CELIPROLOL HYDROCHLORIDE

Main information

  • Trade name:
  • CELIPROLOL HYDROCHLORIDE
  • Dosage:
  • 200 Milligram
  • Pharmaceutical form:
  • Film Coated Tablet
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug

Documents

Localization

  • Available in:
  • CELIPROLOL HYDROCHLORIDE
    Ireland
  • Language:
  • English

Status

  • Source:
  • HPRA - Health Products Regulatory Authority - Ireland
  • Authorization number:
  • PA0408/058/001
  • Authorization date:
  • 18-12-2003
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

IRISHMEDICINESBOARDACT1995,asamended

MedicinalProducts(ControlofPlacingontheMarket)Regulations,2007,asamended

PA0408/058/001

CaseNo:2085471

TheIrishMedicinesBoardinexerciseofthepowersconferredonitbytheabovementionedRegulationsherebygrantsto

RanbaxyIrelandLimited

Spafield,CorkRoad,Cashel,Co.Tipperary,Ireland

anauthorisation,subjecttotheprovisionsofthesaidRegulations,inrespectoftheproduct

CeliprololHydrochloride,200Milligram

theparticularsofwhicharesetoutintheattachedSchedule.Theauthorisationisalsosubjecttothegeneralconditionsasmaybespecifiedin

thesaidRegulationsaslistedonthereverseofthisdocument.

Thisauthorisation,unlesspreviouslyrevoked,shallcontinueinforcefrom06/08/2010.

SignedonbehalfoftheIrishMedicinesBoardthis

________________

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PartII

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

Celiprololhydrochloride200mgfilmcoatedTablets

2QUALITATIVEANDQUANTITATIVECOMPOSITION

Eachtabletcontains200mgceliprololhydrochloride.

Forafulllistofexcipients,seesection6.1

3PHARMACEUTICALFORM

Film-coatedtablet.

Yellowcoloured,capsuleshaped,biconvexfilmcoatedtablets,debossedwith‘200’ononesideofthebreaklineanda

deepbreaklineontheotherside.

Thetabletcanbebrokenintoequalhalves.

4CLINICALPARTICULARS

4.1TherapeuticIndications

Celiprololisindicatedforthetreatmentofhypertension.

4.2Posologyandmethodofadministration

Adults:Theinitialdoseis200mgorally,takenoncedailywithaglassofwater.Celiprololshouldbetakenonrising,

onehourbeforemeals,or2hoursaftermeals.Ifresponseisinadequate,thedosemaybeincreasedto400mgonce

daily,after2to4weeksoftreatmentwith200mgoncedaily.Itmaytakeseveralweeksoftreatmentfortheanti-

hypertensiveeffectofceliprololtobefullyestablished.Thereisnolimitforthedurationoftreatment.Thisdependson

thenatureandseverityofthedisease.Treatmentwithceliprololshouldnotbediscontinuedabruptly,butshouldbe

discontinuedgradually(i.e.overaperiodof7-10days),asdiscontinuingtreatmentabruptlymayleadtoanacute

worseningofthepatient’scondition.

Elderly:Dosageasforadults.

Dosageinrenalimpairment:Thedosageofceliprololshouldbereducedbyhalfinpatientswithcreatinineclearance

valuesof15-40ml/minute.Celiprololisnotrecommendedforpatientswithcreatinineclearancelessthan15

ml/minute.

Dosageinhepaticimpairment:Patientswithhepaticimpairmentshouldalsobecarefullymonitoredaftercommencing

therapyandareduceddosageshouldbeconsidered.

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4.3Contraindications

Celiprololiscontraindicatedinpatientswhoarehypersensitivetoceliprolol,tootherß-adrenergicblockingagentsorto

anyoftheexcipientsofthisproduct.Celiprololisalsocontraindicatedinpatientswith:

Secondorthirddegreeheartblock;

Severebradycardia(pulserateatrestlowerthan50beatsperminutebeforebeginningoftreatment);

Sicksinussyndrome;

Sinoartrialblock;

Untreatedphaeochromocytoma(celiprololmayonlybeadministeredoncethealphareceptorshavebeen

blocked);

Metabolicacidosis;

Hypotension;

Latestagesofperipheralarterialocclusivedisease(stateIIIandIVaccordingtoFontaine);

Overtheartfailure;

Cardiogenicshock;

Severerenalimpairmentwithcreatinineclearancelessthan15mlperminute;and

Severebronchialasthmaandseverechronicobstructivepulmonarydisease.

Celiprololshouldnotbeprescribedforpatientsbeingtreatmentwiththeophylline.Verapamilandbeta-blockersboth

slowA-Vconductionanddepressmyocardialcontractilitythroughdifferentmechanisms.Whenchangingfrom

verapamiltoceliprololandvice-versa,aperiodbetweenstoppingoneandstartingtheotherisrecommended.Neither

thebeta-blockernorthecalciumchannelblockershouldbeadministeredintravenouslywithin48hoursof

discontinuingtheother(seeSection4.5Interactionwithothermedicinalproductsandotherformsofinteraction).

4.4Specialwarningsandprecautionsforuse

Thepharmacokineticsarenotsignificantlydifferentintheelderly,howeverthesepatientsshouldberegularly

monitoredanddueregardmadefordecreasedrenalandliverfunctioninthisagegroup.Celiprololmaybeusedin

patientswithmildtomoderatedegreesofreducedrenalfunctionasceliprololisclearedbybothrenalandnon-renal

excretorypathways.Areductionindosagebyhalfmaybeappropriateinpatientswithcreatinineclearancesinthe

rangeof15to40mlperminute.However,carefulsurveillanceofsuchpatientsisrecommendeduntilsteadystateblood

levelsareachievedwhichtypicallywouldbewithinoneweek.Patientswithhepaticimpairmentshouldalsobe

carefullymonitoredaftercommencingtherapy.

Celiprololshouldonlybeusedwithcautioninpatientswithcontrolledcongestivecardiacfailure(patientstreatedwith

digitalisand/ordiuretics).Evidenceofdecompensationshouldberegardedasasignaltodiscontinuetherapy.

Althoughcardiacselectivebetablockersmayhavelesseffectonlungfunctionthannon-selectivebetablockers,aswith

allbetablockers,theseshouldbeavoidedinpatientswithreversibleobstructiveairwaysdiseaseunlesstherearesome

compellingclinicalreasonsforuse(seeSection4.3Contraindications).

CeliprololshouldbeusedwithcautioninpatientswithfirstdegreeAVblockandinpatientswithPrinzmetal’sangina.

Celiprololmayinducebradycardia.Ifthepulseratedecreasestolessthan50-55beatsperminuteatrestandthepatient

experiencessymptomsrelatedtobradycardia,thedosageshouldbereduced.Treatmentwithceliprololshouldbe

stoppediftheheartratedecreasestolessthan45beatspermin.

Suddenwithdrawalofbeta-adrenoceptorblockingagentsinpatientswithischemicheartdiseasemayresultinthe

appearanceofanginalattacksofincreasedfrequencyorseverityordeteriorationincardiacstate.Althoughnoadverse

effectsduetoabruptcessationofceliprololhavebeenstudiedinclinicaltrials,gradualdiscontinuationoftherapyis

recommended.

Inpatientswithperipheralcirculatorydisorders(Raynaud'sdiseaseorsyndrome,intermittentclaudication),beta

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Beta-blockersshouldbeusedwithcautioninpatientswithapparentorlatentdiabetesmellitusbecausesevere

hypoglycaemicconditionsarepossibleorsymptomsofhypoglycaemiacanbemasked(regularmonitoringofblood

glucosestatusisnecessary)(SeeSection4.5Interactionwithothermedicinalproductsandotherformsofinteraction).

Undertreatmentwithß-blockers(e.g.celiprolol)thesymptomsofthyrotoxicosismaybemasked.

Beta-blockersmayinindividualcasescausepsoriasis,aggravatethesymptomsofthepre-existingdisease,orleadto

psoriasis-likeexanthema.Patientswithahistoryofpsoriasisshouldtakeceliprololonlyaftercarefulconsideration.

Beta-blockersmayincreasesensitivitytoallergensandseverityofanaphylacticreactions.Patientswhohaveahistory

ofseverehypersensitivityandpatientsundergoingdesensitisationtreatmentmaysuffersevereanaphylacticreactions.

Celiprololtherapymustbereportedtotheanaesthetistpriortogeneralanaesthesia.Ifitisdecidedtowithdrawthe

medicinalproductbeforesurgery,48hoursshouldbeallowedtoelapsebetweenthelastdoseandanaesthesia.Inthe

eventofcontinuationofceliprololtreatment,specialcareshouldbeexercisedwhenusinganaestheticagentssuchas

ether,cyclopropaneortrichloroethylene(seesection4.5Interactionwithothermedicinalproductsandotherformsof

interaction).

4.5Interactionwithothermedicinalproductsandotherformsofinteraction

Verapamil(andtoalesserextentdiltiazem)andbeta-blockersbothslowA-Vconductionanddepressmyocardial

contractilitythroughdifferentmechanisms.Whenchangingfromverapamiltoceliprololandvice-versa,aperiod

betweenstoppingoneandstartingtheotherisrecommended.Concomitantadministrationofbothmedicinalproductsis

notrecommendedandshouldonlybeinitiatedwithECGmonitoring.Patientswithpre-existingconduction

abnormalitiesshouldnotbegiventhetwomedicinalproductstogether.

Calciumantagonistsoftheverapamil-ordiltiazem-typeandantiarrhythmicagents(e.g.disopyramide,quinidine,

amiodarone)shouldnotbegivenintravenouslyduringtherapywithceliprololbecausetheco-administrationmaylead

toprofoundhypotensionandatrioventricularblock(seeSection4.3Contraindications).

Celiprololshouldnotbeprescribedforpatientsbeingtreatedwiththeophylline(seeSection4.3Contraindications).

Betablockersmayexacerbatethereboundhypertensionwhichcanfollowthewithdrawalofclonidine.Ifthetwo

medicinalproductsareco-administered,thebeta-adrenoceptorblockingmedicinalproductshouldbewithdrawnseveral

daysbeforediscontinuingclonidine.

ThesimultaneousadministrationofceliprololwithMonoamineoxidaseinhibitors(exceptMOA-Binhibitors)may

enhancethehypotensiveeffectofß-blockersbutalsotheriskofhypertensivecrisis.

Combinationstobeusedwithcaution

Careshouldbetakeninprescribingbeta-adrenoceptorblockerswithClassIantiarrhythmicagents(e.g.disopyramide,

quinidine)andclassIIIantiarrhythmicagents(e.g.amiodarone),becausehypotension,bradycardiaorothercardiac

arrhythmiasand/orheartfailuremayresult.

Certainantiarrhythmicmedicinalproducts(disopyramide,quinidine,amiodarone,sotalol)mayproducttorsadede

pointes.Therefore,ECGmonitoringisnecessary.Incaseoftorsadedepointesadministeringofantiarrhythmicagents

isnotrecommended.

Thesimultaneousadministrationofnifedipinecancauseaseveredecreaseofthebloodpressure.

Thesimultaneousadministrationofceliprololandresperine,alpha-methyldopa,guanfacine,clonidineordigitalis

glycosidescancauseanexcessivereductionintheheartrateoranincreaseintheatrioventricularconductiontime.

Celiprololcanenhancetheeffectofantihypertensivemedicationsthataregivensimultaneously.

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loweringeffect.Beta-adrenergicblockademaymasksymptomsofhypoglycaemia(tachycardia)(seeSection4.4

Specialwarningsandspecialprecautionsforuse).Therefore,itisnotrecommendedthatthebloodglucosevaluesbe

regularlymonitored.

Theco-administrationofanaestheticdrugswithceliprololattenuatesthereflextachycardiaandincreasestheriskof

hypotension.Therefore,beforeadministeringanaestheticagents,theanaesthesiologistsho(seeSection4.4Special

warningsandspecialprecautionsforuse).uldbeinformed.Ananaestheticdrugwithaminimalnegativeinotropic

effectshouldpreferablybeused

Simultaneousadministrationofceliprololandadrenaline,noradrenalineorothersympathomimeticagents(e.g.those

containedincoughmedicineornoseandeyedrops)maycauseanincreaseofbloodpressure.

Simultaneousadministrationofvasodilators,tricyclicantidepressants,barbiturates,phenothiazinesandother

antidepressantsaswellasalcoholcanincreasethehypotensiveeffectofceliprolol.

Ithasbeenshownthatthebioavailabilityofceliprololisimpairedwhenitisgivenwithfood.Co-administrationof

chlorthalidoneandhydrochlorothiazidealsoreducesthebioavailabilityofceliprolol.

4.6Pregnancyandlactation

Pregnancy

Thesafetyofceliprololproductforuseinhumanpregnancyhasnotbeenestablished.

Celiprololpassestheplacentainhumans.Someß-adrenoceptorblockingagentscancauseintrauterinegrowth

retardations.Forthisreasonceliprololshouldbeadministeredduringpregnancyonlyafterseriousrisk-benefit

assessmentbythetreatingphysician.

Treatmentclosetothecalculatedbirthdatecancausebradycardia,hypotension,hypoglycaemiaandneonateasphyxia

inanewborninfant.Forthisreasonthetherapywithceliprololshouldbediscontinued48-72hoursbeforethe

calculateddeliverydate.Ifthisisnotfeasible,theneonatesmustbecarefullymonitoredfor48-72hoursafterbirth.

Lactation

Duringlactation,celiprololshouldonlybeusedfollowingseriousrisk-benefit-assessmentbythetreatingphysician.

Thereisnodataavailableregardingexcretionofceliprololintomother’smilk.Asotherß-adrenergicblockingagents

areexcretedintomother’smilk,excretionofceliprololintobreastmilkispossibleandthesucklinginfantshouldbe

watchedforsignsofß-adrenoreceptorblockade.

4.7Effectsonabilitytodriveandusemachines

IthasbeenshownthatdrivingabilityisunlikelytobeimpairedinpatientstakingCeliprolol.

4.8Undesirableeffects

Occasionaladversereactions,whichareusuallymildandtransienthaveoccurred.Thefollowingundesirableeffects

havebeenobservedduringtreatmentwithceliprololandotherbeta-blockerswiththefollowingfrequencies.Very

common(>10%),common(1-10%),uncommon(0.1-1%),rare(0.01-0.1%),veryrare(<0.01%)includingisolated

reports.

Immunesystemdisorders

Rarely(0.01-0.1%)Anincreaseinantinuclearantibodies(ANA)hasbeenseen,itsclinicalrelevanceisnotclear.

Metabolismandnutritiondisorders

Latentdiabetesmellitusmaycometolight,andapparentdiabetesmellitusmayworsen.Beta-blockersmaymaskthe

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Psychiatricdisorders

Rarely(0.01-0.1%)depressionhasbeenreported.

Veryrare(,0.01%)hallucinations,psychoses

Nervoussystemdisorders

Commonly(1-10%)headacheanddizziness,somnolence,nightmaresandinsomnia(sleepdisturbances),tremorand

sensationofcoldnessintheextremitieshavebeenreported.

Rarely(0.01-0.1%)paraesthesia

Veryrare(<0.01%)confusion

Eyedisorders

Veryrare(<0.01%)impairedvision,dryeyeswithreducedlacrimation(tobeconsideredifthepatientusescontact

lenses).

Earandlabyrinthdisorders

Rarely(0.01-0.1%)tinnitus

Cardiacdisorders

Commonly(1-10%)palpitations,bradycardia,significantdecreaseinbloodpressureincludingwhenstandingupfrom

alyingposition(orthostaticdysregulation),havebeenreported.

Rarely(0.01-0.1%)AV-conductiondisorders,increasedcardiacinsufficiencywithperipheraloedemaand/orexertional

dyspnoea,Raynaud’sphenomen,increaseofsymptomsinpatientswithperipheralcirculatorydisturbances(with

existingintermittentclaudication,inpatientssufferingfromRaynaud’ssyndrome)

Respiratorydisorders

Rarely(0.01-0.1%)hypersensitivitypneumonitis,bronchospasm,asthmaticdyspnoeaespeciallyinpatientswith

bronchialasthmaorahistoryofasthmaticcomplaints.

Gastrointestinaldisorders

Commonly(0.1-1%)nausea,vomiting,abdominalpainandabdominaldiscomfortcanoccur.

Rarely(0.01-0.1%)diarrhoea,constipation.

Skinandsubcutaneoustissuedisorders

Rarely)0.01-0.1%)allergicskinreactions(e.g.itching,flush,rash,pruritus,urticaria,purpura).

Veryrarely(<0.01%)Betaclockerscancausepsoriasisinisolatedcases,worsenthesymptomsofthisdiseaseorleadto

theformationofpsoriasiformexanthemes.

Musculoskeletaldisorders

Commonly(0.1-1%)musclecramps

Rarely(0.01-0.1%)muscleweakness.

Reproductivesystemdisorders

Rarely(0.01-0.1%)impotence

Generaldisordersandadministrationsiteconditions

Commonly(1-10%)fatigue.

Respiratory:bronchospasmmayoccurinpatientswithbronchialasthmaorwithahistoryofbronchialcomplaints.

4.9Overdose

Nodataareavailableregardingoverdoseinhumans.Intheeventofexcessivebradycardia,intravenousatropine

sulphateshouldbeadministeredwithoutdelaytoatotaldoseof2mg.Inadequateresponserequiresintravenous

administrationofabolusdoseofglucagons10mg.Ifrequiredthismayberepeatedorfollowedbyanintravenous

infusionofglucagons1-10mg/hr,dependingonresponse.Ifnoresponse,orglucagonsisunavailable,aslow

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refractorybradycardiaandheartblock.Hypotensionshouldbetreatedwithintravenouscatecholaminesincluding

dopamineanddobutamine.

5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

Pharmacotherapeuticgroup:Betablockingagents,selective

ATCCode:C07AB08

ModeofAction

Celiprololisavasoactive,beta-1selectiveadrenoceptorantagonistwithpartialbeta-2agonistactivityindicatedinmild

tomoderatehypertension.Thebeta-2agonistactivityisthoughttoaccountforitsmildvasodilatingproperties.It

lowersbloodpressureinhypertensivepatientsatrestandonexercise.Theeffectsonheartrateandcardiacoutputare

dependentonthepre-existingbackgroundlevelofsympathetictone.

Underconditionsofstresssuchasexercise,celiprololattenuateschronotropicandinotropicresponsestosympathetic

stimulation.However,atrest,minimalimpairmentofcardiacfunctionisseen.

Celiprololtherapyhasnotbeenshowntoadverselyaffectplasmalipidprofiles.

5.2Pharmacokineticproperties

Celiprololisahydrophiliccompoundthatisincompletelyabsorbedfromthegastrointestinaltract.Bioavailabilityof

orallyadministeredceliprololrangesfrom30to70%dependinguponthedoseadministered.Plasmahalf-lifeis

approximately5-6hoursandpharmacodynamiceffectsarepresentforatleast24hours.Atplasmaconcentrationsof

0.11to0.86µmol/L,celiprololisabout25%boundtohumanplasmaproteins.Afteroncedailyadministration,

celiprololisonlyslightlymetabolisedbeforeexcretioninthebileandurineinalmostequalquantities.

Ithasbeenshownthatthebioavailabilityofceliprololisimpairedwhenitisgivenwithfood.Co-administrationof

chlorthalidone,hydrochlorothiazideandtheophyllinealsoreducesthebioavailabilityofceliprolol.

5.3Preclinicalsafetydata

Preclinicaldatarevealnospecialhazardforhumansbasedonconventionalstudiesofsafetypharmacology,repeated

dosetoxicity,genotoxicity,carcinogenicpotentialandreproductivetoxicity.

6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

Microcrystallinecellulose

Mannitol

Croscarmellosesodium

Colloidalanhydroussilica

Magnesiumstearate

Filmcoatingmaterial:

Hypromellose

Titaniumdioxide(E171)

Macrogol400

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6.2Incompatibilities

Notapplicable.

6.3ShelfLife

3years.

6.4Specialprecautionsforstorage

Storeintheoriginalcontainer

6.5Natureandcontentsofcontainer

BlisterstripscomprisingofwhiteopaquePVCfilmwithabackingofaluminiumfoilcoatedwithheatseallacquer.

Packof10,20,28,30,50,56and100tablets.

6.6Specialprecautionsfordisposal

Nospecialrequirements.

7MARKETINGAUTHORISATIONHOLDER

RanbaxyIrelandLtd

Spafield,CorkRoad

Cashel

CoTipperary

8MARKETINGAUTHORISATIONNUMBER

PA0408/058/001

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

Dateoffirstauthorisation:18December2003

Dateoflastrenewal:26June2007

10DATEOFREVISIONOFTHETEXT

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