On April 18, 2000 the FDA approved Zyvox (linezolid), the first antibacterial drug in a new class to treat infections associated with vancomycin-resistant
Enterococcus faecium (VREF), including cases with bloodstream infection.
Zyvox also received approval for treatment of hospital-acquired pneumonia
and complicated skin and skin structure infections, including cases due
to methicillin-resistant Staphylococcus aureus (MRSA). In addition,
approval was granted for treatment of community-acquired pneumonia and
uncomplicated skin and skin structure infections. The following may be
used to respond to questions.
Infections due to Enterococcus faecium and MRSA are a particular
problem in hospitalized or immunocompromised individuals. These
organisms are often resistant to multiple antibiotics. Vancomycin has,
for many years, served as the treatment of last resort for these
infections. In 1989, the first case of vancomycin-resistant Enterococcus
faecium (VREF) was reported in this country. Since then, there has been
a rapid increase in the incidence of VREF infections, as well as a
dramatic increase in the incidence of MRSA infections. There have been
limited therapeutic options available for patients with these
Zyvox 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 US market for treatment of MRSA infections.
Zyvox's approval was supported by controlled clinical trials that
enrolled more than 4000 patients. The approval for VREF infections was
based on a dose-comparison study in which 145 patients were treated with
Zyvox (600 mg or 200 mg) every 12 hours for VREF infection. Types of
VREF infections studied included complicated intra-abdominal infections,
complicated skin and skin structure infections, urinary tract infections,
and bacteremia of unknown origin. The cure rate for Zyvox was 67 percent
in the high-dose arm and 52 percent in the low-dose arm.
Zyvox was also found to be as effective as vancomycin for treatment
of hospital-acquired pneumonia, including cases due to MRSA, in a
controlled clinical trial involving about 400 patients. The approval for
complicated skin and soft tissue infections, including those caused by
MRSA, was based on a controlled clinical trial of approximately 800
patients comparing linezolid with oxacillin/dicloxacillin. Additional
information on the use of linezolid in the treatment of cases of
hospital-acquired pneumonia and skin and skin structure infection caused
by MRSA came from a supportive study comparing linezolid to
The most frequently reported side effects attributed to Zyvox in the
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, and cause an increase in blood pressure. Patients
receiving Zyvox should inform their physicians if they are taking such
Pharmacia and Upjohn, the drug's manufacturer, anticipates that
therapy with Zyvox will be initiated principally in the hospital or
institutional care setting. Due to concerns about inappropriate use of
antibiotics leading to an increase in resistant organisms, prescribers
should carefully consider alternatives before initiating treatment with
Zyvox in the outpatient setting.
FDA's approval follows the recommendations of the Anti-Infective
Drugs Advisory Committee. Their recommendation for approval of these
indications was based on the results of clinical studies presented at a
meeting of the Committee on March 24, 2000.
Pharmacia and Upjohn, based in Kalamazoo, Mich., developed Zyvox and
will market it in the United States.
Download a PFD containing the Zyvox package insert.