Brand Name: Zyvox
Active Ingredient: linezolid
Indication: Being studied for the treatment of community-acquired pneumonia, hospital-acquired pneumonia, complicated and uncomplicated skin and soft tissue infections, and bacteremia caused by gram-positive bacteria.
Company Name: Pharmacia & Upjohn Inc.
Availability: Prescription only
The oxazolidinones are the first new class of antibiotics to be introduced in over 30 years and Zyvox is being developed as the forerunner of this class. Zyvox has a unique mechanism of action and it has demonstrated in vitro activity against bacteria resistant to other antibiotics, including methicillin-resistant Staphylococci (MRS), multi-resistant strains of S. pneumoniae and vancomycin-resistant enterococci (VRE). Zyvox is currently in Phase III trials and registration applications are expected to be submitted by the end of 1999.
Zyvox: How It Works
Zyvox (linezolid) inhibits initiation of protein synthesis by preventing the formation of the fmet- tRNA:mRNA:30S subunit ternary complex. It has also been shown that oxazolidinones bind to the 50S subunit in a region shared with the peptidyl transferase inhibitor chloramphenicol. Oxazolidinones are not peptidyl transferase inhibitors and it is not known which specific ribosome reaction is inhibited by 50S subunit binding.
Clinical Study Results
An open-label, noncomparative Phase II study involving 273 inpatients with complicated and uncomplicated skin and soft tissue infections reported a clinical success rate (cure or improvement) of 93.2% at long-term follow up. The most commonly isolated organism was Staphylococcus aureus, although S. epidermidis, S. pyogenes and Enterococcus were also isolated. Patients were treated with either low (250 mg three times a day or 375 mg two times a day) or high doses of Zyvox (375 mg three times a day or 625 mg two times a day). Intravenous therapy was instituted for at least three days before switching to oral treatment.
A second Phase II study in adults who were hospitalized for community-acquired pneumonia caused by S. pneumoniae reported clinical and bacteriological success rates of 94.8% and 96.4%, respectively, at long-term follow up. Other organisms that were isolated included S. aureus, Haemophilis species and group B Streptococcus. Of the 126 patients who were evaluable and had received an average of 9 days of therapy, 73 were microbiologically evaluable. Patients were treated with either the low or high dose regimens described above. Intravenous therapy was instituted for at least three days before changing to oral treatment. Zyvox was well tolerated, the most commonly reported adverse effects being headache, nausea, and diarrhea of generally mild to moderate intensity.
Zyvox (linezolid) is rapidly and completely absorbed after oral dosing and there is no need for dose adjustment when switching from the intravenous to oral route. There was no significant difference in the efficacy of Zyvox when given with or with out food. It is anticipated that the metabolism of Zyvox will be unaffected by inhibitors or inducers of cytochrome P-450 and that Zyvox will not affect the metabolism of compounds cleared by this enzyme system.
What The Patient Should Know
As with all antibiotics it is important to finish the entire course of therapy, unless instructed by a physician, and to avoid missing doses.
Zyvox (linezolid) can be taken without regard to meals. The most common side effects that have been reported have include headache, nausea, and diarrhea.