Re: what was the Vioxx news?

[Guest guest]

SEE YOUR DOCTOR if you are worried: (this is response to the person that asked what the news was about Vioxx)

The following is a letter that the FDA made MERCK send to all the doctors. You can read it and decide if it has any relevance to your medical history. The main point is this: “The information below should be taken into consideration and caution should be exercised when VIOXX® (rofecoxib) is used in patients with a medical history of ischemic heart disease.”

Don’t forget that this should be a decision that is made with your doctor. As pointed out before there are other COX-2 drugs out there. The problem comes in if they do not work for you and this one does. All of these COX-2 drugs are much safer than the old NSAIDs (naproxen, ibuprofen etc.) which can cause or are more likely to cause bleeding ulcers.

Read the stuff for yourself and then have an informative conversation with your doctor. If not satisfied try another doctor until you are satisfied you are getting an over whelming opinion about what the best judgment of the entire medical community is. That is my advice if I were worried about it... that is.

THE PDF file is much easier to read than what I copied and pasted here into this e-mail. The link to the FDA site to down load that PDF file is:

http://www.fda.gov/medwatch/SAFETY/2002/vioxx_deardoc.pdf

See other links below as well.

April 2002

Dear Healthcare Professional:

Merck & Co., Inc., would like to bring to your attention recent changes to the current Prescribing

Information and Patient Product Information for VIOXX® (rofecoxib tablets and oral suspension). VIOXX

is a nonsteroidal anti-inflammatory drug (NSAID) that was approved by the United States Food and

Drug Administration (FDA) in May 1999 for relief of the signs and symptoms of osteoarthritis (OA), the

management of acute pain in adults, and the treatment of primary dysmenorrhea.

The Prescribing Information has been revised to reflect the results of the VIOXX Gastrointestinal

Outcomes Research (VIGOR) Study and the FDA approval of VIOXX for the relief of the signs and

symptoms of rheumatoid arthritis in adults. Excerpts of the changes to the Prescribing Information

are provided below.

* * * * *

CLINICAL STUDIES

Rheumatoid Arthritis (RA)

VIOXX has demonstrated significant reduction of joint tenderness/pain and joint swelling compared to

placebo. VIOXX was evaluated for the treatment of the signs and symptoms of RA in two 12-week

placebo- and active-controlled clinical trials that enrolled a total of approximately 2,000 patients.

VIOXX was shown to be superior to placebo on all primary endpoints (number of tender joints, number

of swollen joints, patient and physician global assessments of disease activity). In addition, VIOXX was

shown to be superior to placebo using the American College of Rheumatology 20% (ACR20)

Responder Index, a composite of clinical, laboratory, and functional measures of RA. VIOXX 25 mg

once daily and naproxen 500 mg twice daily showed generally similar effects in the treatment of RA.

A 50-mg dose once daily of VIOXX was also studied; however, no additional efficacy was seen

compared to the 25-mg dose.

Special Studies

The VIGOR study was designed to evaluate the comparative GI safety of VIOXX 50 mg once daily

(twice the highest dose recommended for chronic use in OA and RA) versus naproxen 500 mg twice

daily (common therapeutic dose). The general safety and tolerability of VIOXX 50 mg once daily versus

naproxen 500 mg twice daily was also studied. VIGOR was a randomized, double-blind study (median

duration of 9 months) in 8076 patients with rheumatoid arthritis (RA) requiring chronic NSAID therapy

2

(mean age 58 years). Patients were not permitted to use concomitant aspirin or other antiplatelet

drugs. Patients with a recent history of myocardial infarction or stroke and patients deemed to require

low-dose aspirin for cardiovascular prophylaxis were to be excluded from the study. Fifty-six percent

of patients used concomitant oral corticosteroids. The GI safety endpoints (confirmed by a blinded

adjudication committee) included:

PUBs—symptomatic ulcers, upper GI perforation, obstruction, major or minor upper GI bleeding.

Complicated PUBs (a subset of PUBs)—upper GI perforation, obstruction or major upper GI bleeding.

Study Results

Gastrointestinal Safety in VIGOR

The VIGOR study showed a significant reduction in the risk of development of PUBs, including

complicated PUBs in patients taking VIOXX® (rofecoxib) compared to naproxen (see Table 1).

Table 1

VIGOR—Summary of Patients with Gastrointestinal Safety Events1

COMPARISON TO NAPROXEN

VIOXX 50 mg Naproxen Relative Risk of

daily 1000 mg daily VIOXX compared 95% CI5

GI Safety Endpoints (N=4047)2 (N=4029)2 to naproxen5

n3 (Cumulative n3 (Cumulative

Rate4) Rate4)

PUBs 56 (1.80) 121 (3.87) 0.46* (0.33, 0.64)

Complicated PUBs 16 (0.52) 37 (1.22) 0.43* (0.24, 0.78)

1 As confirmed by an independent committee blinded to treatment, 2N=Patients randomized, 3n=Patients

with events, 4Kaplan-Meier cumulative rate at end of study when at least 500 patients remained (approx.

101/2 months), 5Based on proportional hazard model

*p-value ¾0.005 for relative risk compared to naproxen

The risk reduction for PUBs and complicated PUBs for VIOXXcompared to naproxen (approximately

50%) was maintained in patients with or without the following risk factors for developing a PUB

(Kaplan-Meier cumulative rate at approximately 101/2 months, VIOXX versus naproxen, respectively):

with a prior PUB (5.12, 11.47); without a prior PUB (1.54, 3.27); age 65 or older (2.83, 6.49); or

younger than 65 years of age (1.48, 3.01). A similar risk reduction for PUBs and complicated PUBs

(approximately 50%) was also maintained in patients with or without Helicobacter pylori infection or

concomitant corticosteroid use.

Other Safety Findings: Cardiovascular Safety

The VIGOR study showed a higher incidence of adjudicated serious cardiovascular thrombotic events

in patients treated with VIOXX 50 mg once daily as compared to patients treated with naproxen 500

mg twice daily (see Table 2). This finding was largely due to a difference in the incidence of myocardial

infarction between the groups. (See Table 3.) (See PRECAUTIONS, Cardiovascular Effects.)

Adjudicated serious cardiovascular events (confirmed by a blinded adjudication committee) included:

sudden death, myocardial infarction, unstable angina, ischemic stroke, transient ischemic attack and

peripheral venous and arterial thromboses.

3

Table 2

VIGOR—Summary of Patients with Serious Cardiovascular

Thrombotic Adverse Events1 Over Time

COMPARISON TO NAPROXEN

Treatment Group Patients 4 Months2 8 Months3 101/2 months4

Randomized VIOXX 50 mg 4047 Total number of 17 29 45 events

Cumulative RateÝ 0.46% 0.82% 1.81%*

Naproxen 4029 Total number of 9 15 19 1000 mg events

Cumulative RateÝ 0.23% 0.43% 0.60%

1 Confirmed by blinded adjudication committee, 2Number of patients remaining after 4 months were 3405

and 3395 for VIOXX and naproxen respectively, 3Number of patients remaining after 8 months were 2806

and 2798 for VIOXX and naproxen respectively, 4Number of patients remaining were 531 and 514 for

VIOXX and naproxen respectively.

Ý Kaplan-Meier cumulative rate.

*p-value <0.002 for the overall relative risk compared to naproxen by proportional hazard model

Table 3

VIGOR—Serious Cardiovascular

Thrombotic Adverse Events1

VIOXX 50 mg Naproxen 1000 mg

N2=4047 N2=4029

n3 n3

Any CV thrombotic event 45* 19

Cardiac events 28** 10

Fatal MI/Sudden death 5 4

Non-fatal MI 18** 4

Unstable angina 5 2

Cerebrovascular 11 8

Ischemic stroke 9 8

TIA 2 0

Peripheral 6 1

1Confirmed by blinded adjudication committee, 2N=Patients randomized, 3n=Patients with events

*p-value <0.002 and **p-value ¾0.006 for relative risk compared to naproxen by proportional hazard model

For cardiovascular data from 2 long-term placebo-controlled studies, see PRECAUTIONS,

Cardiovascular Effects.

WARNINGS

Gastrointestinal (GI) Effects—Risk of GI Ulceration, Bleeding, and Perforation

[The standard NSAID warning of gastrointestinal effects is retained, with the following addition:]

Although the risk of GI toxicity is not completely eliminated with VIOXX® (rofecoxib), the results of the

VIOXX GI outcomes research (VIGOR) study demonstrate that in patients treated with VIOXX, the

risk of GI toxicity with VIOXX 50 mg once daily is significantly less than with naproxen 500 mg twice

daily. (See CLINICAL STUDIES, Special Studies, VIGOR.)

4

PRECAUTIONS

Cardiovascular Effects

The information below should be taken into consideration and caution should be exercised when

VIOXX® (rofecoxib) is used in patients with a medical history of ischemic heart disease.

In VIGOR, a study in 8076 patients (mean age 58; VIOXX n=4047, naproxen n=4029) with a median

duration of exposure of 9 months, the risk of developing a serious cardiovascular thrombotic event

was significantly higher in patients treated with VIOXX 50 mg once daily (n=45) as compared to

patients treated with naproxen 500 mg twice daily (n=19). In VIGOR, mortality due to cardiovascular

thrombotic events (7 vs 6, VIOXX vs naproxen, respectively) was similar between the treatment

groups. (See CLINICAL STUDIES, Special Studies, VIGOR, Other Safety Findings: Cardiovascular

Safety.) In a placebo-controlled database derived from 2 studies with a total of 2142 elderly patients

(mean age 75; VIOXX n=1067, placebo n=1075) with a median duration of exposure of approximately

14 months, the number of patients with serious cardiovascular thrombotic events was 21 vs 35

for patients treated with VIOXX 25 mg once daily versus placebo, respectively. In these same 2

placebo-controlled studies, mortality due to cardiovascular thrombotic events was 8 vs 3 for VIOXX

versus placebo, respectively. The significance of the cardiovascular findings from these 3 studies

(VIGOR and 2 placebo-controlled studies) is unknown. Prospective studies specifically designed to

compare the incidence of serious CV events in patients taking VIOXX versus NSAID comparators or

placebo have not been performed.

Because of its lack of platelet effects, VIOXX is not a substitute for aspirin for cardiovascular

prophylaxis. Therefore, in patients taking VIOXX, antiplatelet therapies should not be discontinued

and should be considered in patients with an indication for cardiovascular prophylaxis. (See

CLINICAL STUDIES, Special Studies, Platelets; PRECAUTIONS, Drug Interactions, Aspirin.)

Prospective, long-term studies on concomitant administration of VIOXX and aspirin evaluating

cardiovascular outcomes have not been conducted.

ADVERSE REACTIONS

Rheumatoid Arthritis

Approximately 1,100 patients were treated with VIOXX in the Phase III rheumatoid arthritis efficacy

studies. These studies included extensions of up to 1 year. The adverse experience profile was

generally similar to that reported in the osteoarthritis studies. In studies of at least three months, the

incidence of hypertension in RA patients receiving the 25 mg once daily dose of VIOXX was 10.0%

and the incidence of hypertension in patients receiving naproxen 500 mg twice daily was 4.7%.

DOSAGE AND ADMINISTRATION

Rheumatoid Arthritis

The recommended dose is 25 mg once daily. The maximum recommended daily dose is 25 mg.

Management of Acute Pain and Treatment of Primary Dysmenorrhea

[The following statement has been added:]

Chronic use of VIOXX 50 mg daily is not recommended.

* * * * *

These and other changes are highlighted in the enclosed Prescribing Information and in the Patient

Product Information, both of which are enclosed.

At Merck, we constantly evaluate data concerning our products. You can assist us in this regard by

reporting all adverse experiences involving patients on VIOXX to the Merck National Service Center

at 1-800-672-6372 or the FDA MedWatch program by phone at 1-800-FDA-1088, by FAX at

1-800-FDA-1078, or by mail at MedWatch, HF-2, 5600 Fishers Lane, Rockville, MD 20857.

Please take the time to read the revised Prescribing Information and Patient Product Information for

VIOXX, which are enclosed. Questions from healthcare professionals may be directed to the Merck

National Service Center. Thank you very much for your time and attention.

Sincerely,

Yates, MD

Vice President

Medical & Scientific Affairs

US Human Health

Enclosures: Prescribing Information for VIOXX® (rofecoxib)

Patient Product Information for VIOXX

On 7/25/02 12:10 AM, " J-J-W@... " <J-J-W@...> wrote:

Hi,

My name is Judy and I live in Florida. I just joined this list today and I take Vioxx. Would someone tell me what was said in the news about this drug? i missed it.

Judy - in Florida

On Mon, 22 Jul 2002 23:56:59 -0400 Holifield <@...> writes:

You should see or call your doc.

The media and news reporters in general can be deceiving by boiling things down to very simplistic albeit illogical conclusions. Besides that there are other COX-2s out there if you are convinced this one is not for you because of the side effect profile.

:-)

PS: At least you know it works.

COX-2 Drugs

http://www.celebrex.com/

http://www.vioxx.com/

http://www.bextra.com/

Science of COX-2

http://www.arthritis.co.za/cox.html

On 7/20/02 10:24 PM, " Joy " <jhooper@...> wrote:

Hi Joyce,

Thanks for writing.

Does anyone in the group take Vioxx??? If so please

let me know. I stopped it after the things on the

news the other day, now all my pain is back, I did not

know how much pain I was in until I stopped taking the

vioxx. It is terrible. Thanks..Joy

----- Original Message -----

From: joyce21248@...

Rheumatoid Arthritis

Sent: Friday, July 19, 2002 2:01 PM

Subject: Re: hi diagnoised with RA today +naproxen

HI JOY

I HAVE BEEN ON NAPROXEN NOW FOR ABOUT 4YRS AND I FIND THEM VERY GOOD. IT DOES TAKE A WHILE FOR THEM TO HAVE ANY AFFECT BUT ONCE YOU START TAKING THEM REGULAR I AM SURE YOU WILL FIND THEY HELP ALONG WITH THE OTHER PAINKILLERS. I HAVE TO TAKE 2 X500MG A DAY.....

TAKE CARE

LOVE

JOYCE

XXXXXXXXXXXX