Identification
- Summary
Enmetazobactam is a beta-lactamase inhibitor used to treat complicated urinary tract infections in combination with cefepime.
- Brand Names
- Exblifep
- Generic Name
- Enmetazobactam
- DrugBank Accession Number
- DB18716
- Background
Enmetazobactam is a penicillanic acid sulfone extended-spectrum beta (β)-lactamase (ESBL) inhibitor.1 Because ESBL enzymes can hydrolyze important antibiotics such as penicillins, broad-spectrum cephalosporins and monobactams, ESBL-producing bacteria poses challenges in the treatment of serious infections.3
The combination product of enmetazobactam and cefepime was first approved by the FDA on February 23, 2024, for the treatment of complicated urinary tract infections.5 Enmetazobactam is used as cefepime-sparing therapy by preventing its breakdown by ESBL.
- Type
- Small Molecule
- Groups
- Approved
- Structure
Structure for Enmetazobactam (DB18716)
- Weight
- Average: 314.32
Monoisotopic: 314.068490741 - Chemical Formula
- C11H14N4O5S
- Synonyms
- (2s,3s,5r)-3-methyl-3-((3-methyltriazol-3-ium-1-yl)methyl)-4,4,7-trioxo-4^6-thia-1-azabicyclo(3.2.0)heptane-2-carboxylate
- 1h-1,2,3-triazolium, 3-(((2s,3s,5r)-2-carboxy-3-methyl-4,4-dioxido-7-oxo-4-thia-1-azabicyclo(3.2.0)hept-3-yl)methyl)-1-methyl-, inner salt
- External IDs
- AAI 101
- AAI-101
- AAI101
- OCID-5090
Pharmacology
- Indication
In combination with cefepime, enmetazobactam is indicated for the treatment of adults with complicated urinary tract infections (cUTI) including pyelonephritis caused by designated susceptible microorganisms.4
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Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Used in combination to treat Complicated urinary tract infection Combination Product in combination with: Cefepime (DB01413) •••••••••••• ••••• - Contraindications & Blackbox Warnings
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Enmetazobactam is an antibacterial agent that is active against most gram-positive and gram-negative bacteria.4
- Mechanism of action
Extended-spectrum beta-lactamases (ESBLs) are a group of bacterial serine beta-lactamases that hydrolyze third-generation cephalosporins (3GC), leading to the development of 3GC-resistant bacteria.1,2 When used in combination with cefepime, enmetazobactam protects cefepime from degradation by ESBLs and prevents antibiotic resistance.4
Target Actions Organism AExtended-spectrum beta-lactamase PER-1 inhibitorPseudomonas aeruginosa - Absorption
The mean (SD) Cmax is 19.8 (6.3) µg/mL in patients with cUTI and eGFR greater than or equal to 60 mL/min. The mean AUC0-last is 75.3 (30.8) μgxh/mL.4
- Volume of distribution
Mean (SD) steady state volume of distribution (Vss) is 25.26 (9.97) L in patients with cUTI and eGFR greater than or equal to 60 mL/min..4
- Protein binding
The percent protein binding of enmetazobactam is negligible.4
- Metabolism
Enmetazobactam is minimally metabolized.4
- Route of elimination
About 90% of enmetazobactam is excreted unchanged in urine.4
- Half-life
The mean (SD) half-life is 2.6 (1.1) hours in patients with cUTI and eGFR greater than or equal to 60 mL/min.4
- Clearance
The mean (SD) clearance is 7.6 (2.9) L/h in patients with cUTI and eGFR greater than or equal to 60 mL/min.4
- Adverse Effects
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There is limited information on the acute toxicity (LD50) or overdose of enmetazobactam. Symptoms of overdose may include encephalopathy (disturbance of consciousness including confusion, hallucinations, stupor, and coma), myoclonus, seizures, neuromuscular excitability and nonconvulsive status epilepticus. Enmetazobactam can be removed by hemodialysis.4
- 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 softwareAcenocoumarol The risk or severity of bleeding can be increased when Enmetazobactam is combined with Acenocoumarol. Ambroxol The risk or severity of methemoglobinemia can be increased when Enmetazobactam is combined with Ambroxol. Articaine The risk or severity of methemoglobinemia can be increased when Enmetazobactam is combined with Articaine. BCG vaccine The therapeutic efficacy of BCG vaccine can be decreased when used in combination with Enmetazobactam. Benzocaine The risk or severity of methemoglobinemia can be increased when Enmetazobactam is combined with Benzocaine. - Food Interactions
- No interactions found.
Products
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Name Ingredients Dosage Route Labeller Marketing Start Marketing End Region Image Exblifep Enmetazobactam (0.5 g/1) + Cefepime hydrochloride (2 g/1) Injection, powder, for solution Intravenous Allecra Therapeutics SAS 2024-02-28 Not applicable US 
Categories
- Drug Categories
- Classification
- Not classified
- Affected organisms
- Pseudomonas aeruginosa
- Escherichia coli
- Serratia marcescens
- Proteus mirabilis
- Providencia stuartii
- Providencia rettgeri
- Enterobacter cloacae
- Klebsiella pneumoniae
- Klebsiella oxytoca
- Citrobacter freundii
- Klebsiella aerogenes
Chemical Identifiers
- UNII
- 80VUN7L00C
- CAS number
- 1001404-83-6
- InChI Key
- HFZITXBUTWITPT-YWVKMMECSA-N
- InChI
- InChI=1S/C11H14N4O5S/c1-11(6-14-4-3-13(2)12-14)9(10(17)18)15-7(16)5-8(15)21(11,19)20/h3-4,8-9H,5-6H2,1-2H3/t8-,9+,11-/m1/s1
- IUPAC Name
- 1-{[(2S,3S,5R)-2-carboxylato-3-methyl-4,4,7-trioxo-4lambda6-thia-1-azabicyclo[3.2.0]heptan-3-yl]methyl}-3-methyl-1H-1,2,3-triazol-3-ium
- SMILES
- [H][C@@]12CC(=O)N1[C@@H](C([O-])=O)[C@](C)(CN1C=C[N+](C)=N1)S2(=O)=O
References
- General References
- Bernhard F, Odedra R, Sordello S, Cardin R, Franzoni S, Charrier C, Belley A, Warn P, Machacek M, Knechtle P: Pharmacokinetics-Pharmacodynamics of Enmetazobactam Combined with Cefepime in a Neutropenic Murine Thigh Infection Model. Antimicrob Agents Chemother. 2020 May 21;64(6):e00078-20. doi: 10.1128/AAC.00078-20. Print 2020 May 21. [Article]
- Paterson DL, Bonomo RA: Extended-spectrum beta-lactamases: a clinical update. Clin Microbiol Rev. 2005 Oct;18(4):657-86. doi: 10.1128/CMR.18.4.657-686.2005. [Article]
- Rupp ME, Fey PD: Extended spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae: considerations for diagnosis, prevention and drug treatment. Drugs. 2003;63(4):353-65. doi: 10.2165/00003495-200363040-00002. [Article]
- FDA Approved Drug Products: EXBLIFEP (cefepime and enmetazobactam) for injection, for intravenous use [Link]
- Contemporary OB/GYN: FDA approves enmetazobactam for treatment of cUTIs [Link]
- External Links
- ChemSpider
- 68025157
- 2675985
- ChEMBL
- CHEMBL4458276
Clinical Trials
- Clinical Trials
Phase Status Purpose Conditions Count 3 Completed Treatment Urinary Tract Infection 1 2 Completed Treatment Urinary Tract Infection 1 2 Recruiting Treatment Complicated Urinary Tract Infection 1 1 Completed Other Healthy Volunteers (HV) 2 1 Completed Other PK in Patients With Various Degrees of Renal Impairment 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Injection, powder, for solution Intravenous - Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
- Not Available
- Predicted Properties
Property Value Source logP -4.6 Chemaxon pKa (Strongest Acidic) 2.09 Chemaxon pKa (Strongest Basic) 2.83 Chemaxon Physiological Charge 0 Chemaxon Hydrogen Acceptor Count 6 Chemaxon Hydrogen Donor Count 0 Chemaxon Polar Surface Area 116.28 Å2 Chemaxon Rotatable Bond Count 3 Chemaxon Refractivity 111.61 m3·mol-1 Chemaxon Polarizability 28.34 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
- Not Available
- Chromatographic Properties
Collision Cross Sections (CCS)
Not Available
Targets
- Kind
- Protein
- Organism
- Pseudomonas aeruginosa
- Pharmacological action
- Yes
- Actions
- Inhibitor
- Curator comments
- This is a representative organism. Enmetazobactam works against many gram-negative and gram-positive bacteria.
- General Function
- Beta-lactamase activity
- Specific Function
- Not Available
- Gene Name
- per1
- Uniprot ID
- P37321
- Uniprot Name
- Extended-spectrum beta-lactamase PER-1
- Molecular Weight
- 33572.575 Da
References
- FDA Approved Drug Products: EXBLIFEP (cefepime and enmetazobactam) for injection, for intravenous use [Link]
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Steroid hydroxylase activity
- Specific Function
- Metabolizes several precarcinogens, drugs, and solvents to reactive metabolites. Inactivates a number of drugs and xenobiotics and also bioactivates many xenobiotic substrates to their hepatotoxic ...
- Gene Name
- CYP2E1
- Uniprot ID
- P05181
- Uniprot Name
- Cytochrome P450 2E1
- Molecular Weight
- 56848.42 Da
References
- FDA Approved Drug Products: EXBLIFEP (cefepime and enmetazobactam) for injection, for intravenous use [Link]
Drug created at February 26, 2024 21:59 / Updated at February 28, 2024 23:22