Product Information
Registration Status: ActiveSIVEXTRO FILM-COATED TABLET 200MG is approved to be sold in Singapore with effective from 2015-09-16. It is marketed by MSD PHARMA (SINGAPORE) PTE LTD, with the registration number of SIN14850P.
This product contains Tedizolid Phosphate 200mg in the form of TABLET, FILM-COATED. It is approved for ORAL use.
This product is manufactured by Patheon Inc. in CANADA.
It is a Prescription Only Medicine that can only be obtained from a doctor or a dentist, or a pharmacist with a prescription from a Singapore-registered doctor or dentist.
Description
Tedizolid Phosphate is an oxazolidinone-class antibiotic prodrug indicated in adults for the treatment of acute bacterial skin and skin structure infections (ABSSSI) caused by susceptible isolates of several Gram-positive bacteria. Following administration via oral or intravenous route, tedizolid phosphate prodrug is converted by plasma phosphatases to its active moiety, tedizolid. Once activated, tedizolid exerts its bacteriostatic microbial activity through inhibition of protein synthesis by binding to the 50S ribosomal subunit of susceptible bacteria. Tedizolid is an effective and potent alternative to linezolid for the treatment of patients with Gram-positive ABSSSI due to MRSA or MSSA. Increased potency allows for once daily dosing with reduced total dosages, improving the side effect profile of this drug. Of note, the minimum inhibitory concentrations of tedizolid appear to be largely unaffected by the chloramphenicol-florfenicol resistance (cfr) gene, which has been implicated in a number of published linezolid-resistant organism outbreaks.
Indication
Tedizolid Phosphate is an oxazolidinone antibacterial drug indicated in adults for the treatment of acute bacterial skin and skin structure infections (ABSSSI) caused by susceptible isolates of the following Gram-positive microorganisms: Staphylococcus aureus (including methicillin-resistant [MRSA] and methicillin-susceptible [MSSA] isolates), Streptococcus pyogenes, Streptococcus agalactiae, Streptococcus anginosus Group (including Streptococcus anginosus, Streptococcus intermedius, and Streptococcus constellatus), and Enterococcus faecalis.
Mechanism of Action
After conversion to its active form by phosphatases, tedizolid exerts its antibacterial activity through inhibition of protein synthesis by binding to the 50S ribosomal subunit of susceptible Gram-positive bacteria. Cross-resistance between other non-oxazolidinone antibacterial drugs is unlikely as it inhibits bacterial protein synthesis through a different mechanism.
Pharmacokinetics
- Absorption
- Peak plasma tedizolid concentrations are achieved within approximately 3 hours following oral administration under fasting conditions or at the end of the 1 hour intravenous infusion of tedizolid phosphate. The absolute bioavailability is approximately 91% and no dosage adjustment is necessary between intravenous and oral administration. Oral tedizolid phosphate may be administered with or without food as total systemic exposure is unchanged between fasted and fed conditions.
- Distribution
- Mean steady-state volume of distribution after 200 mg intravenous infusion is between 67-80 L
- Metabolism
- Tedizolid phosphate is a prodrug that is converted by phosphatases to tedizolid, it's microbiologically active form. There are no other significant circulating metabolites beyond tedizolid which accounts for approximately 95% of the AUC. It is also unlikely to be metabolized by CYP450 enzymes in the liver.
- Elimination
Clearance
Clearance of a single oral 200 mg dose is 6.9 L/hr, while steady state clearance is 8.4 L/hr
Toxicity
The most commonly reported adverse effects were nausea, vomiting, diarrhea, nausea, and dizziness. Other reactions that occurred during clinical trials at a rate less than 2% include anemia, tachycardia, blurred vision, oral candidiasis, colitis, decreased white blood cell count, vulvovaginal mycotic infection, paresthesia, hypertension, and urticaria. There are no adequate studies to confirm that tedizolid phosphate is safe to use during pregnancy and should be avoided as it was shown to produce fetal developmental toxicities in mice, rats, and rabbits.
Active Ingredient/Synonyms
[(5R)-3-{3-fluoro-4-[6-(2-methyl-2H-tetrazol-5-yl)pyridin-3-yl]phenyl}-2-oxo-1,3-oxazolidin-5-yl]methyl dihydrogen phosphate | Tedizolid | Torezolid Phosphate | Tedizolid Phosphate |
Source of information: Drugbank (External Link). Last updated on: 3rd July 18. *Trade Name used in the content below may not be the same as the HSA-registered product.