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Vioxx Side Effects

Vioxx, a pain reliever for arthritis patients, was pulled from the market in 2004 after a study linked the drug to an increased risk of heart attacks and strokes. Other rare, but serious reactions to the drug included gastrointestinal bleeding, severe allergic reactions, and kidney and liver problems.  More common side effects included headaches, upset stomach and high blood pressure.

Vioxx, a painkiller once commonly used for joint pain and arthritis, quickly became one of Merck’s best-selling drugs after its debut in 1999. The drug was touted as an effective analgesic for arthritis, with fewer gastrointestinal side effects than traditional nonsteroidal anti-inflammatory drugs (NSAIDS).

But in 2004, the company removed the drug from the market amid concerns about cardiovascular risks, specifically heart attacks and strokes.

The drug’s label had warned of other serious side effects, such as gastrointestinal bleeds, allergic reaction, and kidney and liver problems. It listed the most common side effects of Vioxx as respiratory infections, diarrhea, nausea and headache.

Cardiovascular Risks: Heart Attack and Stroke

Merck’s decision to pull Vioxx (rofecoxib) from pharmacy shelves was based on data from a clinical trial called APPROVe (Adenomatous Polyp Prevention on Vioxx). This study compared the drug to a placebo to determine if a 25-mg dose of Vioxx could prevent the recurrence of colon polyps.

But the trial was halted when it was discovered that the drug led to an increased risk for heart attacks and strokes. Results suggested the drug may have doubled the risk of a stroke or heart attack in patients.

During the trial, 2.4 percent of the 1,287 participants who took rofecoxib suffered a serious cardiac event, including heart attack, angina or sudden death, compared with less than 1 percent of the patients who received a placebo.

A total of 15 patients given rofecoxib had a cerebrovascular event, such as stroke, deadly stroke or transient ischemic attack, while 7 of the participants given a placebo suffered the same reactions.

Some patients who took the drug also developed high blood pressure, fluid build-up known as edema and congestive heart failure, according to a 2005 report in the New England Journal of Medicine.

This increased risk of heart attack was initially determined to be linked to prolonged or chronic use of Vioxx, usually longer than 18 months. However, evidence published in a Canadian journal in 2006 found that approximately 25 percent of patients who suffered a heart attack experienced the cardiac event within two weeks of starting the drug.

Fact
The risk of suffering a heart attack while on Vioxx returns to normal within a month after stopping the drug, according a study by Canadian researchers.

Approximately 60,000 Vioxx lawsuits were filed by individuals and family members of people who suffered heart attacks and strokes while taking the drug. Merck settled those cases for close to $5 billion.

“Vioxx was thought by one FDA account to have caused more than 60,000 deaths from myocardial infarction — from heart attacks — and I couldn’t figure out how is it that we as clinicians could be giving patients drugs that were unsafe and not be aware of the carnage we were causing,” Jeanne Lenzer, associate editor at The BMJ told Drugwatch Podcast. “It took a good while for me to learn the answer to that question, but it turns out that it’s quite possible. Doctors only see … maybe they have several thousand patients in their panel that they care for, and if an older man, say taking Vioxx, dies of a heart attack, we just assume, well he was old, and he’s going die of a heart attack.”

Plaque build-up in arteries
COX-2 inhibitors, like Vioxx, may destabilize plaque build-up in arteries.

How COX-2 Inhibitors Raise Cardiovascular Risks

Since Vioxx’s withdrawal from the market, numerous studies have attempted to explain why the drug increased cardiovascular risks.

Researchers at the Perelman School of Medicine at the University of Pennsylvania concluded in 2012 that the drug’s dangers likely stem from the way it suppresses a chemical called prostacyclin.

Prostacyclin is a prostaglandin, a hormone-like compound made from fats that helps to regulate blood pressure by relaxing the walls of blood vessels. The compound also reduces and removes blood clots.

But Vioxx and other COX-2 inhibitors shut down that mechanism, and in doing so create a “cardiovascular hazard” — or risk factor — comparable to smoking or being a diabetic, according to Dr. Garrett FitzGerald, chair of the department of pharmacology and director of the Institute for Translational Medicine and Therapeutics at the University of Pennsylvania.

COX-2 inhibitors may also promote cardiovascular problems by increasing blood pressure, destabilizing plaque build-up in arteries and causing a hardening of a person’s arteries.

Diarrhea and Nausea Among Most Common Side Effects

Upper respiratory infection was the most commonly reported side effect with Vioxx use, according to the drug’s label. Diarrhea, nausea and other digestive problems were also reported more often, although these occurred less frequently when compared to traditional NSAIDs, such as ibuprofen.

Reported Digestive Complaints During Clinical Trial
Vioxx (12.5 or 25 mg daily) Ibuprofen (2400 mg daily)
Diarrhea 6.5 (percent of users) 7.1 (percent of users)
Nausea 5.2 7.1
Heartburn 4.2 5.2
Dyspepsia 3.5 4.7
Abdominal Pain 3.4 4.6

Other minor side effects of Vioxx included headache, back pain, fatigue, flu-like illnesses, sinus infections, urinary tract infections, bronchitis and dizziness.

Nearly 4 percent of 2,829 patients developed fluid buildup in their legs while using the drug and 3.5 percent developed elevated blood pressure, or hypertension.

GI Bleeds, Kidney Impairment and Liver Problems

Although rare, Vioxx has caused serious gastrointestinal (GI) problems, including stomach and intestinal bleeding and perforation. People who took the drug along with aspirin were at a higher risk of such complications.

Individuals with a history of ulcers or prior episodes of GI bleeding have a 10-fold increased risk for developing a GI bleed than others do when taking NSAIDs. Other factors that may increase this risk include treatment with anticoagulants and treatment with corticosteroids, such as prednisone. Smoking, drinking, older age and poor health can also increase a person’s risk of a GI bleed.

GI bleeds associated with NSAIDs can be hard to recognize because only 20 percent of people develop symptoms.

Other rare but serious side effects associated with Vioxx included:
  • Kidney impairment and/or kidney failure
  • Severe liver problems, including jaundice, hepatitis and liver failure
  • Serious allergic reactions, including anaphylaxis

Please seek the advice of a medical professional before making health care decisions.

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Nurse Amy Keller
Written By Amy Keller Registered Nurse

Amy Keller is a registered nurse and award-winning journalist with 22 years of experience writing about politics, business, health and other topics. At Drugwatch, she draws on her clinical experience and investigative reporting skills to write about consumers’ health concerns such as the safety of online pharmacies. She also provides informed analysis on complex health issues. Some of her qualifications include:

  • Recipient of USF’s Nurse Alumni Nightingale award for excellence in nursing
  • Guest Faculty Speaker, “Moving Forward with Patient- and Family-Centered Care Intensive Training Seminar”
  • Member of Sigma Theta Tau International Honor Society of Nursing

13 Cited Research Articles

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  2. Brindly, L. (2007, August 28). Mouse study may explain Vioxx side effects. Retrieved from https://www.chemistryworld.com/news/mouse-study-may-explain-vioxx-side-effects/3002597.article
  3. Colmenares, C. (2002, October 11). Vioxx linked to heart disease. Retrieved from http://www.mc.vanderbilt.edu/reporter/index.html?ID=2305
  4. Krumholz, H. et al. (2007, January 20). What have we learnt from Vioxx? Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1779871/
  5. Leversque, L.E., Brophy, J.M. & Zhang, B. (2005). The risk for myocardial infarction with cyclooxygenase-2 inhibitors: a population study of elderly adults. Retrieved from https://www.semanticscholar.org/paper/The-risk-for-myocardial-infarction-with-inhibitors%3A-L%C3%A9vesque-Brophy/0ad635ed8b746b819f5aed25465cfe8ea2105cdf
  6. McGill University. (2006, May 3). Study Reveals Vioxx Related Heart Attacks Can Occur Within The First Two Weeks Of Use. Retrieved from https://www.sciencedaily.com/releases/2006/05/060502172943.htm
  7. National Institutes of Health. (2018, October 30). LiverTox: DRUG RECORD ROFECOXIB. Retrieved from https://livertox.nih.gov/Rofecoxib.htm
  8. Penn Medicine News. (2012, May 2). NSAIDS and Cardiovascular Risk Explained, According to Studies from the Perelman School of Medicine. Retrieved from https://www.pennmedicine.org/news/news-releases/2012/may/nsaids-and-cardiovascular-risk
  9. Reinberg, S. (2008, October 14). Vioxx’s Heart Risk Lingered Long After Use Ended. Retrieved from http://www.washingtonpost.com/wp-dyn/content/article/2008/10/13/AR2008101302259.html
  10. Steenhuysen, J. (2008, October 13). Long-term study confirms Vioxx heart risks. Retrieved from https://www.reuters.com/article/us-stroke-vioxx/long-term-study-confirms-vioxx-heart-risks-idUSTRE49C84M20081013
  11. U.S. Food & Drug Administration. (2004, September 30). Vioxx (rofecoxib) Questions and Answers. Retrieved from https://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm106290.htm
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  13. You and Your Hormones. (n.d.). Prostaglandins. Retrieved from http://www.yourhormones.info/hormones/prostaglandins/
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