CLOPIDOGREL ROWEX

Main information

  • Trade name:
  • CLOPIDOGREL ROWEX
  • Dosage:
  • 75 Base Milligrams
  • Pharmaceutical form:
  • Film Coated Tablet
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug

Documents

Localization

  • Available in:
  • CLOPIDOGREL ROWEX
    Ireland
  • Language:
  • English

Status

  • Source:
  • HPRA - Health Products Regulatory Authority - Ireland
  • Authorization number:
  • PA0711/167/001
  • Authorization date:
  • 09-10-2009
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

ClopidogrelRowex75mgfilm-coatedtablets

2QUALITATIVEANDQUANTITATIVECOMPOSITION

Eachfilm-coatedtabletcontains75mgofclopidogrel(asbesilate).

Excipient:eachtabletcontains3.8mghydrogenatedcastoroil.

Forafulllistofexcipients,seesection6.1.

3PHARMACEUTICALFORM

Film-coatedtablet.

Whitetooff-white,marbled,roundandbiconvex.

4CLINICALPARTICULARS

4.1TherapeuticIndications

Clopidogrelisindicatedinadultsforthepreventionofatherothromboticeventsin:

Patientssufferingfrommyocardialinfarction(fromafewdaysuntillessthan35days),ischaemicstroke(from7

daysuntillessthan6months)orestablishedperipheralarterialdisease.

Forfurtherinformationpleaserefertosection5.1.

4.2Posologyandmethodofadministration

Adultsandelderly

Clopidogrelshouldbegivenasasingledailydoseof75mgwithorwithoutfood.

Paediatricpatients

Thesafetyandefficacyofclopidogrelinchildrenandadolescentshavenotyetbeenestablished.

Renalimpairment

Therapeuticexperienceislimitedinpatientswithrenalimpairment(seesection4.4).

Hepaticimpairment

Therapeuticexperienceislimitedinpatientswithmoderatehepaticdiseasewhomayhavebleedingdiatheses(see

section4.4).

4.3Contraindications

Hypersensitivitytotheactivesubstanceortoanyoftheexcipients.

Severeliverimpairment.

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4.4Specialwarningsandprecautionsforuse

Duetotheriskofbleedingandhaematologicalundesirableeffects,bloodcellcountdeterminationand/orother

appropriatetestingshouldbepromptlyconsideredwheneverclinicalsymptomssuggestiveofbleedingariseduringthe

courseoftreatment(seesection4.8).Aswithotherantiplateletagents,clopidogrelshouldbeusedwithcautionin

patientswhomaybeatriskofincreasedbleedingfromtrauma,surgeryorotherpathologicalconditionsandinpatients

receivingtreatmentwithASA,heparin,glycoproteinIIb/IIIainhibitorsornon-steroidalanti-inflammatorydrugs

includingCox-2inhibitors.Patientsshouldbefollowedcarefullyforanysignsofbleedingincludingoccultbleeding,

especiallyduringthefirstweeksoftreatmentand/orafterinvasivecardiacproceduresorsurgery.Theconcomitant

administrationofclopidogrelwithoralanticoagulantsisnotrecommendedsinceitmayincreasetheintensityof

bleedings(seesection4.5).

Ifapatientistoundergoelectivesurgeryandantiplateleteffectistemporarilynotdesirable,clopidogrelshouldbe

discontinued7dayspriortosurgery.Patientsshouldinformphysiciansanddentiststhattheyaretakingclopidogrel

beforeanysurgeryisscheduledandbeforeanynewmedicinalproductistaken.

Clopidogrelprolongsbleedingtimeandshouldbeusedwithcautioninpatientswhohavelesionswithapropensityto

bleed(particularlygastrointestinalandintraocular).

Patientsshouldbetoldthatitmighttakelongerthanusualtostopbleedingwhentheytakeclopidogrelandthatthey

shouldreportanyunusualbleeding(siteorduration)totheirphysician.

ThromboticThrombocytopenicPurpura(TTP)hasbeenreportedveryrarelyfollowingtheuseofclopidogrel,

sometimesafterashortexposure.Itischaracterisedbythrombocytopeniaandmicroangiopathichaemolyticanaemia

associatedwitheitherneurologicalfindings,renaldysfunctionorfever.TTPisapotentiallyfatalconditionrequiring

prompttreatmentincludingplasmapheresis.

Inviewofthelackofdata,clopidogrelcannotberecommendedduringthefirst7daysafteracuteischaemicstroke.

Pharmacogenetics:Basedonliteraturedata,patientswithgeneticallyreducedCYP2C19functionhavelowersystemic

exposuretotheactivemetaboliteofclopidogrelanddiminishedantiplateletresponses,andgenerallyexhibithigher

cardiovasculareventratesfollowingmyocardialinfarctionthandopatientswithnormalCYP2C19function(seesection

5.2).

SinceclopidogrelismetabolisedtoitsactivemetabolitepartlybyCYP2C19,useofdrugsthatinhibittheactivityof

thisenzymewouldbeexpectedtoresultinreduceddruglevelsoftheactivemetaboliteofclopidogrelandareduction

inclinicalefficacy.ConcomitantuseofdrugsthatinhibitCYP2C19shouldbediscouraged(seesection4.5foralistof

CYP2C19inhibitors,seealsosection5.2).AlthoughtheevidenceofCYP2C19inhibitionvarieswithintheclassof

ProtonPumpInhibitors,clinicaloutcomestudiessuggestaninteractionbetweenclopidogrelandpossiblyallmembers

ofthisclass.Therefore,concomitantuseofProtonPumpInhibitorsshouldbeavoidedunlessabsolutelynecessary.

Therapeuticexperiencewithclopidogrelislimitedinpatientswithrenalimpairment.Thereforeclopidogrelshouldbe

usedwithcautioninthesepatients(seesection4.2).

Experienceislimitedinpatientswithmoderatehepaticdiseasewhomayhavebleedingdiatheses.Clopidogrelshould

thereforebeusedwithcautioninthispopulation(seesection4.2).

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4.5Interactionwithothermedicinalproductsandotherformsofinteraction

Oralanticoagulants:theconcomitantadministrationofclopidogrelwithoralanticoagulantsisnotrecommendedsince

itmayincreasetheintensityofbleedings(seesection4.4).

GlycoproteinIIb/IIIainhibitors:clopidogrelshouldbeusedwithcautioninpatientswhomaybeatriskofincreased

bleedingfromtrauma,surgeryorotherpathologicalconditionsthatreceiveconcomitantglycoproteinIIb/IIIainhibitors

(seesection4.4).

Acetylsalicylicacid(ASA):ASAdidnotmodifytheclopidogrel-mediatedinhibitionofADP-inducedplatelet

aggregation,butclopidogrelpotentiatedtheeffectofASAoncollagen-inducedplateletaggregation.However,

concomitantadministrationof500mgofASAtwiceadayforonedaydidnotsignificantlyincreasetheprolongation

ofbleedingtimeinducedbyclopidogrelintake.Apharmacodynamicinteractionbetweenclopidogreland

acetylsalicylicacidispossible,leadingtoincreasedriskofbleeding.Therefore,concomitantuseshouldbeundertaken

withcaution(seesection4.4).

Heparin:inaclinicalstudyconductedinhealthysubjects,clopidogreldidnotnecessitatemodificationoftheheparin

doseoraltertheeffectofheparinoncoagulation.Co-administrationofheparinhadnoeffectontheinhibitionof

plateletaggregationinducedbyclopidogrel.Apharmacodynamicinteractionbetweenclopidogrelandheparinis

possible,leadingtoincreasedriskofbleeding.Therefore,concomitantuseshouldbeundertakenwithcaution(see

section4.4).

Thrombolytics:thesafetyoftheconcomitantadministrationofclopidogrel,fibrinornon-fibrinspecificthrombolytic

agentsandheparinswasassessedinpatientswithacutemyocardialinfarction.Theincidenceofclinicallysignificant

bleedingwassimilartothatobservedwhenthrombolyticagentsandheparinareco-administeredwithASA(seesection

4.8)

Non-SteroidalAnti-InflammatoryDrugs(NSAIDs):inaclinicalstudyconductedinhealthyvolunteers,the

concomitantadministrationofclopidogrelandnaproxenincreasedoccultgastrointestinalbloodloss.However,dueto

thelackofinteractionstudieswithotherNSAIDsitispresentlyunclearwhetherthereisanincreasedriskof

gastrointestinalbleedingwithallNSAIDs.Consequently,NSAIDsincludingCox-2inhibitorsandclopidogrelshould

beco-administeredwithcaution(seesection4.4).

Otherconcomitanttherapy:

SinceclopidogrelismetabolisedtoitsactivemetabolitepartlybyCYP2C19,useofdrugsthatinhibittheactivityof

thisenzymewouldbeexpectedtoresultinreduceddruglevelsoftheactivemetaboliteofclopidogrelandareduction

inclinicalefficacy.ConcomitantuseofdrugsthatinhibitCYP2C19shouldbediscouraged(seesection4.4and5.2).

DrugsthatinhibitCYP2C19includeomeprazoleandesomeprazole,fluvoxamine,fluoxetine,moclobemide,

voriconazol,fluconazol,ticlopidine,ciprofloxacin,cimetidine,carbamazepine,oxcarbazepineandchloramphenicol.

ProtonPumpInhibitors

AlthoughtheevidenceofCYP2C19inhibitionvarieswithintheclassofProtonPumpInhibitors,clinicaloutcome

studiessuggestaninteractionbetweenclopidogrelandpossiblyallmembersofthisclass.Therefore,concomitantuse

ofProtonPumpInhibitorsshouldbeavoidedunlessabsolutelynecessary.

Anumberofotherclinicalstudieshavebeenconductedwithclopidogrelandotherconcomitantmedicinalproductsto

investigatethepotentialforpharmacodynamicandpharmacokineticinteractions.Noclinicallysignificant

pharmacodynamicinteractionswereobservedwhenclopidogrelwasco-administeredwithatenolol,nifedipine,orboth

atenololandnifedipine.Furthermore,thepharmacodynamicactivityofclopidogrelwasnotsignificantlyinfluencedby

thecoadministrationofphenobarbital,cimetidine,oroestrogen.

Thepharmacokineticsofdigoxinortheophyllinewerenotmodifiedbytheco-administrationofclopidogrel.Antacids

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Datafromstudieswithhumanlivermicrosomesindicatedthatthecarboxylicacidmetaboliteofclopidogrelcould

inhibittheactivityofCytochromeP4502C9.Thiscouldpotentiallyleadtoincreasedplasmalevelsofmedicinal

productssuchasphenytoinandtolbutamideandtheNSAIDs,whicharemetabolisedbyCytochromeP4502C9.Data

fromtheCAPRIEstudyindicatethatphenytoinandtolbutamidecanbesafelyco-administeredwithclopidogrel.

Apartfromthespecificmedicinalproductinteractioninformationdescribedabove,interactionstudieswithclopidogrel

andsomemedicinalproductscommonlyadministeredinpatientswithatherothromboticdiseasehavenotbeen

performed.However,patientsenteredintoclinicaltrialswithclopidogrelreceivedavarietyofconcomitantmedicinal

productsincludingdiuretics,betablockers,ACEI,calciumantagonists,cholesterolloweringagents,coronary

vasodilators,antidiabeticagents(includinginsulin),antiepilepticagentsandGPIIb/IIIaantagonistswithoutevidenceof

clinicallysignificantadverseinteractions.

4.6Pregnancyandlactation

Asnoclinicaldataonexposuretoclopidogrelduringpregnancyareavailable,itispreferablenottouseclopidogrel

duringpregnancyasaprecautionarymeasure.

Animalstudiesdonotindicatedirectorindirectharmfuleffectswithrespecttopregnancy,embryonal/foetal

development,parturitionorpostnataldevelopment(seesection5.3).

Itisunknownwhetherclopidogrelisexcretedinhumanbreastmilk.Animalstudieshaveshownexcretionof

clopidogrelinbreastmilk.Asaprecautionarymeasure,breast-feedingshouldnotbecontinuedduringtreatmentwith

ClopidogrelRowex.

4.7Effectsonabilitytodriveandusemachines

Clopidogrelhasnoornegligibleinfluenceontheabilitytodriveandusemachines.

4.8Undesirableeffects

Clopidogrelhasbeenevaluatedforsafetyfor1yearormore.Theclinicallyrelevantadversereactionsobservedinthe

CAPRIEstudiesarediscussedbelow.Overall,clopidogrel75mg/daywascomparabletoASA325mg/dayinCAPRIE

regardlessofage,genderandrace.Inadditiontoclinicalstudiesexperience,adversereactionshavebeenspontaneously

reported.

Bleedingisthemostcommonreactionreportedbothinclinicalstudiesaswellasinpost-marketingexperiencewhereit

wasmostlyreportedduringthefirstmonthoftreatment.

InCAPRIE,inpatientstreatedwitheitherclopidogrelorASA,theoverallincidenceofanybleedingwas9.3%.The

incidenceofseverecaseswas1.4%forclopidogreland1.6%forASA.

Adversereactionsthatoccurredeitherduringclinicalstudiesorthatwerespontaneouslyreportedarepresentedinthe

tablebelow.Theirfrequencyisdefinedusingthefollowingconventions:common( ≥1/100to<1/10);uncommon(≥

1/1,000to<1/100);rare( ≥1/10,000to<1/1,000);veryrare(<1/10,000).Withineachsystemorganclass,adversedrug

reactionsarepresentedinorderofdecreasingseriousness.

SystemOrgan

Class Common Uncommon Rare VeryRare

Bloodandthe

lymphatic

system

disorders Thrombocytopenia,

leucopenia,

eosinophilia Neutropenia,

including

severe

neutropenia Thrombotic

thrombocytopenic

purpura(TTP)(see

section4.4),

aplasticanaemia,

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agranulocytosis,

severe

thrombocytopenia,

granulocytopenia,

anaemia

Immunesystem

disorders Serumsickness,

Anaphylactoid

reactions

Psychiatric

disorders Hallucinations,

confusion

Nervoussystem

disorders Intracranial

bleeding(some

caseswere

reportedwithfatal

outcome),

headache,

paraesthesia,

dizziness Tastedisturbances

Eyedisorders Eyebleeding

(conjunctival,

ocular,retinal)

Earand

labyrinth

disorders Vertigo

Vascular

disorders Haematoma Serious

haemorrhage,

haemorrhageof

operativewound,

vasculitis,

hypotension

Respiratory,

thoracicand

mediastinal

disorders Epistaxis Respiratorytract

bleeding

(haemoptysis,

pulmonary

haemorrhage),

bronchospasm,

interstitial

pneumonitis

Gastrointestinal

disorders Gastrointestinal

haemorrhage,

diarrhoea,

abdominal

pain,dyspepsia Gastriculcerand

duodenalulcer,

gastritis,vomiting,

nausea,

constipation,

flatulence Retroperitoneal

haemorrhage Gastrointestinaland

retroperitoneal

haemorrhagewith

fataloutcome,

pancreatitis,colitis

(including

ulcerativeor

lymphocytic

colitis),stomatitis

Hepato-biliary

disorders Acuteliverfailure,

hepatitis,abnormal

liverfunctiontest

Skinand

subcutaneous

tissuedisorders Bruising Rash,pruritus,skin

bleeding(purpura) Bullousdermatitis

(toxicepidermal

necrolysis,Stevens

JohnsonSyndrome,

erythema

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4.9Overdose

Overdosefollowingclopidogreladministrationmayleadtoprolongedbleedingtimeandsubsequentbleeding

complications.Appropriatetherapyshouldbeconsideredifbleedingsareobserved.Noantidotetothepharmacological

activityofclopidogrelhasbeenfound.Ifpromptcorrectionofprolongedbleedingtimeisrequired,platelettransfusion

mayreversetheeffectsofclopidogrel.

5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

Pharmacotherapeuticgroup:plateletaggregationinhibitorsexcl.heparin,ATCCode:B01AC04.

Clopidogrelselectivelyinhibitsthebindingofadenosinediphosphate(ADP)toitsplateletreceptor,andthesubsequent

ADP-mediatedactivationoftheGPIIb/IIIacomplex,therebyinhibitingplateletaggregation.Biotransformationof

clopidogrelisnecessarytoproduceinhibitionofplateletaggregation.Clopidogrelalsoinhibitsplateletaggregation

inducedbyotheragonistsbyblockingtheamplificationofplateletactivationbyreleasedADP.Clopidogrelactsby

irreversiblymodifyingtheplateletADPreceptor.Consequently,plateletsexposedtoclopidogrelareaffectedforthe

remainderoftheirlifespanandrecoveryofnormalplateletfunctionoccursatarateconsistentwithplateletturnover.

Repeateddosesof75mgperdayproducedsubstantialinhibitionofADP-inducedplateletaggregationfromthefirst

day;thisincreasedprogressivelyandreachedsteadystatebetweenDay3andDay7.Atsteadystate,theaverage

inhibitionlevelobservedwithadoseof75mgperdaywasbetween40%and60%.Plateletaggregationandbleeding

timegraduallyreturnedtobaselinevalues,generallywithin5daysaftertreatmentwasdiscontinued.

Recentmyocardialinfarction(MI),recentstrokeorestablishedperipheralarterialdisease

TheCAPRIEstudyincluded19,185patientswithatherothrombosisasmanifestedbyrecentmyocardialinfarction(<35

days),recentischaemicstroke(between7daysand6months)orestablishedperipheralarterialdisease(PAD).Patients

wererandomisedtoclopidogrel75mg/dayorASA325mg/day,andwerefollowedfor1to3years.Inthemyocardial

angioedema,rash

erythematous,

urticaria,eczema,

lichenplanus

Musculoskeletal

connective

tissueandbone

disorders Musculo-skeletal

bleeding

(haemarthrosis),

arthritis,arthralgia,

myalgia

Renaland

urinary

disorders Haematuria Glomerulonephritis,

bloodcreatinine

increased

General

disordersand

administration

siteconditions Bleedingat

puncturesite Fever

Investigations Bleedingtime

prolonged,

neutrophilcount

decreased,platelet

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Clopidogrelsignificantlyreducedtheincidenceofnewischaemicevents(combinedendpointofmyocardialinfarction,

ischaemicstrokeandvasculardeath)whencomparedtoASA.Intheintentiontotreatanalysis,939eventswere

observedintheclopidogrelgroupand1,020eventswithASA(relativeriskreduction(RRR)8.7%,[95%CI:0.2to

16.4];p=0.045),whichcorresponds,forevery1000patientstreatedfor2years,to10[CI:0to20]additionalpatients

beingpreventedfromexperiencinganewischaemicevent.Analysisoftotalmortalityasasecondaryendpointdidnot

showanysignificantdifferencebetweenclopidogrel(5.8%)andASA(6.0%).

Inasubgroupanalysisbyqualifyingcondition(myocardialinfarction,ischaemicstroke,andPAD)thebenefitappeared

tobestrongest(achievingstatisticalsignificanceatp=0.003)inpatientsenrolledduetoPAD(especiallythosewho

alsohadahistoryofmyocardialinfarction)(RRR=23.7%;CI:8.9to36.2)andweaker(notsignificantlydifferent

fromASA)instrokepatients(RRR=7.3%;CI:-5.7to18.7[p=0.258]).Inpatientswhowereenrolledinthetrialon

thesolebasisofarecentmyocardialinfarction,clopidogrelwasnumericallyinferior,butnotstatisticallydifferentfrom

ASA(RRR=-4.0%;CI:-22.5to11.7[p=0.639]).

Inaddition,asubgroupanalysisbyagesuggestedthatthebenefitofclopidogrelinpatientsover75yearswaslessthan

thatobservedinpatients ≤75years.

SincetheCAPRIEtrialwasnotpoweredtoevaluateefficacyofindividualsubgroups,itisnotclearwhetherthe

differencesinrelativeriskreductionacrossqualifyingconditionsarereal,oraresultofchance.

5.2Pharmacokineticproperties

Afterrepeatedoraldosesof75mgperday,clopidogrelisrapidlyabsorbed.However,plasmaconcentrationsofthe

parentcompoundareverylowandbelowthequantificationlimit(0.00025mg/l)beyond2hours.Absorptionisatleast

50%,basedonurinaryexcretionofclopidogrelmetabolites.

Clopidogrelisextensivelymetabolisedbytheliverandthemainmetabolite,whichisinactive,isthecarboxylicacid

derivative,whichrepresentsabout85%ofthecirculatingcompoundinplasma.Peakplasmalevelsofthismetabolite

(approx.3mg/lafterrepeated75mgoraldoses)occurredapproximately1hourafterdosing.

Clopidogrelisaprodrug.Theactivemetabolite,athiolderivative,isformedbyoxidationofclopidogrelto2-oxo-

clopidogrelandsubsequenthydrolysis.TheoxidativestepisregulatedprimarilybyCytochromeP450isoenzymes2B6

and3A4andtoalesserextentby1A1,1A2and2C19.Theactivethiolmetabolite,whichhasbeenisolatedinvitro,

bindsrapidlyandirreversiblytoplateletreceptors,thusinhibitingplateletaggregation.Thismetabolitehasnotbeen

detectedinplasma.

Thekineticsofthemaincirculatingmetabolitewerelinear(plasmaconcentrationsincreasedinproportiontodose)in

thedoserangeof50to150mgofclopidogrel.

Clopidogrelandthemaincirculatingmetabolitebindreversiblyinvitrotohumanplasmaproteins(98%and94%

respectively).Thebindingisnon-saturableinvitrooverawideconcentrationrange.

Followinganoraldoseof 14

C-labelledclopidogrelinman,approximately50%wasexcretedintheurineand

approximately46%inthefaecesinthe120-hourintervalafterdosing.Theeliminationhalflifeofthemaincirculating

metabolitewas8hoursaftersingleandrepeatedadministration.

Afterrepeateddosesof75mgclopidogrelperday,plasmalevelsofthemaincirculatingmetabolitewerelowerin

subjectswithsevererenaldisease(creatinineclearancefrom5to15ml/min)comparedtosubjectswithmoderaterenal

disease(creatinineclearancefrom30to60ml/min)andtolevelsobservedinotherstudieswithhealthysubjects.

AlthoughinhibitionofADP-inducedplateletaggregationwaslower(25%)thanthatobservedinhealthysubjects,the

prolongationofbleedingwassimilartothatseeninhealthysubjectsreceiving75mgofclopidogrelperday.In

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Thepharmacokineticsandpharmacodynamicsofclopidogrelwereassessedinasingleandmultipledosestudyinboth

healthysubjectsandthosewithcirrhosis(Child-PughclassAorB).Dailydosingfor10dayswithclopidogrel75

mg/daywassafeandwelltolerated.ClopidogrelC

forbothsingledoseandsteadystateforcirrhoticswasmany

foldhigherthaninnormalsubjects.However,plasmalevelsofthemaincirculatingmetabolitetogetherwiththeeffect

ofclopidogrelonADP-inducedplateletaggregationandbleedingtimewerecomparablebetweenthesegroups.

5.3Preclinicalsafetydata

Duringnonclinicalstudiesinratandbaboon,themostfrequentlyobservedeffectswereliverchanges.Theseoccurred

atdosesrepresentingatleast25timestheexposureseeninhumansreceivingtheclinicaldoseof75mg/dayandwerea

consequenceofaneffectonhepaticmetabolisingenzymes.Noeffectonhepaticmetabolisingenzymeswasobservedin

humansreceivingclopidogrelatthetherapeuticdose.

Atveryhighdoses,apoorgastrictolerability(gastritis,gastricerosionsand/orvomiting)ofclopidogrelwasalso

reportedinratandbaboon.

Therewasnoevidenceofcarcinogeniceffectwhenclopidogrelwasadministeredfor78weekstomiceand104weeks

toratswhengivenatdosesupto77mg/kgperday(representingatleast25timestheexposureseeninhumans

receivingtheclinicaldoseof75mg/day).

Clopidogrelhasbeentestedinarangeofinvitroandinvivogenotoxicitystudies,andshowednogenotoxicactivity.

Clopidogrelwasfoundtohavenoeffectonthefertilityofmaleandfemaleratsandwasnotteratogenicineitherratsor

rabbits.Whengiventolactatingrats,clopidogrelcausedaslightdelayinthedevelopmentoftheoffspring.Specific

pharmacokineticstudiesperformedwithradiolabelledclopidogrelhaveshownthattheparentcompoundorits

metabolitesareexcretedinthemilk.Consequently,adirecteffect(slighttoxicity),oranindirecteffect(low

palatability)cannotbeexcluded.

6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

Tabletcore

Macrogol6000

Cellulose,microcrystalline

CrospovidonetypeA

Castoroil,hydrogenated

Tabletcoating

Ethylcellulose

Macrogol6000

Titaniumdioxide(E171)

6.2Incompatibilities

Notapplicable

6.3ShelfLife

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6.4Specialprecautionsforstorage

Storeintheoriginalpackageinordertoprotectfrommoisture.

6.5Natureandcontentsofcontainer

50x1,7,10,14,28,30,50,56,84,90,98and100film-coatedtabletspackedinaluminium/aluminiumblisters

Notallpacksizesmaybemarketed.

6.6Specialprecautionsfordisposal

Nospecialrequirements

7MARKETINGAUTHORISATIONHOLDER

RowexLtd

Bantry

Co.Cork

Ireland

8MARKETINGAUTHORISATIONNUMBER

PA711/167/1

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

Dateoffirstauthorisation:9thOctober2009

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