Linezolid chemical structure
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Zyvox

Linezolid is a synthetic systemic antibiotic drug. more...

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Zyvox

It was the first commercially available oxazolidinone antibiotic and is usually reserved for the treatment of serious bacterial infections where older antibiotics have failed due to antibiotic resistance. Conditions such as skin infections or nosocomial pneumonia where methicillin or penicillin resistance is found are indicators for linezolid use. Compared to the older antibiotics it is quite expensive.

The drug works by inhibiting the initiation of bacterial protein synthesis; it is the only antibiotic to work in this manner. That and its synthetic nature raised hopes that bacteria would be unable to develop resistance to it and also remove the chance of cross-resistance. (However, in 1997 Staphylococcus aureus was first identified in Japan as being resistant to linezolid.) Linezolid is effective against gram-positive pathogens, notably Enterococcus faecium, Staphylococcus aureus, Streptococcus agalactiae, Streptococcus pneumoniae, and Streptococcus pyogenes. It has almost no effect on gram-negative bacteria and is only bacteriostatic against most Enterococcus species.

The oxazolidinone class was discovered by researchers at E.I. duPont de Nemours and reported in 1987. Pharmacia Corporation developed linezolid and FDA approval was granted in April 2000. It is sold in the US under the tradename Zyvox in either tablet form, oral suspension powder, or in an inactive medium for intravenous injection.

Adverse effects

Side effects include rashes, loss of appetite, diarrhea, nausea, constipation and fever. A small number of patients will incur a severe allergic reaction, or tinnitis, or pseudomembranous colitis, or thrombocytopenia. Linezolid is a weak monoamine oxidase inhibitor (MAOI) and cannot be used with tyramine containing foods or pseudoephedrine.

Linezolid is toxic to mitochondria (probably because of the similarity of mitochondrial ribosomes to bacteria mitochondria). Signs of mitochondrial toxicity include lactic acidosis and peripheral neuropathy (Soriano et al., 2005).

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First Antibiotic in New Class of Drugs Fights Resistant Infections - antibacterial drug Zyvox approved by the FDA - Brief Article
From FDA Consumer, 7/1/00

The first in a new class of antibacterial drugs to treat serious infections resistant to other antibiotics has been approved by the Food and Drug Administration. Zyvox (linezolid) was approved April 18, less than a month after an FDA advisory committee reviewed study data and recommended its approval.

Zyvox treats infections, including bloodstream infections, associated with vancomycin-resistant Enterococcus faecium (VREF). Vancomycin has long been the drug of last resort in treating infections resistant to other antibiotics. Zyvox also was approved for the treatment of hospital-acquired pneumonia and complicated skin infections, including those due to methicillin-resistant Staphylococcus aureus (MRSA), for community-acquired pneumonia and for uncomplicated skin and skin structure infections.

Infections due to Enterococcus faecium and MRSA are a particular problem in hospital patients and in people with compromised immunity, such as people with AIDS or cancer. The first case of VREF was reported in this country in 1989. Since then, there has been a rapid increase in the incidence of VREF infections, as well as a dramatic rise in the incidence of MRSA infections.

Last fall, FDA approved Synercid, a combination of two older antibiotics, to treat infections resistant to vancomycin. Zyvox, however, is the first in a new class of synthetic drugs--the oxazolidinone class--approved for use in the United States and the world. It is also the first drug in over 40 years to be introduced into the U.S. market for treatment of MRSA infections.

The most frequently reported side effects attributed to Zyvox in clinical studies were headache, nausea, diarrhea, and vomiting. The most important laboratory test change was a decrease in platelet counts.

Zyvox may interact with certain other drugs, including over-the-counter cold remedies that contain pseudoephedrine or phenylpropanolamine, causing an increase in blood pressure. Patients receiving Zyvox should tell their doctors if they are taking such medications.

Therapy with Zyvox is expected to first take place mainly in hospitals or other institutional settings. Doctors have been advised to consider alternatives before prescribing Zyvox to outpatients, due to concerns about inappropriate use of antibiotics leading to an increase in resistant organisms.

Pharmacia and Upjohn, based in Kalamazoo, Mich., developed Zyvox and will market it in the United States.

COPYRIGHT 2000 U.S. Government Printing Office
COPYRIGHT 2004 Gale Group

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