ACCUPRO

Main information

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

Documents

Localization

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

Status

  • Source:
  • HPRA - Health Products Regulatory Authority - Ireland
  • Authorization number:
  • PPA1447/003/002
  • Authorization date:
  • 01-10-2010
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

Accupro20mgFilm-CoatedTablets

2QUALITATIVEANDQUANTITATIVECOMPOSITION

OnetabletofAccupro20mgcontains21.664mgQuinaprilhydrochloride,quivalentto20mgquinaprilbase.

Excipients:Containslactosemonohydrate.

Forafulllistofexcipients,seesection6.1.

3PHARMACEUTICALFORM

Film-coatedTablets

ProductimportedfromGermany:

White,round,film-coatedtabletswithascorelineandimprintedwith‘20’ononesideonly.

4CLINICALPARTICULARS

4.1TherapeuticIndications

4.2Posologyandmethodofadministration

Fororaluse.

Adults

Hypertension

MonotherapyTherecommendedinitialdosageis10mgoncedaily.Dependinguponclinicalresponse,patient's

dosagemaybetitrated(bydoublingthedose,allowingadequatetimefordosageadjustment)toamaintenancedosage

of20to40mg/daygivenasasingledoseordividedinto2doses.Long-termcontrolismaintainedinmostpatients

withasingledailydosageregimen.Patientshavebeentreatedwithdosagesupto80mg/day.

ConcomitantDiuretics:Inordertodetermineifexcesshypotensionwilloccur,aninitialdosageof5mgofAccuprois

recommendedinpatientswhoarealsobeingtreatedwithadiuretic.AfterthisthedosageofAccuproshouldbe

titrated(bydoublingthedoseallowingadequatetimefordosageadjustment)totheoptimalresponse(seesection4.5

Forthetreatmentofallgradesofessentialhypertension.Accuproiseffectiveasmonotherapy

orconcomitantlywithdiureticsinpatientswithhypertension.

Forthetreatmentofcongestiveheartfailurewhengivenconcomitantlywithadiureticand/orcardiacglycoside.

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CongestiveHeartFailure

Inordertocloselymonitorpatientsforsymptomatichypotension,asingle5mginitialdosageisrecommended.

Afterthis,patientsshouldbetitratedtoaneffectivedose:(upto40mg/day)givenin1or2doseswithconcomitant

diureticand/orcardiacglycosidetherapy.Patientsareusuallymaintainedeffectivelyondosesof10-20mg/daygiven

withconcomitanttherapy.

Inthetreatmentofsevereorunstablecongestiveheartfailure,Accuproshouldalwaysbeinitiatedinhospitalunder

closemedicalsupervision.

Elderly

Agealonedoesnotappeartoaffecttheefficacyorsafetyprofileofquinapril.Therefore,therecommendedinitial

dosageinhypertensionofquinaprilinelderlypatientsis10mggivenoncedailyfollowedbytitrationtotheoptimal

response.

Children(6-12years)

Notrecommended.Safetyandefficacyinchildrenhasnotbeenestablished.

Patientswithrenalinsufficiency

Inpatientswithacreatinineclearanceoflessthan60ml/min,aninitialdosageinessentialhypertensionof5mgonce

dailyisrecommendedfollowedbytitrationtotheoptimalresponse.Kineticdataindicatethattheapparentelimination

half-lifeofquinaprilatincreasesascreatinineclearancedecreases(seesection4.4Specialwarningsandprecautions

foruse).

4.3Contraindications

Hypersensitivitytoanyoftheingredients.

Accuproiscontraindicatedinthesecondandthirdtrimestersofpregnancy(seesections4.4and4.6).

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

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Inclinicalstudiesinhypertensivepatientswithunilateralorbilateralrenalarterystenosis,increasesinbloodurea

nitrogenandserumcreatininehavebeenobservedinsomepatientsfollowingACEinhibitortherapy.Theseincreases

werealmostalwaysreversibleupondiscontinuationoftheACEinhibitorand/ordiuretictherapy.Insuchpatients,

renalfunctionshouldbemonitoredduringthefirstfewweeksoftherapy.

Somepatientswithhypertensionorheartfailurewithnoapparentpre-existingrenalvasculardiseasehavedeveloped

increases(>1.25timestheupperlimitofnormal)inbloodureaandserumcreatinine,usuallyminorandtransient,

especiallywhenquinaprilhasbeengivenconcomitantlywithadiureticandhasbeenobservedin4%and3%

respectivelyofpatientsonmonotherapy.Thisismorelikelytooccurinpatientswithpre-existingrenalimpairment.

Dosagereductionand/ordiscontinuationofadiureticand/orquinaprilmayberequired.

ImpairedHepaticFunction:Quinaprilwhencombinedwithadiureticshouldbeusedwithcautioninpatientswith

impairedhepaticfunctionorprogressiveliverdisease,sinceminoralterationsoffluidandelectrolytebalancemay

precipitatehepaticcoma.Themetabolismofquinapriltoquinaprilatisnormallydependentuponhepaticesterase.

Quinaprilatconcentrationsarereducedinpatientswithalcoholiccirrhosisduetoimpaireddeesterificationofquinapril.

Anaphylactoidreactions

Desensitisation:PatientsreceivingACEinhibitorsduringdesensitizingtreatmentwithhymenopteravenomhave

sustainedlife-threateninganaphylactoidreactions.InthesamepatientsthesereactionshavebeenavoidedwhenACE

inhibitorsweretemporarilywithheld,buttheyhavereappeareduponinadvertentrechallenge.

LDLapheresis:Patientsundergoinglow-densitylipoproteinapheresiswithdextransulphateabsorptionwhentreated

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).

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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,thecough

isnon-productive,persistentandresolvesafterdiscontinuationoftherapy.ACEinhibitor-inducedcoughshould

beconsideredaspartofthedifferentialdiagnosisofcough.

Patientswithrarehereditaryproblemsofgalactoseintolerance,theLapplactasedeficiencyorglucose-galactose

malabsorptionshouldnottakethismedicine.

Pregnancy:

ACEinhibitorsshouldnotbeinitiatedduringpregnancy.UnlesscontinuedACEinhibitortherapyisconsidered

essential,patientsplanningpregnancyshouldbechangedtoalternativeantihypertensivetreatmentswhichhavean

establishedsafetyprofileforuseinpregnancy.Whenpregnancyisdiagnosed,treatmentwithACEinhibitorsshouldbe

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

4.5Interactionwithothermedicinalproductsandotherformsofinteraction

Tetracyclineandotherdrugsthatinteractwithmagnesium:Becauseofthepresenceofmagnesiumcarbonateinthe

formulationAccuprohasbeenshowninhealthyvolunteerstoreducetheabsorptionoftetracyclineinconcomitant

administrationby28-37%.Itisrecommendedthatconcomitantadministrationoftetracyclinebeavoided.

Concomitantdiuretictherapy:Patientstreatedwithdiureticsmayoccasionallyexperienceanexcessivereductionof

bloodpressureafterinitiationoftherapywithAccupro.Thishypotensiveeffectmaybeeffectivelyminimisedby

eitherdiscontinuingthediureticorincreasingthesaltintakepriortotheinitialdoseofAccupro.Ifdiscontinuationof

thediureticisnotpossible,medicalsupervisionshouldbeprovidedforuptotwohoursfollowingadministrationof

theinitialdose(seeSection4.4andSection4.2).

Otheranti-hypertensiveagents:beta-blockers,methyldopaanddiureticsmayenhancethehypotensiveeffectsof

quinapril,andshouldonlybeusedundercarefulsupervision.Concomitantpropranololdidnotaffectthe

pharmacokineticsofquinaprilinasingledosestudy.

Calciumantagonists:ThereisnoexperienceofconcomitantusewithAccupro.

Atorvastatin:Co-administrationofmultiple10mgdosesofatorvastatinwith80mgquinaprilresultedinnosignificant

changeinthesteadystatepharmacokineticparametersofatorvastatin.

Lithium:Increasedserumlithiumlevelsandsymptomsoflithiumtoxicityhavebeenreportedinpatientsreceiving

concomitantlithiumandACEinhibitortherapyduetothesodium-losingeffectoftheseagents.Thesedrugsshouldbe

co-administeredwithcautionandfrequentmonitoringofserumlithiumlevelsisrecommended.Ifadiureticisalso

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Agentsincreasingserumpotassium:Quinaprilisanangiotensin-convertingenzymeinhibitorcapableoflowering

aldosteronelevels,whichinturncanresultinamildelevationinserumpotassium.Concomitanttreatmentswith

potassiumsparingdiuretics,potassiumsupplementsorpotassiumsaltsshouldonlybeusedwithcautionandwith

appropriatemonitoringofserumpotassium,especiallyinpatientswithimpairedrenalfunction,sincebydecreasing

aldosteroneproduction,Accuprooftencausesanincreaseinserumpotassium.

Surgery/anaesthesia:AlthoughnodataareavailabletoindicatethereisaninteractionbetweenAccuproand

anaestheticagentsthatproduceshypotension,cautionshouldbeexercisedwhenpatientsundergomajorsurgeryor

anaesthesiasinceangiotensinconvertingenzymeinhibitorshavebeenshowntoblockangiotensinIIformation

secondarytocompensatoryreninrelease.Thismayleadtohypotensionwhichcanbecorrectedbyvolumeexpansion.

Antidiabeticdrugs:ConcomitantadministrationofACEinhibitorsandanti-diabeticmedicines(insulin,oral

hypoglycaemicagents)maycauseanincreasedbloodglucoseloweringeffectwiththeriskofhypoglycaemia.

Thisphenomenonmaybemorelikelytooccurduringthefirstweeksofcombinedtreatmentandinpatientswithrenal

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).ShouldexposuretoACEinhibitorhaveoccurredfromthesecondtrimesterofpregnancy,

ultrasoundcheckofrenalfunctionandskullisrecommended.InfantswhosemothershavetakenACEinhibitorsshould

becloselyobservedforhypotension(seesections4.3and4.4).

Accuprohasbeenshowntobefoetotoxicintherabbit.WhenACEinhibitorshavebeenusedduringthesecondand

thirdtrimestersofpregnancy,therehavebeenreportsofhypotension,renalfailure,skullhypoplasia,and/ordeathinthe

newborn.Oligohydramnioshasalsobeenreported,presumablyrepresentingdecreasedrenalfunctioninthefoetus;

limbcontractures,craniofacialdeformities,hypoplasticlungdevelopment,andintrauterinegrowthretardationhave

beenreportedinassociationwitholigohydramnios.InfantsexposedinuterotoACEinhibitorsshouldbeclosely

observedforhypotension,oliguria,andhyperkalaemia.Ifoliguriaoccurs,attentionshouldbedirectedtowardsupport

ofbloodpressureandrenalperfusion.

Lactation:

Limitedpharmacokineticdatademonstrateverylowconcentrationsinbreastmilk(seesection5.2).Althoughthese

concentrationsseemtobeclinicallyirrelevant,theuseofAccuproinbreastfeedingisnotrecommendedforpreterm

infantsandforthefirstfewweeksafterdelivery,becauseofthehypotheticalriskofcardiovascularandrenaleffects

andbecausethereisnotenoughclinicalexperience.

Inthecaseofanolderinfant,theuseofAccuproinabreast-feedingmothermaybeconsideredifthistreatmentis

TheuseofACEinhibitorsisnotrecommendedduringthefirsttrimesterofpregnancy(seesection4.4).Theuseof

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4.7Effectsonabilitytodriveandusemachines

Theabilitytoengageinactivitiessuchasoperatingmachineryoroperatingamotorvehiclemaybeimpairedespecially

wheninitiatingquinapriltherapy.

4.8Undesirableeffects

Themostfrequentclinicaladversereactionsinhypertensionandcongestiveheartfailureareheadache,dizziness,

rhinitis,cough,upperrespiratorytractinfection,fatigue,andnauseaandvomiting.

Increases(>1.25timestheupperlimitofnormal)inserumcreatinineandbloodureanitrogenwereobservedin3and

4%respectivelyofthepatientsonmonotherapy.Suchincreasesaremorelikelytooccurinpatientsreceiving

concomitantdiuretictherapythanthoseonmonotherapywithAccupro.Theseobservedincreaseswilloftenreverse

oncontinuedtherapy.

PancreatitishasbeenreportedrarelyinpatientstreatedwithACEinhibitors;insomecasesthishasprovedfatal.

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

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

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:

Common:Pharyngitis.

Uncommon:Urinarytractinfection,Sinusitis.

BloodandLymphaticSystemDisorders:

Rare:Neutropenia,Agranulocytosis,Haemolyticanaemia*,Thrombocytopenia*.

ImmuneSystemDisorders:

Rare:Anaphylactoidreactions*.

PsychiatricDisorders:

Common:Insomnia.

Uncommon:Nervousness,Depression.

MetabolismandNutritionDisorders:

Common:Hyperkalaemia.

NervousSystemDisorders:

Common:Paraesthesia.

Uncommon:Somnolence,Vertigo.

EyeDisorders:

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CardiacDisorders

Uncommon:Anginapectoris,Palpitations,Tachycardia.

VascularDisorders:

Uncommon:Vasodilatation.

Rare:Posturalhypotension*,Syncope*.

Respiratory,ThoracicandMediastinalDisorders:

Common:Dyspnoea.

Rare:Eosinophilicpneumonitis.

GastrointestinalDisorders:

Common:Abdominalpains.

Uncommon:Drymouthorthroat,Flatulence,Pancreatitis*.

HepatobiliaryDisorders

Rare:Hepatitis.

SkinandSubcutaneousTissueDisorders:

Uncommon:Pruritus,rash,Increasedperspiration.

Rare:Alopecia*,Exfoliativedermatitis*,Pemphigus*,Photosensitivityreactions*.

MusculoskeletalandConnectiveTissueDisorders:

Common:Backpain,Myalgia.

Uncommon:Arthralgia.

Reproductivesystemandbreastdisorders:

Uncommon:Impotence.

Generaldisordersandadministrationsiteconditions:

Common:Asthenia.

Uncommon:Edema(peripheralandgeneralized).

4.9Overdose

Nodataareavailablewithrespecttooverdosageinhumans.Themostlikelyclinicalmanifestationwouldbe

symptomsattributabletoseverehypotension,whichshouldnormallybetreatedbyintravenousvolumeexpansion.

Haemodialysisandperitonealdialysishavelittleeffectontheeliminationofquinaprilandquinaprilat.

5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

ATCCode–CO9AA06,ACEinhibitors,plain.

Accuproisrapidlydeesterifiedtoquinaprilat(quinaprildiacid,theprincipalmetabolite)which,inhumanandanimal

studies,isapotentangiotensin-convertingenzyme(ACE)inhibitor.TheprimarymodeofactionofAccuproin

humansandanimalsistoinhibitACE,therebydecreasingvasopressoractivityandaldosteronesecretion.Removalof

angiotensinIInegativefeedbackonreninsecretionleadstoincreasedplasmareninactivity.Accuprohas

antihypertensiveactivityinthepresenceoflowtonormalplasmareninconcentrations.

OtherpossiblemechanismscontributingtotheactivityofACEinhibitorsincludebradykinin-inducedvasodilation,

releaseofprostaglandins,attenuationofsympatheticnervoussystemactivity,andinhibitionoftissueenzyme-

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Administrationof10-40mgofquinapriltopatientswithmildtomoderatehypertensionresultsinareductionofboth

sittingandstandingbloodpressurewithminimaleffectonheartrate.Antihypertensiveactivitycommenceswithinone

hourwithpeakeffectsusuallyachievedbytwotofourhoursafterdosing.Achievementofmaximumbloodpressure

loweringeffectsmayrequiretwoweeksoftherapyinsomepatients.Attherecommendeddoses,antihypertensive

effectsaremaintainedinmostpatientsthroughoutthe24hourdosingintervalandcontinueduringlongtermtherapy.

5.2Pharmacokineticproperties

PeakplasmaAccuproconcentrationsareobservedwithin1houroforaladministration.Theextentofabsorptionis

approximately60%,andisnotinfluencedbyfood.Followingabsorption,Accuproisdeesterifiedtoitsmajoractive

metabolite,quinaprilat,andtominorinactivemetabolites.Accuprohasanapparenthalf-lifeofapproximatelyone

hour.Peakplasmaquinaprilatconcentrationsareobservedapproximately2hoursfollowinganoraldoseofquinapril.

Quinaprilatiseliminatedprimarilybyrenalexcretionandhasaneffectiveaccumulationhalf-lifeof3hours.In

patientswithrenalinsufficiencyandcreatinineclearanceof<40ml/min,peakandtroughquinaprilatconcentrations

increase,timetopeakconcentrationincreases,apparenthalf-lifeincreases,andtimetosteadystatemaybedelayed.

Theeliminationofquinaprilatisalsoreducedinelderlypatients(>65years)andcorrelateswellwiththeimpaired

renalfunctionwhichfrequentlyoccursintheelderly.StudiesinratsindicatethatAccuproanditsmetabolitesdonot

crosstheblood-brainbarrier.

Lactation:

Afterasingleoraldoseof20mgofquinaprilinsixbreast-feedingwomen,theM/P(milktoplasmaratio)forquinaprilwas

0.12.Quinaprilwasnotdetectedinmilkafter4hoursafterthedose.Quinalaprilatmilklevelswereundetectable(<5µg/L)

atalltimepoints.Itisestimatedthatabreastfedinfantwouldreceiveabout1.6%ofthematernalweight-adjusteddosageof

quinapril.

5.3Preclinicalsafetydata

Theresultsofthepreclinicaltestsdonotaddanythingoffurthersignificancetotheprescriber.

6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

Magnesiumcarbonate

Lactosemonohydrate

Gelatin

Crospovidone

Magnesiumstearate

Candelillawax

Hypromellose

Hydroxypropylcellulose

Titaniumdioxide(E171)

Macrogol400

6.2Incompatibilities

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6.3Shelflife

Theshelf-lifeexpirydateofthisproductisthedateshownontheblisterlabelandoutercartonoftheproductonthe

marketinthecountryoforigin.

6.4Specialprecautionsforstorage

Donotstoreabove25 °

6.5Natureandcontentsofcontainer

3blisterstripscontaining10tablets

Eachpackcontains30tablets.

6.6Specialprecautionsfordisposalofausedmedicinalproductorwastematerialsderivedfrom

suchmedicinalproductandotherhandlingoftheproduct

Nospecialrequirements.

7PARALLELPRODUCTAUTHORISATIONHOLDER

G&ALicensingLtd

Ballymurray

Co.Roscommon

Ireland

8PARALLELPRODUCTAUTHORISATIONNUMBER

PPA1447/3/2

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

Dateoffirstauthorisation:1stOctober2010

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