Risky Rx: Drugs used for unapproved purposes can kill, injure patients
"A six-month Knight Ridder investigation has found that patients nationwide are being injured and killed as doctors routinely prescribe drugs in ways the FDA never certified as safe and effective.
Moreover, these unapproved prescriptions are soaring. Over the last year, 115 million such prescriptions were written, nearly double the number of five years ago, an exclusive Knight Ridder analysis of prescriptions for the country's top-selling drugs found.
The practice, called off-label prescribing, often is driven by questionable research, aggressive drug-company marketing and cavalier doctors, and condoned by tepid regulators."
Part 1: Prescribing drugs 'off label' is routine, but can injure, kill patients
Part 2: Drug makers' promotions boost off-label use by doctors
Part 3: FDA oversight of off-label use wanes as prescriptions rise
Discharged and Dishonored: Shortchanging America's Veterans
"Tens of thousands of other veterans have returned from war only to find that they have to fight their own government to win the disability payments they're owed. A Knight Ridder investigation has found that injured soldiers who petition the U.S. Department of Veterans Affairs for those payments are often doomed by lengthy delays, hurt by inconsistent rulings and failed by the veterans representatives who try to help them."
VA's red tape squelches veterans' long-overdue disability claims
"During World War II, commanders gave fighter pilot Frank Fong some of the Army Air Corp's highest honors for heroism and skill: two Distinguished Flying Crosses and eight Air Medals. But it took 48 years for the U.S. Department of Veterans Affairs to concede that a plane crash scarred his left eye and eventually took his sight." World War II pilot battles five decades for plane crash compensation.
"The state pays Michigan's politically powerful veterans charities nearly $4 million a year to help veterans apply for disability and other federal benefits. But no one is overseeing the program to ensure that Michigan taxpayers are getting their money's worth. The result, Knight Ridder found, is that in a state where many veterans are missing out on disability payments that they're due, some veterans groups are getting tens of thousands of dollars but filing only a few claims. One group, the Polish Legion of American Veterans, didn't file a single disability claim during the past two years, a Knight Ridder analysis of the groups' annual activities reports found." Michigan's money to veterans groups goes unregulated
"The pitches from AMVETS are practiced and smooth: Help America's veterans get treatment for their disabilities or monthly checks to compensate for their injuries. Give them the means to avoid homelessness. AMVETS tells potential donors that it's chartered by Congress, which creates the misleading impression that the U.S. government vouches for the organization and is overseeing it.
AMVETS spent $8.5 million in 2004, but according to its tax record only 22 percent of it went for programs that helped veterans ...
Far from watching over AMVETS and the dozens of other veterans groups it's chartered, Congress doesn't even examine the annual reports they're required to file, other than to make sure that they've been filled out properly." Spending practices by veterans groups varies
Amiodarone Coverage
Knight Ridder Washington Bureau, Nov. 4, 2003:
FDA Oversight of 'off-label' drug use wanes as prescriptions rise
http://www.mcclatchydc.com/2003/11/04/28118/fda-oversight-of-off-label-drug.html
Detroit Free Press, Nov. 26, 2004
Warning Stalled as Heart Pill Kills;
Patient Advisory Promised by U.S. Agency Last Year
Each bottle of the drug, amiodarone, is supposed to include an 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 drugmaker assigned to write it.
The delay comes as the FDA is being questioned about its slowness in protecting the public 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
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'll 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. An investigation last year by the Free Press
Earlier this month, a class-action lawsuit was filed in
FDA officials didn't respond to repeated requests for interviews about amiodarone and its efforts to protect consumers. An FDA spokeswoman referred questions to Wyeth, the drugmaker assigned to write the advisory.
Wyeth spokesman Chris Garland said the FDA could approve its advisory as early as December. 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
Dr. Valentin Fuster, chairman of the
"You don't use amiodarone as a drug for this except after everything else fails," said Fuster, who is also director of the cardiovascular institute at
The Free Press
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 drugmaker to be in charge of writing warnings that may reduce sales, or whether the delays are excessive.
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 heart valve replacement surgery on Dec. 3 but died Dec. 19 of liver failure; amiodarone was 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
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
"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."
FACTS ABOUT AMIODARONE
What are amiodarone's risks?
The drug's FDA-approved prescribing label for doctors, which patients rarely see, warns that the drug comes with "substantial toxicity."
- About three fourths of patients taking a 400-milligram dose experienced side effects.
- Lung toxicity harmed as many as 17 percent of patients in some studies, and has been fatal about 10 percent of the them.
- Liver injury is common. Though usually mild, it can be fatal.
- Worsening of the heart rhythm problem.
- When given to pregnant women, the drug has caused serious harm to the fetus.
- Other side effects include thyroid problems and neurological disorders. Vision problems and blindness also have been reported.
Should patients take amiodarone for atrial fibrillation?
The FDA hasn't approved amiodarone to treat atrial fibrillation. However, as with all drugs, doctors can prescribe it "off label" after weighing the risks and benefits.
According to the latest research, particularly a major National Institutes of Health study called AFFIRM, experts say amiodarone generally isn't the first drug a patient should try for atrial fibrillation.
A patient should first try a drug to regulate how fast the heart beats.
Other options include a procedure to destroy the misfiring electrical connection in the heart. Patients also can be treated with various rhythm-control drugs.
What can patients do?
- Talk with your doctor. Ask why he or she chose rhythm control over rate control. For more information about the AFFIRM study, go to www.nhlbi.nih.gov/new/press/02-12-04.htm.
- Don't stop taking amiodarone without a doctor's supervision.
- Make sure your doctor regularly monitors you for signs of lung, liver and thyroid problems.
- Ask your pharmacist for a copy of the official, FDA-approved prescribing label - not just the one-page sheet that pharmacies often hand out with drugs. Or read the label online at www.cordarone.com.
- To report an adverse drug reaction: Go to www.fda.gov/medwatch/how.htm or call 1-888-463-6332.
Year later, FDA backs publication of new warnings on heart drug
By Alison Young
Inquirer
After a delay of more than a year, the Food and Drug Administration has approved publication of new patient warnings for a potentially risky heart drug that millions of Americans are taking.
Patients taking the drug, amiodarone, can read the new warnings online at www.wyeth.combeginning next week and will soon start receiving paper copies when they get or refill prescriptions.
Amiodarone, also sold under the brand names Cordarone and Pacerone, has numerous serious and fatal side effects, including lung toxicity, thyroid problems and liver damage.
The FDA has not responded to repeated requests by the Inquirer Washington Bureau for information about why publication of the amiodarone medication guide - planned since October 2003 - has taken so long.
The guide is undergoing a final edit and will be posted on the Web sometime next week, said Chris Garland, a spokesman for Wyeth, the drug-maker assigned to write it. Details of the guide's contents were not available yesterday.
In general, such guides contain detailed warnings about potential side effects, how the drug should be used, and what conditions the FDA has approved it to treat.
Because of amiodarone's dangers, the FDA approved it only as a drug of last resort for specific life-threatening heart rhythm conditions, called ventricular arrhythmias. But over time, it has gained favor with cardiologists as a treatment for atrial fibrillation, a common and less serious rhythm condition it was never approved to treat.
According to recent pharmaceutical-industry data, doctors wrote more than two million prescriptions in a single year for atrial fibrillation and other heart conditions the drug was not approved to treat. For the year ended July 31, 2003, 82 percent of the drug's retail sales were for unapproved uses, an Inquirer Washington Bureau analysis found last year.
While many cardiologists defend amiodarone's "off-label" use for atrial fibrillation, a recent National Institutes of Health study challenged their long-held beliefs. The study, called AFFIRM, found that less risky drugs that control a patient's heart rate can be as effective as rhythm-control drugs such as amiodarone.
It will be up to the FDA to determine how this information will be distributed to patients taking versions of the drug made by several generic manufacturers,
FDA officials did not respond to requests seeking information about this.
"This was put together on a very aggressive timetable,"
The warnings aren't coming soon enough for families harmed by the drug.
Carol Holcomb said her mother died of pulmonary fibrosis in September after taking amiodarone for about two years for atrial fibrillation.
"I realize it's an effective drug, but the people taking it have to know the risks, and I don't think they do," said Holcomb, who lives in Flourtown,
When her mother, Anna May Gerstlauer, first went to the hospital with breathing problems, Holcomb said, doctors thought she had pneumonia. Only later, when her condition worsened, was the drug suspected. Gerstlauer, who turned 78 in the hospital, died while on a respirator, her daughter said.
Larry Sasich, a pharmacist and analyst at Public Citizen's Health Research Group in
"What I hope the impact will be is that patients ask their physicians hard questions about whether or not I really need this," Sasich said. "Do I need a drug that's not approved for the condition I have where there are substantial risks?"
