US Food and Drug Administration
Approval of synercid for certain vancomycin resistant
infections
FDA Talk Paper
(Sep) T99:44 1999

FDA
TALK PAPER
Food and Drug Administration
U.S. Department of Health and Human Services
Public Health Service 5600 Fishers Lane Rockville, MD 20857
FDA Talk Papers are prepared by the Press Office to guide FDA personnel
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T99-44 Print Media: 301-
827-6242
September 21,1999 Broadcast Media: 301-
827-3434
Consumer Inquiries: 888-
INFO-FDA
APPROVAL OF SYNERCID FOR CERTAIN VANCOMYCIN
RESISTANT INFECTIONS
FDA today approved Synercid, the first antibacterial drug
to treat infections associated with vancomycin-resistant
Enterococcus faecium bacteremia (VREF) when no alternative
treatment is available. Synercid also received approval for
complicated skin and skin structure infections. The following
may be used to respond to questions.
Infections due to Enterococcus faecium are particularly
known to occur in hospitalized or immunocompromised
individuals. This organism is often resistant to multiple
antibiotics. Vancomycin has, for many years, served as the
last resort for treatment of 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.
Synercid, a combination of quinupristin and dalfopristin,
is the first drug in the streptogramin class approved for use
in humans in the United States. The drug has been granted
accelerated approval, a regulatory mechanism that allows early
approval for products intended to treat serious or life-
threatening conditions when they provide meaningful
therapeutic benefit over existing treatments. Accelerated
approval is based on surrogate markers of effectiveness, in
this case, the drug's ability to clear VREF infection from the
bloodstream. A study to verify the clinical benefit (e.g.,
resolution of the specific site of infection) of therapy with
Synercid is underway.
Synercid's approval was supported by clinical trials of
more than 2000 patients; 1222 patients were treated with
Synercid in four non-comparative studies for treatment of VREF
infections. In general, these patients were severely ill,
making many of them unable to be fully evaluated for purposes
of the clinical trials. For those who were able to be
evaluated, based on strict study criteria, the overall
effectiveness rate of Synercid was 52 percent. Sources of
VREF infection included intra-abdominal sites, skin, soft
tissue and the urinary tract. Additionally 330 of the enrolled
VREF patients (out of the original 1222) had VREF bacteremia
of unknown origin. For this subgroup, 90 percent had
clearance of VREF in the first 48 to 72 hours of starting
therapy.
Synercid was also found to be safe and effective for
treatment of skin and soft tissue infections caused by
methicillin-susceptible Staphylcoccus aureas (MSSA) and by
Streptococcus pyogenes in two controlled clinical trials. In
these studies 450 patients enrolled in the Synercid arms were
compared with 443 patients treated with antibacterial drugs
oxacillin or cefazolin.
The most frequently reported side effects attributed to
Synercid in the clinical studies were muscle and joint pain,
nausea, diarrhea, vomiting and rash. In studies in which the
drug was administered through a peripheral vein (e.g., in the
arm) many patients experienced local reactions to the
injection, including pain and inflammation at the catheter
injection site.
FDA's approval follows the recommendations of the Anti-
Infective Drugs Advisory Committee. Their recommendation for
the approval of the VREF indication was based, in addition to
the results of the clinical studies, on the lack of
availability of approved drugs for the treatment of this
resistant infection which may be serious and life-
threatening.
Rhone-Poulenc Rorer, a French company with US
headquarters in Collegeville, Pa., will market Synercid in the
United States.