ACCUPRO 10 MG FILM-COATED TABLETS

Main information

  • Trade name:
  • ACCUPRO 10 MG FILM-COATED TABLETS
  • Dosage:
  • 10 Milligram
  • Pharmaceutical form:
  • Film Coated Tablet
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug

Documents

Localization

  • Available in:
  • ACCUPRO 10 MG FILM-COATED TABLETS
    Ireland
  • Language:
  • English

Other information

Status

  • Source:
  • HPRA - Health Products Regulatory Authority - Ireland
  • Authorization number:
  • PPA0465/135/002A
  • Authorization date:
  • 12-11-2004
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage,interactions,side effects

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

Accupro10mgFilm-coatedTablets

2QUALITATIVEANDQUANTITATIVECOMPOSITION

Eachtabletcontains10mgquinapril(ashydrochloride).

Excipient:Containslactosemonohydrate

Forafulllistofexcipients,seesection6.1.

3PHARMACEUTICALFORM

Film-coatedtablet.

ProductimportedfromtheNetherlandsandtheUK:

Brown,triangularfilm-coatedtabletswithabreaklineand‘10’ononesideandabreaklineonlyontheotherside.

ProductimportedfromGermany:

Whitetriangularfilm-coatedtabletswithabreaklineand‘10’ononesideandabreaklineonlyontheotherside.

4CLINICALPARTICULARS

4.1TherapeuticIndications

Forthetreatmentofallgradesofessentialhypertension.Accuproiseffectiveasmonotherapyorconcomitantly

withdiureticsinpatientswithhypertension.

Forthetreatmentofcongestiveheartfailurewhengivenconcomitantlywithadiureticand/orcardiacglycoside.

TreatmentofcongestiveheartfailurewithAccuproshouldalwaysbeinitiatedunderclosemedicalsupervision.

4.2Posologyandmethodofadministration

Fororaluse.

Adults:

Hypertension

Monotherapy:Therecommendedinitialdosageis10mgoncedaily.Dependinguponclinicalresponse,patient’s

dosagemaybetitrated(bydoublingthedoseallowingtimefordosageadjustment)toamaintenancedosageof20to

40mg/daygivenasasingledoseordividedinto2doses.Long-termcontrolismaintainedinmostpatientswitha

singledailydosageregimen.Patientshavebeentreatedwithdosagesupto80mg/day.

ConcomitantDiuretics:Inordertodetermineifexcesshypotensionwilloccur,aninitialdosageof5mgofAccuprois

recommendedinpatientswhoarealsobeingtreatedwithadiuretic.AfterthisthedosageofAccuproshouldbetitrated

(bydoublingthedoseallowingtimefordosageadjustment)totheoptimalresponse(seesection4.5).

CongestiveHeartFailure:

Inordertocloselymonitorpatientsforsymptomatichypotension,asingle5mginitialdosageisrecommended.After

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and/orcardiacglycosidetherapy.Patientsareusuallymaintainedeffectivelyondosesof10-20mg/daygivenwith

concomitanttherapy.

Inthetreatmentofsevereorunstablecongestiveheartfailure,Accuproshouldalwaysbeinitiatedinhospitalunder

closemedicalsupervision.

Elderly:

Agealonedoesnotappeartoaffecttheefficacyorsafetyprofileofquinapril.

Therefore,therecommendedinitialdosageinhypertensionofquinaprilinelderlypatientsis10mggivenoncedaily

followedbytitrationtotheoptimalresponse.

Children(6-12years):

Notrecommended.Safetyandefficacyinchildrenhasnotbeenestablished.

Patientswithrenalinsufficiency:

Inpatientswithacreatinineclearanceoflessthan60ml/min,aninitialdosageinessentialhypertensionof5mgonce

dailyisrecommendedfollowedbytitrationtotheoptimalresponse.Kineticdataindicatethattheapparentelimination

half-lifeofquinaprilatincreasesascreatinineclearancedecreases.(seesection4.4).

4.3Contraindications

Hypersensitivitytoanyoftheingredients.

AccuproiscontraindicatedintheSecondandthirdtrimestersofpregnancy(Seesections4.4and4.6)

Useinpatientswithsubaorticstenosis.

UseinpatientswithahistoryofangioneuroticoedemarelatingtoprevioustreatmentwithanACEinhibitor.

4.4Specialwarningsandprecautionsforuse

ImpairedRenalFunction:Inpatientswithrenalinsufficiencymonitoringofrenalfunctionduringtherapyshouldbe

performedasdeemedappropriate,althoughinthemajorityrenalfunctionwillnotalterormayimprove.

Asaconsequenceofinhibitingtherenin-angiotensin-aldosteronesystem,changesinrenalfunctionmaybeanticipated

insusceptibleindividuals.

Inpatientswithsevereheartfailurewhoserenalfunctionmaydependontheactivityoftherenin-angiotensin-

aldosteronesystem,treatmentwithACEinhibitorsincludingquinapril,maybeassociatedwitholiguriaand/or

progressiveazotemiaandrarelyacuterenalfailureand/ordeath.

Thehalf-lifeofquinaprilatisprolongedascreatinineclearancefalls.Patientswithacreatinineclearanceof<60ml/min

requirealowerinitialdosageofquinapril.(seesection4.2).Thesepatients’dosageshouldbetitratedupwardsbased

upontherapeuticresponse,andrenalfunctionshouldbecloselymonitoredalthoughinitialstudiesdonotindicatethat

quinaprilproducesfurtherdeteriorationinrenalfunction.

Inclinicalstudiesinhypertensivepatientswithunilateralorbilateralrenalarterystenosis,increasesinbloodurea

nitrogenandserumcreatininehavebeenobservedinsomepatientsfollowingACEinhibitortherapy.Theseincreases

werealmostalwaysreversibleupondiscontinuationoftheACEinhibitorand/ordiuretictherapy.Insuchpatients,renal

functionshouldbemonitoredduringthefirstfewweeksoftherapy.

Somepatientswithhypertensionorheartfailurewithnoapparentpre-existingrenalvasculardiseasehavedeveloped

increases(>1.25timestheupperlimitofnormal)inbloodureaandserumcreatinine,usuallyminorandtransient,

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respectivelyofpatientsonmonotherapy.Thisismorelikelytooccurinpatientswithpre-existingrenalimpairment.

Dosagereductionand/ordiscontinuationofadiureticand/orquinaprilmayberequired.

ImpairedHepaticFunction:Quinaprilwhencombinedwithadiureticshouldbeusedwithcautioninpatientswith

impairedhepaticfunctionorprogressiveliverdisease,sinceminoralterationsoffluidandelectrolytebalancemay

precipitatehepaticcoma.Themetabolismofquinapriltoquinaprilatisnormallydependentuponhepaticesterease.

Quinaprilatconcentrationsarereducedinpatientswithalcoholiccirrhosisduetoimpaireddeesterficationofquinapril.

Anaphylactoidreactions

Desensitisation:PatientsreceivingACEinhibitorsduringdesensitisingtreatmentwithhymentopteravenomhave

sustainedlife-threateninganaphylactoidreactions.InthesamepatientsthesereactionshavebeenavoidedwhenACE

inhibitorsweretemporarilywithheld,buttheyhavereappeareduponinadvertentrechallenge.

LDLapheresis:Patientsundergoinglow-densitylipoproteinapheresiswithdxtran-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.

Intestinalangiooedema:IntestinalangiooedemahasbeenreportedinpatientstreatedwithACEinhibitors.These

patientspresentedwithabdominalpain(withorwithoutnauseaorvomiting);insomecasestherewasnopriorhistory

offacialangiooedemaandC-1esteraselevelswerenormal.Theangiooedemawasdiagnosedbyproceduresincluding

abdominalCTscanorultrasound,oratsurgery,andsymptomsresolvedafterstoppingtheACEinhibitor.Intestinal

angiooedemashouldbeincludedinthedifferentialdiagnosisofpatientsonAceinhibitorspresentingwithabdominal

pain.

CautionshouldbeexercisedinthoseknowntobehypersensitivetootherACEinhibitors,andparticularlythosewith

obstructiveairwaysdisease.

PatientswithahistoryofangioedemaunrelatedtoACEinhibitortherapymaybeatincreasedriskofangioedemawhile

receivinganACEinhibitor(seealsosection4.3).

Otherhypersensitivityreactionshavebeenreported.

Hypotension:SymptomatichypotensionwasrarelyseeninhypertensivepatientstreatedwithAccuprobutitisa

possibleconsequenceofACEinhibitiontherapyparticularlyinsalt/volumedepletedpatientssuchasthosepreviously

treatedwithdiuretics,whohaveadietarysaltreduction,orwhoareondialysis.Anyelectrolyteorfluidinadequacy

shouldbecorrectedpreferablybeforeinitialdoseoftheproduct.Carefulmedicalsupervisionisnecessaryforaperiod

afterdosing.Ifsymptomatichypotensionoccurs,thepatientshouldbeplacedinthesupinepositionand,ifnecessary,

receiveanintravenousinfusionofnormalsaline.Atransienthypotensiveresponseisnotacontra-indicationtofurther

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.

Patientswithrarehereditaryproblemsofgalactoseintolerance,theLapplactasedeficiencyorglucose-galactose

malabsorptionshouldnottakethismedicine.

Pregnancy:ACEinhibitorsshouldnotbeinitiatedduringpregnancy.UnlesscontinuedACEinhibitortherapyis

consideredessential,patientsplanningpregnancyshouldbechangedtoalternativeantihypertensivetreatmentswhich

haveanestablishedsafetyprofileforuseinpregnancy.WhenpregnancyisdiagnosedtreatmentwithACEinhibitors

shouldbestoppedimmediately,and,ifappropriatealternativetherapyshouldbestarted(seesections4.3and4.6)

4.5Interactionwithothermedicinalproductsandotherformsofinteraction

Tetracyclineandotherdrugsthatinteractwithmagnesium:

BecauseofthepresenceofmagnesiumcarbonateintheformulationAccuprohasbeenshowninhealthyvolunteersto

reducetheabsorptionoftetracyclineinconcomitantadministrationby28-37%.Itisrecommendedthatconcomitant

administrationoftetracyclinebeavoided.

Concomitantdiuretictherapy:

Patientstreatedwithdiureticsmayoccasionallyexperienceanexcessivereductionofbloodpressureafterinitiationof

therapywithAccupro.Thishypotensiveeffectmaybeeffectivelyminimisedbyeitherdiscontinuingthediureticor

increasingthesaltintakepriortotheinitialdoseofAccupro.Ifdiscontinuationofthediureticisnotpossible,medical

supervisionshouldbeprovidedforuptotwohoursfollowingadministrationoftheinitialdose.(seesection4.4and

section4.2).

Otheranti-hypertensiveagents:

B-blockers,methyldopaanddiureticsmayenhancethehypotensiveeffectsofquinapril,andshouldonlybeusedunder

carefulsupervision.Concomitantpropranololdidnotaffectthepharmacokineticsofquinaprilinasingledosestudy.

Calciumantagonists:

ThereisnoexperienceofconcomitantusewithAccupro.

Atorvastatin:Co-administrationofmultiple10mgdosesofatorvastatinwith80mgofquinaprilresultedinno

signifigantchangeinthesteadystatepharmacokineticparametersofatorvastatin.

Lithium:

Increasedserumlithiumlevelsandsymptomsoflithiumtoxicityhavebeenreportedinpatientsreceivingconcomitant

lithiumandACEinhibitortherapyduetothesodium-losingeffectoftheseagents.Thesedrugsshouldbeco-

administeredwithcautionandfrequentmonitoringofserumlithiumlevelsisrecommended.Ifadiureticisalsoused,it

mayincreasetheriskoflithiumtoxicity.

Agentsincreasingserumpotassium:

Quinaprilisanangiotensin-convertingenzymeinhibitorcapableofloweringaldosteronelevels,whichinturncan

resultinamildelevationinserumpotassium.Concomitanttreatmentswithpotassiumsparingdiuretics,potassium

supplementsorpotassiumsaltsshouldonlybeusedwithcautionandwithappropriatemonitoringofserumpotassium,

especiallyinpatientswithimpairedrenalfunction,sincebydecreasingaldosteroneproduction,Accuprooftencauses

anincreaseinserumpotassium.

Surgery/anaesthesia:

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hypotension,cautionshouldbeexercisedwhenpatientsundergomajorsurgeryoranaesthesiasinceangiotensin

convertingenzymeinhibitorshavebeenshowntoblockangiotensinIIformationsecondarytocompensatoryrenin

release.Thismayleadtohypotension,whichcanbecorrectedbyvolumeexpansion.

Antidiabeticdrugs:ConcomitantadministrationofACEinhibitorsandanti-diabeticmedicines(insulin,oral

hypoglycaemicagents)maycauseanincreasedbloodglucoseloweringeffectwiththeriskofhypoglycaemia.This

phenomenonmaybemorelikelytooccurduringthefirstweeksofcombinedtreatmentandinpatientswithrenal

impairment.

4.6Fertility,pregnancyandlactation

EpidemiologicalevidenceregardingtheriskofteratogenicityfollowingexposuretoACEinhibitorsduringthefirst

trimesterofpregnancyhasnotbeenconclusive;howeverasmallincreaseinriskcannotbeexcluded.Unlesscontinued

ACEinhibitortherapyisconsideredessential,patientsplanningpregnancyshouldbechangedtoalternative

antihypertensivetreatmentswhichhaveanestablishedsafetyprofileforuseinpregnancy.Whenpregnancyis

diagnosed,treatmentwithACEinhibitorsshouldbestoppedimmediately,andifappropriate,alternativetherapyshould

bestarted.

ExposuretoACEinhibitortherapyduringthesecondandthirdtrimestersisknowntoinducehumanfoetotoxicity

(decreasedrenalfunction,oligohydramnios,skullossificationretardation)andneonataltoxicity(renalfailure,

hypotension,hyperkalaemia.)ShouldexposuretoACEinhibitorhaveoccuredfromthesecondtrimesterofpregnancy,

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,theuseofAccuproinabreastfeedingmothermaybeconsideredifthistreatmentis

necessaryforthemotherandthechildisobservedforanyadverseeffect.

4.7Effectsonabilitytodriveandusemachines

Theabilitytoengageinactivitiessuchasoperatingmachineryoroperatingamotorvehiclemaybeimpairedespecially

wheninitiatingquinapriltherapy.

4.8Undesirableeffects

Themostfrequentclinicaladversereactionsinhypertensionandcongestiveheartfailureareheadache,dizziness,

rhinitis,cough,upperrespiratorytractinfection,fatigue,andnauseaandvomiting.

Increases>1.25timestheupperlimitofnormal)inserumcreatinineandbloodureanitrogenwereobservedin3and

4%respectivelyofthepatientsonmonotherapy.Suchincreasesaremorelikelytooccurinpatientsreceiving

TheuseofACEinhibitorsisnotrecommendedduringthefirsttrimesterofpregnancy(see

section4.4.)TheuseofACEinhibitorsiscontraindicatedduringthe2 nd

and3 rd

trimesterof

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continuedtherapy.

PancreatitishasbeenreportedrarelyinpatientstreatedwithACEinhibitors;insomecasesthishasprovedfatal.

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

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

ThefollowingsideeffectshavebeenobservedassociatedwithACEinhibitortherapy:

Theadversereactionsareclassifiedaccordingtofrequenciesdeterminedfromclinicaltrialsdata.

Verycommon1/10(10%)

Common1/100and<1/10(1%and<10%)

Uncommon1/1000and<1/100(0.1%and<1%)

Rare1/10,000and<1/1000(0.01%and<0.1%)

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

*Ifalistedadversereactiontermwasnotreportedinclinicaltrialsitwasassumedtoberare,basedonreportingrates

versusestimatedproductuseworldwide.

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

VascularDisorders:

Uncommon Vasodilation

Rare Posturalhypotension*,Syncope*

Respiratory,ThoracicandMediastinalDisorders:

Common Dyspnoea

Rare Eosinophillicpneumonitis

GastrointestinalDisorders:

Common Abdominalpains

Uncommon Drymouthorthroat,Flatulence,Pancreatitis*

HepatobiliaryDisorders:

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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–C09AA06,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.Achievementofmaximumbloodpressure

loweringeffectsmayrequiretwoweeksoftherapyinsomepatients.Attherecommendeddoses,antihypertensive

effectsaremaintainedinmostpatientsthroughoutthe24hourdosingintervalandcontinueduringlongtermtherapy.

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

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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

Magnesiumcarbonate

Lactose

Gelatin

Crospovidone

Magnesiumstearate

Candelillawax

Hypromellose

Hyprolose

Titaniumdioxide(E171)

Macrogol400

ProductimportedfromtheUKandtheNetherlandsalsocontainsredironoxide(E172)

6.2Incompatibilities

Notapplicable.

6.3ShelfLife

Theshelf-lifeexpirydateofthisproductisthedateshownonthecontainerandouterpackageoftheproductonthe

marketinthecountryoforigin.

6.4Specialprecautionsforstorage

Donotstoreabove25°C.

Storeintheoriginalpackage.

6.5Natureandcontentsofcontainer

Blisterpacksof28and30tabletscontainedinanoutercardboardcarton.

6.6Specialprecautionsfordisposalofausedmedicinalproductorwastematerialsderivedfrom

suchmedicinalproductandotherhandlingoftheproduct

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7PARALLELPRODUCTAUTHORISATIONHOLDER

PCOManufacturing

Unit10,AshbourneBusinessPark

Rath

Ashbourne

Co.Meath

Ireland

8PARALLELPRODUCTAUTHORISATIONNUMBER

PPA465/135/2

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

Dateoffirstauthorisation:12November2004

Dateofnextrenewal:12November2009

10DATEOFREVISIONOFTHETEXT

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Takeda Pharma A/S recalls batch of Pamol® in packs of 300 film-coated tablets

Takeda Pharma A/S recalls batch of Pamol® in packs of 300 film-coated tablets

Takeda Pharma A/S recalls a batch of Pamol® in packs of 300 film-coated tablets after the discovery of Ibumetin 600 mg containing ibuprofen in some packs. Both types of medicine are used for the treatment of mild pain, but they work in different ways and may cause different adverse reactions.

Danish Medicines Agency

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

12-6-2018

EU/3/10/811 (Celgene Europe B.V.)

EU/3/10/811 (Celgene Europe B.V.)

EU/3/10/811 (Active substance: N-tert-butyl-3-[(5-methyl-2-{[4-(2-pyrrolidin-1-ylethoxy)phenyl]amino}pyrimidin-4-yl)amino] benzenesulfonamide dihydrochloride monohydrate) - Transfer of orphan designation - Commission Decision (2018)3809 of Tue, 12 Jun 2018 European Medicines Agency (EMA) procedure number: EMA/OD/092/10/T/03

Europe -DG Health and Food Safety

12-6-2018

EU/3/10/810 (Celgene Europe B.V.)

EU/3/10/810 (Celgene Europe B.V.)

EU/3/10/810 (Active substance: N-tert-butyl-3-[(5-methyl-2-{[4-(2-pyrrolidin-1-ylethoxy)phenyl]amino}pyrimidin-4-yl)amino] benzenesulfonamide dihydrochloride monohydrate) - Transfer of orphan designation - Commission Decision (2018)3808 of Tue, 12 Jun 2018 European Medicines Agency (EMA) procedure number: EMA/OD/084/10/T/03

Europe -DG Health and Food Safety

12-6-2018

EU/3/10/794 (Celgene Europe B.V.)

EU/3/10/794 (Celgene Europe B.V.)

EU/3/10/794 (Active substance: N-tert-butyl-3-[(5-methyl-2-{[4-(2-pyrrolidin-1-ylethoxy)phenyl]amino}pyrimidin-4-yl)amino] benzenesulfonamide dihydrochloride monohydrate) - Transfer of orphan designation - Commission Decision (2018)3803 of Tue, 12 Jun 2018 European Medicines Agency (EMA) procedure number: EMA/OD/069/10/T/03

Europe -DG Health and Food Safety

12-6-2018

EU/3/11/888 (Gilead Sciences Ireland UC)

EU/3/11/888 (Gilead Sciences Ireland UC)

EU/3/11/888 (Active substance: N-(cyanomethyl)-4-(2-{[4-(morpholin-4-yl)phenyl]amino}pyrimidin-4-yl)benzamide, dihydrochloride salt) - Transfer of orphan designation - Commission Decision (2018)3802 of Tue, 12 Jun 2018 European Medicines Agency (EMA) procedure number: EMA/OD/152/10/T/03

Europe -DG Health and Food Safety