BISOPROLOL

Main information

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

Documents

Localization

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

Status

  • Source:
  • HPRA - Health Products Regulatory Authority - Ireland
  • Authorization number:
  • PA0822/058/001
  • Authorization date:
  • 25-11-2011
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

BisoprololPfizer5mgFilm-coatedTablets

2QUALITATIVEANDQUANTITATIVECOMPOSITION

Eachfilm-coatedtabletcontains5mgofbisoprololfumarateequivalentto4.24mgbisoprolol.

Forafulllistofexcipients,seesection6.1

3PHARMACEUTICALFORM

Film-coatedtablet.

Yellowcoloured,circular,biconvex,film-coatedtabletsdebossedwith‘Iandscoreline’ononesideand‘11’onthe

otherside.Thetabletcanbedividedintoequalhalves.

4CLINICALPARTICULARS

4.1TherapeuticIndications

Managementofhypertension

Managementofchronicstableanginapectoris

4.2Posologyandmethodofadministration

Adults

Thedosageshouldbeindividuallyadjusted.Itisrecommendedtostartwith5mgperday.Theusualdoseis10mg

oncedailywithamaximumrecommendeddoseof20mgperday.

Patientswithrenalimpairment

Inpatientswithsevererenalimpairment(creatinineclearance<20ml/min)thedoseshouldnotexceed10mgonce

daily.Thisdosagemayeventuallybedividedintohalves.

Patientswithsevereliverimpairment

Nodosageadjustmentisrequired,howevercarefulmonitoringisadvised.

Elderly

Nodosageadjustmentisnormallyrequired.Itisrecommendedtostartwiththelowestpossibledose.

Childrenunder12yearsandadolescents

Bisoprololisnotrecommendedforuseinchildrenbelowage12andadolescentsowingtoalackofdataonsafetyand

efficacy.

Durationoftherapyforallindications

Treatmentwithbisoprololisgenerallyalong-termtherapy.

Thetreatmentwithbisoprololmustnotbestoppedabruptlysincethismightleadtoatransitoryworseningofcondition.

Especiallyinpatientswithischaemicheartdisease,treatmentmustnotbediscontinuedsuddenly.Gradualreductionof

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Administration

BisoprololPfizerTabletsaretakeninthemorningwithorwithoutfood.Theyareswallowedwithsomeliquidandnot

tobechewed.

Fororaluse

4.3Contraindications

Bisoprololiscontraindicatedinpatientswith:

acuteheartfailureorduringepisodesofheartfailuredecompensationrequiringi.v.inotropictherapy

cardiogenicshock

secondorthirddegreeAVblock(withoutapacemaker)

sicksinussyndrome

sinoatrialblock

symptomaticbradycardia

symptomatichypotension

severebronchialasthmaorseverechronicobstructivepulmonarydisease

severeformsofperipheralarterialocclusivediseaseorsevereformsofRaynaud'ssyndrome

untreatedphaeochromocytoma(seesection4.4)

metabolicacidosis

Bisoprololiscontra-indicatedinpatientswithhypersensitivitytobisoprololortoanyoftheexcipients

4.4Specialwarningsandprecautionsforuse

Specialwarnings:

Especiallyinpatientswithischaemicheartdiseasethecessationoftherapywithbisoprololmustnotbedoneabruptly

unlessclearlyindicated,becausethismayleadtotransitionalworseningofheartcondition(seesection4.2).

Precautions:

Bisoprololmustbeusedwithcautioninpatientswithhypertensionoranginapectorisandaccompanyingheartfailure.

Bisoprololmustbeusedwithcautionin:

diabetesmellitusshowinglargefluctuationsinbloodglucosevalues.Symptomsofhypoglycaemia(e.g.

tachycardia,palpitationsorsweating)canbemasked,

strictfasting,

ongoingdesensitisationtherapy.Aswithotherbeta-blockers,bisoprololmayincreaseboththesensitivitytowards

allergensandtheseverityofanaphylacticreactions.Epinephrinetreatmentmaynotalwaysyieldtheexpected

therapeuticeffect,

FirstdegreeAVblock,

Prinzmetal'sangina,

peripheralarterialocclusivedisease.Aggravationofsymptomsmayoccurespeciallywhenstartingtherapy.

Patientswithpsoriasisorwithahistoryofpsoriasisshouldonlybegivenbeta-blockers(e.g.bisoprolol)afteracareful

balancingofbenefitsagainstrisks.

Thesymptomsofthyrotoxicosismaybemaskedundertreatmentwithbisoprolol.

Inpatientswithphaeochromocytomabisoprololmustnotbeadministereduntilafteralpha-receptorblockade.

Inpatientsundergoinggeneralanaesthesiabeta-blockadereducestheincidenceofarrhythmiasandmyocardial

ischemiaduringinductionandintubation,andthepost-operativeperiod.Itiscurrentlyrecommendedthatmaintenance

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potentialforinteractionswithotherdrugs,resultinginbradyarrhythmias,attenuationofreflextachycardia,and

decreasedreflexabilitytocompensateforbloodloss.Ifitisthoughtnecessarytowithdrawbeta-blockertherapybefore

surgery,thisshouldbedonegraduallyandcompletedabout48hoursbeforeanaesthesia.

Inbronchialasthmaorotherchronicobstructivepulmonarydiseases,whichmaycausesymptoms,concomitant

bronchodilatingtherapyisrecommended.Occasionallyanincreaseoftheairwayresistancemayoccurinpatientswith

asthma;thereforethedoseofbeta2-stimulantsmayhavetobeincreased.

4.5Interactionwithothermedicinalproductsandotherformsofinteraction

Combinationsnotrecommended

Calciumantagonistsoftheverapamiltypeandtoalesserextentofthediltiazemtype:Negativeeffectoncontractility

andatrio-ventricularconduction.Intravenousadministrationofverapamilinpatientsonbeta-blockertreatmentmay

leadtoprofoundhypotensionandatrio-ventricularblock.

Centrally-actingantihypertensivedrugs(e.g.clonidinemethyldopa,moxonodine,rilmenidine):Concomitantuseof

centrally-actingantihypertensivedrugsmayfurtherdecreasethecentralsympathetictonusandmaythusleadto

reductionofheartrateandcardiacoutputandtovasodilatation.Abruptwithdrawal,particularlyifpriortobeta-blocker

discontinuation,mayincreasetheriskof'reboundhypertension'.

Combinationstobeusedwithcaution

Class-Iantiarrhythmicdrugs(e.g.quinidine,disopyramide;lidocaine,phenytoin;flecainidepropafenone):Effecton

atrio-ventricularconductiontimemaybepotentiatedandnegativeinotropiceffectincreased.

Calciumantagonistsofthedihydropyridinetype(e.g.felodipineandamlodipine):Concomitantusemayincreasethe

riskofhypotension,andanincreaseintheriskofafurtherdeteriorationoftheventricularpumpfunctioninpatients

withheartfailurecannotbeexcluded.

Class-IIIantiarrhythmicdrugs(e.g.amiodarone):Effectonatrio-ventricularconductiontimemaybepotentiated.

Parasympathomimeticdrugs:Concomitantusemayincreaseatrio-ventricularconductiontimeandtheriskof

bradycardia.

Topicalbeta-blockers(e.g.eyedropsforglaucomatreatment)mayaddtothesystemiceffectsofbisoprolol.

Insulinandoralantidiabeticdrugs:Increaseofbloodsugarloweringeffect.Blockadeofbeta-adrenoceptorsmaymask

symptomsofhypoglycaemia.

Anaestheticagents:Attenuationofthereflextachycardiaandincreaseoftheriskofhypotension(seesection4.4).

Digitalisglycosides:Increaseofatrio-ventricularconductiontime,reductioninheartrate.

Non-steroidalanti-inflammatorydrugs(NSAIDs):NSAIDsmayreducethehypotensiveeffectofbisoprolol.

Beta-sympathomimetics(e.g.isoprenaline,dobutamine):Combinationwithbisoprololmayreducetheeffectofboth

agents.

Sympathomimeticsthatactivatebothbeta-andalpha-adrenoceptors(e.g.norepinephrine,epinephrine):Combination

withbisoprololmayunmaskthealpha-adrenoceptor-mediatedvasoconstrictoreffectsoftheseagentsleadingtoblood

pressureincreaseandexacerbatedintermittentclaudication.Suchinteractionsareconsideredtobemorelikelywith

nonselectivebeta-blockers.

Concomitantusewithantihypertensiveagentsaswellaswithotherdrugswithbloodpressureloweringpotential(e.g.

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Combinationstobeconsidered

Mefloquine:increasedriskofbradycardia.

Corticosteroids:decreaseofantihypertensiveeffectduetowaterandsodiumretention.

Monoamineoxidaseinhibitors(exceptMAO-Binhibitors):Enhancedhypotensiveeffectofthebetablockersbutalso

riskofhypertensivecrisis.

Rifampicin:Slightreductionofthehalf-lifeofbisoprololpossibleduetotheinductionofhepaticdrug-metabolizing

enzymes.Normallynodosageadjustmentisnecessary.

Ergotaminederivatives:Exacerbationofperipheralcirculatorydisturbances.

4.6Fertility,pregnancyandlactation

Pregnancy:

Bisoprololhaspharmacologicaleffectsthatmaycauseharmfuleffectsonpregnancyand/orthefetus/newborn.In

general,-adrenoceptorblockingagentsreduceplacentalperfusion,whichhasbeenassociatedwithgrowthretardation,

intrauterinedeath,abortionorearlylabour.Adverseeffects(e.g.hypoglycaemia,bradycardia)mayoccurinthefetus

andnewborninfant.Iftreatmentwith-adrenoceptorblockingagentsisnecessary,

-selectiveadrenoceptorblocking

agentsarepreferable.

Bisoprololisnotrecommendedduringpregnancyunlessclearlynecessary.Iftreatmentwithbisoprololisconsidered

necessary,theuteroplacentalbloodflowandfetalgrowthshouldbemonitored.Incaseofharmfuleffectsonpregnancy

orthefetusalternativetreatmentshouldbeconsidered.Thenewborninfantmustbecloselymonitored.Symptomsof

hypoglycaemiaandbradycardiaaregenerallytobeexpectedwithinthefirst3days.

Lactation:

Therearenodataontheexcretionofbisoprololinhumanbreastmilkorthesafetyofbisoprololexposureininfants.

Therefore,breastfeedingisnotrecommendedduringadministrationofBisoprololPfizer.

4.7Effectsonabilitytodriveandusemachines

Inastudywithcoronaryheartdiseasepatients,bisoprololdidnotimpairdrivingperformance.However,dependingon

theindividualpatientsresponsetotreatmentaneffectontheabilitytodriveavehicleortousemachinescannotbe

excluded.Thisneedstobeconsideredparticularlyatstartoftreatment,uponchangeofmedication,orinconjunction

withalcohol.

4.8Undesirableeffects

Thefollowingundesirableeffectshavebeenobservedduringtreatmentwithbisoprololwiththefollowingfrequencies:

Verycommon(1/10)

Common(1/100to<1/10)

Uncommon(1/1,000to<1/100)

Rare(1/10,000to<1/1,000)

Veryrare(<1/10,000).

Notknown(cannotbeestimatedfromtheavailabledata).

Psychiatricdisorders

Uncommon: depression,sleepdisorders

Rare: nightmares,hallucinations

Nervoussystemdisorders

Common: dizziness*,headache*

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Eyedisorders

Rare: reducedtearflow(tobeconsideredifthepatientusescontactlenses)

Veryrare: conjunctivitis

Earandlabyrinthdisorders

Rare: hearingdisorders

Cardiacdisorders

Uncommon: AV-conductiondisturbances;worseningofpre-existingheartfailure;bradycardia

Vasculardisorders

Common: feelingofcoldnessornumbnessintheextremities,hypotensionespeciallyinpatientswithheartfailure

Uncommon: Orthostatichypotension

Respiratory,thoracicandmediastinaldisorders

Uncommon: bronchospasminpatientswithbronchialasthmaorahistoryofobstructiveairwaydisease

Rare: allergicrhinitis

Gastrointestinaldisorders

Common: gastrointestinalcomplaintssuchasnausea,vomiting,diarrhoea,Constipation

Hepatobiliarydisorders

Rare: hepatitis.

Skinandsubcutaneoustissuedisorders

Rare: hypersensitivityreactionssuchasitching,flush,rash

Veryrare: alopecia.Beta-blockersmayprovokeorworsenpsoriasisorinducepsoriasis-likerash.

Musculoskeletalandconnectivetissuedisorders

Uncommon: muscleweakness,musclecramps

Reproductivesystemandbreastdisorders

Rare: potencydisorders

Generaldisorders

Common: fatigue*

Uncommon:asthenia

Investigations

Rare: increasedtriglycerides,increasedliverenzymes(ALT,AST)

*Thesesymptomsespeciallyoccuratthebeginningofthetherapy.Theyaregenerallymildandusuallydisappear

within1-2weeks.

4.9Overdose

Themostcommonsignsexpectedwithoverdoseofabeta-blockerarebradycardia,hypotension,bronchospasm,acute

cardiacinsufficiencyandhypoglycaemia.Thereislimitedexperiencewithoverdoseofbisoprolol,onlyafewcasesof

overdosewithbisoprololhavebeenreported.Bradycardiaand/orhypotensionwerenoted.Allpatientsrecovered.There

isawideinter-individualvariationinsensitivitytoonesinglehighdoseofbisoprololandpatientswithheartfailureare

probablyverysensitive.

Ingeneral,ifoverdoseoccurs,discontinuationofbisoprololtreatmentandsupportiveandsymptomatictreatmentis

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Basedontheexpectedpharmacologicactionsandrecommendationsforotherbeta-blockers,thefollowinggeneral

measuresmaybeconsideredwhenclinicallywarranted.

Bradycardia:Administerintravenousatropine.Iftheresponseisinadequate,isoprenalineoranotheragentwithpositive

chronotropicpropertiesmaybegivencautiously.Undersomecircumstances,transvenouspacemakerinsertionmaybe

necessary.

Hypotension:Intravenousfluidsandvasopressorsshouldbeadministered.Intravenousglucagonmaybeuseful.

AVblock(secondorthirddegree):Patientsshouldbecarefullymonitoredandtreatedwithisoprenalineinfusionor

temporarypacing.

Acuteworseningofheartfailure:Administeri.v.diuretics,inotropicagents,vasodilatingagents.

Bronchospasm:Administerbronchodilatortherapysuchasisoprenaline,beta2-sympathomimeticdrugsand/or

aminophylline.

Hypoglycaemia:Administeri.v.glucose.

Limiteddatasuggestthatbisoprololishardlydialysable.

5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

Pharmacotherapeuticgroup:Betablockingagents,selective

ATCcode:C07AB07

Bisoprololisahighlybeta1-selective-adrenoceptorblockingagent,lackingintrinsicsympathomimeticandrelevant

membranestabilisingactivity.Itonlyshowslowaffinitytothebeta2-receptorofthesmoothmusclesofbronchiand

vesselsaswellastothebeta2-receptorsconcernedwithmetabolicregulation.Therefore,bisoprololisgenerallynotto

beexpectedtoinfluencetheairwayresistanceandbeta2-mediatedmetaboliceffects.Itsbeta1-selectivityextends

beyondthetherapeuticdoserange.

Bisoprololisusedforthetreatmentofhypertensionandanginapectoris.AswithotherBeta-1-blockingagents,the

methodofactinginhypertensionisunclear.However,itisknownthatBisoprololreducesplasmareninactivity

markedly.

Antianginalmechanism:Bisoprololbyinhibitingthecardiacbetareceptorsinhibitstheresponsegiventosympathetic

activation.Thatresultsinthedecreaseofheartrateandcontractilitythiswaydecreasingtheoxygendemandofthe

cardiacmuscle.

Inacuteadministrationinpatientswithcoronaryheartdiseasewithoutchronicheartfailurebisoprololreducestheheart

rateandstrokevolumeandthusthecardiacoutputandoxygenconsumption.Inchronicadministrationtheinitially

elevatedperipheralresistancedecreases.

5.2Pharmacokineticproperties

Bisoprololisabsorbedalmostcompletelyfromthegastrointestinaltract.Togetherwiththeverysmallfirstpasseffect

intheliver,thisresultsinahighbioavailabilityofapproximately90%.Theplasmaproteinbindingofbisoprololis

about30%.Thedistributionvolumeis3.5l/kg.Thetotalclearanceisapproximately15l/h

Theplasmaeliminationhalf-life(10-12hours)provides24hoursefficacyfollowingaoncedailydosage.

Bisoprololisexcretedfromthebodybytworoutes,50%ismetabolisedbythelivertoinactivemetaboliteswhichare

thenexcretedbythekidneys.Theremaining50%isexcretedbythekidneysinanunmetabolisedform.Since

eliminationtakesplaceinthekidneysandthelivertothesameextentadosageadjustmentisnotrequiredforpatients

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Thekineticsofbisoprololarelinearandindependentofage.

Inpatientswithchronicheartfailure(NYHAstageIII)theplasmalevelsofbisoprololarehigherandthehalflifeis

prolongedcomparedtohealthyvolunteers.Maximumplasmaconcentrationatsteadystateis64±21ng/mlatadaily

doseof10mgandthehalflifeis17±5hours.

5.3Preclinicalsafetydata

Preclinicaldatarevealnospecialhazardforhumansbasedonconventionalstudiesofsafetypharmacology,repeated

dosetoxicity,genotoxicityorcarcinogenicity.Likeother-blockingagents,bisoprololcausedmaternal(decreased

foodintakeanddecreasedbodyweight)andembryo/fetaltoxicity(increasedincidenceofresorptions,reducedbirth

weightoftheoffspring,retardedphysicaldevelopment)athighdosesbutwasnotteratogenic.

6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

Tabletcore:

Cellulose,microcrystalline

CalciumHydrogenPhosphate,Anhydrous

SilicaColloidalAnhydrous

Crospovidone(TypeA)

Magnesiumstearate

Tabletcoat:

Hypromellose6cP(E464)

TitaniumDioxide(E171)

Macrogol400

IronOxideYellow(E172)

6.2Incompatibilities

Notapplicable.

6.3Shelflife

2years

6.4Specialprecautionsforstorage

Storeintheoriginalpackageinordertoprotectfromlight.

6.5Natureandcontentsofcontainer

BisoprololPfizerfilm-coatedtabletsareavailablein–Polyamide/Aluminium/PVC/Paper/Polyester/Aluminiumblisters

andHDPEcontainerwithPPclosurecontainingsilicagelsachet.

Packsizes:

Blisterpack:20,28,30,50,56,60,90,100film-coatedtablets

HDPEcontainerpack:30,500film-coatedtablets

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6.6Specialprecautionsfordisposal

Anyunusedproductorwastematerialshouldbedisposedofinaccordancewithlocalrequirements.

7MARKETINGAUTHORISATIONHOLDER

PfizerHealthcareIreland

9Riverwalk

NationalDigitalPark

CitywestBusinessCampus

Dublin24

Ireland

8MARKETINGAUTHORISATIONNUMBER

PA822/58/1

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

Dateoffirstauthorisation:25thNovember2011

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