Peril or Promise: The Uncertainty of Off-label Prescriptions
by Jennifer Wider, MD
(Washington DC, 11/22/04): The next time
you have a prescription filled, make sure you're taking the medication for
the right reasons. The use of "off-label" prescriptions is on the rise. "Off
label" refers to the use of an FDA approved medication for any purposes other
than what is specifically listed on the drug's labeling as the indication
for that medicine. Doctors frequently prescribe medications off label because
there is evidence that the drug may effectively treat a condition, even if
the drug isn't specifically FDA approved to treat that condition.
For example, drugs tested and approved for
treating seizures are being prescribed off-label for a wide range of conditions
from depression to weight loss. Anti-depressants are being used off-label
to treat premature ejaculation, restless leg syndrome and chronic pain syndromes.
Although it is legal for doctors to prescribe
FDA approved medication for any reason they deem appropriate, it is illegal
for pharmaceutical companies to market drugs for off-label purposes.
"Under current regulations, the FDA can only
allow a drug label to list the specific conditions or indications for which
the pharmaceutical company sought and received approval, based on extensive
testing," said Sherry Marts, Ph.D., vice president of scientific affairs for
the Society for Women's Health Research in Washington, D.C.
There may be sufficient evidence to support
the use of a drug for multiple purposes, but the company that owns the drug
may not sponsor the necessary research trials required for FDA approval, according
to Marts, who was previously involved in the ethical review of clinical research.
"In other circumstances, the clinical research may have been done," adds
Donnica Moore MD, President of Sapphire Women's Health Group, "but the company
may not choose to support the New Drug Application submission process and
the subsequent marketing of the product for business reasons."
On the other hand, sometimes off-label usage
does lead a company to go through all of the steps required to get a new indication
approved for a medicine previously approved for another indication. Prozac,
for example, was originally designed to treat clinical depression but later
it was discovered to be effective for premenstrual dysphoric disorder (PMDD).
"Intermittent dosing worked and it worked rapidly," Marts said. "And the company
was willing to do the clinical trials to get FDA approval." But that's not
true for all drugs which may have other indications that aren't officially
Sometimes, however, off-label usage can lead
to unexpected and undesirable consequences, for consumers as well as for the
pharmaceutical manufacturers. Drugs prescribed for reasons other than what
they were intended for can harm the patient and cost the manufacturing drug
company millions of dollars. For example, Fen-Phen, a combination of the
drugs fenfluramine and phentermine, was widely used off label as appetite
suppressants for the short-term (a few weeks) management of obesity.
"The drug was never recommended for people
who were simply overweight," Marts said. "It was only indicated for people
whose health was threatened by their obesity." It was later discovered that
the combination of these two drugs could cause heart valve problems and fenfluramine
was pulled off the market. Costly lawsuits were quick to follow.
Another high profile case involves Pfizer,
who recently agreed to pay over $400 million in fines and civil damages for
illegally promoting Neurontin, an anti-seizure medication. The company falsely
promoted it for the treatment of other medical conditions ranging from headaches
to attention deficit disorder, despite the lack of scientific evidence.
There are cases when a patient's care requires
the use of off-label treatments. Cancer care is a prime example, where treatments
are rarely approved for general use against cancer. Instead, they are approved
to treat specific stages of specific cancers.
A 1991 government study found that more than
half of cancer patients received at least one drug for an off-label indication.
Off-label use of drugs is widespread in cancer treatment for several reasons.
It is well known that many cancer drugs are
effective against a variety of tumor types.
For example, Cisplatin, produced as Platinol®
by Bristol Myers Squibb, works to stop the uncontrolled growth of cancer cells
by interrupting the copying of DNA in growing cells. Because uncontrolled
cell growth is part of most cancers, cisplatin is often used in the treatment
of thyroid and lung cancers. It is only approved to treat bladder, testicular
and ovarian cancers.
The use of multiple drugs, which is typical
in cancer chemotherapy treatment, is usually an off-label treatment. The FDA
generally does not approve multidrug regimens because the potential number
of combinations is vast.
Medical care is always evolving. When published
research shows that a new treatment approach produces better outcomes for
patients, many doctors will incorporate the findings into their practice,
ahead of formal approval processes which can take years. These timely changes
to care can benefit patients.
Whatever the situation, patients need to
protect themselves by asking doctors about their prescriptions.
"Patients should write their questions down
before walking into the doctor's office," Marts cautioned. Dr. Donnica also
recommends writing down the reason you are taking each medication in black
marker on the medicine bottle so that you don't forget. "This way, if you
see another doctor, it will be clear what medicines you're taking and why
if you just bring all your medicine bottles with you."
Before a doctor hands you a medication, ask
the following questions:
What is the name of the
medication and what is it for?
What is your experience
What kind of side effects
can I expect?
Is the medication safe
to take with other drugs or dietary supplements that I may be taking?
Is there anything I should
avoid while taking it?
What should I do if my
symptoms do not go away?
How long do I need to
continue this medication?
What side effects should
I notify you about?
© October 28, 2004 Society for Women's Health Research
The Society for Women's
Health Research is the nation's only not-for-profit organization
whose sole mission is to improve the health of women through research. Founded
in 1990, the Society brought to national attention the need for the appropriate
inclusion of women in major medical research studies and the resulting need
for more information about conditions affecting women. The Society advocates
increased funding for research on women's health, encourages the study of sex
differences that may affect the prevention, diagnosis and treatment of disease,
and promotes the inclusion of women in medical research studies. Dr. Donnica
Moore has been a member of the Society since 1990 and is a past member of its
Board of Directors.
Created: 11/22/2004  - Donnica Moore, M.D.