Presentation Abstract

Session: 206-New Twists on Antimicrobial Stewardship
Friday, Sep 13, 2013, 8:30 AM -11:00 AM
Presentation Title: K-1544 - How Safe are Antimicrobials Approved by the FDA in the Past 7 Years? Review of the FDA AERS Database
Location: Four Seasons Ballroom 3
Presentation Number: K-1544
Pres. Time: Friday, Sep 13, 2013, 8:45 AM - 9:00 AM
Category: K
Keywords: adverse event; epidemiology; safety
Author(s): T. Khadem1,2, R. P. van Manen3, J. Brown1,2; 1State Univ. of New York at Buffalo, Buffalo, NY, 2Univ. of Rochester Med. Ctr., Rochester, NY, 3Oracle Corp., Redwood Shores, CA
Financial Disclosures:  T. Khadem, None. 
R. P. van Manen,
Oracle Health Sciences Global Business Unit Role(s): Consultant.
J. Brown, None.
Abstract: Background: During the past 7 years the FDA has approved 11 antimicrobial new molecular entities (NME) including: anidulafungin (A), darunavir (DR), maraviroc (M), raltegravir (R), doripenem (DP), telavancin (TV), ceftaroline (C), boceprevir (BC), telaprevir (TR), fidaxomicin (F) and bedaquiline (BQ). Historically, about 3% of FDA approved antimicrobials are removed from the US market due to untoward safety concerns. Our goal was to qualitatively and quantitatively review the FDA AERS database to provide clinicians with a general understanding of the comparative occurrence of clinically important adverse events (AE) seen in antimicrobial NME approved by the FDA in the past 7 years. Methods: Empirica Signal software was used to query AERS from each agent's approval date to December 31, 2012. We calculated a disproportionality statistic, namely the Empirical Bayesian Geometric Mean (EBGM), for reports of antimicrobial AE. The FDA considers an EBGM significant if the 5th percentile of the distribution is at least two (EB05 > 2.0). With use of a disproportionality analysis, antimicrobials were compared with all agents within their antimicrobial therapeutic class. Results: Significant AE signals were seen for 6 of the 11 antimicrobial NME, many of which are not included in package inserts. They include: DP associated hepatic dysfunction (EB05 3.7) , hyperchloremia (EB05 2.6); BC associated weight loss (EB05 2.2); DR associated premature labor (EB05 3.1), sudden infant death syndrome (SIDS) (EB05 2.9), ventricular hypertrophy (EB05 2.7), acute coronary syndromes (EB05 2.4), congenital anomaly in offspring (EB05 2.4); R associated congenital heart valve disorders (EB05 2.5), SIDS (EB05 2.3). Significant AE signals identified but already listed in the package insert include: TV associated acute renal failure; DP associated seizures, thrombocytopenia; BC associated anemia; M associated malignancies, myocardial infarction; R associated hepatitis. Conclusions: There appears to be significant adverse events associated with antimicrobial NME approved in the last 7 years, including those not identified in package inserts. Investigative studies are needed to further explore these statistical associations.

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