September 25, 2013
Newly Approved Antimicrobials Cause More Adverse Events Than Reported

Buffalo, NY—Antimicrobials approved by the FDA over the past 7 years cause more adverse events than reported in package inserts.

That’s according to research presented recently at the Interscience Conference on Anti-Microbial Agents and Chemotherapy in Denver.

Tina Khadem, PharmD, of the State University of New York at Buffalo, presented information about 10 of the 11 antimicrobial new molecular entities approved during that time period—anidulafungin, darunavir, maraviroc, raltegravir, doripenem, telavancin, ceftaroline, boceprevir, telaprevir, and fidaxomicin. (Bedaquiline, the most recently approved antimicrobial, was not represented because of a 5-month delay in the release of the public database, the authors note.)

With about 3% of FDA-approved antimicrobials removed from the U.S. market due to unacceptable safety concerns, the researchers reviewed the FDA Adverse Event Reporting System (AERS) database to determine the comparative occurrence of clinically important adverse events seen in the newly approved antimicrobials through December 31, 2012.

Adverse event signals were detected for six of the 10, according to the presentation, “many of which are not included in package inserts. They include: doripenem-associated hepatic dysfunction and hyperchloremia; boceprevir-associated weight loss; darunavir-associated premature labor, sudden infant death syndrome, ventricular hypertrophy, acute coronary syndromes, and congenital anomaly in offspring; raltegravir-associated congenital heart valve disorders, and sudden infant death syndrome.”

Other adverse events identified already are listed in package inserts, including telavancin-associated acute renal failure; doripenem-associated seizures and thrombocytopenia; boceprevir-associated anemia; maraviroc-associated malignancies and myocardial infarction; and raltegravir-associated hepatitis, the report points out.

“Although clinical trials serve as the gold standard for demonstrating the safety and efficacy of newly approved drugs, unfortunately they allow for study of only a homogenous patient population for a finite period of time and likely do not reflect real-world use,” the authors write. “Furthermore, the number of patients enrolled in drug development trials is not adequate to determine rare, yet serious, adverse events.”

The report adds that, while the AERS database can allow insight into rare adverse events, it lacks the “quantitative exposure estimate to put such rare events into perspective.”

“There appears to be adverse events associated with these antimicrobials approved in the last seven years, including those not identified in package inserts. However, investigative studies are needed to further explore these statistical associations,” the authors write.

U.S. Pharmacist Social Connect