Tedizolid

Tedizolid
Names
Trade namesSivextro
Other namesTR-700, torezolid
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
Drug classOxazolidinone antibiotic[1]
Main usesSkin and skin structure infection[2]
WHO AWaReUnlinkedWikibase error: ⧼unlinkedwikibase-error-statements-entity-not-set⧽
Pregnancy
category
  • US: N (Not classified yet)
    Routes of
    use
    By mouth, intravenous
    External links
    AHFS/Drugs.comMonograph
    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)
    SMILES
    • O=C4O[C@H](CN4c3cc(F)c(c1ccc(nc1)c2nn(nn2)C)cc3)CO
    InChI
    • 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

    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] It is on the World Health Organization's List of Essential Medicines as an alternative to linezolid.[5] In the United States a 6 day course of treatment costs about 2,300 USD as of 2021.[6] This amount in the United Kingdom costs the NHS about £862.[7]

    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.[8][9][10][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.[10] 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][11] 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.[12]

    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).[13]

    Tedizolid is the second treatment approved by the FDA under the new federal law Generating Antibiotic Incentives Now (known as the GAIN Act).[14][15] 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.[15]

    Research

    Tedizolid showed noninferiority to linezolid in two phase-III trials, known as the ESTABLISH trials.[16]

    References

    1. 1 2 3 4 5 6 7 8 "Sivextro EPAR". European Medicines Agency (EMA). Archived from the original on 8 July 2020. Retrieved 5 July 2020. Text was copied from this source which is © European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
    2. 1 2 3 4 5 6 "Tedizolid Monograph for Professionals". Drugs.com. Archived from the original on 25 January 2021. Retrieved 24 September 2021.
    3. 1 2 3 4 5 6 7 8 "Sivextro- tedizolid phosphate tablet, film coated Sivextro- tedizolid phosphate injection, powder, lyophilized, for solution". DailyMed. 22 June 2020. Archived from the original on 26 October 2020. Retrieved 24 October 2020.
    4. Canada, Health (4 May 2016). "Health Canada New Drug Authorizations: 2015 Highlights". www.canada.ca. Archived from the original on 20 February 2020. Retrieved 24 September 2021.
    5. World Health Organization (2023). The selection and use of essential medicines 2023: web annex A: World Health Organization model list of essential medicines: 23rd list (2023). Geneva: World Health Organization. hdl:10665/371090. WHO/MHP/HPS/EML/2023.02.
    6. "Tedizolid Prices, Coupons & Savings Tips - GoodRx". GoodRx. Archived from the original on 7 June 2016. Retrieved 24 September 2021.
    7. BNF (80 ed.). BMJ Group and the Pharmaceutical Press. September 2020 – March 2021. p. 607. ISBN 978-0-85711-369-6.{{cite book}}: CS1 maint: date format (link)
    8. "Drug Approval Package: Sivextro (tedizolid phosphate) Tablets NDA #205435". U.S Food and Drug Administration (FDA). 24 December 1999. Archived from the original on 6 July 2020. Retrieved 5 July 2020.
    9. "Drug Approval Package: Sivextro (tedizolid phosphate) Injection NDA #205436". U.S Food and Drug Administration (FDA). 24 December 1999. Archived from the original on 6 July 2020. Retrieved 5 July 2020.
    10. 1 2 "FDA approves Sivextro to treat skin infections" (Press release). June 2014. Archived from the original on 2017-01-21. Retrieved 2019-12-16.
    11. 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.
    12. "Tedizolid (TR-701): a new oxazolidinone with enhanced potency" Archived 2021-08-29 at the Wayback Machine. Accessed 2015-03-16.
    13. "Cubist Pharmaceuticals to Acquire Trius Therapeutics". July 2013. Archived from the original on 2015-04-02. Retrieved 2021-01-10.
    14. "New FDA task force will support innovation in antibacterial drug development". September 2012. Archived from the original on 2017-01-18. Retrieved 2021-01-10.
    15. 1 2 "Three encouraging steps towards new antibiotics". September 2014. Archived from the original on 2015-03-07. Retrieved 2021-01-10.
    16. "Analysis of the Phase 3 ESTABLISH Trials of Tedizolid versus Linezolid in Acute Bacterial Skin and Skin Structure Infections" Archived 2021-03-12 at the Wayback Machine. Accessed March 16, 2015
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