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]
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)
    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] 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 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. ↑ "Tedizolid Prices, Coupons & Savings Tips - GoodRx". GoodRx. Archived from the original on 7 June 2016. 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.{{cite book}}: 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. Archived from the original on 6 July 2020. Retrieved 5 July 2020.
    8. ↑ "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.
    9. 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.
    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" Archived 2021-08-29 at the Wayback Machine. Accessed 2015-03-16.
    12. ↑ "Cubist Pharmaceuticals to Acquire Trius Therapeutics". July 2013. Archived from the original on 2015-04-02. Retrieved 2021-01-10.
    13. ↑ "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.
    14. 1 2 "Three encouraging steps towards new antibiotics". September 2014. Archived from the original on 2015-03-07. Retrieved 2021-01-10.
    15. ↑ "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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