ASACARD

Main information

  • Trade name:
  • ASACARD Capsule 162.5 Milligram
  • Dosage:
  • 162.5 Milligram
  • Pharmaceutical form:
  • Capsule
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug

Documents

Localization

  • Available in:
  • ASACARD Capsule 162.5 Milligram
    Ireland
  • Language:
  • English

Status

  • Source:
  • HPRA - Health Products Regulatory Authority - Ireland
  • Authorization number:
  • PA1055/001/001
  • Authorization date:
  • 01-10-1999
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

ASACARD162.5mgprolongedreleasehardcapsules

2QUALITATIVEANDQUANTITATIVECOMPOSITION

Eachhardcapsulecontainsacetylsalicylicacid162.5mg.

Forafulllistofexcipients,seesection6.1.

3PHARMACEUTICALFORM

Prolongedreleasecapsule,hard

Thecapsuleshaveawhitebodyandredcap.

4CLINICALPARTICULARS

4.1TherapeuticIndications

ASACARD162.5mgCapsulesareindicatedforsecondaryprophylaxisafterafirstcoronaryorcerebrovascular

ischemicevent:

myocardialinfarction

stableandunstableangina

coronaryangioplasty

transientischemicattack(TIA)

non-haemorrhagicstroke

reductionofgraftpatencyocclusionafterCABG

Insituationswherearapidonsetofactionisrequired(suchasacutetreatmentofmyocardialinfarctionor

unstableangina)thenconventional(immediatereleaseacetylsalicylicacid)shouldbegiven.

4.2Posologyandmethodofadministration

ASACARD162.5mgCapsulesshouldnotbetakenwithoutfirstseekingmedicaladviceonthesuitabilityoftreatment.

Treatmentshouldbelong-termandundermedicalsupervision.

Swallowthecapsulewithwater.

Adults:

OneASACARD162.5mgcapsuleperday(162.5mg).Itisrecommendedthatthecapsulesaretakenatthesametime

eachdaye.g.inthemorning,approximately15minutesbeforefood.

Elderly:

Theusualadultdoseisrecommendedintheabsenceofsevererenalorhepaticinsufficiency(seecontraindicationsand

warnings).

Children:

Donotgivetochildrenandadolescentsunder16years(seesection4.4).

4.3Contraindications

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Gastricpatients,andpatientswhohaveexperiencedgastricpainwhenpreviouslyusingthismedicine

Ahistoryofhaemorrhagiccerebrovascularaccident

Hypersensitivitytosalicylicacidcompounds,suchasacetylsalicylicacid,orprostaglandinsynthetase

inhibitors(e.g.someasthmapatients,whomaysufferanasthmaattackorfaint),ortoanyoftheexcipients.

Severehepaticorrenalinsufficiency

Haemorrhagicdiathesisorcoagulationdisorders,suchashaemophiliaandhypoprothrombinaemia,

Thethirdtrimesterofpregnancy.

Methotrexateusedatdoses>15mg/week(seesection4.5).

4.4Specialwarningsandprecautionsforuse

AsASACARD162.6mgCapsuleisaprolongedreleaseformulation,itsuseisnotrecommendedinacutesituations

(see4.1Indications).

ASACARDisnotsuitableforuseasananti-inflammatory/analgesic/antipyretic.

InpatientswhoarebeingtreatedsimultaneouslywithanticoagulantsitisadvisabletomeasuretheInternational

NormalisationRatio(INR)regularly.Inpatientswithmildormoderatedisordersofthehepaticfunctionthisfunction

mustbemeasuredregularly.Concomitanttreatmentwithanticoagulants(coumarinderivatives,heparin)isnot

recommendedandshouldgenerallybeavoided(seesection4.5).Ifconcurrentusecannotbeavoided,frequent

monitoringoftheINRisindicatedandpatientsshouldbecautionedtowatchforsignsofbleeding,especiallyinthe

gastrointestinaltract.Closemedicalmonitoringisalsonecessaryforpatientswithasthmabronchiale,allergicrhinitis

(acetylsalicylicacid(ASA)maycausesevereurticaria,angioedema,orbronchospasm).Patientswithahistoryofpeptic

ulcerdiseaseshouldavoidusingASA(whichcancausegastricmucosalirritationandbleeding).

Theconcomitantadministrationofthisactivesubstancewithuricosuricagentslikebenzbromarone,probenecid,

sulphinpyrazoneisnotrecommended(seesection4.5).

Acetylsalicylicacidmustbeusedwithcareincasesofveryseveremenstrualbleeding.Itispreferabletostopuseof

acetylsalicylicacidbeforeasurgicalprocedure(includingtoothextraction)becauseoftheriskofaprolongedbleeding

timeoranaggravationofthebleeding.Thelengthoftheinterruptionofthetreatmentshouldbedeterminedonacase-

by-casebasis,butwillusuallybeoneweek.

ThereispossibleassociationbetweenacetylsalicylicacidandReye’ssyndromewhengiventochildren.Reye’s

syndromeisaveryraredisease,whichaffectsthebrainandliver,andcanbefatal.Forthisreasonacetylsalicylicacid

shouldnotbegiventochildrenandadolescentsagedunder16yearsunlessspecificallyindicated(seesection4.2).

Thisproductshouldbeadministeredwithcautioninpatientswithrenalimpairment.

Patientswithhypertensionshouldbemonitoredcarefully.

Patientswithrarehereditaryproblemsofgalactoseintolerance,theLapplactasedeficiencyorglucose-galactose

malabsorptionshouldnottakethismedicinalproduct.

Inpatientswithglucose-6-phosphatedehydrogenase(G6PD)deficiency,somecasesofhaemolyticanaemiahavebeen

reportedwithhighdosesofacetylsalicylicacid,i.e.higherthandailyrecommendeddoses'.

4.5Interactionwithothermedicinalproductsandotherformsofinteraction

Theuseofseveralplateletaggregationinhibitors,i.e.acetylsalicylicacid,NSAIDs,ticlopidine,clopidogrel,tirofiban,

eptifibatide,increasestheriskofbleeding,likewisetheircombinationwithheparinanditsderivatives(hirudine,

fondaparinux),oralanticoagulants(suchasanti-vitaminK)andthrombolytics.Clinicalandbiologicalparametersof

haemostasisshouldberegularlymonitored.

Experimentaldatasuggestthatibuprofenmayinhibittheeffectoflowdoseaspirinonplateletaggregationwhenthey

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datatotheclinicalsituationimplythatnofirmconclusionscanbemadeforregularibuprofenuse,andnoclinically

relevanteffectisconsideredtobelikelyforoccasionalibuprofenuse(seesection5.1).

Contraindicatedcombinations

Methotrexate(usedatdoses>15mg/week):

Thecombineddrugs,methotrexateandASA,increasehaematologicaltoxicityofmethotrexateduetothedecreased

renalclearanceofmethotrexatebyASA.Therefore,theconcomitantuseofmethotrexatewithASACARD162.5mg

Capsulesiscontraindicated(seesection4.3).

Associationsnotrecommended

Uricosuricagents(benzbromarone,probenecid,andsulphinpyrazone):Reducedeffectofuricacidexcretionby

competitionofrenaltubularuricacidelimination.Therefore,concomitantuseofASACARD162.5mgCapsuleswith

uricosuricagentsisnotrecommended(seesection4.4).

Combinationsrequiringprecautionsforuse

Diuretics:

Riskofacuterenalfailureduetothedecreasedglomerularfiltrationviadecreasedrenalprostaglandinsynthesis.

Hydratingthepatientandmonitoringrenalfunctionatthestartofthetreatment.

Systemicglucocorticoids(excepthydrocortisoneusedasareplacementtherapyinAddison’sdisease):

TheconcomitantuseofASAwithglucocorticoidscanleadtoadecreaseinbloodsalicylatelevelduringcorticosteroid

treatmentandariskofsalicylateoverdoseafterthistreatmentisstoppedviaincreasedeliminationofsalicylateby

corticosteroids.Thiscombinationrequiresprecaution.Furthermore,riskofbloodlossinthegastrointestinaltractis

enhanced.

Therefore,dosesofASAshouldbeadjustedduringthecombinationandafterglucocorticoidtreatmentisstopped.

Methotrexateusedatdoseslowerthan15mg/week:

Thecombineddrugs,methotrexateandASA,increasedhaematologicaltoxicityofmethotrexateduetothedecreased

renalclearanceofmethotrexatebyacetylsalicylicacid.Weeklybloodcountchecksshouldbedoneduringthefirst

weeksofthecombination.Enhancedmonitoringinthepresenceofevenmildlyimpairedrenalfunction,aswellasin

elderly.

Heparinusedatcurativedosageorinelderlypatients:

WhenASAisco-administeredwithheparinatcurativedosageorinelderlypatients,thereisanincreasedriskof

bleeding.ClosemonitoringoftheINR,aPTTand/orbleedingtimeshouldbeperformedinthecaseofconcomitant

administrationofbothdrugs,ASACARD162.5mgCapsulesandheparin.

Combinationstobetakenintoaccount

Otheranticoagulants(coumarinderivatives,heparinatpreventivedosage),otherplateletanti-aggregants,anti-vitamin

K,andotherthrombolytics:

Increasedriskofbleeding.

NSAIDS:

Increasedriskofbleedingandofdamageongastrointestinalmucosaandenhancementofprolongedbleedingtime

Antacids:

AntacidscanincreasetherenalexcretionofASAbyalkalinizingtheurine.

Sulphonylureasandinsulins:ThehypoglycaemiceffectmaybepotentiatedbyASA

Alcohol:

Additionoftheirowndamageongastrointestinalmucosaandenhancementofprolongedbleedingtime.

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Pregnancy

Lowdoses(upto100mg/day):

Clinicalstudiesindicatethatdosesupto100mg/dayforrestrictedobstetricaluse,whichrequirespecialised

monitoring,appearsafe.

Dosesof100-500mg/day:

Thereisinsufficientclinicalexperienceregardingtheuseofdosesabove100mg/dayupto500mg/day.Therefore,the

recommendationsbelowfordosesof500mg/dandaboveapplyalsoforthisdoserange.

Dosesof500mg/dayandabove:

Inhibitionofprostaglandinsynthesismayadverselyaffectthepregnancyand/ortheembryo/foetaldevelopment.Data

fromepidemiologicalstudiessuggestanincreasedriskofmiscarriageandofcardiacmalformationandgastroschisis

afteruseofaprostaglandinsynthesisinhibitorinearlypregnancy.Theabsoluteriskforcardiovascularmalformation

wasincreasedfromlessthan1%,uptoapproximately1.5%.Theriskisbelievedtoincreasewithdoseanddurationof

therapy.Inanimals,administrationofaprostaglandinsynthesisinhibitorhasbeenshowntoresultinincreasedpre-and

post-implantationlossandembryo-foetallethality.Inaddition,increasedincidencesofvariousmalformations,

includingcardiovascular,havebeenreportedinanimalsgivenaprostaglandinsynthesisinhibitorduringthe

organogeneticperiod.

Duringthefirstandsecondtrimesterofpregnancy,acetylsalicylicacidshouldnotbegivenunlessclearlynecessary.If

acetylsalicylicacidisusedbyawomanattemptingtoconceive,orduringthefirstandsecondtrimesterofpregnancy,

thedoseshouldbekeptaslowanddurationoftreatmentasshortaspossible.

Duringthethirdtrimesterofpregnancy,allprostaglandinsynthesisinhibitorsmayexposethefoetusto:

cardiopulmonarytoxicity(withprematureclosureoftheductusarteriosusandpulmonaryhypertension);

renaldysfunction,whichmayprogresstorenalfailurewitholigo-hydroamniosis;

themotherandtheneonate,attheendofpregnancy,to:

possibleprolongationofbleedingtime,ananti-aggregatingeffectwhichmayoccurevenatverylowdoses.

inhibitionofuterinecontractionsresultingindelayedorprolongedlabour.

Consequently,acetylsalicylicacidatdosesof100mg/dayandhigheriscontraindicatedduringthethirdtrimesterof

pregnancy.

Lactation

Acetylsalicylicacidpassesintobreastmilk;thereforeASACARD162.5mgcapsulesshouldbeavoidedduringbreast

feeding.

4.7Effectsonabilitytodriveandusemachines

Nostudiesontheeffectsontheabilitytodriveandusemachineshavebeenperformed.Onthebasisofthe

pharmacodynamicprofileand/oradversereactionsprofileitisunlikelythatacetylsalicylicacidaffectstheabilityto

driveandusemachines.

4.8Undesirableeffects

Theundesirableeffectsareoftendose-dependentandareduetothepharmacologicaleffectofacetylsalicylicacid(see

section5.1).Mostundesirableeffectsareusuallyassociatedwiththegastrointestinaltract.

Thefrequenciesoftheadversereactionsbelowaredefinedasfollows:Verycommon(>1/10),Common(>1/100,

<1/10),Uncommon(>1/1,000,<1/100),Rare(>1/10,000,<1/1,000),Veryrare(<1/10,000).

Effectsonthegastrointestinaltract:

Verycommon: gastriccomplaintssuchashyperacidityandnausea

Common: vomiting,gastritis,mildtomoderatebloodlossinthegastrointestinaltract,diarrhea.With

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Uncommon: gastricbleeding,gastriculcers.

Veryrareincludingisolatedreports:gastrointestinalperforation

Effectsonthecentralnervoussystem:

Rare: dizziness,headache,tinnitus.Theseareusuallythefirstindicationsofoverdose(seealso

section4.9)

Haematologicaleffects:

Common: prolongationofthebleedingtime.Thiseffectcanpersistforseveraldaysafterstoppingthe

treatmentandcangiverisetohaemorrhagicrisksintheeventofsurgeryorcanleadtoheavier

menstruation

Uncommon: intracranialbleeding,bloodinurine

Rare: haemorrhagicsyndrome(nosebleeds,bleedinggums,bloodyvomitingandbloodlossviathe

faeces,etc.)

Hypersensitivityreactions:

Uncommon: urticaria,skinrash,angio-oedema,rhinitis,bronchialspasms

Veryrareincludingisolatedreports:anaphylacticshock,aggravationoftheallergicsymptomsoffoodallergy

Skinandsubcutaneoustissuedisorders:

Veryrareincludingisolatedreports:severeskinreactions(e.g.erythemaexsudativummultiforme).

Endocrinedisorders:

Veryrareincludingisolatedreports:hypoglycemia.

Hepatobiliarydisorders:

Veryrareincludingisolatedreports:liverimpairment.

Renalandurinarydisorders:

Veryrareincludingisolatedreports:Acuterenalinsufficiency,especiallyinpatientswithexistingrenalinsufficiency,

heartdecompensation,nephriticsyndromeorconcomitanttreatmentwithdiuretics.

Metabolismandnutritiondisorders:

Veryrareincludingisolatedreports:Low-doseASAcanreducetheexcretionofuricacid(whichcanleadtoacutegout

inpre-disposedpatients).

4.9Overdose

Thefollowingareassociatedwithmoderateintoxication:dizziness,headache,tinnitus,confusionandgastrointestinal

symptoms(nausea,vomitingandgastricpain).

Withsevereintoxication,seriousdisturbancesoftheacid-baseequilibriumoccur.Initialhyperventilationleadsto

respiratoryalkalosis.Subsequentlyarespiratoryacidosisalsooccursasaresultofasuppressiveeffectonthe

respiratorycentre.Ametabolicacidosisalsoarisesduetothepresenceofsalicylate.Giventhatchildren,infantsand

toddlersareoftenonlyseenatalatestageofintoxication,theywillusuallyhavealreadyreachedtheacidosisstage.

Thefollowingcanalsoarise:hyperthermiaandperspiration,leadingtodehydration,restlessness,convulsions,

hallucinationsandhypoglycaemia.Depressionofthenervoussystemcanleadtocoma,cardiovascularcollapseand

respiratoryarrest.Thelethaldoseofacetylsalicylicacidis25-30gram.Plasmasalicylateconcentrationsabove300

mg/l(1.67nmol)suggestintoxication.

Ifatoxicdosehasbeeningestedthenadmissiontohospitalisnecessary.Withmoderateintoxicationanattemptcanbe

madetoinducevomiting;ifthisfails,gastriclavageisindicated.Activatedcharcoal(adsorbent)andsodiumsulphate

(laxative)arethenadministered.Alkalisingoftheurine(250mmolNaHCO

for3hours)whilemonitoringtheurine

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symptomatically.

5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

ASACARD162.5mgCapsulesareanovelformulationofacetylsalicylicacid(ASA)madeupofmicroparticleseach

separatelycoatedwithathin,neutral,non-toxicfilmbasedonethylcellulose.Thisfilmpreventsdirectcontactbetween

theparticlesofacetylsalicylicacidandthegastricmucosa(theethylcellulosefilm-coatingactsasasemi-permeable

membranethatallowstheacetylsalicylicacidtodiffuseprogressively,particularlyintheintestine).Thisprogressive

diffusionresultsinalongerdurationofabsorption.

TheantithromboticeffectofASACARD162.5mgCapsuleshasnotbeendemonstratedinclinicaltrials.Ithasbeen

showntoexertanantiplateleteffectexvivosimilartootheracetylsalicylicacidformulationsbyirreversibleacetylation

ofcyclooxygenase.ThisresultsintheinhibitionofthesynthesisofthromboxaneA2,anaggregatoryand

vasoconstrictiveagent.Theanti-plateleteffectlastsfor4to8daysaftertreatmentwithdrawal.Acetylsalicylicacid

essentiallyblocksthetriggerreactioninthecoagulationsystembutnottheentiresystem.However,highdoses

decreasethesynthesisofcoagulationfactorsintheliver.

Acetylsalicylicacidalsoshowsanalgesic,anti-inflammatoryandantipyreticactivities,butatdoseshigherthanthose

recommendedhere.

WithchronicadministrationofASACARD162.5mgCapsulesthepercentagethromboxaneinhibitionisgreaterthan

90%andissimilartothatseenwithconventionalacetylsalicylicacidformulations.Thromboxaneinhibition,as

measuredbyserumthromboxane,collagen-inducedreleasereactionandcollagen-inducedplateletaggregationwas

demonstratedinaclinicalstudyofASACARD162.5mgCapsulesversusimmediatereleaseacetylsalicylicacid75mg

and150mg.Overafourweekperiodthechangesinthromboxanewerestatisticallysignificantlydifferentbetween

ASACARD162.5mgCapsulesand75mgacetylsalicylicacidintwooutofthreemeasurements.

Itwasnotsignificantlydifferentcomparedtothe150mgdose.ASACARD162.5mgCapsulesdonotsignificantly

inhibitprostacyclinovera28daytreatmentperiodorsignificantlymodifybleedingtime.

Experimentaldatasuggestthatibuprofenmayinhibittheeffectoflowdoseaspirinonplateletaggregationwhenthey

aredosedconcomitantly.Inonestudy,whenasingledoseofibuprofen400mgwastakenwithin8hoursbeforeor

within30minutesafterimmediatereleaseaspirin(81mg),adecreasedeffectofaspirinontheformationof

thromboxaneorplateletaggregationoccurred.However,thelimitationsofthesedataandtheuncertaintiesregarding

extrapolationofexvivodatatotheclinicalsituationimplythatnofirmconclusionscanbemadeforregularibuprofen

use,andnoclinicallyrelevanteffectisconsideredtobelikelyforoccasionalibuprofenuse.

ATCCode-B01AC06-Plateletaggregationinhibitors.

5.2Pharmacokineticproperties

Thecoatingofthemicroparticlesinthecapsulesensurethatacetylsalicylicacidisreleasedthroughouttheday.

FollowingadministrationofASACARD162.5mgcapsulesbloodlevelsofacetylsalicylicacidarevirtually

undetectableandpharmacokineticparameterscannotbecalculatedforASA.

Levelsofsalicylicacid(SA),theprincipalmetaboliteofASApeakataround3hoursafteradministrationof

ASACARD162.5mgcapsules.ThepeaklevelsofSAarebetween2.35and2.80mcg/mlaroundonethirdofthelevels

seenwithconventionalacetylsalicylicacid.Themeanresidence-timeforSAisbetween9and12hours,approximately

threetimeslongerthanthatofconventionalacetylsalicylicacid.

5.3Preclinicalsafetydata

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Acomparative,acutetoxicitystudywasconductedinratsthatreceivedASACARD162.5mgcapsulesincomparison

withnon-film-coatedacetylsalicylicacid.NoLD50valuescouldbedeterminedatadoseof2500mg/kg,thoughthe

LD50intheratwhendosedwithacetylsalicylicacidstartingmaterialwas1400mg/kg.Noclinicalsignswere

observed.

Anatomopathologicalexaminationdidnotshowanylesions,eveninthestomach.

6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

Capsulescontain:

Ethylcellulose

Povidone

Castoroil

Magnesiumstearate

Colloidalanhydroussilica

Tartaricacid

Talc

Capsuleshellcontains:

Gelatin

Titaniumdioxide(E171)

Erythrosine(E127)

Indigotin(E132)

6.2Incompatibilities

Acetylsalicylicacidisincompatiblewithalkalizingagentsthatincreaseitssolubilisation.Inaddition,aluminiumsalts

forminsolublehydroxides.Similarly,acetylsalicylicacidisincompatiblewithcalciumcarbonate.

6.3Shelflife

2years.

6.4Specialprecautionsforstorage

Donotstoreabove25°C.

Storeintheoriginalpackaging.

6.5Natureandcontentsofcontainer

Boxof4,10,28,30or100capsulespackagedinaheat-sealedPVC/PVDC/Foilblisterpack.

Notallpacksizesmaybemarketed.

6.6Specialprecautionsfordisposalofausedmedicinalproductorwastematerialsderivedfrom

suchmedicinalproductandotherhandlingoftheproduct

Nospecialrequirements.

7MARKETINGAUTHORISATIONHOLDER

FlamelTechnologiesSA

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33,AvenueduDrGeorgesLévy

F69693VénissieuxCedex

France

8MARKETINGAUTHORISATIONNUMBER

PA1055/1/1

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

Dateoffirstauthorisation:01October1999

Dateoflastrenewal:20January2008

10DATEOFREVISIONOFTHETEXT

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