Warning Labels: Does FDA Know Best?
by Wyn Snow, Managing Editor
death of Oriole pitcher Steve Bechler has politicized the debate
over what to do about the benefits and dangers of ephedra, putting
enormous pressure on the US Food and Drug Administration( FDA) to
do something fast.
February 28, the FDA announced a proposed rule that would put a
"black box" warning label on the front of all ephedra products,
and provided a 30-day period for public commentary instead of the
usual 90 days. The notice appeared in the Federal Register in
early March. The deadline of April 7th for
submitting comments is approaching quickly.
black box warning label would say:
of ephedra has been associated with heart attacks, strokes,
seizures and death.
question is how best to protect public health, especially when a
substance can be dangerous when taken in excessive amounts, or by
people whose medical conditions make them vulnerable to serious
a warning placed more prominently than those on cigarettes the best
choice for ephedra? Or would a science-based information panel on
warnings and contraindications be a better approach?
are the risks of ephedra?
indicates two clear paths leading to potentially fatal adverse events
is taking more than the recommended dosage. Broward County's medical
examiner, Dr. Joshua Perper, reported that Bechler was taking 150%
of the recommended dosage (three pills instead of two). Ephedra
was found in Bechler's body, and Dr. Perper believes ephedra contributed
to Bechler's death from heat stroke because of its action on blood
vessels. Ephedra can cause either vasodilation or vasoconstriction,
depending on a variety of factors.
second path concerns individuals whose medical condition makes them
more susceptible to the impacts of ephedra. Bechler suffered from
high blood pressure, which is a contraindication for ephedra because
the herb has the effect of raising blood pressure.
Bechler was engaging in a "double whammy" where ephedra is concerned.
is the scientific evidence?
FDA may have been hoping that the RAND report on ephedra would give
them scientific evidence of ephedra's dangers and enable them to
pull all ephedra products off the market. Indeed, the RAND review
of 16,000 adverse event reports did characterize 21 of these as
"sentinel events"meaning that they may indicate a safety problem
but do not prove that ephedra caused the reported incident. These
21 events consisted of 2 deaths, 4 heart attacks, 9 strokes, 1 seizure,
and 5 psychiatric cases involving ephedra in which the RAND report
says "the records appeared thorough and no other contributing factors
RAND study does conclude that ephedra is associated with higher
risks of mild to moderate side effects such as heart palpitations,
psychiatric and upper gastrointestinal effects, and symptoms of
autonomic hyperactivity such as tremor and insomnia, especially
when it is taken with other stimulants.
American Botanical Council (ABC) also conducted an independent review
of the safety literature on ephedra and reached similar conclusions.
Results are presented in an 11-page monograph in their new publication,
The ABC Clinical Guide to Herbs. This monograph contains
an excellent overview of the recent history of controversy surrounding
the safety of ephedra, including cogent and unbiased summaries of
reports by scientific professionals holding different opinions about
whether ephedra is fundamentally dangerous or reasonably safe when
used as directed.
first study comparing the incidence rate of heart attacks, strokes
and seizures between the general population and those taking recommended
levels of ephedra concluded there was "no evidence of increased
risk, even using the most conservative of assumptions."
14 companies that manufacture and market supplements containing
ephedra, an estimated 6.8 billion servings of ephedra were consumed
between 1995 and 1999, a period when sales increased by 700%.
those years, only 66 serious adverse events were reported to those
companies, which constitutes less than 10 such reports per billion
servings. Michael McGuffin, president of the American Herbal Products
Association, says "Even though sales of ephedra supplements increased
more than seven-fold over those five years, there has been no commensurate
increase of adverse events gathered by the FDA."
more details from the ABC monograph, see our story: American
Botanical Council Reviews Ephedra Safety, or download the
monograph itself from the ABC website.)
scientists who conclude that ephedra poses an unacceptable safety
risk, the main source of evidence is the body of adverse event reports
collected by the FDA and by poison control centers throughout the
country. While these reports are troubling and suggestive of a possible
safety problem, the US General Accounting Office (GAO) questioned
the reliability of many of these reports. The FDA's own policy is
that adverse event reports are not a valid scientific basis for
many experts call for more research focusing explicitly on whether
ephedra is safe at the recommended dosage levels that limit ephedra
intake to 100 mg/day, a level lower than that recommended for over-the-counter
drugs containing synthetic ephedrine and pseudoephedrine (see comparison
in our earlier editorial Public
Safety And Health FreedomCan We Have Both?).
new commissioner, Mark B. McClellan, MD and PhD, says "Although
the overall evidence suggests that serious adverse events from ephedra
appear to be infrequent, we know that such events can be very serious
and possibly fatal. We believe that the current scientific evidence
strongly suggests that at least some ephedra products present an
unreasonable risk." The Department of Health and Human Services
(HHS) and the FDA are seeking rapid public comment on:
evidence on health risks associated with ephedra to establish
an up-to-date record as quickly as possible to support new restrictions
on ephedra-containing products
the currently available evidence and medical literature present
a "significant or unreasonable risk of illness or injury" from
dietary supplements containing ephedra
strong new warning label on any ephedra products that continue
to be marketed
has already disallowed companies to make claims that ephedra enhances
sports performance. Both the RAND report and the ABC literature
review found no evidence to support this claim.
challenge for public health
a supplement can be shown to be dangerous under certain circumstances,
how do we best protect public health? How do we weigh the potential
public benefit to a large segment of the population, namely an aid
to weight loss, against the potential for serious harm to a small
fraction of the population?
risk-versus-benefit concerns exist for pharmaceutical drugs. FDA
Commissioner Dr. McClellan says, "We believe that FDA's system for
regulating synthetic versions of the chemicals in ephedra appears
to have a much better track record of safety."
no public comparisons of adverse event reports are being made between
ephedra and OTC products with synthetic ephedrine and pseudoephedrine,
so it is difficult to assess the accuracy of McClellan's statement.
Adverse events do occur with OTC drugs of all kinds; manufacturers
are required to report them to the FDA. SupplementQuality.com is
currently seeking information from the FDA about adverse events
with ephedrine and pseudoephedrine in order to compare the incidence
of such reports for both herbal and synthetic products, and will
report on their response when we receive a reply.
requirements for OTC drugs
(OTC) drugs are required to carry warnings and contraindications
on their labels. These messages are standardized for each of 55
different categories of OTC drugs (eg, cold remedies containing
information from scientific panels of experts, the FDA writes monographs
for each of these categories. These monographs establish the text
of the warnings that must be published on the product label. Among
other things, this information includes a dosage level that should
not be exceeded in 24 hours, and lists medical conditions where
people should not take the product.
the FDA's own standard for developing warning labels is science
basedwhereas the proposed warning label for ephedra is quite
unlike those for OTC drugs. Instead, it resembles those for cigarettes,
where strong scientific evidence exists that smoking causes canceryet
solid scientific evidence is lacking for ephedra.
new label program offers alternative to FDA proposed label
experts have characterized the problem with ephedra and other botanicals
as one of perception. The public thinks of dietary supplements as
inherently safe, and therefore has no qualms about ingesting excess
quantities of them whereas they generally would not do so with an
fill the gap formed by the absence of any federally mandated label
warnings, the American Botanical Council (ABC) has launched a new
safety-labeling program that can play the same role as FDA's monographs
on OTC drugs.
to Mark Blumenthal, executive director of the American Botanical
Council, "The ABC safety labeling program is designed to provide
consumers with rational and science-based information on how to
use supplements safely, without any federally mandated warnings
or precautions. Our Safety Information Sheets present a rational
interpretation of the literature on the safety aspects of a particular
herbtogether with accurate, useful information on contraindications,
adverse effects, potential interactions with prescription and over-the-counter
drugs, pregnancy and lactation warnings, and other guidelines."
warnings would be based on these Safety Information Sheets, using
information from ABC's monographs, which would be continually updated
for scientific accuracy. (For additional details, see story: New
Labeling Program Delivers Safety Information for Herbal Products.)
of the iceberg
publicizing the new proposed warning label and seeking public comment,
FDA Commissioner Dr. McClellan also says, "To give us the strongest
possible basis for further regulatory action, we are asking for
quick comments on whether these dietary supplements present an unreasonable
risk of harm, and whether it makes sense for the FDA to seek new
authority in this area."
statement strongly suggests that the FDA wants to reopen the debate
on how best to regulate botanicals, a debate concluded in 1994 by
the passage of the Dietary Supplement Health and Education Act (DSHEA).
Many experts on both sides of the fence agree that DSHEA, like most
results of compromise legislation, does have its flawsand
concerns about how best to establish scientific information on the
safety of botanicals is warranted.
SupplementQuality.com agrees with the FDA's own statement before
Congress that it has enough regulatory authority to remove dangerous
products from the marketplace. We believe the solution to determining
the safety of individual botanicals lies in the Supreme Court's
preference for dealing with potentially misleading information:
Supply more information, not less.
general, we do not believe there is a safety problem with herbs,"
says ABC's Blumenthal. "However, we think it is important to provide
consumers and health professionals with accurate guidelines for
the responsible use of herbal products."
agrees. ABC's safety-labeling program, based on Safety Information
Sheets developed from the monographs in The ABC Clinical Guide
to Herbs, puts accurate and comprehensive safety information,
warnings and contraindications right where it is needed most: on
the bottle and in the hands of consumers.
both health freedom and public health
the question is what kind of society we want to live in.
we allow government to limit our access to products that are beneficial
to most but cannot be tolerated by a few? Or shall we ensure that
everyone can freely choose from a rich array of products whose accompanying
label information enables people to make safe choices based on individual
circumstances and need?
FDA states: All interested parties may send written comments
on these issues involving ephedra until
April 7, 2003, either electronically
or by regular mail to
Management Branch (HFA-305)
Food and Drug Administration
5630 Fishers Lane, Room 1061
Rockville MD 20852.
Botanical Council. "Ephedra." The ABC Clinical Guide to Herbs,
2003, pages 110-121. www.herbalgram.org.
and Drug Administration. "HHS Acts to Reduce Potential Risks of
Dietary Supplements Containing Ephedra." Press release on FDA website,
28 February 2003. www.fda.gov/bbs/topics/NEWS/2003/NEW00875.html.
Blumenthal, executive director of the American Botanical Council
and editor of HerbalGram. Private communication, 24 March
Poison Control System. "Ephedra." Clinical Toxicology Review,
Vol. 18, No. 10, July 1996. www.maripoisoncenter.com/ctr/9607ephedra.html.