Vioxx Frequently Asked Questions

What is Vioxx?

Vioxx (rofecoxib) is a prescription COX-2 inhibitor nonsteroidal anti-inflammatory drug (NSAID). Vioxx works by inhibiting the COX-2 form of the COX enzyme to block production of prostaglandins. Prostaglandins are hormone-like substances that contribute to the symptoms of pain, fever and inflammation. Vioxx was used to treat arthritis, acute pain in adults, and painful menstrual cycles. Vioxx 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. Vioxx was later approved for the relief of the signs and symptoms of rheumatoid arthritis in adults and children. It comes as a tablet and a liquid that is usually taken once a day orally with or without food.

> Back to Top

What is the COX enzyme?

The cyclooxygenase (COX) enzyme has two forms: COX-1 and COX-2. COX-1 is found in a lot of cells all the time, notably the lining of the stomach where it regulates acid production. COX-2 is not present in most cells normally, only appearing when things are going wrong. As a result, COX-2 was thought to be responsible for the bad effects of the COX enzyme—pain and inflammation. Vioxx was developed based on this belief that COX-2 was responsible for the bad effects of the COX enzyme and to reduce or even eliminate the gastrointestinal risks involved with the non-selective (traditional) NSAIDs like Aspirin ( acetylsalicylic acid, ASA), Ibuprofen, Nabumetone and Naproxen, that inhibit both COX-1 and COX-2 enzymes. However, COX-2 serves other purposes besides its role in inflammation. Among the purposes the COX-2 enzyme serves is that it plays a major role in controlling the cardiovascular system - stopping platelets from forming blood clots (thrombi - plural form of thrombus) in the heart, and preventing damage to vessels. It also serves other functions that are beyond the scope of this FAQ to explain.

> Back to Top

Why has Vioxx been withdrawn from the market?

New research shows that a major Vioxx side effect is a greatly increased risk of cardiovascular (CV) events such as heart attack or stroke if used long-term.

> Back to Top

Were there any warning flags that led to Merck's recall of Vioxx?

Ever since the FDA sent a warning letter to Merck in 1999 calling Merck's promotional materials "false and misleading," and when the FDA directed Merck to send a letter to healthcare professionals with warnings involving the safety of its medication in 2002, Vioxx was headed for trouble. It's no surprise Merck finally decided to pull the plug, and on September 30, 2004, Merck withdrew Vioxx from the shelves. The timeline below shows the warning flag that led to the Vioxx drug recall:

  • May 14, 1999. The Food and Drug Administration (FDA) approved the drug Vioxx manufactured by Merck, Inc., for relief of the signs and symptoms of osteoarthritis, the management of acute pain and the treatment of primary dysmenorrheal (menstrual cramping).

  • December, 1999. The FDA sent warning letters to Merck regarding misrepresentation of safety information in promotional material, calling the material "false and misleading."

  • November 23, 2000. An article in the New England Journal of Medicine reported the results of a randomized trial called the Vioxx Gastrointestinal Outcomes Research trial (VIGOR). The results of this trial, which was sponsored by Merck, revealed a 53 percent decrease in the risk of upper gastrointestinal toxicity, but a five-fold increase in the risk of myocardial infarction for Vioxx compared with Naproxen.

  • September 17, 2001. Merck received a letter from the FDA, warning the manufacturer from engaging in a promotional campaign for Vioxx that minimized the potentially serious cardiovascular findings that were observed in the VIGOR study.

  • April 1, 2002. Merck announced that it had won approval from the FDA to market Vioxx for the acute treatment of migraine with or without aura in adults.

  • April 11, 2002. The FDA approved a supplemental application for the use of Vioxx for the treatment of rheumatoid arthritis. It also approved a new label which added text regarding the new indication and precautions based on the results of the VIGOR trial.

  • April 11, 2002. Merck sent a "Dear Healthcare Professional" letter to physicians outlining the new label for Vioxx. The revised label recommended that physicians "use caution" in prescribing Vioxx for patients with ischemic heart disease and that 50 mg. a day is not recommended for chronic use. The April 2002 letter mentioned that the VIGOR study showed a higher incidence of serious cardiovascular thrombotic events including sudden death, myocardial infarction, unstable angina, transient ischemic attack (TIA) and peripheral venous and arterial thromboses. It also noted that in the phase III rheumatoid arthritis efficacy studies, the incidence of hypertension in rheumatoid arthritis patients receiving 25 mg. of Vioxx once daily was 10 percent, as compared to the incidence of hypertension in patients receiving 500 mg. of Naproxen twice daily at 4.7 percent.

  • September 9, 2004. Merck announced that Vioxx had received approval from the FDA for the treatment of juvenile rheumatoid arthritis (JRA) in children 2 years and older and who weigh at least 22 pounds.

  • September 27, 2004. The Data Safety Monitoring Board for an ongoing long-term study of Vioxx (APPROVe) recommended that the study be stopped for safety reasons. 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 taken the drug for longer than 18 months.

  • September 28, 2004. Merck and FDA officials met. At that meeting the FDA was informed that Merck was voluntarily withdrawing Vioxx from the marketplace.

> Back to Top

What evidence supports the withdrawal?

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, a 156-week (three-year) trial, Vioxx was compared with placebo (sugar pill). The purpose of the trial was to see if the 25 mg dose of Vioxx was effective in preventing the recurrence of colon polyps. This trial was stopped early because there was an increased risk of serious cardiovascular events, such as heart attack and stroke, after 18 months of continuous treatment with Vioxx.

> Back to Top

Did the Food and Drug Administration (FDA) require this action?

No. Merck made this decision independent of input from the FDA. The FDA agrees with the company that there appears to be significant safety concerns for patients, particularly those taking the drug long-term. The FDA plans to work closely with Merck to coordinate the withdrawal of this product from the U.S. market.

> Back to Top

What action did the FDA take?

The FDA issued a public health advisory concerning the use of Vioxx. This advisory is based on Merck voluntarily withdrawing Vioxx from the market due to safety concerns.

> Back to Top

Why wasn't the APPROVe trial stopped earlier?

The APPROVe trial began enrollment in 2000 and 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 that Vioxx carried any increased risk of cardiovascular events.

> Back to Top

What did the FDA know about the risk of heart attack and stroke when it approved Vioxx?

The FDA originally approved Vioxx in May 1999. The original safety data included approximately 5,000 patients taking Vioxx and did not show an increased risk of heart attack or stroke. A later study, VIGOR (VIOXX Gastrointestinal Outcomes Research), was primarily designed to look at the effects of Vioxx on gastrointestinal (GI) 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 the over-the-counter drug naproxen. However, the study also showed that patients taking Vioxx were four times more likely to have a heart attack, stroke or other serious cardiovascular event.

The VIGOR study was discussed at a February 2001 Arthritis Advisory Committee, and the new safety information from this study was added to the Vioxx labeling in April 2002. Merck then began to conduct longer-term trials to obtain more data on the risk for heart attack and stroke associated with the long-term use of Vioxx.

> Back to Top

What are NSAIDs?

NSAIDs are a large group of drugs that have pain-relieving (analgesic) and fever reducing (antipyretic) effects, as well as the effect of reducing inflammation when used over time. The anti-inflammatory effects may take anywhere from a few days to three weeks to take effect. Non-selective (traditional) NSAIDs like Ibuprofen, aspirin, Nabumetone and Naproxen work by inhibiting both the COX-1 and COX-2 enzymes to stop the production of prostaglandins, while COX-2 inhibitors only block the COX-2 enzyme. Common uses for NSAIDs are:

  • Treatment of pain and inflammation associated with arthritis (inflammation and resulting pain of one or more joints, a common characteristic of over 200 rheumatic diseases with Osteoarthritis (OA) and Rheumatoid Arthritis (RA) being the most common forms).
  • Back pain and sciatica (pain down into the leg, which travels below the knee, and may involve the foot - may occur alone or accompanied by low back pain).
  • Sprains, strains and rheumatism (a chronic autoimmune disease with inflammation of the joints and marked deformities).
  • Dental Pain
  • Post-operative pain
  • Menstrual cramps (primary dysmenorrhoea - mild, and menorrhagia - heavy).
  • Pain from kidney stones (renal colic).
  • Reduction of fevers
  • Migraines (recurrent severe headaches generally accompanied by an aura (classic migraine), nausea, vomiting, and dizziness).
  • Other painful conditions, particularly those with symptoms of inflammation.

NSAIDs come in different formulas and in over-the-counter (OTC) and prescription strengths. Some may work better for you than others. Your physician can help you find the dose and medication that works best for you. Tell your physician if you are pregnant, have high blood pressure, asthma, or a history of kidney or liver disease, or have had ulcers in the past. People over age 65 must be especially careful when taking NSAIDs. Also tell your doctor about other medications you are taking. NSAIDs may intensify or counteract the effects of some medications. Both the risk and the severity of side effects increase the longer you take NSAIDs.

> Back to Top

Does the withdrawal of Vioxx from the market 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. Chronic use of NSAIDs has risks which include abdominal pain, nausea, indigestion, gastrointestinal (stomach) bleeding, as well as liver and kidney (renal) toxicity. However, COX-2 inhibitors generally do not have as high a risk for gastrointestinal problems. Patients using these drugs for a long period of time (longer than two weeks) should be under the care of a doctor.

> Back to Top

Was there a request for a Vioxx recall by the FDA?

The FDA did not request a Vioxx recall. This product is being voluntarily withdrawn from the market by Merck.

> Back to Top

Can my pharmacist continue to fill my prescription for Vioxx?

No. Merck is initiating a market withdrawal in the U.S. to the pharmacy level. This means Vioxx will no longer be available at pharmacies.

> Back to Top

What other drugs are similar to Vioxx?

Vioxx is related to the non-selective (traditional) NSAIDs aspirin, Ibuprofen, Nabumetone, Naproxen, Ketoprofen and other traditional NSAIDs. Celebrex (celecoxib) and Bextra (valdecoxib) manufactured by Pfizer are other COX-2 inhibitor NSAIDs that are similar to Vioxx. None of these similar drugs has been withdrawn. Consult with your physician to determine which is the right Vioxx alternative for you.

> Back to Top

I had a prescription for Vioxx, and now that Vioxx is off the market, what questions should I ask my doctor in choosing a different COX-2 inhibitor?

There are four questions that should be considered when considering a COX-2 inhibitor NSAID:

  1. Is the COX-2 inhibitor agent selective? (An agent must be more than 100-fold more COX-2 selective than COX-1 to meet this criteria.)

  2. Does the COX-2 inhibitor agent have a sparing effect for stomach ulcers and other gastrointestinal bleeding and complications?

  3. Does the COX-2 inhibitor agent spare platelet function? (This is particularly important for those at risk for heat attacks, strokes or other cardiovascular condition caused by blood clots.)

  4. Is the COX-2 inhibitor agent effective clinically?

> Back to Top

How can I report a serious Vioxx side effect to the FDA?

The 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 (800) FDA-1088

> Back to Top

Where can I get more information on Vioxx?

You can obtain more information from Merck at: www.merck.com and www.vioxx.com, or (888) 36VIOXX ((888) 368-4699)

To find out more about Vioxx from the FDA Visit the FDA's Drug Information web page at: www.fda.gov/cder.

Call Drug Information at (888) INFO-FDA (888) 463-6332)

SOURCES: Food and Drug Administration (FDA) - www.fda.gov. WebMD Drug Reference from Multum Information Services: "Rofecoxib (oral)." Merck's Vioxx Web site - vioxx.com. Medinfo - medinfo.co.uk. ars technica "Vioxx and the coxib controversy" - arstechnica.com. If you've taken Vioxx and suffered a heart attack, stroke or you've been diagnosed with another condition that could be linked with your use of Vioxx you need to contact an experienced and qualified Vioxx lawyer NOW! No matter what state you live in, click a panel to contact a Vioxx attorney. Any of these attorneys will be able to help you determine the best course of action in regards to your situation and/or claim. Remember, pharmaceutical and defective drug lawsuit claims, including Vioxx class action claims are governed by federal laws, so state boundaries won't stop you from getting the best possible lawyer to help you with your potential claim.

> Back to Top