Download one that I'm not aware

ct
101
1
one
2
is
that
I'm
aware
to
some of
tolerance
we know
to
not
with
maintain
raises
the
of
the
other
drugs
a drug
effect.
other
good
if
you
titrate
7
a higher
level
8
change
lots
9
taking
in
an ephedrine
product
10
times
higher
dose,
then
that
11
situation.
Dr.
Ricaurte
12
But
13
better
about
14
effects
of
15
develops,
16
heart
17
And
18
exercise
19
up,
20
high
21
the
and
the
these
heart
22
CNS effects.
there
is
the
blood
pressure
those
are
the
blood
and
Whereas,
products
24
putting
people
25
other
predisposing
cases
body
in
continually
has
this
dangerous
tolerance
-the
rest.
who might
have
small
your
I think
--
out
we all
rate
goes
pressure
and
hours,
and
ingesting
the
that's
aneurysm
a problem
REPORTING ASSOCIATES
(301)
390-5150
the
increased.
heart
to
then
of
I mean,
blood
when
it
that
is
a chance
bringing
three
cardiovascular
the
case
to
answer
and
days,
MOFFITT
two
day
for
factor
has
to
to
you
now you're
dose
high
the
then
stimulation
and
that
dose
and
where
pressure
throughout
the
23
the
maintain
rate
and
is
the
dose
also
your
the
a sustained
if
it
be a very
But
compounds,
we don't
heart
could
and
variability
may be able
there
and
that
there
their
that
tolerance
products,
but
I think
but
the
change
I think
is
products.
you
titrate
that
Because
Clearly
effects
and
between
or
people
And
of
on.
cardiovascular
that
concern,
because
data
or
some
that
ct
102
would
3
not
have
otherwise
occurred
DR.
JONES:
DR.
LIEBERMAN:
Last
question
from
the
panel
Dr.
Lieberman.
4
5
Research
Institute
of
6
two-part
question
for
7
question
is,
8
ephedrine-like
9
have
given
are
11
question
12
data
sold
Dr.
your
is
for
Dr.
speaks
13
DR.
LOVE:
14
types
of
products
15
issue
of
the
16
the
17
scheme
18
focus
19
dietary
20
on Drugs
21
comment
table
to
dietary
about
these
because
than
the
this
is
again,
talking
they
23
products
are
regulated
that
24
question
had
to
25
available
do with
those
MOFFITT
products,
of
about
today,
were
really
trying
in
from
this
that
differently.
not
might
a generic
REPORTING ASSOCIATES
(301)
390-5150
to
these
the
Center
to
area.
those
But
that
off
a different
effects
in
the
the
I am confident
data
the
as I talked
I understand
the
they
surveillance
under
may have
very
part
about
a
do you
when
any
I am not
LIEBERMAN:
and
issue?
on the
think
ephedrine
So we were
products.
I don't
The
situation
regulated
specifically
Love.
the
OTC products
are
I have
products
there
products.
on anything
from
particular
the
supplement
DR.
that
in
food
just
and
is,
Army
supplements,
And
Love
we were
Dr.
about
in
Well,
effects
and
concerns
concerns
U.S.
Medicine,
Woosley
as OTC decongestants?
that
22
Lieberman,
Environmental
products
similar
10
Dr.
my
be
question
ct
103
1
about
2
differently.
your
opinion
3
on whether
they
We have
asked
DR. LOVE:
4
in
5
available
6
type
7
different
8
products.
the
past
and
in
there
their
products.
has
been
database
or
Remember
ingredients
9
than
DR. WOOSLEY:
10
have
11
benefit
12
pharmacological
13
an informed
14
drug,
15
response,
16
realize
17
that
the
and
that
effect
label,
from
pharmacology
20
beta-blockers
21
stimulates
22
the
23
cardiovascular
24
any
25
some harm
wrong
of
also
the
dose
-if
any
used
is
being
reviewed
to
it,
is
used
with
FDA as a
some
taking
is
a risk
there
by the
keeps
and
death.
the
harm.
central
is
I do
there
I mean,
though,
sympathetic
or
yes,
because
value
say
heart
reduce
the
very
it
a risk
and
they
benefit
ratio
that.
I would
19
that,
a drug
these
supplement
say
So there
or
contain
dietary
assess.
a person
benefit.
come
events
can
a medical
reason
that
18
is
do reviews
adverse
less
been
to
information
but
that
it's
there
the
can
you
them
products
the
be regulated
limited
I would
same concern,
ratio
the
should
blood
And
wrong
cardiovascular
MOFFITT
a broad
if
you
look
at
vessels
anything
nervous
that
system
individual
So I think
in
that
is
probably
going
you
should
stimulate
population.
REPORTING ASSOCIATES
(301)
390-5150
to
cause
assume
will
The
that
have
question
104
is,
is
it
inform
being
the
public
DR.
questions
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used
and
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identify
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8
accommodate
and
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for
keep
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like
Sunshine
11
relates
to
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learned
a long
13
everything
14
therapeutic
15
way
off,
16
the
later
17
back
that
18
that
the
19
divided
20
I have
21
that
Products.
then
to
have
up,
the
total
24
products
25
effect
the
therapeutic
the
right
we can
to
Dr.
ask.
reports.
Jerry
McLaughlin
three
questions.
index
of
you
says.
it
off
is
50.
I could
two,
effective
and
is
one
of
you
to
we learned
dose
those
certainly
a
ephedrine
Michigan
Find
I
that
I challenge
of
the
saying
to
too.
first
believe
the
reduced
Nature
ephedrine.
And
for
from
The
the
can't
exists
dose
McLaughlin.
50
calculations
help
figure
now.
second
number
from
would
so that
University
index
you
brief
index
lethal
if
patient.
question
was way
and
and
very
we have
Fong
three
speeches
floor,
that
of
The
23
Harry
my Merck
out
ago
index
and
been
now to
so that
therapeutic
time
me turn
record
I have
that
by
22
the
and
value.
Let
the
DR. MCLAUGHLIN:
10
supervision
You have
on the
just
all
9
you.
floor.
yourselves
proper
some medical
Thank
microphones
6
the
with
JONES:
from
are
under
of
which
thing
people
you
What
MOFFITT
is,
is
no one
who are
are
that
is
using
extracting
number?
reporting
the
these
I've
REPORTING ASSOCIATES
(301)
390-5150
on
ephedra
adverse
heard
it
ct
105
1
quoted
2
Products
3
doses
4
probably
5
we sell.
6
how many
7
doses
8
of
9
that
on 20/20
by
someone
Association
a year,
that
relating
a year,
Americans
are
a lot
try
11
their
12
suspect
13
20 million
and
of
take
risk
obese
those
the
of
that
we are
people
14
the
that
you
15
1,100
16
of
17
things
that
use
all
the
18
which
there
are
ten
people
19
million
in
20 million
last
people.
people
20
the
ten
Let's
that
time
get
the
person
22
chlorophenocol.
23
adverse
effects
24
overall
population.
25
neglected
of
200,000
dies
So the
that.
is
very
And
And
MOFFITT
then
reduce
diseases.
I
a population
us?
of
the,re
adverse
a some of
like
polio
are
effects
the
other
vaccine
polio
of
products.
That
look
like
of
to
or
in
one
vaccine.
Some antibiotics
21
and
ephedra
get
and
something
probably
that
54 percent
least,
take
years
sure
2 billion
at
associated
telling
that
quite
that
may be taking
are
not
appetite
at
that's
products
those
to
their
looking
And what
reports
need
off
from
I'm
overweight,
people
death
of
considering
or
curb
amount
taking
I suspect
2 billion
I suspect
a year,
are
Herbal
approximately
the
doses
but
American
that.
to
how many people
the
is
like
Two billion
10
it
something
close
from
chlorophenol,
aplastic
anemia
total
instances
small
when
all
the
finally,
one
you
that
of
these
look
at
reports
on the
REPORTING ASSOCIATES
(301)
390-5150
takes
the
today
report
about
106
ct
1
the
baboons
2
I couldn't
3
dose
4
was
5
methamphetamine
6
milligrams
7
lowest
help
that
!@-?
but
5 milligrams
are
11
going
12
listening,
13
to
baboons
the
kilo.
the
times
out
that
diet
those
for
the
it
was
Now,
more
the
audience,
are
the
5
So even
lowest
you
said
than
that.
and
your
Okay.
.5?
So your
then.
lowest
is
Okay.
--
damaged,
methamphetamine
taken
dose.
to
of
person.
who do take
point
Even
dose.
of
70 times
usual
neurons
The dose
when
like
some people
to
to
70 kilogram
is
times
the
itself
So seven
seven
dopaminergic
notice
per
per
dose
10
dose
okay
there
But
the
was
I am
people
abusers
who are
me address
very
tolerant
methamphetamine.
DR.
14
15
because
16
two
17
5,
18
issues
19
adjustments
20
for
21
interspecies
22
adjustments
23
low
24
being.
25
their
was given
8
9
getting
this
points
was
with
in
per
kilogram.
that
difference
the
part
of
the
issue
of
dose.
When you
two
very
make.
One is
mass
using
principles
scaling.
Once
. 5 milligram
per
per
on a milligram
need
second
MOFFITT
kilogram
to
make
point
you
--
basis
I would
there
It
are
wasn't
consider
an adjustment
of
do those
kilogram
that
quickly
important
to
has
body
drug
The
are
one
in
the
latter
to
there
dose,
So you
the
regard
* 5 milligrams
of
Let
RICAURTE:
dose
for
the
becomes
human
adjustment.
make
is
REPORTING ASSOCIATES
(301)
390-5150
that
for
the
107
ct
1
ephedrine,
we don't
methamphetamine,
dose
that
this
point
to
draw
conclusions
the
those
in
fully
the
brain
or
at
too
think
much,
much
at
So
early
as have
effects
lowest
toxicity.
such
neurotoxic
DR.
panel
to
JONES:
Any
a stage
been
drawn
lower
than
on animals.
this
DR. LOVE:
point
that
we
rate
is
14
We do not
have
information
15
and
16
information
17
enumerator
18
underreported,
19
denominator;
and
20
help
that.
that
and
correct
one,
we know
provide
that
we have
knowing
DR. MCLAUGHLIN:
from
this
comment
it
goes
we can
access
to
members
I'll
ways.
the
Yes
we have
massively
no information
the
both
do incidence
that.
is
on
on a
of
doses
give
you
some
like
to
address
does
tomorrow.
23
DR.
24
DR. WOOSLEY:
therapeutic
have
that
his
but
where
we could
but
us with
information
I think
We do not
prevalence.
responses
questions.
Well,
reporting
21
other
McLaughlin's
Dr.
13
25
are
the
know.
12
22
--
for
defined
we are
humans
don't
indeed
dopamine
think
about
produce
I just
10
11
we haven't
I just
doses
that
8
9
know,
produces
at
that
as yet
JONES:
i ndex
Dr.
issue,
MOFFITT
Woosley.
I would
because
therapeutic
REPORTING ASSOCIATES
(301)
390-5150
the
index
not
ct
108
1
implies
that
2
impossible
3
someone
4
know
5
safety
6
incidence
7
another
8
the
9
is
to
that
there
is
Agency
to
give
you
a risk
11
then
give
you
If
to
of
these
14
trial
to
answer
15
should
16
and
animal
2 or
or
JONES:
the
ways
types
of
to
of
harm.
the
society
deserves
are
you,
products
benefit,
and
I don't
and
taking
a control
think
from
animal
taking
these
Dr.
that
trials
people
people
Thank
of
the
need
document
extrapolating
when
in
the
would
3 billion
questions
We
Agency
control
to
the
these
tissues
DR.
17
enough
products,
be guessing
one
it's
until
calculate
you
assessment
are
the
these
ratio
a careful
doses
to,
and
and
products.
really
evaluated
do large
there
to
do that;
benefit
13
these
at
alluded
always
them
of
order
just
to
has
ask
value
In
approach
value,
index
underreporting
databases.
as Lori
therapeutic
a therapeutic
a proven
10
18
a per
calculate
shows
12
I
there's
we
baths
drugs.
Woosley.
Ms.
Culmo.
MS. CULMO:
19
Can I quickly
address
20
denominator
issue?
Industry
consistently
21
denominator
of
2 to
3 billion
servings
22
alluded
fact
that
23
tomorrow.
24
information
25
number
to
the
It
will
be on servings
on actual
of
reports
he could
denominators
where
MOFFITT
consumers
give
the
relates
sold.
her
sold.
He just
data
There
consumed.
have
reported
REPORTING ASSOCIATES
(301)
390-5150
this
is
not
We have
that
a
ct
109
1
they
have
2
discontinue
3
there
taken
the
the
is
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product
product
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5
MR. SIEGNER:
7
and
8
like
9
Lieberman
JONES:
with
the
I am here
to
I can
don't,
11
the
12
quote,
13
issue
14
repeatedly
15
from
16
believe
17
issue
18
no significant
19
labeled
20
happy
'96
get
adverse
at
Center
it
stated
use
to
of
because
23
background
24
is
this
25
Center
important
for
Evaluation
to
Drug
to
to
issue
from
the
I
record
can
provide
correct
in
the
the
but
this
came up
point
someone
and
addressed
effect
of
that
that
we have
database
again,
I
from
I would
be
panel.
that
I wanted
hear
and
consumption
put
everything
MOFFITT
effects.
up and
And,
we'll
Evaluation
side
one
McNamara
Dr.
Research
the
effects
afternoon
risk
got
products.
Another
22
Drug
that
at
a
I would
OTC database
and
something
and
that
and
the
Wyntrob,
the
provide
21
with
adverse
Phelps
exactly
meeting
for
was Dr.
and
words
events
that
and
meeting
the
Siegner,
First
as a quote
committee
sir.
question
OTC use
SO
time.
West
industry.
to
effects.
this
Yes,
is
had
adverse
Hyman,
the
this
I may not
the
of
about
offer
you.
of
partially
advisory
of
firm
and
at
My name
on behalf
raised
10
Thank
law
address
of
denominator
DR.
partner
time
because
4
6
one
more
rates,
into
and
to
raise
simply
information
on
and
this
I think
perspective.
Research
from
REPORTING ASSOCIATES
(301)
390-5150
The
FDA
ct
110
1
submitted
2
the
docket
is
important
and
a written
and
this
to
I will
just
report.
It's
conclusions.
adverse
evaluation
is
this
in
read
the
quote
not
the
only
"It
is
possible
events
are
of
spontaneous
occurrences
9
necessarily
causally
The
11
product,
12
further
13
associated
availability
with
And
15
you
mention
16
to
17
questioning
1%
is
19
required
20
as
21
I commend
feel
divulge
is
22
DR.
Woosley
24
But
25
what
did
I am sure
his
is
that
as well.
he would
are.
MOFFITT
the
Dr.
Jones,
everybody
is
supposed
I am not
but
are
everybody
doing
I think
going
to
it
be
conflicts
do that.
And
that.
We have
asked
I'm
sure
Those
to
risks
on potential
be happy
uses.
including
here,
not
not
a point,
members
for
of
products."
information
Culmo
are
products
potential
these
that
one
serious
be useful
conflicts.
JONES:
conflicts
the
this
appropriate,
Cynthia
would
industry
is
and
ephedra
objectivity
the
their
reported
information
beginning
anybody's
to
of
potential
if
to
finally
the
any
important
23
then
at
mention
use
it
population
data
it
morning
from
the
to
background
the
of
the
this
but
that
events
I think
conclusion
conclusion
in
characterization
And
record
coincidental
usage
adverse
docket.
additional
or
the
the
related
of
market
14
I
the
have
8
10
in
of
to
of
people.
Dr.
Dr.
Ricaurte
did.
state
for
the
us who
are
public
REPORTING ASSOCIATES
(301)
390-5150
record
ct
111
1
employees
are
2
MR. SIEGNER:
any
10
gotten
have
any
Dr.
Ricaurte,
you
et
Thank
indicated
in
you
know
--
support
John
17
questions,
18
would
19
concerns,
20
subsequent
21
here
for
22
some
forms
23
those
24
in
to
ask
to
Siegner.
state
record.
briefly
where
my knowledge,
interest
Funding
even
lunch
time
you
or
comments
and
from
you've
do not
I have
so
government
This
you
are
or
from
to
express
we would
know,
gentleman,
MOFFITT
for
--
yes,
get
to
of
pickup
comments
to
then
questions,
any
you
with
And
I believe
those
running
gentleman
further
for
invite
NIH.
We are
three
we can't
available
the
my studies
questions.
have
some
for
Okay.
those
that
we have
that
funding
I do see
do indeed
sessions,
of
good.
take
if
and
Very
but
so I will
those,
All
directly
JONES:
questions
writing
to
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close
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please
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RICAURTE:
Hopkins
16
want
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research?
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at
though
funded,
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JONES:
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know,
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15
25
and,
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DR. RICAURTE:
13
14
JONES:
funding
11
12
DR.
potential,
8
9
property
[Laughter.]
3
7
public
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REPORTING ASSOCIATES
(301)
390-5150
are
are
you
can
raise
to
the
record
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sir.
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112
1
MR. REINHART:
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wanted
3
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to
ask
you
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People
questions;
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on the
punitive
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of
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pathophysiology
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DR. WOOSLEY:
The
you
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consistent
Woosley
Was there
about
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pathophysiology?
7
8
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sympathomimetic
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recall
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14
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15
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But
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DR. RICAURTE:
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MR. REINHART:
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cases
norepinephrine.
RICAURTE:
as you've
are
23
of
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question.
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MR REINHART:
13
25
those
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24
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REPORTING ASSOCIATES
(301)
390-5150
nut
to
ct
113
1
crack,
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methamphetamine
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DR.
JONES:
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attorney,
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any
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Dr.
Woosley,
13
percentage
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exhibited
15
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give
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the
published
19
alkaloids
20
studies
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22
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23
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140
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our
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are
GI
the
GI system.
MR. GREEN:
24
else
studies
DR. LOVE:
16
this
a quick
ephedrine
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since
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MR. GREEN:
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MR. REINHART:
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of
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25
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MOFFITT
Of the
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Dr.
Woosley,
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REPORTING ASSOCIATES
(301)
390-5150
problems
that
you
among
ct
114
1
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group
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people?
DR. WOOSLEY:
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MR. LAFABI:
public
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Armstrong
State
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YOU I in
terms
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review
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CFSAN and
23
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24
opinions
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but
of
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of
MOFFITT
at
keep
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face
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in
here
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in
if
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46 and
REPORTING ASSOCIATES
(301)
390-5150
not
brief
41 from
reasonable,
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take
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hundreds
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health
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25
Hi,
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13
hear
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professor
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ct
115
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conservative
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DR.
JONES:
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MR. LAFABI:
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MR. LAFABI:
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18
sentence
19
in
20
the
21
restricts
22
drugs.
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23
at-risk
populations
24
alkaloids.
25
of
one
the
--
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a sentence.
my presentation
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regard,
I say,
I find
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federal
policy
in
United
access
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the
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DR. RICAURTE:
17
to
and
factors
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taking
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ephedrine
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REPORTING ASSOCIATES
(301)
390-5150
pharmacology
lie
my
on
ct
116
1
rationale
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in
3
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analog.
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needed
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DR. WOOSLEY:
8
think
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was
said
industry
to
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earlier,
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10
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people
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14
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15
available
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identified
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reasonable
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REPORTING ASSOCIATES
(301)
390-5150
what
record,
more
ct
117
1
system,
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data.
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REPORTING ASSOCIATES
(301)
390-5150
1:lO
be
ct
118
1
AFTERNOON
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DR.
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Dr.
Page,
Hutchins,
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note
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Medicine
Cardiovascular
16
Clinical
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17
Department
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review
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Adams.
Jones,
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the
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of
Department
of
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Education
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9
JONES:
noted:
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chair
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REPORTING ASSOCIATES
(301)
390-5150
ct
119
1
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meeting;
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18
reviewed
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review
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prepared
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in
panel
FDA released
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16
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reports.
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assessments
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members
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REPORTING ASSOCIATES
(301)
390-5150
this
ct
120
1
So the
2
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use
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14
supplements
15
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for
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data
19
over-the-counter
20
for
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22
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23
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24
address
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MOFFITT
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25
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REPORTING ASSOCIATES
(301)
390-5150
event
ct
121
1
reports.
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In
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25
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REPORTING ASSOCIATES
(301)
390-5150
rates
no
ct
122
1
purposesl'
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19
over
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20
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reports
22
FDA from
1993
23
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24
comes
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25
comes
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ago,
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1996
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REPORTING ASSOCIATES
(301)
390-5150
to
1994,
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it
ct
123
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what
was
certainly
14
analysis.
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15
mentioned,
was
16
of
17
a rise
18
rise.
19
the
20
people
21
was
these
again,
still
22
what
24
same yellow
25
estimated
there
were
amount
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their
Monte1
numerous
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other
knowledge
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or
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and
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if
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the
be
I
numbers
we don't
see
it
continue
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of
course,
these
reports
and
decreased
products
could
a definitive
thing
numbers
decreased;
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certainly
certainly
rise
would
if
scare
use,
this
be worrisome.
In
23
time.
supplements;
interesting
that
dramatic
away
but
this
FDA had
increases
come dramatically
number
slide,
on.
reporting;
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is
around
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due
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1996
th is
events?
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In
and
Is
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receiving
a broadcast
13
events
to
this.
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to
issue
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before
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12
meant
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adverse
one
on ephedrine
had
for
serious
not
one
release
reason
I mentioned
publicity.
1994
the
ephedrine
Well,
In
is
we see
fact,
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happening.
line
is
is
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And now
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line
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which
is
on the
the
c
servings
sold
MOFFITT
based
on a survey
REPORTING ASSOCIATES
(301)
390-5150
1'11
discuss
ct
124
1
in
2
number
3
a small
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increased
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later.
mill
ions
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sample
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dietary
adverse
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attention
in
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Federal
Reqister
10
media
11
assuming
12
divergence
13
with
Effects
17
is
18
course,
19
is
are
of
summary
that
they
publicity
are
nonspecificity
of
So in
22
dietary
23
to
24
occurring
25
compare
try
the
manufacturers
the
of
has
is
risk
rates
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of
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continued
media
their
report
in
a fair
amount
of
blip
rates
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and
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and
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estimate
among
these
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prove
difficult
at
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least
ephedrine
rates.
discern.
and,
heard
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address
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users,
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reporting
had
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serious
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MOFFITT
spontaneous
incidence
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panel
risk
of
to
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try
data
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with
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to
supplements,
to
the
which
a concern
20
limitations,
see
reports
underreporting,
always
21
the
association.
So in
16
has
received
curves
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on a survey
reporting
reporting
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based
FDA released
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say
increased
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the
to
years.
if
We don't
of
14
reporting
and
and
that
true
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that
1997,
coverage.
sold
supplements
events
8
it
supplements
in
dietary
serious
suffice
serving
dramatically
If
15
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group.
some of
of
these
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goals.
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adverse
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second,
estimates
REPORTING ASSOCIATES
(301)
390-5150
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of
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125
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with
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along.
15
and
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June
17
of
18
supporting,
19
all
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to
for
1,
their
of
usee
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heart
attacks,
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point
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of
out
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the
try
amount
of
to
As you'll
of
see,
assumptions
if
all
of
associated
anything,
--
if
some of
events
we used
all
1997
through
March
events,
whether
or
insufficient
occurred
and
you
want
to
use
as possible".
this
really
incidence
time.
be as
l'conservative
I will
events
to,
to
calculate
anything,
have
try
to
in
users.
risk,
13
number
among
We were
--
need
was,
risk
them.
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on strokes,
do you
to
goal
calculations
term
focus
seizures.
4
5
to
and
is
the
events
first
thing
1999.
were
to
we need
FDA from
We included
all
attributable,
data.
that
as we go
reported
31,
they
those
We assumed
they
occurred
that
they
on exposure
ephedrine.
Some specifics
21
22
included
unstable
23
MI could
not
24
the
25
They
angina
based
and
be excluded.
population-based
are
about
statistics
on hospitalized
MOFFITT
these.
all
This
For
sudden
is
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death
important
exclude
patients
these
who
REPORTING ASSOCIATES
(301)
390-5150
MIS we
in
which
because
of
patients.
survive
to
ct
126
1
come
to
hospital.
So,
again,
2
will
be overestimating
risk
in
3
to
4
we included
5
do,
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the
population
and
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What
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data
from
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and
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discussing.
at
of
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group
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vaccines
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events
14
18 percent.
15
aware
that
16
again
it
was
study
was
events
37 percent.
time
of
Again,
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heightened
probably
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are
percent;
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in
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active
some
medications
we'll
be
rates
for
seizures
in
this
after
was
the
MI among
of
high.
study
studies.
are
from
that
stroke
studies
other
awareness
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for
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reporting
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relative
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do not;
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of
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rates?
series
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and
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the
drugs
at
studies
I think
similarly
strokes,
literature.
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a group
of
most
are
the
10
And
subtypes
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ephedra
statistics.
all
if
another
adverse
Cardiac
arrest,
physicians
were
going
on so
surveillance
may be high.
17
But
this
18
adverse
events
19
studies
of
20
various
medications
21
what
that
a range
The
reality
the
reporting
sure
23
we may see
increased
24
publicity,
the
25
are
in
fact
the
types
of
looking
at.
not
dietary
supplements
were
is,
that
serious
These
are
and
vaccines.
it
is
impossible
to
know
rate
is.
Specific
to
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reporting
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MOFFITT
for
we are
medications
22
unusual
is
these
because
are
population,
of
severe
and,
REPORTING ASSOCIATES
(301)
390-5150
for
mass
events
therefore
that
are
ct
127
1
less
2
acute
3
exposure
4
five
5
reporting
6
supplement
7
hypothesized
8
in
9
direct
likely
and
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in
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reporting
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which
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here.
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line.
events
in
general.
some suggestions
there's
mechanisms
14
Now,
15
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unclear.
16
to
Dr.
17
percent
18
carefully
19
was
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20
all
dietary
21
acknowledges
22
report
23
reporting
24
was
you
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And
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MOFFITT
for
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going
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read
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REPORTING ASSOCIATES
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390-5150
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aware
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is
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rates
course
general.
surveys
dietary
heard
If
ephedra.
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comment
which
a could
all
as
drugs
one
in
in
of
occur
on some
at
to
which
supplements
rates.
all
to
about
been
pharmaceutical
the
events
see
has
to
statement
you'll
dietary
and
know,
I want
of
as far
looking
the
decrease
rates;
adverse
that
based
no,
literature
reporting
reports
This
causes
to
effects
We may see
underreporting
of
common
relation
latent
of
--
other
temple
because
literature
supplement
to
close
are
down
study
for
be attributable
occurred
--
10
25
to
A
ct
128
the
only
example
tryptophan
which
aphelia
reported.
9
percent;
and
the
the
certainly
11
on other
12
do.
rates
15
the
16
Federal
17
calculations.
of
our
20
see
is
of
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22
there
23
by
24
performed
by one
with
25
anonymous
survey
of
an independent
American
Walker
Herbal
MOFFITT
was
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serious
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events
read
Medical
essentially
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our
survey
Products
Arthur
42 companies,
of
for
the
some
20
were.
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about
as I mentioned,
was
commissioned
Association
Andersen.
we
at
in
1 to
estimates
which
on the
1997
a range,
Well,
and
FDA used
enumerator.
time?
risk
based
in
at
based
reporting
the
alkaloids
the
I think,
we used
how sensitive
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and
American
was what
however,
denominator
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that,
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1 percent.
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of
on ephedra
21
was
of
And we used
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to
Dr.
which
calculation
we had
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percent
in
We may use
what
18
use
included
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time
caused
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So for
14
may know
up to
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data.
13
paper
Journal
you
So the
that
50 percent
if
in
was underreporting.
follow
And
10
19
in
calculate
8
you
there
FDA report
they
given
syndrome
that
Association
was
as,
myalgia
concerned
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that
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REPORTING ASSOCIATES
(301)
390-5150
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13,
the
ct
129
1
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estimate
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assume
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13 companies,
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in
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in
terms
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are
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percent.
11
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12
were
to
that
the
number
15
and
the
16
time
have
to
19
slide.
only
companies
We are
this,
that
a worst-case
which
will
this
said
see
events
persons
sell
estimate
increase
our
represented
60 percent.
risk.
75
We really
how sensitive
all
the
our
members
adjusted
years
estimates
of
for
in
place
reporting
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use
we have
proportion
in
this
same
frame.
I want
slide.
that
an
assumptions.
of
17
18
be conservative
perhaps
So we have
14
exposed.
clearly
time
We could
13
time
the
is
exposure
our
we calculated
country.
This
trying
sales.
data
person
to
entire
assume
sales
of
again
Okay.
8
annual
number
going
on annual
No,
20
In
to
wait,
I don't
We wanted
to
order
21
risk.
22
literature
23
population-based
24
range
25
age
to
review
of
range
turn
risk
now to
want
compare
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of
U.S.
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MOFFITT
to
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event.
to
to
studies
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to
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nest
background
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representing
There
Next
a comprehension
studies
tried
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the
we performed
and
cases.
first
this
epidemiology
statistics
from
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some
REPORTING ASSOCIATES
(301)
390-5150
a
a similar
issues
with
ct
130
1
this
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out
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point
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3
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4
Assuming
5
the
sales
6
all
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7
exposure;
8
one
9
reported.
in
first
event.
a 10 percent
from
these
this
is
this
10
at
3.6
per
11
in
the
population
12
--
population
the
risk
15
the
estimated
16
dramatic
of
estimated
20
usage
21
assuming
22
manufacturers,
23
as you
24
percent
25
but
20 to
60 per
no way
saying
that
at
rate
This
19
the
seizures
is
increase
per
here
person
all
companies
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background
hundred
rate
thousand
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certainly
MOFFITT
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the
estimate
reduces
is
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reporting
estimated
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drops
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here
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seizure
seizure
as changing
The yellow
that
of
changes
as well
10 percent
the
ephedra
I am saying
with
percentage
products.
see,
All
years
ephedra
can
AERs were
rate.
slide
reporting
still
all.
certainly
in
100,000
of
the
not
statistics.
14
rate
below
is
the
rate
is
of
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18
which
This
of
This
an estimated
100,000.
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17
in
in
were
years
period.
period
assume
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We calculated
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rate
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in
is
Seizure
reporting
we estimated
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is
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rate
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REPORTING ASSOCIATES
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390-5150
the
is
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goes
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events
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background
The next
is
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ephedra
strokes
rate
5
was
This
6
changed
7
almost
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There's
9
two
slide
all
of
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remarks
11
this
gray
box
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5 to
60.
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13
number;
14
looked
15
five
16
who belong
17
effect
is
here
is
from
to
19
year-olds
20
50 to
21
again,
22
estimates.
we're
25
really
studies
So along
with
that
realizing
that
second
comparing
looking
MOFFITT
in
goes
point
at
is
45,
the
of
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age
of
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worker
to
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60 as an upper
really
all
limit,
just
to
to
another
rate,
It's
impossible
a range.
The
up dramatically,
I want
rate
we
population.
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this
of
healthy
a population
rate
one
age
the
from
an actual
women under
a younger
100,000.
just
of
slide,
goes
AERs that
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make
the
last
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women over
to
in
of
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not
sort
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in
essentially
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the
strokes
strokes
23
say
in
For
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range
rate.
to
have
within
a wide
all
the
100
is
study.
used.
and
of
HMOs.
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18
are
bit
population
hard
estimates
they
this
the
on the
consumption
I didn't
very
occurred
is
and
a little
the
40 percent
at
rates
rate
100,000
60 depending
how those
One,
estimated
per
shows
sorry,
is
to
that's
I'm
Our
7.1
assumptions
here.
population,
rate.
users
three
by reporting
10
24
stroke
point
out
REPORTING ASSOCIATES
(301)
390-5150
is
that
we are
to
say
ct
132
1
what
2
consistency
3
population
4
differences.
5
Fen-Phen
6
market
7
the
8
this
9
distinct
pathology,
10
of
abnormalities
11
servings.
the
actual
is.
with
the
reported
range
and
we're
And
--
or
at
estimated
was
I'll
the
time
also
you
percent.
So the
the
14
increased
risk
15
dramatic
risk
16
we don't
see
17
concern
and
here
estimated
19
with
the
20
same
study
that
for
that
now to
myocardial
lower
rate
in
the
population.
of
young
women here,
And
again
as we very
24
will
mention
25
from
people
the
and
was
the
based
prevalence
on case
was
was
that
1
30-fold
kind
of
a range,
infarction
100,000,
certainly
of
we have
per
23
from
this
there
looking
realizing
when
rather,
prevalence
5.1
numbers
removed
30 percent
was
22
example,
abnormalities,
rate
21
dramatic
and
that.
Turning
18
was
incidence
was
we're
one
because
The population-based
13
the
for
just
valve
situation
was
with
a
textrafenfloamine,
of
but
or
for
looking
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prevalence
looking
range
and
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valve
We are
give
Fenflordamine
12
1
number
change,
but,
again,
consistent
with
again
is
that
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age
these
is
assumptions
of
range.
consistent
This
our
most
the
again,
our
the
the
numbers
Rhe other
MI studies
that
were
are
thing
I
all
:
under
'MOFFITT
45,
and
30 percent
REPORTING ASSOCIATES
(301)
390-5150
of
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MIS
133
that
we saw in
And
if
you
down.
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take
those
So it's
numerous
6
numerous
7
estimates.
8
and
9
control
in
we tried
to
group,
11
population
12
a risk
13
exercise
14
sudden
15
the
16
percent
it
limitations
obtain
to
vary
for
can
17
the
the
younger
19
that
data
20
don't
think
that
21
risk
factors
for
22
course,
23
other
this
or
25
adverse
morning
women under
disapproved
events.
summary,
this
not
is
an association
However,
MOFFITT
that
out
50
the
have
in
collected
age
45 I
significant
And,
of
incidence.
an attempt
between
even
pick
they
disease.
of
and
especially
think
them
a range
that
factors.
statistics
cardiovascular
is
We know
don't
in
use
obesity
statistics
certainly
to
that
infraction
1 don't
we had
general
myocardial
risk
of
range
a true
disease.
--
In
24
to
know
heard
50 percent
upsets
not
this
cardiovascular
for
make
population
populations
but
to
a reasonable
This
The population-based
18
come
There
incidence
we certainly
AERs had
45.
compare.
over
comparing
You also
of
will
We had
it
The population
population.
age
here
to
our
in
be a trigger
death.
hard
be conservative.
statistics
factor
dots
this.
to
we're
of
is
variability
the
compare.
to
We tried
characteristics,
to
fact
over
these
hard
assumptions
10
were
out,
quite
And
are
reports
under
ephedra
our
REPORTING ASSOCIATES
(301)
390-5150
to
prove
and
estimates
that
134
we believe
2
events
3
seizure,
4
consistent
5
expected
are
in
likely
to
ephedrine
users,
strokes,
6
7
will
8
consensus
and
simply
in
hear
with
Based
on this
and
our
the
other
10
information
does
11
the
12
alkaloids
13
directed,
14
the
15
of
16
alkaloids,
17
100
mg of
18
all
we believe
19
available
dietary
and
and
not
more
than
dietary
22
The panel
23
information
24
next
25
again,
now,
didn't
a lot
on this
but
These
were
over-the-counter
MOFFITT
I will
our
between
ephedrine
when
used
directed"
as
according
is
serving
total
to
limits
ephedrine
of
not
more
than
warnings,
over-the-counter
products.
are
containing
have
read
association.
appropriate
with
question
you
available
of
alkaloids
supplements
slide.
"as
and
consistent
The next
the
consumption
ephedrine,
that
I will
events
25 milligrams
total
data
which
daily
events
use.
containing
define
total
of
an association
adverse
ephedrine
21
the
recommendation;
and
20
that
supplements
I would
AHPA trade
of
of
may be
rate
members,
demonstrate
serious
users
other
question
feels
not
the
panel
first
these
ephedrine
of
rates
background
of
The panel
of
the
incidents
estimated
MIS among
absence
to
use
the
the
from
9
overestimate
there
indications
ephedrine
of
time
alkaloids?
to
review
go through
some multiple
ephedrine
for
a little
dose
studies,
looking
REPORTING ASSOCIATES
(301)
390-5150
bit
at
ct
135
1
weight
loss.
And
2
is
fold.
One,
3
that
4
morning,
5
limited
6
this
two
have
shown
with
to
show
weight
the
loss,
placebo-controlled
study
9
will
this
be presenting
tomorrow,
looking
supplements
at
placebo-controlled
with
or
all
three,
blood
and
review
of
these
containing
18
about
the
hypothesis
this
they
are
that
management.
to
review
right
a randomize
after
study
Huber
--
and
he
as I understand,
different
dietary
alkaloids,
showed
randomized
significant
weight
loss
effect
on heart
rate
no significant
pressure.
So are
16
heard
slide
studies
support
ephedrine
which
are
studies
three
containing
there
small
able
8
that
up this
are
weight
were
putting
as you
They
for
We also
of
you
certainly
effective
7
purpose
ephedra.
but
is
the
there
indications?
data
Well,
we believe
ephedrine
alkaloids
the
based
dietary
on a
supplements
may be useful
in
weight
management.
The
with
user
third
question,
are
characteristics?
21
issues
about
this
22
conclusion
23
absence
of
24
between
ephedrine
25
adverse
events
is
or
data
You're
from
our
other
consensus
clearly
MOFFITT
is
demonstrating
dietary
when
panel
used
supplements
as directed,
outcomes
going
associated
to
members,
that
hear
but
given
some
our
the
an association
and
serious
the
presence
REPORTING ASSOCIATES
(301)
390-5150
or
ct
136
1
absence
2
determined.
there
3
was
this
However
4
lead
to
serious
5
idiosyncratic
6
reactions
7
recommended
8
ingested
acceptable
serious
overdosing
adverse
events,
reactions
and
The
10
were
sizes
11
consensus
12
the
13
perspective.
14
this
15
of
so the
study.
this
after
panel
I reviewed
I don't
think
16
sufficient.
I think
that
17
limitations
18
about
19
from
great
which
the
the
25
should
any
from
others
are
were
going
the
for
their
to
review
to
present
my own quick
study
several
definitive
between
met
was we
epidemiological
you
that
study
was
severe
conclusions
PPA hemorrhagic
stroke
study.
Finally,
dietary
at
a chance
study
give
prevented
association
20
24
use
panel
have
the
conclusions.
about
rare
skin
stroke
our
didn't
I'll
23
be
can
very
came with
hemorrhagic
detail.
of
and/of
with
as they
I understand
in
22
overuse
including
reactions
PPA and
made aware
reached
minor
may occur
allergic
serving
and
cannot
food.
9
21
population
bt
those.
this
the
the
panel,
other
I'd
like
I think
these
a lot.
We believe
supplements
contain
MOFFITT
are
containing
appropriate
consensus
to
just
important;
that
all
statements
go through
we thought
labeling
ephedrine
directions
some
of
alkaloids
and
REPORTING ASSOCIATES
(301)
390-5150
warnings
for
ct
137
1
the
public
2
approved
3
products.
as adopted
for
4
over-the-counter
We also
5
legible
6
purchasing
and
7
their
by AHPA and
product.
You'll
hear
consensus
but
9
data
available
do not
10
with
ephedrine
alkaloids
11
as a cause
14
show
death.
was
that
review
pathology
that
is
dietary
that
consistent
supplements
an independent
be assembled
of
to
Hutchins
the
a pattern
should
prior
by Dr.
containing
panel
be readily
for
data
We believe
pathologic
should
consumer
statement
multidisciplinary
a clinical
the
those
alkaloids
these
pathology
8
of
that
to
the
to
ephedrine
believe
available
similar
all
to
death
perform
reported
to
provide
a
FDA.
15
We also
16
more
17
Institutes
18
Human
19
consider
20
unresolved
believe
comprehensive
of
21
scientific
Health,
Services
and
further
in
order
to
database,
the
The Department
industry
controlled
of
should
work
studies
to
National
Health
together
and
to
address
issues.
Our
last
slide,
22
that
preparations
that
23
that
are
without
24
instructions,
25
with
claims
that
marketed
contain
serving
of
size
achieving
MOFFITT
we believe
that
very
ephedrine
responsible
alkaloids
and
label
limitations,
an altered
strongly
or
state
REPORTING ASSOCIATES
(301)
390-5150
are
of
marketed
ct
138
1
consciousness
2
drugs
3
excessive
should
Dr.
so-called
because
they
street
promote
abuse.
that
I will
end
and
turn
it
over
to
1
[Applause.
DR.
have
the
PAGE:
first
9
Toxichemica
11
Thank
you,
I am Norbert
going
to
published
literature
on the
13
ephedrine
alkaloids
containing
14
save
I'm
to
15
products.
going
I might
17
this
18
you'll
19
hazardous
20
agencies
21
number
22
haven't
23
Administration.
24
knowledgeable
25
risk
time
to
see
the
from
mention
Ephedra
slide
assessments
and
the
been
assessments
some time.
health
on has
in
and
Could
we
I am a partner
been
I'm
the
area
prepared
briefly
adverse
about
effects
dietary
to
I've
quite
To
as ephedra
been
on the
the
and
a large
with
doing
federal
staff
one
of
a
I really
Drug
myself
hazard
as
with
The only
Food
at
but
allied
assessments
consider
of
really
Council,
been
risk
the
of
I am a consultant
Education
I've
the
supplements.
these
that
agencies.
But
MOFFITT
very
refer
this
for
of
Page,
speak
12
16
Kimmel.
International.
I'm
time
Dr.
slide.
Panel,
in
including
Page.
7
10
and
And with
6
8
euphoria
be prohibited
use
4
5
or
fairly
assessments
number
REPORTING ASSOCIATES
(301)
390-5150
of
and
ct
139
criteria
documents
2
I'm
3
literature
4
review
5
providing
6
But
7
structure
going
of
the
to
searching
11
So we've
12
done,
13
literature.
of
did
go a few
14
analyze
of
in
the
there
23
24
25
very
is
not
small
only
metabolized
a very
the
of
going
the
to
of
of
they
the
is
that
PPA literature
ephedra
and
have
the
in
they
to
products.
In
appropriate.
First,
it
going
minute
but
getting
scientifically
that?
literature.
however
the
Love
actually
add
problems
on the
--
of
Dr.
amount
PPA is
is
to
also
only
go into
of
present
ephedra
in
that.
a few
Also
that
PPA.
A third
pharmacological
job
concern
amounts
products
to
FDA docket.
complement
bulk
job
effects
is
ephedra
to
good
we're
Why do I say
only
the
some of
the
heavily
health
this
be
address
some serious
very
my opinion
we will
to
a pretty
My major
the
and
I want
that
I have
relying
FDA's
an independent
references
an excellent
interpretation.
18
all,
retrieving
I think,
done
on the
FDA report.
They
and
specifically
literature
specifically
the
staff.
agencies.
Now we have
First
are
focus
published
of
10
16
various
some additional
I want
and
the
to
report.
8
9
for
reason,
and
MOFFITT
there's
toxicological
substantial
differences
REPORTING ASSOCIATES
(301)
390-5150
between
is
140
PPA and
2
alkaloids
3
third
both
in
issues
ephedra
a pseudoephedrine
ephedra
products.
since
4
I'm
5
products.
6
slide
I think
7
pretty
similar
8
to
90 percent
9
is
the
going
12
There's
13
very
was
to
14
products.
16
have
17
at
Gurley
and
his
18
looked
at
19
no PPA and
20
this
is
21
and
3.1.
six
this.
I'm
team.
In
the
of
down
here,
24
2000
he expanded
25
products.
but
in
not
going
the
three
the
the
it
study
and
he found
MOFFITT
in
actually
that
to
90
two
pseudoephedrine.
and
PPA in
the
one
very
ephedra
show
in
small
study,
recent
that
two
1997
three
looked
in
30 to
really
studies
alkaloid
another
40
products.
of
products,
had
data
commercial
first
total
had
the
his
existing.
a number
ephedra
Gurley
23
usually
one
with
the
and
seen
he had
ephedra
here
this
ephedra
and
methylephedrine,
been
other
percent
in
from
a PPA in
have
of
the
And
and
look
looked
Dr.
the
already
I think
ephedrine
others,
There
22
see
alkaloids,
Let's
15
can
PPA in
I came out
amount
with
who will.
Fong
here,
whereas
as you
amounts
you
by Dr.
accepted
a few
speakers
that
I have
main
dwell
now about
earlier
ephedra,
ephedra
small
talk
what
generally
I won't
other
mention
it
But
major
to
I might
10
11
we have
the
Dr.
they
which
had
amounts,
content
the
study
at
14 he found
REPORTING ASSOCIATES
(301)
390-5150
.61
and
.3
should
be
in
year
the
20 ephedra
no PPA at
ct
141
1
all.
2
.16
In
to
the
other
six
. 25 milligrams
3
Now,
4
that
there
5
dose,
6
we we're
per
keep
in
even
talking
Lee
3 percent
of
9
are
used
TEA consistent
10
to
be with
FDA also
11
and
12
in
13
ephedra
14
off-the-shelf,
15
and
in
another
study
products
16
little
in
18
products
19
amounts.
most
products
that
21
major
22
PPA,
23
small.
24
Wilkerson
25
et
al
ephedra
PPA,
take
up the
to
however,
It
used
PPA.
the
varies
found
both
there's
from
with
of
the
about
4.3
methods
of
can
percent
they
of
he took
and
have
1.8
here
PPA
percent.
there's
In
very
those
small
metabolism
of
be demethylated
is
metabolism.
4 percent
REPORTING ASSOCIATES
(301)
390-5150
to
extremely
Beckett
found
but
nine
not
demethylation
publisher.
and
percent
extremely
issue
who used
products
no PPA.
Ephedrine
amount
MOFFITT
it's
he
content
at
he did
see
so
which
1995
5.1
. 2 percent
can
where
alkaloids
popular
nine,
do have
Let's
20
are
those
you
in
he looked
amounts.
So I think
17
these
a
--
alkaloids
about
recently
of
trace
the
paper
in
we will
and
Betz
that
heard
amount.
ephedra
PPA.
first
and
and
head
small
total
review
more
amounts.
you've
what
published
of
his
small
30 milligrams
that's
a very
the
very
I think
as 20,
recently
found
he found
that
but
about
8
two
mind
more,
also
were
dose.
may be as much
perhaps
7
there
and
Bob and
in
4.3
ct
142
1
Basalt
and
2
Cravey
Now the
3
they
4
out
5
actually
6
that
7
so we really
8
any
9
metabolism.
show
8 to
that
is
much
not
don't
Wilkinson
using
normal
of
an alkaline
about
and
it
is
this
is
there
that
was
the
if
this
is
does
increase
percent.
an
a study
by
the
fact
that
But,
by and
rather
in
individual
promoted
is
The
metabolism
and
the
whether
though
PPA.
18.2
point
used
may have
eight,
to
as to
urine,
to
up to
individuals
their
large
minimal
in
around
5 percent.
The other
16
other
routes
ingestion
use
much
where
I want
Dollery
information
we do know
Ph of
report
reference
that
ephedra
went
Dollery's
that
know
What
4 percent.
metabolism.
situation
has
used
a secondary
publication
individual
4 to
is
underlying
it
came over
20 percent
a 1975
there
study
'97
FDA has
Dollery
metabolism
18
in
of
of
is
exposure.
dietary
products
that
inhalation?
issue
it
appropriate
We were
talking
supplements,
is
given
by nasal
And my opinion,
I think
appropriate.
are
The
according
to
23
absorbed
slower
24
pharmacokinetics
25
So I don't
the
alkaloids
references
than
in
ever
in
at
the
problem
MOFFITT
pure
it
appropriate
is
products
listed,
they
but
metabolism
is
with
information
using
to
or
this
alkaloids
use
about
spray
ephedra
I've
to
quite
REPORTING ASSOCIATES
(301)
390-5150
are
the
basic
similar.
from
ct
143
1
other
routes.
2
I want
to
present
3
kind
of
4
it's
also
cardiovascular
effects,
5
about
the
cardiovascular
effects
will.
interesting
But
subjects
9
10
to
in
day,
in
also
this
And
product
they
and
just
it
compared
14
capsules
15
ephedra
is
the
which
is
tables
16
dose
et
of
someone
speed
up there's
And what
for
herb
to
the
results.
Basically
complete
for
all
forms;
I don't
think
elimination
Kinetic
20
one
compartment
first-order
21
consistent
22
there
23
tablets
24
is
25
maximum
across
slower
or
is
time
the
pretty
from
period
level
MOFFITT
in
did
that
of
absorption
it's
debate
of
the
readily
about
that,
straightforward,
and
that
They
The main
a longer
any
literature.
solutions.
peak
three
model
absorption
they
solution.
there's
is
this
ma huang
are
the
and
no PPA in
ephedra
19
one
50
pressure
ephedra.
powered
absorbed,
in
frequently.
pharmacokinetics
18
or
blood
12
twice
dose
to
else
subjected
ma huang
quite
finely
be talking
al,
blood
is
pharmacokinetics
since
the
primarily
I think
I won't
the
is
there
the
a total
measured
17
is
with
that
and
Here
nearly
paper
Wyden,
he had
they
sampled
11
study,
words
and
they
deals
25 milligram
other
milligrams
in
one
thing
time
blood.
in
to
seems
did
capsules
REPORTING ASSOCIATES
(301)
390-5150
find
to
that
than
from
the
capsules
reach
It's
it's
the
getting
be
ct
144
1
close
2
in
to
the
four
hours
tablet
3
or
In
in
coming
5
later
6
valuation
7
about
the
8
found
a slightly
9
from
10
pretty
I'm
than
good
11
14
the
15
ephedrine
16
example
17
They
18
products.
the
FDA has
been
21
themselves.
22
ephedra
23
pseudoephedrine
24
available
25
are
only
to
get
it's
not
is
at
a
in
basically
study
ephedra
and
he
alkaloids
So it
seems
like
a
the
extent
of
the
into
a few
effect
of
however,
pseudoephedrine
used
in
the
quickly,
these
a fair
the
which
the
11 journal
MOFFITT
ephedra
products.
the
on
for
and
so on.
on PPA medical
are
the
11 articles
to
the
ephedra
amount
of
literature
also
And
products;
preparations
been
document.
reports
actually
literature
medical
epinephrin,
has
FDA's
that
literature
pertaining
I mean,
reports
in
asthmatic
There's
in
if
peak
time
to
caps.
only
published
--
a similar
absorption
I want
Real
have
did
slower
included
20
or
half
also
concluded,
those
19
the
the
Gurley
adverse
and
also
two
absorption
significant
But
gel
the
reaching
is
sure.
There's
with
than
system.
Now,
deal
got
slower,
from
less
you've
that
not
same.
pills
13
bit
whether
with
form.
words,
a little
time;
literature.
solution
other
4
12
compared
involving
that
products
on the
ephedrine
and
prepared
and
But,
anyway,
12 cases.
REPORTING ASSOCIATES
(301)
390-5150
the
there
ct
145
1
Two serious
2
was
an athlete
3
the
pathology
4
pathologist,
5
with
6
products
7
were
8
therefore,
9
is
with
repair.
really
been
there,
There
had
the
prior
risk
factors
the
association
Second
11
infarct.
weeks
been
and
that
pathology.
according
and
to
it
24 hours.
a necrosis
to
In
I have
But
the
was
no exposure
which
12
building
and
13
products
in
14
had
15
valley,
16
products
major
the
ephedra
addition
there
mentioned.
with
ephedra
is
a stroke
case
The man was
but
consuming
addition
to
heart
it's
and
17
So,
product
there
literature
19
one
thing
20
out
of
21
psychiatric
22
any
23
would
24
of
25
product.
is
on the
that
I think
the
five
also
of
ephedra
stand
where
nor
appear
cases
But
these
though
that
may have
there
MOFFITT
are
in
the
other
papers
not
cases
is
temporal
many
factors.
were
in
the
three
and
cases
history
ephedra
open
the
as serious,
a previous
the
many
with
risk
whether
in
frame
overdosing
there
an
He also
other
out,
of
products.
products,
was
body
the
there's
conditions,
or
of
this
amounts
patent
case
a list
intensive
ephedra
defect,
are
does
in
and
excessive
the
a clear
This
la
engaged
he's
a congenital
those
a death
questionable.
10
role
is
cardiac
a couple
within
one
existing
has
for
other
events,
to
product
related
to
other
risk
factors
a couple
dietary
REPORTING ASSOCIATES
(301)
390-5150
had
question.
relationship
been
of
involved.
It
ct
146
1
On the
2
definitely
3
cases
4
four
5
label.
two
related
the
hypertension
to
the
had
daily
So it
6
was
role
8
9
of
consumed
strictly
one
there's
something
in
probably
triggered
10
it
be some other
11
like
12
there
was
there
that's
also
was
had
acolytes,
16
to
18
very
low
The
other
in
pseudoephedrine
about
herbs.
23
25
eight
There
to
ephedrine
and
In
literature
is
was
the
the
author
supplement
that
said
ephedrine,
it
but
did
look
On intulethias
you
doses
and
see
the
and
calcium,
is
certainly
the
levels
individual
and
intake.
thing
is,
case
it
S ince
in
case
after
the
use,
protein
fluid
last
hours
reactions
24
in
measured
The
than
on the
clear
One thing
does
high
this
the
more
not
hepatitis.
high
high
of
does
necessarily
mediated
extremely
ephedrine
dietary
not
is
fact,
product.
long-term,
a diet
It
in
the
this
immune
one
one
as recommended
case.
alkaloids,
it
in
fact
were
overdosing.
ephedrine
could
these
In
allowance
Hepatitis,
7
overdosing.
individual
times
cases
there
the
erythroderma.
the
individual
of
ephedrine
and
calculi.
is
a history
was
related
prior
over-the-counter
This
occurred
ingested
Chinese
sensitization
and
alkaloid
products
pseudoephedrine
summary
not
it's
relevant
MOFFITT
my opinion
to
this
that
analysis
REPORTING ASSOCIATES
(301)
390-5150
the
PPA
of
ephedra
147
products
the
2
Also,
3
injection
4
consumption,
5
factors.
the
few
the
products
overdose
Thank
reasons
serious
ephedra
the
I have
adverse
were
are
stated.
effects
related
due
to
from
to
other
the
excessive
risk
you.
[Applause.]
7
DR.
PAGE:
DR.
KARCH:
I'd
like
to
introduce
Dr.
Steven
Karch.
9
10
Steven
11
Francisco.
12
interest
13
deaths,
14
considered
15
extensively
16
parent
17
Karch.
I'm
I'm
is
in
to
confined
19
alkaloids.
20
a cardiac
the
afternoon.
literature
the
subject
San
drug-related
is
text
1997
in
my principal
of
standard
is
examiner
pathologist,
on the
both
My name
medical
investigation
be the
in
to
Good
an assistant
my textbook
generally
and
it
iteration
was
and
quoted
in
the
review.
We're
18
going
to
speak
cardiovascular
The AERs will
21
Professor
Hutchinson.
22
pathologic
changes
23
ephedra
24
reported.
25
for
reported
of
6
8
reasons
exposure
--
complications
be discussed
Briefly,
or
any
was
MOFFITT
is
of
that
for
consistent
are
the
shortly
he found
evidence
responsible
My own review
my comments
ephedra
by
no consistent
the
any
with
REPORTING ASSOCIATES
(301)
390-5150
of
epidemic
the
his
deaths
findings
or
148
1
and
I've
have
2
the
hearts
3
is
4
pathological
that
of
is
6
of
published
7
alkaloids
8
cardiovascular
9
contains
at
C of
it
and
literature
percent
is
than
both
in
new
23
example,
24
much
25
receptors
all
are
review
of
ephedrine
purported
38 or
It
40 percent
but
the
a third
24,
were
this
all
isomers
of
of
effects
is
in
vitro
recent
that
greater
refer
only
to
than
does
MOFFITT
primary
reports
were
occurring
synthetic
that
and
the
one
the
34
ephedrine
to
studies
beta
are
and
phenylpropanolamine.
ephedrine
for
none
19 or
to
document
not
research
to
21 percent;
related
a naturally
affinity
these
exerted
clearly
the
case
about
reading
terms
to
to
from
fairly
entitled
literature,
12 of
about
This
22
is
effects
which
amounting
half,
considers
or
complications.
56 citations
studies;
just
clear
of
my own review
clinical
with
neurologic
of
textbooks.
pseudoephedrine
18
mainly
several
apparent.
on toxic
primary
almost
prospective
of
FDA docket
deals
the
and
features
94 references
to
examine
individuals,
the
and
all
to
no consistency
Of the
more
these
literature
and
meetings
16
opportunity
pathologic
Part
not
the
from
there
5
10
had
the
It
FDA
be equivalent
toxicity
case
and
produced.
there
are
demonstrating,
lR2S
and
isomer
beta
pseudoephedrine
REPORTING ASSOCIATES
(301)
390-5150
for
has
two
and
that
ct
149
1
conversely
phenylpropanolamine
2
In
3
molecular
4
phenylpropanolamine
5
safety
spite
of
all
level
of
In
contains
8
and/or
For
10
ephedrine
11
combination
12
However,
13
cases
is
listed
16
source
17
in
18
the
19
of
20
survey
what
mentions
it
and
and
abused,
stimulant
FDA has
other
for
documents
caffeine.
are
even
about
ingested.
phenylpropanolamine
drugs,
a 1994
chosen
in
support
was not
is
with
or
ephedra
down,
misleading
used
in
ephedrine
no reference
the
in
when
phenylpropanolamine
FDA says
same time
simply
vasculitis
offered
the
review
are
likely
or
contains
about
inappropriate.
FDA says
citations
track
is
the
on the
questions
I feel
the
the
affinity.
at
FDA literature
example,
ephedra
you
itself
textbook
the
to
like
and
the
which
statement.
ignore
the
the
At
paucity
household
so forth.
The
FDA literature
22
contradict
some of
23
significant
increase
24
pressures
25
doses
occur
of
that
as commonly
if
21
I feel
conclusions.
two
The
are
raise
particularly
the
14
of
less
so heavily
to
the
much
differences
mistaken
with
where
15
and
addition
simply
clear
FDA relies
data
a number
9
very
the
ephedra
6
7
these
has
ephedrine
in
its
includes
own conclusions.
in
normal
equal
MOFFITT
review
diastolic
and
intensive
to
or
The
greater
data
which
FDA says
systolic
subjects
than
REPORTING ASSOCIATES
(301)
390-5150
with
60
oral
a
ct
150
milligrams.
The
2
citation
82.
3
paper
and
4
done
normal
5
change
sole
This
it
discusses
tensive
At
7
series
a
have
9
maximal
of
done
12
sure
13
instance,
14
pseudoephedrine
15
to
16
recovery
17
pressure,
I8
there
19
V02mas.
why
they
weren't
there
20
is
21
double-blind,
22
exercising
23
These
24
pseudoephedrine,
25
maximal
are
in
V02maxes
pulse
to
are
up and
a
which
for
with
you,
and
new,
so I'm
included.
For
120 milligrams
of
and
subjected
them
There
was
no change
in
rate
in
diastolic
pressure,
maximal
placebo
Ten
systolic
heart
trials
healthy
and
rate
these
women
exercise
and
I truly
mean maximal.
of
60,
treated
with
rate,
MOFFITT
up to
no changes
diastolic
a recovery
or
not
males
in
did
dummy.
had
no
mention
even
here
them
gave
heart
1993
double
maximal
of
no change
in
were
whom showed
effect
was no change
no change
Clemens
all
testing.
there
that
physiologists
these
healthy
stress
time,
was
six
of
FDA fails
pressure
1981,
to
submaximal
the
picked
in
a review
studies
half
some of
not
Bright
earlier
it's
is
testing.
listed
that
statement
a paper,
by exercise
stress
notice
this
pressure
no blood
exercise
you'll
blood
same time
studies
11
seven
in
the
I've
is
individuals;
demonstrated
10
for
statement
whatsoever
6
support
systolic
REPORTING ASSOCIATES
(301)
390-5150
time,
blood
or
were
151
pressure.
2
In
Dr.
White's
3
variable
effects
4
milligrams
of
5
experience
an increase
6
was
7
believe
a
pressure
were
to
that
in
by Rosanne
11
every
12
volunteers,
13
weightlessness,
14
measurable
in
1999
At
17
measured
18
and
19
very
20
Jacob
21
last
22
recreational
23
athletes,
24
called
25
something
the
through
and
had
which
year,
mission
were
Canadian
that's
the
paper
pseudoephedrine
it
affect
was
a dozen
on any
in
on the
been
involved
just
fit
of
were
Space
been
of
either
these
by Bell
are
and
Medicine
healthy
people
the
paper
not
Warrior
effects
mentioned
and
nine
have
Some of
as the
Aviation
these
studies
wrong.
such
a part
these
not
is
Forces
MOFFITT
is
a simulated
that
have
runners,
they
the
that
study
to
systolic
recently
papers
studies
the
increase
significant
I think
zero
same time
appeared
did
parameter.
important
convincing
20
hard-pressed
in
of
In
given
the
I'm
all
more
males.
their
at
of,
1997,
that
increase
a group
exercise
I think
And
was
again,
half
pressure,
120 milligrams
to
in
12 volunteers
the
blood
cardiovascular
15
in
millimeter
healthy
ignored
in
finally,
12 hours
16
but
diastolic
And,
10
in
8 millimeters.
eight
not
published
noticed
ephedrine,
confined
9
study
male,
professional
who did
Test,
Canadian
what
which
Army
REPORTING ASSOCIATES
(301)
390-5150
is
is
basic
ct
152
training.
And
wearing
with
about
and
milligrams
of
change
diastolic
maximal
pulse
time,
9
longer.
the
caffeine
I
11
since
12
says
13
ephedrine,
14
sources.
15
literature
16
you
17
taking
ia
doses
note
400
of
19
20
pound,
21
2000
75 milligrams
pressure,
there
was
there
only
of
second
22
And
23
she
was
24
milligrams
also
of
the
was
a day
The
only
for
was
MOFFITT
accept
The
use
in
the
per
day
FDA
of
as one
of
the
world
And
a 35-year-old
man
and
a 28-year-old
per
day
another
taking
other
recovery
to
cited
who was
was
ten
in
liberal
14 years.
ephedrine
overweight
no
exercised
cases
ephedrine
person
third
in
cardiomyopathy.
cigarette-smoking-woman
milligrams
is
no change
with
have
four
first
for
ephedrine.
difficult
a ephedrine
prednisone
was
reported
375
there
they
it
taken
was no change
I might
the
ran
of
pressure
been
I think
that
they
having
systolic
course
cardiomyopathy.
has
fact
after
particularly
milligrams
The
and
an interesting
alleging
will
it
achieved
and
kilometer
gear,
ran
change
this
a 3.2
combat
there
cardiomyopathy
In
ran
achieved,
find
I have
in
blood
only
10
of
they
was no change
a
25
people
25 pounds
placebo,
There
these
more
321-
taking
for
eight
woman,
than
two
years.
I believe
1000
years.
case,
and
I wouldn't
REPORTING ASSOCIATES
(301)
390-5150
grams
have
ct
153
1
cited
it,
2
to
3
225
4
attempt.
bit
it
14-year-old
is
of
The
6
infarction
7
but
8
involve
9
involving
of
that
been
reported.
the
eight
hour,
every
Ephedrine
artery
spasms
receptors.
16
is
offered
given
former
high
but
in
user
which
21
of
sympathetic
enervation
22
parasympathetic
23
ephedrine
24
reports
25
these
its
unopposed,
to
of
be magnified.
coronary
both
spasms
an
coronary
were
heart
leaving
them
who
was
was
given
high
deprived
the
leaving
the
Alpha
effects
There
have
been
no other
in
a
a norepeneprine
They
the
two
patients
One of
was
again
the
ephedrine
users
two.
MOFFITT
drop
adrenergic
involve
may.
means
from
however,
probably
anesthetics
nose
Well,
of
anesthetics.
spinal
that
case
spasms.
true;
as it
cases
many months.
may result
support
and
be that
for
true
milligrams
stimulation
clearly
spinal
cocaine
depleted,
by
are
an ephedrine
coronary
damage
induced
This
citations
been
cardiac
and
that's
one
six
day,
and
yes,
the
ephedrine,
every
a suicide
offered
was
taking
ischemia
Well,
And
refers
after
in
myocardia
user
taking
hour,
FDA says
failure
citations
an ephedrine
who was
FDA document,
heart
phenylpropanolamine.
abuser
the
the
phenylpropanolamine
FDA says
have
seven
in
who developed
milligrams
5
cited
REPORTING ASSOCIATES
(301)
390-5150
besides
of
154
The
2
anesthesiologists
3
to
skeletal
6
ephedrine
7
to
8
The
9
amount
10
of
The
5
was
of
FDA says
shifting
following
the
relevance
not.
potassium
adrenergic
Three
to
agents
certain
like
a
individuals
references
suicide
pseudoephedrine,
second
12
attempted
13
3000
milligrams
14
cans
of
15
phenylpropanolamine.
16
attributed
suicide
are
who took
theophylline,
referenced
who took
of
cited.
an unknown
and
to
citation
no
soft
that
drink,
a ephedrine
it
an unknown
was
amount
in
this
shift
instance
and
ephedrine,
50
750 milligrams
attempted
drug,
an
be roughly
potassium
another
of
of
would
and
Why the
Lastly
involves
375 milligrams
caffeine,
caffeinated
17
testing
is
may predispose
an attempted
The
19
but
of
use
in
was performed.
11
took
observation
.apparent,
dysrhythmias.
toxicology
18
quite
supplements
alkaloids
first
this
food
muscle
cardiac
of
is
consumers
4
relevance
of
should
escapes
suicide
be
me.
who
no toxicology
was performed.
Ephedrine
20
21
a ephedrine
22
cerebrovascular
23
hemorrhage
24
events
25
Most
and
brain
and
those
hemorrhage.
pseudoephedrine
accidents
that
of
and
vasculitis.
were
were
reported
overdoses
MOFFITT
have
secondary
Well,
actually
that
The
been
to
only
FDA says
implicated
intercranial
half
involved
occurred
REPORTING ASSOCIATES
(301)
390-5150
of
the
ephedrine.
in
IV drug
in
ct
155
1
users
and
the
diagnoses
2
histologically
3
phenylpropanolamine,
4
ephedrine,
5
citations
No.
6
diagnoses
of
proved
9
they
comes
been,
that
are
comments
have
not
been
they
things
important
11
these
compounds.
One of
the
12
farther
than
FDA and
--
13
isomers
to
14
sympathomimetic
15
other
16
shortens
17
development
be identical
reason
of
have
of
ephedrine
20
heart.
So I don't
21
have
24
have
caused
25
know
which
really
the
as forthcoming
safety
of
all
even
the
all
same,
there
statement
that
and
is
no
ephedrine
facilitates
the
arrhythmias.
studies
of
electrophysiology
see
some
goes
considers
considers
as
overlooked
the
no published
on the
64.
how the
of
statement
the
the
could
included.
Two of
unpredictable
which
FDA
the
FDA consultants
cardiac
been
of
considering
period
re-entry
effects
23
the
the
No.
may have
be the
refractory
19
22
to
explain
There
been
and
drugs
to
the
18
to
of
reference
the
10
the
in
taking
disputing
to
and
was
One of
a letter
made
have
might
one
theophylline.
cellulitis
they
and
a combination
actually
I feel
was
two,
other
and
71 is
vasculitis
only
the
When it
reviewers
in
caffeine
7
8
of
the
variations
reactions.
specific
MOFFITT
FDA consultants
in
individual
One even
enzymes
believe
in
the
that
sensitivity
argues
that
bowel
REPORTING ASSOCIATES
(301)
390-5150
and
may
"we
liver
do not
ct
156
1
metabolize
ephedrine.
2
exaggerated
3
because
4
two
5
that
6
genetic
sensitivity
they
lack
comments
to
is
And
this
pharmacology
of
9
understood.
Finally
factors,
11
reasons
12
susceptibility
13
presence
of
14
coronary
artery
already
17
fact
18
of
19
number
of
adverse
20
States
is
now in
people
In
22
recommended
23
but
24
there's
products
extremely
every
has
Ephedra
and
MOFFITT
risk
unlikely
for
individual
due
disorders
or
hypertension.
of
to
the
such
course
as
would
drugs,
that
quote
and
but
in
United
the
in
"millions
ephedrine,
reported
apply
the
hundreds."
I believe
not
excessive
reason
the
individual
medical
containing
how
well
is
states
conclusion
doses
that
be possible
reactions
the
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25
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The
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fail
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REPORTING ASSOCIATES
(301)
390-5150
such
different
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157
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[Applause.]
9
DR.
10
Dr.
11
you.
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Ph.D.
Jones,
FARBER:
and panel
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gives
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16
recertified
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board
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17
International.
19
associate.
times
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government.
22
director
23
pesticide
24
scientists
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25
regulatory
toxicologists,
The
of
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MOFFITT
last
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background
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20 years.
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Effects
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four
Health
program.
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you,
a slide
40 years
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in
thank
my relevant
certified
Page
21
of
certification.
Dr.
20
I have
1960;
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18
and
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and
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pharmacology
class
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Farber
as a toxicologist;
15
afternoon
members
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just
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the
for
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as
EPA's
chief
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largest
REPORTING ASSOCIATES
(301)
390-5150
was
health
of
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group
of
158
ct
1
regulatory
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18
pharmacokinetic
takes
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Center
for
slide
here
--
the
276
adverse
affect
basis
or
a risk
studies,
of
in
please?
discuss
if
and
approval
to
this
mention
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reports
year.
process
for
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21
in
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literature
support
22
I'd
like
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just
discuss
some of
23
reliability
of
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276
of
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from
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evaluated
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animals
20
25
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with
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24
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March
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many
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serving
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Toxicology
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my colleague,
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Dr.
Dr.
Page
and
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Page,
Dr.
found
FDA.
of
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reports.
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REPORTING ASSOCIATES
(301)
390-5150
recently
containing
159
1
ma huang
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reports
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17
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22
records
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23
records.
24
lacking
25
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MOFFITT
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analysis.
age
handwriting
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for
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Food
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REPORTING ASSOCIATES
(301)
390-5150
on
160
dose
at
dose
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file
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202 AERs,
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9
analysis
on this
decisions
based
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These
276
slides
files,
the
10
11
12
similar
to
13
original
14
are
15
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really
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23
risk.
24
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25
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regulatory
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MOFFITT
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case
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REPORTING ASSOCIATES
(301)
390-5150
be
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15
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16
AERs.
17
significant
18
analysis
and
19
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experts
20
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21
slide
22
selected
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of
of
judgment
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AERs
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sure
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that
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in
Page
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MOFFITT
recent
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Dr.
we did
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23
25
I'm
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5
own disclaimers
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REPORTING ASSOCIATES
(301)
390-5150
or
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is
degree
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15
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17
causality
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20
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21
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24
exercise
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REPORTING ASSOCIATES
(301)
390-5150
made
the
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afternoon.
MOFFITT
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1994.
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REPORTING ASSOCIATES
(301)
390-5150
this
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24
[Applause.]
25
DR.
supplements,
they
risk
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when
concern
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safe;
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are
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that
is,
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very
HUTCHINS:
MOFFITT
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My name
is
Grover
REPORTING ASSOCIATES
(301)
390-5150
on
data
causality
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for
in
agree
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experts
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165
I'm
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reports
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association
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16
alkaloids.
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17
likely
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death
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18
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19
AER to
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7
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MOFFITT
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REPORTING ASSOCIATES
(301)
390-5150
for
likely
166
ct
1
consistent
pathologies
2
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4
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Toxicology
24
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REPORTING ASSOCIATES
(301)
390-5150
negative
167
ct
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in
and
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performed,
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deaths
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23
coronary
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24
vessels.
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25
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MOFFITT
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eight.
divided
these.
three
in
and
significant
obstructing
had
symptoms
consistent
with
REPORTING ASSOCIATES
(301)
390-5150
the
in
risk
coronary
third
168
ct
1
artery
disease,
2
Each
3
alkaloids
4
deaths
5
of
of
these
patients
for
here
were
presence
8
inflammatory
9
unknown
10
about
11
positive
findings
two
of
The one
cause.
and
toxicity,
seems
caused
more
appropriate
but
in
my view
artery
the
the
the
the
presence
disease.
demonstrated
This
heart.
myocardium
case
had
taken
case
for
one
however,
well-recognized
14
other
ephedrine
coronary
in
performed.
the
autopsy
in
not
by
instances
reaction
was
adequately
of
myocarditis
a month
taken
periods,
explained
and
In
7
had
a varying
symptoms
6
an autopsy
however,
since
the
is
an
usually
of
materials
day
and
for
did
myocarditis
of
sudden
unexpected
to
attribute
the
have
is
a very
deaths,
outcome
a
it
to
that.
Four
15
of
cases
None
16
vascular
disease.
17
autopsy
performed.
18
very
unclear.
19
the
12 most
20
context
21
intercranial
22
of
of
the
The
Two of
probably
24
dissections.
25
aorta,
these
the
the
cerebral
had
on exposure
ones
at
the
One,
first
an
was
bottom
hemorrhages
hemorrhage.
and
by
individuals
hypertensive
pre-existing
in
the
were
the
second
a carotid
occlusion
cause.
Two of
23
explained
information
them,
aneurysm
unknown
of
were
typically
This
the
deaths
is
a tearing
occurs
MOFFITT
were
in
the
explained
of
the
context
by
wall
of
REPORTING ASSOCIATES
(301)
390-5150
of
some
aortic
the
an
169
ct
1
abnormality
2
in
in
many
The
found
very
to
of
8
fact
far
more
and
These
dissection.
exposure
11
those
12
cases,
13
doing
14
to
15
their
the
death
in
16
hypothermia
to
108
17
phenomenally
18
agents
There
cases.
unfortunate
high
both
to
19
20
radnomyalysis
21
context
22
indication
23
Blood
24
been
25
toxicology
first
case
two
cases
of
that
bile
and
negative,
historical
information
was
the
and
to
of
to
a
there
in
case
exposure,
REPORTING ASSOCIATES
(301)
390-5150
the
death.
were
muscle
for
of
to
his
deaths
other
exposure
really
was positive
the
of
listed
exposed
Again,
in
who were
done.
MOFFITT
unclear
group
related
a breakdown
exercise.
was
was
prior
The other
extreme
aorta
autopsy,
cases
been
months
is
the
two
not
two
which
form
genetic
of
is
a
that
exercise
which
He had
was
It
at
first
was
dissection.
individuals
and
least
of
was
of
degrees,
is
aorta
me a interesting
fasting
the
is
the
alkaloids
the
and
there
tissues
outcomes
high.
at
to
in
case
discovered
were
temperatures
case
this
ephedrine
strenuous
for
first
aortic
that
wall
basis.
of
to
were
aortic
second
connective
however,
very
the
the
10
the
the
history
predisposes
9
in
probable
of
of
a familial
that
family
weakening
that
has
be dilated
strong
seems
structure
instances
3
4
the
due
in
was
the
the
one
agent.
there
but
to
no
had
170
There
in
will,
are
a sense
3
necrotizing
4
uncertain
cause
the
early
feeding.
and
infectious
to
to
I have
illness
because
individual
related
to
14
some days.
15
death
at
19
these
20
agents
21
of
that
these
25
general
in
here
was
and
with
part
related
the
the
was
flu-like
The
symptoms.
had
have
been
exposure
been
going
a week
on for
before
the
was performed.
category
in
it
are
two
was not
what
the
have
explained
deaths
possible
cause
had
of
to
death
exposure
remain
my view,
summary
for
were
least
could
that
stopped
and
information
symptoms
problems
of
in
arrive
was
to
in
the
that
category
outcomes.
In
24
clinical
as with
Both
unexplained
explanations
the
had
as to
these,
at
died
unclear.
pulmonary
individuals.
23
of
were
autopsy
a conclusion
22
kind
you
of
alkaloids
there
final
careful
and
has
characterized
cardiac
The
an entity
prematurity
ephedrine
case
if
child
The exposure
no autopsy
16
with
is
She had
and
is
probably
of
other
also
13
18
It
deaths,
premature
this
my view
The
odd
old
associative
intake
scant.
of
a five-day
etiology.
connection
despite
sort
enterocolitis,
maternal
17
two
all
among
death
were
well-recognized
the
22 AERs that
found
in
causes
20 of
of
I reviewed,
the
death
cases;
in
c
population
albeit
MOFFITT
some are
rather
REPORTING ASSOCIATES
(301)
390-5150
uncommon
the
171
ct
In
common.
the
two
cases
where
1
others
2
death
3
consistent
with
general
experience
4
you
look
at
information
5
really
6
individual
was unexplained
really
don't
In
8
clinical
9
nor
10
ephedrine
11
factor
13
use
of
14
explanation
evidence
to
the
from
death
is
only
ephedrine
in
that
15
Thank
you.
16
[Applause.
17
DR. HUTCHINS:
18
DR. OLNEY:
in
St.
Louis.
21
director
of
22
Washington
23
program
24
divisions
25
and
I have
the
the
of
For
in
why
you
the
the
two
of
exposure
or
cases,
to
causat
unexplained
ive
deaths
the
be a speculative
John
Dr.
I'm
John
30 years'
as are
Olney
Olney,
at
will
Washington
clinical
listed
focusing
speak.
of
University
experience
service
a thirty-year
funded
now
Professor
consultation
neuroscience
MOFFITT
group
outcome.
and
research
that
could
psychiatry
NIH
the
of
my perspective.
Neuropathology
University
in
if
no consistency
show
alkaloids
for
20
is
autopsies
a contributing
was
Psychiatry
some cases
of
that
critically
features
alkaloids
19
an incidence
with
I found
pathologic
It
12
is
cause
died.
there
in
this
in
conclusion
or
was
your
understand
has
7
and
the
as
at
research
by
five
different
there
on stroke,
REPORTING ASSOCIATES
(301)
390-5150
perinatal
172
ct
1
brain
damage,
2
disease,
epilepsy,
schizophrenia,
alcohol
head
trauma,
Alzheimer's
drug
addiction,
and
fetal
syndrome.
I have
4
also
5
research.
Thirty
6
monosodium
glutamate,
7
additive
8
hyperthalmus
years
destroys
artificial
sweetener
11
neurotoxic
properties.
12
evidence
13
increased
15
listed
16
of
17
career
18
five
19
other
20
National
of
from
to
the
Ephedra
23
ask
24
of
25
neurological
me to
ephedrine
immature
also
ingestion
one
last
30 years.
awards
and
of
Sciences.
the
to
has
been
to
pertaining
cause
I've
to
as a
every
received
the
as a consultant
Specifically
Council.
evidence
them
Institutes
renewed
member
serving
of
to
research
And
elected
I'm
National
perform
same
published
awards,
award
MOFFITT
the
several
That
psychiatric
the
tumors.
was
alkaloids
has
NutraSweet
That
evaluate
that
brain
Education
or
flavor
malignant
Why am I here?
22
the
I have
that's
the
Academy
21
used
also
NIMH,
scientist.
honorary
that
I discovered
linking
received
for
in
And
Health.
years
cells
NutraSweet
incidence
Mental
I discovered
ago
potentially
there
toxicology
MSG, a widely
years
10
I've
food
brain.
Twenty
14
ago
nerve
or
9
conducted
or
to
contribute
disorders.
REPORTING ASSOCIATES
(301)
390-5150
they
the
potential
to
an
173
ct
The
1
evidence
2
adverse
event
reports
3
alkaloids
to
nervous
4
of
5
consultants.
the
adverse
7
examined
the
8
of
ephedrine
9
or
experimental
systems
disturbances
including
reports
review
and
identified
12
nervous
system.
13
reports
because
14
Nevertheless
15
outside
16
them
17
links
the
28 adverse
event
rate
they
nervous
have
to
the
system
of
each
effects
humans
19
cases
report
20
ephedrine
21
cases
22
disqualified
23
signifies
24
have
not
identified
25
they
can
agree
agreed
alkaloid
were
due
those
to
that
their
a single
MOFFITT
links
to
Stall
and
found
only
linked
to
both
expert
ephedrine
two
of
these
already
This
information.
adverse
it
event.
Remarkably
two
asked
how strongly
strongly
FDA had
these
two
Stall
an adverse
insufficient
FDA and
closely
to
of
the
information.
and
terms
to
12 of
28 reports
and
ingestion.
among
that
in
FDA
pertaining
Ricaurte
Ricaurte
they
reports,
insufficient
all
alkaloids
Doctors
event
reports
provided
Drs.
ephedrine
were
also
FDA disqualified
However,
consultants,
that
from
adverse
FDA submitted
18
FDA by outside
pertaining
on the
all
animals.
11
of
for
Stall
literature
Concerning
to
the
ephedrine
Ricaurte
world
includes
linking
alkaloids
10
examined
putatively
event
Drs.
6
I've
consultants
event
report
alkaloids
REPORTING ASSOCIATES
(301)
390-5150
that
to
174
ct
1
adverse
nervous
In
2
system
a cover
effects.
letter
3
that
ephedrine
4
risk
he identified
5
but
6
to
7
and/or
8
ephedrine
alkaloids
in
9
chloride,
or
table
to
not
the
predisposed
kidney
and
There
16
that
FDA considers
that
they
in
risk.
the
salt,
blood
high
But
the
public,
a predisposition
alkaloids
This
doses.
which
but
stated
general
same category
to
as sodium
poses
to
places
a health
individuals
pressure
or
who
certain
diseases.
are
many
such
food-related
so harmless
require
and
are
for
given
the
substances
general
public
no regulatory
attention.
reliable
evidence
controlled,
industry
not
adverse
24
controlled.
trials
recommended
taken
associated
23
the
comes
human
milligrams
25
the
Ricaurte
ephedrine
abusive
public
Concerning
18
to
ingest
general
heart
a health
who
stimulants
to
Dr.
who have
or
common
FDA,
not
individuals
illnesses
other
pose
pertains
specific
certain
risk
are
alkaloids
to
nervous
MOFFITT
literature,
of
a significantly
animal
that
ephedrine
four
is
times
compared
the
25
per
higher
studies,
most
placebo-
demonstrate
exceed
effects
the
randomized,
that
to
system
Concerning
from
dosage
not
with
world
day
incidence
to
they
REPORTING ASSOCIATES
(301)
390-5150
placebo-
do not
is
of
ct
175
demonstrate
a neurotoxic
administered
at
massively
5
Ricaurte
6
could
perhaps
7
later
on.
one
that
8
9
doses
abusive
If
that
in
wishes
me what
10
believe
11
alkaloids
the
that
are
13
regarding
14
the
with
15
ephedrine
16
the-counter
17
no concern
18
potential
19
with
20
caffeine
21
so forth.
apparent
and
its
about
various
the
The
logical
conclusion
24
ephedrine
either
25
poses
a public
that
been
FDA does
alone
health
MOFFITT
or
not
in
hazard.
marketed
and
really
they
drinks,
this
of
and
FDA
that
with
REPORTING ASSOCIATES
(301)
390-5150
abuse
amounts
believe
did
shown
together
from
combination
If
or
soft
arguing
years
FDA has
large
i nated
many
that
as over-
consumed
and
caffe
appears
potential
when
caffeine
tea,
to
health.
For
effect
coffee,
clear
ephedrine
It
adverse
of
not
my observations
the
even
is
FDA appears
public
decades,
agents
we
study
containing
several
from
is
that
it
but
--
sources
precedent
in
FDA position.
have
by Dr.
monkeys
self-contradictory.
these
23
used
you
analogs
drugs
of
22
is
studies
squirrel
supplements
share
FDA position
the
FDA position,
to
this
in
doses
hazardous
I will
be considered
FDA espouses,
dietary
unless
context.
to
the
ephedrine
discuss
he referred
position
12
to
discuss
of
would
a human
Concerning
to
action
caffeine
believe
that
ct
176
1
they
would
have
2
stringent
3
counter
ephedrine
drugs
4
sources
and
intake
The
substantiated
7
ephedrine
8
in
9
system;
this
10
adverse
event
11
could
12
to
13
strongly
14
that
15
event
16
literature
17
In
not
If
belief
identify
to
FDA position
and
various
seem to
be
FDA believes
in
reasonable
for
the
doses
nervous
by a single
two
adverse
event
they
that
expert
consultants
report
could
pertaining
agree
alkaloid
was
consumption.
supported
by a single
So
adverse
not
supported
by the
world
it's
not
supported
by
FDA precedent.
19
protection
standards.
20
standards
AHPA being
21
Association.
22
protection
23
standards
24
is
standards
including
to
say
First
the
--
a word
about
I will
discuss
American
developed
set
of
responsible
its
example,
MOFFITT
the
FDA precedent.
AHPA has
For
over-the-
It's
I want
upon
not
FDA and
not
more
of
these
supported
that
contradicts
Now,
enforces
not
ephedrine
is
report.
18
is
system
linked
it
hazardous
any
use
with
consumed
or
report.
develop
caffeine.
by evidence.
nervous
fact
of
does
doses
the
together
when
to
for
FDA position
alkaloids
reasonable
trying
control
heavy
6
25
been
regulatory
5
the
already
Herbal
label
AHPA
Products
a sound
health
health
health
protection
practices
which
membership.
AHPA sets
doses
limitations
REPORTING ASSOCIATES
(301)
390-5150
for
ct
177
1
ephedra
products
2
ephedrine
3
recommends
4
heart
disease,
5
their
physician
6
are
sound
7
err
on the
8
consumer
not
per
four
or
with
various
before
using
of
of
per
high
other
recommendations
side
25 milligrams
servings
individuals
day,
blood
illnesses
and
pressure,
with
products.
because
cautiousness
AHPA
consult
a ephedra
simply
and
its
These
best
on the
side
to
of
protection.
I want
10
using
11
for
12
allows
13
processed
14
products
15
to
16
Nevertheless,
17
pressure
18
ephedra
to
a couple
of
individuals
table
19
exceed
serving,
that
9
have
to
foods
in
or
doses
salt
in
bulk
is
added
labels.
on blood
hazardous
but
or
FDA
to
Ephedra
recommended
no effect
consult
FDA standards
pressure,
warning
AHPA warns
to
blood
be sold
without
little
Table
high
to
used
AHPA and
examples.
with
salt
if
compare
by AHPA,
appear
pressure.
individuals
with
physician
before
using
is
present
their
high
blood
products.
Caffeine,
20
high
21
caffeinated
soft
22
chronically,
in
23
millions
24
There's
25
than
a known
concentrations
of
in
drinks,
large
consumers,
no proof
caffeine,
that
but
stimulant,
many products:
and
so forth,
amounts,
some of
ephedrine
and
whom are
ingested
tens
in
alkaloids
that
tea,
is
by millions,
AHPA recommends
MOFFITT
coffee,
in
this
are
ephedra
REPORTING ASSOCIATES
(301)
390-5150
of
room.
less
safe
ct
178
1
products
not
be used
attempt
coffee,
to
tea,
in
restrict
or
set
the
6
to
be taking
7
understand
8
over
9
failure
stage
that
11
effects.
has
13
have
been
the
14
like
monosodium
15
the
16
allows
17
infants
18
It
19
very
20
regulation
21
But
22
a consumer
carefully,
I do want
the
evidence
25
standards
foods
that
food
and
I don't
done
to
are
are
in
products
care
the
more
by the
MOFFITT
that
examined
than
that
toxic
that
and
labels
and
to
fed
at
to
all.
be regulated
whether
the
itself.
from
be effective.
based
on all
based
on
FDA ordinarily
REPORTING ASSOCIATES
(301)
390-5150
to
FDA
be responsible
and
side
substances
are
industry
to
saying
strict
is
should
standpoint,
I have
caffeine
personally
regulations
by
toxic
amounts
warning
that
their
substances
any
any
by FDA or
me close
that
that
that
fully
on foods
and
substances
these
you
potentially
It
without
protection
Let
24
to
children
my belief
23
and
labels
salt
used
AHPA seems
FDA for
my concern.
glutamate
be added
is
table
of
brain,
and
warning
been
subject
immature
is
not
I've
me mention
of
have
that
that
let
critical
that
of
So that
from,
adequate
additives
It
point
approach.
been
FDA does
consumption
examples
the
coming
I've
whereas,
drinks.
simple
making
I'm
require
12
to
very
for
years
contain
public
soft
a responsible
to
10
the
are
where
the
doses,
caffeinated
These
to
restricted
of
179
1
requires,
2
conclude
3
supplements
4
AHPA and
5
recommended
6
if
7
get
8
guidelines
9
me that
I consider
that
if
it
reasonably
ephedrine
are
safe
used
in
label
used
keeping
other
draft
already
in
doses
with
similar
would
Thank
in
dietary
recommended
all
other
And
I might
followed
add
similar
step
that
could
to
by AHPA it
be a gigantic
by
APHA-
organizations
some regulations
being
to
contained
instructions.
and
that
alkaloids
if
FDA and APHA or
together
reasonable
the
seems
to
forward.
you.
[Applause.]
MR. ADAMS:
Adams.
I'm
a senior
Interactive
on the
16
the
18
and
abuse
containing
I was
ephedrine
by
references
to
of
ephedra
addiction.
alkaloids
been
And
case
in
is
abuse
research
23
have
probably
actually
24
Poll
which
25
at
not
you
I'm
the
MOFFITT
the
data
products
in
several
liability
of
and
a typical
of
vice
president
Interactive.
us,
have
a principal
some of
referenced.
Harris
probably
Edgar
consultants
reports
senior
heard
is
Harris
because
made to
I am currently
clinical
--
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of
at
review
their
one
My name
president
asked
FDA and
have
afternoon.
vice
liability
reports
addiction
Good
Many
we conduct
heard
investigator,
the
of.
I study
REPORTING ASSOCIATES
(301)
390-5150
for
of
Harris
you
ct
180
1
investigated
abuse
2
hydrocodone
3
principal
investigator
4
liability
of
5
1,300
in
over
of
11,000
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subjects.
And
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nicotine
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over
subjects.
6
Previously
7
five
8
and
9
prevention
10
liability
months
was
in
I spent
the
director
United
of
States
the
research
at
23 years
Public
division
the
actually
of
National
23 years
Health
Service
epidemiology
and
Institute
on Drug
Abuse.
11
There,
12
for
the
13
of
14
various
15
heroine,
drug
among
abuse
consequences
and
17
survey
and
18
of
Council
19
epidemiology.
As you
21
pharmacy,
22
policy
24
associated
25
including
and
other
drugs
et
cetera.
can
pharmacology,
evaluation
to
the
two
a measure
abuse
the
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in
I have
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Group
abuse
background
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health
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cases
MOFFITT
is
my educational
and
and
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to
as a expert
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for
as an advisor
responsible
associated
responsible
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23
prevalence
Europe
I was
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not
also
served
things,
network
methamphetamine,
I was
20
warning
medications
16
the
other
that
were
independence
that
were
possibly
and
included
REPORTING ASSOCIATES
(301)
390-5150
misuse
in
the
is
181
insufficient
data
group
2
or
abuse.
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to
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information
in
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4
statistical
manual
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6
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and
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the
and
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avoid
and
for
is
16
network
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looked
from
in
legal
repeated
the
World
Health
at
1989
the
use
and
of
other
focuses
24
drug
25
tolerance
including
and
on the
therapy
as smoking
damage
to
is
use
health
activities,
here
to
on a plane.
harmful
causes
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use
An obvious
replacement
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In
both
loss
of
consequences.
dependence
MOFFITT
and
or
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there
on obligations
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or
problems.
Dependence.
Manual
the
Organization
purposes.
The key
is
part
as repeated
occupational
there
of
WHO classification,
obligations.
developments
23
identified
such
misuse
social,
me review
manual.
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regulations
repeated
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definitions
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9
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REPORTING ASSOCIATES
(301)
390-5150
or
of
a
ct
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1
suff
icient.
2
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Withdrawal
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ic
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and
of
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see
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such
as being
15
disorderly
conduct,
16
continued
substance
17
recurrent
social
18
fights
situations
which
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21
substance.
22
require
23
withdrawal
24
to
get
25
in
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require
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and
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amounts
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dependence
criteria
of
cannot
over
MOFFITT
for
this
substance
you've
class
taking
of
or
larger
the
period
ever
dependence
no tolerance
withdrawal,
a longer
if
amounts
substance
of
REPORTING ASSOCIATES
(301)
390-5150
time
taken
that
was
ct
183
intended,
to
a persistent
cut
down
time
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spent
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substance,
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important
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use,
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12
things.
13
taken;
14
was
15
it
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whether
or
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adverse
events
18
outcome
was.
it
age,
had
You
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case.
21
actually
the
case
22
reports
23
didn't
24
refer
25
there's
it,
see
of
effects,
substance
of
to
having
such
as an
this
slide.
for
use,
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a typical
me note
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et
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cited
thing
MOFFITT
being
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whether
cetera;
and
data
11918
two
dose
content,
hospitalized;
of
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caffeine,
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show
of
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up there.
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case
of
addiction.
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clinical
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REPORTING ASSOCIATES
(301)
390-5150
the
is
in
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because
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ephedrine,
20
note
All
duration,
not
from
knowledge
to
weight,
ma huang,
19
going
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obtain
of
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busy.
sex,
taken,
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a great
by drinking.
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One,
use,
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or
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11
efforts
recover
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recurring
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10
or
occupational
given
unsuccessful
necessary
substance
social
or
substance
activities
uses
and
desire
expert
If
I
Ct
184
1
YOU will
2
did
3
dependence.
4
typically
5
clinical
not
have
note
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word
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term
6
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people
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three
tablets
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weight
less
14
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went
up to
15
recommendation.
16
unclear
17
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be safe.
bought
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case
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from.
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ma huang,
20
experience
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abusive.
22
taking
the
23
letter
whether
or
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WHO and
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the
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think
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it.
MOFFITT'REPORTING
ASSOCIATES
(301)
390-5150
stop
to
stops
her
own
taking
the
drug
ct
185
Again,
to
go through
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drugs.
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experiencing
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going
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are
listed
She did
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11
Case
12
said
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13
cocaine
14
based
15
here,
12837
he began
use.
using
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The
first
note
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17
other
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to
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cases
that
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19
Essentially
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20
intentional
overdose.
21
that
The next
22
Essent
ially
23
associated
24
trends
25
tees
Dawn was
with
of
and
drug
new abuse
blues
MOFFITT
one
of
I want
to
talk
up to
look
at
entities.
followed
no
--
by FDA as abuse
abuse,
using
and
to
monitor
For
the
an abuser
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the
overdoses,
set
dependent,
which
all
He
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be considered
cases
thing
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and
a cocaine
not
out
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medication
that
thrown
were
is
the
So he became
on criteria
16
technically
discuss
are
the
or
misuse.
wh ich
was
about
is
the
pattern
system.
REPORTING ASSOCIATES
(301)
390-5150
an
Dawn.
consequences
example,
Dawn
two
of
in
the
In
80s
Dawn
ct
186
1
drug
2
in
3
practice;
the
4
approve
labeling.
5
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twice,
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or
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criteria
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drugs
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a manner
defined
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And
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is
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really
12
reasons.
13
intentional
14
It
most
15
should
be excluded
16
at
data
There
is
part
of
for
17
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one
abuse
psychic
Dawn data
effects
is
19
enhance
any
emotional
20
these
are
actually
21
help
study,
et
cetera,
from
Three
points
here.
that's
24
episodes
25
was
was
in
Dawn,
an increase
use
of
1989
the
MOFFITT
abuse
of
Suicide
of
drug
anytime
that
what
of
the
abuse.
criteria
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pain,
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an increase
in
other
suicide
a variety
which
or
reduced
there
of
the
and
you
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concerns.
definition
23
any
there
diagnostic
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22
for
a symptom
18
mental
use
piece
not
other
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meets
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Other
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take
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typically
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And
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says
you
marijuana
effect,
11
it
and
that
cocaine,
these
if
a day,
drugs
medical
drugs
words
then
in
psychic
prescription
acceptable
other
aspirin
abuse
of
over-the-counter
times
heroin,
for
the
of
In
four
use
with
four
for
is
as the
to
improve
physical
state,
stay
awake,
One is,
1998.
part
of
or
and
relax,
Dawn report.
--
mid-90s
is
these
You
and
you
can
are
ephedrine
can
then
see
see
that
a decrease
REPORTING ASSOCIATES
(301)
390-5150
there
in
ct
187
1
the
last
two
2
years,
You
3
of
4
than
5
third
6
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of
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can
see
13
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15
that
16
hospitals
17
the
18
associated
19
abuse
is
if
you
like
1,119
the
of
the
is
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look
at
in
warning
23
cases
are
24
fact,
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25
comparison,
less
about
a
could
use
of
use,
at
two
likely
to
have
half
are
other
years.
MOFFITT
factor
over-the10.
So
150
reports
in
The
key
is
despite
the
to
that
consequences
by
the
drug
of
mentions
of
substantially,
ephedrine
attempted
attempted
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be decreasing.
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over-the-counter
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to
number
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all
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essentially
8 and
measured
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all
typical
products,
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last
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least
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weighting
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occur
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might
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on about
now projected
that
know;
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to
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or
to
To reiterate,
in
which
States
1989
network,
in
cases
somewhere
report
with
percent
evidence
usually
alcohol
three
it's
based
increase
22
the
clearly
mentions,
United
between
is
that
ephedrine
all
percent;
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ephedrine
products
21
all
with
number
in
which
20
0.2
of
50 percent.
some problems.
estimate
10
by
terms
around
Essentially
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in
combination
for
roughly
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percent
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7
see
average
cents
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by
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suicide,
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medications
REPORTING ASSOCIATES
(301)
390-5150
50
in
And
the
in
same
ct
188
1
indication.
2
32,000
You can
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15
backed
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products
sole
the
21
increasing
not
Dawn data
with
associated
in
the
abuse
and
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were
And
in
in
1999,
and
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the
of
fact
a meeting
reached
that
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basically
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of
consequences
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are
use
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consequence.
significant
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--
evidence
Americans
without
on the
slide.
government's
apparently
see
last
product.
of
based
a significant
is
millions
there
that
a significant
federal
problems
and
other
you
Dr.
you
would
indicators
substantially.
Thank
23
[Applause.]
24
DR.
panel,
the
inappropriate
same conclusion,
22
25
appear
issue
by the
to
would
scheduling
If
expect
of
the
19
piece
consequences
were
this
not
abuse
on the
by
the
cetera.
associated
which
is
off,
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widespread
of
it
going
11
20
on this
accounts
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events
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et
consequences
attempts
Finally,
red
17,000,
The majority
suicide
acetaminophen
conclusion
a decline
8
3
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ibuprofen
so,
4
see
again,
you.
JONES:
for
Thank
respecting
MOFFITT
time
Adams,
and
keeping
REPORTING ASSOCIATES
(301)
390-5150
and
to
things
the
ct
189
1
concise
and
the
point.
Let
me turn
4
DR.
SALIVE:
5
I have
3
Dr.
reports
7
role
8
wanted
9
--
and
of
to
for
questions,
11
product
adverse
12
the
13
pathologists
14
their
15
dermatologic
is
same
occurs
stopped
and
16
this,
that?
DR.
17
fundamental
18
and,
yes,
19
there
20
somewhere
21
their
the
only
the
any
where
product,
the
readminister
I won't
and
ask
clinicians
there
case
I
FDA report
is
the
the
but
were
were
some
cardiology.
What
you're
down
by Coke
were
some cases
KIMMEL:
I do not
and
whether
use
product
the
possible
cases
the
reoccur.
possibly
about
these
in
I believe
FARBER:
set
DR.
then
about
all
rechallenge,
with
symptoms
and
in
cited
of
of
comment
positive
event
sort
cases
the
some cases
NIH.
You rev .iewed
effects
about
are
Sal .ve,
a question.
I understood
ask
there
the
I'm
think
talking
many,
sure
anyone
many
but
about
decades
very,
we have
has
is
very
the
them
DR.
might
24
be less
DR.
reasonable
SALIVE:
KIMMEL:
But
likely
would
due
few.
number
off
the
top
I be correct
to
say
I think
is
a
to
that
chance?
certainly
assumption.
MOFFITT
REPORTING ASSOCIATES
(301)
390-5150
a
ago,
head.
22
those
my co11 eagues
Marcel
coincidental
10
23
to
Salive.
6
25
to
of
ct
190
DR.
1
2
did
3
probably
when
FARBER:
there
was
gave
that
in
the
to
AER a high
probability.
DR.
KIMMEL:
The problem
5
DR.
FARBER:
Frankly,
DR.
KIMMEL:
It
that
we
rechallenge
with
we
--
there
weren't
many
of
them.
7
8
with
9
larger
dechallenge
strokes,
11
is
12
don't
is,
the
with
fact
alone
for
adverse
that
you
from
number.
which
events
don't
was
like
have
an MI.
The
problem
a much
MIS and
another
So it's
--
hard
there
and
I
think.
what
15
DR.
SALIVE:
The
I was
speaking
of.
DR.
KIMMELL:
16
products
and
17
that
the
product
18
for
those
types
19
isolation
20
dechallenge
21
know
22
strokes.
of
then
at
acute
not
cases
of
JONES:
24
DR.
FARBER:
those
MI.
I mean,
events
I think
rechallenge
of
the
you
product
stop
MI,
does
in
other
happen
helpful.
the
that
mean
words,
in
obviously
And
recurrent
I don't
MI or
Farber.
Page
points
dechallenge/rechallenge
MOFFITT
that
time,
Dr.
if
another
particular
DR.
of
the
from
But
have
a particular
is
any
was
of
challenge
Right.
don't
23
most
a small
course
dechallenge
13
is
of
number
10
14
analysis
a dechallenge
4
6
25
I the
out
to
me that
situations
REPORTING ASSOCIATES
(301)
390-5150
in
it
was
ct
191
1
generally
.L
the
an allergic
phenomena
DR.
JONES:
Dr.
DR.
BURSTEIN:
NIH.
I have
that
was
reported
in
AER.
4
c
Center
6
regarding
7
specifically
8
you
9
tested
because
10
looked
at
11
also
12
some of
13
product.
at
some of
the
just
clarify
14
15
study.
16
of
17
commercial
kinetic
study
of
White
that
some of
therapies
supplement
product
study
studies
that
caffeine
my data
pertain
It
have
on the
me get
did
was
products
contain
ma huang.
called
the
that
depending
Let
Could
product
that
Right.
Page
colleagues.
versus
may differ
The White
a dietary
and
products
Dr.
presented,
I know
PAGE:
Okay.
you
specific
entity
Clinical
for
me the
kinetics
DR.
Burstein,
a question
the
herbal
the
Aaron
for
single
contain
Burstein.
to
was
on the
the
use
the
ma huang.
18
19
h"
DR. BURSTEIN:
20
that
21
the
22
products
study
refer
to
same group,
with
it
later
goes
24
DR. BURSTEIN:
point
out
on to
the
entity
study
authors
product
in
in
combination
caffeine.
DR.
to
that
as a single
23
25
I believe
PAGE:
that
That's
So,
that
MOFFITT
/_“_.,
correct.
slow
I think
that
absorption
rate
REPORTING ASSOCIATES
(301)
390-5150
.
..I
_,c
,,.,.
”
.._
is
important
has
only
ct
192
1
been
documented
2
you
3
hypothesis
for
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of
these
is
absorption
between
the
those
single
entity
products
with
that
the
caffeine
such
that
there's
combination
product
and
caffeine
the
actually
speeds
really
products
when
to
rate
no difference
and
synthetic
ephedrine.
DR.
reason
I didn't
that
10
much
all
PAGE:
the
You probably
really
about
emphasize
the
same is
are
it.
absorption.
probably
right.
That's
We really
So I think
a conservative
the
know
call
them
approach
on it.
11
12
DR.
JONES:
13
DR.
SCHWETZ:
14
quick
ones
for
15
selected
for
16
analysis
published
17
could
into
that
20
selected
whole
group
from
21
March
of
23
24
deaths
25
in
March
in
I have
of
And
reported
the
are
the
the
two
22 deaths
results
of
that
they
someplace
your
record?
The
AERs that
KIMMEL:
I think
22 deaths
were
we reviewed
included
and
they
came
from
in
were
22 deaths
were
the
--
it
was
'97.
DR.
FARBER:
the
276 AERs reported
of
questions,
How were
review?
or
three
that.
DR.
in
Schwetz.
Hutchins.
DR. HUTCHINS:
19
22
your
be put
18
Dr.
Dr.
this
year.
MOFFITT
The
They
out
were
not
about
Food
selected,
REPORTING ASSOCIATES
(301)
390-5150
total
in
Drug
they
ct
193
1
were
the
total
2
DR.
3
the
number
4
Are
those
5
among
seven
these
of
deaths
SCHWETZ:
7 deaths
Yeah,
from
that
were,
but
8
DR.
I do not
KIMMEL:
9
March
10
recall
11
attributable
12
just
the
attributable,
13
that
were
provided
14
think
it
1997,
if
seven
17
submitted
18
these
went
not
19
21
completed
22
submit
23
has
to
25
Hutchins.
this
this
morning.
morning
was
be my assumption
all
deaths
I don't
the
felt
deaths.
way
at
the
record
that
all
March
since
specific
We didn't
through
--
'97,
they
were
look
at
all
in
I
deaths
fact,
I
1999.
And my other
more
included
recall
reviewer
by FDA from
that
sure.
we looked
is
question
information
regarding
that
your
is
can
be
evaluation
of
records?
HUTCHINS:
11 cases
that
in
DR.
24
for
all
there
first
that
know
the
SCHWETZ :
DR.
on the
would
correct.
which
all
to
death
20
I'm
in
DR.
whether
I remembered
to
It
It
amongst
15
16
AERS.
information
referred
DR. HUTCHINS:
they
the
I thought
the
were
in
22?
6
7
number
do with
for
that
the
a few
next
I looked
11,
I have
denominator.
MOFFITT
written
but
a brief
at.
report
I haven't
I would
be happy
days.
SCHWETZ:
the
I have
one
other
Thank
question
you
REPORTING ASSOCIATES
(301)
390-5150
Dr.
that
to
194
1
Several
2
fact
3
but
that
people
there
how does
4
are
that
DR.
several
KIMMEL:
basis
6
submitted
7
plus
8
average
servings
per
9
assuming
normal
use,
10
directions,
11
I can
12
estimate
the
we were
in
the
the
docket
able
to
you
survey
of
13
person
DR.
assuming
see
like
to
15
you
can
time
it
if
16
how many people
17
use?
you
calculate
18
DR.
19
at
20
days
21
and
amount
22
use
prescription
23
doing
24
try
25
prescriptions
all.
This
exposed
the
are
average
you
would
from
I don't
have
it
an estimate
on total
dose
per
records
the
of
can't
It
for
number
but
are
one-time
what
an
of
with
events
I'd
users
else
do they
from
number
and
just
but
so that
that
this
of
total
you
drug
number
REPORTING ASSOCIATES
(301)
390-5150
would
in
AERs where
or
person
doses
like
written.
MOFFITT
And
it's
know
a prescription
of
time.
record
tell
is
assessment
to
the
exposure
day.
an
essentially
to
users,
is
sizes
days.
for
You
purely
serving
like,
need
KIMMEL:
servings
person
person
on the
been
according
the
multi-time
same type
estimate
use
year
done
of
we could
how many people
based
of
if
has
number
So,
per
was
average
day.
SCHWETZ:
14
total
the
denominator?
which
calculate
details
the
calculation
was
to
servings
into
we calculated
show
to
billion
The
data
to
made reference
translates
5
of
have
of
they
ct
195
1
There
2
person
level
3
duration,
4
a one
5
as the
6
22 month
no individual
data.
There's
so we can's
slice
total
follow-up
JONES:
level
information
that
This
over
number
data
of
or
on time
all.
exposure
the
as the
DR.
not
of
with
periods
patient
assess
amount
denominator
7
8
is
is
the
and
purely
22 months
events
in
those
numerator.
Dr.
Philen,
did
you
have
a
question?
9
DR.
PHILEN:
10
DR.
JONES:
11
One question
12
for
taking
13
recommendations
14
the
15
recommendation,
16
has
17
studies
No.
No?
then
some effort
basis
there
for
been
done
18
AUDIENCE
to
19
council
20
actually
the
21
scientific
question.
22
and
they
23
question
24
that
Michael
25
talk
tomorrow,
of
because
four
from
know
what
times
related
clinical
PARTICIPANT:
Committee
a legal
a day,
compounds,
trial,
dosing
probably
it
was
McGuffin,
don't
done
President
I would
MOFFITT
If
you
of
AHPA,
question
I helped
and
to
respect?
Ephedra
kind
I know
drawn
AHPA
dosing
25 milligrams,
that
that
I comment
I wanted
a controlled
in
me.
labeling
so forth.
the
is
from
toward
and
was
Okay.
please,
rather
put
the
know
several
of
respectfully
the
I'm
and
that
that
panel
a
together
answer
years
AHPA,
to
ago.
is
request
REPORTING ASSOCIATES
(301)
390-5150
is
that
I know
going
to
we wait
ct
196
1
until
he talks,
2
he can
DR.
3
information
4
my interpretation
5
counter
6
day,
7
total
ephedrine
8
sorry
if
9
report
KIMMEL:
from
dose
instance
of
11
and
she
12
which
13
alkaloids
in
14
ephedrine
equivalent
15
would
16
that
17
the
18
personal
it
well
25 milligrams
be 11.75.
is
it
not
you
it
of
was
least
as high
in
point
JONES:
it
This
is
drawn
who wrote
less
than
and
I don't
is
from
ephedrine
remember
up total
ephedrine
but
it's
really
those
the
product
feeling
essentially
So for
a
potency
my personal
fact
in
I'm
34 milligrams,
I think
That
--
relative
add
a
last
Dr.
nd over-the-counter
So at
is
lower
than
my own sort
total
reasoning.
my reason
sorts
of
of
for
data
as
as evidence.
Other
23
[No response.]
24
DR.
come
if
product
22
25
an example,
of
times
Enchiosa,
is
terms
Over-the-
six
the
products.
clinical
was
--
that
but
in
addition
wrong
comment
over-the-counter
is,
In
a little
up to
150 milligrams.
was,
the
DR.
21
is
gives
product
19
asking
reasonable.
being
pseudoephedrine
actually
you
this
alkaloids.
for
give
of
FDA did
this
I can
issue.
standpoint
I pronounce
for
that
scientific
of
10
20
But
hot
ephedrine
total
address
to
the
questions
JONES:
microphone
MOFFITT
from
the
Questions
and
identify
from
panel?
the
yourself
floor?
Please
please.
REPORTING ASSOCIATES
(301)
390-5150
.
.”
_, ,.. .^
ct
197
1
2
MR. REINHART:
for
Pure
Foods.
3
DR.
4
the
5
unless
6
would
7
information
8
meeting
9
clarity.
panel
to
Dr.
I have
JONES:
which
him
is
10
group
done,
12
meta
analysis
13
It
14
here.
seems
or
of
that
15
DR.
16
meta
analysis.
17
summary,
there's
18
analysis
really
Per
nothing
are
20
DR.
statements
is
22
other
23
some types
24
better
25
would
that
studies.
term
If
of
We did
there
MOFFITT
NIH
estimates
analysis
a trial,
--
should
DHHS and
summary
meta
be worth
So you
are
would
although
to
has
one
your
rigorous
appropriate
the
method
call
of
it
per
a
se.
randomized
need
seek
literature?
analyze
to
to
formal
I would
meta
you
the
clarity,
do any
series
to
KIMMEL:
of
like
speak
applicable
MR. REINHART:
as part
criteria
I can
case
questions
and
published
analysis
19
21
to
is
The
for
reviewed
KIMMEL:
presenting
clear
specifically
intend
peer
meta
panel
People
Schwetz.
your
not
Looking
do you
is
question.
by the
MR. REINHART:
11
is
his
we would
Dr.
address
question
restate
where
for
that
should
presented
Reinhart,
a question
you
to
Jeffrey
The panel
Schwetz's
like
Yes,
Meta
trials.
double
blinds.
of
consensus
our
be considerations
and
others
are,
for
be helpful
I would
REPORTING ASSOCIATES
(301)
390-5150
for
feel
lack
that
of
I think
caution
a
that
that
I
ct
198
1
think
2
useless.
meta
analysis
3
case
MR. REINHART:
4
could,
5
the
6
scientific
7
those
you
context
of
the
series
Backing
characterize
your
FDA's
agreement?
or
essent
up from
method
Doctor
of
ially
meta
analysis
analysis
within
nonsignificant
Would
you
say
you
Could
you
restate
for
fulfilled
the
quest
criteria?
8
9
for
DR.
I'm
not
KIMMEL:
quite
10
sure
I understand
MR. REINHART:
11
come reasonably
12
significant
close
scientific
13
DR.
14
I'm
15
significant
16
maybe
17
that
ia
agreement."
to
not
sure
there
your
the
FDA's
FDA says
analysis
not
is
sure
the
on the
a definition
"significant
Next
question,
21
MS. FUGH-BERMAN:
Adriane
JONES:
reports
and
in
24
included
in
the
25
But
I'm
Thank
Health
the
analysis
of
DR.
23
which
can.
20
Women's
of
panel
MR. REINHART:
National
doctrine
or
analyses
particularly
MOFFITT
I was
not
aware
scientific
please.
Fugh-Berman,
There
literature
I have
curious
answer
you.
Network.
medical
and
of
so I can't
19
22
fulfill
definition
agreement
else
is
Did
I'm
scientific
someone
it?
agreement?
KIMMEL:
what
ion?
that
seen
about
are
this
one
case
REPORTING ASSOCIATES
(301)
390-5150
a number
were
not
afternoon.
that
was
of
ct
199
1
left
out
2
And
3
case
4
Thiaharates
5
wrote
of
Dr.
Karch's
I was wondering,
of
the
6
DR.
7
a cardiomyopathy.
a
finally
got
9
cardiac
pathologist
and
I've
11
It's
12
cardiomyopathy
13
the
14
course,
the
a chance
garden
them
to
15
not
16
shown
to
17
correct
other
ia
referring
19
have
a history
20
report
with
to
21
the
Dr.
Theohardies
a cardiac
pathologist.
same case,
of
me if
DR.
22
have
23
you're
right,
24
you've
got
cardiac
you
PAGE:
reviewed
to
it's
pathologist.
care
Well,
the
medical
but
I'd
not
paper
but
disease.
I would
records,
be happy
not
it
to
with
and,
had
I would
it
And
of
been
like
was
23-year-old
see
any
clear,
included
I believe
to
to
pretty
that's
And
that
not
pathologists.
of
speaker.
it's
and
is
and
Right,
you
I
slides
cardiac
why
former
because
them
that's
a cardiac
the
the
seen
the
since
myocarditis.
examine
to
by
with
it
a florid
MS. FUGH-BERMAN:
out
it.
I left
myocarditis,
spite
left
familiar
about
who has
and
he's
is
to
variety
in
you're
Well,
It
why you
was published
editor
KARCH:
shown
list,
that
I know
to
on cardiomyopathies.
Karch,
23-year-old
a letter
report
Dr.
which
10
25
the
to
Dr.
Page
did
I have
not
the
it.
just
indicate
that
and
a I don't
think
take
a look
at
I
what
offer.
I did
have
MOFFITT
that
listed,
by
the
way,
as my
REPORTING ASSOCIATES
(301)
390-5150
i
ct
200
1
number
one
2
case
DR.
3
aspect
about
4
investigator
5
to
6
and
we maybe
7
the
bottle
8
death
9
investigator
pick
as you
FARBER:
that
case.
went
into
up samples,
that
pseudoephedrine
11
is
12
calculations
13
regards
14
insignificant
15
pseudoephedrine
16
wonders
17
particular
another
When the
the
of
young
only
that
sample
was
analyzed
and
are
assumed
at
levels
off
shown
was not
where
the
urine
in
sample.
here.
The product
20
Ripped
Fuel
21
once
22
the
product
23
and
not
which
twice
that
in
is
to
his
a day
that
in
you're
only
urine
the
his
and
Drug
contain
And
Tufts
this
of
ephedrine,
One
from
in
that
an interesting
to
said
recommended
case.
being
was
he had
confused
Twinlabs
been
dosages.
contains
in
almost
urine.
implicated
saying
a Food
or
I admit
sister
was
before
from
coming
is
was
he found,
whatsoever.
the
It
that
that
try
death,
found
ephedrine
to
by
negligible
found
apartment
that
professor
almost
Drug
somewhat
ephedrine
MS. FUGH-BERMAN:
taking
Is
that
pseudoephedrine
ephedrine?
24
DR.
plain
or
taken
made by the
some very
and
bottle
as an ephedrine-related
to
or
Food
open
and
not
interesting
men's
logically
he was using
19
25
There's
that
described
18
saw.
the
sort
and
10
probably
and
FARBER:
simple,
the
MOFFITT
It's
sample
in
the
AER record.
was picked
up and
REPORTING ASSOCIATES
(301)
390-5150
It's
analyzed