Adverse Events Uncovered with New Antibiotics, Antivirals

the MPR take:

While manufacturers are required to study the safety of their drug products before they are brought to market, these trials may be limited and may not identify the full scope of potential adverse events. Using the FDA Adverse Event Reporting System database, researchers sought to determine clinically meaningful adverse events reported for 15 relatively new amtimicrobial agents: anidulafungin, bedaquiline, boceprevir, ceftaroline, dalbavancin, darunavir, dolutegravir, doripenem, fidaxomicin, maraviroc, raltegravir, simeprevir, sofosbuvir, telaprevir, and telavancin. A relative reporting ratio (RRR) was used to estimate the occurrence of an adverse event with a drug compared to the occurrence of the same effect in similar agents or with all FDA-approved drugs; an RRR0.5 of ≥2.0 was considered clinically meaningful. Due to a delay in release of data, bedaquiline, dolutegravir, simeprevir, sofosbuvir, and dalbavancin were not included in the analysis. For six of the remaining agents, 17 adverse signals with RRR0.5 >2.0 were identified; 10 of these were not included in the most recent prescribing information. These adverse events included: 

  • Doripenem: hepatic dysfunction (RRR0.5 3.7); hyperchloremia (RRR0.5 2.6) 
  • Boceprevir: weight loss (RRR0.5 2.2) 
  • Darunavir: premature labor (RRR0.5 3.1); sudden infant death syndrome(SIDS) (RRR0.5 2.9); ventricular hypertrophy (RRR0.5 2.7); acute coronary syndrome (RRR0.5 2.4); congenital anomaly in offspring (RRR0.5 2.4)
  • Raltegravir: congenital heart valve disorders (RRR0.5 2.5); SIDS (RRR0.5 2.3).

Although the disproportionality analysis suggests a link between these antimicrobials and serious adverse events, causality cannot be inferred and the potential mechanism of these events is unknown. The authors conclude that more research needs to be done to investigate these adverse events given the limitations of the study.

Study Objective: 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.

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