There's been a lot of debate regarding ways
to reduce drug costs. One method has been available in the US
for years -- the use of generic versus brand-name drugs. Insurance
companies claim that generics are just as effective as the
brand-name versions. However, a recent study warns that some
generic epilepsy drugs are not as effective.
According to the Center for Drug Evaluation
and Research (CDER) of the US Food and Drug Administration (FDA),
a generic drug is the same as a brand-name drug in dosage,
safety, strength, how it is taken, quality, performance and
intended use. It is referred to as identical, or "bioequivalent,"
to the brand-name drug.
However, Ilo E. Leppik, MD, clinical
professor of neurology and pharmacy and director of the
epilepsy clinical research program at the University of
Minnesota in Minneapolis, warns that this is an overly
simplistic definition, and that the issues are not so black
and white. Case in point: The epilepsy drug phenytoin (Dilantin).
When the state of Minnesota switched epilepsy patients on Medicaid
from brand-name Dilantin to the generic version, patients
experienced more seizures.
Although in most instances less-expensive
generic drugs are as safe as their brand-name counterparts, Dr.
Leppik believes that each generic substitution merits careful
consideration by your physician.
GENERIC DRUGS: THE BASICS
Like all new products, drugs are
developed under patent protection. The patent protects
the drug manufacturer's investment by giving the company
the sole right to market the drug while the patent is in
effect. After the patent expires, other drug manufacturers
can apply to the FDA to sell generic versions of the medicine.
These are less costly to consumers (although Dr. Leppik points
out that the price for generic drugs is not as discounted as
in the past and the price gap is narrowing).
While the approval process for a generic
drug is not as rigorous, the drug still has to meet the same
rigid standards as the original drug. According to the
FDA, it must...
Contain the same active ingredients
(although inactive ingredients may vary).
Be identical in strength, dosage and means
of administration.
Have the same use(s).
Be bioequivalent -- acting on the body with
the same strength and similar bioavailablity as the same
dosage of a sample of a given substance.
Meet the same requirements for identity,
strength, purity and quality.
Be manufactured under the same strict standards.
THE DILANTIN SAGA
The FDA approved the generic form of Dilantin,
namely phenytoin, in 1998. However, according to Dr. Leppik, Mylan
Pharmaceuticals, Inc.'s testing did not meet the standards of
clinical care on Dilantin testing protocol. He explains that in
the FDA research, generic phenytoin and brand-name Dilantin were
bioequivalent (had the same effect on the body) when people were
fasting, but this does not accurately reflect how people live
and take their medicines in the real world. Moreover, the study
was done on volunteers not receiving phenytoin regularly, and
they were given a single dose each -- also conditions that are
very different from what is seen in practice.
Generic phenytoin has been periodically
substituted for Dilantin with extremely serious results. All
epilepsy drugs have a very narrow therapeutic range, meaning
that the dose at which the drug is effective and at which it
becomes toxic are very close. Even a small dose or absorption
change can have life-threatening implications for patients.
Dr. Leppik says that the Dilantin saga
unfolded like a detective story. It all started when formerly
stable epilepsy patients suddenly began appearing at clinics
and emergency rooms throughout Minnesota with unexpected seizures.
Researchers knew that something was wrong, but they couldn't
pinpoint the reason.
Dr. Leppik and his team took a closer look
at the eight patients at his clinic who had suddenly begun
having seizures. They examined their medical records from when
they were taking Dilantin... when the state switched them to its
generic equivalent without informing their physicians... and after
Dr. Leppik and his colleagues switched them back to Dilantin.
Researchers discovered a 30% decrease in blood levels of phenytoin
during administration of the generic drug. It was this that brought
on the increased seizures, even though the prescribed dosages
were the same.
Dr. Leppik called the Minnesota Department of
Health and reported the situation. In response, the state
changed the rule and put an end to automatic generic
substitutions. However, he warns that the battle is
not over -- the neighboring state of Wisconsin is
threatening to allow generic substitution
for Dilantin.
In the long run, this type of
substitution is penny-wise and pound-foolish. Dr.
Leppik notes that the cost savings from using generic
phenytoin versus brand-name Dilantin for epilepsy is
roughly two cents per pill. When epilepsy goes uncontrolled
and seizures result, this small savings is more than offset
by the cost of emergency room visits and hospitalizations.
The bottom line? The story of Dilantin is
a cautionary tale that demonstrates the importance of examining
each medication individually. Naturally, you want the most
effective drug at the best price, and it's a great idea to
save money by using generics. But first discuss the possible
health ramifications with your physician. If you decide to go
with the generic, be sure your doctor chooses one with an identical
format. The generic should emulate the entire original,
not just the "active ingredient."
Sources...
Ilo E. Leppik, MD, clinical professor
of neurology and pharmacy and director of the Epilepsy
Clinical Research Program, University of Minnesota,
Minneapolis. Dr. Leppik is past president of the
American Epilepsy Society and past chairman of the
Professional Advisory Board of the Epilepsy
Foundation of America.
