ASCAL

Main information

  • Trade name:
  • ASCAL Tablets Effervescent 100 Milligram
  • Dosage:
  • 100 Milligram
  • Pharmaceutical form:
  • Tablets Effervescent
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug

Documents

Localization

  • Available in:
  • ASCAL Tablets Effervescent 100 Milligram
    Ireland
  • Language:
  • English

Status

  • Source:
  • HPRA - Health Products Regulatory Authority - Ireland
  • Authorization number:
  • PA1332/011/001
  • Authorization date:
  • 13-06-2006
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

AscalBrisperCardio-Neuro100mgeffervescenttablets

2QUALITATIVEANDQUANTITATIVECOMPOSITION

Oneeffervescenttabletcontains100mgcarbasalatecalcium,correspondingto78mgacetylsalicylicacid.

Excipient:containsLactoseMonohydrate150.0mg.

Forafulllistofexcipients,seesection6.1.

3PHARMACEUTICALFORM

Effervescenttablet.

White-tocream-coloured,round,flattabletwithbevellededge.

4CLINICALPARTICULARS

4.1TherapeuticIndications

Ascalisindicatedforsecondarypreventionafterafirstmyocardialorcerebrovasculareventlinkedtoatherosclerosis:

Myocardialinfarction

Unstableandstableanginapectoris

Strokeandtransientischaemicattackprovidedthatintracanialhaemorrhagesareexcluded.

Graftocclusionafteraorta-coronarybypass.

4.2Posologyandmethodofadministration

Secondarypreventionofmyocardialinfarction:

Inacutecasesaloadingdoseofaninitial2effervescenttablets(200mgcarbasalatecalcium,correspondingto156mg

acetylsalicylicacid)perdayshouldbetakenonthefirstday,followedby1to2effervescenttablets(100mgcarbasalate

calcium,correspondingto78mgacetylsalicylicacid,to200mgcarbasalatecalcium,correspondingto156mg

acetylsalicylicacid)perday.Inacutecases,thefirstdosemustbetakenassoonaspossibleafterthediagnosis.

Secondarypreventionofunstableandstableanginapectoris:

Inacutecasesaloadingdoseofaninitial2effervescenttablets(200mgcarbasalatecalcium,correspondingto156mg

acetylsalicylicacid)perdayshouldbetakenonthefirstday,followedby1to2effervescenttablets(100mgcarbasalate

calcium,correspondingto78mgacetylsalicylicacid,to200mgcarbasalatecalcium,correspondingto156mg

acetylsalicylicacid)perday.Inacutecases,thefirstdosemustbetakenassoonaspossibleafterthediagnosis.

Secondarypreventionofstrokeandtransientischaemicattackprovidedthatintracanialhaemorrhagesareexcluded:

Inacutecasesaloadingdoseofaninitial2effervescenttablets(200mgcarbasalatecalcium,correspondingto156mg

acetylsalicylicacid)perdayshouldbetakenonthefirstday,followedby1effervescenttablet(100mgcarbasalate

calcium,correspondingto78mgacetylsalicylicacid)perday.Inacutecases,thefirstdosemustbetakenassoonas

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Secondarypreventionofgraftocclusionafteraorta-coronarybypass:

Inacutecasesaloadingdoseofaninitial2effervescenttablets(200mgcarbasalatecalcium,correspondingto156mg

acetylsalicylicacid)perdayshouldbetakenonthefirstday,followedby1to2effervescenttablets(100mgcarbasalate

calcium,correspondingto78mgacetylsalicylicacid,to200mgcarbasalatecalcium,correspondingto156mg

acetylsalicylicacid)perday.Inacutecases,thefirstdosemustbetakenassoonaspossibleaftertheaorta-coronarybypass.

Ascal100mgmustbetakeninsolution.Dissolvetheeffervescenttabletinaglassofwateruntilthesolutionisclearand

thendrink.Donotgivetochildrenandadolescentsagedunder16years(seesection4.4)

4.3Contraindications

pepticulcerand/orgastrointestinalhaemorrhages

gastricpatients,andpatientswhohaveexperiencedgastricpainwhenpreviouslyusingthemedicine

ahistoryofhaemorrhagiccerebrovascularaccident.

hypersensitivitytosalicylicacidcompounds,suchasacetylsalicylicacid,orprostaglandinsynthetase

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

severehepaticorrenalinsufficiency

haemorrhagicdiathesisorcoagulationdisorders,suchashaemophiliaandhypoprothrombinaemia

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

Doses>128mgcarbasalatecalcium/daywhichisequivalentto100mgacetylsalicylicacid/day(1tablet

{productname}/day)duringthethirdtrimesterofpregnancy.

4.4Specialwarningsandprecautionsforuse

InpatientswhoarebeingtreatedsimultaneouslywithanticoagulantsitisadvisabletomeasuretheInternational

NormalisationRatio(INR)regularly.Inpatientswithmildormoderatedisordersofthehepaticfunctionthisfunctionmust

bemeasuredregularly.

Concomitanttreatmentwithanticoagulants(coumarinderivatives,heparin)isnotrecommendedandshouldgenerally

beavoided(seesection4.5).Ifconcurrentusecannotbeavoided,frequentmonitoringoftheINRisindicatedand

patientsshouldbecautionedtowatchforsignsofbleeding,especiallyinthegastrointestinaltract.

Closemedicalmonitoringisalsonecessaryforpatientswithasthmabronchiale,allergicrhinitis(ASAmaycause

severeurticaria,angioedema,orbronchospasm).PatientswithahistoryofpepticulcerdiseaseshouldavoidusingASA

(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.

Inpatientswithglucose-6-phosphatedehydrogenase(G6PD)deficiency,somecasesofhaemolyticanaemiahavebeen

reportedwithhighdosesofacetylsalicylicacid,i.e.higherthandailyrecommendeddoses.

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malabsorptionshouldnottakethismedicinalproduct.

Liverfunctiontestsshouldbeperformedregularlyinpatientspresentingslightormoderatehepaticinsufficiency.

4.5Interactionwithothermedicinalproductsandotherformsofinteraction

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

eptifibatide,increasestheriskofbleeding,likewisetheircombinationwithheparinanditsderivatives(hirudine,

fondaparinux),oralanticoagulantsandthrombolytics.Clinicalandbiologicalparametersofhaemostasisshouldbe

regularlymonitored.

Contra-indicatedcombinations

-Methotrexate(usedatdoses>15mg/week):thecombineddrugs,methotrexateandASA,increasehaematological

toxicityofmethotrexateduetothedecreasedrenalclearanceofmethotrexatebyASA.Therefore,theconcomitantuse

ofmethotrexatewithAscaliscontra-indicated(seesection4.3).

Notrecommendedassociations

-Uricosuricsagents(benzbromarone,probenecid,andsulphinpyrazone):reducedeffectofuricacidexcretionby

competitionofrenaltubularuricacidelimination.Therefore,theconcomitantuseofAscalwithuricosuricsagentsis

not-recommended(seesection4.4).

Combinationsrequiringprecautionsforuse

-Diuretics:riskofacuterenalfailureduetothedecreasedglomerularfiltrationviadecreasedrenalprostaglandin

synthesis.Hydratingthepatientandmonitoringrenalfunctionatthestartofthetreatment.

-Systemicglucocorticoids(excepthydrocortisoneusedasareplacementtherapyinAddison’sdisease):the

concomitantuseofASAwithglucocorticoidscanleadtoadecreaseinbloodsalicylatelevelduringcorticosteroid

treatmentandariskofsalicylateoverdoseafterthistreatmentisstoppedviaincreasedeliminationofsalicylateby

corticosteroids.Thiscombinationsrequiresprecaution.Furthermore,riskofbloodlossinthegastrointestinaltractis

enhanced.Therefore,dosesofASAshouldbeadjustedduringthecombinationandafterglucocorticoidtreatmentis

stopped.

-Methotrexateusedatdoseslowerthan15mg/week:thecombineddrugs,methotrexateandASA,increased

haematologicaltoxicityofmethotrexateduetothedecreasedrenalclearanceofmethotrexatebyacetylsalicylicacid.

Weeklybloodcountchecksshouldbedoneduringthefirstweeksofthecombination.Enhancedmonitoringinthe

presenceofevenmildlyimpairedrenalfunction,aswell,asinelderly.

-Heparinusedatcurativedosageorinelderlypatients:whenASAisco-administeredwithheparinatcurativedosage

orinelderlypatients,thereisanincreasedriskofbleeding.ClosemonitoringoftheINR,aPTTand/orbleedingtime

shouldbeperformedinthecaseofconcomitantadministrationofbothdrugs,Ascal100mgandheparin.

Combinationstobetakenintoaccount

-Otheranticoagulants(coumarinderivatives,heparinatpreventivedosage),otherplateletanti-aggregantsandother

thrombolytics:increasedriskofbleeding.

-NSAIDs:increasedriskofbleedingandofdamageongastro-intestinalmucosaandenhancementofprolonging

bleedingtime

-Ibuprofen:Experimentaldatasuggestthatibuprofenmayinhibittheeffectoflowdoseaspirinonplateletaggregation

whentheyaredosedconcomitantly.However,thelimitationsofthesedataandtheuncertaintiesregarding

extrapolationofexvivodatatotheclinicalsituationimplythatnofirmconclusionscanbemadeforregularibuprofen

use,andnoclinicallyrelevanteffectisconsideredtobelikelyforoccasionalibuprofenuse(seesection5.1).

-Antacids:AntacidscanincreasetherenalexcretionofASAbyalkalinisingtheurine.

-Alcohol:additionoftheirowndamageongastro-intestinalmucosaandenhancementofprolongingbleedingtime

4.6Fertility,pregnancyandlactation

Pregnancy

Lowdoses,upto128mgcarbasalatecalcium/daywhichisequivalentto100mg

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Clinicalstudiesindicatethatdosesupto100mgacetylsalicylicacid/dayforrestrictedobstetricaluse,whichrequire

specialisedmonitoring,appearsafe.

Dosesofmorethan128mgupto640mgcarbasalatecalcium/daywhichisequivalentto100-500mgacetylsalicylic

acid/day(morethan1tablet{productname}/day):

Thereisinsufficientclinicalexperienceregardingtheuseofdosesabove100mgacetylsalicylicacid/dayupto500mg

acetylsalicylicacid/day.Therefore,thefollowingrecommendationsfordosesof500mgacetylsalicylicacid/dayand

aboveapplyalsoforthisdoserange:

Inhibitionofprostaglandinsynthesismayadverselyaffectthepregnancyand/ortheembryo/foetaldevelopment.Data

fromepidemiologicalstudiessuggestanincreasedriskofmiscarriageandofcardiacmalformationandgastroschisis

afteruseofaprostaglandinsynthesisinhibitorinearlypregnancy.Theabsoluteriskforcardiovascularmalformation

wasincreasedfromlessthan1%,uptoapproximately1.5%.Theriskisbelievedtoincreasewithdoseanddurationof

therapy.Inanimals,administrationofaprostaglandinsynthesisinhibitorhasbeenshowntoresultinincreasedpre-and

post-implantationlossandembryo-foetallethality.Inaddition,increasedincidencesofvariousmalformations,

includingcardiovascular,havebeenreportedinanimalsgivenaprostaglandinsynthesisinhibitorduringthe

organogeneticperiod.Duringthefirstandsecondtrimesterofpregnancy,acetylsalicylicacidshouldnotbegiven

unlessclearlynecessary.Ifacetylsalicylicacidisusedbyawomanattemptingtoconceive,orduringthefirstand

secondtrimesterofpregnancy,thedoseshouldbekeptaslowanddurationoftreatmentasshortaspossible.

Duringthethirdtrimesterofpregnancy,allprostaglandinsynthesisinhibitorsmayexposethefoetusto:

cardiopulmonarytoxicity(withprematureclosureoftheductusarteriosusandpulmonaryhypertension);

renaldysfunction,whichmayprogresstorenalfailurewitholigo-hydroamniosis;

themotherandtheneonate,attheendofpregnancy,to:

possibleprolongationofbleedingtime,ananti-aggregatingeffectwhichmayoccurevenatverylowdoses.

inhibitionofuterinecontractionsresultingindelayedorprolongedlabour.

Consequently,128mgcarbasalatecalcium/daywhichisequivalentto100mgacetylsalicylicacid/dayandhigher(more

than1tablet{productname}/day)iscontraindicatedduringthethirdtrimesterofpregnancy.

Lactation

Acetylsalicylicacidisexcretedintothematernalmilkinsmallamounts.Sinceafterincidentalusenoadverseeffects

wereobservedintheinfant,100mgacetylsalicylicacidcanbetakenonceduringbreastfeedingasindicatedinthe

posology(notmorethan1tabletperday).Withchronicuseorintakeofhighdoses,breastfeedingshouldbestopped.

4.7Effectsonabilitytodriveandusemachines

Nostudiesontheeffectsontheabilitytodriveandusemachineshavebeenperformed.

Onthebasisofthepharmacodynamicprofileand/oradversereactionsprofileitisunlikelythatcarbasalatecalciumaffects

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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,diarrhoea.Withlong-

termorrepeatedusethisbloodlosscanleadtoanaemia.

Uncommon:gastricbleeding,gastriculcers

Veryrareincludingisolatedreports:gastrointestinalperforation

Effectsonthecentralnervoussystem:

Rare:dizziness,headache,tinnitus.Theseareusuallythefirstindicationsofoverdose(seealsosection4.9)

Haematologicaleffects:

Common:prolongationofthebleedingtime.Thiseffectcanpersistforseveraldaysafterstoppingthe

treatmentandcangiverisetohaemorrhagicrisksintheeventofsurgeryorcanleadtoheaviermenstruation

Uncommon:intracranialbleeding,bloodinurine

Rare:haemorrhagicsyndrome(nosebleeds,bleedinggums,bloodyvomitingandbloodlossviathefaeces,

etc.)

Hypersensitivityreactions:

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

Veryrareincludingisolatedreports:anaphylacticshock,aggravationoftheallergicsymptomsoffood

allergy

Skinandsubcutaneoustissuedisorders:

Veryrareincludingisolatedreports:severeskinreactions(e.g.erythemaexsudativummultiforme),

Endocrinedisorders:

Veryrareincludingisolatedreports:hypoglycemia.

Hepatobiliarydisorders:

Veryrareincludingisolatedreports:liverimpairment.

Renalandurinarydisorders:

Veryrareincludingisolatedreports:Acuterenalinsufficiency,especiallyinpatientswithexistingrenal

insufficiency,heartdecompensation,nephroticsyndromeorconcomitanttreatmentwithdiuretics

Metabolismandnutritiondisorders:

Veryrareincludingisolatedreports:Low-doseASAcanreducetheexcretionofuricacid(whichcanleadto

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4.9Overdose

Thefollowingareassociatedwithmoderateintoxication:dizziness,headache,tinnitus,confusionandgastrointestinal

symptoms(nausea,vomitingandgastricpain).

Withsevereintoxication,seriousdisturbancesoftheacid-baseequilibriumoccur.Initialhyperventilationleadsto

respiratoryalkalosis.Subsequentlyarespiratoryacidosisoccursasaresultofasuppressiveeffectontherespiratory

centre.Ametabolicacidosisalsoarisesduetothepresenceofsalicylate.Giventhatchildren,infantsandtoddlersare

oftenonlyseenatalatestageofintoxication,theywillusuallyhavealreadyreachedtheacidosisstage.

Thefollowingcanalsoarise:hyperthermiaandperspiration,leadingtodehydration,restlessness,convulsions,

hallucinationsandhypoglycaemia.Depressionofthenervoussystemcanleadtocoma,cardiovascularcollapseand

respiratoryarrest.Thelethaldoseofacetylsalicylicacidis25-30gram.Plasmasalicylateconcentrationsabove300

mg/l(1,67mmol/l)suggestintoxication.

Ifatoxicdosehasbeeningestedthenadmissiontohospitalisnecessary.Withmoderateintoxicationanattemptcanbe

madetoinducevomiting;ifthisfails,gastriclavageisindicated.Activatedcharcoal(adsorbent)andsodiumsulphate

(laxative)arethenadministered.Alkalisingoftheurine(250mmolNaHCO

for3hours)whilemonitoringtheurine

pHisindicated.Haemodialysisisthepreferredtreatmentforsevereintoxication.Treatothersignsofintoxication

symptomatically.

5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

Pharmacotherapeuticgroup:Antithromboticagents,Plateletaggregrationinhibitorsexcl.Heparin

ATCcode: B01AC08

Ascal100mgcontainscarbasalatecalcium,acomplexofcalciumacetylsalicylicacidandureathatisfullysolubleina

smallamountofwater.Eacheffervescenttabletcontainstheequivalentof78mgofacetylsalicylicacidwhich,after

solution,isfullyavailableasanionforabsorption.

Thevolumeofureaisverysmall(13.1%)thereforeevenathighdosesitformsonlyafractionofthevolumethatisfound

asametaboliteinnormalproteinmetabolism.

Carbasalatecalciumisathrombocyteaggregationinhibitor.Theantithromboticeffectisduetotheirreversibleacetylating

oftheenzymecyclo-oxygenaseinthethrombocyte,throughwhichtheformationoftheprostaglandinthromboxaneA

inhibited.Duetotheirreversiblenatureofthebinding,theeffectpersistsforthelifespanofathrombocyte(7-10days)and

theeffectiscumulativeafterrepeateddosing.AsaresultitispossibletoachievemaximumthromboxaneA

inhibition

afterinitiallyhigherstartingdosefollowedbylowermaintenancedosestocompensateforthecreationofnew

thrombocytes.

Experimentaldatasuggestthatibuprofenmayinhibittheeffectoflowdoseaspirinonplateletaggregationwhenthey

aredosedconcomitantly.

Inonestudy,whenasingledoseofibuprofen400mgwastakenwithin8hbeforeorwithin30minafterimmediate

releaseaspirindosing(81mg),adecreasedeffectofASAontheformationofthromboxaneorplateletaggregation

occurred.However,thelimitationsofthesedataandtheuncertaintiesregardingextrapolationofexvivodatatothe

clinicalsituationimplythatnofirmconclusionscanbemadeforregularibuprofenuse,andnoclinicallyrelevanteffect

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5.2Pharmacokineticproperties

ABSORPTION

Afteroraladministration,acetylsalicylicacidisrapidlyabsorbedintheproximalpartofthesmallbowel.Themaximum

plasmaconcentrationisreachedafter0.5-2hours.However,aconsiderablepartofthedoseishydrolysedinthegastricwall

duringabsorption.Simultaneousingestionoffooddelaystheuptakeofacetylsalicylicacid(lowerpeakplasma

concentrations).

DISTRIBUTION

Thevolumeofdistributionofacetylsalicylicacidisapprox.0.20l/kgbodyweight.Thefirstconversionproductformed

fromacetylsalicylicacid,anti-inflammatorilyeffectivesalicylicacid,isboundtoplasmaproteins,primarilyalbumin,to

the90%level.

Salicylicaciddiffusesslowlytothesynoviaandthesynovialfluid.Itpenetratestheplacentaandpassesoverintothe

maternalmilk.

BIOTRANSFORMATION

Acetylsalicylicacidisprimarilyconvertedintosalicylicacidbyhydrolysis.Thehalf-lifeofacetylsalicylicacidisshort,

approx.15-20minutes.

Salicylicacidisthenconvertedintoglycineacidandglucoronicacidconjugatesandtracesofgentisinicacid.Athigher

therapeuticdosestheconversioncapacityofsalicylicacidisalreadyexceededandthepharmacokineticsisnon-linear.

Thisleadstoaprolongationoftheapparenteliminationhalf-lifeofsalicylicacidfromafewhourstoapproximately24

hours.

EXCRETION

Excretionisprimarilyviathekidneys.

ThetubularresorptionofsalicylicacidispH-dependent.Byalkalisingtheurinetheproportionofunchangedsalicylicacid

intheexcretionincreasesfromapprox.10%toapprox.80%.

5.3Preclinicalsafetydata

Mutagenicandcarcinogenicpotential.

Theacetylsalicylicacidhasbeenassessedinmanyinvitroandinvivopre-clinicalstudies.Takentogethertheresults

didn'trevealanymutageniceffect.

Longtermstudiesonratandmousedidn'trevealanycarcinogeniceffect.

6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

lactosemonohydrate

adipicacid(E355)

sodiumhydrogencarbonate(E500a)

magnesiumstearate(E470b)

crospovidone(E1202)

povidoneK90(E1201)

6.2Incompatibilities

Notapplicable.

6.3Shelflife

Shelflifeofthemedicinalproductaspackagedforsale(30effervescenttablets):3years;

Shelflifeafterfirstopeningthecontainer:1month.

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Shelflifeafterfirstopeningthecontainer:3months.

Shelflifeofthemedicinalproductaspackagedforsale(100effervescenttablets):2years;

Shelflifeafterfirstopeningthecontainer:100days.

6.4Specialprecautionsforstorage

Donotrefrigerateorfreeze.

Storeintheoriginalpackaging,inordertoprotectfrommoisture.

Keepthecontainertightlyclosed.

Donotstoreabove30°C.

6.5Natureandcontentsofcontainer

30,90or100effervescenttabletsinapolypropylenetabletcontainerwithpolyethylenecap(containingadesiccant

cartridge),packedinacardboardouterbox.

Notallpacksizesmaybemarketed

6.6Specialprecautionsfordisposalandotherhandling

Nospecialrequirements

7MARKETINGAUTHORISATIONHOLDER

MedaHealthSalesIrelandLimited

Unit35/35,BlockA

DunboyneBusinessPark

Dunboyne

Co.Meath

Ireland

8MARKETINGAUTHORISATIONNUMBER

PA1332/11/1

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

Dateoffirstauthorisation:25February2005

Dateoflastrenewal:9February2009

10DATEOFREVISIONOFTHETEXT

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