start: 1324
• Page End: 1329
• Publication Date: 2014-11-25
• Subjects: Chemotherapy -- Periodicals; Pharmacology -- Periodicals; Drug Therapy -- Periodicals; Pharmacology -- Periodicals; 615.1
• DOI: 10.1002/phar.1519
• Languages: English
• ISSNs: 0277-0008

Abstract

<abstract abstract-type="main" id="phar1519-abs-0001"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="phar1519-sec-0001" sec-type="section"> <title>Study Objective</title> <p>To review quantitatively and qualitatively the U.S. Food and Drug Administration (FDA) Adverse Event Reporting System (AERS) 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 since 2006: anidulafungin, darunavir, maraviroc, raltegravir, doripenem, telavancin, ceftaroline, boceprevir, telaprevir, fidaxomicin, bedaquiline, dolutegravir, simeprevir, sofosbuvir, and dalbavancin.</p> </sec> <sec id="phar1519-sec-0002" sec-type="section"> <title>Design</title> <p>Retrospective analysis.</p> </sec> <sec id="phar1519-sec-0003" sec-type="section"> <title>Data Source</title> <p>FDA AERS database.</p> </sec> <sec id="phar1519-sec-0004" sec-type="section"> <title>Measurements and Main Results</title> <p>Empirica Signal software was used to query the AERS database from November 1968 to December 2012. Using disproportionality analyses, we calculated a relative reporting ratio (RRR) estimate for reports of antimicrobial adverse events. The RRR 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‐approved prescription drugs. Common industry practice considers an RRR meaningful if the 5th percentile of the distribution is at least 2 (RRR<sub>05</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 database. Seventeen adverse signals with an RRR<sub>05</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‐to‐date manufacturers' package inserts for four of the six agents: doripenem‐associated hepatic dysfunction (RRR<sub>05</sub> 3.7) and hyperchloremia (RRR<sub>05</sub> 2.6); boceprevir‐associated weight loss (RRR<sub>05</sub> 2.2); darunavir‐associated premature labor (RRR<sub>05</sub> 3.1), sudden infant death syndrome (RRR<sub>05</sub> 2.9), ventricular hypertrophy (RRR<sub>05</sub> 2.7), acute coronary syndrome (RRR<sub>05</sub> 2.4), and congenital anomaly in offspring (RRR<sub>05</sub> 2.4); and raltegravir‐associated congenital heart valve disorders (RRR<sub>05</sub> 2.5) and SIDS (RRR<sub>05</sub> 2.3).</p> </sec> <sec id="phar1519-sec-0005" sec-type="section"> <title>Conclusion</title> <p>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.</p> </sec> </abstract>