E-drug: FDA warns Merck
-------------------------------------------------------------------------
[Copied as fair use. HH]
BMJ 2001;323:767 (6 October 2001)
FDA warns Merck over its promotion of rofecoxib
Deborah Josefson, San Francisco
The US Food and Drug Administration has issued a warning letter to
the pharmaceutical company Merck for misrepresenting the safety
of their blockbuster anti-inflammatory drug, rofecoxib (Vioxx).
Rofecoxib, a selective cyclo-oxygenase-2 (COX 2) inhibitor, was
approved by the administration in May 1999 for the relief of acute
pain, osteoarthritis, and dysmenorrhoea. The drug was heavily
promoted by Merck and touted as safer than and superior to
non-selective, non-steroidal anti-inflammatory drugs such as
ibuprofen and naproxen.
In its letter the FDA criticised Merck for playing down the possible
risk of stroke associated with rofecoxib and for minimising potential
drug interactions of rofecoxib with warfarin. The risk of stroke was
found in an analysis of a large study, dubbed the VIGOR (Vioxx
gastrointestinal outcomes research) trial, which compared 50 mg a
day of rofecoxib with 500 mg twice a day of naproxen in patients
with rheumatoid arthritis (New England Journal of Medicine
2000;343:1520-8). The VIGOR trial was a randomised, double
blind, placebo controlled study of 4047 patients taking rofecoxib
and 4029 taking naproxen. Patients were followed for an average
of nine months. The study found that rofecoxib was significantly
less ulcerogenic than naproxen and that patients taking rofecoxib
had a 60% lower risk of serious gastrointestinal events such as
perforations, obstructions, and upper gastrointestinal bleeds than
patients taking naproxen. The relative risk was 0.4 (95%
confidence interval, 0.2 to 0.8; P=0.005). The annual rate of these
events was 1.4% among patients taking naproxen, compared with
0.6 % among patients taking rofecoxib. However, an analysis of
the VIGOR study by cardiologist Eric Topol and colleagues at the
Cleveland Clinic in Ohio (JAMA 2001;286:954-9) showed that
patients taking rofecoxib had a higher relative risk of developing
adverse cardiovascular events such as ischaemic strokes, unstable
angina, and myocardial infarctions than the patients taking
naproxen (relative risk 2.38 (95% confidence interval 1.39 to 4.00;
P=0.002). Their study suggested that rofecoxib might be
prothrombotic and urged further research to see if this was so. The
FDA charged that Merck was aware of the cardiovascular risk
associated with rofecoxib and minimised it in a press release and in
its promotional materials.
In a press release Merck responded that the VIGOR study's data
falsely inflated the cardiovascular risk of rofecoxib because it
compared the drug with naproxen, which has blood thinning
properties similar to aspirin.
--
Send mail for the `E-Drug' conference to `e-drug@usa.healthnet.org'.
Information and archive http://satellife.healthnet.org/programs/edrug.html
Mail administrative requests to `majordomo@usa.healthnet.org'.
For additional assistance, send mail to: `owner-e-drug@usa.healthnet.org'.