Download Prescribing Information

tions are given into the anterolateral aspect of the thigh, through clothing if necessary. The accompanying Patient
Information Leaflet and Wrap Label should also be reviewed with the patient.
Adrenaclick is capable of delivering one dose of either 0.15 mg or 0.3 mg (0.15 mL or 0.3 mL) of epinephrine. This
DOSAGE
DOSAGE
AND ADMINISTRATION
ADMINISTRATION
dose is available for auto-injection by
the patient.AND
®
®
The
physician
prescribes
Adrenaclick
should
review
this
Information
in detail
who
prescribes
Adrenaclick
review
this Prescribing
Prescribing
Information
detail with the
Selection of the appropriate Adrenaclick dosage strength is determined
according
to patient insert
body weight.
patient. This review should include the proper use of Adrenaclick to ensure that subcutaneous or intramuscular injec0.15the
mganterolateral
For use byaspect
patientsofwho
weigh through
15 - 30 clothing
kilogramsif (approximately
- 66 pounds) Patient
tionsAdrenaclick
are given into
the thigh,
necessary. The
the
anterolateral
The33accompanying
accompanying
Patient
Adrenaclick
0.3and
mgWrap
ForLabel
use by
patients
who
weigh
30with
kilograms
(approximately 66 pounds) or greater
Information
Leaflet
and
Wrap
Label
should
also
reviewed
with
patient.
Information
Leaflet
should
also
bebereviewed
thethe
patient.
The usual dose
of epinephrine
for allergic
emergencies
in0.15
patients
weigh
30 mL
kilograms
or greater
is 0.3 mg This
(0.3
Adrenaclick
capable
delivering
one dose
dose
either 0.15
mg or who
of epinephrine.
ofof delivering
one
ofof either
mg
0.3 mg
(0.15
or 0.3 mL)
is capable
mL) ofis epinephrine.
dose
available for auto-injection
auto-injection by
by the
the patient.
patient.
Since the ofdoses
of epinephrine
delivereddosage
from Adrenaclick
are
fixed, the
physician
should
consider
other forms of
Selection
appropriate
Adrenaclick
dosage
strengthisisdetermined
determined
according
patientbody
bodyweight.
weight.
the appropriate
Adrenaclick
strength
according
totopatient
injectable epinephrine if doses lower than those available from Adrenaclick are felt to be necessary. The prescribing
Adrenaclick
mg
For
use
patients
kilograms
(approximately
33
66
pounds)
0.15
by
who
weigh
15
30
kilograms
(approximately
33
66
pounds)
physician should carefully assess each patient to determine the most appropriate dose of epinephrine, recognizing the
Adrenaclicknature
use by patients
kilograms
(approximately66
66pounds)
pounds)ororgreater
greater
0.3 mgof theForreactions
kilograms
(approximately
for whichwho
thisweigh
drug 30
is30being
prescribed.
life-threatening
The
usual
dose
of
epinephrine
for
allergic
emergencies
in
patients
who
weigh
30
kilograms
or
greater
is
mg
mg (0.3
(0.3
Patients should be instructed to periodically visually inspect the epinephrine solution for particulate 0.3
matter
and
mL)
ofof epinephrine.
epinephrine.
discoloration.
If the solution contains particulate matter or develops a pinkish color or becomes darker than slightly
yellow,the
thedoses
patientofshould
immediately
contact
physicianare
for fixed,
a replacement,
sinceshould
these changes
that the
Since
epinephrine
delivered
fromtheir
Adrenaclick
the physician
considerindicate
other forms
of
effectiveness
of the drug
productlower
maythan
be decreased.
injectable
epinephrine
if doses
those available from Adrenaclick are felt to be necessary.
necessary. The prescribing
physician should carefully assess each patient to determine the most appropriate dose of epinephrine, recognizing the
life-threatening
nature ofof the
the reactions
reactionsfor
forwhich
whichHOW
thisdrug
drug
beingprescribed.
prescribed.
this
isisbeing
life-threatening nature
SUPPLIED
Patients
be instructed
to periodically
inspect
the epinephrine
solution forinjection,
particulate
and
should
particulate
Adrenaclick
is a patient
(or caregiver)
actuated visually
product that
contains
1.1 mL of epinephrine
USPmatter
(1 mg/mL),
discoloration.
IfIf the
solution
contains
matter
develops
pinkish
darker
thecan
solution
contains
particulate
matter
develops aaVOLUME
pinkish color
color orIS
or becomes
becomes
darker
than
slightly
of which one dose
be delivered
byparticulate
auto-injection.
THEororREMAINING
THAT
LEFT
AFTER
THISthan
FIXEDslightly
DOSE
yellow,
patient
should
immediatelycontact
contact
theirphysician
physician
a WITH
replacement,
since
changes
indicate
should
immediately
their
forfora replacement,
since
these
changes
indicate
thatthat
the
CANNOTtheBEpatient
FURTHER
ADMINISTERED
AND
SHOULD
BE
DISCARDED
THE DEVICE
ASthese
OUTLINED
IN THE
PATIENT
the
effectiveness
the drug
product
be decreased.
effectiveness
ofLEAFLET.
theofdrug
product
may may
be decreased.
INFORMATION
Adrenaclick 0.15 mg is available in a Two-Pack carton, NDC 52054-803-02, containing two Adrenaclick 0.15 mg
HOW SUPPLIED
SUPPLIED
HOW
auto-injectors.
Adrenaclick
patient
(or caregiver)
actuated carton,
productNDC
that 52054-804-02,
contains 1.1 mLcontaining
of epinephrine
injection, USP
Adrenaclick is0.3a mg
is available
in a Two-Pack
two Adrenaclick
0.3(1mgmg/mL),
which
auto-injection.
THETHE
REMAINING
VOLUME
THATTHAT
IS LEFT
AFTERAFTER
THIS FIXED
DOSE
of
which one
onedose
dosecan
canbebedelivered
deliveredbyby
auto-injection.
REMAINING
VOLUME
IS LEFT
THIS FIXED
auto-injectors.
CANNOT
BE FURTHER
ADMINISTERED
AND SHOULD
DISCARDED
WITH THE DEVICE
AS OUTLINED
THE PATIENT
DOSE
CANNOT
BE FURTHER
ADMINISTERED
AND BE
SHOULD
BE DISCARDED
WITH THE
DEVICE ASINOUTLINED
IN
INFORMATION
LEAFLET.
THE
PATIENT INFORMATION
LEAFLET.
PROTECT FROM LIGHT. STORE AT ROOM TEMPERATURE, 20°-25°C (68°-77°F) WITH EXCURSIONS PERMITTED
Adrenaclick 0.15
0.15 mg
mg
available(59°-86°F).
Two-Pack
carton,NDC
NDC52054-803-02,
52054-803-02,
containing
twoAdrenaclick
Adrenaclick0.15
0.15
available
ininaaTwo-Pack
carton,
two
mgmg
PROTECT
FROM
FREEZING. DOcontaining
NOT REFRIGERATE.
TO isis15°-30°C
auto-injectors.
auto-injectors.
®
PRESCRIBING INFORMATION
PRESCRIBING INFORMATION
each unit delivers 0.15 mg or 0.3 mg of epinephrine
®
DESCRIPTION
FPO
51006-04
FPO
each unit delivers
0.15 mg
or 0.31.1mg
epinephrine
® auto-injector
Adrenaclick
contains
mLofepinephrine
injection, USP (1 mg/mL), from which one dose of either 0.15
mg (0.15 mL) or 0.3 mg (0.3 mL) each is available for use by injection. The dose is administered by auto-injection
® as directed. The remaining volume is not available for use and
after the
prepares
fires0.3Adrenaclick
each
unitpatient
delivers
0.15 and
mg or
mg of epinephrine
should be discarded. See PATIENT DIRECTIONS FOR USE on the accompanying Patient Information Leaflet.
51006-04
This single, available dose of epinephrine injection, USP contains either 0.15 mg or 0.3 mg l-epinephrine, sodium
DESCRIPTION
DESCRIPTION
chloride, chlorobutanol and sodium bisulfite, all sealed
under nitrogen.
®
containscatecholamine.
injection,
USP
oneonedose
ofasof
either
0.15
Adrenaclick
contains
1.1 mL epinephrine
epinephrine
injection,
USP(1(1mg/mL),
mg/mL),from
fromwhich
which
dose
either
0.15
Epinephrine isauto-injector
a sympathomimetic
Its naturally
occurring
l-isomer,
which
is twenty
times
active
as
(0.15 mL)
mL)isorobtained
0.3 mg
mL)
each
by by
auto-injection
mg
(0.15
mgin(0.3
(0.3
mL)
each
isavailable
availablefor
foruse
use
byinjection.
injection.The
Thedose
doseisracemate.
isadministered
administered
auto-injection
the d-isomer,
pure
form
byisseparation
from
thebysynthetically
produced
®
®
andand
after the patient
patient prepares
preparesand
andfires
firesAdrenaclick
Adrenaclick asasdirected.
directed. The
The remaining
remainingvolume
volumeisisnotnotavailable
availableforforuseuse
Chemically,
epinephrine
1-(3,4-dihydroxyphenyl)-2-(methylamino)ethanol
withPatient
the following
structure:
Leaflet.
PATIENT
DIRECTIONS FOR
FOR USE
USE on
onthe
theaccompanying
accompanying
Patient
Information
should
be discarded.
SeeisPATIENT
DIRECTIONS
Information
Leaflet.
0.15
mgmg
or 0.3
mg mg
l-epinephrine,
sodium
This single,
single, available
available dose
doseofofepinephrine
epinephrineinjection,
injection,USP
USPcontains
containseither
either
0.15
or 0.3
l-epinephrine,
sodium
chloride, chlorobutanol and sodium bisulfite,
bisulfite, all
all sealed
sealedunder
undernitrogen.
nitrogen.
Epinephrine is aa sympathomimetic
sympathomimeticcatecholamine.
catecholamine. Its
Itsnaturally
naturallyoccurring
occurringl-isomer,
l-isomer,which
whichisistwenty
twentytimes
timesasas
active
active
as as
the d-isomer, is obtained inin pure
pure form
form by
byseparation
separationfrom
fromthe
thesynthetically
syntheticallyproduced
producedracemate.
racemate.
Chemically, epinephrine is 1-(3,4-dihydroxyphenyl)-2-(methylamino)ethanol
1-(3,4-dihydroxyphenyl)-2-(methylamino)ethanol with
with the
the following
followingstructure:
structure:
Epinephrine deteriorates rapidly on exposure to air or light, turning pink from oxidation to adrenochrome and brown
from the formation of melanin. Epinephrine solutions thatOH
show evidence of discoloration should be discarded.
Adrenaclick contains no latex. HO
C–CH2NHCH3
CLINICAL PHARMACOLOGY
H
HO
©2013
AllAll
rights
reserved.
ThisThis
product
andand
the the
©2013Amedra
AmedraPharmaceuticals
PharmaceuticalsLLC,
LLC,Horsham,
Horsham,PA.PA.
rights
reserved.
product
use
more
of of
United
States
Patents
5,358,489;
usethereof
thereofisisproprietary
proprietaryand
andprotected
protectedunder
underoneoneor or
more
United
States
Patents
5,358,489;
5,833,669;
7,905,352;
7,621,891;
7,927,303;
5,833,669;5,665,071;
5,665,071;5,695,472;
5,695,472;7,297,136;
7,297,136;
7,905,352;
7,621,891;
7,927,303;
Printed 5,540,664;
in5,540,664;
USA
Revised
January, 2013
7,931,618;
patents
in countries
other
thanthan
the the
U.S.U.S.
7,931,618;8,187,224;
8,187,224;
and/orrelated
related
patents
in countries
other
Forand/or
inquiries
call 1-888-894-6528
Epinephrine is the drug of choice for the emergency treatment of severe allergic reactions (Type I) to allergens, such as
in certain insect
venoms,
foods, or
It canturning
also bepink
usedfrom
in the
treatment
ofadrenochrome
anaphylaxis ofand
unknown
those presentdeteriorates
Epinephrine
rapidly
on exposure
to drugs.
air or light,
oxidation
to adrenochrome
brown
causethe
(idiopathic
exercise-induced
anaphylaxis.
when
given intramuscularly
or subcutaformation
ofof melanin.
solutions
that
evidence
should
from
formationanaphylaxis)
melanin.orEpinephrine
solutions
thatshow
showEpinephrine,
evidenceofofdiscoloration
discoloration
shouldbebediscarded.
discarded.
neously, has a rapid onset and short duration of action. Epinephrine acts on both alpha and beta adrenergic receptors.
Adrenaclick contains no latex.
Through its action on alpha adrenergic receptors, epinephrine lessens the vasodilation and increased vascular permereaction andPHARMACOLOGY
can lead to loss of intravascular fluid volume and hypotension.
ability that occurs during an anaphylacticCLINICAL
CLINICAL
PHARMACOLOGY
Through its action on beta adrenergic receptors, epinephrine causes bronchial smooth muscle relaxation that helps
treatment
of severe
Epinephrine
is
the
drug
of
choice
for
the
emergency
reactions
(Type I) toalso
allergens,
such as
alleviate bronchospasm, wheezing, and dyspnea that may occur
during allergic
anaphylaxis.
Epinephrine
helps alleviate
can
also be
be used
used
those
present
in certain
insect venoms,
ItItcan
also
in the treatment
of anaphylaxissymptoms
of unknown
pruritus,
urticaria,
and angioedema,
andfoods,
may or
bedrugs.
effective
in relieving
gastrointestinal
and genitourinary
of
or exercise-induced
anaphylaxis.
when
given intramuscularly
intramuscularly
cause
(idiopathic
anaphylaxis)
anaphylaxis.
when
given
or subcutabecause
of its relaxer
effects on the smooth
muscle Epinephrine,
ofEpinephrine,
the stomach,
intestine,
uterus and urinary
bladder.
anaphylaxis
Epinephrine acts
acts on both alpha and beta adrenergic receptors.
neously, has a rapid onset and short duration of action. Epinephrine
Through its action on alpha adrenergic receptors, epinephrine lessens the vasodilation and increased vascular permeINDICATIONS AND USAGE
ability that occurs during an anaphylactic reaction and can lead to loss of intravascular fluid volume and hypotension.
Adrenaclick
(epinephrine
USP)
is
in the emergency
treatmentsmooth
of severe
allergic
reactions
Through
its action
on beta
betainjection,
adrenergic
receptors,
epinephrine
causes bronchial
muscle
relaxation
that(Type
helpsI)
adrenergic indicated
includingbronchospasm,
anaphylaxis towheezing,
stingingandinsects
Hymenoptera,
which includes
bees,also
wasps,
alleviate
dyspnea(e.g.
thatorder
may
during
Epinephrine
helps hornets,
alleviate
may occur
occur
during anaphylaxis.
anaphylaxis.
drugs,
yellow jackets
andand
fireangioedema,
ants), and biting
insects
(e.g. triatoma,
mosquitos),
allergenand
immunotherapy,
pruritus,
urticaria,
and may
be effective
in relieving
gastrointestinal
genitourinary foods,
symptoms
of
diagnostic testing
(e.g.
radiocontrast
media),
and ofother
allergens,
as welluterus
asuterus
anaphylaxis
tobladder.
unknown
becausesubstances
itsrelaxer
relaxer
effects
thesmooth
smooth
muscle
ofthethestomach,
stomach,intestine,
intestine,
urinary
bladder.
anaphylaxis
ofof its
effects
ononthe
muscle
andandurinary
substances (idiopathic anaphylaxis) or exercise-induced anaphylaxis. Adrenaclick is intended for immediate
administration in patients with a history INDICATIONS
of anaphylactic reactions.
Selection of the appropriate dosage strength is
ANDUSAGE
USAGE
INDICATIONS
AND
determined according to patient body weight (See DOSAGE AND ADMINISTRATION section).
Adrenaclick (epinephrine
(epinephrine injection,
injection, USP)
USP) isis indicated
indicated in the emergency treatment of severe allergic reactions (Type I)
within insects
minutes (e.g.
afterorder
exposure
and consist
of flushing,
Such reactions
may occur
including
anaphylaxis
Hymenoptera,
which
includes apprehension,
bees, wasps, syncope,
hornets,
anaphylaxis
to stinging
Hymenoptera,
tachycardia,
thready
or
unobtainable
pulse
associated
with a fallmosquitos),
in blood pressure,
vomiting,
yellow jackets and fire ants), and biting insects
(e.g. triatoma,
allergenconvulsions,
immunotherapy,
foods,diarrhea
drugs,
and
abdominal
cramps,
involuntary
voiding,
wheezing,
dyspnea
due
to
laryngeal
spasm,
pruritus,
rashes,
urticaria,
diagnostic testing substances (e.g. radiocontrast media), and other allergens, as well as anaphylaxis to unknown
or
angioedema.
Adrenaclick
is
designed
as
emergency
supportive
therapy
only
and
is
not
a
replacement
or
substisubstances (idiopathic anaphylaxis) or exercise-induced anaphylaxis.
Adrenaclick is intended for immediate
anaphylaxis. Adrenaclick
immediate
tute for immediate
medicalwith
care.a history of anaphylactic reactions.
administration
in patients
reactions. Selection
Selection ofof the
the appropriate
appropriate dosage strength is
determined
accordingtotopatient
patientbody
bodyweight
weight(See
(See
DOSAGE
ADMINISTRATION
section).
determined according
DOSAGE
ANDAND
ADMINISTRATION
section).
Printed in USA
Such reactions may occur within minutes after exposure and consist of flushing,
flushing, apprehension,
apprehension, syncope,
tachycardia, thready or unobtainable pulse associated with a fall in blood
blood pressure,
pressure, convulsions,
convulsions, vomiting, diarrhea
and abdominal
abdominalcramps,
cramps,involuntary
involuntary
voiding,
wheezing,
dyspnea
to laryngeal
rashes,
voiding,
wheezing,
dyspnea
due todue
laryngeal
spasm, spasm,
pruritus, pruritus,
rashes, urticaria,
urticaria,
or angioedema.
designed supportive
as emergency
only and or
is substinot a
or angioedema.
Adrenaclick isAdrenaclick
designed asisemergency
therapysupportive
only and istherapy
not a replacement
replacement
or substitute
immediate medical care.
tute for immediate
medicalforcare.
Rx
only.
%
Adrenaclick 0.3
0.3 mg
mg isis available
availableininaaTwo-Pack
Two-Packcarton,
carton,
NDC
52054-804-02,containing
containingtwo
twoAdrenaclick
Adrenaclick0.30.3mgmg
NDC
52054-804-02,
auto-injectors.
auto-injectors.
PROTECTFROM
FROMLIGHT.
LIGHT.STORE
STOREAT
ATROOM
ROOM TEMPERATURE,
TEMPERATURE, 20°-25°C (68°-77°F) WITH EXCURSIONS
PROTECT
EXCURSIONS PERMITTED
PERMITTED
(59°-86°F). PROTECT
PROTECTFROM
FROM FREEZING.
FREEZING. DO
DONOT
NOT REFRIGERATE.
REFRIGERATE.
15°-30°C (59°-86°F).
TO 15°-30°C
Rx only.
only.
%
Manufactured for and Distributed by: Amedra Pharmaceuticals LLC, Horsham, PA 19044
©2013 Amedra Pharmaceuticals LLC, Horsham, PA. All rights reserved. This product and the
use thereof is proprietary and protected under one or more of United States Patents 5,358,489;
5,540,664; 5,833,669; 5,665,071; 5,695,472; 7,297,136; 7,905,352; 7,621,891; 7,927,303;
7,931,618; 8,187,224; and/or related patents in countries other than the U.S.
Manufactured
for and
by: Amedra
Pharmaceuticals
LLC, Horsham,
PA 19044
Manufactured
forDistributed
and Distributed
by: Amedra
Pharmaceuticals
LLC, Horsham,
PA 19044
RevisedJanuary,
April, 2013
Revised
2013
For
1-888-894-6528
For inquiries
inquiries call 1-888-894-6528
CONTRAINDICATIONS
There are no absolute contraindications to the use of epinephrine in a life-threatening allergic reaction.
(3) Drug Interactions
Patients who receive epinephrine while concomitantly taking cardiac glycosides or diuretics should be observed
carefully for the development of cardiac arrhythmias.
WARNINGS
The effects of epinephrine may be potentiated by tricyclic antidepressants, monoamine oxidase inhibitors, sodium
levothyroxine, and certain antihistamines, notably chlorpheniramine, tripelennamine, and diphenhydramine.
Adrenaclick should only be injected into the anterolateral aspect of the thigh. Accidental injection into the hands or
feet may result in loss of blood flow to the affected area and should be avoided. DO NOT INJECT INTO BUTTOCK. If
there is an accidental injection into these areas, advise the patient to inform the healthcare provider of the accidental
injection when he/she goes to the nearest emergency room for further treatment of anaphylaxis.
The cardiostimulating and bronchodilating effects of epinephrine are antagonized by beta-adrenergic blocking drugs,
such as propranolol. The vasoconstricting and hypertensive effects are antagonized by alpha-adrenergic blocking
drugs, such as phentolamine. Ergot alkaloids and phenothiazines may also reverse the pressor effects of epinephrine.
Avoid possible inadvertent intravascular administration. Large doses or accidental intravenous injection of epinephrine
may result in cerebral hemorrhage due to a sharp rise in blood pressure. DO NOT INJECT INTRAVENOUSLY. Rapidly
acting vasodilators can counteract the marked pressor effects of epinephrine if there is such inadvertent administration.
Epinephrine is the preferred treatment for serious allergic reactions or other emergency situations even though this
product contains sodium bisulfite, a sulfite that may, in other products, cause allergic-type reactions including
anaphylactic symptoms or life-threatening or less severe asthmatic episodes in certain susceptible persons.
The alternatives to using epinephrine in a life-threatening situation may not be satisfactory. The presence of a sulfite
in this product should not deter administration of the drug for treatment of serious allergic or other emergency
situations, even if the patient is sulfite-sensitive.
Epinephrine should be administered with caution to patients with cardiac arrhythmias, coronary artery or organic heart
disease, or hypertension. In patients with coronary insufficiency or ischemic heart disease, epinephrine may precipitate or aggravate angina pectoris as well as produce ventricular arrhythmias. It should be recognized that the
presence of these conditions is not a contraindication to epinephrine administration in an acute, life-threatening situation.
Epinephrine is light sensitive and should be stored in the carrying-case provided. Store at room temperature
(20º-25ºC/68º-77ºF) with excursions permitted to 15º-30ºC (59º-86ºF). Do not refrigerate; protect from freezing.
Patients should periodically check the solution in Adrenaclick for any discoloration and/or precipitates. If the solution
is discolored or contains a precipitate, the patient should replace their Adrenaclick.
PRECAUTIONS
(1) General
Adrenaclick is not intended as a substitute for immediate medical care. In conjunction with the administration of
epinephrine, the patient should seek appropriate medical care. More than two sequential doses of epinephrine should
only be administered under direct medical supervision.
Epinephrine is essential for the treatment of anaphylaxis. Patients with a history of severe allergic reactions should be
instructed about the circumstances under which epinephrine should be used (See INDICATIONS AND USAGE Section).
It should be determined that the patient is at risk of future anaphylaxis, since there are some concerns in specific
patients with epinephrine administration. (a) Epinephrine should be used with caution in patients with cardiac
arrhythmias, coronary artery or organic heart disease, hypertension, or in patients who are on medications that may
sensitize the heart to arrhythmias, e.g., digitalis, diuretics, or anti-arrhythmics. In such patients, epinephrine may
precipitate or aggravate angina pectoris as well as produce ventricular arrhythmias. (b) The effects of epinephrine may
be potentiated by tricyclic antidepressants and monoamine oxidase inhibitors. (c) Some patients may be at greater
risk of developing adverse reactions after epinephrine administration. These include patients with hyperthyroidism,
cardiovascular disease, hypertension, diabetes, and elderly individuals, and pregnant women. It must be noted that,
despite these concerns, epinephrine is essential for the treatment of anaphylaxis. Therefore, patients with these
conditions, or any other person who might be in a position to administer epinephrine to a patient with these conditions
experiencing anaphylaxis, should be instructed about the circumstances under which epinephrine should be used.
(2) Information for Patients
Complete patient information, including dosage, directions for proper administration, and precautions, can be found
inside each Adrenaclick package within the Patient Information Leaflet.
Epinephrine may produce symptoms and signs that include an increase in pulse rate, the sensation of a more forceful
heartbeat, palpitations, a throbbing headache, pallor, feelings of overstimulation, anxiety, weakness, shakiness,
dizziness, or nausea. These signs and symptoms usually subside rapidly, especially with rest, quiet, and recumbency.
Patients with hypertension or hyperthyroidism may develop more severe or persistent effects, and patients with coronary
artery disease could experience angina. Patients with diabetes may develop increased blood glucose levels following
epinephrine administration. Patients with Parkinson’s disease may notice a temporary worsening of symptoms.
(4) Carcinogenesis, Mutagenesis, Impairment of Fertility
There are no data from either animal or human studies regarding the carcinogenicity or mutagenicity of epinephrine,
and no studies have been conducted to determine its potential for the impairment of fertility. This should not prevent
the use of epinephrine under the conditions noted under INDICATIONS AND USAGE section.
(5) Pregnancy
Pregnancy Category C. Epinephrine has been shown to have developmental effects in rabbits at a subcutaneous dose
of 1.2 mg/kg (approximately 30 times the maximum recommended daily subcutaneous or intramuscular dose on a
mg/m2 basis), in mice at a subcutaneous dose of 1 mg/kg (approximately 7 times the maximum recommended daily
subcutaneous or intramuscular dose on a mg/m2 basis), and in hamsters at a subcutaneous dose of 0.5 mg/kg
(approximately 5 times the maximum recommended daily subcutaneous or intramuscular dose on a mg/m2 basis).
These effects were not seen in mice at a subcutaneous dose of 0.5 mg/kg (approximately 3 times the maximum
recommended daily subcutaneous or intramuscular dose on a mg/m2 basis). Although there are no adequate and
well-controlled studies in pregnant women, epinephrine crosses the placenta and could lead to fetal anoxia,
spontaneous abortion or both. Therefore, epinephrine should be used in pregnancy only if the potential benefit
justifies the potential risk to the fetus.
ADVERSE REACTIONS
Adverse reactions to epinephrine include transient, moderate anxiety; apprehensiveness; restlessness; tremor;
weakness; dizziness; sweating; palpitations; pallor; nausea and vomiting; headache, and/or respiratory difficulties.
These symptoms occur in some persons receiving therapeutic doses of epinephrine, but are more likely to occur in
patients with hypertension or hyperthyroidism. Large doses of epinephrine can cause acute hypertension.
Arrhythmias, including fatal ventricular fibrillation, have been reported, particularly in patients with underlying cardiac
disease or those receiving certain drugs [see (3) Drug Interactions]. Rapid rises in blood pressure have produced
cerebral hemorrhage, particularly in elderly patients with cardiovascular disease. Angina may occur in patients with
coronary artery disease. The potential for epinephrine to produce these types of adverse reactions does not
contraindicate its use in an acute, life-threatening allergic reaction.
OVERDOSAGE
Epinephrine is rapidly inactivated in the body, and treatment following overdose with epinephrine is primarily
supportive. If necessary, pressor effects may be counteracted by rapidly acting vasodilators or alpha-adrenergic blocking drugs. If prolonged hypotension follows such measures, it may be necessary to administer another pressor drug.
Overdosage of epinephrine may produce extremely elevated arterial pressure, which may result in cerebrovascular
hemorrhage, particularly in elderly patients.
If an epinephrine overdose induces pulmonary edema that interferes with respiration, treatment consists of a rapidly
acting alpha-adrenergic blocking drug and/or respiratory support.
Epinephrine overdosage can also cause transient bradycardia followed by tachycardia, and these may be
accompanied by potentially fatal cardiac arrhythmias. Premature ventricular contractions may appear within one
minute after injection and may be followed by multifocal ventricular tachycardia (prefibrillation rhythm). Subsidence
of the ventricular effects may be followed by atrial tachycardia and occasionally by atrioventricular block. Treatment
of arrhythmias consists of administration of a beta-adrenergic blocking drug such as propranolol.
Overdosage sometimes results in extreme pallor and coldness of the skin, metabolic acidosis, and kidney failure.
Suitable corrective measures must be taken in such situations.