|
Questions
and Answers About "Off-Label" Use of Prescription Drugs
The following is a general
summary of issues surrounding the "off-label" use of prescription drugs,
and applications to potential Parkinson’s Disease treatments.
Q. What is "off-label" use of
a drug?
A. "Off-label" (or
"unapproved") use refers to the use of a drug for a disease not listed
on the label, or in a dose or by a route not listed on the label.
Q. Is this legal?
A. Yes. Physicians, based on
their knowledge and on available current information, may use a drug
for a use not indicated in the "approved" labeling if it seems
reasonable or appropriate.
Q. How common is this
practice?
A. A sampling of prescriptions in 2001, found “21 percent were
intended to treat medical conditions for which the drugs lacked
specific approval from the U.S. Food and Drug Administration (FDA),
though other published research suggested possible benefits. … about
three of every four of those prescriptions were for conditions for
which there were little or no evidence of the drugs' effectiveness.”
(“Medications widely prescribed…”)
Q. Why does FDA permit this?
A. Since the early 1960s, the
Food, Drug and Cosmetic Act has required that drugs used in the United
States be both safe and effective. The label information, whether on
the container, in the package insert, in the Physicians Desk Reference
(PDR), or in any advertising, can indicate a drug's use only in
certain "approved" doses and routes of administration for a particular
condition. The Food and Drug Administration (in the U.S.; there are
other similar agencies in other countries) has no authority over the
practice of medicine. Their major responsibility is to assure that
the evidence from clinical trials shows that the drug is safe and
effective for use as indicated. They also have the authority to
regulate the commercial promotion of approved drug products, which
extends to prohibiting a company from promoting unapproved uses of its
drugs.
Q
What are some of the benefits and risks of off-label use?
 |
It may offer flexibility and innovation in
treatments. |
|
|
Patients may be able to try an off-label prescription if
FDA-approved drugs haven't worked for them. |
|
|
Patients who are not eligible or able to
participate in clinical trials may be offered possibly useful
treatments. |
|
|
It may help build individual knowledge bases of
treatments that work best for specific patients.
|
Risks include:
|
|
Off-label uses are
not given the same degree of scientific scrutiny for safety or
efficacy as labeled indications. |
|
|
A potential for
dangerous interactions with other medications. |
|
|
Possible denial of
coverage under health insurance plans.
|
But for
patients with serious and life-threatening
medical conditions, the potential benefits of treatment might outweigh
the increased risk associated with off-label use.
Q. Are FDA-approved drugs
being researched and developed for other conditions?
A. Yes, due to escalating costs and long
time frames of new drug development, some researchers and
pharmaceutical companies are looking again at drugs that have already
been approved by the FDA and combinations of these drugs that might be
utilized for other conditions. In such cases, the clinical trial and
FDA approval process could be significantly faster. Phase I trials
might be waived if drug safety in humans has already been proven at
the dose strength, frequency and duration stated in the label.
However, there are problems financing such trials. Due to economic
concerns, most pharma companies may be hesitant to fund research on
new indications for their products that are now available as generics.
Another possibility is that the company may have carried out
some studies on the off-label use as part of its initial application
for marketing approval, but the FDA did not find that the studies met
the required high standards for approval. For example, a drug may be
labeled for use in a certain population (e.g., age) merely because
there were too few patients in another population for the clinical
trial to be statistically valid.
Q. Are any treatments in development for PD available to
patients off-label?
A.
Yes. Several potential new Parkinson’s treatments have been approved
and/or are in use for other conditions. Among those being tracked in
the Parkinson Pipeline Project database (www.pdpipeline.org),
as of July 2007, are:
Abilify (aripiprazole) – Currently in use as an antipsychotic.
In phase IV trial for treating psychosis associated with Parkinson’s.
Keppra (levetiracetam)
– Currently in use as an antiepileptic. In phase IV clinical trial
for treatment of levodopa-induced dyskinesia.
Zonegran (zonisamide) – Also in use as an antiepileptic. A
phase III study in Japan of its use in Parkinson’s found it improved
all main Parkinson disease symptoms including tremor and dyskinesias.
Approval as a PD treatment is being applied for in Japan.
Namenda (memantine hydrochloride)
-
Currently used for moderate to severe Alzheimer's. In phase IV trial
for treatment of cognitive
impairment and dementia in Parkinson's Disease.
DynaCirc (isradipine)
- Currently prescribed for high blood pressure and stroke.
Pre-clinical research with mice found it might offer neuroprotection
for dopamine neurons. Currently in a phase I trial to determine safety
of higher doses.
Minocycline
–
Currently in use as an antibiotic. A phase II futility trial for
possible neuroprotective benefits (NET-PD) concluded that further
study would be worthwhile.
PD-02 (Creatine)
– A dietary supplement used by athletes to improve performance. Since
it plays a role in mitochondrial energy production, and there is
evidence of mitochondrial dysfunction in Parkinson's Disease, it is
thought creatine might provide neuroprotection. Currently in an NINDS
phase III trial.
NOTE: The Parkinson Pipeline Project does not promote or recommend
medications – either FDA approved or those in clinical development,
labeled or off-label. These decisions should be made in consultation
with patients’ doctors and pharmacists. The PPP believes that it is
important for PWP to have information about all treatment options, so
that they can make informed decisions.
References:
Bright, JL. Positive outcomes through the appropriate use of off-label
Prescribing (letter). Archives of Internal Medicine, 2006: 166,
2555
Medications widely prescribed without
scientific evidence, study finds. Stanford Univ. Center for Health
Policy, CHP/PCOR News, May 8, 2006. Accessed at:
http://healthpolicy.stanford.edu/news/medications_widely_prescribed_without_scientific_evidence_study_finds_20060508/#
Nightingale, Stuart L.,
Editorial, American Family Physician, August 1, 2003.
Off-label use of prescription
drugs (NLM Bibliography, Dec. 1996) Accessed at:
http://www.nlm.nih.gov/archive/20040830/pubs/cbm/offlabel.html
Radley, DC , Finklestein SN, Stafford R. Off-label prescribing among
office based physicians. Archives of Internal Medicine, 2006:
166. 1021-6
Tiwary, A. Devesh, "Off-Label
Use of Prescription Drugs should be Regulated by the FDA", accessed
at
http://leda.law.harvard.edu/leda/search/toc.php3?handle=HLS.Library.Leda/tiwarya-off_label_use
Authors of this article:
W. H. DeCamp, Parkinson
Pipeline Project
L. Herman, Parkinson Pipeline
Project, Therapies Coordinator
July 24, 2007
|
