Tedizolid: Difference between revisions
Mikewilson1 (talk | contribs) Add DrugBank ID |
Anypodetos (talk | contribs) New ATC code; not a stub; minor fixes |
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| legal_US = Rx-only |
| legal_US = Rx-only |
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| legal_status = |
| legal_status = |
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| routes_of_administration = |
| routes_of_administration = Oral, intravenous |
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<!--Pharmacokinetic data--> |
<!--Pharmacokinetic data--> |
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| bioavailability = |
| bioavailability = 91% |
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| protein_bound = |
| protein_bound = 70–90% |
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| metabolism = |
| metabolism = |
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| elimination_half-life = |
| elimination_half-life = 12 hours |
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| excretion = Feces |
| excretion = Feces |
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| CAS_number_Ref = {{cascite|changed|??}} |
| CAS_number_Ref = {{cascite|changed|??}} |
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| CAS_number = 856867-55-5 |
| CAS_number = 856867-55-5 |
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| ATC_prefix = |
| ATC_prefix = J01 |
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| ATC_suffix = |
| ATC_suffix = XX11 |
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| StdInChI_Ref = {{stdinchicite|correct|chemspider}} |
| StdInChI_Ref = {{stdinchicite|correct|chemspider}} |
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| StdInChI = 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 |
| StdInChI = 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 |
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| ChEMBL_Ref = {{ebicite|changed|EBI}} |
| ChEMBL_Ref = {{ebicite|changed|EBI}} |
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| ChEMBL = 1257051 |
| ChEMBL = 1257051 |
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| synonyms = TR-701 |
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<!--Chemical data--> |
<!--Chemical data--> |
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| smiles = O=C4O[C@H](CN4c3cc(F)c(c1ccc(nc1)c2nn(nn2)C)cc3)CO |
| smiles = O=C4O[C@H](CN4c3cc(F)c(c1ccc(nc1)c2nn(nn2)C)cc3)CO |
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}} |
}} |
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'''Tedizolid |
'''Tedizolid phosphate''' (formerly '''torezolid phosphate''', trade name '''Sivextro'''),<ref name=Nov2011>{{cite news |url=http://www.signonsandiego.com/news/2011/oct/31/trius-grows-lead-antibiotic-moves-forward/ |title=Trius grows as lead antibiotic moves forward |date=31 Oct 2011 }}</ref> is an [[oxazolidinone]]-class antibiotic. Tedizolid phosphate is a [[phosphate ester]] prodrug of the active compound tedizolid. It was developed by [[Cubist Pharmaceuticals]], following acquisition of [[Trius Therapeutics]] (originator: Dong-A Pharmaceuticals), and is marketed, under the trade name Sivextro, for the treatment of acute bacterial skin and skin structure infections (also known as [[complicated skin and skin-structure infections]] (cSSSIs)).<ref>{{cite news |url=http://investors.cubist.com/Mobile/file.aspx?IID=4093793&FID=18531897 |title=Cubist Pharmaceuticals to Acquire Trius Therapeutics |date=July 2013 }}</ref> |
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Tedizolid has been approved by the U.S Food and Drug Administration on June 20, 2014, for the treatment of acute bacterial skin and skin structure infections (ABSSSI) caused by certain susceptible bacteria, including Staphylococcus aureus (including methicillin-resistant strains (MRSA) and methicillin-susceptible strains), various Streptococcus species (S. pyogenes, S. agalactiae, and S. anginosus Group including S. anginosus, S. intermedius, and S. constellatus), and Enterococcus faecalis.<ref name ="FDA Approval">{{cite news |url=http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm402174.htm |title=FDA approves Sivextro to treat skin infections |date=June 2014 }}</ref><ref name= "Prescribing Info">[http://sivextro.com/pdf/sivextro-prescribing-info.pdf "Sivextro Prescribing info"]. Lexington, MA: Cubist.Updated March 2015.</ref> Tedizolid is a second-generation oxazolidinone that is 4-to-16-fold more potent against staphylococci and enterococci compared to [[linezolid]].<ref>[http://informahealthcare.com/doi/abs/10.1517/13543784.2012.660250 "Tedizolid (TR-701): a new oxazolidinone with enhanced potency"]. Accessed 2015-03-16.</ref> The recommended dosage for treatment is 200 mg once daily for a total duration of six days, either orally (with or without food) or through an intravenous injection (if patient is older than 18 years old).<ref name="Prescribing Info"/> |
Tedizolid has been approved by the U.S Food and Drug Administration on June 20, 2014, for the treatment of acute bacterial skin and skin structure infections (ABSSSI) caused by certain susceptible bacteria, including Staphylococcus aureus (including methicillin-resistant strains (MRSA) and methicillin-susceptible strains), various Streptococcus species (S. pyogenes, S. agalactiae, and S. anginosus Group including S. anginosus, S. intermedius, and S. constellatus), and Enterococcus faecalis.<ref name ="FDA Approval">{{cite news |url=http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm402174.htm |title=FDA approves Sivextro to treat skin infections |date=June 2014 }}</ref><ref name= "Prescribing Info">[http://sivextro.com/pdf/sivextro-prescribing-info.pdf "Sivextro Prescribing info"]. Lexington, MA: Cubist.Updated March 2015.</ref> Tedizolid is a second-generation oxazolidinone that is 4-to-16-fold more potent against staphylococci and enterococci compared to [[linezolid]].<ref>[http://informahealthcare.com/doi/abs/10.1517/13543784.2012.660250 "Tedizolid (TR-701): a new oxazolidinone with enhanced potency"]. Accessed 2015-03-16.</ref> The recommended dosage for treatment is 200 mg once daily for a total duration of six days, either orally (with or without food) or through an intravenous injection (if patient is older than 18 years old).<ref name="Prescribing Info"/> |
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==Mechanism of |
==Mechanism of action== |
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Tedizolid phosphate is a prodrug activated by plasma or intestinal phosphatases to tedizolid following administration of the drug either orally or intravenously.<ref name="Prescribing Info"/> The prodrug tedizolid is called "TR-701", while the active moiety is called "TR-700".<ref>[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2715649/ "In Vitro Activity of TR-700, the Active Ingredient of the Antibacterial Prodrug TR-701, a Novel Oxazolidinone Antibacterial Agent"]. Accessed 2015-03-16.</ref> Once activated, tedizolid exerts its bacteriostatic microbial activity through inhibition of protein synthesis by binding to the 50S ribosomal subunit of the bacteria.<ref name="Prescribing Info"/> |
Tedizolid phosphate is a prodrug activated by plasma or intestinal phosphatases to tedizolid following administration of the drug either orally or intravenously.<ref name="Prescribing Info"/> The prodrug tedizolid is called "TR-701", while the active moiety is called "TR-700".<ref>[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2715649/ "In Vitro Activity of TR-700, the Active Ingredient of the Antibacterial Prodrug TR-701, a Novel Oxazolidinone Antibacterial Agent"]. Accessed 2015-03-16.</ref> Once activated, tedizolid exerts its bacteriostatic microbial activity through inhibition of protein synthesis by binding to the 50S ribosomal subunit of the bacteria.<ref name="Prescribing Info"/> |
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[[Category:Pyridines]] |
[[Category:Pyridines]] |
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[[Category:Organofluorides]] |
[[Category:Organofluorides]] |
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{{antibiotic-stub}} |
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Revision as of 10:56, 6 January 2016
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| Clinical data | |
|---|---|
| Trade names | Sivextro |
| Other names | TR-701 |
| Routes of administration | Oral, intravenous |
| ATC code | |
| Legal status | |
| Legal status |
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| Pharmacokinetic data | |
| Bioavailability | 91% |
| Protein binding | 70–90% |
| Elimination half-life | 12 hours |
| Excretion | Feces |
| Identifiers | |
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| CAS Number | |
| DrugBank | |
| ChemSpider | |
| UNII | |
| KEGG | |
| ChEBI | |
| ChEMBL | |
| CompTox Dashboard (EPA) | |
| ECHA InfoCard | 100.249.430 |
| Chemical and physical data | |
| Formula | C17H15FN6O3 |
| Molar mass | 370.338 g/mol g·mol−1 |
| 3D model (JSmol) | |
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  (what is this?) (verify) | |
Tedizolid phosphate (formerly torezolid phosphate, trade name Sivextro),[1] is an oxazolidinone-class antibiotic. Tedizolid phosphate is a phosphate ester prodrug of the active compound tedizolid. It was developed by Cubist Pharmaceuticals, following acquisition of Trius Therapeutics (originator: Dong-A Pharmaceuticals), and is marketed, under the trade name Sivextro, for the treatment of acute bacterial skin and skin structure infections (also known as complicated skin and skin-structure infections (cSSSIs)).[2]
Tedizolid has been approved by the U.S Food and Drug Administration on June 20, 2014, for the treatment of acute bacterial skin and skin structure infections (ABSSSI) caused by certain susceptible bacteria, including Staphylococcus aureus (including methicillin-resistant strains (MRSA) and methicillin-susceptible strains), various Streptococcus species (S. pyogenes, S. agalactiae, and S. anginosus Group including S. anginosus, S. intermedius, and S. constellatus), and Enterococcus faecalis.[3][4] Tedizolid is a second-generation oxazolidinone that is 4-to-16-fold more potent against staphylococci and enterococci compared to linezolid.[5] The recommended dosage for treatment is 200 mg once daily for a total duration of six days, either orally (with or without food) or through an intravenous injection (if patient is older than 18 years old).[4]
Mechanism of action
Tedizolid phosphate is a prodrug activated by plasma or intestinal phosphatases to tedizolid following administration of the drug either orally or intravenously.[4] The prodrug tedizolid is called "TR-701", while the active moiety is called "TR-700".[6] Once activated, tedizolid exerts its bacteriostatic microbial activity through inhibition of protein synthesis by binding to the 50S ribosomal subunit of the bacteria.[4]
Clinical trials
Tedizolid proved its noninferiority to linezolid in two phase-III trials, known as the ESTABLISH trials.[7]
Tedizolid is the second treatment approved by the FDA under the new federal law Generating Antibiotic Incentives Now (known as the GAIN Act).[8][9] New antibiotics manufactured under this new act will be designed as a Qualified Infectious Disease Product (QIDP), allowing an expedited review by the FDA and an additional five years of market exclusivity.[9]
Adverse effects
The most common adverse effects found in the clinical trials were nausea, headache, diarrhea, vomiting, and dizziness.[4] Tedizolid has also been found to have hematologic effects, as shown in Phase-I studies in which subjects exposed to doses longer than 6 days showed a possible dose and duration effect on hematologic parameters.[4] Its safety in patients with decreased levels of white blood cells has not been established; thus, alternative treatments should be considered.[3] Patients on tedizolid are also at low risk of peripheral and optic neuropathy, similar to other members of the oxazolidinone class.[4]
References
- ^ "Trius grows as lead antibiotic moves forward". 31 Oct 2011.
- ^ "Cubist Pharmaceuticals to Acquire Trius Therapeutics". July 2013.
- ^ a b "FDA approves Sivextro to treat skin infections". June 2014.
- ^ a b c d e f g "Sivextro Prescribing info". Lexington, MA: Cubist.Updated March 2015.
- ^ "Tedizolid (TR-701): a new oxazolidinone with enhanced potency". Accessed 2015-03-16.
- ^ "In Vitro Activity of TR-700, the Active Ingredient of the Antibacterial Prodrug TR-701, a Novel Oxazolidinone Antibacterial Agent". Accessed 2015-03-16.
- ^ "Analysis of the Phase 3 ESTABLISH Trials of Tedizolid versus Linezolid in Acute Bacterial Skin and Skin Structure Infections". Accessed March 16, 2015
- ^ "New FDA task force will support innovation in antibacterial drug development". September 2012.
- ^ a b "Three encouraging steps towards new antibiotics". September 2014.