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Knight Ridder Newspapers
WASHINGTON - A highly toxic heart drug continues to be prescribed to millions of patients nationwide without the detailed consumer warnings promised by the U.S. Food and Drug Administration more than a year ago.
Each bottle of the drug, amiodarone, is supposed to include a new advisory that warns of its many risks and symptoms of fatal side effects and explains how the medication is supposed to be used. But the advisory, planned since October 2003, remains in draft form, bouncing back and forth between the FDA and the drug maker assigned to write it.
The delay comes as the FDA is being questioned about its slowness in protecting Americans from deadly drugs, including the arthritis drug Vioxx, which was pulled off the market this fall.
"How many people are dying right now as we speak as a result of their procrastination?" asked Karen Muccino of Los Alamitos, Calif., whose father died Feb. 20 of lung damage caused by amiodarone. Despite his training as an obstetrician, Muccino's father never realized his dry cough was a symptom of a potentially fatal side effect, Muccino said.
She said she's livid that the FDA didn't immediately issue the patient warnings last fall. "He would have been taken off the drug three months earlier and his life would have been saved," she said.
Sen. Charles Grassley, chairman of the Senate Finance Committee, said Tuesday that he will look into the delays in the amiodarone warnings.
"What's happening with this drug goes to the heart of questions about how long it takes the FDA to act when known risks or dangers exist," said Grassley, R-Iowa. "The FDA and drug companies might know about risks, but it doesn't do any good if doctors and patients don't know about them too."
Like most patients, Muccino's father was taking amiodarone for atrial fibrillation, a common condition in which the heart beats out of rhythm. The FDA never approved the drug to treat that condition.
Patients taking amiodarone have died from lung and liver damage, gone blind or suffered from other side effects. Yet it's routinely prescribed for common heart rhythm problems despite the availability of safer alternatives. The FDA has approved amiodarone only for more severe disorders, called ventricular arrhythmias, and then only as a treatment of last resort.
According to recent data, doctors wrote more than 2 million prescriptions in a single year for atrial fibrillation and other heart conditions that amiodarone wasn't approved to treat. A Knight Ridder investigation last year found that those prescriptions represented 82 percent of all the amiodarone dispensed from retail pharmacies during the 12-month period ending July 31, 2003.
Earlier this month, a class-action lawsuit was filed in New Jersey that accuses drug makers of promoting amiodarone for common heart ailments in an effort to boost profits. The suit contends that more than 1,000 people died, 100 had vision problems and thousands of others suffered severe medical complications.
FDA officials didn't respond to repeated requests for interviews about amiodarone and its efforts to protect consumers. An FDA spokeswoman instead referred questions to Wyeth, the drug maker assigned to write the advisory.
Wyeth spokesman Chris Garland said the FDA could approve its advisory as early as next month. Wyeth, which sells the drug under the brand name Cordarone, was given the job of writing the informational guide because it was the first company to sell the drug. Amiodarone currently is sold by several generic manufacturers, as well as under another brand name, Pacerone.
When the FDA approved amiodarone for sale in the United States, it recognized that it was a dangerous drug and told doctors to be careful about its use.
Dr. Valentin Fuster, the chairman of the American College of Cardiology's treatment guidelines committee for atrial fibrillation, said amiodarone shouldn't be the first drug a doctor tries when treating the disorder.
"You don't use amiodarone as a drug for this except after everything else fails," said Fuster, who's also director of the cardiovascular institute at Mount Sinai Medical Center in New York City. "Amiodarone carries a higher risk than other drugs."
Knight Ridder found that patients routinely got little information about its risks or alternative therapies. Over the years, the FDA has cited various manufacturers for downplaying the drug's risks and for promoting it as a first-line therapy.
In October 2003, Dr. Janet Woodcock, who at the time ran the FDA's drug division, said the agency would take the rare action of requiring the advisory in all amiodarone prescriptions.
Because of the dangers posed by the drug, Woodcock said the information would be written and distributed quickly, certainly by early 2004. "Obviously this drug is a very risky drug," she said then.
Woodcock, now the FDA's acting deputy commissioner for operations, didn't respond to requests for an interview over the past week. Nor would anyone at the FDA respond to written questions about the appropriateness of allowing a drug maker to be in charge of writing warnings that may reduce its sales, or whether the delays are excessive.
The FDA first asked Wyeth to write the guide on Dec. 19 and the company gave the FDA a first draft on Aug. 23. "That was in advance of what the FDA asked us and what we told them we would do," Garland said. "We told them we would submit by November."
The FDA sent back its first comments on the guide on Sept. 21, Garland said. And Wyeth replied in October. The draft is currently with the FDA, he said, adding that the process is happening very quickly by drug regulation standards.
"Normally the FDA can take up to six months to respond to an initial filing," he said.
Meanwhile, patients taking amiodarone continue to die.
Doctors in St. Paul, Minn., told 48-year-old Bob Hanson only that amiodarone was "difficult to tolerate" when it was prescribed last December to treat a slight atrial fibrillation, said his widow, Mary McGurran.
Hanson underwent successful heart valve replacement surgery on Dec. 3 but died Dec. 19 of liver failure, with amiodarone listed in the autopsy report as a possible cause.
"I'm thinking `difficult to tolerate,' that means it's going to make him nauseous," said McGurran, who lives with the couple's three children in Minneapolis.
Despite asking detailed questions about all her husband's medications, McGurran said no one told her the drug wasn't approved to treat his atrial fibrillation, nor did they discuss any of the risks.
"I questioned everything. That's what kills me. I questioned everything and I swear it didn't do any good," said McGurran, a geriatric social worker.
Officials at Regions Hospital in St. Paul, where Hanson was first given amiodarone intravenously, then sent home with pills, declined to comment. In a letter McGurran received this week, hospital officials said a team will be evaluating her husband's care and the use of amiodarone. Hanson's surgeon didn't respond to requests for an interview.
"This was much more than one 48-year-old man that should not have died," McGurran said. "He died because of systemic problems with drug marketing and with the FDA not providing sufficient safeguards."
In the lawsuit against Wyeth and several other makers of amiodarone, patients and their families accused the drug makers of a nearly 20-year scheme to push doctors to prescribe the drug for unapproved uses while concealing and downplaying its risks.
"It's our belief there has been one long over-promotion of this drug," said David Harris, a Naples, Fla., attorney who filed the suit Nov. 10 in Atlantic County Superior Court in New Jersey. Officials at Wyeth, the lead defendant in the case, had no comment about the suit.
Karen Muccino is one of five plaintiffs. Her father, Dr. John Muccino, 69, had suffered from chronic atrial fibrillation since he was in his 40s, she said. When his heart was out of rhythm, it made him tired. He was put on various medications over the years with varying degrees of success. In October 2002, doctors put him on amiodarone, she said.
About a year later he developed a dry cough. The cough worsened and by New Year's Day 2004 he was very ill with what he thought was a bad cold. Within days he was hospitalized with what seemed to be pneumonia. A lung biopsy, however, found it was amiodarone lung damage, Karen Muccino said. Her father died after being taken off a respirator on Feb. 20.
"There must be changes made and there must be some accountability," said Muccino, a nurse by training and the vice president of a health care firm. "There are so many medications that have labels on them saying `take with food or milk,' but you have a drug like this that has such slight warnings of an impending fatal situation and it isn't noted on the prescription bottle, which is totally ridiculous."
To read Knight Ridder's investigation of the off-label use of drugs, including amiodarone, go to www.realcities.com/mld/krwashington/news/special-packages/riskyrx/
(c) 2004, Knight Ridder/Tribune Information Services.
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