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Vioxx Withdrawn After Study Suggests It May
Double the Risk of Heart Attack
Increased risk of serious cardiovascular events,
including heart attacks and strokes, found in test of arthritis drug
Sept. 30, 2004 – In a stunning announcement today,
drug-maker Merck & Co. announced the withdrawal of the popular
anti-inflammatory drug Vioxx from the market due to a study they were
conducting that shows patients taking the drug face twice the risk of
heart attack compared to those in the test taking a placebo. The FDA,
that approved the drug in 1999, also issued a public health advisory and
news release. It is used by many senior citizens for
arthritis.
“Vioxx is a prescription COX-2 selective,
non-steroidal anti-inflammatory drug (NSAID) that was approved by FDA in
May 1999 for the relief of the signs and symptoms of osteoarthritis, for
the management of acute pain in adults, and for the treatment of
menstrual symptoms. It is also approved for the relief of the signs and
symptoms of rheumatoid arthritis in adults and children,” says the FDA.
The health advisory said, “The risk that an
individual patient taking Vioxx will suffer a heart attack or stroke
related to the drug is very small. Patients who are currently taking
Vioxx should contact their physician for guidance regarding
discontinuation and alternative therapies.’
FDA is working closely with Merck to coordinate the
withdrawal of this product from the U.S. market place. Healthcare
professionals are advised to contact Merck at 1-888-368-4699 or at
www.merck.com or at the FDA’s Drug Information Office at
301-827-4573 or 1-888-463-6332 or go to Vioxx Information on FDA’s
website at:
www.fda.gov/cder/drug/infopage/vioxx/default.com for
questions about this product.
Below is more information from the FDA and Merck,
including
>
FDA News Release
>
Merck News Release
>
FDA Public Health Advisory
> About the Drug by FDA
>
Q&A by FDA
FDA Issues Public Health Advisory on Vioxx as its Manufacturer
Voluntarily Withdraws the Product
FDA News Release 9/30/04
The Food and Drug Administration (FDA) today
acknowledged the voluntary withdrawal from the market of Vioxx (chemical
name rofecoxib), a non-steroidal anti-inflammatory drug (NSAID)
manufactured by Merck & Co. FDA today also issued a Public Health
Advisory to inform patients of this action and to advise them to consult
with a physician about alternative medications.
Merck is withdrawing Vioxx from the market after
the data safety monitoring board overseeing a long-term study of the
drug recommended that the study be halted because of an increased risk
of serious cardiovascular events, including heart attacks and strokes,
among study patients taking Vioxx compared to patients receiving
placebo. The study was being done in patients at risk of developing
recurrent colon polyps.
"Merck did the right thing by promptly reporting
these findings to FDA and voluntarily withdrawing the product from the
market," said Acting FDA Commissioner Dr. Lester M. Crawford. "Although
the risk that an individual patient would have a heart attack or stroke
related to Vioxx is very small, the study that was halted suggests that,
overall, patients taking the drug chronically face twice the risk of a
heart attack compared to patients receiving a placebo."
Dr. Crawford added that FDA will closely monitor
other drugs in this class for similar side effects. "All of the NSAID
drugs have risks when taken chronically, especially of gastrointestinal
bleeding, but also liver and kidney toxicity. They should only be used
continuously under the supervision of a physician."
FDA approved Vioxx in 1999 for the reduction of
pain and inflammation caused by osteoarthritis, as well as for acute
pain in adults and for the treatment of menstrual pain. It was the
second of a new kind of NSAID (Cox-2 selective) approved by FDA.
Subsequently, FDA approved Vioxx to treat the signs and symptoms of
rheumatoid arthritis in adults and children.
At the time that Vioxx and other Cox-2 selective
NSAIDs were approved, it was hoped that they would have a lower risk of
gastrointestinal ulcers and bleeding than other NSAIDs (such as
ibuprofen and naproxen). Vioxx is the only NSAID demonstrated to have a
lower rate of these side effects.
Merck contacted FDA on September 27, 2004, to
request a meeting and to advise the agency that the long-term study of
Vioxx in patients at increased risk of colon polyps had been halted.
Merck and FDA officials met the next day, September 28, and during that
meeting the company informed FDA of its decision to remove Vioxx from
the market voluntarily.
In June 2000, Merck submitted to FDA a safety study
called VIGOR (Vioxx Gastrointestinal Outcomes Research) that found an
increased risk of serious cardiovascular events, including heart attacks
and strokes, in patients taking Vioxx compared to patients taking
naproxen. After reviewing the results of the VIGOR study and other
available data from controlled clinical trials, FDA consulted with its
Arthritis Advisory Committee in February 2001 regarding the clinical
interpretation of this new safety information. In April 2002, FDA
implemented labeling changes to reflect the findings from the VIGOR
study. The labeling changes included information about the increase in
risk of cardiovascular events, including heart attack and stroke.
Recently other studies in patients taking Vioxx
have also suggested an increased risk of cardiovascular events. FDA was
in the process of carefully reviewing these results, to determine
whether further labeling changes were warranted, when Merck informed the
agency of the results of the new trial and its decision to withdraw
Vioxx from the market.
Additional information about this withdrawal of
Vioxx, as well as questions and answers for patients, is available
online at
http://www.fda.gov/cder/drug/infopage/vioxx/default.htm.
Merck
Announces Voluntary Worldwide Withdrawal of VIOXX®
Merck News Release,
Sept. 30,2004
WHITEHOUSE STATION,
N.J., Sept. 30, 2004 - Merck &. Co., Inc. today announced a voluntary
worldwide withdrawal of VIOXX® (rofecoxib), its arthritis and acute pain
medication. The company's decision, which is effective immediately, is
based on new, three-year data from a prospective, randomized,
placebo-controlled clinical trial, the APPROVe (Adenomatous Polyp
Prevention on VIOXX) trial.
The trial, which is
being stopped, was designed to evaluate the efficacy of VIOXX 25 mg in
preventing recurrence of colorectal polyps in patients with a history of
colorectal adenomas. In this study, there was an increased relative
risk for confirmed cardiovascular events, such as heart attack and
stroke, beginning after 18 months of treatment in the patients taking
VIOXX compared to those taking placebo. The results for the first 18
months of the APPROVe study did not show any increased risk of confirmed
cardiovascular events on VIOXX, and in this respect, are similar to the
results of two placebo-controlled studies described in the current U.S.
labeling for VIOXX.
"We are taking this
action because we believe it best serves the interests of patients,"
said Raymond V. Gilmartin, chairman, president and chief executive
officer of Merck. "Although we believe it would have been possible to
continue to market VIOXX with labeling that would incorporate these new
data, given the availability of alternative therapies, and the questions
raised by the data, we concluded that a voluntary withdrawal is the
responsible course to take."
APPROVe was a
multi-center, randomized, placebo-controlled, double-blind study to
determine the effect of 156 weeks (three years) of treatment with VIOXX
on the recurrence of neoplastic polyps of the large bowel in patients
with a history of colorectal adenoma. The trial enrolled 2,600 patients
and compared VIOXX 25 mg to placebo. The trial began enrollment in
2000.
VIOXX was launched in
the United States in 1999 and has been marketed in more than 80
countries. In some countries, the product is marketed under the
trademark CEOXX. Worldwide sales of VIOXX in 2003 were $2.5 billion.
Results of the VIGOR
(VIOXX Gastrointestinal Outcomes Research) study, released in March
2000, demonstrated that the risk of gastrointestinal toxicity with VIOXX
was less than with naproxen, but indicated an increased risk of
cardiovascular events versus naproxen. However, in other studies
including Merck's Phase III studies that were the basis of regulatory
approval of the product, there was not an increased risk of
cardiovascular events with VIOXX compared with placebo or VIOXX compared
with other non-naproxen non-steroidal anti-inflammatory drugs (NSAIDs).
Merck began long-term randomized clinical trials to provide an even more
comprehensive picture of the cardiovascular safety profile of VIOXX.
"Merck has always
believed that prospective, randomized, controlled clinical trials are
the best way to evaluate the safety of medicines. APPROVe is precisely
this type of study - and it has provided us with new data on the
cardiovascular profile of VIOXX," said Peter S. Kim, Ph.D., president of
Merck Research Laboratories. "While the cause of these results is
uncertain at this time, they suggest an increased risk of confirmed
cardiovascular events beginning after 18 months of continuous therapy.
While we recognize that VIOXX benefited many patients, we believe this
action is appropriate."
Merck has informed the
U.S. Food and Drug Administration and regulatory authorities in other
countries of its decision. The company also is in the process of
notifying health care practitioners in the United States and other
countries where VIOXX is marketed. Patients who are currently taking
VIOXX should contact their health care providers to discuss
discontinuing use of VIOXX and possible alternative treatments. In
addition, patients and health care professionals may obtain information
from
www.merck.com and
www.vioxx.com, or may call (888) 36-VIOXX (1-888-368-4699).
The results of
clinical studies with one molecule in a given class are not necessarily
applicable to others in the class. Therefore, the clinical significance
of the APPROVe trial, if any, for the long-term use of other drugs in
this class, consisting of COX-2 specific inhibitors and NSAIDs, is
unknown. The company will work with regulatory authorities in the 47
countries where ARCOXIA is approved to assess whether changes to the
prescribing information for this class of drugs, including ARCOXIA, are
warranted. Merck is continuing to seek approval for ARCOXIA in other
countries, including the United States.
Merck will continue
its extensive clinical program to collect additional longer-term data
for ARCOXIA, its medication for arthritis and acute pain.
With regard to
financial guidance, prior to today's announcement, Merck remained
comfortable with its 2004 earnings per share guidance of $3.11 to
$3.17. The company currently expects earnings per share to be
negatively affected by $0.50 to $0.60 as a result of today's
announcement. This estimate includes foregone sales, writeoffs of
inventory held by Merck, customer returns of product previously sold and
costs to undertake the pullback of the product. Included in this cost
estimate is the expectation of foregone fourth quarter sales of VIOXX of
$700 million to $750 million. In addition, Merck expects that worldwide
approximately one month of inventory is held by customers and will be
returned.
At this point it is
uncertain which of these costs will be recorded in the third quarter and
which will be recorded in the fourth quarter. Therefore, at this point,
Merck is retracting the third quarter guidance it had previously
provided.
Merck will report
third-quarter earnings on Oct. 21. At that point, the company will
provide additional information regarding the costs for product
withdrawal.
About Merck
Merck & Co., Inc. is a global
research-driven pharmaceutical company. Merck discovers, develops,
manufactures and markets a broad range of innovative products to improve
human and animal health, directly and through its joint ventures.
Forward Looking
Statement
This press release contains "forward-looking statements" as that
term is defined in the Private Securities Litigation Reform Act of
1995. These statements involve risks and uncertainties, which may cause
results to differ materially from those set forth in the statements.
The forward-looking statements may include statements regarding product
development, product potential or financial performance. No
forward-looking statement can be guaranteed, and actual results may
differ materially from those projected. Merck undertakes no obligation
to publicly update any forward-looking statement, whether as a result of
new information, future events, or otherwise. Forward-looking
statements in this press release should be evaluated together with the
many uncertainties that affect Merck's business, particularly those
mentioned in the cautionary statements in Item 1 of Merck's Form 10-K
for the year ended Dec. 31, 2003, and in its periodic reports on Form
10-Q and Form 8-K (if any), which the company incorporates by reference.
VIOXX® (rofecoxib) is
a registered trademark of Merck & Co., Inc.
FDA Public Health
Advisory: Safety of Vioxx
Merck & Co., Inc. today announced a voluntary
withdrawal of Vioxx from the U.S. market due to safety concerns. Vioxx
is a prescription COX-2 selective, non-steroidal anti-inflammatory drug
(NSAID) that was approved by FDA in May 1999 for the relief of the signs
and symptoms of osteoarthritis, for the management of acute pain in
adults, and for the treatment of menstrual symptoms. It is also approved
for the relief of the signs and symptoms of rheumatoid arthritis in
adults and children.
The Agency was informed by Merck & Co., Inc. on
September 27, 2004, that the Data Safety Monitoring Board for an ongoing
long-term study of Vioxx (APPROVe) had recommended that the study be
stopped early for safety reasons. The study was being conducted in
patients at risk for developing recurrent colon polyps. The study
showed an increased risk of cardiovascular events (including heart
attack and stroke) in patients on Vioxx compared to placebo,
particularly those who had been taking the drug for longer than 18
months. Based on this new safety information, Merck and FDA officials
met the next day, September 28, 2004, and during that meeting FDA was
informed that Merck was voluntarily withdrawing Vioxx from the market
place.
The risk that an individual patient taking Vioxx
will suffer a heart attack or stroke related to the drug is very small.
Patients who are currently taking Vioxx should contact their physician
for guidance regarding discontinuation and alternative therapies.
FDA is working closely with Merck to coordinate the
withdrawal of this product from the U.S. market place. Healthcare
professionals are advised to contact Merck at 1-888-368-4699 or at
www.merck.com or at the FDA’s Drug Information Office at
301-827-4573 or 1-888-463-6332 or go to Vioxx Information on FDA’s
website at:
www.fda.gov/cder/drug/infopage/vioxx/default.com for
questions about this product.
FDA
Information About the Drug
Vioxx (rofecoxib)
Merck & Co., Inc. announced a voluntary withdrawal
of Vioxx (rofecoxib) from the U.S. and worldwide market due to safety
concerns of an increased risk of cardiovascular events (including heart
attack and stroke) in patients on Vioxx. Vioxx is a prescription COX-2
selective, non-steroidal anti-inflammatory drug (NSAID) that was
approved by FDA in May 1999 for the relief of the signs and symptoms of
osteoarthritis, for the management of acute pain in adults, and for the
treatment of menstrual symptoms, and was later approved for the relief
of the signs and symptoms of rheumatoid arthritis in adults and
children.
Questions and
Answers About Vioxx (rofecoxib)
1. What action did Merck take today?
Merck announced a voluntary worldwide withdrawal of
Vioxx (rofecoxib).
2. What is Vioxx?
Vioxx is a COX-2 selective nonsteroidal
anti-inflammatory drug (NSAID). Vioxx is also related to the
nonselective NSAIDs , such as ibuprofen and naproxen. Vioxx is a
prescription medicine used to relieve signs and symptoms of arthritis,
acute pain in adults, and painful menstrual cycles.
3. Did FDA require this action?
No, Merck made this decision independent of input
from FDA. The Agency has not had an opportunity to review the data from
the study that was stopped in the depth that Merck has, but agrees with
the company that there appear to be significant safety concerns for
patients, particularly those taking the drug chronically.
FDA plans to work closely with Merck to coordinate
the withdrawal of this product from the US market.
4. What action did FDA take today?
FDA issued a public health advisory concerning the
use of Vioxx. This advisory is based on Merck & Co., Inc. voluntarily
withdrawing Vioxx from the market due to safety concerns.
5. What should I do if I am currently taking
Vioxx?
The risk that an individual patient will suffer a
heart attack or stroke related to Vioxx is very small. We encourage
people taking Vioxx to contact their physician to discuss discontinuing
use of Vioxx and alternative treatments. Any decision about which drug
product to take to treat your symptoms should be made in consultation
with your physician based on an assessment of your specific treatment
needs.
6. What are the likely long-term health
effects, if any, of taking this product?
The new study shows that Vioxx may cause an
increased risk in cardiovascular events such as heart attack and strokes
during chronic use.
7. What evidence supports the Public Health
Advisory?
Merck’s decision to withdraw Vioxx from the market
is based on new data from a trial called the APPROVe [ Adenomatous Polyp
Prevention on VIOXX] trial. In the APPROVe trial, Vioxx was compared to
placebo (sugar-pill). The purpose of the trial was to see if Vioxx 25
mg was effective in preventing the recurrence of colon polyps. This
trial was stopped early because there was an increased risk for serious
cardiovascular events, such as heart attacks and strokes, first observed
after 18 months of continuous treatment with Vioxx compared with
placebo.
8. Why wasn’t the APPROVe trial stopped
earlier?
The APPROVe trial began enrollment in 2000. The
trial was being monitored by an independent data safety monitoring board
(DSMB). It was not stopped earlier because the results for the first 18
months of the trial did not show any increased risk of confirmed
cardiovascular events on Vioxx.
9. What did FDA know about the risk of heart
attack and stroke when it approved Vioxx?
FDA originally approved Vioxx in May 1999. The
original safety database included approximately 5000 patients on Vioxx
and did not show an increased risk of heart attack or stroke. A later
study, VIGOR (VIOXX GI Outcomes Research), was primarily designed to
look at the effects of Vioxx on side effects such as stomach ulcers and
bleeding and was submitted to the FDA in June 2000. The study showed
that patients taking Vioxx had fewer stomach ulcers and bleeding than
patients taking naproxen, another NSAID, however, the study also showed
a greater number of heart attacks in patients taking Vioxx. The VIGOR
study was discussed at a February 2001 Arthritis Advisory Committee and
the new safety information from this study was added to the labeling for
Vioxx in April 2002. Merck then began to conduct
longer-term trials to obtain more data on the risk for heart attack and
stroke with chronic use of Vioxx.
10. Is FDA’s expedited review process putting
riskier drugs on the market?
No. Vioxx received a six-month priority review
because the drug potentially provided a significant therapeutic
advantage over existing approved drugs due to fewer gastrointestinal
side effects, including bleeding. A product undergoing a priority
review is held to the same rigorous standards for safety, efficacy, and
quality that FDA expects from all drugs submitted for approval.
11. What other drugs are similar to Vioxx?
Vioxx is a COX-2 selective, nonsteroidal
anti-inflammatory drug (NSAID). Other
COX-2 selective NSAIDs on the market at this time
are Celebrex (celecoxib) and Bextra (valdecoxib). Vioxx is also related
to the nonselective NSAIDs, such as ibuprofen and naproxen. You should
consult your physician to determine which treatment is right for you.
12. Does today’s action suggest that other drugs
in the same class are dangerous?
The results of clinical studies with one drug in a
given class do not necessarily apply to other drugs in the same class.
All of the NSAIDs have risks when taken chronically, especially of
gastrointestinal (stomach) bleeding, but also liver and kidney
toxicity. Patients using these drugs for a long period of time (longer
than two weeks) should be under the care of a physician.
13. Will Vioxx be recalled?
FDA did not request a recall of Vioxx. This
product is being voluntarily withdrawn from the market by Merck.
14. Can my pharmacist continue to fill my
prescription for Vioxx?
No, Merck is initiating a market withdrawal in the
United States to the pharmacy level. This means Vioxx will no longer be
available at pharmacies.
15. How can I report a serious side effect with
Vioxx to FDA?
FDA encourages anyone aware of a serious adverse
reaction to make a MedWatch report. You can report an adverse event in
two ways:
Visit
www.fda.gov/medwatch and click
on "How to Report"
Call 1-800-FDA-1088
16. Where can I get more information?
You can obtain more information from Merck at:
www.merck.com and
www.vioxx.com , or
1-888-36VIOXX (1-888-368-4699)
To find out more about Vioxx from FDA:
Visit our Drug Information web page at:
www.fda.gov/cder
Call Drug Information at: 888-INFO-FDA
(888-463-6332)
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