Identification
- Summary
Eravacycline is a tetracycline antibiotic used to treat complicated intra-abdominal infections.
- Brand Names
- Xerava
- Generic Name
- Eravacycline
- DrugBank Accession Number
- DB12329
- Background
Eravacycline, known as Xerava by Tetraphase Pharmaceuticals, is a fully synthetic fluorocycline antibiotic of the tetracycline class with activity against clinically significant gram-negative, gram-positive aerobic, and facultative bacteria. This includes most of those bacteria resistant to cephalosporins, fluoroquinolones, β-lactam/β-lactamase inhibitors, multidrug-resistant strains, and carbapenem-resistant Enterobacteriaceae, and the majority of anaerobic pathogens 1. It was first approved by the FDA on August 27, 2018 4. Eravacycline has demonstrated superior potency to that of antibiotics that are currently being marketed for intraabdominal infections 3.
- Type
- Small Molecule
- Groups
- Approved, Investigational
- Structure
Structure for Eravacycline (DB12329)
- Weight
- Average: 558.563
Monoisotopic: 558.212592137 - Chemical Formula
- C27H31FN4O8
- Synonyms
- Eravacyclina
- Eravacycline
- Eravacyclinum
- External IDs
- TP-434
Pharmacology
- Indication
Eravacycline is a tetracycline class antibacterial indicated for the treatment of complicated intra-abdominal infections in patients 18 years of age and older Label.
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Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Treatment of Intraabdominal infections •••••••••••• - Contraindications & Blackbox Warnings
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Eravacycline is an antibiotic that disrupts bacterial protein synthesis, treating complicated intraabdominal infections Label.
- Mechanism of action
Eravacycline is a fluorocycline antibacterial of the tetracycline class of antibacterial drugs. Eravacycline disrupts bacterial protein synthesis by binding to the 30S ribosomal subunit, preventing the incorporation of amino acid residues into elongating peptide chains. In general, eravacycline is bacteriostatic against gram-positive bacteria (e.g., Staphylococcus aureus and Enterococcus faecalis); however, in vitro bactericidal activity has been shown against certain strains of Escherichia coli and Klebsiella pneumoniae Label.
Target Actions Organism A30S ribosomal protein S4 inhibitorEscherichia coli (strain K12) - Absorption
Following single-dose intravenous administration, eravacycline AUC (area under the curve) and Cmax (maximum concentration) increase dose-proportionally for doses from 1 mg/kg - 3 mg/kg (3 times the approved dose). There is approximately 45% accumulation following intravenous dosing of 1 mg/kg every 12 hours Label.
- Volume of distribution
The volume of distribution at steady-state is approximately 321 L Label.
- Protein binding
Protein binding of eravacycline to human plasma proteins increases with increasing plasma concentrations, with 79% to 90% (bound) at plasma concentrations ranging from 100 to 10,000 ng/mL Label.
- Metabolism
Eravacycline is metabolized primarily by CYP3A4- and FMO-mediated oxidation Label.
- Route of elimination
Following a single intravenous dose of radiolabeled eravacycline 60 mg, approximately 34% of the dose is excreted in urine and 47% in feces as unchanged eravacycline (20% in urine and 17% in feces) and metabolites Label.
- Half-life
The mean elimination half-life is 20 hours Label.
- Clearance
17.82 L/min (standard deviation of 3.4) 2.
- Adverse Effects
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The most common adverse reactions (incidence ≥ 3%) are infusion site reactions, nausea, and vomiting Label. Less common (incidence ≥ 1%) adverse effects are palpitations, chest pain, acute pancreatitis, pancreatic necrosis, hypocalcemia, dizziness, dysgeusia, anxiety, insomnia, depression, pleural effusion, dyspnea, rash and hyperhidrosis Label.
The following are various side effects that may occur due to eravacycline use Label:
Hypersensitivity: Life-threatening anaphylaxis has been reported with the administration of eravacycline. Antibacterial drugs and should be avoided in patients with known hypersensitivity to tetracycline-class antibacterial drugs Label.
Tooth Discoloration/enamel hypoplasia: The use of this drug during tooth development (last half of pregnancy, infancy and childhood to the age of 8 years) may lead to the permanent discoloration of teeth (yellow-grey-brown) Label.
Inhibition of bone growth: The use of eravacycline during the second and third trimester of pregnancy, infancy and childhood until the age of 8 years old may cause reversible inhibition of bone growth. All tetracyclines form a stable calcium complex in bone-forming tissue Label.
Clostridium difficile-Associated diarrhea: Clostridium difficile associated diarrhea (CDAD) has been reported with use of the majority of antibacterial agents, and may range in severity from mild diarrhea to fatal colitis. Treatment with antibacterial agents changes the normal flora of the colon, leading to an overgrowth of C. difficile.
Tetracycline class adverse reactions: This drug is structurally similar to tetracycline-class antibacterial drugs and may have similar adverse reactions. Adverse reactions including photosensitivity, pseudotumor cerebri, and anti-anabolic action which has led to increased BUN, azotemia, acidosis, hyperphosphatemia, pancreatitis, and abnormal liver function tests, have been reported for other tetracycline-class antibacterial agents, and may occur with eravacycline. Discontinue eravacycline if any of these adverse reactions are suspected or observed Label.
Potential for microbial overgrowth: The use of eravacycline may result in overgrowth of non-susceptible organisms, including fungi. If such infections occur, discontinue eravacycline and manage with appropriate therapy Label.
Development of drug-resistant bacteria: Prescribing eravacycline in the absence of a proven or strongly suspected bacterial infection is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria Label.
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs Browse all" title="About SNP Mediated Effects/ADRs" id="snp-actions-info" class="drug-info-popup" href="javascript:void(0);">
- Not Available
Interactions
- Drug Interactions Learn More" title="About Drug Interactions" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">
- 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 softwareAbametapir The serum concentration of Eravacycline can be increased when it is combined with Abametapir. Acenocoumarol Eravacycline may increase the anticoagulant activities of Acenocoumarol. Acitretin The risk or severity of pseudotumor cerebri can be increased when Acitretin is combined with Eravacycline. Alitretinoin The risk or severity of pseudotumor cerebri can be increased when Alitretinoin is combined with Eravacycline. Ambroxol The risk or severity of methemoglobinemia can be increased when Eravacycline is combined with Ambroxol. - Food Interactions
- Avoid St. John's Wort. This herb induces CYP3A metabolism and may reduce serum levels of eravacycline. Dose adjustment may be necessary for co-administration.
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 Eravacycline dihydrochloride WK1NMH89VJ 1334714-66-7 JYCNMRVZELJVAW-RZVFYPHASA-N - Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Xerava Injection, powder, for solution 100 mg Intravenous Paion Deutschland Gmb H 2022-05-04 Not applicable EU 
Xerava Injection, powder, for solution 50 mg Intravenous Paion Deutschland Gmb H 2020-12-16 Not applicable EU Xerava Injection, powder, lyophilized, for solution 50 mg/1 Intravenous Tetraphase Pharmaceuticals, Inc. 2018-09-10 Not applicable US 
Xerava Injection, powder, for solution 100 mg Intravenous Paion Deutschland Gmb H 2022-05-04 Not applicable EU Xerava Injection, powder, for solution 50 mg Intravenous Paion Deutschland Gmb H 2020-12-16 Not applicable EU
Categories
- ATC Codes
- J01AA13 — Eravacycline
- J01AA — Tetracyclines
- J01A — TETRACYCLINES
- J01 — ANTIBACTERIALS FOR SYSTEMIC USE
- J — ANTIINFECTIVES FOR SYSTEMIC USE
- Drug Categories
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as tetracyclines. These are polyketides having an octahydrotetracene-2-carboxamide skeleton, substituted with many hydroxy and other groups.
- Kingdom
- Organic compounds
- Super Class
- Phenylpropanoids and polyketides
- Class
- Tetracyclines
- Sub Class
- Not Available
- Direct Parent
- Tetracyclines
- Alternative Parents
- Naphthacenes / Anthracenecarboxylic acids and derivatives / Alpha amino acid amides / Tetralins / P-fluorophenols / Aryl ketones / N-arylamides / Aralkylamines / Cyclohexenones / Aryl fluorides show 12 more
- Substituents
- 4-fluorophenol / 4-halophenol / Alcohol / Alpha-amino acid amide / Alpha-amino acid or derivatives / Amine / Amino acid or derivatives / Anthracene carboxylic acid or derivatives / Aralkylamine / Aromatic heteropolycyclic compound show 35 more
- Molecular Framework
- Aromatic heteropolycyclic compounds
- External Descriptors
- Not Available
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- 07896928ZC
- CAS number
- 1207283-85-9
- InChI Key
- HLFSMUUOKPBTSM-ISIOAQNYSA-N
- InChI
- InChI=1S/C27H31FN4O8/c1-31(2)20-13-8-11-7-12-14(28)9-15(30-16(33)10-32-5-3-4-6-32)21(34)18(12)22(35)17(11)24(37)27(13,40)25(38)19(23(20)36)26(29)39/h9,11,13,20,34,36-37,40H,3-8,10H2,1-2H3,(H2,29,39)(H,30,33)/t11-,13-,20-,27-/m0/s1
- IUPAC Name
- (4S,4aS,5aR,12aS)-4-(dimethylamino)-7-fluoro-3,10,12,12a-tetrahydroxy-1,11-dioxo-9-[2-(pyrrolidin-1-yl)acetamido]-1,4,4a,5,5a,6,11,12a-octahydrotetracene-2-carboxamide
- SMILES
- [H][C@@]12CC3=C(F)C=C(NC(=O)CN4CCCC4)C(O)=C3C(=O)C1=C(O)[C@]1(O)C(=O)C(C(N)=O)=C(O)[C@@H](N(C)C)[C@]1([H])C2
References
- General References
- Solomkin J, Evans D, Slepavicius A, Lee P, Marsh A, Tsai L, Sutcliffe JA, Horn P: Assessing the Efficacy and Safety of Eravacycline vs Ertapenem in Complicated Intra-abdominal Infections in the Investigating Gram-Negative Infections Treated With Eravacycline (IGNITE 1) Trial: A Randomized Clinical Trial. JAMA Surg. 2017 Mar 1;152(3):224-232. doi: 10.1001/jamasurg.2016.4237. [Article]
- Connors KP, Housman ST, Pope JS, Russomanno J, Salerno E, Shore E, Redican S, Nicolau DP: Phase I, open-label, safety and pharmacokinetic study to assess bronchopulmonary disposition of intravenous eravacycline in healthy men and women. Antimicrob Agents Chemother. 2014;58(4):2113-8. doi: 10.1128/AAC.02036-13. Epub 2014 Jan 27. [Article]
- Thakare R, Dasgupta A, Chopra S: Eravacycline for the treatment of patients with bacterial infections. Drugs Today (Barc). 2018 Apr;54(4):245-254. doi: 10.1358/dot.2018.54.4.2800623. [Article]
- Xerava Approval History [Link]
- FDA Approved Drug Products: XERAVA (eravacycline) injection [Link]
- External Links
- PubChem Compound
- 54726192
- PubChem Substance
- 347828591
- ChemSpider
- 28495485
- 2055906
- ChEMBL
- CHEMBL1951095
- Wikipedia
- Eravacycline
- FDA label
- Download (194 KB)
- MSDS
- Download (22 KB)
Clinical Trials
- Clinical Trials Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">
Phase Status Purpose Conditions Count 3 Completed Treatment Complicated Appendicitis / Complicated Intra-Abdominal Infections (cIAIs) 1 3 Completed Treatment Complicated Intra-Abdominal Infections (cIAIs) 1 3 Completed Treatment Complicated Urinary Tract Infection 2 2 Completed Treatment Complicated Intra-Abdominal Infections (cIAIs) 1 2 Not Yet Recruiting Treatment Hematological Malignancy / Neutropenia 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Injection, powder, for solution Intravenous 100 MG Injection, powder, for solution Intravenous 50 MG Injection, powder, lyophilized, for solution Intravenous 100 mg/1 Injection, powder, lyophilized, for solution Intravenous 50 mg/1 Injection, powder, lyophilized, for solution Intravenous 50 mg - Prices
- Not Available
- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US8796245 No 2014-08-05 2029-08-07 US US8906887 No 2014-12-09 2030-12-28 US US10961190 No 2021-03-30 2037-10-19 US US11578044 No 2017-10-19 2037-10-19 US
Properties
- State
- Solid
- Experimental Properties
- Not Available
- Predicted Properties
Property Value Source Water Solubility 0.838 mg/mL ALOGPS logP 0.24 ALOGPS logP -3.5 Chemaxon logS -2.8 ALOGPS pKa (Strongest Acidic) 2.96 Chemaxon pKa (Strongest Basic) 9 Chemaxon Physiological Charge -1 Chemaxon Hydrogen Acceptor Count 10 Chemaxon Hydrogen Donor Count 6 Chemaxon Polar Surface Area 193.73 Å2 Chemaxon Rotatable Bond Count 5 Chemaxon Refractivity 144.16 m3·mol-1 Chemaxon Polarizability 53.6 Å3 Chemaxon Number of Rings 5 Chemaxon Bioavailability 0 Chemaxon Rule of Five No 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
- Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 226.48743 predictedDeepCCS 1.0 (2019) [M+H]+ 228.88301 predictedDeepCCS 1.0 (2019) [M+Na]+ 234.79553 predictedDeepCCS 1.0 (2019)
Targets
- Kind
- Protein
- Organism
- Escherichia coli (strain K12)
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Translation repressor activity, nucleic acid binding
- Specific Function
- One of two assembly initiator proteins for the 30S subunit, it binds directly to 16S rRNA where it nucleates assembly of the body of the 30S subunit.With S5 and S12 plays an important role in trans...
- Gene Name
- rpsD
- Uniprot ID
- P0A7V8
- Uniprot Name
- 30S ribosomal protein S4
- Molecular Weight
- 23468.915 Da
References
- Zhanel GG, Cheung D, Adam H, Zelenitsky S, Golden A, Schweizer F, Gorityala B, Lagace-Wiens PR, Walkty A, Gin AS, Hoban DJ, Karlowsky JA: Review of Eravacycline, a Novel Fluorocycline Antibacterial Agent. Drugs. 2016 Apr;76(5):567-88. doi: 10.1007/s40265-016-0545-8. [Article]
- Grossman TH, Starosta AL, Fyfe C, O'Brien W, Rothstein DM, Mikolajka A, Wilson DN, Sutcliffe JA: Target- and resistance-based mechanistic studies with TP-434, a novel fluorocycline antibiotic. Antimicrob Agents Chemother. 2012 May;56(5):2559-64. doi: 10.1128/AAC.06187-11. Epub 2012 Feb 21. [Article]
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Vitamin d3 25-hydroxylase activity
- Specific Function
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
- Gene Name
- CYP3A4
- Uniprot ID
- P08684
- Uniprot Name
- Cytochrome P450 3A4
- Molecular Weight
- 57342.67 Da
References
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Substrate
- General Function
- Serotonin binding
- Specific Function
- Catalyzes the oxidative deamination of biogenic and xenobiotic amines and has important functions in the metabolism of neuroactive and vasoactive amines in the central nervous system and peripheral...
- Gene Name
- MAOA
- Uniprot ID
- P21397
- Uniprot Name
- Amine oxidase [flavin-containing] A
- Molecular Weight
- 59681.27 Da
References
- Eravacycline FDA label [File]
Drug created at October 20, 2016 21:57 / Updated at October 07, 2021 12:09