FDA News

FDA approves Recarbrio for complicated UTIs, intra-abdominal infections

Photo of Keith Kaye
Keith S. Kaye

The FDA approved Merck’s three-drug combination antibiotic injection, Recarbrio, for the treatment of complicated UTIs and complicated intra-abdominal infections.

According to Merck, the antibiotic is indicated for patients aged 18 years or older who have limited or no alternative treatment options for complicated UTIs (cUTIs), including acute pyelonephritis, and complicated intra-abdominal infections (cIAIs) caused by specified gram-negative bacteria, including carbapenem-resistant Enterobacteriaceae (CRE).

“Today, we now have a toolkit of therapeutics, that includes a few different agents to choose from that provide safer, effective alternatives for the treatment of CRE and other resistant gram-negatives,” Keith S. Kaye, MD, MPH, Infectious Disease News Editorial Board member and professor of internal medicine and director of clinical research in the division of infectious diseases at the University of Michigan Medical School, told Infectious Disease News.

Recarbrio contains imipenem/cilastatin and relebactam, a new beta-lactamase inhibitor.

“Imipenem-relebactam offers a unique choice within this newer class of advanced beta-lactam and beta-lactamase inhibitor (BLI) combinations,” Kaye said.

“It couples an old-school carbapenem (imipenem) with a relatively broad-spectrum BLI. The fact that it is an inhibitor that can inhibit [Klebsiella pneumoniae carbapenemase], [extended-spectrum beta-lactamases (ESBLs)] and cephalosporinases like AmpC is unique. In doing so, it not only provides enhanced activity against ESBLs and CREs, it also, in some cases, restores susceptibility of imipenem against Pseudomonas.”

Two trials assessed Recarbrio’s safety — one included patients with cUTIs, and the other patients with cIAIs. The most common side effects reported were nausea, diarrhea, headache, fever and increased liver enzymes, and some patients taking ganciclovir reported generalized seizures.

Patients taking ganciclovir should not use Recarbrio “unless the benefits outweigh the risks,” the FDA said. Patients taking valproic acid or divalproex sodium also should avoid Recarbrio to prevent possible seizures, according to the agency.

“This agent is a welcome treatment alternative for resistant gram-negatives, including CRE, ESBLs and P. aerunginosa,” Kaye said. “From an efficacy perspective in term of clinical outcomes such as mortality, there is a significant advantage to using imipenem-relebactam compared to imipenem plus colistin. Also, from a safety and a nephrotoxicity perspective, there are notable advantages.

“This points to the fact that while colistin is an important antimicrobial that we have had to lean on historically for treatment of resistant pathogens like CRE, newer agents like imipenem-relebactam not only offer a safety advantage in term so nephrotoxicity but also offer a [pharmacokinetic/pharmacodynamic] advantage in terms of safely attainable effective levels in the serum and anatomic locations of active infection.” – by Marley Ghizzone

Disclosures: Kaye reports receiving funding from the NIH and Agency for Healthcare Research and Quality and grant support from Merck, and serving as a consultant for Allergan, Melinta, Merck, Nabriva, Shinogi and Xellia.

Photo of Keith Kaye
Keith S. Kaye

The FDA approved Merck’s three-drug combination antibiotic injection, Recarbrio, for the treatment of complicated UTIs and complicated intra-abdominal infections.

According to Merck, the antibiotic is indicated for patients aged 18 years or older who have limited or no alternative treatment options for complicated UTIs (cUTIs), including acute pyelonephritis, and complicated intra-abdominal infections (cIAIs) caused by specified gram-negative bacteria, including carbapenem-resistant Enterobacteriaceae (CRE).

“Today, we now have a toolkit of therapeutics, that includes a few different agents to choose from that provide safer, effective alternatives for the treatment of CRE and other resistant gram-negatives,” Keith S. Kaye, MD, MPH, Infectious Disease News Editorial Board member and professor of internal medicine and director of clinical research in the division of infectious diseases at the University of Michigan Medical School, told Infectious Disease News.

Recarbrio contains imipenem/cilastatin and relebactam, a new beta-lactamase inhibitor.

“Imipenem-relebactam offers a unique choice within this newer class of advanced beta-lactam and beta-lactamase inhibitor (BLI) combinations,” Kaye said.

“It couples an old-school carbapenem (imipenem) with a relatively broad-spectrum BLI. The fact that it is an inhibitor that can inhibit [Klebsiella pneumoniae carbapenemase], [extended-spectrum beta-lactamases (ESBLs)] and cephalosporinases like AmpC is unique. In doing so, it not only provides enhanced activity against ESBLs and CREs, it also, in some cases, restores susceptibility of imipenem against Pseudomonas.”

Two trials assessed Recarbrio’s safety — one included patients with cUTIs, and the other patients with cIAIs. The most common side effects reported were nausea, diarrhea, headache, fever and increased liver enzymes, and some patients taking ganciclovir reported generalized seizures.

Patients taking ganciclovir should not use Recarbrio “unless the benefits outweigh the risks,” the FDA said. Patients taking valproic acid or divalproex sodium also should avoid Recarbrio to prevent possible seizures, according to the agency.

“This agent is a welcome treatment alternative for resistant gram-negatives, including CRE, ESBLs and P. aerunginosa,” Kaye said. “From an efficacy perspective in term of clinical outcomes such as mortality, there is a significant advantage to using imipenem-relebactam compared to imipenem plus colistin. Also, from a safety and a nephrotoxicity perspective, there are notable advantages.

“This points to the fact that while colistin is an important antimicrobial that we have had to lean on historically for treatment of resistant pathogens like CRE, newer agents like imipenem-relebactam not only offer a safety advantage in term so nephrotoxicity but also offer a [pharmacokinetic/pharmacodynamic] advantage in terms of safely attainable effective levels in the serum and anatomic locations of active infection.” – by Marley Ghizzone

Disclosures: Kaye reports receiving funding from the NIH and Agency for Healthcare Research and Quality and grant support from Merck, and serving as a consultant for Allergan, Melinta, Merck, Nabriva, Shinogi and Xellia.