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| Clinical data | |
|---|---|
| Trade names | Sivextro |
| Other names | TR-700, torezolid[1] |
| AHFS/Drugs.com | Monograph |
| MedlinePlus | a614038 |
| License data | |
| Routes of administration | By mouth, intravenous |
| ATC code | |
| Legal status | |
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| Pharmacokinetic data | |
| Bioavailability | 91% |
| Protein binding | 70–90% |
| Elimination half-life | 12 hours |
| Excretion | Feces |
| Identifiers | |
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| PubChem CID | |
| DrugBank | |
| ChemSpider | |
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| KEGG | |
| ChEBI | |
| ChEMBL | |
| CompTox Dashboard (EPA) | |
| ECHA InfoCard | 100.249.430 |
| Chemical and physical data | |
| Formula | C17H15FN6O3 |
| Molar mass | 370.344 g·mol−1 |
| 3D model (JSmol) | |
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Tedizolid, sold under the brand name Sivextro (by Merck) 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 for the treatment of acute bacterial skin and skin structure infections (also known as complicated skin and skin-structure infections (cSSSIs)).[5][medical citation needed]
The most common side effects include nausea (feeling sick), headache, diarrhea 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 authorized for medical use in the European Union in March 2015.[4] Tedizolid phosphate is a therapeutic alternative on the World Health Organization's List of Essential Medicines.[8]
Medical uses
[edit]Tedizolid is indicated for the treatment of acute bacterial Skin and skin structure infections (ABSSSI) caused by certain susceptible bacteria, including Staphylococcus aureus (including methicillin-resistant strains, methicillin-resistant Staphylococcus aureus (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.[6][7][9][3] Tedizolid is a second-generation oxazolidinone derivative that is 4-to-16-fold more potent against staphylococci and enterococci compared to linezolid.[10] 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
[edit]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]
Pharmacokinetic/pharmacodynamic (PK/PD) properties
[edit]Tedizolid tablets have an oral bioavailability of >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 vancomycin-resistant Enterococcus (VRE) and methicillin-resistant Staphylococcus aureus (MRSA) is time dependent. Correlations are closest between fAUC24/MIC and the tedizolid PK/PD index against MRSA and VRE. To achieve 1 kill (90% of organisms killed in every step), 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.[12]
Clinical trials
[edit]Tedizolid proved its noninferiority to linezolid in two phase-III trials, known as the ESTABLISH trials.[13]
Tedizolid is the second treatment approved by the US Food and Drug Administration (FDA) under the Generating Antibiotic Incentives Now (known as the GAIN Act) federal law.[14][15] New antibiotics manufactured under the act will be designated as a Qualified Infectious Disease Product (QIDP), allowing an expedited review by the FDA and an additional five years of market exclusivity.[15]
Adverse effects
[edit]The most common adverse 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]
References
[edit]- ^ "Trius grows as lead antibiotic moves forward". 31 October 2011.
- ^ "Health Canada New Drug Authorizations: 2015 Highlights". Health Canada. 4 May 2016. Retrieved 7 April 2024.
- ^ 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.
- ^ 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 copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
- ^ "Cubist Pharmaceuticals to Acquire Trius Therapeutics". July 2013. Archived from the original on 2 April 2015. Retrieved 17 March 2015.
- ^ 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.
- ^ 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.
- ^ World Health Organization (2025). The selection and use of essential medicines, 2025: WHO Model List of Essential Medicines, 24th list. Geneva: World Health Organization. hdl:10665/382243.
- ^ a b "FDA approves Sivextro to treat skin infections" (Press release). June 2014. Archived from the original on 21 January 2017. Retrieved 16 December 2019.
- ^ "Tedizolid (TR-701): a new oxazolidinone with enhanced potency". Accessed 2015-03-16.
- ^ 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): 3236–3239. doi:10.1128/AAC.00228-09. PMC 2715649. PMID 19528279.
- ^ Carcione D, Intra J, Andriani L, Campanile F, Gona F, Carletti S, et al. (September 2023). "New Antimicrobials for Gram-Positive Sustained Infections: A Comprehensive Guide for Clinicians". Pharmaceuticals. 16 (9): 1304. doi:10.3390/ph16091304. PMC 10536666. PMID 37765112.
- ^ "Analysis of the Phase 3 ESTABLISH Trials of Tedizolid versus Linezolid in Acute Bacterial Skin and Skin Structure Infections". Accessed March 16, 2015
- ^ "New FDA task force will support innovation in antibacterial drug development". September 2012. Archived from the original on 25 September 2012.
- ^ a b "Three encouraging steps towards new antibiotics". September 2014. Archived from the original on 7 March 2015. Retrieved 17 March 2015.
External links
[edit]- "Tedizolid Injection: MedlinePlus Drug Information". MedlinePlus.
