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INDICATIONS
INDICATIONSAND
ANDUSAGE
USAGE
Pradaxa
Pradaxa®®(dabigatran
(dabigatranetexilate
etexilatemesylate)
mesylate)capsules
capsulesisisindicated:
indicated:
•• totoreduce
reducethe
therisk
riskof
ofstroke
strokeand
andsystemic
systemicembolism
embolismininpatients
patientswith
with
non-valvular
non-valvularatrial
atrialfifibrillation
brillation
IMPORTANT
IMPORTANTSAFETY
SAFETYINFORMATION
INFORMATION
WARNING:
WARNING:(A)
(A)PREMATURE
PREMATUREDISCONTINUATION
DISCONTINUATIONOF
OFPRADAXA
PRADAXAINCREASES
INCREASES
THE
THERISK
RISKOF
OFTHROMBOTIC
THROMBOTICEVENTS,
EVENTS,(B)
(B)SPINAL/EPIDURAL
SPINAL/EPIDURALHEMATOMA
HEMATOMA
(A)
(A)PREMATURE
PREMATUREDISCONTINUATION
DISCONTINUATIONOF
OFPRADAXA
PRADAXAINCREASES
INCREASESTHE
THERISK
RISKOF
OF
THROMBOTIC
THROMBOTICEVENTS
EVENTS
Premature
Prematurediscontinuation
discontinuationof
ofany
anyoral
oralanticoagulant,
anticoagulant,including
includingPRADAXA,
PRADAXA,
increases
increasesthe
therisk
riskof
ofthrombotic
thromboticevents.
events.IfIfanticoagulation
anticoagulationwith
withPRADAXA
PRADAXAisis
discontinued
discontinuedfor
foraareason
reasonother
otherthan
thanpathological
pathologicalbleeding
bleedingor
orcompletion
completion
of
ofaacourse
courseof
oftherapy,
therapy,consider
considercoverage
coveragewith
withanother
anotheranticoagulant
anticoagulant
(B)
(B)SPINAL/EPIDURAL
SPINAL/EPIDURALHEMATOMA
HEMATOMA
Epidural
Epiduralor
orspinal
spinalhematomas
hematomasmay
mayoccur
occurin
inpatients
patientstreated
treatedwith
withPRADAXA
PRADAXA
who
whoare
arereceiving
receivingneuraxial
neuraxialanesthesia
anesthesiaor
orundergoing
undergoingspinal
spinalpuncture.
puncture.
These
Thesehematomas
hematomasmay
mayresult
resultin
inlong-term
long-termor
orpermanent
permanentparalysis.
paralysis.
Consider
Considerthese
theserisks
riskswhen
whenscheduling
schedulingpatients
patientsfor
forspinal
spinalprocedures.
procedures.
Factors
Factorsthat
thatcan
canincrease
increasethe
therisk
riskof
ofdeveloping
developingepidural
epiduralor
orspinal
spinal
hematomas
hematomasin
inthese
thesepatients
patientsinclude:
include:
•• use
useof
ofindwelling
indwellingepidural
epiduralcatheters
catheters
•• concomitant
concomitantuse
useof
ofother
otherdrugs
drugsthat
thataffect
affecthemostasis,
hemostasis,such
suchas
as
non-steroidal
non-steroidalanti-infl
anti-inflammatory
ammatorydrugs
drugs(NSAIDs),
(NSAIDs),platelet
plateletinhibitors,
inhibitors,
other
otheranticoagulants
anticoagulants
•• aahistory
historyof
oftraumatic
traumaticor
orrepeated
repeatedepidural
epiduralor
orspinal
spinalpunctures
punctures
•• aahistory
historyof
ofspinal
spinaldeformity
deformityor
orspinal
spinalsurgery
surgery
•• optimal
optimaltiming
timingbetween
betweenthe
theadministration
administrationof
ofPRADAXA
PRADAXAand
andneuraxial
neuraxial
procedures
proceduresisisnot
notknown
known
Monitor
Monitorpatients
patientsfrequently
frequentlyfor
forsigns
signsand
andsymptoms
symptomsof
ofneurological
neurological
impairment.
impairment.IfIfneurological
neurologicalcompromise
compromiseisisnoted,
noted,urgent
urgenttreatment
treatmentisis
necessary.
necessary. Consider
Considerthe
thebenefi
benefitstsand
andrisks
risksbefore
beforeneuraxial
neuraxialintervention
interventionin
in
patients
patientswho
whoare
areor
orwill
willbe
beanticoagulated.
anticoagulated.
CONTRAINDICATIONS
CONTRAINDICATIONS
PRADAXA
PRADAXAisiscontraindicated
contraindicatedininpatients
patientswith:
with:
-- active
activepathological
pathologicalbleeding;
bleeding;
-- known
knownserious
serioushypersensitivity
hypersensitivityreaction
reaction(e.g.,
(e.g.,anaphylactic
anaphylacticreaction
reactionor
or
anaphylactic
anaphylacticshock)
shock)totoPRADAXA;
PRADAXA;
-- mechanical
mechanicalprosthetic
prostheticheart
heartvalve
valve
WARNINGS
WARNINGS&&PRECAUTIONS
PRECAUTIONS
Increased
IncreasedRisk
Riskof
ofThrombotic
ThromboticEvents
Eventsafter
afterPremature
PrematureDiscontinuation
Discontinuation
Premature
Prematurediscontinuation
discontinuationof
ofany
anyoral
oralanticoagulant,
anticoagulant,including
includingPRADAXA,
PRADAXA,
ininthe
theabsence
absenceof
ofadequate
adequatealternative
alternativeanticoagulation
anticoagulationincreases
increasesthe
therisk
risk
of
ofthrombotic
thromboticevents.
events. IfIfPRADAXA
PRADAXAisisdiscontinued
discontinuedfor
foraareason
reasonother
otherthan
than
pathological
pathologicalbleeding
bleedingor
orcompletion
completionof
ofaacourse
courseof
oftherapy,
therapy,consider
considercoverage
coverage
with
withanother
anotheranticoagulant
anticoagulantand
andrestart
restartPRADAXA
PRADAXAas
assoon
soonas
asmedically
medically
appropriate.
appropriate .
Risk
Riskof
ofBleeding
Bleeding
andcan
cancause
causesignifi
significant
cantand,
and,
•• PRADAXA
PRADAXAincreases
increasesthe
therisk
riskofofbleeding
bleedingand
sometimes,fatal
fatalbleeding.
bleeding.Promptly
Promptlyevaluate
evaluateany
anysigns
signsor
orsymptoms
symptomsofof
sometimes,
bloodloss
loss(e.g.,
(e.g.,aadrop
dropininhemoglobin
hemoglobinand/or
and/orhematocrit
hematocritor
orhypotension).
hypotension).
blood
DiscontinuePRADAXA
PRADAXAininpatients
patientswith
withactive
activepathological
pathologicalbleeding.
bleeding.
Discontinue
Riskfactors
factorsfor
forbleeding
bleedinginclude
includeconcomitant
concomitantuse
useofofmedications
medicationsthat
that
•• Risk
increasethe
therisk
riskofofbleeding
bleeding(e.g.,
(e.g.,anti-platelet
anti-plateletagents,
agents,heparin,
heparin,fifibrinolytic
brinolytic
increase
therapy,and
andchronic
chronicuse
useofofNSAIDs).
NSAIDs).PRADAXA’s
PRADAXA’santicoagulant
anticoagulantactivity
activityand
and
therapy,
half-lifeare
areincreased
increasedininpatients
patientswith
withrenal
renalimpairment.
impairment.
half-life
ReversalofofAnticoagulant
AnticoagulantEffect:
Effect: AAspecifi
specificcreversal
reversalagent
agent(idarucizumab)
(idarucizumab)
•• Reversal
fordabigatran
dabigatranisisavailable
availablewhen
whenreversal
reversalofofthe
theanticoagulant
anticoagulanteffect
effectofof
for
dabigatranisisneeded:
needed:
dabigatran
•• For
Foremergency
emergencysurgery/urgent
surgery/urgentprocedures
procedures
•• InInlife-threatening
life-threateningor
oruncontrolled
uncontrolledbleeding
bleeding
COPYRIGHT
COPYRIGHT©
©2016
2016BOEHRINGER
BOEHRINGERINGELHEIM
INGELHEIMPHARMACEUTICALS,
PHARMACEUTICALS,INC.
INC.
WARNINGS
WARNINGS&&PRECAUTIONS
PRECAUTIONS
Risk
Riskof
ofBleeding
Bleeding(cont’d)
(cont’d)
Hemodialysis
Hemodialysiscan
canremove
removedabigatran;
dabigatran;however
howeverclinical
clinicalexperience
experiencefor
for
hemodialysis
hemodialysisas
asaatreatment
treatmentfor
forbleeding
bleedingisislimited.
limited. Prothrombin
Prothrombincomplex
complex
concentrates
concentratesor
orrecombinant
recombinantFactor
FactorVIIa
VIIamay
maybe
beconsidered
consideredbut
buttheir
theiruse
use
has
hasnot
notbeen
beenevaluated.
evaluated. Protamine
Protaminesulfate
sulfateand
andvitamin
vitaminKKare
arenot
notexpected
expected
totoaffect
affectdabigatran
dabigatrananticoagulant
anticoagulantactivity.
activity. Consider
Consideradministration
administrationofof
platelet
plateletconcentrates
concentrateswhere
wherethrombocytopenia
thrombocytopeniaisispresent
presentor
orlong-acting
long-acting
antiplatelet
antiplateletdrugs
drugshave
havebeen
beenused.
used.
Thromboembolic
Thromboembolicand
andBleeding
BleedingEvents
Eventsin
inPatients
Patientswith
withProsthetic
Prosthetic
Heart
HeartValves
Valves
The
Theuse
useofofPRADAXA
PRADAXAisiscontraindicated
contraindicatedininpatients
patientswith
withmechanical
mechanical
prosthetic
prostheticvalves
valvesdue
duetotoaahigher
higherrisk
riskfor
forthromboembolic
thromboembolicevents,
events,especially
especially
ininthe
thepost-operative
post-operativeperiod,
period,and
andan
anexcess
excessofofmajor
majorbleeding
bleedingfor
forPRADAXA
PRADAXA
vs.
vs.warfarin.
warfarin.Use
UseofofPRADAXA
PRADAXAfor
forthe
theprophylaxis
prophylaxisofofthromboembolic
thromboembolicevents
events
ininpatients
patientswith
withAFib
AFibininthe
thesetting
settingofofother
otherforms
formsofofvalvular
valvularheart
heartdisease,
disease,
including
includingbioprosthetic
bioprostheticheart
heartvalve,
valve,has
hasnot
notbeen
beenstudied
studiedand
andisisnot
not
recommended.
recommended.
Effect
Effectof
ofP-gp
P-gpInducers
Inducers&&Inhibitors
Inhibitorson
onDabigatran
DabigatranExposure
Exposure
Concomitant
Concomitantuse
useofofPRADAXA
PRADAXAwith
withP-gp
P-gpinducers
inducers(e.g.,
(e.g.,rifampin)
rifampin)reduces
reduces
exposure
exposuretotodabigatran
dabigatranand
andshould
shouldgenerally
generallybe
beavoided.
avoided. P-gp
P-gpinhibition
inhibition
and
andimpaired
impairedrenal
renalfunction
functionare
aremajor
majorindependent
independentfactors
factorsininincreased
increased
exposure
exposuretotodabigatran.
dabigatran. Concomitant
Concomitantuse
useofofP-gp
P-gpinhibitors
inhibitorsininpatients
patientswith
with
renal
renalimpairment
impairmentisisexpected
expectedtotoincrease
increaseexposure
exposureofofdabigatran
dabigatrancompared
compared
totoeither
eitherfactor
factoralone.
alone.
Reduction
ReductionofofRisk
RiskofofStroke/Systemic
Stroke/SystemicEmbolism
EmbolismininNVAF
NVAF
•• For
Forpatients
patientswith
withmoderate
moderaterenal
renalimpairment
impairment(CrCl
(CrCl30-50
30-50mL/min),
mL/min),reduce
reduce
the
thedose
doseofofPRADAXA
PRADAXAtoto75
75mg
mgtwice
twicedaily
dailywhen
whendronedarone
dronedaroneor
orsystemic
systemic
ketoconazole
ketoconazoleisiscoadministered
coadministeredwith
withPRADAXA.
PRADAXA.
•• For
Forpatients
patientswith
withsevere
severerenal
renalimpairment
impairment(CrCl
(CrCl15-30
15-30mL/min),
mL/min),avoid
avoid
concomitant
concomitantuse
useofofPRADAXA
PRADAXAand
andP-gp
P-gpinhibitors.
inhibitors.
ADVERSE
ADVERSEREACTIONS
REACTIONS
The
Themost
mostserious
seriousadverse
adversereactions
reactionsreported
reportedwith
withPRADAXA
PRADAXAwere
wererelated
related
totobleeding.
bleeding.
•• Most
Mostfrequent
frequentadverse
adversereactions
reactionsleading
leadingtotodiscontinuation
discontinuationofofPRADAXA
PRADAXA
were
werebleeding
bleeding&&gastrointestinal
gastrointestinal(GI)
(GI)events.
events.
•• PRADAXA
PRADAXA150
150mg
mgresulted
resultedininhigher
higherrates
ratesofofmajor
majorand
andany
anyGI
GIbleeds
bleeds
comparedtotowarfarin.
warfarin.
compared
patients≥75
≥75years
yearsofofage,
age,the
therisk
riskofofmajor
majorbleeding
bleedingmay
maybe
begreater
greater
•• InInpatients
withPRADAXA
PRADAXAvs
vswarfarin.
warfarin.
with
Patientson
onPRADAXA
PRADAXA150
150mg
mghad
hadan
anincreased
increasedincidence
incidenceofofGI
GIadverse
adverse
•• Patients
reactions. These
Thesewere
werecommonly
commonlydyspepsia
dyspepsia(including
(incl udingabdominal
abdominalpain
pain
reactions.
upper,abdominal
abdominalpain,
pain,abdominal
abdominaldiscomfort,
discomfort,and
andepigastric
epigastricdiscomfort)
discomfort)
upper,
and
andgastritis-like
gastritis-likesymptoms
symptoms(including
(includingGERD,
GERD,esophagitis,
esophagitis,erosive
erosivegastritis,
gastritis,
gastric
gastrichemorrhage,
hemorrhage,hemorrhagic
hemorrhagicgastritis,
gastritis,hemorrhagic
hemorrhagicerosive
erosivegastritis,
gastritis,
and
andGI
GIulcer).
ulcer).
Other
OtherMeasures
MeasuresEvaluated
Evaluated
NVAFpatients,
patients,aahigher
higherrate
rateofofclinical
clinicalMI
MIwas
wasreported
reportedininpatients
patientswho
who
InInNVAF
receivedPRADAXA
PRADAXA(0.7/100
(0.7/100patient-years
patient-yearsfor
for150
150mg
mgdose)
dose)than
thanininthose
those
received
whoreceived
receivedwarfarin
warfarin(0.6).
(0.6).
who
NOAC=novel
NOAC=noveloral
oralanticoagulant;
anticoagulant;NVAF=non-valvular
NVAF=non-valvularatrial
atrialfifibrillation;
brillation;
SE=systemic
SE=systemicembolism;
embolism;RE-LY=Randomized
RE-LY=RandomizedEvaluation
Evaluationof
ofLong-term
Long-term
anticoagulant
anticoagulanttherapY;
therapY;HR=hazard
HR=hazardratio;
ratio;CI=confi
CI=confidence
denceinterval.
interval.
Please
Pleasesee
seeaccompanying
accompanyingbrief
briefsummary
summaryof
offull
fullPrescribing
PrescribingInformation.
Information.
References:
References:1.
1.Data
Dataon
onfifile.
le.Boehringer
BoehringerIngelheim
IngelheimPharmaceuticals,
Pharmaceuticals,Inc.
Inc.
2.
2.Connolly
ConnollySJ,
SJ,Wallentin
WallentinL,L,Yusuf
YusufS.
S.Additional
Additionalevents
eventsininthe
theRE-LY
RE-LYTrial
Trial
[Letter
[Letterto
tothe
theEditor].
Editor].NNEngl
EnglJJMed.
Med.2014;371(15):1464-1465.
2014;371(15):1464-1465.
ALL
ALLRIGHTS
RIGHTSRESERVED.
RESERVED.
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PRINTEDIN
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