RECARBRIO

(imipenem, cilastatin, and relebactam) for injection 1.25 g

Mechanism of action

Discover RECARBRIO: A broad-coverage carbapenem/novel BLI combination

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Discover RECARBRIO

RECARBRIO®. Imipenem: A broad-coverage carbapenem; Cilastatin: Renal dehydropeptidase inhibitor; Relebactam: A novel betalactamase inhibitor that helps restore the activity of imipenem Chart: Percent of isolates susceptible in vitro
aIsolates collected from intra-abdominal and urinary tract infection samples in the United States from 2015 to 2017 for the SMART surveillance program.

The clinical significance of in vitro data is unknown.

Mechanisms of beta lactam resistance in gram-negative organisms include the production of beta-lactamases, up-regulation of efflux pumps, and loss of outer membrane porins. lmipenem/relebactam retains activity in the presence of the tested efflux pumps. lmipenem/relebactam has shown activity against some isolates of P. aeruginosa and Enterobacteriaceae that produce relebactam-susceptible beta­lactamases concomitant with loss of entry porins. lmipenem/relebactam is not active against isolates containing metallo-beta-lactamases (MBLs), oxacillinases with carbapenemase activity, as well as certain alleles of GES.

Methicillin-resistant staphylococci should be considered resistant to imipenem. lmipenem is inactive in vitro against Enterococcus faecium, Stenotrophomonas maltophilia, and some isolates of Burkholderia cepacia.

Antimicrobial activity

RECARBRIO™ (imipenem, cilastatin, and relebactam) has been shown to be active against most isolates of the following bacteria, both in vitro and in clinical infections.

Hospital-acquired Bacterial Pneumonia and Ventilator-associated Bacterial Pneumonia (HABP/VABP)
Aerobic Bacteria
Gram-negative Bacteria
  • Acinetobacter calcoaceticus-baumannii complex
  • Enterobacter cloacae
  • Escherichia coli
  • Haemophilus influenzae
  • Klebsiella aerogenes
  • Klebsiella oxytoca
  • Klebsiella pneumoniae
  • Pseudomonas aeruginosa
  • Serratia marcescens
Complicated Urinary Tract Infections (cUTI)
Aerobic Bacteria
Gram-negative Bacteria
  • Enterobacter cloacae
  • Escherichia coli
  • Klebsiella aerogenes
  • Klebsiella pneumoniae
  • Pseudomonas aeruginosa
Complicated Intra-abdominal Infections (cIAI)
Aerobic Bacteria
Gram-negative Bacteria
  • Citrobacter freundii
  • Enterobacter cloacae
  • Escherichia coli
  • Klebsiella aerogenes
  • Klebsiella oxytoca
  • Klebsiella pneumoniae
  • Pseudomonas aeruginosa
Anaerobic Bacteria
Gram-negative Bacteria
  • Bacteroides caccae
  • Bacteroides fragilis
  • Bacteroides ovatus
  • Bacteroides stercoris
  • Bacteroides thetaiotaomicron
  • Bacteroides uniformis
  • Bacteroides vulgatus
  • Fusobacterium nucleatum
  • Parabacteroides distasonis
Reference

1. Karlowsky JA et al. J Glob Antimicrob Resist.2020;21:223-228.

Indications

RECARBRIO is indicated for the treatment of patients 18 years of age and older with hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia (HABP/VABP), 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 indicated 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.

RECARBRIO is indicated 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.

Approval of the cUTI and cIAI indications is based on limited clinical safety and efficacy data for RECARBRIO.

Usage

To reduce the development of drug-resistant bacteria and maintain the effectiveness of RECARBRIO and other antibacterial drugs, RECARBRIO should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy.

Selected Safety Information

  • Hypersensitivity Reactions: RECARBRIO is contraindicated in patients with a history of known severe hypersensitivity (severe systemic allergic reaction such as anaphylaxis) to any component of RECARBRIO. Serious and occasionally fatal hypersensitivity (anaphylactic) reactions have been reported in patients receiving therapy with beta-lactams. Before initiating therapy with RECARBRIO, careful inquiry should be made concerning previous hypersensitivity reactions to carbapenems, penicillins, cephalosporins, other beta-lactams, and other allergens. If a hypersensitivity reaction to RECARBRIO occurs, discontinue the therapy immediately.
  • Seizures and Other Central Nervous System (CNS) Adverse Reactions: CNS adverse reactions, such as seizures, confusional states, and myoclonic activity, have been reported during treatment with imipenem/cilastatin, a component of RECARBRIO, especially when recommended dosages of imipenem were exceeded. These have been reported most commonly in patients with CNS disorders (eg, brain lesions or history of seizures) and/or compromised renal function.
  • Anticonvulsant therapy should be continued in patients with known seizure disorders. If CNS adverse reactions including seizures occur, patients should undergo a neurological evaluation to determine whether RECARBRIO should be discontinued.
  • Increased Seizure Potential Due to Interaction with Valproic Acid: Concomitant use of RECARBRIO, with valproic acid or divalproex sodium may increase the risk of breakthrough seizures. Avoid concomitant use of RECARBRIO with valproic acid or divalproex sodium or consider alternative antibacterial drugs other than carbapenems.
  • Clostridioides difficile–Associated Diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including RECARBRIO, and may range in severity from mild diarrhea to fatal colitis. Careful medical history is necessary since CDAD has been reported to occur over two months after the administration of antibacterial agents. If CDAD is suspected or confirmed, ongoing antibacterial drug use not directed against C difficile may need to be discontinued.
  • Development of Drug-Resistant Bacteria: Prescribing RECARBRIO in the absence of a proven or strongly suspected bacterial infection or prophylactic indication is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria.
  • Adverse Reactions: The most frequently reported adverse reactions occurring in ≥2% of cUTI and cIAI patients treated with RECARBRIO were diarrhea (6%), nausea (6%), headache (4%), vomiting (3%), alanine aminotransferase increased (3%), aspartate aminotransferase increased (3%), phlebitis/infusion site reactions (2%), pyrexia (2%), and hypertension (2%). The most frequently reported adverse reactions occurring in ≥5% of HABP/VABP patients treated with RECARBRIO were aspartate aminotransferase increased (11.7%), anemia (10.5%), alanine aminotransferase increased (9.8%), diarrhea (7.9%), hypokalemia (7.9%), and hyponatremia (6.4%).
US-TIX-0025801/21