Tedizolid

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Tedizolid
Tedizolid.svg
Systematic (IUPAC) name
(5R)-3-{3-fluoro-4-[6-(2-methyl-2H-tetrazol-5-yl)pyridin-3-yl]phenyl}-5-(hydroxymethyl)-1,3-oxazolidin-2-one
Clinical data
Trade names Sivextro
Legal status
Routes Oral, intravenous
Pharmacokinetic data
Bioavailability 91%
Protein binding 70-90%
Half-life 12 hours
Excretion Feces
Identifiers
CAS number 856867-55-5 N
ATC code None
ChemSpider 9409096 YesY
UNII 97HLQ82NGL YesY
KEGG D09685 YesY
ChEBI CHEBI:82717 YesY
ChEMBL CHEMBL1257051 N
Chemical data
Formula C17H15FN6O3 
Molecular mass 370.338 g/mol
 N (what is this?)  (verify)

Tedizolid (formerly torezolid[1]), marketed as the phosphate salt under the trade name Sivextro, is an oxazolidinone drug being developed by Cubist Pharmaceuticals following acquisition of Trius Therapeutics (originator: Dong-A Pharmaceuticals) for complicated skin and skin-structure infections (cSSSIs), including those caused by methicillin-resistant Staphylococcus aureus (MRSA).[2]

Tedizolid has been approved by the FDA on June 20, 2014, for the treatment of MRSA skin infections. As an oxazolidinone, it has activity against several other Gram-positive pathogens, including methicillin-susceptible Staphylococcus aureus, Streptococcus pyogenes, Streptococcus agalactiae, enterococci, coagulase-negative staphylococci, and linezolid-resistant staphylococci. Tedizolid is marketed as a second-generation oxazolidinone that has potentially four- to 16-fold potency against MRSA relative to linezolid. [3]

Tedizolid phosphate is a prodrug activated by plasma phosphatases to tedizolid. The prodrug tedizolid is called "TR-701", while the active moiety is called "TR-700".[4][5]As a member of the oxazolidinone class, tedizolid exerts its microbial activity through inhibition of bacterial translation and protein synthesis.

Clinical trials[edit]

Tedizolid proved its noninferiority to linezolid in two phase-III trials.[6]

On June 20, 2014, tedizolid was approved in the US by the Food and Drug Administration (FDA) for the treatment of ABSSSI.[7] It can be taken orally or given by intravenous injection.[8] Sivextro is the second treatment approved by the FDA under the new federal Generating Antibiotic Incentives Now law, known as the GAIN Act. That law gives drug makers priority review and an additional five years of market exclusivity to spur the development of new antibiotics to fight the rise of drug-resistant “superbugs”.

Adverse effects[edit]

The most common adverse effects found in the clinical trials include nausea, headache, diarrhea, vomiting, and dizziness.[9] Phase-I studies of tedizolid found a possible dose and duration effect on hematologic parameters beyond 6 days of treatment.[9] Its safety in patients with decreased levels of white blood cells has not been established; thus, alternative treatments should be considered.[7] Patients on tedizolid are also at low risk of peripheral and optic neuropathy, similar to other members of the oxazolidinone class.[9]

References[edit]

  1. ^ "Trius grows as lead antibiotic moves forward". 31 Oct 2011. 
  2. ^ "Trius Completes Enrollment In Phase 2 Clinical Trial Evaluating Torezolid (TR-701) In Patients With Complicated Skin And Skin Structure Infections". Jan 2009. 
  3. ^ Tedizolid Phosphate (Sivextro): A Second-Generation Oxazolidinone to Treat Acute Bacterial Skin and Skin Structure Infections. Accessed 2014-10-28.
  4. ^ PMID 19528279 In vitro activity of TR-700, the active ingredient of the antibacterial prodrug TR-701, a novel oxazolidinone antibacterial agent.
  5. ^ PMID 19218276 TR-700 in vitro activity against and resistance mutation frequencies among Gram-positive pathogens.
  6. ^ "Cubist announces publication of pivotal data from Sivextro" Accessed October 29, 2014
  7. ^ a b "FDA Approval" Accessed October 29, 2014
  8. ^ Weisman, Robert (June 20, 2014). "FDA approves new Cubist antibiotic". Boston Globe. 
  9. ^ a b c "Prescribing Information" Accessed October 29, 2014