ACCUPRO

Main information

  • Trade name:
  • ACCUPRO Film Coated Tablet 5 Milligram
  • Dosage:
  • 5 Milligram
  • Pharmaceutical form:
  • Film Coated Tablet
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug

Documents

Localization

  • Available in:
  • ACCUPRO Film Coated Tablet 5 Milligram
    Ireland
  • Language:
  • English

Other information

Status

  • Source:
  • HPRA - Health Products Regulatory Authority - Ireland
  • Authorization number:
  • PPA1447/003/001
  • Authorization date:
  • 25-07-2008
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage,interactions,side effects

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

Accupro5mgFilm-CoatedTablets

2QUALITATIVEANDQUANTITATIVECOMPOSITION

Eachtabletcontains:

Quinaprilhydrochloride5.416mg(Equivalentto5mgquinaprilbase).

ContainsLactose

Forexcipients,seeSection,6.1.

3PHARMACEUTICALFORM

Film-coatedTablets

ProductImportedfromGreece

Brown,ellipticalfilm-coatedtabletwithabreaklineandimprintedwiththedosagestrength‘5’onbothsides

4CLINICALPARTICULARS

4.1TherapeuticIndications

1.Forthetreatmentofallgradesofessentialhypertension.Accuproiseffectiveasmonotherapyorconcomitantlywith

diureticsinpatientswithhypertension.

2.Forthetreatmentofcongestiveheartfailurewhengivenconcomitantlywithadiureticand/orcardiacglycoside.

TreatmentofcongestiveheartfailurewithAccuproshouldalwaysbeinitiatedunderclosemedicalsupervision.

4.2Posologyandmethodofadministration

Fororaluse.

Adults

Hypertension

Monotherapy:Therecommendedinitialdosageis10mgoncedaily.Dependinguponclinicalresponse,patient'sdosage

maybetitrated(bydoublingthedose,allowingadequatetimefordosageadjustment)toamaintenancedosageof20to

40mg/daygivenasasingledoseordividedinto2doses.Long-termcontrolismaintainedinmost

patientswithasingledailydosageregimen.Patientshavebeentreatedwithdosagesupto80mg/day.

ConcomitantDiuretics:Inordertodetermineifexcesshypotensionwilloccur,aninitialdosageof5mgofAccuprois

recommendedinpatientswhoarealsobeingtreatedwithadiuretic.AfterthisthedosageofAccuproshouldbetitrated

(bydoublingthedoseallowingadequatetimefordosageadjustment)totheoptimalresponse(seesection4.5

Interactionwithothermedicinalproductsandotherformsofinteraction).

CongestiveHeartFailure

Inordertocloselymonitorpatientsforsymptomatichypotension,asingle5mginitialdosageisrecommended.After

this,patientsshouldbetitratedtoaneffectivedose:(upto40mg/day)givenin1or2doseswithconcomitantdiuretic

and/orcardiacglycosidetherapy.

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Inthetreatmentofsevereorunstablecongestiveheartfailure,Accuproshouldalwaysbeinitiatedinhospitalunder

closemedicalsupervision.

Elderly

Agealonedoesnotappeartoaffecttheefficacyorsafetyprofileofquinapril.Therefore,therecommendedinitial

dosageinhypertensionofquinaprilinelderlypatientsis10mggivenoncedailyfollowedbytitrationtotheoptimal

response.

Children(6-12years)

Notrecommended.Safetyandefficacyinchildrenhasnotbeenestablished.

Patientswithrenalinsufficiency

Inpatientswithacreatinineclearanceoflessthan60ml/min,aninitialdosageinessentialhypertensionof5mgonce

dailyisrecommendedfollowedbytitrationtotheoptimalresponse.Kineticdataindicatethattheapparentelimination

half-lifeofquinaprilatincreasesascreatinineclearancedecreases(seesection4.4Specialwarnings

andprecautionsforuse).

4.3Contraindications

Hypersensitivitytoanyoftheingredients

Useinpatientswithsubaorticstenosis.

UseinpatientswithahistoryofangioneuroticoedemarelatingtoprevioustreatmentwithanACEinhibitor.

Secondandthirdtrimestersofpregnancy(seesections4.4and4.6).

4.4Specialwarningsandprecautionsforuse

Pregnancy:ACEinhibitorsshouldnotbeinitiatedduringpregnancy.UnlesscontinuedACEinhibitortherapyis

consideredessential,patientsplanningpregnancyshouldbechangedtoalternativeantihypertensivetreatmentswhich

haveanestablishedsafetyprofileforuseinpregnancy.Whenpregnancyisdiagnosed,treatmentwithACEinhibitors

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

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%

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Dosagereductionand/ordiscontinuationofadiureticand/orquinaprilmayberequired.

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

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Hypoglycaemia:ACEinhibitorsmayenhanceinsulinsensitivityandhavebeenassociatedwithhypoglycaemiain

diabeticpatientsoninsulinororalhypoglycaemicagents;closermonitoringofdiabeticpatientsmayberequired,

especiallyinthefirstfewweeksoftreatment.

Cough:CoughhasbeenreportedwiththeuseofACEinhibitorsincludingquinapril.Characteristically,thecoughis

non-productive,persistentandresolvesafterdiscontinuationoftherapy.ACEinhibitor-inducedcoughshouldbe

consideredaspartofthedifferentialdiagnosisofcough.

Patientswithrarehereditaryproblemswithgalactoseintolerance,theLapplactasedeficiencyorglucose-galactose

malabsorptionshouldnottakethismedicine.

4.5Interactionwithothermedicinalproductsandotherformsofinteraction

Tetracyclineandotherdrugsthatinteractwithmagnesium:Becauseofthepresenceofmagnesiumcarbonateinthe

formulationAccuprohasbeenshowninhealthyvolunteerstoreducetheabsorptionoftetracyclineinconcomitant

administrationby28-37%.Itisrecommendedthatconcomitantadministrationoftetracyclinebeavoided.

Concomitantdiuretictherapy:Patientstreatedwithdiureticsmayoccasionallyexperienceanexcessivereductionof

bloodpressureafterinitiationoftherapywithAccupro.Thishypotensiveeffectmaybeeffectivelyminimizedbyeither

discontinuingthediureticorincreasingthesaltintakepriortotheinitialdoseofAccupro.Ifdiscontinuationofthe

diureticisnotpossible,medicalsupervisionshouldbeprovidedforuptotwohours

followingadministrationoftheinitialdose(seeSection4.4SpecialwarningsandprecautionsforuseandSection4.2

Posologyandmethodofadministration).

Otheranti-hypertensiveagents:beta-blockers,methyldopaanddiureticsmayenhancethehypotensiveeffectsof

quinapril,andshouldonlybeusedundercarefulsupervision.Concomitantpropranololdidnotaffectthe

pharmacokineticsofquinaprilinasingledosestudy.

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:AlthoughnodataareavailabletoindicatethereisaninteractionbetweenAccuproand

anaestheticagentsthatproduceshypotension,cautionshouldbeexercisedwhenpatientsundergomajorsurgeryor

anaesthesiasinceangiotensinconvertingenzymeinhibitorshavebeenshowntoblockangiotensinIIformation

secondarytocompensatoryreninrelease.Thismayleadtohypotensionwhichcanbecorrectedbyvolumeexpansion.

Antidiabeticdrugs:ConcomitantadministrationofACEinhibitorsandanti-diabeticmedicines(insulin,oral

hypoglycaemicagents)maycauseanincreasedbloodglucoseloweringeffectwiththeriskofhypoglycaemia.This

phenomenonmaybemorelikelytooccurduringthefirstweeksofcombinedtreatmentandinpatientswithrenal

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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

necessaryforthemotherandthechildisobservedforanyadverseeffect.

4.7Effectsonabilitytodriveandusemachines

Theabilitytoengageinactivitiessuchasoperatingmachineryoroperatingamotorvehiclemaybeimpairedespecially

wheninitiatingquinapriltherapy.

4.8Undesirableeffects

Themostfrequentclinicaladversereactionsinhypertensionandcongestiveheartfailureareheadache,dizziness,rhinitis,cough,

upperrespiratorytractinfection,fatigue,andnauseaandvomiting.

Increases(>1.25timestheupperlimitofnormal)inserumcreatinineandbloodureanitrogenwereobservedin3and4%

respectivelyofthepatientsonmonotherapy.Suchincreasesaremorelikelytooccurinpatientsreceivingconcomitantdiuretic

therapythanthoseonmonotherapywithAccupro.Theseobservedincreaseswilloftenreverseoncontinuedtherapy.

TheuseofACEinhibitorsisnotrecommendedduringthefirsttrimesterofpregnancy

(seesection4.4).TheuseofACEinhibitorsiscontraindicatedduringthe2ndand3rd

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Renaldysfunction,hypotension,hyperkalaemia,neutropenia,agranulocytosis,angioneuroticoedemaoftheface,extremities,lips,

tongue,glottisand/orlarynxhasbeenreportedrarely(seesection4.4Specialwarningsandprecautionsforuse).

ThefollowingsideeffectshavebeenobservedassociatedwithACEinhibitortherapy:Theadversereactionsareclassified

accordingtofrequenciesdeterminedfromclinicaltrialsdata.

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,basedonreportingratesversus

estimatedproductuseworldwide.

InfectionsandInfestations:

Common:Pharyngitis

Uncommon:Urinarytractinfection,Sinusitis

BloodandLymphaticSystemDisorders:

Rare:Neutropenia,agranulocytosis,Haemolyticanaemia*,Thrombocytopenia*

ImmuneSystemDisorders:

Rare:Anaphylactoidreaction*

PsychiatricDisorders:

Common:Insomnia

Uncommon:Nervousness,Depression

MetabolismandNutritionDisorders:

Common:Hyperkalaemia

NervousSystemDisorders:

Common:Paraesthesia

Uncommon:Somnolence,Vertigo

EyeDisorders:

Uncommon:Amblyopia

CardiacDisorders:

Uncommon:Anginapectoris,Palpitations,Tachycardia

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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*,Photosensitivityreaction*

MusculoskeletalandConnectiveTissueDisorders:

Common:Backpain,myalgia

Uncommon:Arthralgia

Reproductivesystemandbreastdisorders:

Uncommon:Impotence

Generaldisordersandadministrationsiteconditions:

Common:Asthenia

Uncommon:Edema(peripheralandgeneralized)

4.9Overdose

Nodataareavailablewithrespecttooverdosageinhumans.Themostlikelyclinicalmanifestationwouldbesymptoms

attributabletoseverehypotension,whichshouldnormallybetreatedbyintravenousvolumeexpansion.

Haemodialysisandperitonealdialysishavelittleeffectontheeliminationofquinaprilandquinaprilat.

5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

ATCCode–CO9AA06,ACEinhibitors,plain.

Accuproisrapidlydeesterifiedtoquinaprilat(quinaprildiacid,theprincipalmetabolite)which,inhumanandanimal

studies,isapotentangiotensin-convertingenzyme(ACE)inhibitor.TheprimarymodeofactionofAccuproinhumans

andanimalsistoinhibitACE,therebydecreasingvasopressoractivityandaldosteronesecretion.Removalof

angiotensinIInegativefeedbackonreninsecretionleadstoincreasedplasmareninactivity.Accuprohas

antihypertensiveactivityinthepresenceoflowtonormalplasmareninconcentrations.

OtherpossiblemechanismscontributingtotheactivityofACEinhibitorsincludebradykinin-inducedvasodilation,

releaseofprostaglandins,attenuationofsympatheticnervoussystemactivity,andinhibitionoftissue

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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-lifeofapproximatelyonehour.

Peakplasmaquinaprilatconcentrationsareobservedapproximately2hoursfollowinganoraldoseofquinapril.

Quinaprilatiseliminatedprimarilybyrenalexcretionandhasaneffectiveaccumulationhalf-lifeof3hours.Inpatients

withrenalinsufficiencyandcreatinineclearanceof40ml/min,peakandtroughquinaprilatconcentrationsincrease,

timetopeakconcentrationincreases,apparenthalf-lifeincreases,andtimetosteadystatemaybedelayed.The

eliminationofquinaprilatisalsoreducedinelderlypatients(>65years)andcorrelateswellwiththeimpairedrenal

functionwhichfrequentlyoccursintheelderly.StudiesinratsindicatethatAccuproanditsmetabolitesdonotcross

theblood-brainbarrier.

Lactation:

Afterasingleoraldoseof20mgofquinaprilinsixbreast-feedingwomen,theM/P(milktoplasmaratio)forquinapril

was0.12.Quinaprilwasnotdetectedinmilkafter4hoursafterthedose.Quinalaprilatmilklevelswereundetectable

(<5µg/L)atalltimepoints.Itisestimatedthatabreastfedinfantwouldreceiveabout1.6%ofthematernalweight-

adjusteddosageofquinapril.

5.3Preclinicalsafetydata

Theresultsofthepreclinicaltestsdonotaddanythingoffurthersignificancetotheprescriber.

6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

Heavymagnesiumcarbonate

Lactosemonohydrate

Gelatin

Crospovidone

Magnesiumstearate

Candelilla

OpadryBrownY-5-9020Gcontaining:

Hypromellose

Hyprolose

Titaniumdioxide(E171)

Macrogol400

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6.2Incompatibilities

Notapplicable.

6.3Shelflife

Theshelf-lifeexpirydateofthisproductshallbethedateshownonthecontainerandouterpackageoftheproductin

thecountryoforigin.

6.4Specialprecautionsforstorage

Donotstoreabove25°C.

6.5Natureandcontentsofcontainer

Blisterpacksof28tabletscontainedinanoverlabelledoutercardboardcarton.

6.6Specialprecautionsfordisposalandotherhandling

Nospecialrequirements.

7PARALLELPRODUCTAUTHORISATIONHOLDER

G&ALicensing

Ballymurray

Co.Roscommon

Ireland

8PARALLELPRODUCTAUTHORISATIONNUMBER

PPA1447/3/1

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

DateofFirstAuthorisation:25thJuly2008

10DATEOFREVISIONOFTHETEXT

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4-2-2019


Opinion/decision on a Paediatric investigation plan (PIP): Edurant,Rilpivirine (hydrochloride), decision type: , therapeutic area: , PIP number: P/0322/2018

Opinion/decision on a Paediatric investigation plan (PIP): Edurant,Rilpivirine (hydrochloride), decision type: , therapeutic area: , PIP number: P/0322/2018

Opinion/decision on a Paediatric investigation plan (PIP): Edurant,Rilpivirine (hydrochloride), decision type: , therapeutic area: , PIP number: P/0322/2018

Europe - EMA - European Medicines Agency

1-2-2019


Summary of opinion: Doxolipad,doxorubicin hydrochloride,  31/01/2019,  Negative

Summary of opinion: Doxolipad,doxorubicin hydrochloride, 31/01/2019, Negative

Summary of opinion: Doxolipad,doxorubicin hydrochloride, 31/01/2019, Negative

Europe - EMA - European Medicines Agency

31-1-2019


Opinion/decision on a Paediatric investigation plan (PIP): Ciprofloxacin (hydrochloride), decision type: , therapeutic area: , PIP number: P/0253/2018

Opinion/decision on a Paediatric investigation plan (PIP): Ciprofloxacin (hydrochloride), decision type: , therapeutic area: , PIP number: P/0253/2018

Opinion/decision on a Paediatric investigation plan (PIP): Ciprofloxacin (hydrochloride), decision type: , therapeutic area: , PIP number: P/0253/2018

Europe - EMA - European Medicines Agency

31-1-2019


Opinion/decision on a Paediatric investigation plan (PIP): Cariprazine (hydrochloride), decision type: , therapeutic area: , PIP number: P/0301/2018

Opinion/decision on a Paediatric investigation plan (PIP): Cariprazine (hydrochloride), decision type: , therapeutic area: , PIP number: P/0301/2018

Opinion/decision on a Paediatric investigation plan (PIP): Cariprazine (hydrochloride), decision type: , therapeutic area: , PIP number: P/0301/2018

Europe - EMA - European Medicines Agency

29-1-2019


Chlorphenoxamine hydrochloride : List of nationally authorised medicinal products - PSUSA/00010361/201805

Chlorphenoxamine hydrochloride : List of nationally authorised medicinal products - PSUSA/00010361/201805

Chlorphenoxamine hydrochloride : List of nationally authorised medicinal products - PSUSA/00010361/201805

Europe - EMA - European Medicines Agency

28-1-2019


Opinion/decision on a Paediatric investigation plan (PIP): Sarizotan (hydrochloride), decision type: , therapeutic area: , PIP number: P/0287/2018

Opinion/decision on a Paediatric investigation plan (PIP): Sarizotan (hydrochloride), decision type: , therapeutic area: , PIP number: P/0287/2018

Opinion/decision on a Paediatric investigation plan (PIP): Sarizotan (hydrochloride), decision type: , therapeutic area: , PIP number: P/0287/2018

Europe - EMA - European Medicines Agency

28-1-2019

Clomicalm (Elanco GmbH)

Clomicalm (Elanco GmbH)

Clomicalm (Active substance: Clomipramine hydrochloride) - Centralised - Transfer Marketing Authorisation Holder - Commission Decision (2019)720 of Mon, 28 Jan 2019 European Medicines Agency (EMA) procedure number: EMEA/V/C/000039/T/0030

Europe -DG Health and Food Safety

23-1-2019


Orphan designation: 3-(5-Amino-2-methyl-4-oxoquinazolin-3(4H)-yl)piperidine-2,6-dione hydrochloride-, Treatment of diffuse large B-cell lymphoma, 27/06/2016, Positive

Orphan designation: 3-(5-Amino-2-methyl-4-oxoquinazolin-3(4H)-yl)piperidine-2,6-dione hydrochloride-, Treatment of diffuse large B-cell lymphoma, 27/06/2016, Positive

Orphan designation: 3-(5-Amino-2-methyl-4-oxoquinazolin-3(4H)-yl)piperidine-2,6-dione hydrochloride-, Treatment of diffuse large B-cell lymphoma, 27/06/2016, Positive

Europe - EMA - European Medicines Agency

22-1-2019


Orphan designation: Doxorubicin hydrochloride (in heat-sensitive liposomes), Treatment of hepatocellular carcinoma, 23/02/2011, Positive

Orphan designation: Doxorubicin hydrochloride (in heat-sensitive liposomes), Treatment of hepatocellular carcinoma, 23/02/2011, Positive

Orphan designation: Doxorubicin hydrochloride (in heat-sensitive liposomes), Treatment of hepatocellular carcinoma, 23/02/2011, Positive

Europe - EMA - European Medicines Agency

16-1-2019

EU/3/18/2125 (Isabelle Ramirez)

EU/3/18/2125 (Isabelle Ramirez)

EU/3/18/2125 (Active substance: Benserazide hydrochloride) - Orphan designation - Commission Decision (2019)221 of Wed, 16 Jan 2019 European Medicines Agency (EMA) procedure number: EMA/OD/0000001719

Europe -DG Health and Food Safety

16-1-2019

EU/3/10/833 (FGK Representative Service GmbH)

EU/3/10/833 (FGK Representative Service GmbH)

EU/3/10/833 (Active substance: Doxorubicin hydrochloride (in heat-sensitive liposomes)) - Transfer of orphan designation - Commission Decision (2019)237 of Wed, 16 Jan 2019 European Medicines Agency (EMA) procedure number: EMA/OD/0000003113

Europe -DG Health and Food Safety

16-1-2019

EU/3/16/1672 (Celgene Europe B.V.)

EU/3/16/1672 (Celgene Europe B.V.)

EU/3/16/1672 (Active substance: 3-(5-amino-2-methyl-4-oxoquinazolin-3(4H)-yl)piperidine-2,6-dione hydrochloride) - Transfer of orphan designation - Commission Decision (2019)236 of Wed, 16 Jan 2019 European Medicines Agency (EMA) procedure number: EMA/OD/0000003283

Europe -DG Health and Food Safety

11-1-2019


Opinion/decision on a Paediatric investigation plan (PIP): Octenidine (dihydrochloride), decision type: , therapeutic area: , PIP number: P/0240/2018

Opinion/decision on a Paediatric investigation plan (PIP): Octenidine (dihydrochloride), decision type: , therapeutic area: , PIP number: P/0240/2018

Opinion/decision on a Paediatric investigation plan (PIP): Octenidine (dihydrochloride), decision type: , therapeutic area: , PIP number: P/0240/2018

Europe - EMA - European Medicines Agency

13-12-2018


Overview of comments received on 'Pegylated liposomal doxorubicin hydrochloride concentrate for solution 2 mg/ml product-specific bioequivalence guidance' (EMA/CHMP/800775/2017)

Overview of comments received on 'Pegylated liposomal doxorubicin hydrochloride concentrate for solution 2 mg/ml product-specific bioequivalence guidance' (EMA/CHMP/800775/2017)

Overview of comments received on 'Pegylated liposomal doxorubicin hydrochloride concentrate for solution 2 mg/ml product-specific bioequivalence guidance' (EMA/CHMP/800775/2017)

Europe - EMA - European Medicines Agency

13-12-2018


Pegylated liposomal doxorubicin hydrochloride concentrate for solution 2 mg/ml product-specific bioequivalence guidance

Pegylated liposomal doxorubicin hydrochloride concentrate for solution 2 mg/ml product-specific bioequivalence guidance

Pegylated liposomal doxorubicin hydrochloride concentrate for solution 2 mg/ml product-specific bioequivalence guidance

Europe - EMA - European Medicines Agency

11-12-2018


Epinephrine mepivacaine hydrochloride, mepivacaine norepinephrine, mepivacaine: List of nationally authorised medicinal products - PSUSA/00001979/201803

Epinephrine mepivacaine hydrochloride, mepivacaine norepinephrine, mepivacaine: List of nationally authorised medicinal products - PSUSA/00001979/201803

Epinephrine mepivacaine hydrochloride, mepivacaine norepinephrine, mepivacaine: List of nationally authorised medicinal products - PSUSA/00001979/201803

Europe - EMA - European Medicines Agency

28-11-2018


Opinion/decision on a Paediatric investigation plan (PIP): Fenfluramine (hydrochloride), decision type: , therapeutic area: , PIP number: P/0177/2018

Opinion/decision on a Paediatric investigation plan (PIP): Fenfluramine (hydrochloride), decision type: , therapeutic area: , PIP number: P/0177/2018

Opinion/decision on a Paediatric investigation plan (PIP): Fenfluramine (hydrochloride), decision type: , therapeutic area: , PIP number: P/0177/2018

Europe - EMA - European Medicines Agency

28-11-2018


Opinion/decision on a Paediatric investigation plan (PIP): Mexiletine (hydrochloride), decision type: , therapeutic area: , PIP number: P/0210/2018

Opinion/decision on a Paediatric investigation plan (PIP): Mexiletine (hydrochloride), decision type: , therapeutic area: , PIP number: P/0210/2018

Opinion/decision on a Paediatric investigation plan (PIP): Mexiletine (hydrochloride), decision type: , therapeutic area: , PIP number: P/0210/2018

Europe - EMA - European Medicines Agency

28-11-2018

Econor (Elanco GmbH)

Econor (Elanco GmbH)

Econor (Active substance: Valnemulin hydrochloride) - Centralised - Transfer Marketing Authorisation Holder - Commission Decision (2018)8038 of Wed, 28 Nov 2018 European Medicines Agency (EMA) procedure number: EMEA/V/C/42/T/54

Europe -DG Health and Food Safety

28-11-2018


Opinion/decision on a Paediatric investigation plan (PIP): ( 2R)-2-Amino-1-[3-( {2-[p-( 4-{3-[ (3,S-diamino-6-chloro-2-pyrazinyl)ca rbonyl ]guanidino }butyl )phenoxy ]ethyl}{ 3-[ ( 2R)-2-am ino-6-guanidinohexanoyla mino] propyl }amino )propylamino ]-6-gu

Opinion/decision on a Paediatric investigation plan (PIP): ( 2R)-2-Amino-1-[3-( {2-[p-( 4-{3-[ (3,S-diamino-6-chloro-2-pyrazinyl)ca rbonyl ]guanidino }butyl )phenoxy ]ethyl}{ 3-[ ( 2R)-2-am ino-6-guanidinohexanoyla mino] propyl }amino )propylamino ]-6-gu

Opinion/decision on a Paediatric investigation plan (PIP): ( 2R)-2-Amino-1-[3-( {2-[p-( 4-{3-[ (3,S-diamino-6-chloro-2-pyrazinyl)ca rbonyl ]guanidino }butyl )phenoxy ]ethyl}{ 3-[ ( 2R)-2-am ino-6-guanidinohexanoyla mino] propyl }amino )propylamino ]-6-guanidino-1-hexanone hexahydrochloride, decision type: , therapeutic area: , PIP number: P/0134/2018

Europe - EMA - European Medicines Agency

28-11-2018


Opinion/decision on a Paediatric investigation plan (PIP): naloxone (hydrochloride), decision type: , therapeutic area: , PIP number: P/0146/2018

Opinion/decision on a Paediatric investigation plan (PIP): naloxone (hydrochloride), decision type: , therapeutic area: , PIP number: P/0146/2018

Opinion/decision on a Paediatric investigation plan (PIP): naloxone (hydrochloride), decision type: , therapeutic area: , PIP number: P/0146/2018

Europe - EMA - European Medicines Agency

27-11-2018


Opinion/decision on a Paediatric investigation plan (PIP): (R)-2-amino-3-phenylpropylcarbamate hydrochloride (solriamfetol), decision type: , therapeutic area: , PIP number: P/0207/2018

Opinion/decision on a Paediatric investigation plan (PIP): (R)-2-amino-3-phenylpropylcarbamate hydrochloride (solriamfetol), decision type: , therapeutic area: , PIP number: P/0207/2018

Opinion/decision on a Paediatric investigation plan (PIP): (R)-2-amino-3-phenylpropylcarbamate hydrochloride (solriamfetol), decision type: , therapeutic area: , PIP number: P/0207/2018

Europe - EMA - European Medicines Agency

26-11-2018

Wakix (Bioprojet Pharma)

Wakix (Bioprojet Pharma)

Wakix (Active substance: Pitolisant hydrochloride) - Centralised - Yearly update - Commission Decision (2018)7974 of Mon, 26 Nov 2018

Europe -DG Health and Food Safety

21-11-2018

EU/3/18/2082 (Takeda Pharma A/S)

EU/3/18/2082 (Takeda Pharma A/S)

EU/3/18/2082 (Active substance: 5-{(1R,2R)-2-[(cyclopropylmethyl)amino]cyclopropyl}-N-(tetrahydro-2H-pyran-4-yl)thiophene-3-carboxamide monohydrochloride) - Orphan designation - Commission Decision (2018)7791 of Wed, 21 Nov 2018 European Medicines Agency (EMA) procedure number: EMA/OD/040/18

Europe -DG Health and Food Safety

13-11-2018

EU/3/17/1836 (Zogenix GmbH)

EU/3/17/1836 (Zogenix GmbH)

EU/3/17/1836 (Active substance: Fenfluramine hydrochloride) - Transfer of orphan designation - Commission Decision (2018)7576 of Tue, 13 Nov 2018 European Medicines Agency (EMA) procedure number: EMA/OD/233/16/T/01

Europe -DG Health and Food Safety

13-11-2018

EU/3/13/1219 (Zogenix GmbH)

EU/3/13/1219 (Zogenix GmbH)

EU/3/13/1219 (Active substance: Fenfluramine hydrochloride) - Transfer of orphan designation - Commission Decision (2018)7575 of Tue, 13 Nov 2018 European Medicines Agency (EMA) procedure number: EMA/OD/140/13/T/01

Europe -DG Health and Food Safety

1-11-2018

Dexdomitor (Orion Corporation)

Dexdomitor (Orion Corporation)

Dexdomitor (Active substance: dexmedetomidine hydrochloride) - Centralised - Yearly update - Commission Decision (2018)7380 of Thu, 01 Nov 2018

Europe -DG Health and Food Safety

31-10-2018

Evista (Daiichi Sankyo Europe GmbH)

Evista (Daiichi Sankyo Europe GmbH)

Evista (Active substance: Raloxifene hydrochloride) - Centralised - Yearly update - Commission Decision (2018)7342 of Wed, 31 Oct 2018

Europe -DG Health and Food Safety

26-9-2018

Sileo (Orion Corporation)

Sileo (Orion Corporation)

Sileo (Active substance: Dexmedetomidine hydrochloride) - Centralised - Yearly update - Commission Decision (2018)6325 of Wed, 26 Sep 2018

Europe -DG Health and Food Safety

10-8-2018

Brinavess (Correvio)

Brinavess (Correvio)

Brinavess (Active substance: vernakalant hydrochloride) - Centralised - Transfer Marketing Authorisation Holder - Commission Decision (2018)5523 of Fri, 10 Aug 2018 European Medicines Agency (EMA) procedure number: EMEA/H/C/1215/T/31

Europe -DG Health and Food Safety

30-7-2018

Segluromet (Merck Sharp and Dohme B.V.)

Segluromet (Merck Sharp and Dohme B.V.)

Segluromet (Active substance: ertugliflozin / metformin hydrochloride) - Centralised - Transfer Marketing Authorisation Holder - Commission Decision (2018)5103 of Mon, 30 Jul 2018 European Medicines Agency (EMA) procedure number: EMEA/H/C/4314/T/2

Europe -DG Health and Food Safety

30-7-2018

Ceplene (Noventia Pharma Srl)

Ceplene (Noventia Pharma Srl)

Ceplene (Active substance: Histamine dihydrochloride) - Centralised - Renewal - Commission Decision (2018)5116 of Mon, 30 Jul 2018 European Medicines Agency (EMA) procedure number: EMEA/H/C/796/R/36

Europe -DG Health and Food Safety

23-7-2018

Optruma (Eli Lilly Nederland B.V.)

Optruma (Eli Lilly Nederland B.V.)

Optruma (Active substance: Raloxifene hydrochloride) - Centralised - Yearly update - Commission Decision (2018)4893 of Mon, 23 Jul 2018

Europe -DG Health and Food Safety

12-7-2018

Econor (Elanco Europe Ltd)

Econor (Elanco Europe Ltd)

Econor (Active substance: Valnemulin hydrochloride) - Centralised - Yearly update - Commission Decision (2018)4580 of Thu, 12 Jul 2018

Europe -DG Health and Food Safety

11-7-2018

Ariclaim (Eli Lilly Nederland B.V.)

Ariclaim (Eli Lilly Nederland B.V.)

Ariclaim (Active substance: duloxetine hydrochloride) - Centralised - Withdrawal - Commission Decision (2018)4515 of Wed, 11 Jul 2018

Europe -DG Health and Food Safety

5-7-2018

Scientific guideline:  Draft pegylated liposomal doxorubicin hydrochloride concentrate for solution 2 mg/ml product-specific bioequivalence guidance, draft: consultation open

Scientific guideline: Draft pegylated liposomal doxorubicin hydrochloride concentrate for solution 2 mg/ml product-specific bioequivalence guidance, draft: consultation open

This document provides product-specific guidance on the demonstration of the bioequivalence of pegylated liposomal doxorubicin hydrochloride concentrate for solution 2 mg/ml.

Europe - EMA - European Medicines Agency

3-7-2018

Efficib (Merck Sharp and Dohme B.V.)

Efficib (Merck Sharp and Dohme B.V.)

Efficib (Active substance: sitagliptin / metformin hydrochloride) - Centralised - Transfer Marketing Authorisation Holder - Commission Decision (2018) 4254 of Tue, 03 Jul 2018 European Medicines Agency (EMA) procedure number: EMEA/H/C/896/T/90

Europe -DG Health and Food Safety

3-7-2018

Ristfor (Merck Sharp and Dohme B.V.)

Ristfor (Merck Sharp and Dohme B.V.)

Ristfor (Active substance: sitagliptin / metformin hydrochloride) - Centralised - Transfer Marketing Authorisation Holder - Commission Decision (2018) 4249 of Tue, 03 Jul 2018 European Medicines Agency (EMA) procedure number: EMEA/H/C/1235/T/77

Europe -DG Health and Food Safety

3-7-2018

Velmetia (Merck Sharp and Dohme B.V.)

Velmetia (Merck Sharp and Dohme B.V.)

Velmetia (Active substance: sitagliptin / metformin hydrochloride) - Centralised - Transfer Marketing Authorisation Holder - Commission Decision (2018) 4252 of Tue, 03 Jul 2018 European Medicines Agency (EMA) procedure number: EMEA/H/C/862/T/93

Europe -DG Health and Food Safety

3-7-2018

Janumet (Merck Sharp and Dohme B.V.)

Janumet (Merck Sharp and Dohme B.V.)

Janumet (Active substance: sitagliptin / metformin hydrochloride) - Centralised - Transfer Marketing Authorisation Holder - Commission Decision (2018) 4251 of Tue, 03 Jul 2018 European Medicines Agency (EMA) procedure number: EMEA/H/C/861/T/90

Europe -DG Health and Food Safety

29-6-2018

EU/3/18/2028 (BioCryst UK Ltd)

EU/3/18/2028 (BioCryst UK Ltd)

EU/3/18/2028 (Active substance: (R)-1-(3-(aminomethyl) phenyl)-N-(5-((3-cyanophenyl)(cyclopropylmethylamino)methyl)-2-fluorophenyl)-3-(trifluoromethyl)-1H-pyrazole-5-carboxamide dihydrochloride) - Orphan designation - Commission Decision (2018)4173 of Fri, 29 Jun 2018 European Medicines Agency (EMA) procedure number: EMA/OD/003/18

Europe -DG Health and Food Safety