Arthritis sufferers may see relief
with re-approval of Cox-2 pain relievers
panel reviews Celebrex, Vioxx and Bextra
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The U.S. Food and Drug
Administration's joint advisory committee split on whether Merck's
withdrawn Vioxx and Pfizer's Bextra should be marketed, in light of
increased cardiovascular risk with the Cox-2 inhibitors.
joint Arthritis Drugs/Drug Safety & Risk Management Advisory
Committee voted 17-15 that the overall risk-benefit profile for
Vioxx (rofecoxib) supports marketing in the United States.
was withdrawn in September due to data from the APPROVe trial that
showed an increased risk of cardiovascular events. The acronym for
the trial name refers to adenomatous polyp prevention on Vioxx.
Merck indicated that it will consider reintroducing Vioxx,
depending on the outcome of the advisory committee meeting.
The vote can be seen as slightly favorable for Merck; however,
the almost equal number of votes opposing reintroduction of Vioxx
allows the FDA a certain latitude in negotiations on whether and how
to allow the drug back onto the market.
The committee voted 17-13 with two abstentions that Bextra (valdecoxib)
should continue to be marketed.
Many committee members believed that it is difficult to
extrapolate data from a coronary bypass surgery trial of valdecoxib,
which showed an increased risk of cardiovascular events, to the
population of arthritis patients in whom the Cox-2 is used
The committee recommended continued marketing of Pfizer's
Celebrex (celecoxib) by a 31-1 vote. The group felt that the drug
was on the low end of risk for cardiovascular events at the 200 mg
per day dose used in many arthritis patients. The committee had
greater concerns about higher doses.
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For the three Cox-2s, the committee recommended "black box"
warnings on cardiovascular risk, and many committee members felt
that direct-to-consumer advertising would be inappropriate.
Stronger warnings should be applied to Vioxx, as well as
potentially second-line or third-line use if the product were to be
returned to market, the committee said. Many panel members also said
that reintroduction should be limited to a 12.5 mg dose rather than
the previously marketed 25 mg to 50 mg doses.
Warnings, although not necessarily a black box, were also
recommended for all nonsteroidal anti-inflammatory agents, including
over-the-counter medications such as ibuprofen, regarding a
potential class effect on cardiovascular function.
However, most committee members
believed the warning should be individualized by agent, especially
for naproxen, which the committee thought had already shown a
neutral or potentially beneficial effect on cardiovascular function
in various studies.
and Drug Administration]