ACCUPRO

Main information

  • Trade name:
  • ACCUPRO Film Coated Tablet 20 Milligram
  • Dosage:
  • 20 Milligram
  • Pharmaceutical form:
  • Film Coated Tablet
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug

Documents

Localization

  • Available in:
  • ACCUPRO Film Coated Tablet 20 Milligram
    Ireland
  • Language:
  • English

Other information

Status

  • Source:
  • HPRA - Health Products Regulatory Authority - Ireland
  • Authorization number:
  • PPA1328/045/001
  • Authorization date:
  • 20-10-2006
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage,interactions,side effects

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

Accupro20mgFilm-coatedTablets

2QUALITATIVEANDQUANTITATIVECOMPOSITION

Eachfilm-coatedtabletcontains20mgquinaprilbase(equivalentto21.664quinaprilhydrochloride).

Excipients:Lactosemonohydrate.

Forafulllistofexcipients,seesection6.1.

3PHARMACEUTICALFORM

Film-coatedtablet.

ProductimportedfromItaly:

Brownroundtabletwithascorelineonbothsidesandthestrength'20'ononeside

ProductimportedfromGermany:

White,roundtabletwithascorelineonbothsidesandthestrength'20'imprintedononesideonly.

Thescorelineistoallowforbreakingforeaseofswallowingandnottodivideintoequalhalves.

4CLINICALPARTICULARS

4.1TherapeuticIndications

(1)Forthetreatmentofallgradesofessentialhypertension.Accuproiseffectiveasmonotherapyorconcomitantlywith

diureticsinpatientswithhypertension.

(2)Forthetreatmentofcongestiveheartfailurewhengivenconcomitantlywithadiureticand/orcardiacglycoside.

TreatmentofcongestiveheartfailurewithAccuproshouldalwaysbeinitiatedunderclosemedicalsupervision.

4.2Posologyandmethodofadministration

Fororaluse.

Adults

Hypertension

Monotherapy:Therecommendedinitialdosageis10mgoncedaily.Dependinguponclinicalresponse,patient'sdosage

maybetitrated(bydoublingthedoseallowingadequatetimefordosageadjustment)toamaintenancedosageof20to

40mg/daygivenasasingledoseordividedinto2doses.Long-termcontrolismaintainedinmostpatientswitha

singledailydosageregimen.Patientshavebeentreatedwithdosagesupto80mg/day.

ConcomitantDiuretics:Inordertodetermineifexcesshypotensionwilloccur,aninitialdosageof5mgofAccuprois

recommendedinpatientswhoarealsobeingtreatedwithadiuretic.AfterthisthedosageofAccuproshouldbetitrated

(bydoublingthedoseallowingtimefordosageadjustment)totheoptimalresponse(seesection4.5Interactionwith

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CongestiveHeartFailure

Inordertocloselymonitorpatientsforsymptomatichypotension,asingle5mginitialdosageisrecommended.After

this,patientsshouldbetitratedtoaneffectivedose:(upto40mg/day)givenin1or2doseswithconcomitantdiuretic

and/orcardiacglycosidetherapy.

Patientsareusuallymaintainedeffectivelyondosesof10-20mg/daygivenwithconcomitanttherapy.

Inthetreatmentofsevereorunstablecongestiveheartfailure,Accuproshouldalwaysbeinitiatedinhospitalunder

closemedicalsupervision.

Elderly

Agealonedoesnotappeartoaffecttheefficacyorsafetyprofileofquinapril.Therefore,therecommendedinitial

dosageinhypertensionofquinaprilinelderlypatientsis10mggivenoncedailyfollowedbytitrationtotheoptimal

response.

Children(6-12years)

Notrecommended.Safetyandefficacyinchildrenhasnotbeenestablished.

Patientswithrenalinsufficiency

Inpatientswithacreatinineclearanceoflessthan60ml/min.,aninitialdosageinessentialhypertensionof5mgonce

dailyisrecommendedfollowedbytitrationtotheoptimalresponse.Kineticdataindicatethattheapparentelimination

half-lifeofquinaprilatincreasesascreatinineclearancedecreases(seesection4.4Specialwarningsandprecautionsfor

use).

4.3Contraindications

Hypersensitivitytoanyoftheingredients

Accuproiscontraindicatedthroughoutsecondandthirdtrimesterofpregnancy.

Useinpatientswithsubaorticstenosis.

UseinpatientswithahistoryofangioneuroticoedemarelatingtoprevioustreatmentwithanACEinhibitor.

4.4Specialwarningsandprecautionsforuse

ImpairedRenalFunction:Inpatientswithrenalinsufficiencymonitoringofrenalfunctionduringtherapyshouldbe

performedasdeemedappropriate,althoughinthemajorityrenalfunctionwillnotalterormayimprove.

Asaconsequenceofinhibitingtherenin-angiotensin-aldosteronesystem,changesinrenalfunctionmaybeanticipated

insusceptibleindividuals.Inpatientswithsevereheartfailurewhoserenalfunctionmaydependontheactivityofthe

renin-angiotensin-aldosteronesystem,treatmentwithACEinhibitorsincludingquinapril,maybeassociatedwith

oliguriaand/orprogressiveazotemiaandrarelyacuterenalfailureand/ordeath.

Thehalf-lifeofquinaprilatisprolongedascreatinineclearancefalls.Patientswithacreatinineclearanceof<60ml/min

requirealowerinitialdosageofquinapril(seesection4.2Posologyandmethodofadministration).Thesepatients'

dosageshouldbetitratedupwardsbasedupontherapeuticresponse,andrenalfunctionshouldbecloselymonitored

althoughinitialstudiesdonotindicatethatquinaprilproducesfurtherdeteriorationinrenalfunction.

Inclinicalstudiesinhypertensivepatientswithunilateralorbilateralrenalarterystenosis,increasesinbloodurea

nitrogenandserumcreatininehavebeenobservedinsomepatientsfollowingACEinhibitortherapy.Theseincreases

werealmostalwaysreversibleupondiscontinuationoftheACEinhibitorand/ordiuretictherapy.Insuchpatients,renal

functionshouldbemonitoredduringthefirstfewweeksoftherapy.

Somepatientswithhypertensionorheartfailurewithnoapparentpre-existingrenalvasculardiseasehavedeveloped

increases>1.25timestheupperlimitofnormal)inbloodureaandserumcreatinine,usuallyminorandtransient,

especiallywhenquinaprilhasbeengivenconcomitantlywithadiureticandhasbeenobservedin4%and3%

respectivelyofpatientsonmonotherapy.Thisismorelikelytooccurinpatientswithpre-existingrenalimpairment.

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ImpairedHepaticFunction:Quinaprilwhencombinedwithadiureticshouldbeusedwithcautioninpatientswith

impairedhepaticfunctionorprogressiveliverdisease,sinceminoralterationsoffluidandelectrolytebalancemay

precipitatehepaticcoma.Themetabolismofquinapriltoquinaprilatisnormallydependentuponhepaticesterase.

Quinaprilatconcentrationsarereducedinpatientswithalcoholiccirrhosisduetoimpaireddeesterificationofquinapril.

Anaphylactoidreactions

Desensitisation:PatientsreceivingACEinhibitorsduringdesensitisingtreatmentwithhymenopteravenomhave

sustainedlife-threateninganaphylactoidreactions.InthesamepatientsthesereactionshavebeenavoidedwhenACE

inhibitorsweretemporarilywithheld,buttheyhavereappeareduponinadvertentrechallenge.

LDLapheresis:Patientsundergoinglow-densitylipoproteinapheresiswithdextran-sulphateabsorptionwhentreated

concomitantlywithanACEinhibitorhavereportedanaphylactoidreactions.

Haemodialysis:Patientshaemodialysedusinghigh-fluxpolyacrylonitrile('AN69')membranesarehighlylikelyto

experienceanaphylactoidreactionsiftheyaretreatedwithACEinhibitors.Thiscombinationshouldthereforebe

avoided,eitherbyuseofalternativeantihypertensivedrugsoralternativemembranesforhaemodialysis.

Angioneuroticoedema:AngioneuroticoedemahasbeenreportedrarelywithACEinhibitorsincludingAccupro.In

somecasessymptomshavebeenobservedupto2yearsafterinitiationoftreatment.Suchreactionsshouldberegarded

asanindicationtodiscontinuetherapyimmediatelyandthepatientcloselymonitored.Whereswellingisconfinedto

theface,lipsandmouth,theconditionwillusuallyresolvewithoutfurthertreatment,althoughantihistaminesmaybe

usefulinrelievingsymptoms.Thesepatientsshouldbefollowedcarefullyuntiltheswellinghasresolved.However,

wherethereisinvolvementofthetongue,glottisorlarynx,likelytocauseairwaysobstruction,appropriatetherapy

suchassubcutaneousadrenaline(0.5mL1:1000)shouldbeadministeredpromptlywhenindicated.

BlackpatientsreceivingACEinhibitortherapyhavebeenshowntohaveahigherincidenceofangioedemacompared

tonon-blackpatients.

Intestinalangioedema:IntestinalangioedemahasbeenreportedinpatientstreatedwithACEinhibitors.Thesepatients

presentedwithabdominalpain(withorwithoutnauseaorvomiting);insomecasestherewasnopriorhistoryoffacial

angioedemaandC-1esteraselevelswerenormal.Theangioedemawasdiagnosedbyproceduresincludingabdominal

CTscanorultrasound,oratsurgery,andsymptomsresolvedafterstoppingtheACEinhibitor.Intestinalangioedema

shouldbeincludedinthedifferentialdiagnosisofpatientsonACEinhibitorspresentingwithabdominalpain

CautionshouldbeexercisedinthoseknowntobehypersensitivetootherACEinhibitors,andparticularlythosewith

obstructiveairwaysdisease.PatientswithahistoryofangioedemaunrelatedtoACEinhibitortherapymaybeat

increasedriskofangioedemawhilereceivinganACEinhibitor(seealsosection4.3Contraindications).

Otherhypersensitivityreactionshavebeenreported.

Hypotension:SymptomatichypotensionwasrarelyseeninhypertensivepatientstreatedwithAccuprobutitisa

possibleconsequenceofACEinhibitiontherapyparticularlyinsalt/volumedepletedpatientssuchasthosepreviously

treatedwithdiuretics,whohaveadietarysaltreduction,orwhoareondialysis.Anyelectrolyteorfluidinadequacy

shouldbecorrectedpreferablybeforeinitialdoseoftheproduct.Carefulmedicalsupervisionisnecessaryforaperiod

afterdosing.Ifsymptomatichypotensionoccurs,thepatientshouldbeplacedinthesupinepositionand,ifnecessary,

receiveanintravenousinfusionofnormalsaline.Atransienthypotensiveresponseisnotacontraindicationtofurther

doses;however,lowerdosesofquinapriloranyconcomitantdiuretictherapyshouldbeconsideredifthiseventoccurs.

Neutropenia/agranulocytosis:ACEinhibitorshavebeenrarelyassociatedwithagranulocytosisandbonemarrow

depressioninpatientswithuncomplicatedhypertensionbutmorefrequentlyinpatientswithrenalimpairment,

especiallyiftheyalsohavecollagenvasculardisease.AswithotherACEinhibitors,monitoringofwhitebloodcell

countsinpatientswithcollagenvasculardiseaseand/orrenaldiseasesshouldbeconsidered.

Hypoglycaemia:ACEinhibitorsmayenhanceinsulinsensitivityandhavebeenassociatedwithhypoglycaemiain

diabeticpatientsoninsulinororalhypoglycaemicagents;closermonitoringofdiabeticpatientsmayberequired,

especiallyinthefirstfewweeksoftreatment.

Cough:CoughhasbeenreportedwiththeuseofACEinhibitorsincludingquinapril.Characteristically,thecoughis

non-productive,persistentandresolvesafterdiscontinuationoftherapy.ACEinhibitor-inducedcoughshouldbe

consideredaspartofthedifferentialdiagnosisofcough.

Pregnancy:ACEinhibitorsshouldnotbeinitiatedduringpregnancy.UnlesscontinuedACEinhibitortherapyis

consideredessential,patientsplanningpregnancyshouldbechangedtoalternativeantihypertensivetreatmentswhich

haveanestablishedsafetyprofileforuseinpregnancy.Whenpregnancyisdiagnosed,treatmentwithACEinhibitors

shouldbestoppedimmediately,and,ifappropriate,alternativetherapyshouldbestarted(seesections4.3and4.6).

Patientswithrarehereditaryproblemswithgalactoseintolerance,theLapplactasedeficiencyorglucose-galactose

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4.5Interactionwithothermedicinalproductsandotherformsofinteraction

Tetracyclineandotherdrugsthatinteractwithmagnesium:Becauseofthepresenceofmagnesiumcarbonateinthe

formulationAccuprohasbeenshowninhealthyvolunteerstoreducetheabsorptionoftetracyclineinconcomitant

administrationby28-37%.Itisrecommendedthatconcomitantadministrationoftetracyclinebeavoided.

Concomitantdiuretictherapy:Patientstreatedwithdiureticsmayoccasionallyexperienceanexcessivereductionof

bloodpressureafterinitiationoftherapywithAccupro.Thishypotensiveeffectmaybeeffectivelyminimisedbyeither

discontinuingthediureticorincreasingthesaltintakepriortotheinitialdoseofAccupro.

Ifdiscontinuationofthediureticisnotpossible,medicalsupervisionshouldbeprovidedforuptotwohoursfollowing

administrationoftheinitialdose(seeSection4.4Specialwarningsandspecialprecautionsforuseandsection4.2

Posologyandmethodofadministration).

Otheranti-hypertensiveagents:B-blockers,methyldopaanddiureticsmayenhancethehypotensiveeffectsofquinapril,

andshouldonlybeusedundercarefulsupervision.Concomitantpropranololdidnotaffectthepharmacokineticsof

quinaprilinasingledosestudy.

Calciumantagonists:ThereisnoexperienceofconcomitantusewithAccupro.

Atorvastatin:Co-administrationofmultiple10mgdosesofatorvastatinwith80mgquinaprilresultedinnosignificant

changeinthesteadystatepharmacokineticparametersofatorvastatin.

Lithium:Increasedserumlithiumlevelsandsymptomsoflithiumtoxicityhavebeenreportedinpatientsreceiving

concomitantlithiumandACEinhibitortherapyduetothesodium-losingeffectoftheseagents.Thesedrugsshouldbe

co-administeredwithcautionandfrequentmonitoringofserumlithiumlevelsisrecommended.Ifadiureticisalso

used,itmayincreasetheriskoflithiumtoxicity.

Agentsincreasingserumpotassium:Quinaprilisanangiotensin-convertingenzymeinhibitorcapableoflowering

aldosteronelevels,whichinturncanresultinamildelevationinserumpotassium.Concomitanttreatmentswith

potassiumsparingdiuretics,potassiumsupplementsorpotassiumsaltsshouldonlybeusedwithcautionandwith

appropriatemonitoringofserumpotassium,especiallyinpatientswithimpairedrenalfunction,sincebydecreasing

aldosteroneproduction,Accuprooftencausesanincreaseinserumpotassium.

Surgery/anaesthesia:AlthoughnodataareavailabletoindicatethereisaninteractionbetweenAccuproandanaesthetic

agentsthatproduceshypotension,cautionshouldbeexercisedwhenpatientsundergomajorsurgeryoranaesthesia

sinceangiotensinconvertingenzymeinhibitorshavebeenshowntoblockangiotensinIIformationsecondaryto

compensatoryreninrelease.Thismayleadtohypotensionwhichcanbecorrectedbyvolumeexpansion.

Antidiabeticdrugs:ConcomitantadministrationofACEinhibitorsandanti-diabeticmedicines(insulin,oral

hypoglycaemicagents)maycauseanincreasedbloodglucoseloweringeffectwiththeriskofhypoglycaemia.This

phenomenonmaybemorelikelytooccurduringthefirstweeksofcombinedtreatmentandinpatientswithrenal

impairment.

4.6Fertility,pregnancyandlactation

Pregnancy:

EpidemiologicalevidenceregardingtheriskofteratogenicityfollowingexposuretoACEinhibitorsduringthefirst

trimesterofpregnancyhasnotbeenconclusive;howeverasmallincreaseinriskcannotbeexcluded.Unlesscontinued

ACEinhibitortherapyisconsideredessential,patientsplanningpregnancyshouldbechangedtoalternative

antihypertensivetreatmentswhichhaveanestablishedsafetyprofileforuseinpregnancy.Whenpregnancyis

diagnosed,treatmentwithACEinhibitorsshouldbestoppedimmediately,and,ifappropriate,alternativetherapy

shouldbestarted.

ExposuretoACEinhibitortherapyduringthesecondandthirdtrimestersisknowntoinducehumanfoetotoxicity

(decreasedrenalfunction,oligohydramnios,skullossificationretardation)andneonataltoxicity(renalfailure,

hypotension,hyperkalaemia).(Seesection5.3)

ShouldexposuretoACEinhibitorshaveoccurredfromthesecondtrimesterofpregnancy,ultrasoundcheckofrenal

functionandskullisrecommended.InfantswhosemothershavetakenACEinhibitorsshouldbecloselyobservedfor

TheuseofACEinhibitorsisnotrecommendedduringthefirsttrimesterofpregnancy(seesection4.4).Theuseof

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Lactation:Limitedpharmacokineticdatademonstrateverylowconcentrationsinbreastmilk(seesection5.2).

Althoughtheseconcentrationsseemtobeclinicallyirrelevant,theuseofAccuproinbreastfeedingisnot

recommendedforpreterminfantsandforthefirstfewweeksafterdelivery,becausethereisnotenoughclinical

experience.

Inthecaseofanolderinfant,theuseofAccuproinabreast-feedingmothermaybeconsideredifthistreatmentis

necessaryforthemotherandthechildisobservedforanyadverseeffect.

4.7Effectsonabilitytodriveandusemachines

Theabilitytoengageinactivitiessuchasoperatingmachineryoroperatingamotorvehiclemaybeimpairedespecially

wheninitiatingquinapriltherapy.

4.8Undesirableeffects

Themostfrequentclinicaladversereactionsinhypertensionandcongestiveheartfailureareheadache,dizziness,

rhinitis,cough,upperrespiratorytractinfection,fatigue,andnauseaandvomiting.

Increases>1.25timestheupperlimitofnormal)inserumcreatinineandbloodureanitrogenwereobservedin3and

4%respectivelyofthepatientsonmonotherapy.Suchincreasesaremorelikelytooccurinpatientsreceiving

concomitantdiuretictherapythanthoseonmonotherapywithAccupro.Theseobservedincreaseswilloftenreverseon

continuedtherapy.

PancreatitishasbeenreportedrarelyinpatientstreatedwithACEinhibitors;insomecasesthishasprovedfatal.

Renaldysfunction,hypotension,hyperkalaemia,neutropenia,agranulocytosis,angioneuroticoedemaoftheface,

extremities,lips,tongue,glottisand/orlarynxhasbeenreportedrarely(seesection4.4Specialwarningsand

precautionsforuse).

ThefollowingsideeffectshavebeenobservedassociatedwithACEinhibitortherapy:Theadversereactionsare

classifiedaccordingtofrequenciesdeterminedfromclinicaltrialsdata.

Verycommon ≥1/10(≥10%)

Common ≥1/100and<1/10(≥1%and<10%)

Uncommon ≥1/1000and<1/100(≥0.1%and<1%)

Rare ≥1/10,000and<1/1000(≥0.01%and0.1%)

Veryrare<1/10,000(<0.1%)

*Ifalistedadversereactiontermwasnotreportedinclinicaltrialsitwasassumedtoberare,basedonreportingrates

versusestimatedproductuseworldwide.

InfectionsandInfestations:

CommonPharyngitis

UncommonUrinarytractinfection,Sinusitis

BloodandLymphaticSystemDisorders:

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ImmuneSystemDisorders:

RareAnaphylactoidreaction*

PsychiatricDisorders:

CommonInsomnia

UncommonNervousness,Depression

MetabolismandNutritionDisorders:

CommonHyperkalaemia

NervousSystemDisorders:

CommonParaesthesia

UncommonSomnolence,Vertigo

EyeDisorders:

UncommonAmblyopia

CardiacDisorders:

UncommonAnginapectoris,Palpitations,Tachycardia

VascularDisorders:

UncommonVasodilatation

RarePosturalhypotension*,Syncope*

Respiratory,ThoracicandMediastinalDisorders:

CommonDyspnoea

RareEosinophilicpneumonitis

GastrointestinalDisorders:

CommonAbdominalpains

UncommonDrymouthorthroat,Flatulence,Pancreatitis*

HepatobiliaryDisorders:

RareHepatitis

SkinandSubcutaneousTissueDisorders:

UncommonPruritus,rash,Increasedperspiration

RareAlopecia*,Exfoliativedermatitis*,Pemphigus*,Photosensitivityreaction*

MusculoskeletalandConnectiveTissueDisorders:

CommonBackpain,myalgia

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Reproductivesystemandbreastdisorders:

UncommonImpotence

Generaldisordersandadministrationsiteconditions:

CommonAsthenia

UncommonEdema(peripheralandgeneralized)

4.9Overdose

Nodataareavailablewithrespecttooverdosageinhumans.Themostlikelyclinicalmanifestationwouldbesymptoms

attributabletoseverehypotension,whichshouldnormallybetreatedbyintravenousvolumeexpansion

Haemodialysisandperitonealdialysishavelittleeffectontheeliminationofquinaprilandquinaprilat.

5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

ATCCode–CO9AAO6,ACEinhibitors,plain

Accuproisrapidlyde-esterifiedtoquinaprilat(quinaprildiacid,theprincipalmetabolite),which,inhumanandanimal

studies,isapotentangiotensin-convertingenzyme(ACE)inhibitor.TheprimarymodeofactionofAccuproinhumans

andanimalsistoinhibitACE,therebydecreasingvasopressoractivityandaldosteronesecretion.Removalof

angiotensinIInegativefeedbackonreninsecretionleadstoincreasedplasmareninactivity.Accuprohas

antihypertensiveactivityinthepresenceoflowtonormalplasmareninconcentrations.

OtherpossiblemechanismscontributingtotheactivityofACEinhibitorsincludebradykinin-inducedvasodilation,

releaseofprostaglandins,attenuationofsympatheticnervoussystemactivity,andinhibitionoftissueenzyme-

convertingactivity.

Administrationof10-40mgofquinapriltopatientswithmildtomoderatehypertensionresultsinareductionofboth

sittingandstandingbloodpressurewithminimaleffectonheartrate.Antihypertensiveactivitycommenceswithinone

hourwithpeakeffectsusuallyachievedbytwotofourhoursafterdosing.

Achievementofmaximumbloodpressureloweringeffectsmayrequiretwoweeksoftherapyinsomepatients.Atthe

recommendeddoses,antihypertensiveeffectsaremaintainedinmostpatientsthroughoutthe24hourdosinginterval

andcontinueduringlongtermtherapy.

5.2Pharmacokineticproperties

PeakplasmaAccuproconcentrationsareobservedwithin1houroforaladministration.Theextentofabsorptionis

approximately60%,andisnotinfluencedbyfood.Followingabsorption,Accuproisdeesterifiedtoitsmajoractive

metabolite,quinaprilat,andtominorinactivemetabolites.Accuprohasanapparenthalf-lifeofapproximatelyonehour.

Peakplasmaquinaprilatconcentrationsareobservedapproximately2hoursfollowinganoraldoseofquinapril.

Quinaprilatiseliminatedprimarilybyrenalexcretionandhasaneffectiveaccumulationhalf-lifeof3hours.Inpatients

withrenalinsufficiencyandcreatinineclearanceof ≤40ml/min,peakandtroughquinaprilatconcentrationsincrease,

timetopeakconcentrationincreases,apparenthalf-lifeincreases,andtimetosteadystatemaybedelayed.The

eliminationofquinaprilatisalsoreducedinelderlypatients>65years)andcorrelateswellwiththeimpairedrenal

functionwhichfrequentlyoccursintheelderly.StudiesinratsindicatethatAccuproanditsmetabolitesdonotcross

theblood-brainbarrier.

Lactation:Afterasingleoraldoseof20mgofquinaprilinsixbreast-feedingwomen,theM/P(milktoplasmaratio)

forquinaprilwas0.12Quinaprilwasnotdetectedinmilkafter4hoursafterthedose.

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Itisestimatedthatabreastfedinfantwouldreceivedabout1.6%ofthemeternalweight-adjusteddosageofquinapril.

5.3Preclinicalsafetydata

Theresultsofthepreclinicaltestsdonotaddanythingoffurthersignificancetotheprescriber.

6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

ProductfromItaly:

Magnesiumcarbonate

Lactose

Gelatin

Crospovidone

Magnesiumstearate

Candelillawax

Hypromellose

Hyprolose

Titaniumdioxide(E171)

Macrogol400

Redironoxide(E172).

ProductfromGermany:

Magnesiumcarbonate

Lactose

Gelatin

Crospovidone

Magnesiumstearate

Candelillawax

Hypromellose

Hyprolose

Titaniumdioxide(E171)

Macrogol400

6.2Incompatibilities

Notapplicable

6.3ShelfLife

Theshelf-lifeexpirydateofthisproductshallbethedateshownonthecontainerandouterpackageoftheproducton

themarketinthecountryoforigin.

6.4Specialprecautionsforstorage

Donotstoreabove25°C

6.5Natureandcontentsofcontainer

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6.6Specialprecautionsfordisposalofausedmedicinalproductorwastematerialsderivedfrom

suchmedicinalproductandotherhandlingoftheproduct

Nospecialrequirements

7PARALLELPRODUCTAUTHORISATIONHOLDER

B&SHealthcare

Unit4

BradfieldRoad

Ruislip

Middlesex

HA40NU

UnitedKingdom

8PARALLELPRODUCTAUTHORISATIONNUMBER

PPA1328/45/1

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

DateofFirstAuthorisation:20thOctober2006

10DATEOFREVISIONOFTHETEXT

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