FDA Under Fire: Drug Safety, What to Do?

New allegations from an FDA scientist that the agency is failing at its job of ensuring the safety of the drugs it approves has many Americans thinking twice before taking their daily dose.

But before you throw out your prescription bottle, experts say there are many more sides of the story to consider.

First, no one should stop taking a prescription medicine without consulting their doctor. Second, all medications carry some degree of risk and weighing the benefits versus the risks of a particular drug is a decision that should be made on an individual basis.

“All medicines have risks and potential side effects. That’s why there is a drawn out, detailed 10-15 year drug approval process so that FDA reviewers can ascertain what the potential risks may be and then they can determine whether the benefits outweigh the risks,” says Jeff Trewhitt, spokesman for the Pharmaceutical Research and Manufacturers of America (PhRMA).

Despite the recent allegations, Trewhitt says the FDA drug approval process is still widely considered to be the world’s gold standard for safe and effective treatment.

“One of the things that is very important to remember is that the FDA — using its scientific consensus process and not just one drug reviewer — makes important safety decisions,” Trewhitt tells WebMD. “What was heard yesterday was the opinion of one drug reviewer.”

In testimony before the Senate Finance Committee yesterday, FDA scientist David J. Graham, MD, MPH, told lawmakers that the agency is “incapable of protecting America against another Vioxx,” referring to the widely used arthritis drug that was pulled from the market on Sept. 30 after studies showed it increased the risk of heart attack.

Aside from criticizing the FDA for not acting sooner to protect Americans from the potential risks associated with Vioxx, Graham also warned that five additional popular prescription drugs should be closely monitored due to safety concerns. Graham fingered Crestor, Bextra, Meridia, Serevent, and Accutane in his statement.

FDA Response

In a statement released late last night, Steven Galson, MD, acting director of the FDA’s Center for Drug Evaluation and Research, said Graham’s congressional testimony “does not reflect the views of the agency.”

“The FDA evaluates the safety and effectiveness of all drugs independently on a case-by-case basis before they are approved to enter the marketplace and also evaluates reported adverse events with all drugs already on the market to assess whether unforeseen safety concerns need to be addressed,” says Galson.

During his testimony, Graham, who is an associate science director at the FDA’s Office of Drug Safety, said that the recommendations of drug safety reviewers are often overruled by officials in the FDA’s Office of New Drugs. He asked lawmakers to create an independent drug safety monitoring office free of the influence from regulators who approve new drugs.

But Galson says the FDA’s Office of New Drugs is already an independent office and is separate from the office that reviews drug safety. Both offices report to Galson, as the acting director of the Center for Drug Evaluation and Research.

To address post-approval drug safety concerns, Galson says he recently asked the Institute of Medicine (IOM) to look at the structure of the FDA’s post-marketing surveillance program and to give their advice on whether additional changes are needed to the agency's approach to drug safety.

Trewhitt says the decision to conduct an independent review of the FDA’s post-approval drug safety monitoring efforts is a wise one, as the number of new drugs approved by the FDA has increased in recent years.

Drug Companies React to Safety Concerns

Many of the drugs Graham pointed out are already under heightened scrutiny by the FDA. But Galson says, “The five specific drugs that Dr. Graham identified in his oral testimony are currently approved as safe and effective for use in the United States.”

In statements and interviews with WebMD following Graham’s testimony, the pharmaceutical companies that produce the drugs say they are safe and effective when used as directed.

Serevent:

Use: Treats asthma and chronic obstructive pulmonary disease (COPD).

Concerns: The FDA added a new black box warning to the label of Serevent in August 2003, after a study showed a small increased risk of life-threatening asthma attacks and deaths in people using the drug.

Response: In a statement, GlaxoSmithKline says it stands firmly behind Serevent. “Any issues concerning mortality associated with Serevent have been fully considered by the FDA, resulting in a black box warning that was included in the medicine’s label.”

Crestor:

Use: Part of a class of widely used drugs known as statins, Crestor is used to treat unhealthy cholesterol levels.

Concerns:Earlier this year, European public health officials issued a new warning label for Crestor. The label warned of the potentially toxic muscle damaging effect of the drug and stated that people over 65, those with underactive thyroid, and people with kidney problems may be most at risk, especially at the higher 40-milligram-per-day dose. Following the European warning, the FDA said it was evaluating those reports and urged doctors in the U.S. to carefully follow existing precautions on the drug’s label regarding the risk of muscle damage.

Response: The drug’s manufacturer, AstraZeneca, says Crestor’s application for FDA approval was the most extensive ever for a statin, and it was unanimously recommended for approval by the FDA’s advisory board in July 2003. In a statement released today, AstraZeneca officials say, “We have been assured today at senior levels in the FDA that there is no concern in relation to Crestor's safety.”

Meridia

Use: Weight loss

Concerns: In 2002, the group Public Citizen petitioned the FDA to withdraw its approval of Meridia after it claimed studies showed that the drug may increase blood pressure and heart rate and offers only a small benefit at the cost of serious side effects.

Response: In a statement emailed to WebMD, Abbott Laboratory spokeswoman Laureen Cassidy says Meridia is one of the few drugs available for the treatment of obesity. Cassidy says a two-year study of Meridia showed that only 6 percent stopped using the drug due to side effects.

Bextra

Use:The drug is in the same class of Cox-2 inhibitors as Vioxx and is used to treat pain and arthritis.

Concerns: Two studies have linked the drug to an increase in heart attacks, including one released earlier this month at an American Heart Association conference that showed that Bextra doubled the risk for heart attacks and strokes among people with arthritis or heart disease. The FDA has planned an advisory committee meeting to discuss the safety of Cox-2 inhibitors in February 2005.

Response: Pfizer says it will participate in the FDA’s Cox-2 safety meeting in February. Spokeswoman Jeanne Traflet says, “Bextra has been found safe and effective when used as indicated to treat OA/RA (osteoarthritis and rheumatoid arthritis) and pain due to menstruation. As previously announced, Pfizer is committed to conducting further studies to confirm the longer-term safety profile of Bextra in those patients who require chronic treatment for arthritis with a Cox-2 inhibitor.”

Accutane

Use: Treatment of severe acne

Concerns: Studies have shown the drug can cause birth defects if women take the drug while pregnant. It has also been linked to a possible risk of depression when used by adolescents. The drug’s label states that Accutane should not be used by women who are pregnant or may become pregnant. In February, an FDA advisory committee recommended stricter patient tracking rules for patients who use Accutane. In October, a bipartisan group of U.S. lawmakers has accused the Bush administration of moving too slowing on adopting new safety measures regarding Accutane.

Response: Accutane maker Roche Pharmaceuticals was unavailable for comment at press time

By Jennifer Warner, reviewed by Brunilda Nazario, MD

SOURCES: FDA. Jeff Trewhitt, spokesman, Pharmaceutical Research and Manufacturers of America (PhRMA). Jeanne Traflet, public relations director, Pfizer Pharmaceuticals. News release, GlaxoSmithKline. News release, AstraZeneca. News release, Abbott Laboratories. WebMD Medical News: “Scientist: FDA Incapable of Protecting Safety.”