Tedizolid
Identification
- Summary
Tedizolid is an oxazolidinone class antibiotic that inhibits bacterial protein synthesis and is proven to be effective in the treatment of certain Gram-positive bacterial infections.
- Generic Name
- Tedizolid
- DrugBank Accession Number
- DB14569
- Background
Drug-resistant bacteria, such as methicillin-resistant Staphylococcus aureus, vancomycin-resistant Enterococcus faecium, and penicillin-resistant Streptococcus penumoniae, represent a massive public health threat.5,8 Tedizolid is a member of the oxazolidinone class of antibiotics, which includes the previously approved linezolid and is generally effective against multidrug-resistant Gram-positive bacteria. Tedizolid is indicated for the treatment of acute bacterial skin and skin structure infections (ABSSSI) and is generally more effective and more tolerable than linezolid.14,5,1
Tedizolid was approved by the FDA on June 20, 2014, for sale by Cubist Pharmaceuticals as tedizolid phosphate (SIVEXTRO®). This product is currently available as both an oral tablet and as a powder for intravenous injection.14
- Type
- Small Molecule
- Groups
- Approved, Investigational
- Structure
- Weight
- Average: 370.344
Monoisotopic: 370.11896653 - Chemical Formula
- C17H15FN6O3
- Synonyms
- Tedizolid
- Torezolid
- External IDs
- DA 7157
- DA-7157
- TR 700
- TR-700
Pharmacology
- Indication
Tedizolid is indicated for the treatment of acute bacterial infections of the skin and skin structure (ABSSSI). To prevent drug resistance, tedizolid should only be used for infections that are caused by susceptible bacteria.14
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
Tedizolid is an oxazolidinone antibiotic that works by inhibiting protein synthesis by bacterial ribosomes.14,2,5 However, oxazolidinone antibiotics can also bind to human mitochondrial, but not cytoplasmic, ribosomes.3,7 Mitochondrial protein synthesis inhibition is associated with adverse patient effects such as neurological, hematological, and gastrointestinal toxicity, although tedizolid is tolerated better than the related linezolid.1 Alternative therapies should be considered when treating neutropenic patients with ABSSSI. Clostridium difficile-associated diarrhea has been reported in patients treated with tedizolid.14
- Mechanism of action
Despite renewed efforts to combat the spread of antimicrobial resistance, multidrug-resistant organisms, including gram-positive bacteria such as methicillin-resistant Staphylococcus aureus, remain a threat.8,5 Oxazolidinones represent a relatively new class of antibacterials inhibiting protein synthesis that is generally capable of overcoming resistance to other bacterial protein synthesis inhibitors.14,5,6
Protein synthesis involves the action of ribosomes, multi-subunit complexes composed of both protein and ribosomal RNA (rRNA) substituents. Translocation along the length of a messenger RNA and concomitant protein synthesis involves the action of the A, P, and E sites of the peptidyltransferase centre (PTC), which accepts charged aminoacyl-tRNAs and catalyzes the formation of peptide bonds between them. The bacterial 70S ribosome comprises a small (30S) and a large (50S) subunit.9
Early studies into the mechanism of action of oxazolidinone antibiotics suggested that they inhibit a step in the initiation of protein synthesis.4 However, this mechanism was inconsistent with mapped resistance mutations, and later studies involving cross-linking and direct structural determination of the binding site revealed that oxazolidinones, including both linezolid and tedizolid, bind in the A site of the PTC by interacting with the 23S rRNA component.3,2 The structural studies also revealed that oxazolidinone binding alters the conformation of a conserved nucleotide in the 23S rRNA (U2585 in Escherichia coli), which renders the PTC non-productive for peptide bond formation.2 Hence, tedizolid exerts its effect through inhibiting bacterial protein synthesis.14
Target Actions Organism A23S ribosomal RNA inhibitorEnteric bacteria and other eubacteria - Absorption
Tedizolid reaches peak plasma concentrations within three hours for oral administration and within one hour following intravenous administration; the absolute oral bioavailability is approximately 91%. Food has no effect on absorption. When given once daily, either orally or intravenously, tedizolid reaches steady-state concentrations in approximately three days.14,10,11
The Cmax for tedizolid after a single dose/at steady-state is 2.0 ± 0.7/2.2 ± 0.6 mcg/mL for oral administration, and 2.3 ± 0.6/3.0 ± 0.7 mcg/mL for intravenous administration, respectively. Similarly, the Tmax has a median (range) of 2.5 (1.0 - 8.0)/3.5 (1.0 - 6.0) hrs for the oral route and 1.1 (0.9 - 1.5)/1.2 (0.9 - 1.5) hrs when given intravenous. The AUC is 23.8 ± 6.8/25.6 ± 8.4 mcg*hr/mL for oral and 26.6 ± 5.2/29.2 ± 6.2 mcg*hr/mL for intravenous.14,10,11
- Volume of distribution
The volume of distribution for tedizolid following a single intravenous dose of 200 mg is between 67 and 80 L.14 In a study involving oral administration of 200 mg tedizolid to steady-state, the volume of distribution was 108 ± 21 L, while a single 600 mg oral dose resulted in an apparent volume of distribution of 113.3 ± 19.3 L.12,13 Tedizolid has been observed to penetrate the interstitial space of both adipose and skeletal muscle tissue and is also found in the epithelial lining fluid as well as in alveolar macrophages.14,12,13
- Protein binding
Approximately 70 to 90% of tedizolid is bound to human plasma proteins.14,1,12,13
- Metabolism
Tedizolid is administered as a phosphate prodrug that is converted to tedizolid (the circulating active moiety). Prior to excretion, the majority of tedizolid is converted to an inactive sulphate conjugate in the liver, though this is unlikely to involve the action of cytochrome P450-family enzymes.14,1
- Route of elimination
When given as a single oral dose, approximately 82% of tedizolid is excreted via the feces and 18% in urine. The majority is found as the inactive sulphate conjugate, with only 3% recovered unchanged. Over 85% of the elimination occurs within 96 hours.14,1
- Half-life
Tedizolid has a half-life of approximately 12 hours.14,11,10
- Clearance
Tedizolid has an apparent oral clearance of 6.9 ± 1.7 L/hr for a single dose and 8.4 ± 2.1 L/hr at steady-state. The systemic clearance is 6.4 ± 1.2 L/hr for a single dose and 5.9 ± 1.4 L/hr at steady-state.14,11,10
- 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
Toxicity information regarding tedizolid is not readily available. Patients experiencing an overdose are at an increased risk of severe adverse effects such as nausea, headache, dizziness, diarrhea, and vomiting. Symptomatic and supportive measures are recommended.14
- 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 Tedizolid is combined with Acenocoumarol. Ambroxol The risk or severity of methemoglobinemia can be increased when Tedizolid is combined with Ambroxol. Articaine The risk or severity of methemoglobinemia can be increased when Tedizolid is combined with Articaine. BCG vaccine The therapeutic efficacy of BCG vaccine can be decreased when used in combination with Tedizolid. Benzocaine The risk or severity of methemoglobinemia can be increased when Tedizolid is combined with Benzocaine. Benzyl alcohol The risk or severity of methemoglobinemia can be increased when Tedizolid is combined with Benzyl alcohol. Bupivacaine The risk or severity of methemoglobinemia can be increased when Tedizolid is combined with Bupivacaine. Butacaine The risk or severity of methemoglobinemia can be increased when Tedizolid is combined with Butacaine. Butamben The risk or severity of methemoglobinemia can be increased when Tedizolid is combined with Butamben. Capsaicin The risk or severity of methemoglobinemia can be increased when Tedizolid is combined with Capsaicin. 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.
Categories
- ATC Codes
- J01XX11 — Tedizolid
- Drug Categories
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as phenylpyridines. These are polycyclic aromatic compounds containing a benzene ring linked to a pyridine ring through a CC or CN bond.
- Kingdom
- Organic compounds
- Super Class
- Organoheterocyclic compounds
- Class
- Pyridines and derivatives
- Sub Class
- Phenylpyridines
- Direct Parent
- Phenylpyridines
- Alternative Parents
- Fluorobenzenes / Aryl fluorides / Oxazolidinones / Tetrazoles / Carbamate esters / Heteroaromatic compounds / Organic carbonic acids and derivatives / Azacyclic compounds / Oxacyclic compounds / Hydrocarbon derivatives show 6 more
- Substituents
- 3-phenylpyridine / Alcohol / Aromatic heteromonocyclic compound / Aryl fluoride / Aryl halide / Azacycle / Azole / Benzenoid / Carbamic acid ester / Carbonic acid derivative show 19 more
- Molecular Framework
- Aromatic heteromonocyclic compounds
- External Descriptors
- organofluorine compound, carbamate ester, tetrazoles, primary alcohol, pyridines, ring assembly, oxazolidinone (CHEBI:82717)
- Affected organisms
- Staphylococcus
- Enterococcus
- Streptococcus
Chemical Identifiers
- UNII
- 97HLQ82NGL
- CAS number
- 856866-72-3
- InChI Key
- XFALPSLJIHVRKE-GFCCVEGCSA-N
- InChI
- InChI=1S/C17H15FN6O3/c1-23-21-16(20-22-23)15-5-2-10(7-19-15)13-4-3-11(6-14(13)18)24-8-12(9-25)27-17(24)26/h2-7,12,25H,8-9H2,1H3/t12-/m1/s1
- IUPAC Name
- (5R)-3-{3-fluoro-4-[6-(2-methyl-2H-1,2,3,4-tetrazol-5-yl)pyridin-3-yl]phenyl}-5-(hydroxymethyl)-1,3-oxazolidin-2-one
- SMILES
- CN1N=NC(=N1)C1=NC=C(C=C1)C1=C(F)C=C(C=C1)N1C[C@H](CO)OC1=O
References
- Synthesis Reference
Katharina Reichenbacher, Robert J. Duguid, Jacqueline A. Ware, Douglas Phillipson. "Forms of R)-3-(4-(2-(2-methyltetrazol-5-yl)pyridin-5-yl)-3-fluorophenyl)-5-hydroxymethyl oxazolidin-2-one dihydrogen phosphate." U.S. Patent US9624250B2, issued April 18, 2017.
- General References
- Roger C, Roberts JA, Muller L: Clinical Pharmacokinetics and Pharmacodynamics of Oxazolidinones. Clin Pharmacokinet. 2018 May;57(5):559-575. doi: 10.1007/s40262-017-0601-x. [Article]
- Wilson DN, Schluenzen F, Harms JM, Starosta AL, Connell SR, Fucini P: The oxazolidinone antibiotics perturb the ribosomal peptidyl-transferase center and effect tRNA positioning. Proc Natl Acad Sci U S A. 2008 Sep 9;105(36):13339-44. doi: 10.1073/pnas.0804276105. Epub 2008 Aug 29. [Article]
- Leach KL, Swaney SM, Colca JR, McDonald WG, Blinn JR, Thomasco LM, Gadwood RC, Shinabarger D, Xiong L, Mankin AS: The site of action of oxazolidinone antibiotics in living bacteria and in human mitochondria. Mol Cell. 2007 May 11;26(3):393-402. doi: 10.1016/j.molcel.2007.04.005. [Article]
- Shinabarger DL, Marotti KR, Murray RW, Lin AH, Melchior EP, Swaney SM, Dunyak DS, Demyan WF, Buysse JM: Mechanism of action of oxazolidinones: effects of linezolid and eperezolid on translation reactions. Antimicrob Agents Chemother. 1997 Oct;41(10):2132-6. [Article]
- Koulenti D, Xu E, Mok IYS, Song A, Karageorgopoulos DE, Armaganidis A, Lipman J, Tsiodras S: Novel Antibiotics for Multidrug-Resistant Gram-Positive Microorganisms. Microorganisms. 2019 Aug 18;7(8). pii: microorganisms7080270. doi: 10.3390/microorganisms7080270. [Article]
- McCusker KP, Fujimori DG: The chemistry of peptidyltransferase center-targeted antibiotics: enzymatic resistance and approaches to countering resistance. ACS Chem Biol. 2012 Jan 20;7(1):64-72. doi: 10.1021/cb200418f. Epub 2011 Dec 30. [Article]
- McKee EE, Ferguson M, Bentley AT, Marks TA: Inhibition of mammalian mitochondrial protein synthesis by oxazolidinones. Antimicrob Agents Chemother. 2006 Jun;50(6):2042-9. doi: 10.1128/AAC.01411-05. [Article]
- Laxminarayan R, Van Boeckel T, Frost I, Kariuki S, Khan EA, Limmathurotsakul D, Larsson DGJ, Levy-Hara G, Mendelson M, Outterson K, Peacock SJ, Zhu YG: The Lancet Infectious Diseases Commission on antimicrobial resistance: 6 years later. Lancet Infect Dis. 2020 Apr;20(4):e51-e60. doi: 10.1016/S1473-3099(20)30003-7. Epub 2020 Feb 11. [Article]
- Ling C, Ermolenko DN: Structural insights into ribosome translocation. Wiley Interdiscip Rev RNA. 2016 Sep;7(5):620-36. doi: 10.1002/wrna.1354. Epub 2016 Apr 27. [Article]
- Flanagan S, Fang E, Munoz KA, Minassian SL, Prokocimer PG: Single- and multiple-dose pharmacokinetics and absolute bioavailability of tedizolid. Pharmacotherapy. 2014 Sep;34(9):891-900. doi: 10.1002/phar.1458. Epub 2014 Jul 3. [Article]
- Flanagan SD, Bien PA, Munoz KA, Minassian SL, Prokocimer PG: Pharmacokinetics of tedizolid following oral administration: single and multiple dose, effect of food, and comparison of two solid forms of the prodrug. Pharmacotherapy. 2014 Mar;34(3):240-50. doi: 10.1002/phar.1337. Epub 2013 Aug 7. [Article]
- Housman ST, Pope JS, Russomanno J, Salerno E, Shore E, Kuti JL, Nicolau DP: Pulmonary disposition of tedizolid following administration of once-daily oral 200-milligram tedizolid phosphate in healthy adult volunteers. Antimicrob Agents Chemother. 2012 May;56(5):2627-34. doi: 10.1128/AAC.05354-11. Epub 2012 Feb 13. [Article]
- Sahre M, Sabarinath S, Grant M, Seubert C, Deanda C, Prokocimer P, Derendorf H: Skin and soft tissue concentrations of tedizolid (formerly torezolid), a novel oxazolidinone, following a single oral dose in healthy volunteers. Int J Antimicrob Agents. 2012 Jul;40(1):51-4. doi: 10.1016/j.ijantimicag.2012.03.006. Epub 2012 May 13. [Article]
- FDA Approved Products: Sivextro (tedizolid phosphate) tablet and injection [Link]
- External Links
- KEGG Drug
- D09685
- ChemSpider
- 9409096
- BindingDB
- 50491954
- 1540825
- ChEBI
- 82717
- ChEMBL
- CHEMBL1257051
- ZINC
- ZINC000043100956
- PDBe Ligand
- U7V
- Wikipedia
- Tedizolid
- PDB Entries
- 6wrs
Clinical Trials
- Clinical Trials
Phase Status Purpose Conditions Count 4 Completed Other Cystic Fibrosis (CF) 1 4 Not Yet Recruiting Treatment Infective Endocarditis (IE) 1 3 Completed Treatment Bacterial Infections 1 3 Completed Treatment Bacterial skin infections / Skin Diseases, Infectious 1 3 Completed Treatment Skin and Subcutaneous Tissue Bacterial Infections 1 2 Active Not Recruiting Treatment Bone and Joint Infections 1 2 Completed Other Cellulitis / Erysipelas / Major Cutaneous Abscess 1 2 Not Yet Recruiting Treatment Multidrug Resistant Tuberculosis / Tuberculosis (TB) 1 1 Completed Basic Science Bacterial Infections 1 1 Completed Basic Science Healthy Subjects (HS) 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Injection, powder, for solution Intravenous 200 MG Tablet, film coated Oral 200 mg Injection, powder, lyophilized, for solution Intravenous 200 mg - Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) 256.8 https://pdf.hres.ca/dpd_pm/00032313.PDF water solubility 0.1 mg/mL https://pdf.hres.ca/dpd_pm/00032313.PDF pKa 1.8, 6.5 https://pdf.hres.ca/dpd_pm/00032313.PDF - Predicted Properties
Property Value Source Water Solubility 0.382 mg/mL ALOGPS logP 0.95 ALOGPS logP 2.12 Chemaxon logS -3 ALOGPS pKa (Strongest Acidic) 14.61 Chemaxon pKa (Strongest Basic) -1.7 Chemaxon Physiological Charge 0 Chemaxon Hydrogen Acceptor Count 7 Chemaxon Hydrogen Donor Count 1 Chemaxon Polar Surface Area 106.26 Å2 Chemaxon Rotatable Bond Count 4 Chemaxon Refractivity 115.06 m3·mol-1 Chemaxon Polarizability 36.84 Å3 Chemaxon Number of Rings 4 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter Yes 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
Targets

References
- Wilson DN, Schluenzen F, Harms JM, Starosta AL, Connell SR, Fucini P: The oxazolidinone antibiotics perturb the ribosomal peptidyl-transferase center and effect tRNA positioning. Proc Natl Acad Sci U S A. 2008 Sep 9;105(36):13339-44. doi: 10.1073/pnas.0804276105. Epub 2008 Aug 29. [Article]
- Leach KL, Swaney SM, Colca JR, McDonald WG, Blinn JR, Thomasco LM, Gadwood RC, Shinabarger D, Xiong L, Mankin AS: The site of action of oxazolidinone antibiotics in living bacteria and in human mitochondria. Mol Cell. 2007 May 11;26(3):393-402. doi: 10.1016/j.molcel.2007.04.005. [Article]
- Shinabarger DL, Marotti KR, Murray RW, Lin AH, Melchior EP, Swaney SM, Dunyak DS, Demyan WF, Buysse JM: Mechanism of action of oxazolidinones: effects of linezolid and eperezolid on translation reactions. Antimicrob Agents Chemother. 1997 Oct;41(10):2132-6. [Article]
- FDA Approved Products: Sivextro (tedizolid phosphate) tablet and injection [Link]
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Inhibitor
- Curator comments
- Tedizolid displays weak reversible inhibition of both MAO-A and MAO-B in vitro.
- 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
- Flanagan S, Bartizal K, Minassian SL, Fang E, Prokocimer P: In vitro, in vivo, and clinical studies of tedizolid to assess the potential for peripheral or central monoamine oxidase interactions. Antimicrob Agents Chemother. 2013 Jul;57(7):3060-6. doi: 10.1128/AAC.00431-13. Epub 2013 Apr 22. [Article]
- FDA Approved Products: Sivextro (tedizolid phosphate) tablet and injection [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Inhibitor
- Curator comments
- Tedizolid displays weak reversible inhibition of both MAO-A and MAO-B in vitro.
- General Function
- Primary amine oxidase activity
- 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
- MAOB
- Uniprot ID
- P27338
- Uniprot Name
- Amine oxidase [flavin-containing] B
- Molecular Weight
- 58762.475 Da
References
- Flanagan S, Bartizal K, Minassian SL, Fang E, Prokocimer P: In vitro, in vivo, and clinical studies of tedizolid to assess the potential for peripheral or central monoamine oxidase interactions. Antimicrob Agents Chemother. 2013 Jul;57(7):3060-6. doi: 10.1128/AAC.00431-13. Epub 2013 Apr 22. [Article]
- FDA Approved Products: Sivextro (tedizolid phosphate) tablet and injection [Link]
Drug created at July 20, 2018 20:44 / Updated at April 16, 2021 04:48