Download Nikch, Hargrave, Devans SC Doyle ,* ,,&torneys and Counselors

*,
i
‘.
,*
Nikch, Hargrave,
Devans
SCDoyle
,,&torneys
and Counselors
at Law
/j,\ \ t : APU TNERSHlP
INCLlJDlNG
PROFESSlONAL
CORPORATIONS
ONE
NEW
ROCKEFELLER
YORK,
CABLE:
SUITE
ROCHESTER,
NEW
YORK
l4.303
1716)
546-8000
CABLE:
NIXONHARG
ROCHESTER
TELEX:978450
1200,1090
VERMONT’
WASHINGTON,
(202)
D.C.
AVENUE,
N.W.
TELEX:
U.S.
1305)
September
26,
1983
Dockets
Management
Branch
Food and Drug Administration
Department
of Health
and
Human Services
Room 4-62
5600 Fishers
Lane
Rockville,
Maryland
20857
PETITION
.
The undersigned
submits
this
petition
on behalf
of Thompson Medical
Company,
Inc.
under
21 CFR 10.30
to
request
the Commissioner
of Food and Dugs to open the
administrative
records
in the Over-the-Counter
Drug
Reviews
of W e ight
Control
Drug Products
(Docket
No.
81N-0022)
and Cold,
Cough,
Allergy,
Bronchodilator,
and
Antiasthmatic
Drug Products
(Docket
No. 76N-0052N)
to
accept
the enclosed
materials
relating
to the
recently-published
study
conducted
at the Intermountain
Regional
Poison
Control
Center
and Department
of Pharmacy
Practice,
University
of Utah,
Salt
Lake City,
Utah.
The
administrative
materials
to
RevietJ.
Action
Requested
undersigned
respectfully
requests
that
the
record
be opened to permit
the enclosed
referenced
OTC Drug
be considered
in the
B.
Statement
10020
NEW
YORK
66521
SUITE
510
FiRST NATIONAL BANKOF PALM BEACH B”,LDlNG
842-3600
IO01
A.
PLAZA
YORK
20005
JUPITER,
CITIZEN
NEW
IZl2)
686-4100
NlXONHARG
of
Grounds
The grounds
on which
petitioner
relies
are that
phenylpropanolamine
hydrochloride
(PPA) is one of the
ingredients
of weight
control
products
and nasal
decongestants
which
are the subjects,
respectively,
of the
above-referenced
proposed
OTC Drug Products
Monographs.
The Panel Monographs
concluded
that
PPA and its
salts
are
WlGiiW.4~
FLORIDA
748-1002
ONE
33458
Dockets
Management
September
26, 1983
Page 2
Branch
safe
and effective
for OTC weight
control
and oral
nasal
decongestant
use in the specified
dosages.
The Tentative
Final
Monograph
has not yet been published
in either
Review.
In the preamble
to the Advance
Notice
of Proposed
RulemaKing
in the Weight
Control
Drug Products
Review
(47
Fed.
Reg.
8466,
et
seq.,
February
25,
1982),
the
-_-- ---Commissioner
requested
further
studies
regarding
the
safety
of PPA for use in weight
control
products.
The enclosed
materials
summarize
a study
demonstrating
the safety
of PPA in weight
control
products.
Since
the same ingredient
is involved
in both
types
of products,
the enclosed
materials
are highly
significant
to the agency's
OTC Drug Reviews
of both
weight
control
and cough/cold
drug products.
Therefore,
these
materials
should
be considered
in both
Reviews
at
the earliest
possible
time
c. Certification
The undersigned
certifies
that,
to the best
knowledge
and belief
of the undersigned,
this
petition
includes
all
information
and views
on which
the petition
relies,
and that
it includes
representative
data
and
information
known to the petitioner
which
are unfavorable
to the petition.
& Doyle
Suite
1200
1090 Vermont
Avenue,
N.W.
Washington,
D. C. 20005
(202)
842-3600
\
SCIENTIFIC
.
REPORTS
l
Papers published
data
anaiysis.
and
in this
section
interpretation.
arc reviewed
.
by at least two qualifiel
mav
Papers accePted
result
from
referees
for accuracy,
research, critieaf
origi,lal
s&ntifk
experimental des
soundness,
literature
reviews
or weI! documented
f
investigati0nS.
API
rjc
__-_._ESTIPAT!QtI
L2m.--'m,,k.
Intcrmwrtain
(Received
June
SEV&!K
fgp~~&;E$.
fK!K-PRESCRil'i'O:!
i? 'I-C Ffw
-.i--i'jfT A,.*=.L - w.-.-,t-...L
,
Pharm
D and David
C Spocrke.
Jr,
P?S, RPha
Brent
R Ekins.
;nd
Dtpartncnt
of P)?arnracy
Practice,
Regional
Poison
Control
Center
84132
Salt
LGkt. City,
Utah
University
of Utah,
18,
-V'F
TC:"!T.!TY
1381;
(!F
l!evision
Received
September
The American
compulsion
to be slim;
combined with the conclusions
of a non-government advisory
panel's
recommendations
in
Narch of 1979 indicating
benzocaine
and
phenylpropanolamine
(PPA) in over-thecounter
(OTC) weight control
products
to
be safe and effective,
have increased
the
use and the availability
of these drugs
in American homes.
Weight control
products
obtained
without
a prescription
fall
into
two classes:
spmpathomimetic-containing
products
and those without.
Those without
mq- contain
vitamins,
methylcellulose,
benzocaine,
fructose,
lethicin,
and grapefruit
extract,
The sympathomimetic-containing weight control
products
may contain
any of the above with PPA alone or combined
with caffeine.
Table 1 lists
some of the
common commercially
available
products.
thile
PPA is reported
safe in doses for
weight control
(11, there are limited
data
about the toxic effects
of PPA when taken
in overdose
(2-5).
There is mounting evidence of serious
toxicity
when taken in‘
combinat%on with other drugs (6-6) and
in hypersensitive
persons using normal
Caffeine
is not an innocuous
doses
(g-20).
drug (12,221.
Although serious
toxicity
from caffeine
is rare,
its danger is well
documented (23-28).
Caffeine
in combination
. _
: With PPA will
contribute
to the toxicity
in possibly
both overdosage
and in regular
"
lrIETfIODS
i
.\ . 1
The patients
for this
prospective
study
were either
children
or adults who had
ingested
a non-proprietary
sympathomimeticcontaining
weight control
product.
The
study period was for 5 months.
Patients
who met the following
criteria
were included:
History
of ingestion
of
a srmpathomimet
ictPresent
3400
address:
South,
Valley
west.Valley
West
City,.
4160 West
Hospital,
Utah
84120
Vet
Hum Toxic01
1362;
November
Accepted
Comonly Available
Table 1.
lant-containing
$98:)
12,
Over-The-Counter
Appetite
Suppressant
Stimu-
Products
P roduc t
Hanufacturer
PFA
(4
Other
Sub-
Caffeine
bg)
stances
Anorexin
Pick Your
tlenu Weight
Loss Program
Anorex in
SRA Qharm
2s
100
--
Anorexin
SDA Pharm
50
200
--
Appedr ine
Kaax Strength
Thompson
)ledical
2s
100
+
Appress
Tablets
North
American
2s
100
--
Ayds Appetite
Suppressant
Oroptets
(0.6
ml”12
drops),
Purex
2s
0
--
Extra
Strength
Putex
‘15
200
--
:“s
200
0
-w-
75
200
--
75
37-s
200
-
Cne-Span
Aydr
(Red
Capsule)
Purex
Ayds AU/PM
Appet i te Sup-
pressan t Capsules
Yellow Cap.
Blue Cap.
1. ; doses.
g.y .
The purpose of this report
is to describe
the range of presenting
signs and symptoms
following
ingestion
of OTC sympathomimeticcontalng
weight
control
products
and to
estimate
the toxic dose and sequelae
from
.
such overdose.
i2,
t
Cenadex
sules
Central
Cap-
Codex in
Arco
Coffee
Break
Cubes We i ght
Reduction
Plan
Coffee-Off
Coffee.
and
Pharm
O’Conner
Drug
Westport
Qhacm Sates
Tea,
25
Hedicat
Cant rol
rules
Cap-
Thompson
Hedical
75
Con t rot
Drops/
Thompson
Hedicat
25
0.2 ml-4 drops
g*
2
Apr
I983
we
2s
Thompson
a New We
0
I.1
0
--
CD
,#*
.
:
+
!”
Tib&e
i raduc
1 (cant
:
t*
Manufacturer
l”Yli
PPA
hg)
Caffeine
W
Other
Sub-
Westpoint
Pharm Sales
25
0
Day Trim
Westpoint
Pharm Sales
75
0
75
--
Dexada r
PIUS
Republ ic
Drug
75
Dex-A-Diet
Capsule5
(formerly
DexA-Diet
II)
O’Conner
\ Drug
75
Dex-A-Diet
Drops
(formerly
Dex-ADiet
il)/O.6
O’Conner
Drug
25
Dex-A-Diet
Lite
CapSul es
O’Conner
Drug
75
0
Dexatrim
Capsules
Thompson
Medical
50
200
Thompson
Medical
75
Dexatrim
Caffeine-Free
Ex Strength
Capsules
Thompson
Medical
75
Diadbx
Capsules
Tablets
O’Conner
Drug
Dictac
Pre*Weal Die& Aid
Drops/O.2
ml5 drops
SO
200
0
+
1x
0
0
+
+
Other
SUiP
stances
O’Conner
Drug
25
0
+
0
Grapefruit
O’tonner
Diet
Plan
Drug
Vi th Diadax
Ex Strength
ViFort if ied
tamin
Continuous
Action
Capsules
--
Al leghany
Hungrex
75
0
+
25
0
wm
.
Pharmacal
--
200
Hungrex
0
Plus
50
25
ii
Uenley
James Labs
25
0
ey
Labs
25
0
-
See
Dietcap
L Perrigo
SO
Dietcap
withOut
Caffeine
L Perrigo
75
0
Dietguard
Day Diet
Whi tehal
Lab
2s
0
--
0
+
Pharmex
Weight
LOSS
Group
Super
75
0
-we
Odrinex
Phenopro-75
Ex Strength
H K Lab
PPA - Max
Strength
Al leghany
Pharmaca 1
Pro-Dax
D’Conner
Drug
21
66
Prolamine
Capsules
Thompson
kkdical
PVH Appetite
‘Control
Cap-
JB
WI 11 iams
140
--
200
--
0
w-
soles
.
75
37.5
I
200
33.33
Alleghany
Pharnacal
VW
----
50
Ai leghany
Pharmacai
Lemmon
Odrinex
Henley
James Labs
UL
60
Grapefruit
Diet Plan
Mi th Diadax
Chewable
Tablets
Ex Strength
--
Dibtac
Max
Strength
Capsules
Once-A-Day
Twice-A-Day
Dyna-Slim
Sharpe
Nationals
Capsules
Henley
James tabs
Trim
+
Caffeine
(ms)
D’Conner
Drug
Permathene-12
14
Plan
0
Diet
Obestat
Uenl
25
Tablets
ml
James
O’Conncr
Drug
Grapefruit
Diet
Plan
With Diadax
Dietac
12 Hr
Diet
Aid
Capsules
Diet
Grapefruit
Chewable
0
0
Republ ic
Drug
Dietat
PreHeal
Diet
Aid
Tablets
?PA
(-3)
Tablets
25
Ex
hanufacturer
Plus
fluidex
Delco
Dcxa-Da r
Capsules
Dexatrim
Strength
Capsules
Product
.
Cool Down
5 Tablets
DelcoPro
Tablets
Capsules
‘
Present
Amoun t ?
75
0
0
200
PVH Appet
Suppressant
Sip
Vet
Hum ToxicOt
and
Slender
S1 implan
Strength
Spant
2.2
Ex
Plus
rot
Spantrol
Strength
Plus
Super
0
i tc
EX
Odrinex
AprT&f
JB
Williams
25
0
Al leghany
Pharmaca I
25
0
Whi teworth
75
200
--
North
American
45
50
+
North
American
75
150
+
25
100
*-
Fox
Pharmaca
I
‘-a
vm
.
-
I
Table
Symptoms. Treatment
3.
Total
Me
Symptomatic
Number
(2)
19
3 (15.8)
3-5
14
2 (14)
6-12
2
1 (SO)
D-2
19
If-2t
only
6 (85.7)
7
,22
l-2
dosage
of
Phenylpropanolamine/Caffeine
Onset of
.Symptoms
(hr)
Ouration
133
10.5
460
40
9
10
150
9.8
500
34
3
11
-4
12
300
8.2
800
22
0
2
575
8.8
1400
26
5
10
680
1s
1
4
1
12t9.48
15
2Ok14.5
5
235
stration
(20).
Common side effects
from
overdose
associated
with
PPA include
hypertension
(2,4,12-X4,19,20),
severe
headache:
(2,4,11-13,191,
blurred
vision
(13).
confu.
sion
(4,5,13,16,18,19),
vomiting
(2.12.191,
and seizures
(2,5,13,20)..
Caffeine
is'8
natur8lly
OCCUrring
alkaloj
is rarely
associated
with
SeriOUS
adverse
reactions
or fatalities
(22).
A
possible
explanation
for the low frequencv
of serious
reactions
is the high
incidence
and prominent
central
nervous
of gastritis
system
side
effects
with
relatively
small
Pharmacologic
effects
on the centra
doses.
nervous
and digestive
systems
can be seen
with
as littIe
a dose as 50 mg.
A therapeu
tic
dose is near 100-200
mg (27).
Caffeine
stimulates
the cerebral
cortex,
the thalamu
the
vasomotor
and respiratory
centers
(21,
22,24-27).
Cardiac
stimulation
resulting
in a variety
of arrhythmias
have been repor
ed (21,23,25).
The combination
of caffeine
with
PPA produces
a pharmacologic
synergism
accentuating
some action
of each drug.
which
Physician
evaluation
was required
only
Seventy-seven
percent
16 times
(22.85$).
of the time the problem
was managed at
home with
only
demulcents
to delay
absorption
or the induction
of enesis
using
syrup
managed
in
Of the patients
of ipecac.
only
two required
hospitalizathe hospital,
tion,
64% were discharged
from the emergency
department
in ICSS than
4 h, and the remaining discharged
in an average
of S .25 h .
The duration
of treatment
in the health
care facility
and the
therapy
performed
are noted
in Table
5.
The dose at which
symptoms
developed
PPA alone
was 17.5 mg/kg.
This
is
not
suggestive
of a minimum toxic
dose,
rather
a dose
that
predictably
produced
symptoms
in the study
patients.
ghen PPA/
caffeine
combinations
were involved
in
children
(age Q-51,
a toxic
dose for PPA
was close
to
10 mg/kg (average
total
dose
was 140 mg).
The caffeine
doses averaged
37 mg/kg with
an average
total
dose of
480 mg producing
symptoms.
All adults
studied
were symptomatic,
suggestin*
that
early
demonstrable
clinical
finding:
are
expected
and that
symptoms
are not a good
early
descriminator
between
the low versus
the high
end of toxicity.
for
DISCUSSION
Phenylpropanolamine
is a sympathomimetic
amine structurally
similar
to amphetamine,
ephedrine
and metaraminol.
The pharmacologic
as a direct
actions
of PPA are described
alpha
8drenergiC
effect
and an indirect
acting
amine producing
release
of norepinephrine
from storage
site
at nerve
endings
Its structural
formula
protects
(8,111.
it from rapid
degradation
allowing
for
extended
duration
of action
from oral
adminiSymptom
(Hay be Marc
symptom per case)
Nausea or
Nervousness
Headache
one
Table
d
:
20
12
10
vomiting
5. Treatment
Performed
in the Health
Care
Duration
Health
of
Cafe
*
Dirz iness
Drowsiness
Ueakness
Disorientation
Shortness
of breath
Hot flashes
lncfcased
urination
Flushed
.
6
Numbness
1
:
2
2
1
1
t
hands
Tine
in
Facility
Treat=ent
Performed
Ipecac
Activated
Cathartic
Charcoal
Intravenous
Phenobarbi
(hr)
49
I
2
9
5
la
hydration
tal
.I
Vet
Hum Toxic01
3,
2
Apr 1983
and Duration
of Time
Facility
(Number)
the
it-‘,
8-14
.I4
8
Tachycardia
of
I
and Frequency
No
than
No
Treatment
3
units.
Symptom Complaint
Ipecac
Given
<l
The type of symptoms
and frequency
noted
the study
patients
are listed
in Table
nausea
or vomiting,
nervousness,
4.
Ileadache,
.and tachycardia
were most often
seen.
Almost
all
symptoms
appeared
within
the first
In approximately
one-third
two hours.
symptoms
persisted
for up
of the cases,
to 6 h. another
one-third
of the cases
. had symptoms
for up to 10 to 12 h, and
had symptoms
persistthe remaining
one-third
ing
for widely
varying
lengths
of time.
4.
by Age
2-4
in
‘lable
Combination
Es t i-mated Dose Ingested
B Y Symptomatic
Patients
PPA
Caffeine
mg/kg
mg
mgk
mg
(hr)
2
(100)
19
and Dosage
I
;
1
Table
PyAA-fuct
1.
I-
* rtanufacturer
PPA
hg)
Catlaine
h9)
Other
Substances
“‘-in2
Drops/
Alva A m m o
-r ml=5 drops Pharmacal
25
O
+
Thinz
BackAlva Amco
To-Nature
Pharmacal
Tablet
Reducing Plan - Ex
Strength Formula
75
+
--
fhi w-Span
)lax Strength
Alva
75
+
WV
Trim
Down
Ajem
75
we
UnitroI
75
.a-
Plan
Diet
tepsules
0
0
Vita
Slim
Thompson
hedical
50
0
+
Porter
and
Dietsch
25
25
*
Drug
Republic
Drug
CdpSUieS
X-11 Rcducing Plan
Tablet
Amco
Pharrnacrl
containing
weight
control
product,
subsequent
treatment,
follow-up
or evaluation
by the
poison
control
center
staff
or at a treatment
facility.
All ages were included.
For
patients
evaluated
and treated
at home,
telephone
contact
was maintained
to resolution
of symptoms or for twelve
hours,
whichever was longer.
Patients
were excluded
from the study
for the following
reasons:
ingestion
of significant
amounts
of other
.drugs
conconunitant
with
the
study
drugs,
,lck of satisfactory
history,
and patients
&hose condition
was later
determined
to
be of another
origin.
RESULTS
During the five months of the study,
a total
of 70 patients
met the criteria
of the study.
The data
from these
patients
form the basis
of this
report.
Thirtyfour
percent
of the patients
were male
(24) and 652 were female
(46) despite
a
mean even sex ration
in the O-5 age group.
The ages studied
ranged
from 9 m to 20
p (mean 5.0 y, SD = 5.74 y) for males,
and 13-54 y (mean 13.4 y, SD 12.1 y) for
females.
The patients
were divided
into two groups:
Those involved
with
accidental
childhood
ingestion
(9 m to 8 y) and the self-destructrve
or substance
abuse patients
(age llThe ages and sex ratios
of the
54.
former
group were near equal
with no striking
In the intentional
group
differences.
there
is a 1:6.5
ratio
of mnles
to females
and a distribution
of ages in females
which
indicates
the
m isuse
of these
substances
is not
limited
to a discrete
age group.
The preponderance
of females
using
these
substances
compared
to males
may be indica‘ive
of the more likely
purchaser
of diet
1.,. ..-.ids.
Young adults
(ages
13-21
y)
Comprised
301. of all
cases and almost
75% of the
intentional
group.
Children
ages O-5 accounted
for 5G?: of all
cases seen.
Vet
Hum Toxic01
2 is
a
t of the
products
invol;
some cases several
non-proprietary
*in
the 70 cases.
ftt
products
were involved.
Dexatr
imo
(reyl
ar or extra-strength
1 products
accounted
for 71.4% of all
the products
involved
suggesting
ready availability
in the homes
from either
advertising
or
sales
success.
Both Dexatrimo
products
are combinations
of PPA and caffeine.
Ten cases (14.3%)
involved
only
PPA, the remaining
60 cases
(85.7%)
involved
combinations
of both PPA
and caffeine
in varying
doses and amounts.
No products
with
only
caffeine
were involved.
None of the PPA-only
cases
involving
children
under
14 developed
symptoms although
small
amounts
were generally
ingested.
All of the patients
over
14 who ingested
The
only
PPA developed
mild
symptoms.
symptoms
described
in these
four
patients
included
nausea,
vomiting,
abdominal
cramps,
headache,
hot flashes,
diaphoresis,
dyspnea,
irritability
and tachycardia
(140 beatsfmin).
In patients
with
only
PPA involved,
the
onset
of symptoms
was usually
within
30
rain to 1 h and the duration
of symptoms
Only one patient
required
averaged
13 h.
hospitalization.
An estimated
ingested
dose in the symptomatic
patients
was 17.5
mg/kg.
The
fixed
dosage
ratios
of
PPA to
caffeine
(Table 1) ranges
from a low of 1:l to a
at a given
dose
high of 1:4.
Therefore,
of PPA the amount of caffeine
present
in
the product
may vary
by a factor
of four.
This makes defining
the dosages
of either
PPA or caffeine
in combination
difficult
Table
3 describes
with the available
data.
symptomatic
patients
by age with
the
estimated doses of PPA and caffeine
ingested
and the dose to weight relationship.
All
patients
over
age 13 were symptomatic
regardChildren
less of the history
of ingestion.
in the O-2$ y age range
generally
took
Table
2.
Brands
of
Diet
Aids
involved
in Seventy
Human Poisonings.
grand
Name
Appedrinc
Exposures
Maximum
Strength
Control
Dex-A-Diet
11
4,
1
5
f
-7.1
1
i
1.4
1.4
29
41.4
21
30.0
6
8.6
Hungrex
1
1.4
Permathene-12
1
1.4
Dexatt
im
Dexatr
im Extra
Dietac:
Pre-Meal
Maximum
Pre-Real
12 Hour
Oiet
Strength
1
Aid
Tablets
Strength
Once-A-Day
Diet
Aid Drops
Diet
Aid
1
:
Qhen-Pro-75
1.4
Super
r.4
Qdrinex
X-11
2.9
1.4
Unknown
2,
2
Av
1983
6D
5:
-_I
..,"
br
caffeine
raises
questions
;tbout
. .+of*PPd with
the stxrious
react
ions nt)ted
in earlier
published
reports.
The Gureau of Drugs/FDA
is current
Ly preparing
a report
on serious
,-orbidity
and mortality
assocjated
with
.iet pills
containing
PP.%, cnffeine,
and
cphedr ine,
singly
or in combination
with
each other
(Kawazo HE:
Personal
ComqunicaLions.
FDA, February
1982).
The discrepancy
in the severity
of reactions
in the FDA
report
and the current
study
suggests
many
questions.
The incidence
of such react ions,
their
mechanisms
of action
and the true
hazard
to the community
from such products
remains
to be addressed.
5.
6.
I
popularity
of OTC diet
aids will
cant inue to produce
signif
icant
numbers of ingestions,
both accidental
and intent
ional.
The results
of this
study
indicate
the majority
of overdoses
involving
OTC diet
aids wi13. not be serious
and may
only require
decontamination
of the digestive
care.
tract
and supportive
U’e recommend
that
emesis be induced
with reported
ingesmore
than
tions
of diet
aids
involving
8-10 mg of PPA in children.
Deliberate
by adults
require
careful
consiingestions
derat ion of the history
of ingest ion,
the
agents
involved,
and the intent
of the victim.
In most cases,
emesis
should
be induced
in all adult
poisonings
unless
there
is
strong
evidence
not to.
In children
a
dose of S-10 mg/kg would be expected
to
produce
only mild
symptoms;
however,
the
..impact and trauma
of forced
emesis
is conless hazardous
and preferable
to
c-c’ -&dered
‘-,‘allowing
a victim
to develop
even mild
spmptoms.
The use of this
dose as a cutoff
for the induction
of emesis
is consistent
with
our clinical
impression
that
amounts
tolerated
of PPA below
this
quantity
are well
and are not expected
to result
in’any
more
serious
side effects.
Obviously,
if the
history
of ingestion
cannot
reliably
be
ascertained
treatment
should
be performed.
Physicians
and poison
control
centers
should
recognize
that
these
agents
can produce
life-threatening
cardiac
arrhythmias,
hypertension,
and other
serious
effects.
7.
8.
9.
10.
k8,
Senekjian
failure
due
renal
fled J 74:1548-lSt9.
Salmon PR:
HO.
to
Hypertensive
Knight
phenylpropanolanine.
1981.
crisis
with
15.
60-61,
Lancet
LA:
PhenylpropanolamineJAMA 223(3):324-325,
LC,
Kimura
Annals
CC:
Allergy
Allergy
&O(l)
JJ, Sweet
hypotension
(Trimolets).
1973.
to
~32-34,
B, et al:
lfyperby
induced
Hed J Aost
I:
1979.
of
the
Lancet
appetite
suppressant
2 (8132):42-43,
1979.
Convulsive
seizures
due
J Hed Sot NJ 76:591-592.
to
phenyl1979.
1980.
reaction
caused
Am J Psychiat
17.
Amphetamine-l
ike react ions to phenylDiet2
AJ:
JAMA 245:601-602,
1981.
propanolamine.
,
Achor
HB, Extein
1:
Diet
aids,
mania, and affecAm J Psychiat
I38:392,
lYeI.
tive
illness.
le.
Paul i MW:
oral
diet
19%
Psychotic
agents.
16.
Schaffer
CB,
by proprietary
137:1256-1257,
Phenylpropanolamine
Whyte
JC:
Hed J Aust
1:71.5, 1981.
19.
Elliott
CF.
hypertension.
20.
Bernstein
E, Diskant
BM:
Phenylpropanolamine:
Ann Emerg
a potentially
hazardous
drug.
311-315,
1982.
Turner
JE, Cravey
RH:
A fatal
ingestion
caffeine.
Clin
Tox lO(3) :341-344,
1977.
22.
23.
1
24.
28.
t&Gee MB:
Caffeine
J Forensic
female.
Josephson
CW, Stine
a case of paroxysmal
5~776-778,
3,
and
Med
11:
of
poisoning
in a 19 year
oid
Sci 25(1):29-32,
1980.
RJ:
Caffeine
intoxication:
atria1
tachycardia.
JACEP
1976.
Sul! ivan
JL:
Caffeine
poisoning
in an infant.
J Peds YO66):1OZ2-1023,
1977.
Kulkarni
PB. Dorand
RD:
Caffeine
toxicity
in
neonate.
Pediatrics
64(2) :254-255,
1979.
a
Shen W, D’Souza
TC:
Cola-induced
psycotic
organic
brain
syndrome.
Rocky Mt Ned J 76(6):312313.
1979.
Banner
U, Czajka
overdose
in
PA:
Acute
caffeine
the neonate.
Am J Dis Child
134:495-498.
1980.
MY
DC,
2
Long
T.
secondary
Emerg
Toxic01
indomathacin.
Hypertension
and cerebral
hemorrhage
King J:
Hed J Aust
2~258,
after
trimolets
ingestion.
1979.
Hcrowitz
JD, Lang WJ, Xwes
LG, et al:
Hywrtensive
responses
by phenylpropanoiamine
in Jnorectic
Lancet
1 (8159):
and decongestant
preparations.
Eskarnade.
Hun
RB, Vasquez
arrhythmias.
Speer F, Carrasco
phenylpropanolamine,
city
Vet
with
1979.
14.
1:
acute
South
Peterson
induced
Vandongen
R:
Severe
Hyper tenaf an appetite
suppressant
Deocampo
PO:
propanoiamine.
after
Sci 25:
at:
Lee KY, Beilin
LJ,
sion
after
ingestion
(phenylpropanolamine)
1 (8126):1110-1111,
13.
27.
et
Cuthbert fiF, Greenberg
HP, Morley
SW: cough
and
cold
rerredies:
a potential
danger
to patients
on monoamine
oxidase
inhibitors.
Br tied J 1:
404-406,
1969.
Mctaren
EH:
Severe
hypertension
produced
by
interaction
of phenylpropanolamine
with
methyldopa
and oxprenolol.
Brit
Hed J 2:283-284,
1976.
175-176.
26.
TF,
Pheny]Lancet
Bennett
WH:
Hazards
phenylpropanolamine.
25.
Ouffy
G:
12.
REFERESCES
outcome
of
J Forensic
Lonnerholm
disturbances.
1979.
Jb, &Neil
tension
and postural
phenylpropanolamine
21.
Reports
thwenias
G, Wiaerlov
E,
propanolamine
and mental
1978.
11. Horowitz
The challenge
to pharmacists
and physicians
is fo educate
the consuming
public
to the
safety
and proper
use of these
and other
substances
for weight
reduction.
Treatment
of serious
adverse
reactions
or overdosage
with OTC diet
aids will
continue
to be
a clinical
problem
as long
as the
public
demand
for
this
method of weight
control
.
remains
constant.
Consumer
‘03.
1: 13;’
2:1367-1368,
The
likely
Anon : The new diet
pills.
~4-16,
1982.
Delayed
fatal
Patterson
FK:
possible
Ru-tussz
overdose.
349-352,
1ycvo.
Med J
Apr
ned
1993
tO:549,
Madden
to street
1981.
Caffeine
R, et al:
drug
ingestion.
toxiAnn