Recarbrio (imipenem, cilastatin, and relebactam) - 4 indications

Scroll down for information on each indication:

• for the treatment of complicated intra-abdominal and urinary tract infections; approved July 2019
• for hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia; approved June of 2020

General Information

Recarbrio is a combination of imipenem, a penem antibacterial, cilastatin, a renal dehydropeptidase inhibitor, and relebactam, a betalactamase inhibitor.

Recarbrio is specifically indicated for the following:

• Complicated Urinary Tract Infections (cUTI), including Pyelonephritis, in patients 18 years of age and older who have limited or no alternative treatment options, for the treatment of complicated urinary tract infections (cUTI), including pyelonephritis, caused by the following susceptible gram-negative microorganisms: Enterobacter cloacae, Escherichia coli, Klebsiella aerogenes, Klebsiella pneumoniae, and Pseudomonas aeruginosa.
• Complicated Intra-abdominal Infections (cIAI) in patients 18 years of age and older who have limited or no alternative treatment options for the treatment of complicated intra-abdominal infections (cIAI) caused by the following 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.
• to treat hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia (HABP/VABP) in patients 18 years of age and older caused by the following susceptible Gram-negative microorganisms: Acinetobacter calcoaceticus-baumannii complex, Enterobacter cloacae, Escherichia coli, Haemophilus influenzae, Klebsiella aerogenes, Klebsiella oxytoca, Klebsiella pneumoniae, Pseudomonas aeruginosa and Serratia marcescens

Recarbrio is supplied as a solution for intravenous infusion. The recommended dose is 1.25 grams (imipenem 500mg, cilastatin 500 mg, and relebactam 250 mg) administered by intravenous (IV) infusion over 30 minutes every 6 hours in patients 18 years of age and older with creatinine clearance (CLcr) of 90 mL/min or greater. A dose reduction is recommended for patients with CLcr less than 90 mL/min. The severity and location of infection, as well as clinical response should guide the duration of therapy. Please see drug label for specific dose adjustments. The recommended duration of treatment with Recarbrio is 4 days to 14 days. 

Mechanism of Action

Recarbrio is a combination of imipenem, a penem antibacterial, cilastatin, a renal dehydropeptidase inhibitor, and relebactam, a betalactamase inhibitor. Cilastatin limits the renal metabolism of imipenem and does not have antibacterial activity. The bactericidal activity of imipenem results from binding to PBP 2 and PBP 1B in Enterobacteriaceae and Pseudomonas aeruginosa and the subsequent inhibition of penicillin binding proteins (PBPs). Inhibition of PBPs leads to the disruption of bacterial cell wall synthesis. Imipenem is stable in the presence of some beta lactamases. Relebactam has no intrinsic antibacterial activity. Relebactam protects imipenem from degradation by certain serine beta lactamases such as Sulhydryl Variable (SHV), Temoneira (TEM), Cefotaximase-Munich (CTX-M), Enterobacter cloacae P99 (P99), Pseudomonas-derived cephalosporinase (PDC), and Klebsiella-pneumoniae carbapenemase (KPC).

Side Effects

Adverse effects associated with the use of Recarbrio may include, but are not limited to, the following:

• diarrhea
• nausea
• headache
• vomiting
• alanine aminotransferase increased
• aspartate aminotransferase increased
• phlebitis/infusion site reactions
• pyrexia
• hypertension

Indications 1 and 2 - for the treatment of complicated intra-abdominal and urinary tract infections

approved July 2019

Clinical Trial Results

The determination of efficacy and safety of Recarbrio was supported in part by the previous findings of the efficacy and safety of imipenem/cilastatin for the treatment of cIAI and cUTI. The contribution of relebactam to Recarbrio was primarily established in vitro and in animal models of infection. Imipenem/cilastatin plus relebactam was studied in cIAI and cUTI including pyelonephritis in randomized, blinded, active-controlled, multicenter trials. These trials provided only limited efficacy and safety information.

Indications 3 and 4 - for hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia

approved June of 2020

Clinical Trial Results

The FDA approval of Recarbrio for HABP/VABP was based on results of the pivotal Phase 3 RESTORE-IMI 2 trial that compared Recarbrio 1.25 grams (imipenem 500 mg/cilastatin 500 mg/relebactam 250 mg) to piperacillin/tazobactam 4.5 grams (PIP/TAZ, piperacillin 4000 mg/tazobactam 500 mg), each administered intravenously every six hours for seven to 14 days, for the treatment of adult patients with HABP/VABP. Recarbrio met the primary and key secondary endpoints, demonstrating non-inferiority to PIP/TAZ in 28-day all-cause mortality and clinical response at early follow-up, respectively.