ACCUPRO 20 MG FILM-COATED TABLETS

Main information

  • Trade name:
  • ACCUPRO 20 MG FILM-COATED TABLETS
  • Dosage:
  • 20 Milligram
  • Pharmaceutical form:
  • Film Coated Tablet
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug

Documents

Localization

  • Available in:
  • ACCUPRO 20 MG FILM-COATED TABLETS
    Ireland
  • Language:
  • English

Other information

Status

  • Source:
  • HPRA - Health Products Regulatory Authority - Ireland
  • Authorization number:
  • PPA0465/135/003A
  • Authorization date:
  • 12-11-2004
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage,interactions,side effects

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

Accupro20mgFilm-coatedTablets

2QUALITATIVEANDQUANTITATIVECOMPOSITION

Eachtabletcontains20mgquinapril(ashydrochloride).

Excipients:Containslactosemonohydrate

Forafulllistofexcipients,seesection6.1

3PHARMACEUTICALFORM

Film-coatedtablets

ProductimportedfromGreeceandTheNetherlands:

Brown,film-coated,roundtabletswithabreaklineononesideand‘20’ontheotherside.

ProductimportedfromGermany:

White,film-coated,roundtabletswithabreaklineononesideand‘20’ontheotherside.

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

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 14/04/2011 CRN 2091269 page number: 1

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,

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 14/04/2011 CRN 2091269 page number: 2

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

countsinpatientswithcollagenvasculardiseaseand/orrenaldiseasesshouldbeconsidered.

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 14/04/2011 CRN 2091269 page number: 3

diabeticpatientsoninsulinororalhypoglycaemicagents;closermonitoringofdiabeticpatientsmayberequired,

especiallyinthefirstfewweeksoftreatment.

Cough:CoughhasbeenreportedwiththeuseofACEinhibitorsincludingquinapril.Characteristically,thecoughis

non-productive,persistentandresolvesafterdiscontinuationoftherapy.ACEinhibitor-inducedcoughshouldbe

consideredaspartofthedifferentialdiagnosisofcough.

Patientswithrarehereditaryproblemswithgalactoseintolerance,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-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

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 14/04/2011 CRN 2091269 page number: 4

convertingenzymeinhibitorshavebeenshowntoblockangiotensinIIformationsecondarytocompensatoryrenin

release.Thismayleadtohypotension,whichcanbecorrectedbyvolumeexpansion.

Antidiabeticdrugs:ConcomitantadministrationofACEinhibitorsandanti-diabeticmedicines(insulin,oral

hypoglycaemicagents)maycauseanincreasedbloodglucoseloweringeffectwiththeriskofhypoglycaemia.This

phenomenonmaybemorelikelytooccurduringthefirstweeksofcombinedtreatmentandinpatientswithrenal

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

TheuseofACEinhibitorsisnotrecommendedduringthefirsttrimesterofpregnancy(see

section4.4.)TheuseofACEinhibitorsiscontraindicatedduringthe2 nd

and3 rd

trimesterof

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 14/04/2011 CRN 2091269 page number: 5

concomitantdiuretictherapythanthoseonmonotherapywithAccupro.Theseobservedincreaseswilloftenreverseon

continuedtherapy.

PancreatitishasbeenreportedrarelyinpatientstreatedwithACEinhibitors;insomecasesthishasprovedfatal.

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

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

precautionsforuse).

ThefollowingsideeffectshavebeenobservedassociatedwithACEinhibitortherapy:Theadversereactionsare

classifiedaccordingtofrequenciesdeterminedfromclinicaltrialsdata.

Verycommon ≥1/10(≥10%)

Common ≥1/100and<1/10(≥1%and<10%)

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

Rare ≥1/10,000and<1/1000(≥0.01%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

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 14/04/2011 CRN 2091269 page number: 6

HepatobiliaryDosirders:

Rare:Hepatitis

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

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,

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 14/04/2011 CRN 2091269 page number: 7

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

Gelatine

Crospovidone

Magnesiumstearate

Candelilla

Hypromellose

Hyprolose

Titaniumdioxide(E171)

Macrogol400

ProductimportedfromGreeceandtheNetherlandsalsocontainsredironoxide(E172).

6.2Incompatibilities

Notapplicable.

6.3ShelfLife

Theshelf-lifeexpirydateofthisproductisthedateshownonthecontainerandouterpackageoftheproductonthe

marketinthecountryoforigin.

6.4Specialprecautionsforstorage

Donotstoreabove25°C.

Storeintheoriginalpackage.

6.5Natureandcontentsofcontainer

Blisterpacksof14,28or30tabletscontainedinanoutercardboardcarton.

6.6Specialprecautionsfordisposalofausedmedicinalproductorwastematerialsderivedfrom

suchmedicinalproductandotherhandlingoftheproduct

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 14/04/2011 CRN 2091269 page number: 8

7PARALLELPRODUCTAUTHORISATIONHOLDER

PCOManufacturing

Unit10,AshbourneBusinessPark

Rath

Ashbourne

Co.Meath

Ireland

8PARALLELPRODUCTAUTHORISATIONNUMBER

PPA465/135/3

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

Dateoffirstauthorisation:12November2004

Dateofnextrenewal:12November2009

10DATEOFREVISIONOFTHETEXT

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 14/04/2011 CRN 2091269 page number: 9

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

Europe - EFSA - European Food Safety Authority EFSA Journal

21-2-2017

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