Safety In Using Five Drugs. A day after an FDA official raised safety concerns about five widely prescribed medicines, doctors and patients had the same question: Should they still use the drugs?
David Graham, the Food and Drug Administration’s associate director of drug safety, testified before a Senate committee Thursday that not only had his agency not given enough weight to safety concerns about the recalled painkiller Vioxx, but he also said regulators should be looking closely at five other drugs.
They are: Pfizer Inc.’s Bextra, a pain reliever in the same class as Vioxx; Crestor, a cholesterol-lowering drug manufactured by AstraZeneca PLC; Meridia, a weight-loss drug made by Abbott Laboratories; the acne drug Accutane made by Roche Holding AG; and Serevent, an asthma medicine from GlaxoSmithKline PLC.
Manufacturers of these drugs on Thursday defended their products, most of which already have the U.S. regulatory agency’s “black box” warnings the strongest alert on their labels regarding safety issues. The five drugs Graham said warrant closer scrutiny have been approved as safe and effective by the FDA and “continue to be closely monitored with regard to safety and the balance of benefit to risk,” FDA spokeswoman Kathleen Quinn said Friday.
Medical experts say patients taking those medications should not stop doing so without consulting with their physicians. Still, each of the medicines Graham criticized has been controversial. Here is why:
Bextra, in the same chemical class as Vioxx, was shown in a recent preliminary study to double the risk of heart attack and stroke among patients with heart disease, researchers reported at the annual meeting of the American Heart Association. Pfizer had already told regulators it intends to add to Bextra’s packaging a black box warning that Bextra can cause potentially fatal skin reactions.
Crestor, a cholesterol medicine, has been linked to kidney failure and potentially life-threatening muscle damage. The consumer advocacy group Public Citizen asked the FDA in August to investigate AstraZeneca, alleging the drugmaker delayed reporting 23 cases of serious side effects. They included 19 cases of muscle weakening or rhabdomyolysis and four incidents of kidney damage.
asthma-related deaths in patients
Serevent, an asthma treatment, carries a boxed warning of a “small but significant increased risk” in asthma-related deaths in patients receiving the drug. The FDA said there were 13 deaths out of 13,174 patients treated for 28 weeks, versus four on placebo. The analysis also suggested the risk may be greater in black patients than Caucasians.
Meridia, an anti-obesity drug, increases blood pressure and heart rates and has been associated with a number of deaths and adverse reactions since it was introduced.
Accutane, an acne drug, can cause brain and heart defects, mental retardation and other abnormalities in babies of pregnant women taking the drug. Roche Holding and generic makers in February started a national registry mandating women cannot get their monthly supply of Accutane without a negative pregnancy test. They are told to use two forms of contraception while taking the drug.
Spokespersons for the five drugs’ makers have said they are safe and effective when used as directed.
Public Citizen, founded by Ralph Nader, has asked the FDA to remove Crestor and Meridia from the market. Sidney M. Wolfe, the director of Public Citizen’s Health Research Group, said Friday he also thinks Bextra should be pulled from the market.
“All these drugs are very problematic,” Wolfe said. He added when people in the FDA like Graham raise questions, “their views are usually squelched. The FDA is too beholden to the manufacturers.”
The problems “are generally known within the FDA, but the agency silences people who criticize the drugs or the policies,” he said.
Daniel A. Hussar, a professor of pharmacy at University of the Sciences in Philadelphia, said Bextra was the only drug of the five Graham mentioned he thinks should be removed from the market. He said studies have indicated an increased risk of heart attacks and an association with a rare, but potentially fatal, skin reaction.
However, consumers should not be “unnecessarily alarmed” about health risks, he said. “Physician offices have to be overwhelmed with calls, but I think the alarm is excessive. When the drugs are appropriately used, and in appropriate doses, they can be safe.”
Pfizer spokeswoman Mariann Caprino said her company is “committed to conducting long-term studies of Bextra” to detect possible problems.
AstraZeneca, maker of Crestor, said it remains “fully confident” the drug is safe. “We have been assured by the highest levels at the FDA that there are no new concerns about Crestor’s safety and that Dr. Graham’s testimony does not reflect the views of the FDA,” said spokesman Steve Lampert.
Laureen Cassidy, a spokeswoman for Abbott Laboratories, said: “Science continues to support the safe use of Meridia to treat obesity, the leading health epidemic in the U.S. Meridia has been extensively studied in more than 100 clinical trials involving more than 12,000 patients throughout the world.”
GlaxoSmithKline said Serevent “is safe and effective when used appropriately” and according to labeling guidelines, and it has a “black box” warning on its label.
LaRoche Holdings spokeswoman Carolyn Glynn said Accutane is reserved for “the most serious forms of acne unresponsive to other therapies.”
The company and other generic manufacturers have a new national registry to monitor Accutane prescriptions. “This is something we have been very focused on for 23-plus years. It was a surprise to us that we ended up as one of the five drugs,” she said. Though it wasn’t mentioned that Roche is still involved in the Accutane lawsuit flurry that started since the drug’s inception on the US market.