Read Those Black-Box Drug Label Warnings, They Will Make You Sick
by Bill Sardi: Two
Doctors Challenge the FDA Over the Publicís Misunderstanding of
What FDA-Approved Means
If you are
taking pills for high blood pressure, high blood sugar or high cholesterol,
and you are a bit jittery when reading about all those potential
side effects associated with prescription drugs, you might want
to avoid reading product inserts and black-box warnings altogether.
The experience is like reading a Halloween horror story and the
stress just might cause release
of more cholesterol from your liver and raise
your blood sugar, which in turn can elevate
There is no
better example of how the FDA punts on safety issues and uses Black
Box warnings to get drug manufacturers off the hook than Avandia.
Safety concerns over Avandia (rosiglitazone), an anti-diabetic drug
that was approved by the Food & Drug Administration (FDA) in
arise until 2007. By then sales of Avandia pills exceeded $3
billion a year.
Even with all
the potential side effects including premature death listed in these
warning boxes, one thing the FDA does not require of drug manufacturers
or of itself is to assist consumers in determining the relative
risks posed from one drug to another.
The FDA approves
drugs on the basis of working better than an inactive placebo pill.
Does the FDA have any obligation to educate consumers that the drugs
it approves may not be as safe as other drugs in its class? Obviously,
the FDA does not feel the need to inform the public of comparable
risks between different drugs prescribed for the same purpose.
Avandia (rosiglitazone) and Actos (pioglitazone) serve as an example.
The composite risk for strokes, heart attacks, heart failure and
death is 68%
higher for Avandia (rosiglitazone) than for pioglitazone. Avandia
produces a harmful outcome in 1 of every 60 users over a period
of 1 year.
patients understand the drug they are taking has become controversial
in the US and has been suspended from use in Europe? Probably not.
The FDAís decision
to maintain restricted availability of Avandia runs counter
to the recommendation of a senior scientist, Dr. Gerald Dal
Pan, who advised the agency to pull Avandia from the market altogether.
Dal Pan heads the FDAís Office of Surveillance and Epidemiology,
which oversees the safety of drugs that have previously been approved.
The FDA also
ordered a halt to a study that would reveal how Avandia compared
to another similar drug, Actos.
outside the US have called Avandia into question because it shows
"a degree of toxicity that should not have allowed it to remain
on the market for so long."
The FDA is
pretending to do its diligence in demanding long-term safety studies
after a drug is initially approved based upon data from relatively
small groups, but pharmaceutical companies are dragging their feet
before they finalize follow-up safety studies. That is why it took
almost 8 years to discover side mortal risks associated with Avandia.
example is Meridia (sibutramine). A safety trial of Meridia,
a weight loss drug, was committed to in 2002, began in January 2003,
completed in 2009 and published in September 2010, 3 years after
the drug had been approved. It is no longer being marketed.
In an article
The Avandia Scandal Proves Big Pharma Needs Stronger Ethical Standards"
(Bioethics, Oct 2010), researchers argue that "for-profit
pharmaceutical companies have a moral obligation to warn patients
of any data that indicates risks associated with their product."
But Avandiaís manufacturer intentionally left out some reports of
adverse events when it presented data to the FDA. Some bioethicists
advocate large financial penalties be imposed upon companies that
may attempt to hide any negative data and if pharmaceutical companies
cannot act in good conscience, they should set up bioethics committees
to provide them with one. Forget the fines, the drug makers build
that into the price. How about prison time?
a synthetic drug prescribed to improve insulin resistance among
patients with adult-onset diabetes. It also exhibits beneficial
properties for the heart and blood vessels, though inconsistently.
There are some studies showing Avandia use results in more heart
attacks and heart failure. However, the data
is mixed and perplexing for this drug.
Even in Canada
where Avandia had been restricted researchers believe limitations
donít go far enough. Health Canada issued a letter advising doctors
to restrict use of this drug to those patients for whom all other
treatments to control their blood sugar have failed or are not appropriate.
By comparison, the European Medicine Agency yanked rosiglitazone
off the market. So the burden to ensure safety has been placed upon
The US FDAís
Black Box warning issued in 2007 is another weak-kneed example.
Rosiglitazone (Avandia) is not
the first drug in its class to be withdrawn or recalled. Troglitazoneís
earlier downfall casts a dark shadow over this entire class of drugs.
Some investigators call the FDAís Black Box warning a farce.
Clinic cardiologist said: "Itís taken too long to stop the
use of a drug that clearly was harming people. Weíve got to fix
who as an investigator for Senator Charles Grassley (R-Iowa) and
the Senate Finance Committee, accused the manufacturer of Avandia
of burying negative information and said the FDA is being too timid.
"When you look at all the evidence provided by Congress to
the FDA about misconduct by the drug maker, and when you look at
the numerous independent studies saying that the drug is harming
patients, what evidence does the FDA want to have to make a decision
that a drug needs to be yanked? What evidence do you need?"
Dr. Janet Woodcock,
who heads the FDA division that evaluates medicines, said "There
is still considerable uncertainty of the magnitude and existence
of this cardiovascular risk." But why decide in favor of the
drug rather than the patients. Drugs donít get approved because
they "might" work.
by Avandiaís manufacturer said it still has faith in its product.
"The company continues to believe that Avandia is an important
treatment for patients with type 2 diabetes and is now working with
the FDA to implement the required actions," said its chief
But Time magazine
reporters fully described the drug manufacturerís irresponsibility
here. Time magazineís report entitled: "After
Avandia: Does The FDA Have A Drug Problem?" said this:
before a 2007 article in the New England Journal of Medicine
showed that the diabetes drug Avandia was linked to a 43% increase
in heart attacks compared with other medications or placebos,
a group of scientists and executives from the drug's maker, gathered
in a conference room at the offices of the Food and Drug Administration
in White Oak, Md. The goal: to convince regulators that the evidence
that the company's $3 billion-a-year blockbuster drug caused heart
problems was inconclusive.
manufacturer didn't tell the FDA was that on May 14, 2007, two
days before the White Oak meeting, the drug makerís Global Safety
Board had noted that a new assessment of Avandia studies "strengthens
the [cardiac-risk] signal observed in the [previous] analysis."
Or that eight days earlier, the company's head of research and
development, had sent an e-mail to its chief medical officer saying
Avandia patients showed an "increased risk of ischemic event ranging
from 30% to 43%!" Or that the day before the meeting, the company
had produced a preliminary draft report that showed patients on
Avandia had a 46% greater likelihood of heart attack than those
in a control group.
past two decades, as drug after drug has been recalled after winning
FDA approval, it has been hard not to wonder if FDA regulators
have been captured by the drug industry. FDA critics and industry
monitors charge that the drug-approval process is too easy for
pharmaceutical companies to game. It is in some ways an unsurprising
development. The FDA serves a public insatiably hungry for new
medicines. Yet the agency does not have responsibility for performing
safety testing. It relies on drug companies to perform all premarket
testing on drugs for safety and efficacy.
reveal that the FDA doesn't have a complete or accurate list of
prescription drugs on the market and is missing or has incomplete
information on one-third of the drug-safety and efficacy trials
also threw tomatoes at Avandia. The New
England Journal of Medicine weighed in on the controversy.
So did the
Medical Journal, which said: "It was, as one Food and
Drug Administration (FDA) adviser put it, a "perfect regulatory
storm" Ė a combination of problematic data, uncertain clinical
need, politics, and poor drug company behavior."
The FDA warning
had an effect, but it was not enough. While the absolute number
of filled prescriptions for rosiglitazone decreased from 1.3 million
monthly at the peak (in January 2007) to slightly more than 317,000
in June 2009, a lot of Americans were still taking the drug.
A law group
in Canada has gone so far as to
file class-action lawsuits against Health Canada and the manufacturer
of Avandia for not fully informing patients they faced an increased
risk for serious medical events when taking this drug.
Why do we even
have an FDA? Did anyone agree with the FDAís position on Avandia?
Congress? Consumer watchdogs? Doctors groups?
For those diabetic
patients who continue to take Avandia, avoidance of side effects
is another aspect of drug information that the FDA skips over.
with Avandia has been in determining the underlying cause of adverse
events. Some researchers in Europe believe Avandiaís problem may
emanate from over-dosage
or decreased elimination of the drug among patients at high-risk
for heart and blood vessel disease. But over-dosage is a cop-out.
mechanisms behind heart side effects associated with Avandia (rosiglitazone)
use may be linked to the selection of oils in the diet. When laboratory
mice were fed a corn oil diet + rosiglitazone they were found to
exhibit inflammation that stimulates heart enlargement which was
when animals were fed the drug + fish oil.
to be an increased
risk for bone fractures when taking this class of drugs, and
that is a dire sign.
It is possible
that the drug induces loss of calcium from bone which is then deposited
in arteries, stiffening them and increasing the risk for adverse
events like strokes and heart attacks.
promotes calcification of arteries which is countered
by an herbal supplement.
him mail] is a frequent writer on health and political
topics. His health writings can be found at www.naturalhealthlibrarian.com.
latest book is Downsizing
© 2011 Bill Sardi Word of Knowledge Agency, San Dimas, California.
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