Tedizolid

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Tedizolid
Tedizolid.svg
Names
Trade namesSivextro
Other namesTR-700, torezolid
  • (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
Drug classOxazolidinone antibiotic[1]
Main usesSkin and skin structure infection[2]
Pregnancy
category
  • US: N (Not classified yet)
Routes of
use
By mouth, intravenous
External links
AHFS/Drugs.comMonograph
US NLMTedizolid
MedlinePlusa614038
Legal
Legal status
Pharmacokinetics
Bioavailability91%
Protein binding70–90%
Elimination half-life12 hours
ExcretionFeces
Chemical and physical data
FormulaC17H15FN6O3
Molar mass370.344 g·mol−1
3D model (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 antibiotic used for skin and skin structure infection including cellulitis and skin abscesses.[2][1] This includes cases due to meticillin-resistant Staphylococcus aureus (MRSA).[1] It can be given by mouth or by gradual injection into a vein.[2]

Common side effects include nausea, headache, diarrhea, and vomiting.[1] Other side effects may include Clostridioides difficile infection.[2] Safety in pregnancy and breastfeeding is unclear.[2] It is in the oxazolidinone class of medications and works by blocking bacteria from making protein.[1]

Tedizolid was approved for medical use in the United States in 2014 and Canada and Europe in 2015.[1][2][4] In the United States a 6 day course of treatment costs about 2,300 USD as of 2021.[5] This amount in the United Kingdom costs the NHS about £862.[6]

Medical uses

Tedizolid is used 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.[7][8][9][3][1]

Dosage

The recommended dosage for treatment is 200 mg once daily for a total duration of six days, either by mouth (with or without food) or through an intravenous injection (if patient is older than 18 years old).[3]

Side effects

The most common side effects found in the clinical trials were nausea, headache, diarrhea, vomiting, and dizziness.[3] Tedizolid has also been found to have hematologic (blood) 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.[3] Its safety in patients with decreased levels of white blood cells has not been established.[9] Patients on tedizolid are also at low risk of peripheral and optic neuropathy, similar to other members of the oxazolidinone class.[3]

Mechanism of action

Tedizolid phosphate (TR-701) is a prodrug activated by plasma or intestinal phosphatases to tedizolid (TR-700) following administration of the drug either orally or intravenously.[3][10] Once activated, tedizolid exerts its bacteriostatic microbial activity through inhibition of protein synthesis by binding to the 50S ribosomal subunit (on the acceptor site) of the bacteria.[3]

Tedizolid phosphate

Chemistry

Tedizolid is a second-generation oxazolidinone derivative that is 4-to-16-fold more potent against staphylococci and enterococci compared to linezolid.[11]

History

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).[12]

Tedizolid is the second treatment approved by the FDA under the new federal law Generating Antibiotic Incentives Now (known as the GAIN Act).[13][14] 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.[14]

Research

Tedizolid showed noninferiority to linezolid in two phase-III trials, known as the ESTABLISH trials.[15]

References

  1. 1.0 1.1 1.2 1.3 1.4 1.5 1.6 1.7 "Sivextro EPAR". European Medicines Agency (EMA). Retrieved 5 July 2020. Text was copied from this source which is © European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
  2. 2.0 2.1 2.2 2.3 2.4 2.5 "Tedizolid Monograph for Professionals". Drugs.com. Retrieved 24 September 2021.
  3. 3.0 3.1 3.2 3.3 3.4 3.5 3.6 3.7 "Sivextro- tedizolid phosphate tablet, film coated Sivextro- tedizolid phosphate injection, powder, lyophilized, for solution". DailyMed. 22 June 2020. Retrieved 24 October 2020.
  4. Canada, Health (4 May 2016). "Health Canada New Drug Authorizations: 2015 Highlights". www.canada.ca. Retrieved 24 September 2021.
  5. "Tedizolid Prices, Coupons & Savings Tips - GoodRx". GoodRx. Retrieved 24 September 2021.
  6. BNF (80 ed.). BMJ Group and the Pharmaceutical Press. September 2020 – March 2021. p. 607. ISBN 978-0-85711-369-6.CS1 maint: date format (link)
  7. "Drug Approval Package: Sivextro (tedizolid phosphate) Tablets NDA #205435". U.S Food and Drug Administration (FDA). 24 December 1999. Retrieved 5 July 2020.
  8. "Drug Approval Package: Sivextro (tedizolid phosphate) Injection NDA #205436". U.S Food and Drug Administration (FDA). 24 December 1999. Retrieved 5 July 2020.
  9. 9.0 9.1 "FDA approves Sivextro to treat skin infections" (Press release). June 2014. Archived from the original on 2017-01-21. Retrieved 2019-12-16.
  10. Schaadt R, Sweeney D, Shinabarger D, Zurenko G (August 2009). "In vitro activity of TR-700, the active ingredient of the antibacterial prodrug TR-701, a novel oxazolidinone antibacterial agent". Antimicrobial Agents and Chemotherapy. 53 (8): 3236–9. doi:10.1128/AAC.00228-09. PMC 2715649. PMID 19528279.
  11. "Tedizolid (TR-701): a new oxazolidinone with enhanced potency". Accessed 2015-03-16.
  12. "Cubist Pharmaceuticals to Acquire Trius Therapeutics". July 2013.
  13. "New FDA task force will support innovation in antibacterial drug development". September 2012.
  14. 14.0 14.1 "Three encouraging steps towards new antibiotics". September 2014.
  15. "Analysis of the Phase 3 ESTABLISH Trials of Tedizolid versus Linezolid in Acute Bacterial Skin and Skin Structure Infections". Accessed March 16, 2015

External links

External sites:
Identifiers: