Recarbrio (imipenem, cilastatin, and relebactam)

The following drug information is obtained from various newswires, published medical journal articles, and medical conference presentations.

Company:

Approval Status:

Approved July 2019

Specific Treatments:

complicated intra-abdominal and urinary tract infections

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.

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. 

Clinical Results

FDA Approval

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.

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

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).

Additional Information

For additional information regarding complicated intra-abdominal and urinary tract infections or Recarbrio, please visit the Recarbrio web page.