After years of litigation, a comprehensive settlement was proposed in November under which Merck agreed to compensate plaintiffs who can show, under certain conditions, that taking Vioxx is connected to their having suffered a heart attack or stroke.  More than 48,500 of about 50,000 people—about 97 percent of all eligible claimants—registered, exceeding the 85 percent required threshold.  In addition, Merck extended the enrollment deadline to October 30, 2008 for eligible plaintiffs.  According to the Associated Press, “payouts are expected at a minimum of $5,000 up to a few million dollars” to “former Vioxx users, or their survivors.”  To be eligible, “They must have had pending lawsuits or tolling agreements, which suspend the statute of limitations, as of November 9, 2007, the date the settlement was reached.”

Merck pulled Vioxx from the market on September 30, 2004 after its study showed that long-term Vioxx users had twice the risk of heart attack and stroke.  Merck also agreed to a $58 million settlement with Washington, the District of Columbia and 28 other states in May over deceptive marketing of Vioxx.  In April, two reports published in the Journal of the American Medical Association (JAMA) found that two Merck-funded studies investigating the benefits of Vioxx in Alzheimer’s minimized death rates.  The reports also revealed that Merck hired outside firms to write Vioxx studies, paying prominent researchers to list their names as research authors.

A consent judgment against Merck, filed in Suffolk Superior Court, prevents the New Jersey-based drug maker from misleading consumers in future advertising and mandates full disclosure of all known risks of Merck drugs.  The judgment bans the deceptive use of scientific data when marketing doctors and “ghost writing” articles and studies and addresses conflict of interest issues.  Also, Merck must obtain Food & Drug Administration (FDA) approval for direct to consumer television drug advertisements and must comply with regulatory recommendations if the FDA calls for a delay in such advertising.  In 2000, Merck spent $160.8 million on direct to consumer Vioxx marketing.

Vioxx—refecoxib—is in a class of drugs called nonsteroidal anti-inflammatory drugs (NSAIDs) and works by reducing substances that cause inflammation, pain, and fever.  A three-year study aimed at showing that Vioxx—at a 25-milligram dose—prevents recurrence of polyps in the colon and rectum was ceased when Merck discovered a higher heart risk compared to patients taking placebos.  Prior to the Vioxx withdrawal, the FDA announced that patients taking Vioxx had a 50 percent greater chance of heart attack and sudden cardiac death and patients taking the highest recommended daily dosage of Vioxx had three times the risk of heart attack and sudden cardiac death as those not taking standard painkillers.

The move to pull the COX-2 inhibitor off the market on September 30, 2004 shocked the arthritis world and rocked the stock value of Merck.

The Reason

The decision to recall Vioxx followed a three year trial, known as APPROVe (Adenomatous Polyp Prevention on Vioxx), which was a multi-center, randomized, placebo-controlled, double-blind study to determine the effect of Vioxx on the recurrence of neoplastic polyps of the large bowel in patients with a history of colorectal adenoma.

The trial which begain in 2000, involved 2,600 patients and compared Vioxx 25 mg. to placebo. The study revealed that an increased risk of cardiovascular complications began 18 months after patients started taking Vioxx.

The History

Merck CEO Rymond Gilmartin said, “We are taking this action because we believe it best serves the interests of patients.” Vioxx, which was launched in the United States in 1999 for the treatment of arthritis has been marketed in 80 countries and used by 84 million people worldwide.

What Lies Ahead?

Acting FDA Commissioner Dr. Lester M. Crawford stated in a press release that the FDA will closely monitor other drugs in this class for similar side effects. Crawford added, “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.”

There are existing lawsuits filed against Merck because of Vioxx and some analysts predict there will be more provoked by the recall. What will this mean for other COX-2 inhibitors? It is expected to impact them in some way. Will it cause a surge in the popularity and use of Celebrex (Celecoxib) and Bextra (Valdecoxib)? Will Novartis’ yet-to-be approved Prexige (Lumiracoxib) be affected? Even Merck has another COX-2 inhibitor, Arcoxia (Etoricoxib) , which has been highly-anticipated and expected to get FDA-approval soon.

The Vioxx Recall was prompted after a three year trial known as Adenomatous Polyp Prevention On Vioxx conducted a double blind study to determine Vioxx Side Effects. The trial discovered through 2,600 patients using a Vioxx 25 mg. tablet that there was a serious risk of cardiovascular problems in patients using the drug.

Currently, FDA Commissioner Dr. Lester M. Crawford has stated that the FDA will monitor drugs in this class action lawsuit for similar side effects. The FDA has concluded that Vioxx Side Effects can include gastrointestinal bleeding, liver, and kidney toxicity. The Vioxx Lawsuits filed against Merck are expected to impact the company in some way.

VIOXX®
(rofecoxib tablets and oral suspension)
VIOXX (rofecoxib) is described chemically as 4-[4-(methylsulfonyl)phenyl]-3-phenyl-2(5H)-furanone. It has the following chemical structure:

Rofecoxib is a white to off-white to light yellow powder. It is sparingly soluble in acetone, slightly soluble in methanol and isopropyl acetate, very slightly soluble in ethanol, practically insoluble in octanol, and insoluble in water. The empirical formula for rofecoxib is C17H14O4S, and the molecular weight is 314.36

Each tablet of VIOXX for oral administration contains either 12.5 mg, 25 mg, or 50 mg of rofecoxib and the following inactive ingredients: croscarmellose sodium, hydroxypropyl cellulose, lactose, magnesium stearate, microcrystalline cellulose, and yellow ferric oxide. The 50 mg tablets also contain red ferric oxide.

Each 5 mL of the oral suspension contains either 12.5 or 25 mg of rofecoxib and the following inactive ingredients: citric acid (monohydrate), sodium citrate (dihydrate), sorbitol solution, strawberry flavor, xanthan gum, and purified water.

Added as preservatives are sodium methylparaben 0.13% and sodium propylparaben 0.02%.