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| Clinical data | |
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| Trade names | Sivextro |
| Other names | TR-700, torezolid[1] |
| AHFS/Drugs.com | Monograph |
| MedlinePlus | a614038 |
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| Routes of administration | By mouth,intravenous |
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| Pharmacokinetic data | |
| Bioavailability | 91% |
| Protein binding | 70–90% |
| Eliminationhalf-life | 12 hours |
| Excretion | Feces |
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| CompTox Dashboard(EPA) | |
| ECHA InfoCard | 100.249.430 |
| Chemical and physical data | |
| Formula | C17H15FN6O3 |
| Molar mass | 370.344 g·mol−1 |
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Tedizolid, sold under the brand nameSivextro (by Merck) is anoxazolidinone-classantibiotic. Tedizolid phosphate is aphosphate ester prodrug of the active compound tedizolid. It was developed byCubist Pharmaceuticals, following acquisition ofTrius Therapeutics (originator: Dong-A Pharmaceuticals), and is marketed for the treatment of acute bacterial skin and skin structure infections (also known ascomplicated skin and skin-structure infections (cSSSIs)).[5][medical citation needed]
The most common side effects includenausea (feeling sick),headache,diarrhea andvomiting.[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 theWorld Health Organization's List of Essential Medicines.[8]
Tedizolid isindicated for the treatment of acute bacterialSkin and skin structure infections (ABSSSI) caused by certain susceptible bacteria, includingStaphylococcus aureus (including methicillin-resistant strains,methicillin-resistantStaphylococcus aureus (MRSA), and methicillin-susceptible strains), variousStreptococcus species (S. pyogenes,S. agalactiae, andS. anginosus group includingS. anginosus,S. intermedius, andS. constellatus), andEnterococcus faecalis.[6][7][9][3] Tedizolid is a second-generationoxazolidinone derivative that is 4-to-16-fold more potent against staphylococci and enterococci compared tolinezolid.[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 ofacute bacterial skin and skin structure infections (ABSSSI) in adults.[4]
Tedizolid phosphate (TR-701) is aprodrug activated by plasma or intestinalphosphatases to tedizolid (TR-700) following administration of the drug either orally or intravenously.[3][11] Once activated, tedizolid exerts itsbacteriostatic microbial activity through inhibition of protein synthesis by binding to the50S ribosomal subunit (on the acceptor site) of the bacteria.[3]
Tedizolid tablets have an oralbioavailability of >90%. Tedizolid has higher binding to plasma proteins (80%), longerhalf-life, and a largervolume of distribution compared tolinezolid. It is primarily metabolized by the liver as an inactivesulphate conjugate (phase II reaction), with no metabolism bycytochrome P-450 enzymes. Less than 20% of the drug is excreted unchanged in the urine. Tedizolid bactericidal activity onvancomycin-resistantEnterococcus (VRE) andmethicillin-resistantStaphylococcus 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 inneutropenic 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]
Tedizolid proved itsnoninferiority tolinezolid in two phase-III trials, known as the ESTABLISH trials.[13]
Tedizolid is the second treatment approved by the USFood and Drug Administration (FDA) under theGenerating Antibiotic Incentives Now (known as the GAIN Act) federal law.[14][15] New antibiotics manufactured under the act will be designated as aQualified Infectious Disease Product (QIDP), allowing an expedited review by the FDA and an additional five years of market exclusivity.[15]
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 inPhase-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 andoptic neuropathy, similar to other members of the oxazolidinone class.[3]
