Tedizolid

Last updated
Tedizolid
Tedizolid.svg
Clinical data
Trade names Sivextro
Other namesTR-700
AHFS/Drugs.com Monograph
MedlinePlus a614038
Routes of
administration 		By mouth, intravenous
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailability 91%
Protein binding 70–90%
Elimination half-life 12 hours
Excretion Feces
Identifiers
  • (5R)-3-{3-fluoro-4-[6-(2-methyl-2H-tetrazol-5-yl)pyridin-3-yl]phenyl}-5-(hydroxymethyl)-1,3-oxazolidin-2-one
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard 100.249.430 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C17H15FN6O3
Molar mass 370.344 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 Yes check.svgY
  • Key:XFALPSLJIHVRKE-GFCCVEGCSA-N Yes check.svgY
 X mark.svgNYes check.svgY  (what is this?)    (verify)

Tedizolid (formerly torezolid, trade name Sivextro), [3] 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)). [4]

Contents

The most common side effects include nausea (feeling sick), headache, diarrhoea and vomiting. [2] These side effects were generally of mild or moderate severity. [2]

Tedizolid was approved for medical use in the United States in June 2014, [5] [6] and for medical use in the European Union in March 2015. [2]

Medical uses

Tedizolid was approved by the U.S Food and Drug Administration (FDA) on June 20, 2014, with the indication 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 . [5] [6] [7] [1] Tedizolid is a second-generation oxazolidinone derivative that is 4-to-16-fold more potent against staphylococci and enterococci compared to linezolid. [8] 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). [1]

In the European Union tedizolid is indicated for the treatment of acute bacterial skin and skin structure infections (ABSSSI) in adults. [2]

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. [1] [9] 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. [1]

Tedizolid phosphate Tedizolid phosphate.svg
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. [10]

Clinical trials

Tedizolid proved its noninferiority to linezolid in two phase-III trials, known as the ESTABLISH trials. [11]

Tedizolid is the second treatment approved by the FDA under the new federal law Generating Antibiotic Incentives Now (known as the GAIN Act). [12] [13] 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. [13]

Adverse effects

The most common adverse effects found in the clinical trials were nausea, headache, diarrhea, vomiting, and dizziness. [1] 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. [1] Its safety in patients with decreased levels of white blood cells has not been established. [7] Patients on tedizolid are also at low risk of peripheral and optic neuropathy, similar to other members of the oxazolidinone class. [1]

Related Research Articles

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<span class="mw-page-title-main">Linezolid</span> Antibiotic medication

Linezolid is an antibiotic used for the treatment of infections caused by Gram-positive bacteria that are resistant to other antibiotics. Linezolid is active against most Gram-positive bacteria that cause disease, including streptococci, vancomycin-resistant enterococci (VRE), and methicillin-resistant Staphylococcus aureus (MRSA). The main uses are infections of the skin and pneumonia although it may be used for a variety of other infections including drug-resistant tuberculosis. It is used either by injection into a vein or by mouth.

<span class="mw-page-title-main">Clindamycin</span> Antibiotic

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<span class="mw-page-title-main">Tigecycline</span> Chemical compound

Tigecycline, sold under the brand name Tygacil, is a tetracycline antibiotic medication for a number of bacterial infections. It is a glycylcycline administered intravenously. It was developed in response to the growing rate of antibiotic resistant bacteria such as Staphylococcus aureus, Acinetobacter baumannii, and E. coli. As a tetracycline derivative antibiotic, its structural modifications has expanded its therapeutic activity to include Gram-positive and Gram-negative organisms, including those of multi-drug resistance.

2-Oxazolidone is a heterocyclic organic compound containing both nitrogen and oxygen in a 5-membered ring.

<span class="mw-page-title-main">Oritavancin</span> Pharmaceutical drug

Oritavancin, sold under the brand name Orbactiv among others, is a semisynthetic glycopeptide antibiotic medication for the treatment of serious Gram-positive bacterial infections. Its chemical structure as a lipoglycopeptide is similar to vancomycin.

<span class="mw-page-title-main">Dalbavancin</span> Antibiotic used to treat MRSA

Dalbavancin, sold under the brand names Dalvance in the US and Xydalba in the EU among others, is a second-generation lipoglycopeptide antibiotic medication. It belongs to the same class as vancomycin, the most widely used and one of the treatments available to people infected with methicillin-resistant Staphylococcus aureus (MRSA).

<span class="mw-page-title-main">Delafloxacin</span> Chemical compound

Delafloxacin sold under the brand name Baxdela among others, is a fluoroquinolone antibiotic used to treat acute bacterial skin and skin structure infections.

<span class="mw-page-title-main">Ceftaroline fosamil</span> Chemical compound

Ceftaroline fosamil (INN), brand name Teflaro in the US and Zinforo in Europe, is a cephalosporin antibiotic with anti-MRSA activity. Ceftaroline fosamil is a prodrug of ceftaroline. It is active against methicillin-resistant Staphylococcus aureus (MRSA) and other Gram-positive bacteria. It retains some activity of later-generation cephalosporins having broad-spectrum activity against Gram-negative bacteria, but its effectiveness is relatively much weaker. It is currently being investigated for community-acquired pneumonia and complicated skin and skin structure infection.

Skin and skin structure infections (SSSIs), also referred to as skin and soft tissue infections (SSTIs), or acute bacterial skin and skin structure infections (ABSSSIs), are infections of skin and associated soft tissues. Historically, the pathogen involved has most frequently been a bacterial species—always, since redescription of SSSIs as ABSSSIs—and as such, these infections require treatment by antibiotics.

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<span class="mw-page-title-main">Lipoglycopeptide</span> Class of chemical compounds

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<span class="mw-page-title-main">Cubist Pharmaceuticals</span> Defunct American pharmaceutical company

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<span class="mw-page-title-main">Lefamulin</span> Chemical compound

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<span class="mw-page-title-main">Contezolid</span> Chemical compound

Contezolid is an antibiotic of the oxazolidinone class. It is effective against Staphylococcus aureus, methicillin-resistant Staphylococcus aureus (MRSA), Streptococcus pyogenes, Streptococcus agalactiae, and other bacteria.

References

  1. 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. Retrieved 24 October 2020.
  2. 1 2 3 4 5 "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.
  3. ↑ "Trius grows as lead antibiotic moves forward". 31 Oct 2011.
  4. ↑ "Cubist Pharmaceuticals to Acquire Trius Therapeutics". July 2013.
  5. 1 2 "Drug Approval Package: Sivextro (tedizolid phosphate) Tablets NDA #205435". U.S. Food and Drug Administration (FDA). 24 December 1999. Retrieved 5 July 2020.
  6. 1 2 "Drug Approval Package: Sivextro (tedizolid phosphate) Injection NDA #205436". U.S. Food and Drug Administration (FDA). 24 December 1999. Retrieved 5 July 2020.
  7. 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.
  8. ↑ "Tedizolid (TR-701): a new oxazolidinone with enhanced potency". Accessed 2015-03-16.
  9. ↑ 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.
  10. ↑ 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.
  11. ↑ "Analysis of the Phase 3 ESTABLISH Trials of Tedizolid versus Linezolid in Acute Bacterial Skin and Skin Structure Infections". Accessed March 16, 2015
  12. ↑ "New FDA task force will support innovation in antibacterial drug development". September 2012.
  13. 1 2 "Three encouraging steps towards new antibiotics". September 2014.
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