Antiplatelet drug is a generic term, describing agents which decrease platelet aggregation

and inhibit thrombus formation. Antiplatelet drugs are most effective for arterial clots that are
composed largely of platelets.
Platelets are critical in haemostasis and the development of arterial thrombi. Damaged
endothelium activates platelets which respond by adhering and aggregating. Their release of
thromboxane A2 and adenosine diphosphate (ADP amplifies and propagates the process by
stimulating surrounding platelets. The production of thrombin via the coagulation cascade is
also accelerated, stabilising the thrombus by the conversion of fibrinogen to fibrin. Different
classes of antiplatelet drugs act at different !unctures in this process.
Aspirin
"on#selective, irreversible inhibitor of cyclo#oxygenase which catalyses the production of
thromboxane and prostaglandins.
Antithrombotic action derives from reduction in thromboxane A2.
Aspirin also has analgesic, anti#inflammatory and anti#oxidant properties. $ome of the
beneficial actions of aspirin in patients with cardiovascular disease (%&D may be related to
these as well as its antithrombotic effect, although some of these effects are only apparent at
much higher doses.
Clopidogrel
An ADP receptor antagonist that competitively inhibits ADP from binding to platelet
receptors, preventing ADP#mediated up#regulation of glycoprotein ('P ((b)(((a receptor,
again bloc*ing amplification of platelet aggregation.
Direct comparison of clopidogrel may indicate that it is a slightly more effective
antiplatelet drug than aspirin # for example, when compared head#to#head in the %lopidogrel
versus Aspirin in Patients at +is* of (schaemic ,vents (%AP+(, trial.-ut a high ""T (2..
to prevent one additional event and high incremental cost (given aspirin/s low cost have
meant that use of clopidogrel alone is limited to those who cannot tolerate aspirin
prophylaxis.012 3ore importantly, clopidogrel is routinely used in the treatment of acute
coronary system (A%$ and post#percutaneous coronary intervention (P%( stenting in
con!unction with aspirin.
Prasugrel
Prasugrel is a novel prodrug from the same family as clopidogrel, with more efficient
platelet inhibition.
%urrent "ational (nstitute for 4ealth and %linical ,xcellence ("(%, guidance
recommends prasugrel in combination with aspirin in acute coronary syndrome (A%$
patients undergoing percutaneous coronary intervention (P%( when5
immediate P%( is necessary for $T segment elevation myocardial infarction ($T,3(6 or
stent thrombosis occurred during treatment with clopidogrel6 or the patient has diabetes
mellitus
Dipyridamole
The mechanism is not fully understood but it is thought to act by inhibiting adenosine
upta*e into platelets and reducing ADP#induced aggregation.
Dipyridamole also has vasodilating properties that can ma*e it unsuitable for use in those
with severe coronary artery disease, unstable angina, recent myocardial infarction (3( or left
ventricular outflow obstruction.
Glycoprotein IIb/IIIa antagonists
Abciximab was the original 'P ((b)(((a antagonist and is a monoclonal antibody with a
much prolonged duration compared to newer agents, eg eptifibatide which is a non#peptide
antagonist.
These drugs inhibit the final common pathway of platelet aggregation where fibrinogen
binds to 'P ((b)(((a receptor.
All re7uire intravenous administration under specialist supervision. Patients receiving these
drugs re7uire very close monitoring, usually on coronary care units (%%8s.
Thromboxane A2 and ADP are !ust two of over 9. *nown platelet agonists. -loc*ade by
aspirin and clopidogrel will not affect the platelet/s ability to be stimulated by other agonists
whilst use of a 'P ((b)(((a antagonist should inhibit aggregate formation whatever agonist
influences the platelet.
"eutralising antibodies to abciximab form, so it can only be used once.
'P ((b)(((a antagonists can cause severe bleeding, most often from the site of femoral
puncture for percutaneous transluminal coronary angioplasty (PT%A. (t can ta*e over :2
hours for platelet function to be restored after stopping an infusion.
Other agents
Ticagrelor # licensed for use with aspirin in preventing atherothrombotic events in acute
coronary syndrome (A%$ for :2 months, and can be used for both medical management or
where further coronary intervention is planned. (f it needs to be continued beyond this then
the diagnosis should be confirmed by a cardiology specialist.
Indications
Primary prevention of cardiovascular disease (%&D5
Previously, aspirin was recommended for those without apparent %&D in whom the
total %&D ris* over :. years is ;2.<, and for almost all diabetic patients over the age of =.
years. The evidence to support this unlicensed indication is not robust and thus current
guidance is that aspirin should not be used in primary prevention (including in those with
diabetes mellitus or hypertension.0:22 -ut note5 aspirin is increasingly being used in the
primary prevention of some cancers # particularly bowel cancer.
%lopidogrel and dipyridamole are neither indicated nor licensed for primary prevention
of cardiovascular (%& events.
$econdary prevention of %&D5
(n those with established atherosclerotic disease, low#dose aspirin (>= mg daily is
recommended indefinitely for long#term secondary prevention. Antithrombotic Trialists/
%ollaboration (ATT% provided evidence that this reduces the ris* of any serious vascular
event by 2=< and vascular mortality by a sixth.
3odified#release dipyridamole 2.. mg bd plus low#dose aspirin (=. mg or >= mg daily
is recommended for secondary prevention following an ischaemic stro*e or a transient
ischaemic attac* (T(A for a period of two years from the most recent event, based on the
second ,uropean $tro*e Prevention (,P$#2 trial. ,P$#2/s findings have been replicated by
the more recent ,uropean)Australasian $tro*e Prevention in +eversible (schaemia Trial
(,$P+(T study. ,vidence of long#term benefit was not established by ,P$#2, so "(%,
guidance limited treatment duration to two years with preventative treatment reverting to
standard treatment (eg low#dose aspirin but it should probably continue with no time limit.
?here aspirin is contra#indicated or genuinely not tolerated (ie proven hypersensitivity
or history of severe low#dose aspirin#induced dyspepsia, clopidogrel >= mg daily is a
suitable alternative to aspirin (or aspirin plus dipyridamole post#stro*e.
There may be a role for triple antiplatelet therapy in the secondary prevention of %&D
but this is as yet unlicensed.
Acute ischaemic events5
3yocardial ischaemia
A single dose of aspirin @.. mg and clopidogrel @.. mg (A.. mg # unlicensed in some
centres prior to urgent percutaneous coronary intervention (P%( should be given as soon as
possible after an ischaemic event (both non#$T segment elevation myocardial infarction
("$T,3( and $T,3(, preferably dispersed in water or chewed.
%lopidogrel >= mg daily is licensed for the treatment of acute coronary syndrome (A%$
B $T elevation, in combination with aspirin (usually following loading doses.
Post#P%( clopidogrel >= mg should continue for one month if a bare metal stent is
inserted and :2 months if a drug#eluting stent is inserted. Thereafter, treatment should revert
to low#dose aspirin alone.
,ptifibatide and tirofiban are licensed for use with heparin and aspirin to prevent early
3( in patients with unstable angina or "$T,3( where early percutaneous transluminal
coronary angioplasty (PT%A is desirable but delay is li*ely.
P%(5 abciximab is licensed as an ad!unct to heparin and aspirin for the prevention of
ischaemic complications in high#ris* patients undergoing P%(, and "(%, suggests that 'P
((b)(((a inhibitors be used as ad!uncts where the procedure is complex or is delayed and in
patients with diabetes.
,ptifibatide5 this is also used in "$T,3( where the last episode of chest pain was
within 21 hours.
+arely, 'P ((b)(((a inhibitors are used in complex patients with unstable angina or an
acute coronary syndrome (A%$ which is not responding to conventional therapy (under
specialist supervision.
%erebral ischaemia
Acute ischaemic stro*e # thrombolyse if appropriate and follow with aspirin @.. mg
once daily for :1 days. (f not able to be thrombolysed then aspirin alone should be given.
Aspirin caused an excess of about two intracranial and four extracranial haemorrhages per
:,... people treated, but these small ris*s were more than offset by the reductions in death
and disability from other causes.
Cong#term management of both T(A or ischaemic stro*e # dipyridamole 2.. mg bd with
aspirin >= mg once daily.
(f aspirin cannot be used then modified#release dipyridamole is the choice.
(f there are reasons why both aspirin and dipyridamole cannot be used # clopidogrel >=
mg would be the alternative, although this is currently unlicensed.
Atrial fibrillation (AD carries a high ris* of stro*e and other thromboembolic events.
?arfarin is more efficacious than aspirin at preventing stro*e (particularly in those at highest
ris* but carries a greater ris* of ma!or haemorrhage5
Everall baseline ris* is =: stro*es per :,... patient years.
?arfarin will prevent 2F stro*es at the cost of :: ma!or bleeds.
Aspirin will prevent :A stro*es at the cost of A ma!or bleeds.
Primary care doctors worry that their patients tend to be older, sic*er and with more
comorbidities than research patients and thus at higher ris* of side#effects.
"ew oral anticoagulant drugs, eg dabigatran, are li*ely to become an option for moderate#
to high#ris* groups in the future and may replace warfarin.
Decisions for those with moderate ris* are obviously hardest # lac* of clear#cut evidence
means that the decision to use warfarin or aspirin in this group should be individual, based on
ris* of bleeding and personal preference. -leeding ris* with warfarin is higher where5
Age is over >= years.
There is concurrent treatment with non#steroidal anti#inflammatory drugs ("$A(Ds.
There is a past history of bleeding.
Polypharmacy.
8ncontrolled hypertension.
"(%, also recommends5
$tart antithrombotic treatment where indicated as soon as possible following diagnosis
of AD.
Treatment decisions should be made in the same way for paroxysmal AD.
+ecent research in AD suggests that patients who are unsuitable for anticoagulants may get
additional benefit if aspirin and clopidogrel are combined rather than using aspirin alone.
Pre#eclampsia is associated with excessive production of thromboxane so antiplatelet
agents have been proposed as possible therapy to prevent or delay the development of pre#
eclampsia. A %ochrane review02F2 found that antiplatelet agents (primarily low#dose aspirin
did indeed have small#to#moderate benefits in the prevention of pre#eclampsia but research
evidence is still re7uired as to which women are most li*ely to benefit, when to start
treatment, suitable dose, etc. Antiplatelet drugs are not licensed for this use.
Cautions and contra-indications
$ee individual drug profiles, but some general or important points5
All antiplatelet drugs can cause bleeding. Avoid in patients who are at a high ris* of
bleeding or where the conse7uences of bleeding would be severe # for example, active peptic
ulcer disease, uncontrolled hypertension.
4ypersensitivity and allergy. "(%, guidance suggests that true hypersensitivity to aspirin
(characterised by rash, urticaria and angio#oedema is rare.
Aspirin can cause bronchospasm and worsen pre#existing asthma. A systematic review
estimated the prevalence of aspirin#exacerbated asthma in adults with pre#existing asthma as
2: < (from oral provocation testing. Drom this, it suggests that approximately F.< of
asthmatics can ta*e aspirin safely but caution should be exercised. Always chec* about
previous experiences with aspirin and other "$A(Ds and warn to stop aspirin if their asthma
deteriorates. 4igh#ris* features for developing aspirin#induced asthma include severe asthma,
nasal polyps, urticaria and rhinitis.
4ypertension should be controlled (blood pressure (-P G:=.)9. mm 4g before
commencing treatment.
$ide#effects
$ee individual drugs. All antiplatelet drugs can cause gastrointestinal ('( disturbance and
bleeding # dipyridamole is the least ris*y (but is rarely used alone to the high ris* associated
with the 'P ((b)(((a antagonists.
Interactions
%hec* the individual drug. -e wary of co#prescribing with other drugs that increase ris* of
bleeding (ie warfarin and heparin, other antiplatelet drugs, corticosteroids, iloprost. Adding
clopidogrel to aspirin increases the antiplatelet effect but also increases the ris* of bleeding so
is only !ustified where the ris* is outweighed by the potential benefit.
Treatment issues
$creening, ris* assessment and communication
Appropriate identification of patients remains a challenge5
3any of the guidelines advocate case#finding of those at high %& ris* by screening.
Asymptomatic adults aged 1. years and over (younger where there is a family history of
premature cardiovascular disease (%&D should receive opportunistic comprehensive %&
ris* assessment using Hoint -ritish $ocieties/ (H-$ ris* prediction charts.
The $cottish (ntercollegiate 'uidelines "etwor* ($('" suggests five#yearly reviews of
the same groups.
-y the age of =., 9.< of the 8I population are at sufficient %& ris* to re7uire treatment
according to current guidelines, and normal symptom#free individuals become /patients/.
$creening ma*es sense from a population perspective where lives are undoubtedly saved
but, on an individual basis, a small reduction in %& ris* will lead to very little absolute
benefit with all the disadvantages of medicalising lives.
%ommunicating balances of ris* and benefit to individuals is demanding. ,ven where
figures derived from clinical trials can be applied straightforwardly to a patient/s case, it is
impossible to predict whether a particular individual will benefit, be harmed or receive no
effect either way from a particular treatment. $haring this uncertainty is very difficult.
4igh#ris* individuals for primary and secondary prevention should be identifiable from
disease registers. %&D prevention (including the use of antiplatelet drugs within a practice
can be audited against H-$/ standards.
The new 'eneral 3edical $ervices (n'3$ contract uses antiplatelet therapy as a 7uality
indicator in three domains (%4D 9, $T+EI, F and AD @ so it is particularly important to
consider treatment (where appropriate and record contra#indications or side#effects to meet
targets.
3edicine management
+outine monitoring of antiplatelet treatment for primary and secondary prevention is not
usually re7uired.
(t should be remembered that antiplatelet therapy reduces but does not eliminate the ris*
of %& events. ?here patients suffer a %& event whilst on antiplatelet medication, it should
not be assumed that they are /resistant/ to the drug/s antiplatelet effect or that a switch to
another agent would offer any greater protection. True resistance to the antiplatelet action of
aspirin or clopidogrel may occur in a small proportion of patients but there are no reliable
tests available currently to confirm this.0@=2 $ee* expert advice.
?hat dose of aspirinJ Antithrombotic Trialists/ %ollaboration (ATT% provided good
evidence that lower doses of aspirin (>=#:=. mg were no less effective than higher ones,
with a reduced rate of bleeding complications.0:=2 %ommon practice is to prescribe >= mg
daily for primary and secondary prevention of %&D, although a lot of cardiologists seem to
use :=. mg daily.
'( side#effects are common with aspirin5
Advise patients to report any abdominal pain, melaena or rectal bleeding urgently.
There is no evidence that enteric coating or dispersible formulations of aspirin lessen
the ris*.
,nsure that it is ta*en with food.
%o#prescription of symptomatic or preventative medication # for example,
maintenance dose protein pump inhibitor (PP( # should be used prior to switching to
clopidogrel where similar side#effects may occur.
'ood communication between primary and secondary care is important. Dor example5
,nsuring that where aspirin is given for acute coronary syndrome (A%$, it is
documented and passed on to paramedics)admitting team.
Discharge plans from %%8)stro*e unit should ma*e it clear, to primary care and to the
patient, what the long#term plan for medication is and, in particular, when to stop clopidogrel
or dipyridamole.
,nsure mechanisms for stopping clopidogrel and dipyridamole at the correct times
through regular medication reviews.
Auditing prescribing of clopidogrel and dipyridamole will help to ensure that their use
falls within the limited indications.
,lective surgery # stopping antiplatelet drugs
The usual advice is that aspirin should be stopped =#9 days prior to surgery0@A2 and
clopidogrel stopped seven days before to reduce the ris* of bleeding complications.
4owever, it has been suggested that stopping aspirin leads to a rapid loss of protection and
even rebound increased ris* of ischaemic event.
There also is the ris* that the drug may not be restarted.
This may ma*e us 7uestion the wisdom of stopping antiplatelet agents, in high#ris*
individuals, for minor surgical procedures, such as s*in or cataract surgery.
(n general, aspirin should be stopped where the ris* of postoperative bleeding is high (eg
during ma!or surgery or where the conse7uences of even minor bleeding are significant (eg
retinal and intracranial surgery.
---------------------------------------------------------------------------------------------------------------------------
-----------
abciximab (Reopro !"
Platelet aggregation inhibition5 (P%(5 ..2= mg)*g (& :.KA. minute prior to P%(, then ..:2=
mcg)*g)minute (3aximum :. mcg)min (& (nfusion x :2 hours.
The safety and efficacy of Abciximab have only been investigated with concomitant
administration of heparin and aspirin as described in %C("(%AC $T8D(,$. (n patients with
failed P%ls, the continuous infusion of Abciximab should be stopped because there is no
evidence for Abciximab efficacy in that setting. (n the event of serious bleeding that cannot
be controlled by compression, Abciximab and heparin should be discontinued immediately.
Dilter the bolus in!ection using a sterile, non#pyrogenic, low protein#binding ..2 or ..22 m m
filter (3illipore $C'&.2=C$ or e7uivalent.
Aggrenox (dipyridamole/A#A!"
I$DICA%IO$#5 A''+,"EL (aspirin)extended#release dipyridamole is indicated to
reduce the ris* of stro*e in patients who have had transient ischemia of the brain or
completed ischemic stro*e due to thrombosis.
DO#AG& A$D AD'I$I#%RA%IO$5 The recommended dose of A''+,"EL
(aspirin)extended#release dipyridamole is one capsule given orally twice daily, one in the
morning and one in the evening. The capsules should be swallowed whole without chewing.
A''+,"EL capsules may be administered with or without food.
A''+,"EL is not interchangeable with the individual components of aspirin and
PersantineM Tablets.
#upplied5 ,ach hard gelatin capsule contains 2.. mg dipyridamole in an extended#release
form and 2= mg aspirin, as an immediate#release sugar#coated tablet. 02.. mg )2= mg2
anagrelide (Agrylin !"
I$DICA%IO$#5 A'+NC(" %apsules are indicated for the treatment of patients with
thrombocythemia, secondary to myeloproliferative disorders, to reduce the elevated platelet
count and the ris* of thrombosis and to ameliorate associated symptoms including thrombo#
hemorrhagic events.
DO#AG& A$D AD'I$I#%RA%IO$5 Treatment with A'+NC(" %apsules should be
initiated under close medical supervision. The recommended starting dosage of A'+NC("
is .. = mg orally four times daily or : mg orally twice daily which should be maintained for
at least one wee*. Dosage should then be ad!usted to the lowest effective dosage re7uired to
reduce and maintain platelet count below A..,...)C, and ideally to the normal range. The
dosage should be increased by not more than ..= mg)day in any one wee*. Dosage should
not exceed :. mg)day or 2.= mg in a single dose.
#upplied5 0 ..= mg , : mg capsule2
cilosta(ol (Pletal !
'echanism o) Action5
The mechanism of the effects of cilostaOol tablets on the symptoms of intermittent
claudication is not fully understood. %ilostaOol tablets and several of its metabolites are
cyclic A3P (cA3P phosphodiesterase ((( inhibitors (PD, ((( inhibitors, inhibiting
phosphodiesterase activity and suppressing cA3P degradation with a resultant increase in
cA3P in platelets and blood vessels, leading to inhibition of platelet aggregation and
vasodilation, respectively.
%ilostaOol tablets reversibly inhibits platelet aggregation induced by a variety of stimuli,
including thrombin, ADP, collagen, arachidonic acid, epinephrine, and shear stress. ,ffects
on circulating plasma lipids have been examined in patients ta*ing cilostaOol tablets.
I$DICA%IO$# A$D *#AG&
%ilostaOol is indicated for the reduction of symptoms of intermittent claudication, as
indicated by an increased wal*ing distance.
CO$%RAI$DICA%IO$#
%ilostaOol and several of its metabolites are inhibitors of phosphodiesterase (((. $everal
drugs with this pharmacologic effect have caused decreased survival compared to placebo in
patients with class (((#(& congestive heart failure. %ilostaOol is contraindicated in patients
with congestive heart failure of any severity.
%ilostaOol is contraindicated in patients with haemostatic disorders or active pathologic
bleeding, such as bleeding peptic ulcer and intracranial bleeding. %ilostaOol inhibits platelet
aggregation in a reversible manner.
%ilostaOol is contraindicated in patients with *nown or suspected hypersensitivity to any of
its components.
Dosing (Adults!5 Peripheral vascular disease5 :.. mg orally twice daily ta*en at least @.
minutes before or 2 hours after brea*fast and dinner. Dosage should be reduced to =. mg
twice daily during concurrent therapy with inhibitors of %NP@A1 or %NP2%:9.
#upplied5 =. mg, :.. mg tablet.
clopidogrel (Pla+ix !"
I$DICA%IO$#" Plavix (clopidogrel bisulfate is indicated for the reduction of
atherothrombotic events as follows5
P +ecent 3(, +ecent $tro*e or ,stablished Peripheral Arterial Disease5 Dor patients with a
history of recent myocardial infarction (3(, recent stro*e, or established peripheral arterial
disease, Plavix has been shown to reduce the rate of a combined endpoint of new ischemic
stro*e (fatal or not, new 3( (fatal or not, and other vascular death.
P Acute %oronary $yndrome5 Dor patients with non#$T#segment elevation acute coronary
syndrome (unstable angina)non#Q#wave 3( including patients who are to be managed
medically and those who are to be managed with percutaneous coronary intervention (with
or without stent or %A-', Plavix has been shown to decrease the rate of a combined
endpoint of cardiovascular death, 3(, or stro*e as well as the rate of a combined endpoint of
cardiovascular death, 3(, stro*e, or refractory ischemia.
Dor patients with $T#segment elevation acute myocardial infarction, Plavix has been shown
to reduce the rate of death from any cause and the rate of a combined endpoint of death, re#
infarction or stro*e. This benefit is not *nown to pertain to patients who receive primary
angioplasty.
DO#AG& A$D AD'I$I#%RA%IO$"
Recent 'I, Recent #tro-e, or &stablished Peripheral Arterial Disease
The recommended daily dose of Plavix is >= mg once daily.
Acute Coronary #yndrome
Dor patients with non#$T#segment elevation acute coronary syndrome (unstable angina)non#
Q#wave 3(, Plavix should be initiated with a single @..#mg loading dose and then
continued at >= mg once daily. Aspirin (>= mg#@2= mg once daily should be initiated and
continued in combination with Plavix. (n %8+,, most patients with Acute %oronary
$yndrome also received heparin acutely.
Dor patients with $T#segment elevation acute myocardial infarction, the recommended dose
of Plavix is >= mg once daily, administered in combination with aspirin, with or without
thrombolytics. Plavix may be initiated with or without a loading dose (@.. mg was used in
%CA+(TN ## +eview %C("(%AC $T8D(,$.
Plavix can be administered with or without food.
"o dosage ad!ustment is necessary for elderly patients or patients with renal disease.
#upplied5 >= mg, @.. mg tablet.
dipyridamole (Persantine !"
I$DICA%IO$#" Dipyridamole is indicated as an ad!unct to coumarin anticoagulants in the
prevention of postoperative thromboembolic complications of cardiac valve replacement.
DO#AG& A$D AD'I$I#%RA%IO$"
Ad!unctive 8se in Prophylaxis of Thromboembolism after %ardiac &alve +eplacement
The recommended dose is >=#:.. mg four times daily as an ad!unct to the usual warfarin
therapy. Please note that aspirin is not to be administered concomitantly with coumarin
anticoagulants.
#upplied5 2= mg, =. mg and >= mg tablets.
epti)abatide (Integrilin !"
AD'I$I#%RA%IO$"
Administration5 .olus5 withdraw dose from :.ml vial and give by (& push over :#2
minutes. Continuous in)usion5 administer calculated rate directly from :..ml vial.
Properties5 Enset5 within : hr. T:)2 R 2.= hours. Platelet fcn restored in S 1hours after
discontinuation. 0#upplied5 ..>= mg)ml (:..ml vial. 2. mg):. ml vial.2
DO#AG&
Acute Coronary #yndrome5 The recommended adult dosage of eptifibatide in patients with
acute coronary syndrome and normal renal function is an intravenous bolus of :F. Tg)*g
(maximum5 22.A mg over :#2 minutes as soon as possible following diagnosis, followed by
a continuous infusion of 2.. Tg)*g)min (maximum5 := mg)hour until hospital discharge or
initiation of %A-' surgery, up to >2 hours. (f a patient is to undergo a percutaneous
coronary intervention (P%( while receiving eptifibatide, the infusion should be continued up
to hospital discharge, or for up to :F#21 hours after the procedure, whichever comes first,
allowing for up to 9A hours of therapy. %oncurrent aspirin (:A.#@2= mg initially and daily
thereafter and heparin therapy (target aPTT =.#>. seconds are recommended.
Dosing ad/ustment in renal impairment5 Patients with %+%C less than =. ml)min5 The
recommended adult dosage of eptifibatide in patients with acute coronary syndrome with an
estimated %+%C G=. ml)min (using the %oc*croft#'ault e7uation is an (& bolus of :F.
Tg)*g (maximum5 22.A mg as soon as possible following diagnosis, immediately followed
by a continuous infusion of :.. Tg)*g)min (maximum5 >.= mg)hour.
Percutaneous Coronary Inter+ention (PCI!5 The recommended adult dosage of
eptifibatide in patients with normal renal function is an intravenous bolus of :F. Tg)*g
(maximum5 22.A mg over :#2 minutes administered immediately before the initiation of P%(
followed by a continuous infusion of 2.. Tg)*g)min (maximum5 := mg)hour and a second
:F. Tg)*g bolus (maximum5 22.A mg :. minutes after the first bolus. (nfusion should be
continued until hospital discharge, or for up to :F to 21 hours, whichever comes first. A
minimum of :2 hours of infusion is recommended. %oncurrent aspirin (:A.#@2= mg :#21
hours before P%( and daily thereafter and heparin therapy (A%T 2..#@.. seconds during
P%( are recommended. 4eparin infusion after P%( is discouraged.
Dosing ad/ustment in renal impairment5 Patients with %+%C less than =. mC)min5 The
recommended adult dose of eptifibatide in patients with an estimated %+%C G =. ml)min
(using the %oc*croft#'ault e7uation is an (& bolus of :F. Tg)*g (maximum5 22.A mg
administered immediately before the initiation of the procedure, immediately followed by a
continuous infusion of :.. Tg)*g)min (maximum5 >.= mg)hour and a second :F. Tg)*g
bolus (maximum5 22.A mg administered :. minutes after the first. (n patients who undergo
coronary artery bypass graft surgery, eptifibatide infusion should be discontinued prior to
surgery.
*se the Coc-cro)t-Gault e0uation 1ith actual body 1eight to calculate CRC25
3ales5
0(:1. K age x (actual body wt in *g 2
########################################
>2 x (serum creatinine
Demales5
0(:1. K age x (actual body wt in *g x (..F=2
##############################################
>2 x (serum creatinine
prasugrel - &33I&$%4
I$DICA%IO$# A$D *#AG&
Acute Coronary #yndrome
,ffientU is indicated to reduce the rate of thrombotic cardiovascular (%& events (including
stent thrombosis in patients with acute coronary syndrome (A%$ who are to be managed
with percutaneous coronary intervention (P%( as follows5
##Patients with unstable angina (8A or non#$T#elevation myocardial infarction ("$T,3(.
##Patients with $T#elevation myocardial infarction ($T,3( when managed with primary or
delayed P%(.
,ffient has been shown to reduce the rate of a combined endpoint of cardiovascular death,
nonfatal myocardial infarction (3(, or nonfatal stro*e compared to clopidogrel. The
difference between treatments was driven predominantly by 3(, with no difference on
stro*es and little difference on %& death 0see %linical $tudies (:1 # pac*age insert2.
(t is generally recommended that antiplatelet therapy be administered promptly in the
management of A%$ because many cardiovascular events occur within hours of initial
presentation. (n the clinical trial that established the efficacy of ,ffient, ,ffient and the
control drug were not administered to 8A)"$T,3( patients until coronary anatomy was
established. Dor the small fraction of patients that re7uired urgent %A-' after treatment with
,ffient, the ris* of significant bleeding was substantial 0see ?arnings and Precautions (=.22.
-ecause the large ma!ority of patients are managed without %A-', however, treatment can
be considered before determining coronary anatomy if need for %A-' is considered
unli*ely. The advantages of earlier treatment with ,ffient must then be balanced against the
increased rate of bleeding in patients who do need to undergo urgent %A-'.
DO#AG& A$D AD'I$I#%RA%IO$
(nitiate ,ffient treatment as a single A. mg oral loading dose and then continue at :. mg
orally once daily. Patients ta*ing ,ffient should also ta*e aspirin (>= mg to @2= mg daily.
,ffient may be administered with or without food2.
Dosing in Cow ?eight Patients
%ompared to patients weighing A. *g, patients weighing G A. *g have an increased
exposure to the active metabolite of prasugrel and an increased ris* of bleeding on a :. mg
once daily maintenance dose. %onsider lowering the maintenance dose to = mg in patients G
A. *g. The effectiveness and safety of the = mg dose have not been prospectively studied.
5O6 #*PP2I&D
,ffient (prasugrel = mg is supplied as a yellow, elongated hexagonal, film#coated, non#
scored tablet debossed with V= 3'V on one side and with V1>A.V on the other side.
= mg tablets are supplied as follows5
-ottles of > # "D% ...2#1>A.#>A
-ottles of @. # "D% ...2#1>A.#@.
,ffient (prasugrel :. mg is supplied as a beige, elongated hexagonal, film#coated, non#
scored tablet debossed with V:. 3'V on one side and V1>=9V on the other side.
:. mg tablets are supplied as follows5
-ottles of @. K "D% ...2#1>=9#@.
-listers (D 9.P "D% ...2#1>=9#>>
ticagrelor -.RI2I$%A4
D&#CRIP%IO$
4('4C('4T$ ED P+,$%+(-("' ("DE+3AT(E"
These highlights do not include all the information needed to use -+(C("TA safely and
effectively. $ee full prescribing information for -+(C("TA.
-+(C("TAU (ticagrelor tablets, for oral use
(nitial 8.$. Approval5 2.::
-+(C("TA contains ticagrelor, a cyclopentyltriaOolopyrimidine, inhibitor of platelet
activation and aggregation mediated by the P2N:2 ADP#receptor.
I$DICA%IO$# A$D *#AG&
Acute Coronary #yndromes
-+(C("TA is a P2N:2 platelet inhibitor indicated to reduce the rate of thrombotic
cardiovascular events in patients with acute coronary syndrome (A%$ (unstable angina,
non#$T elevation myocardial infarction, or $T elevation myocardial infarction. -+(C("TA
has been shown to reduce the rate of a combined endpoint of cardiovascular death,
myocardial infarction or stro*e compared to clopidogrel. The difference between treatments
was driven by %& death and 3( with no difference in stro*e. (n patients treated with P%(, it
also reduces the rate of stent thrombosis.
-+(C("TA has been studied in A%$ in combination with aspirin. 3aintenance doses of
aspirin above :.. mg decreased the effectiveness of -+(C("TA. Avoid maintenance doses
of aspirin above :.. mg daily
DO#AG& A$D AD'I$I#%RA%IO$
(nitiate -+(C("TA treatment with a :F. mg (two 9. mg tablets loading dose and continue
treatment with 9. mg twice daily.
After the initial loading dose of aspirin (usually @2= mg, use -+(C("TA with a daily
maintenance dose of aspirin of >=#:.. mg.
A%$ patients who have received a loading dose of clopidogrel may be started on
-+(C("TA.
-+(C("TA can be administered with or without food.
A patient who misses a dose of -+(C("TA should ta*e one 9. mg tablet (their next dose at
its scheduled time.
5O6 #*PP2I&D
-+(C("TA (ticagrelor 9. mg is supplied as a round, biconvex, yellow, film#coated tablet
mar*ed with a W9.X above WTX on one side.
-ottles of A. K "D% .:FA#.>>>#A.
-ottles of :F. K "D% .:FA#.>>>#:F
:.. count 4ospital 8nit Dose K "D% .:FA#.>>>#@9
ticlopidine (%iclid !"
I$DICA%IO$#5
##To reduce the ris* of thrombotic stro*e (fatal or nonfatal in patients who have experienced
stro*e precursors, and in patients who have had a completed thrombotic stro*e. -ecause
T(%C(D is associated with a ris* of life#threatening blood dyscrasias including thrombotic
thrombocytopenic purpura (TTP, neutropenia)agranulocytosis and aplastic anemia, T(%C(D
should be reserved for patients who are intolerant or allergic to aspirin therapy or who have
failed aspirin therapy.
##As ad!unctive therapy with aspirin to reduce the incidence of subacute stent thrombosis in
patients undergoing successful coronary stent implantation.
DO#AG& A$D AD'I$I#%RA%IO$"
#tro-e5 The recommended dose of T(%C(D is 2=. mg bid ta*en with food. Ether doses have
not been studied in controlled trials for these indications.
Coronary Artery #tenting5 The recommended dose of T(%C(D is 2=. mg bid ta*en with
food together with antiplatelet doses of aspirin for up to @. days of therapy following
successful stent implantation.
#upplied5 2=. mg tablet.
tiro)iban (Aggrastat !"
Dosing5 ..1 mcg)*g)min for @. minutes, followed by ..: mcg)*g)min. Therapy should
continue through angiography and for :2#21 hours after angioplasty or atherectomy.
Dosing ad/ustment in renal impairment5
("ote5 +educe dose by =.< if %+%C G @. ml)min # ..2 mcg)*g)min x @. min, followed by
...= mcg)*g)min.
Preparation5 Add :2.= mg (=. ml to 2..ml "$ or D=?. Total volumeR 2=.ml.
%oncentrationR =. mcg)ml. Er add 2= mg (:..ml to 1.. ml D=? or "$.
#upplied5 2=. mcg)ml#=. ml vial (:2.= mg)=.ml.