The US Food and Drug Administration (FDA) has approved the antibacterial drug trio imipenem, cilastatin, and relebactam (Recarbrio, Merck) for complicated urinary tract infection (cUTI) and complicated intra-abdominal infection (cIAI) in adults for whom “limited or no treatment options are available.”
“Recarbrio provides an important addition to our toolkit in the ongoing fight against infections caused by certain Gram-negative pathogens,” Keith Kaye, MD, professor of medicine and director of research for the division of infectious diseases, University of Michigan Heath System, and a principal investigator in the clinical program, said in a company news release.
“Recarbrio offers an additional treatment option for patients with cIAI and cUTI who have limited and, in some cases, no alternative therapeutic options,” he added.
The three-drug combination is given by injection that contains previously approved antibiotics — imipenem-cilastatin — and a new beta-lactamase inhibitor, relebactam.
The approval follows consideration of efficacy and safety findings for imipenem-cilastatin from in vitro studies and animal models of infection for relebactam. The safety of the drug trio was studied in one trial of 298 adults with cUTI (99 treated with drug combination) and one trial of 347 adults with cIAI (117 treated with drug combination). Participants received the study drug at the proposed dose, according to an FDA news release.
The most frequently seen adverse events in patients who received imipenem/cilastatin/relebactam were diarrhea, nausea, headache, fever, and elevated liver enzymes.
Patients taking ganciclovir should not take imipenem/cilastatin/relebactamunless the benefits outweigh the risks because there have been reports of generalized seizures. The drug trio should also not be used in those taking valproic acid or divalproex sodium for seizure management because a reduced valproic acid level may result in seizures.
The drug trio is intended for cUTI, including pyelonephritis, resulting from susceptible Gram-negative microorganisms Enterobacter cloacae, Escherichia coli, Klebsiella aerogenes, Klebsiella pneumoniae, and Pseudomonas aeruginosa.
The drug combination is also intended for cIAI resulting from susceptible Gram-negative microorganisms Bacteroides caccae, Bacteroides fragilis, Bacteroides ovatus, Bacteroides stercoris, Bacteroides thetaiotaomicron, Bacteroides uniformis, Bacteroides vulgatus, Citrobacter freundii, Enterobacter cloacae, Escherichia coli, Fusobacterium nucleatum, Klebsiella aerogenes, Klebsiella oxytoca, Klebsiella pneumoniae, Parabacteroides distasonis, and Pseudomonas aeruginosa.
The FDA designated the drug combination a qualified infectious disease product, a designation given to antibacterial and antifungal drugs used in the treatment of serious or potentially fatal infections under the Generating Antibiotic Incentives Now title of the FDA Safety and Innovation Act. The drug product was also given priority review.
The FDA said in the news release that “addressing the threat of antimicrobial-resistant infections” is a “key global challenge” the agency must face. In addition, the FDA is working to facilitate the development of safe and effective new treatments for serious infections.
“The FDA remains focused on facilitating the development of safe and effective new antibacterial drugs to give patients more options to fight serious infections,” Ed Cox, MD, MPH, director for the Office of Antimicrobial Products in the FDA’s Center for Drug Evaluation and Research, said in the release. “It is important that the use of Recarbrio be reserved for situations when there are limited or no alternative antibacterial drugs for treating a patient’s infection.”