Identification
- Summary
Relebactam is a beta-lactamase inhibitor used to prevent hydrolysis of beta-lactam antibiotics, leading to increased effectiveness.
- Brand Names
- Recarbrio
- Generic Name
- Relebactam
- DrugBank Accession Number
- DB12377
- Background
Relebactam is a diazabicyclooctane beta-lactamase inhibitor, similar in structure to avibactam.5,6 It includes a piperidine ring which reduces export from bacterial cells by producing a positive charge.6 It is currently available in a combination product which includes imipenem and cilastatin to treat complicated urinary tract infections (UTIs), pyelonephritis, and complicated intra-abdominal infections in adults.Label It is considered to be a last-line treatment option and gained FDA approval as part of the combination product RecarbrioⓇ in July 2019.9
- Type
- Small Molecule
- Groups
- Approved, Investigational
- Structure
Structure for Relebactam (DB12377)
- Weight
- Average: 348.37
Monoisotopic: 348.110355554 - Chemical Formula
- C12H20N4O6S
- Synonyms
- Relebactam
- Relebactam anhydrous
- External IDs
- MK-7655
Pharmacology
- Indication
Relebactam is indicated in combination with imipenem and cilastatin for the treatment of complicated urinary tract infections (including pyelonephritis), and complicated intra-abdominal infections caused by susceptible organisms in adults.Label
Reduce drug development failure ratesBuild, train, & validate machine-learning modelswith evidence-based and structured datasets.Build, train, & validate predictive machine-learning models with structured datasets.- Associated Conditions
- Contraindications & Blackbox Warnings
Avoid life-threatening adverse drug eventsImprove clinical decision support with information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events & improve clinical decision support.- Pharmacodynamics
Relebactam prevents the hydrolysis of imipenem, allowing it to exert its bactericidal effect.
- Mechanism of action
Relebactam is a beta-lactamase inhibitor known to inhibit many types of beta-lactamases including Ambler class A and Ambler class C enzymes, helping to prevent imipenem from degrading in the body.Label,3,4,5 Similar to the structurally-related avibactam, first, relebactam binds non-covalently to a beta-lactamase binding site, then, it covalently acylates the serine residue in the active site of the enzyme.2,5,7 In contrast to some other beta-lactamase inhibitors, once relebactam de-acylates from the active site, it can reform it's 5 membered ring and is capable of rebinding to target enzymes.5
Target Actions Organism ABeta-lactamase TEM inhibitorEscherichia coli ABeta-lactamase SHV-1 inhibitorEscherichia coli ABeta-lactamase CTX-M inhibitorEscherichia coli ABeta-lactamase (KPC-2) inhibitorKlebsiella pneumoniae ABeta-lactamase inhibitorEnterobacter cloacae - Absorption
Currently, relebactam is only available as an intravenous product; therefore, there is no relevant absorption data in the literature.
- Volume of distribution
Relebactam has a volume of distribution of approximately 19 L with both single and steady state dosing.Label,1,2
- Protein binding
Relebactam is approximately 22% plasma protein bound.Label,8
- Metabolism
Relebactam does not undergo significant metabolism and can be found mostly unchanged in human plasma.Label
- Route of elimination
Approximately 90-100% of relebactam is renally eliminated.Label,1,2
- Half-life
Relebactam has a half-life of 1.2 hours as per official FDA labeling.Label Values reported in pharmacokinetic studies vary from 1.35-1.8 hours.1,2
- Clearance
Relebactam has a reported total clearance of approximately 130-150 mL/min (8 L/h).Label,1,2 About 30% of the total drug clearance can be attributed to active tubular secretion.Label
- Adverse Effects
Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates.Improve decision support & research outcomes with our structured adverse effects data.- Toxicity
If overdose with the combination product which includes relebactam, imipenem and cilastatin occurs, the drug should be stopped immediately and the patient should be provided with supportive care.Label Relebactam, imipenem, and cilastatin may be removed via hemodialysis; however, the use of hemodialysis to manage cases of overdose has not been studied.Label
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Integrate drug-drug
interactions in your softwareAbemaciclib The excretion of Abemaciclib can be decreased when combined with Relebactam. Acetylsalicylic acid The excretion of Relebactam can be decreased when combined with Acetylsalicylic acid. Acyclovir The excretion of Relebactam can be decreased when combined with Acyclovir. Aminohippuric acid The excretion of Relebactam can be decreased when combined with Aminohippuric acid. Apalutamide The excretion of Relebactam can be decreased when combined with Apalutamide. Ataluren The excretion of Relebactam can be decreased when combined with Ataluren. Avatrombopag The excretion of Relebactam can be decreased when combined with Avatrombopag. Baricitinib The excretion of Relebactam can be decreased when combined with Baricitinib. Benzoic acid The excretion of Relebactam can be decreased when combined with Benzoic acid. Benzylpenicillin The excretion of Relebactam can be decreased when combined with Benzylpenicillin. 
Identify potential medication risksEasily compare up to 40 drugs with our drug interaction checker.Get severity rating, description, and management advice.Learn more - Food Interactions
- No interactions found.
Products
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- Product Ingredients
Ingredient UNII CAS InChI Key Relebactam sodium EX0546AJ8R 1502858-91-4 MMUZXOWPDRLGBD-UXQCFNEQSA-M - Mixture Products
Name Ingredients Dosage Route Labeller Marketing Start Marketing End Region Image Recarbrio Relebactam (250 mg/100mL) + Cilastatin (500 mg/100mL) + Imipenem (500 mg/100mL) Injection, powder, for solution Intravenous Merck Sharp & Dohme Llc 2020-01-06 Not applicable US 
Recarbrio Relebactam (250 mg) + Cilastatin sodium (500 mg) + Imipenem monohydrate (500 mg) Injection, powder, for solution Intravenous Merck Sharp & Dohme B.V. 2020-12-23 Not applicable EU 
Categories
- ATC Codes
- J01DH56 — Imipenem, cilastatin and relebactam
- Drug Categories
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as alpha amino acid amides. These are amide derivatives of alpha amino acids.
- Kingdom
- Organic compounds
- Super Class
- Organic acids and derivatives
- Class
- Carboxylic acids and derivatives
- Sub Class
- Amino acids, peptides, and analogues
- Direct Parent
- Alpha amino acid amides
- Alternative Parents
- Piperidinecarboxamides / 1,3-diazepanes / Imidazolidinones / Organic sulfuric acids and derivatives / Secondary carboxylic acid amides / Dialkylamines / Azacyclic compounds / Organic oxides / Hydrocarbon derivatives / Carbonyl compounds
- Substituents
- 1,3-diazepane / 2-piperidinecarboxamide / Aliphatic heteropolycyclic compound / Alpha-amino acid amide / Amine / Azacycle / Carbonyl group / Carboxamide group / Diazepane / Hydrocarbon derivative
- Molecular Framework
- Aliphatic heteropolycyclic compounds
- External Descriptors
- Not Available
- Affected organisms
- Pseudomonas aeruginosa
- Escherichia coli
- Bacteroides fragilis
- Enterobacter cloacae
- Klebsiella pneumoniae
- Klebsiella oxytoca
- Citrobacter freundii
- Bacteroides thetaiotaomicron
- Klebsiella aerogenes
- Bacteroides caccae
- Bacteroides ovatus
- Bacteroides stercoris
- Bacteroides uniformis
- Bacteroides vulgatus
- Fusobacterium nucleatum
- Parabacteroides distasonis
Chemical Identifiers
- UNII
- 1OQF7TT3PF
- CAS number
- 1174018-99-5
- InChI Key
- SMOBCLHAZXOKDQ-ZJUUUORDSA-N
- InChI
- InChI=1S/C12H20N4O6S/c17-11(14-8-3-5-13-6-4-8)10-2-1-9-7-15(10)12(18)16(9)22-23(19,20)21/h8-10,13H,1-7H2,(H,14,17)(H,19,20,21)/t9-,10+/m1/s1
- IUPAC Name
- [(1R,2S,5R)-7-oxo-2-[(piperidin-4-yl)carbamoyl]-1,6-diazabicyclo[3.2.1]octan-6-yl]oxidanesulfonic acid
- SMILES
- OS(=O)(=O)ON1[C@H]2C[N@]([C@@H](CC2)C(=O)NC2CCNCC2)C1=O
References
- General References
- Rhee EG, Rizk ML, Calder N, Nefliu M, Warrington SJ, Schwartz MS, Mangin E, Boundy K, Bhagunde P, Colon-Gonzalez F, Jumes P, Liu Y, Butterton JR: Pharmacokinetics, Safety, and Tolerability of Single and Multiple Doses of Relebactam, a beta-Lactamase Inhibitor, in Combination with Imipenem and Cilastatin in Healthy Participants. Antimicrob Agents Chemother. 2018 Aug 27;62(9). pii: AAC.00280-18. doi: 10.1128/AAC.00280-18. Print 2018 Sep. [Article]
- Crass RL, Pai MP: Pharmacokinetics and Pharmacodynamics of beta-Lactamase Inhibitors. Pharmacotherapy. 2019 Feb;39(2):182-195. doi: 10.1002/phar.2210. Epub 2019 Jan 20. [Article]
- Papp-Wallace KM, Barnes MD, Alsop J, Taracila MA, Bethel CR, Becka SA, van Duin D, Kreiswirth BN, Kaye KS, Bonomo RA: Relebactam Is a Potent Inhibitor of the KPC-2 beta-Lactamase and Restores Imipenem Susceptibility in KPC-Producing Enterobacteriaceae. Antimicrob Agents Chemother. 2018 May 25;62(6). pii: AAC.00174-18. doi: 10.1128/AAC.00174-18. Print 2018 Jun. [Article]
- Barnes MD, Bethel CR, Alsop J, Becka SA, Rutter JD, Papp-Wallace KM, Bonomo RA: Inactivation of the Pseudomonas-Derived Cephalosporinase-3 (PDC-3) by Relebactam. Antimicrob Agents Chemother. 2018 Apr 26;62(5). pii: AAC.02406-17. doi: 10.1128/AAC.02406-17. Print 2018 May. [Article]
- Zhanel GG, Lawrence CK, Adam H, Schweizer F, Zelenitsky S, Zhanel M, Lagace-Wiens PRS, Walkty A, Denisuik A, Golden A, Gin AS, Hoban DJ, Lynch JP 3rd, Karlowsky JA: Imipenem-Relebactam and Meropenem-Vaborbactam: Two Novel Carbapenem-beta-Lactamase Inhibitor Combinations. Drugs. 2018 Jan;78(1):65-98. doi: 10.1007/s40265-017-0851-9. [Article]
- Jones JA, Virga KG, Gumina G, Hevener KE: Recent Advances in the Rational Design and Optimization of Antibacterial Agents. Medchemcomm. 2016 Sep 1;7(9):1694-1715. doi: 10.1039/C6MD00232C. Epub 2016 Jul 7. [Article]
- Wong D, van Duin D: Novel Beta-Lactamase Inhibitors: Unlocking Their Potential in Therapy. Drugs. 2017 Apr;77(6):615-628. doi: 10.1007/s40265-017-0725-1. [Article]
- Rizk ML, Rhee EG, Jumes PA, Gotfried MH, Zhao T, Mangin E, Bi S, Chavez-Eng CM, Zhang Z, Butterton JR: Intrapulmonary Pharmacokinetics of Relebactam, a Novel beta-Lactamase Inhibitor, Dosed in Combination with Imipenem-Cilastatin in Healthy Subjects. Antimicrob Agents Chemother. 2018 Feb 23;62(3). pii: AAC.01411-17. doi: 10.1128/AAC.01411-17. Print 2018 Mar. [Article]
- FDA Approved Drug Products: Recarbrio (imipenem, cilastatin, and relebactam) for intravenous injection [Link]
- External Links
- PubChem Compound
- 44129647
- PubChem Substance
- 347828625
- ChemSpider
- 31137585
- BindingDB
- 1858
- 2268500
- ChEMBL
- CHEMBL3112741
- ZINC
- ZINC000043206319
- Wikipedia
- Relebactam
- MSDS
- Download (211 KB)
Clinical Trials
- Clinical Trials
Phase Status Purpose Conditions Count 4 Enrolling by Invitation Other Critically Ill Patients / Obesity 1 4 Recruiting Other Bacterial Pneumonia / Cystic Fibrosis (CF) 1 4 Withdrawn Treatment Antibiotic Resistant Infection / Carbapenem-Resistant Enterobacteriaceae Infection / Gram-Negative Bacterial Infections / KPC 1 3 Completed Treatment Bacterial Infections 1 3 Completed Treatment Bacterial Pneumonia 1 3 Completed Treatment Complicated Intra-Abdominal Infections (cIAIs) / Complicated Urinary Tract Infection 1 3 Recruiting Treatment Hospital Acquired Bacterial Pneumonia or Ventilator-Associated Bacterial Pneumonia 1 2 Completed Treatment Intraabdominal Infections 1 2 Completed Treatment Pyelonephritis / Urinary Tract Infection 1 2 Recruiting Treatment Hematopoietic and Lymphoid System Neoplasm / Malignant Solid Neoplasms 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Injection, powder, for solution Intravenous Powder, for solution Intravenous - Prices
- Not Available
- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US8487093 No 2013-07-16 2029-11-19 US
Properties
- State
- Solid
- Experimental Properties
- Not Available
- Predicted Properties
Property Value Source Water Solubility 2.91 mg/mL ALOGPS logP -2 ALOGPS logP -3.1 Chemaxon logS -2.1 ALOGPS pKa (Strongest Acidic) -2 Chemaxon pKa (Strongest Basic) 10.03 Chemaxon Physiological Charge 0 Chemaxon Hydrogen Acceptor Count 6 Chemaxon Hydrogen Donor Count 3 Chemaxon Polar Surface Area 128.28 Å2 Chemaxon Rotatable Bond Count 4 Chemaxon Refractivity 77.54 m3·mol-1 Chemaxon Polarizability 32.83 Å3 Chemaxon Number of Rings 3 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter No Chemaxon Veber's Rule No Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
- Not Available
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted GC-MS Spectrum - GC-MS Predicted GC-MS Not Available Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS Not Available
Targets
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Use our structured and evidence-based datasets to unlock newinsights and accelerate drug research.
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- Kind
- Protein
- Organism
- Escherichia coli
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- TEM-type are the most prevalent beta-lactamases in enterobacteria; they hydrolyze the beta-lactam bond in susceptible beta-lactam antibiotics, thus conferring resistance to penicillins and cephalosporins. TEM-3 and TEM-4 are capable of hydrolyzing cefotaxime and ceftazidime. TEM-5 is capable of hydrolyzing ceftazidime. TEM-6 is capable of hydrolyzing ceftazidime and aztreonam. TEM-8/CAZ-2, TEM-16/CAZ-7 and TEM-24/CAZ-6 are markedly active against ceftazidime. IRT-4 shows resistance to beta-lactamase inhibitors.
- Specific Function
- Beta-lactamase activity
- Gene Name
- bla
- Uniprot ID
- P62593
- Uniprot Name
- Beta-lactamase TEM
- Molecular Weight
- 31514.865 Da
References
- Zhanel GG, Lawrence CK, Adam H, Schweizer F, Zelenitsky S, Zhanel M, Lagace-Wiens PRS, Walkty A, Denisuik A, Golden A, Gin AS, Hoban DJ, Lynch JP 3rd, Karlowsky JA: Imipenem-Relebactam and Meropenem-Vaborbactam: Two Novel Carbapenem-beta-Lactamase Inhibitor Combinations. Drugs. 2018 Jan;78(1):65-98. doi: 10.1007/s40265-017-0851-9. [Article]
- Kind
- Protein
- Organism
- Escherichia coli
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Beta-lactamase activity
- Specific Function
- Not Available
- Gene Name
- bla
- Uniprot ID
- P0AD63
- Uniprot Name
- Beta-lactamase SHV-1
- Molecular Weight
- 31223.635 Da
References
- Zhanel GG, Lawrence CK, Adam H, Schweizer F, Zelenitsky S, Zhanel M, Lagace-Wiens PRS, Walkty A, Denisuik A, Golden A, Gin AS, Hoban DJ, Lynch JP 3rd, Karlowsky JA: Imipenem-Relebactam and Meropenem-Vaborbactam: Two Novel Carbapenem-beta-Lactamase Inhibitor Combinations. Drugs. 2018 Jan;78(1):65-98. doi: 10.1007/s40265-017-0851-9. [Article]
- Kind
- Protein group
- Organism
- Escherichia coli
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Not Available
- Specific Function
- Beta-lactamase activity
Components:
References
- Zhanel GG, Lawrence CK, Adam H, Schweizer F, Zelenitsky S, Zhanel M, Lagace-Wiens PRS, Walkty A, Denisuik A, Golden A, Gin AS, Hoban DJ, Lynch JP 3rd, Karlowsky JA: Imipenem-Relebactam and Meropenem-Vaborbactam: Two Novel Carbapenem-beta-Lactamase Inhibitor Combinations. Drugs. 2018 Jan;78(1):65-98. doi: 10.1007/s40265-017-0851-9. [Article]
- Kind
- Protein
- Organism
- Klebsiella pneumoniae
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Not Available
- Specific Function
- Beta-lactamase activity
- Gene Name
- KPC-2
- Uniprot ID
- Q93LQ9
- Uniprot Name
- Beta-lactamase
- Molecular Weight
- 31114.99 Da
References
- Zhanel GG, Lawrence CK, Adam H, Schweizer F, Zelenitsky S, Zhanel M, Lagace-Wiens PRS, Walkty A, Denisuik A, Golden A, Gin AS, Hoban DJ, Lynch JP 3rd, Karlowsky JA: Imipenem-Relebactam and Meropenem-Vaborbactam: Two Novel Carbapenem-beta-Lactamase Inhibitor Combinations. Drugs. 2018 Jan;78(1):65-98. doi: 10.1007/s40265-017-0851-9. [Article]
- Kind
- Protein
- Organism
- Enterobacter cloacae
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Beta-lactamase activity
- Specific Function
- This protein is a serine beta-lactamase with a substrate specificity for cephalosporins.
- Gene Name
- ampC
- Uniprot ID
- P05364
- Uniprot Name
- Beta-lactamase
- Molecular Weight
- 41301.33 Da
References
- Zhanel GG, Lawrence CK, Adam H, Schweizer F, Zelenitsky S, Zhanel M, Lagace-Wiens PRS, Walkty A, Denisuik A, Golden A, Gin AS, Hoban DJ, Lynch JP 3rd, Karlowsky JA: Imipenem-Relebactam and Meropenem-Vaborbactam: Two Novel Carbapenem-beta-Lactamase Inhibitor Combinations. Drugs. 2018 Jan;78(1):65-98. doi: 10.1007/s40265-017-0851-9. [Article]
Transporters
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Sodium-independent organic anion transmembrane transporter activity
- Specific Function
- Plays an important role in the excretion/detoxification of endogenous and exogenous organic anions, especially from the brain and kidney. Involved in the transport basolateral of steviol, fexofenad...
- Gene Name
- SLC22A8
- Uniprot ID
- Q8TCC7
- Uniprot Name
- Solute carrier family 22 member 8
- Molecular Weight
- 59855.585 Da
References
- Chan G, Houle R, Lin M, Yabut J, Cox K, Wu J, Chu X: Role of transporters in the disposition of a novel beta-lactamase inhibitor: relebactam (MK-7655). J Antimicrob Chemother. 2019 Jul 1;74(7):1894-1903. doi: 10.1093/jac/dkz101. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Sodium-independent organic anion transmembrane transporter activity
- Specific Function
- Mediates saturable uptake of estrone sulfate, dehydroepiandrosterone sulfate and related compounds.
- Gene Name
- SLC22A11
- Uniprot ID
- Q9NSA0
- Uniprot Name
- Solute carrier family 22 member 11
- Molecular Weight
- 59970.945 Da
References
- Chan G, Houle R, Lin M, Yabut J, Cox K, Wu J, Chu X: Role of transporters in the disposition of a novel beta-lactamase inhibitor: relebactam (MK-7655). J Antimicrob Chemother. 2019 Jul 1;74(7):1894-1903. doi: 10.1093/jac/dkz101. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Monovalent cation:proton antiporter activity
- Specific Function
- Solute transporter for tetraethylammonium (TEA), 1-methyl-4-phenylpyridinium (MPP), cimetidine, N-methylnicotinamide (NMN), metformin, creatinine, guanidine, procainamide, topotecan, estrone sulfat...
- Gene Name
- SLC47A1
- Uniprot ID
- Q96FL8
- Uniprot Name
- Multidrug and toxin extrusion protein 1
- Molecular Weight
- 61921.585 Da
References
- Chan G, Houle R, Lin M, Yabut J, Cox K, Wu J, Chu X: Role of transporters in the disposition of a novel beta-lactamase inhibitor: relebactam (MK-7655). J Antimicrob Chemother. 2019 Jul 1;74(7):1894-1903. doi: 10.1093/jac/dkz101. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Drug transmembrane transporter activity
- Specific Function
- Solute transporter for tetraethylammonium (TEA), 1-methyl-4-phenylpyridinium (MPP), cimetidine, N-methylnicotinamide, metformin, creatinine, guanidine, procainamide, topotecan, estrone sulfate, acy...
- Gene Name
- SLC47A2
- Uniprot ID
- Q86VL8
- Uniprot Name
- Multidrug and toxin extrusion protein 2
- Molecular Weight
- 65083.915 Da
References
- Chan G, Houle R, Lin M, Yabut J, Cox K, Wu J, Chu X: Role of transporters in the disposition of a novel beta-lactamase inhibitor: relebactam (MK-7655). J Antimicrob Chemother. 2019 Jul 1;74(7):1894-1903. doi: 10.1093/jac/dkz101. [Article]
Drug created at October 20, 2016 22:08 / Updated at February 21, 2021 18:53