Tedizolid

Source: Wikipedia, the free encyclopedia.
Tedizolid
Clinical data
Trade namesSivextro
Other namesTR-700, torezolid[1]
AHFS/Drugs.comMonograph
MedlinePlusa614038
License data
intravenous
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailability91%
Protein binding70–90%
Elimination half-life12 hours
ExcretionFeces
Identifiers
  • (5R)-3-{3-fluoro-4-[6-(2-methyl-2H-tetrazol-5-yl)pyridin-3-yl]phenyl}-5-(hydroxymethyl)-1,3-oxazolidin-2-one
JSmol)
  • O=C4O[C@H](CN4c3cc(F)c(c1ccc(nc1)c2nn(nn2)C)cc3)CO
  • 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 checkY
  • Key:XFALPSLJIHVRKE-GFCCVEGCSA-N checkY
 ☒NcheckY (what is this?)  (verify)

Tedizolid, sold under the brand name Sivextro is an

complicated skin and skin-structure infections (cSSSIs)).[5][medical citation needed
]

The most common side effects include nausea (feeling sick), headache, diarrhoea and vomiting.[4] These side effects were generally of mild or moderate severity.[4]

Tedizolid was approved for medical use in the United States in June 2014,[6][7] and for medical use in the European Union in March 2015.[4]

Medical uses

Tedizolid was approved by the U.S

oxazolidinone derivative that is 4-to-16-fold more potent against staphylococci and enterococci compared to linezolid.[9] 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).[3]

In the European Union tedizolid is indicated for the treatment of acute bacterial skin and skin structure infections (ABSSSI) in adults.[4]

Mechanism of action

Tedizolid phosphate (TR-701) is a

50S ribosomal subunit (on the acceptor site) of the bacteria.[3]

Tedizolid phosphate

Pharmacokinetic/pharmacodynamic (PK/PD) properties

Tedizolid tablets have an oral bioavailability >90%. Tedizolid has higher binding to plasma proteins (80%), longer half-life, and a larger volume of distribution compared to linezolid. It is primarily metabolized by the liver as an inactive sulphate conjugate (phase II reaction), with no metabolism by cytochrome P-450 enzymes. Less than 20% of the drug is excreted unchanged in the urine. Tedizolid bactericidal activity on VRE and MRSA is time dependent. Correlations are closest between fAUC24/MIC and the tedizolid PK/PD index against MRSA and VRE. To achieve 1 log10 kill, tedizolid fAUC24/MIC in neutropenic mouse models with a thigh infection with VRE and MRSA should be 14.2 and 138.5, respectively. The post-antibiotic effects of tedizolid against VRE and MRSA are 2.39 and 0.99 h, respectively.[11]

Clinical trials

Tedizolid proved its noninferiority to linezolid in two phase-III trials, known as the ESTABLISH trials.[12]

Tedizolid is the second treatment approved by the FDA under the new federal law

Qualified Infectious Disease Product (QIDP), allowing an expedited review by the FDA and an additional five years of market exclusivity.[14]

Adverse effects

The most common adverse effects found in the clinical trials were nausea, headache, diarrhea, vomiting, and dizziness.

Phase-I studies in which subjects exposed to doses longer than 6 days showed a possible dose and duration effect on hematologic parameters.[3] Its safety in patients with decreased levels of white blood cells has not been established.[8] Patients on tedizolid are also at low risk of peripheral and optic neuropathy, similar to other members of the oxazolidinone class.[3]

References

  1. ^ "Trius grows as lead antibiotic moves forward". 31 Oct 2011.
  2. ^ "Health Canada New Drug Authorizations: 2015 Highlights". Health Canada. 4 May 2016. Retrieved 7 April 2024.
  3. ^ a b c d e f g h "Sivextro- tedizolid phosphate tablet, film coated Sivextro- tedizolid phosphate injection, powder, lyophilized, for solution". DailyMed. 22 June 2020. Retrieved 24 October 2020.
  4. ^ a b c d e "Sivextro EPAR". European Medicines Agency (EMA). 17 September 2018. Retrieved 5 July 2020. Text was copied from this source which is © European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
  5. ^ "Cubist Pharmaceuticals to Acquire Trius Therapeutics". July 2013.
  6. ^ a b "Drug Approval Package: Sivextro (tedizolid phosphate) Tablets NDA #205435". U.S. Food and Drug Administration (FDA). 24 December 1999. Retrieved 5 July 2020.
  7. ^ a b "Drug Approval Package: Sivextro (tedizolid phosphate) Injection NDA #205436". U.S. Food and Drug Administration (FDA). 24 December 1999. Retrieved 5 July 2020.
  8. ^ a b "FDA approves Sivextro to treat skin infections" (Press release). June 2014. Archived from the original on 2017-01-21. Retrieved 2019-12-16.
  9. ^ "Tedizolid (TR-701): a new oxazolidinone with enhanced potency". Accessed 2015-03-16.
  10. PMID 19528279
    .
  11. PMID 37765112
    .
  12. ^ "Analysis of the Phase 3 ESTABLISH Trials of Tedizolid versus Linezolid in Acute Bacterial Skin and Skin Structure Infections". Accessed March 16, 2015
  13. ^ "New FDA task force will support innovation in antibacterial drug development". September 2012.
  14. ^ a b "Three encouraging steps towards new antibiotics". September 2014.

External links

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