Not All Drugs Are the Same After All
Jim Higgins
http://www.nytimes.com/2009/12/19/health/19patient.html?_r=1&hpw
LET me start by saying I�m a fan of generic drugs. They save Americans
billions of dollars each year and give us access to wonderful drugs at
affordable prices. I�ve recommended generics in this column many times
and use them myself when possible.
But there is a gnawing concern among some doctors and researchers that
certain prescription generic drugs may not work as well as their
brand-name counterparts. The problem is not pervasive, but it�s
something consumers should be aware of � especially now that more
insurers insist that patients take generic medications when they are
available.
Let me also prepare the groundwork for what I hope will be full and
frank reader comments, by acknowledging that this issue is controversial.
Joe Graedon, who has been writing about pharmaceuticals for three
decades and runs a consumer advocacy Web site, the People�s Pharmacy
(peoplespharmacy.com), was 100 percent behind generics for many years.
�We were the country�s leading generic enthusiasts,� he told me
recently. But over the last eight or nine years, Mr. Graedon began
hearing about �misadventures� from people who read his syndicated
newspaper column, also called The People�s Pharmacy.
The stories were typically from patients who were switched from a brand
name drug to a generic one and had side effects or found that their
symptoms returned � or even became worse than before they were
medicated. Most recently Mr. Graedon has been hearing complaints on his
Web site about generic forms of the antidepressant Wellbutrin XL 300
(known as Budeprion XL 300 in one generic form), the heart medicine
Toprol XL (metoprolol succinate) and the antiseizure medicine Keppra
(levetiracetam).
�Consumers are told generics are identical to brand name drugs, but that
is clearly not always the case,� Mr. Graedon said.
Some specialists, particularly cardiologists and neurologists, are
concerned about generic formulations of drugs in which a slight
variation could have a serious effect on a patient�s health. The
American Academy of Neurology has a position paper that says, in part,
�The A.A.N. opposes generic substitution of anticonvulsant drugs for the
treatment of epilepsy without the attending physician�s approval.�
But insurers tend to argue otherwise. On Thursday, ExpressScripts, which
handles drug insurance for big employers, put out a news release
announcing results of a study it sponsored that found no difference in
hospitalizations or emergency-room visits for people on brand-name
epilepsy drugs compared with those taking generics.
The Food and Drug Administration, meanwhile, says it stands behind
generic medications and its methods for approving them.
�We have not seen any scientific studies that show generics do not hold
up as well as brand name drugs,� says Gary J. Buehler, director of the
agency�s office of generic drugs. �We believe the generic drugs we
approve work in everyone.�
The American Medical Association concurs. A spokeswoman for the group
told me in an e-mail message, �the A.M.A. position is that as a whole
generic drugs do work as well as name-brand drugs.�
Yet, after hundreds of consumers posted messages about problems with the
generic drug Budeprion XL 300 on the People�s Pharmacy Web site, Mr.
Graedon worked with an independent laboratory, ConsumerLab.com, to test
the drug, which in other generic versions is typically known as bupropion.
The lab found that Budeprion XL 300 released the active drug at a
different rate than the brand name Wellbutrin XL 300. Mr. Graedon and
the lab conjecture that the different dissolution rates might be to
blame for the reported side effects and lower effectiveness of Budeprion.
But Mr. Buehler at the F.D.A. explained to me that over the course of 24
hours a patient ends up with the same amount of the drug in the
bloodstream, so there should be no reason for a variation in
effectiveness. �We remain puzzled,� he said.
The maker of Budeprion XL 300, Teva Pharmaceutical Industries, recently
announced that it would conduct a clinical trial comparing its product
against the original, Wellbutrin XL.
A Teva spokeswoman said in an e-mail message that the company was
working with the F.D.A. on a study �specifically designed to answer the
questions raised following the recent anecdotal commentary on generic
budeprion.�
�We believe the study and the resulting data will provide further
scientific support for the product�s bioequivalence to the innovator
drug,� she said.
To parse that statement � or at least understand �bioequivalence� � it
is worth taking a step back to consider what a generic drug is and how
it gets approved.
When a name-brand drug�s patent expires, other manufacturers are
generally free to create their own version of that product. If a drug is
popular, a dozen or more companies may rush in to create a copy of it.
According to F.D.A. rules, the new generic version must �have the same
active ingredient, strength and dosage form� as the brand name or
reference product.
A generic medication must also be bioequivalent to the brand name drug,
meaning that it must �be shown to give blood levels that are very
similar to� the brand name product, according to a fact sheet on the
F.D.A.�s Web site. Generally, the only test that a maker of a generic
medication must perform to receive F.D.A. approval is one that
establishes the �bioequivalence� of the product. This test is done on
healthy volunteers and compares the blood levels of the reference drug
to the generic one.
According to Mr. Buehler of the F.D.A., to be considered bioequivalent,
the generic drug must reach a blood serum level that is 80 to 125
percent of what the reference product achieves. But Mr. Buehler said
that in reality the spread was not nearly that large. He noted that the
F.D.A. conducted a large study and found that the average difference in
absorption into the body between a generic and brand name drug was only
3.5 percent.
Some specialists, though, worry that the allowable range for
bioequivalence is too wide, especially for patients who are taking
medication to control problems like arrhythmias or seizures.
If a patient with the heart arrhythmia known as atrial fibrillation who
also has risk markers for stroke gets a blood thinner for which the
levels are too low, �there is risk for stroke, and if the levels are too
high it could result in bleeding,� says James A. Reiffel, a cardiologist
and professor of clinical medicine at Columbia.
Neurologists who treat epilepsy have similar concerns. Two studies
published last year in the journal Neurology found that patients who
switched from a brand-name product to a generic one had more seizures or
higher hospitalization rates.
�For many drugs, generics are just fine,� said Kimford Meador, a
professor of neurology at Emory University.
�But when you�re taking a seizure medication, the therapeutic window is
narrow,� Dr. Meador said. �If the absorption of the drug is slightly
different between brand and generic or between generics, then the
patient could have a seizure, and that seizure could lead to serious
injury or perhaps even death.�
The problem is not just in changing from a name-brand drug to a generic,
Dr. Meador said, but also switching from generic to generic. And the
patient may not even know the change is happening.
When patients are on maintenance medication for which a generic is
available, they might be given a different version of the generic drug
when refilling their prescriptions. A pharmacy might stock one generic
for a few months, and then switch to another a few months later, if the
store is offered a better deal on it.
A pharmacist is not required to notify the patient of the change,
although some choose to do so.
So for a few months you might receive a drug that was on the low side in
the bioequivalence test, and then be switched to one on the high side of
the test.
Stephanie Ford, 29, who spoke on condition that she not be otherwise
identified, had been taking Lamictal to control her bipolar disorder.
When a generic version came out two years ago, her insurer switched her
to it.
Ms. Ford found that the generic drug, lamotrigine, worked just as well
as the name brand and cost her just $10 a month instead of the $45
copayment she had been spending on the brand name. (For a person without
insurance, Lamictal can cost about $300 a month, depending on the dosage.)
But when her insurer then urged her to order her medication by mail, she
received another generic version of Lamictal and her symptoms returned.
�After about a week,� she wrote in an e-mail message, �I noticed a
difference in my emotional state (and nothing changed in my life) and by
a week and a half, I had digressed to the state I had been before being
on medication.�
Ms. Ford has found a local pharmacy that carries the original generic.
She now buys the medication directly from that store. Because her
insurer charges her a $5 penalty for not using mail order, her copayment
is now $15.
She says her condition has once again stabilized.
--
Civis Romanus Sum
AndyS
It also makes me wonder how much of these personal
experiences are psychosomatic. Just the idea of being
given a "cheaper" version will influence the affects on
many people, which is why sugar pills often produce
the same effects as a valid drug in field tests......
I'm not saying that these stories aren't true --- I'm just
questioning whether the pshchological effect of feeling one
is being given a "cheap copy" might account for many of
the negative effects.
I know that my wife swears by brand name grocery
products , even when the store equivalents are manufactured
by the same company in the same plant but given a
store label. She feels that paying $3 for a sack of flour
MUST make better tasting bread than a $1 loaf of bread.....
and that paying $2 a pound for an apple JUST HAS TO BE
better quality than a $.50 a pound apple...
A lot of things go on in our minds that we attribute
to reality..... that just ain't so.
Andy in Eureka, Texas
AndyS
> That's the nature of the beast, along with "sell by dates" which
> if ignored, will cause immediate death or serious health issues.
>
Andy comments:
Yeah. I would pay more attention if the product had
an "eat by" date.... or "certain death if not consumed by .... "
date....
Same thing for something edible that drops on the floor.
Many many people treat all floors as the same.....
If a biscuit drops on the floor of my wife's kitchen, I
don't hesitate to pick it up and eat it, since her floor is
as clean as her kitchen table. On the other hand, if
a biscuit falls on the floor of a Walmart men's bathroom,
I write it off as mouse food immediately...... One rule
does NOT fit all...
That being said, (and still in the mood for ranting), I WILL
acknowledge that some brands are better than store brands.
With mayonaisse, only Kraft and Heilman's is worth buying,
from my own experience in trying to economize. Some brands
of cheap instant coffee should be fed only to prisoners at
Guantanamo, in my opinion.... And beer ? Well, it just depends
on what you want. Steel Reserve is 8.2% and very very
strong, but it only has a faint beer-like taste. I am not
personally familiar with the animal urine that I think it
probably tastes like, but after a glass one just doesn't
think about these things. On the other hand, Red Dog
is only around 5.6% and is a delight to the palate.
I guess there are some things that make a difference to me,
that I am willing to pay more for....... but I will experiment with
something more economical before making an outrageous
disparagement of the "quality" of a new product.
And what exactly is "quality".... My wife equates quality
with high price. I equate quality with the ability of a product
to perform the same as it did when I bought it for a long long
long time without disappoint. In that vein, I have no problem
with the "quality" of my Kia automobile. I have passed many
a Lexus on the roadside, waiting for the tow truck.....
OK..... I'm out of steam...... Thanks for taking the time
to listen...
Andy in Eureka, Texas
clams_casino
>On Sat, 19 Dec 2009 07:17:19 -0800 (PST), AndyS <andys...@juno.com>
>wrote:
>
>
>
>>Andy comments:
>>
>> She feels that paying $3 for a sack of flour
>>MUST make better tasting bread than a $1 loaf of bread.....
>>and that paying $2 a pound for an apple JUST HAS TO BE
>>better quality than a $.50 a pound apple...
>>
>>
>
>
>
Three times this year, I went for the tote of apples at 79 cents/ lb
only to find them small, low on flavor and typically bruised. This week,
I sprang for the $1.49 /lb version of the same type apple. They were
larger, much more flavorful & minimal bruising. Often times, you do get
what you pay for.
As for that $1-2 loaf of bread - why bother. It's like going to Pizza
Hut or Olive Garden. Why bother?.
Jim Higgins
>>
>> It also makes me wonder how much of these personal
>> experiences are psychosomatic. Just the idea of being
>> given a "cheaper" version will influence the affects on
>> many people, which is why sugar pills often produce
>> the same effects as a valid drug in field tests......
>>
>> I'm not saying that these stories aren't true --- I'm just
>> questioning whether the pshchological effect of feeling one
>> is being given a "cheap copy" might account for many of
>> the negative effects.
>>
>> I know that my wife swears by brand name grocery
>> products , even when the store equivalents are manufactured
>> by the same company in the same plant but given a
>> store label. She feels that paying $3 for a sack of flour
>> MUST make better tasting bread than a $1 loaf of bread.....
>> and that paying $2 a pound for an apple JUST HAS TO BE
>> better quality than a $.50 a pound apple...
>
> if ignored, will cause immediate death or serious health issues.
>
>
>> to reality..... that just ain't so.
>>
>> Andy in Eureka, Texas
>
In the case of tetracycline it gets a bit toxic as it runs past its
expiration date.
--
Civis Romanus Sum
BluesMa
> On Sat, 19 Dec 2009 10:58:49 -0800 (PST), AndyS <andys...@juno.com>
> wrote:
> liquid, etc. Big, big savings and my clothes and dishes get just
> as clean.
>
> Isn't it amazing how many times, perhaps hundreds, a detergent
> such as Tide has been touted to be "new and improved"?
Absolutely.
I use Suave shampoo, which hereabouts sells for .97 a bottle.
Been using it for decades.
My long hair is shiny and clean with no dire effects from NOT
using the six dollar product.
I draw the economizing line at champaign. Mum's Cordon Rouge
is definitely worth the price.
It's all about priorities right ??? ;-)