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
  • US: C (Risk not ruled out)
Oral, intravenous
Pharmacokinetic data
Bioavailability 91%
Protein binding 70-90%
Half-life 12 hours
Excretion Feces
Identifiers
856867-55-5 N
None
ChemSpider 9409096 YesY
UNII 97HLQ82NGL YesY
KEGG D09685 YesY
ChEBI CHEBI:82717 YesY
ChEMBL CHEMBL1257051 N
Chemical data
Formula C17H15FN6O3
370.338 g/mol
 N (what is this?)  (verify)

Tedizolid Phosphate (formerly torezolid phosphate, TR-701),[1] marketed as the phosphate salt under the trade name Sivextro, is an oxazolidinone-class antibiotic developed by Cubist Pharmaceuticals, following acquisition of Trius Therapeutics (originator: Dong-A Pharmaceuticals), for the treatment of acute bacterial skin and skin structure infections (also known as complicated skin and skin-structure infections (cSSSIs)).[2]

Sivextro 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 (Streptococcus pyogenes, Streptococcus agalactiae, Streptococcus anginosus Group (including Streptococcus anginosus, Streptococcus intermedius, and Streptococcus 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[edit]

Tedizolid phosphate is a prodrug activated by plasma 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[edit]

Tedizolid proved its noninferiority to linezolid in two phase-III trials, known as the ESTABLISH trials.[7]

Sivextro 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[edit]

The most common adverse effects found in the clinical trials were nausea, headache, diarrhea, vomiting, and dizziness.[4] Sivextro 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[edit]