FDA’s Biggest Blunders

Merck’s Vioxx, a nonsteroidal anti-inflammatory (NSAID) painkiller, made headlines in 2004 when the company voluntarily withdrew it from the U.S. market following reports of increased rates of strokes and heart attacks in patients taking the drug chronically. Vioxx was the most famous of more than a dozen drugs withdrawn from the market since 2000.

But withdrawal of drugs is not a new phenomenon. In fact, the Food and Drug Administration (FDA) took on its modern form as a reaction to the horrific side effects of the drug thalidomide, introduced in Europe in the 1950s as a sleep aid and treatment for morning sickness in pregnant women.

By 1962, it was evident that thalidomide caused severe limb deformities, and Frances Kelsey, the FDA’s medical officer at the time, kept the drug off of the market. In Europe, 8,000 babies were born with defects resulting from the drug. That tragedy prompted a Congressional bill that gave the FDA the authority to raise the safety bar and require that companies prove the effectiveness of drugs before they could be marketed in the United States.

FDA failures

Recently, the FDA has come under attack for not living up to its mission. The agency failed to catch serious side effects in a number of drugs before they were approved, thus forcing embarrassing withdrawals.

Critics attribute these failures to the agency’s close ties with the medical industry. These close ties are exemplified by the 1992 Prescription Drug User Fees Act, which requires industry to pay user fees that help fund the agency’s review of new drugs for approval.

Part of the purpose of the legislation was to shorten the approval times and get drugs to market more quickly. But according to a 2002 report by the Government Accounting Office (GAO), the legislation ultimately caused increased workload for the FDA’s reviewers. There was also a slight increase in the percentage of drugs that had to be withdrawn from the market.

The side effect of withdrawing drugs

The flip side of the decision to withdraw a drug due to rare, serious side effects is that it can leave some patients with few therapeutic options. For example, some patients objected to the withdrawal of Zelnorm, a drug used to treat irritable bowel syndrome.

Seriously ill patients “should be able to take a risk,” says Peter Barton Hutt, senior counsel at the law firm Covington & Burling LLP, and former FDA chief counsel.

But Diana Zuckerman, president of the National Research Center for Women & Families, argues that it isn’t that simple.

“The problem is that patients aren’t really told ([about a drug’s risks). Doctors aren’t giving that information, partly because they don’t spend that much time with patients and partly because they don’t know themselves—they haven’t read all 10 studies (performed on a drug).”

The FDA’s Hall of Shame

Vioxx

What it is: Vioxx is a COX-2 selective nonsteroidal anti-inflammatory (NSAID) painkiller related to drugs such as ibuprofen and naproxen.

Why it was taken off the market: The result of a clinical study showed an increased risk of serious cardiovascular events such as heart attacks and strokes.

Expiration date: Merck withdrew Vioxx from the worldwide markets in 2004.

Bextra

What it is: Like Vioxx, Bextra is an NSAID painkiller.

Why it was taken off the market: Two short-term studies indicated potential increases in cardiovascular events such as heart attacks and strokes and increased risk of serious skin reactions. The FDA also concluded that Bextra had no unique advantages over other NSAIDs. FDA scientists decided that the known cardiovascular risks of other NSAIDs demonstrated in long-term trials justified a request for withdrawal.

Expiration date: Pfizer withdrew Bextra from the U.S. market in 2005.

Zelnorm

What it is: Zelnorm is a drug to treat irritable bowel syndrome (IBS).

Why it was taken off the market: 29 studies showed that 13 of 11,614 patients taking the drug had heart problems. One of 7,031 patients on placebo experienced the problem. About 500,000 people were taking the drug at the time of its withdrawal. Novartis continues to market the drug in Europe, citing its belief that the trial results were a fluke.

Expiration date: Novartis withdrew Zelnorm from U.S. markets in March 2007. IBS patient groups objected to the withdrawal, arguing that the benefits outweighed the risks. The FDA responded to complaints from patients and physicians by creating a restricted-access program for patients that have no therapeutic alternatives or who had satisfactory outcomes on previous treatment with Zelnorm.

Tysabri

What it is: Tysabri is a drug that treats multiple sclerosis.

Why it was taken off the market: After three patients in a clinical study developedprogressive multifocal leukoencephalopathy (PML, a serious brain infection), the FDA halted trials of the multiple sclerosis drug until the company could prove that no additional cases of PML had occurred.

Expiration date: Biogen-Idec withdrew Tysabri from the worldwide market in 2005. In 2006 it was allowed back on the market with a risk-minimization program with mandatory patient registration and follow-up.

NeutroSpec

What it is: NeutroSpec is an antibody labeled with a radioactive marker that was used to diagnose appendicitis in patients that show some but not all of the clinical signs of appendicitis.

Why it was taken off the market: While the agent was on the market, 17 patients who received NeutroSpec experienced life-threatening side effects soon after it was injected, including shortness of breath, low blood pressure, and cardiac and pulmonary arrest. Two patients died. About 11,000 patients received NeutroSpec while it was on the market.

Expiration date: Palatin Technologies withdrew NeutroSpec from the U.S. market in 2005.

Cylert

What it is: Cylert is a drug used to treat Attention Deficit Hyperactivity Disorder (ADHD).

Why it was taken off the market: The FDA learned of 13 reports of liver failure leading to liver transplant or death. The number of cases reported was small, but patients taking the drug had a liver failure rate of 10-25 times the rate of liver failure in the general population.

Expiration date: Abbott withdrew Cylert from the U.S. market in 2005.

Permax

What it is: Permax is a drug used to treat Parkinson’s disease.

Why it was taken off the market: Two studies confirmed previous findings that Permax is associated with increased chance of blood backflow to aortic valves of the heart. Symptoms include shortness of breath, fatigue and heart palpitations. In 2006, about 12,000 patients received prescriptions in the US.

Expiration date: In 2007, Valeant Pharmaceuticals voluntarily withdrew Permax from the U.S. market. Two other companies, Par and Teva, withdrew generic versions.

Baycol

What it is: Baycol is a cholesterol-lowering drug.

Why it was taken off the market: Reports of sometimes fatal rhabdomyolysis—a severe muscle condition. All statins cause rare cases of rhabdomyolysis, but Baycol patients experienced it at a significantly higher rate than patients on other statins. The FDA received reports of 31 deaths related to Baycol.

Expiration date: Bayer withdrew Baycol from the U.S. market in 2001.

Palladone

What it is: Palladone is a narcotic painkiller in a slow-release capsule.

Why it was taken off the market: Severe side effects were reported when Palladone was taken with alcohol. Alcohol use caused high levels of the drug in the body, with potentially fatal effects such as the depression or halting of breathing and coma.

Expiration date: Purdue Pharma withdrew Palladone from the U.S. market in 2005.

See a list of all recalled drugs since 1980

For more information:

• FDA Drug Safety Alerts and Labeling Changes
• Consumer Reports: “Best Buy Drugs”
• Public Citizen: “Worst Pills”

Do you trust the FDA?