Tedizolid

From Wikipedia, the free encyclopedia
  (Redirected from Torezolid)
Jump to: navigation, search
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
Pregnancy
category
  • US: C (Risk not ruled out)
Legal status
Routes of
administration
Oral, intravenous
Pharmacokinetic data
Bioavailability 91%
Protein binding 70-90%
Biological half-life 12 hours
Excretion Feces
Identifiers
CAS Registry 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 Phosphate (formerly torezolid phosphate, TR-701),[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[edit]

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[edit]

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[edit]

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[edit]