ACCUPRO 5 MG FILM-COATED TABLETS

Main information

  • Trade name:
  • ACCUPRO 5 MG FILM-COATED TABLETS
  • Dosage:
  • 5 Milligram
  • Pharmaceutical form:
  • Film Coated Tablet
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug

Documents

Localization

  • Available in:
  • ACCUPRO 5 MG FILM-COATED TABLETS
    Ireland
  • Language:
  • English

Other information

Status

  • Source:
  • HPRA - Health Products Regulatory Authority - Ireland
  • Authorization number:
  • PPA0465/135/001A
  • Authorization date:
  • 12-11-2004
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage,interactions,side effects

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

Accupro5mgFilm-coatedTablets.

2QUALITATIVEANDQUANTITATIVECOMPOSITION

Eachtabletcontains5mgquinapril(ashydrochloride).

Excipient:Containslactosemonohydrate

Forafulllistofexcipients,seesection6.1.

3PHARMACEUTICALFORM

Film-coatedtablet

ProductimportedfromGreece:

Brown,ellipticalfilm-coatedtabletswithabreaklineand‘5’onbothsides.

4CLINICALPARTICULARS

4.1TherapeuticIndications

Forthetreatmentofallgradesofessentialhypertension.Accuproiseffectiveasmonotherapyorconcomitantly

withdiureticsinpatientswithhypertension.

Forthetreatmentofcongestiveheartfailurewhengivenconcomitantlywithadiureticand/orcardiacglycoside.

TreatmentofcongestiveheartfailurewithAccuproshouldalwaysbeinitiatedunderclosemedicalsupervision.

4.2Posologyandmethodofadministration

Fororaluse.

Adults:

Hypertension

Monotherapy:Therecommendedinitialdosageis10mgoncedaily.Dependinguponclinicalresponse,patient’s

dosagemaybetitrated(bydoublingthedoseallowingadequatetimefordosageadjustment)toamaintenancedosage

of20to40mg/daygivenasasingledoseordividedinto2doses.Long-termcontrolismaintainedinmostpatients

withasingledailydosageregimen.Patientshavebeentreatedwithdosagesupto80mg/day.

ConcomitantDiuretics:Inordertodetermineifexcesshypotensionwilloccur,aninitialdosageof5mgofAccuprois

recommendedinpatientswhoarealsobeingtreatedwithadiuretic.AfterthisthedosageofAccuproshouldbetitrated

(bydoublingthedoseallowingtimefordosageadjustment)totheoptimalresponse(seesection4.5).

CongestiveHeartFailure:

Inordertocloselymonitorpatientsforsymptomatichypotension,asingle5mginitialdosageisrecommended.After

this,patientsshouldbetitratedtoaneffectivedose:(upto40mg/day)givenin1or2doseswithconcomitantdiuretic

and/orcardiacglycosidetherapy.Patientsareusuallymaintainedeffectivelyondosesof10-20mg/daygivenwith

concomitanttherapy.

Inthetreatmentofsevereorunstablecongestiveheartfailure,Accuproshouldalwaysbeinitiatedinhospitalunder

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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,

especiallywhenquinaprilhasbeengivenconcomitantlywithadiureticandhasbeenobservedin4%and3%

respectivelyofpatientsonmonotherapy.Thisismorelikelytooccurinpatientswithpre-existingrenalimpairment.

Dosagereductionand/ordiscontinuationofadiureticand/orquinaprilmayberequired.

ImpairedHepaticFunction:Quinaprilwhencombinedwithadiureticshouldbeusedwithcautioninpatientswith

impairedhepaticfunctionorprogressiveliverdisease,sinceminoralterationsoffluidandelectrolytebalancemay

precipitatehepaticcoma.Themetabolismofquinapriltoquinaprilatisnormallydependentuponhepaticesterease.

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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

countsinpatientswithcollagenvasculardiseaseand/orrenaldiseasesshouldbeconsidered.

Hypoglycaemia:ACEinhibitorsmayenhanceinsulinsensitivityandhavebeenassociatedwithhypoglycaemiain

diabeticpatientsoninsulinororalhypoglycaemicagents;closermonitoringofdiabeticpatientsmayberequired,

especiallyinthefirstfewweeksoftreatment.

Cough:CoughhasbeenreportedwiththeuseofACEinhibitorsincludingquinapril.Characteristically,thecoughis

non-productive,persistentandresolvesafterdiscontinuationoftherapy.ACEinhibitor-inducedcoughshouldbe

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Patientswithrarehereditaryproblemswithgalactoseintolerance,theLapplactasedeficiencyorglucose-galactose

malabsorptionshouldnottakethismedicine.

Pregnancy:ACEinhibitorsshouldnotbeinitiatedduringpregnancy.UnlesscontinuedACEinhibitortherapyis

consideredessential,patientsplanningpregnancyshouldbechangedtoalternativeantihypertensivetreatmentswhich

haveanestablishedsafetyprofileforuseinpregnancy.

Whenpregnancyisdiagnosed,treatmentwithACEinhibitorsshouldbestoppedimmediately,and,ifappropriate,

alternativetherapyshouldbestarted(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-administrationofmultiple10mgdosesofatorvastatinwith80mgquinaprilresultedinnosignifigant

changeinthesteadystatepharmacokineticparametersofatorvastatin.

Lithium:

Increasedserumlithiumlevelsandsymptomsoflithiumtoxicityhavebeenreportedinpatientsreceivingconcomitant

lithiumandACEinhibitortherapyduetothesodium-losingeffectoftheseagents.Thesedrugsshouldbeco-

administeredwithcautionandfrequentmonitoringofserumlithiumlevelsisrecommended.Ifadiureticisalsoused,it

mayincreasetheriskoflithiumtoxicity.

Agentsincreasingserumpotassium:

Quinaprilisanangiotensin-convertingenzymeinhibitorcapableofloweringaldosteronelevels,whichinturncan

resultinamildelevationinserumpotassium.Concomitanttreatmentswithpotassiumsparingdiuretics,potassium

supplementsorpotassiumsaltsshouldonlybeusedwithcautionandwithappropriatemonitoringofserumpotassium,

especiallyinpatientswithimpairedrenalfunction,sincebydecreasingaldosteroneproduction,Accuprooftencauses

anincreaseinserumpotassium.

Surgery/anaesthesia:

AlthoughnodataareavailabletoindicatethereisaninteractionbetweenAccuproandanaestheticagentsthatproduces

hypotension,cautionshouldbeexercisedwhenpatientsundergomajorsurgeryoranaesthesiasinceangiotensin

convertingenzymeinhibitorshavebeenshowntoblockangiotensinIIformationsecondarytocompensatoryrenin

release.Thismayleadtohypotension,whichcanbecorrectedbyvolumeexpansion.

Antidiabeticdrugs:ConcomitantadministrationofACEinhibitorsandanti-diabeticmedicines(insulin,oral

hypoglycaemicagents)maycauseanincreasedbloodglucoseloweringeffectwiththeriskofhypoglycaemia.This

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impairment.

4.6Fertility,pregnancyandlactation

Pregnancy:

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

concomitantdiuretictherapythanthoseonmonotherapywithAccupro.Theseobservedincreaseswilloftenreverseon

continuedtherapy.

PancreatitishasbeenreportedrarelyinpatientstreatedwithACEinhibitors;insomecasesthishasprovedfatal.

TheuseofACEinhibitorsisnotrecommendedduringthefirsttrimesterofpregnancy(see

section4.4.)TheuseofACEinhibitorsiscontraindicatedduringthe2 nd

and3 rd

trimesterof

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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%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:Eosinophilicpneumonitis

GastrointestinalDisorders:

Common:Abdominalpains

Uncommon:Drymouthorthroat,Flatulence,Pancreatitis*

HepatobiliaryDosirders:

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SkinandSubcutaneousTissueDisorders:

Uncommon:Pruritus,rash,Increasedperspiration

Rare:Alopecia*,Exfoliativedermatitis*,Pemphigus*,Photosensitivityreaction*

MusculoskeletalandConnectiveTissueDisorders:

Common:Backpain,myalgia

Uncommon:Arthralgia

Reproductivesystemandbreastdisorders:

Uncommon:Impotence

Gerneraldisordersandadministrationsiteconditions:

Common:asthenia

Uncommon:Edema(peripheralandgeneralised)

4.9Overdose

Nodataareavailablewithrespecttooverdosageinhumans.Themostlikelyclinicalmanifestationwouldbesymptoms

attributabletoseverehypotension,whichshouldnormallybetreatedbyintravenousvolumeexpansion.

Haemodialysisandperitonealdialysishavelittleeffectontheeliminationofquinaprilandquinaprilat.

5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

ATCCode–CO9A AO6,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

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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

Hypromellose

Hyprolose

Titaniumdioxide(E171)

Macrogol400

Ironoxidered(E172)

6.2Incompatibilities

Notapplicable.

6.3ShelfLife

Theshelf-lifeexpirydateofthisproductisthedateshownonthecontainerandouterpackageoftheproductonthe

marketinthecountryoforigin.

6.4Specialprecautionsforstorage

Donotstoreabove25°C

Storeintheoriginalpackage.

6.5Natureandcontentsofcontainer

Blisterpacksof28tabletscontainedinanoutercardboardcarton.

6.6Specialprecautionsfordisposalofausedmedicinalproductorwastematerialsderivedfrom

suchmedicinalproductandotherhandlingoftheproduct

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7PARALLELPRODUCTAUTHORISATIONHOLDER

PCOManufacturing

Unit10,AshbourneBusinessPark

Rath

Ashbourne

Co.Meath

Ireland

8PARALLELPRODUCTAUTHORISATIONNUMBER

PPA465/135/1

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

Dateoffirstauthorisation:12November2004

Dateofnextrenewal12November2009

10DATEOFREVISIONOFTHETEXT

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3-8-2018

Scientific guideline:  Ledipasvir/sofosbuvir film-coated tablet 90 mg/400 mg product-specific bioequivalence guidance, adopted

Scientific guideline: Ledipasvir/sofosbuvir film-coated tablet 90 mg/400 mg product-specific bioequivalence guidance, adopted

Ledipasvir/sofosbuvir film-coated tablet 90 mg/400 mg product-specific bioequivalence guidance

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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