BISOPROLOL FUMARATE 5 MG TABLETS

Main information

  • Trade name:
  • BISOPROLOL FUMARATE 5 MG TABLETS
  • Dosage:
  • 5 Milligram
  • Pharmaceutical form:
  • Tablets
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug

Documents

Localization

  • Available in:
  • BISOPROLOL FUMARATE 5 MG TABLETS
    Ireland
  • Language:
  • English

Status

  • Source:
  • HPRA - Health Products Regulatory Authority - Ireland
  • Authorization number:
  • PA0281/095/001
  • Authorization date:
  • 08-02-2001
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

PartII

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

BisoprololFumarate5mgtablets

2QUALITATIVEANDQUANTITATIVECOMPOSITION

Eachtabletcontainsbisoprololfumarate5mg

Forfulllistofexcipients,seesection6.1.

3PHARMACEUTICALFORM

Tablet

Paleyellowroundbiconvex,with‘BIS’over‘5’ononeside.

4CLINICALPARTICULARS

4.1TherapeuticIndications

Bisoprololfumaratecanbeusedforthemanagementofhypertensionandthemanagementofanginapectoris.

4.2Posologyandmethodofadministration

Forhypertensionandanginapectoristheusualdosagerangesfrom5to20mgofbisoprololfumarate.

Adults:Theusualdoseis10mgoncedailywithamaximumrecommendeddoseof20mgperday.Insomepatients5

mgperdaymaybeadequate.

Inpatientswithfinalstageimpairmentofrenal(creatinineclearance,20ml/min)orliverfunction,thedoseshouldnot

exceed10mgbisoprololoncedaily.Experienceoftheuseofbisoprololinrenaldialysispatientsislimited;however

thereisnoevidencethatthedosageregimenneedstobealtered.

Elderly:Nodosageadjustmentisnormallyrequiredbut5mgperdaymaybeadequateinsomepatients;asforother

adults,dosesmayhavetobereducedincasesofsevererenalorhepaticdysfunction.

Children:Thereisnopaediatricexperiencewithbisoprolol,thereforeitsusecannotberecommendedforchildren.

Inpatientswithischaemicheartdisease,treatmentshouldnotbewithdrawnabruptly;gradualdosagereductionover

1-2weeksisrecommended.

Administration

Oraluse.

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 22/09/2007 CRN 2039842 page number: 1

4.3Contraindications

Acuteheartfailureorduringepisodesofheartfailuredecompensationrequiringi.v.inotropictherapy

Cardiogenicshock

AVblockofsecondorthirddegree(withoutapacemaker)

Sicksinussyndrome

Sinoatrialblock

Bradycardiawithlessthan60beats/minbeforestartoftherapy

Hypotension(systolicbloodpressurelessthan100mmHg)

Severebronchialasthmaorseverechronicobstructivepulmonarydisease

LatestagesofperipheralarterialocclusivediseaseandRaynaud'ssyndrome

Untreatedphaeochromocytoma(seesection4.4Specialwarningsandprecautionsforuse)

Metabolicacidosis

Hypersensitivitytobisoprololortoanyoftheexcipients

4.4Specialwarningsandprecautionsforuse

-adrenergicblockingagentshavebeenusedsafelyandefficaciouslyinelderlypatients.However,elderlypatients

maybemoresusceptibletosomeadverseeffectsoftheseagents.Elderlypatientsaremorelikelytohaveage-related

peripheralvasculardisease,whichmayrequirecautioninpatientsreceiving-adrenergicblockingagents.Inaddition

theriskof-blocker-inducedhypothermiamaybeincreasedinelderlypatients.

Otherformulationsofbisoprololcontainingmedicinalproductsareusedinthetreatmentofchronicheartfailure.The

useof-blockingagentsinthisindicationneedsaverycautiousapproachandshouldbestartedwithaverystrict

titrationphase.Inthisphaseincrementsarenecessaryallofwhicharenotpossiblewiththecurrentmedicinalproduct.

Thisproductshouldthereforenotbeusedinthetreatmentofchronicheartfailure.

Bisoprololmustbeusedwithcautionin:

Bronchospasm(bronchialasthma,obstructiveairwaysdiseases):

Inbronchialasthmaorotherchronicobstructivelungdiseases,whichmaycausesymptoms,bronchodilating

therapyshouldbegivenconcomitantly.Occasionallyanincreaseoftheairwayresistancemayoccurinpatients

withasthma;thereforethedoseofbeta2-stimulantsmayhavetobeincreased.

Diabetesmellituswithlargefluctuationsinbloodglucosevalues;symptomsofhypoglycaemiacanbemasked.

-adrenergicblockingagentsmaymasktachycardiaassociatedwithhypoglycemia,butnotdizzinessand

sweating; -adrenergicblockingagentsmayadverselyaffectrecoveryfromhypoglycemiaandimpair

peripheralcirculation;theseeffectsmaytheoreticallybemorelikelywiththenoncardioselectiveagentsandless

likelywithlabetalolandcardioselectiveagents.

Strictfasting

Ongoingdesensitisationtherapy

AVblockoffirstdegree

Prinzmetal'sangina

Peripheralarterialocclusivedisease(intensificationofcomplaintsmighthappenespeciallyduringthestartof

therapy)Raynaud’ssyndromeandotherperipheralvasculardiseases(-adrenergicblockingagentsmayreduce

peripheralcirculationandworsentheseconditions).

Generalanaesthesia:Inpatientsundergoinggeneralanaesthesiabeta-blockadereducestheincidenceof

arrhythmiasandmyocardialischemiaduringinductionandintubation,andthepost-operativeperiod.Itis

currentlyrecommendedthatmaintenancebeta-blockadebecontinuedperi-operatively.Theanaesthetistmustbe

awareofbeta-blockadebecauseofthepotentialforinteractionswithotherdrugs,resultinginbradyarrhythmias,

attenuationofthereflextachycardiaandthedecreasedreflexabilitytocompensateforbloodloss.Ifitisthought

necessarytowithdrawbeta-blockertherapybeforesurgery,thisshouldbedonegraduallyandcompletedabout48

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 22/09/2007 CRN 2039842 page number: 2

Aswithotherbeta-blockers,bisoprololmayincreaseboththesensitivitytowardsallergensandtheseverityof

anaphylacticreactions.Adrenalinetreatmentdoesnotalwaysgivetheexpectedtherapeuticeffect.

Patientswithpsoriasisorwithahistoryofpsoriasisshouldonlybegivenbeta-blockers(e.g.bisoprolol)after

carefullybalancingthebenefitsagainsttherisks.

Inpatientswithphaeochromocytomabisoprololmustnotbeadministereduntilafteralpha-receptorblockade.

Undertreatmentwithbisoprololthesymptomsofathyreotoxicosismaybemasked.

Hepaticfunctionimpairment:Metabolismof-adrenergicblockingagentsthatundergohepaticmetabolismmaybe

decreased;patientswithimpairedhepaticfunctionmayrequirelowerdosesof-adrenergicblocking-agents.

Myastheniagravis:-adrenergicblockingagentsmaypotentiateamyastheniccondition,includingmuscleweakness

anddoublevision.

Renalfunctionimpairment:Mayimpair-adrenergicblockingagentclearance;riskofreducedrenalbloodflow;

patientswithimpairedrenalfunctionmayrequirereduceddosesof-adrenergicblockingagents.

Hyperthyroidism:-adrenergicblockingagentsmaymasktachycardiasymptoms;abruptwithdrawalmayintensify

symptoms.

4.5Interactionwithothermedicinalproductsandotherformsofinteraction

Combinationsnotrecommended

Calciumantagonistsoftheverapamiltypeandtoalesserextentofthediltiazemtype:Negativeinfluenceon

contractilityandatrio-ventricularconduction.Intravenousadministrationofverapamilinpatientson-blocker

treatmentmayleadtoprofoundhypotensionandatrioventricularblock.

Clonidine:Increasedriskof"reboundhypertension"aswellasexaggerateddecreaseinheartrateandcardiac

conduction.

Monoamineoxidaseinhibitors(exceptMAO-Binhibitors):Enhancedhypotensiveeffectof-blockersbutalsoriskof

hypertensivecrisis.

Combinationstobeusedwithcaution

Calciumantagonistsofthedihydropyridinetypesuchasfelodipineandamlodipine:Concomitantusemayincreasethe

riskofhypotension,andanincreaseintheriskofafurtherdeteriorationoftheventricularpumpfunctioninpatients

withheartfailurecannotbeexcluded.

Class-Iantiarrhythmicdrugs(e.g.disopyramide,quinidine):Effectonatrialconductiontimemaybepotentiatedand

negativeinotropiceffectmaybeincreased.

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

Parasympathomimeticdrugs:Atrio-ventricularconductiontimemaybeincreased.

Otherbeta-blockers,includingeyedrops,haveadditiveeffects.

Insulinandoralantidiabeticdrugs:Intensificationofbloodsugarloweringeffect.Blockadeofbeta-adrenoreceptors

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 22/09/2007 CRN 2039842 page number: 3

Anaestheticagents:Attenuationofthereflextachycardiaandincreaseoftheriskofhypotension.Continuationof-

blockadereducestheriskofarrhythmiaduringinductionandintubation.Theanaesthesiologistshouldbeinformed

whenthepatientisreceivingbisoprolol.

Digitalisglycosides:Reductionofheartrate,increaseofatrio-ventricularconductiontime.

Prostaglandinsynthetaseinhibitingdrugs:Decreasedhypotensiveeffect.

Ergotaminederivatives:Exacerbationofperipheralcirculatorydisturbances.

Sympathomimeticagents:Combinationwithbisoprololmayreducetheeffectofbothagents.Higherdosesof

epinephrinemaybenecessaryfortreatmentofallergicreactions.

Tricyclicantidepressants,barbiturates,phenothiazinesaswellasotherantihypertensiveagents:Increasedblood

pressureloweringeffect.

Rifampicin:Slightreductionofthehalf-lifeofbisoprololpossibleduetotheinductionofhepaticdrug-metabolising

enzymes.Normallynodosageadjustmentisnecessary.

Combinationstobeconsidered

Mefloquine:increasedriskofbradycardia

4.6Pregnancyandlactation

Pregnancy:

Bisoprololhaspharmacologicaleffectsthatmaycauseharmfuleffectsonpregnancyand/orthefoetus/newborn.In

general,beta-adrenoceptorblockersreduceplacentalperfusion,whichhasbeenassociatedwithgrowthretardation,

intrauterinedeath,abortionorearlylabour.Adverseeffects(e.g.hypoglycaemiaandbradycardia)mayoccurinthe

foetusandnewborninfant.Iftreatmentwithbeta-adrenoceptorblockersisnecessary,beta1-selectiveadrenoceptor

blockersarepreferable.

Bisoprololshouldnotbeusedduringpregnancyunlessclearlynecessary.Iftreatmentwithbisoprololisconsidered

necessary,theuteroplacentalbloodflowandthefoetalgrowthshouldbemonitored.Incaseofharmfuleffectson

pregnancyorthefoetusalternativetreatmentshouldbeconsidered.Thenewborninfantmustbecloselymonitored.

Symptomsofhypoglycaemiaandbradycardiaaregenerallytobeexpectedwithinthefirst3days.

Lactation:

Itisnotknownwhetherbisoprololissecretedintobreastmilk,thereforebreastfeedingisnotrecommendedduring

administrationofbisoprolol.

4.7Effectsonabilitytodriveandusemachines

Inastudywithcoronaryheartdiseasepatients,bisoprololdidnotimpairdrivingperformance.However,dueto

individualvariationsinreactionstothedrug,theabilitytodriveavehicleortooperatemachinerymaybeimpaired.

Thisshouldbeconsideredparticularlyatstartofthetreatmentanduponchangeofmedicationaswellasinconjunction

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 22/09/2007 CRN 2039842 page number: 4

4.8Undesirableeffects

Thefollowingdataresultsfrompost-marketingexperiencewithbisoprolol:

Common(>1%and<10%),uncommon(>0.1%and<1%),rare(>0.01%and<0.1%),veryrare(<0.01%),singlecases.

Cardiacdisorders:

Uncommon:bradycardia,AV-stimulusdisturbances,worseningofheartfailure.

Earandlabyrinthdisorders:

Rare:hearingimpairment.

Eyedisorders:

Rare:reducedtearflow(tobeconsideredifthepatientuseslenses).

Veryrare:conjunctivitis.

Gastrointestinaldisorders:

Common:Nausea,vomiting,diarrhoea,constipation.

Generaldisorders:

Uncommon:Muscularweaknessandcramps.

Hepatobiliarydisorders:

Rare:increasedliverenzymes(ALAT,ASAT),hepatitis.

Metabolismandnutritiondisorders:

Rare:Increasedtriglycerides.

Nervoussystemdisorders:

Common:Tiredness*,exhaustion*,dizziness*,headache*.

Uncommon:Sleepdisturbances,depression.

Rare:Nightmares,hallucinations.

Reproductivesystemandbreastdisorders:

Rare:Potencydisorders.

Respiratory,thoracicandmediastinaldisorders:

Uncommon:Bronchospasminpatientswithbronchialasthmaorahistoryofobstructiveairwaysdisease.

Rare:allergicrhinitis.

Skinandsubcutaneoustissuedisorders:

Rare:hypersensitivityreactions(itching,flush,rash).

Veryrare:beta-blockersmayprovokeorworsenpsoriasisorinducepsoriasis-likerash,alopecia.

Vasculardisorders:

Common:Feelingofcoldnessornumbnessintheextremities.

Uncommon:orthostatichypotension.

*Thesesymptomsespeciallyoccuratthebeginningofthetherapy.Theyaregenerallymildandusuallydisappear

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 22/09/2007 CRN 2039842 page number: 5

4.9Overdose

Themostcommonsignsexpectedwithoverdosageofa-blockerarebradycardia,hypotension,bronchospasm,acute

cardiacinsufficiencyandhypoglycaemia.Todateafewcasesofoverdose(maximum:2000mg)withbisoprololhave

beenreported.Bradycardiaand/orhypotensionwerenoted.Allpatientsrecovered.Thereisawideinterindividual

variationinsensitivitytoonesinglehighdoseofbisoprolol.

Ifoverdoseoccurs,bisoprololtreatmentshouldbestoppedandsupportiveandsymptomatictreatmentshouldbe

provided.Limiteddatasuggestthatbisoprololishardlydialysable.Basedontheexpectedpharmacologicactionsand

recommendationsforotherbeta-blockers,thefollowinggeneralmeasuresshouldbeconsideredwhenclinically

warranted.

Bradycardia:Administerintravenousatropine.Iftheresponseisinadequate,isoprenalineoranotheragentwithpositive

chronotropicpropertiesmaybegivencautiously.Undersomecircumstances,transvenouspacemakerinsertionmaybe

necessary.

Hypotension:Intravenousfluidsandvasopressorsshouldbeadministered.Intravenousglucagonmaybeuseful.

AVblock(secondorthirddegree):Patientsshouldbecarefullymonitoredandtreatedwithisoprenalineinfusionor

transvenouscardiacpacemakerinsertion.

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

Bronchospasm:Administerbronchodilatortherapysuchasisoprenaline,beta2-sympathomimeticdrugsand/or

aminophylline.

Hypoglycaemia:Administeri.v.glucose.

5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

Pharmacotherapeuticgroup:Betablockingagents,selective

ATCcode:C07AB07

Bisoprololisapotent,highly1-selectiveadrenoreceptorblockingagentdevoidofintrinsicsympathomimeticactivity

andwithoutrelevantmembranestabilisingactivity.

Aswithother1-blockingagents,themodeofactioninhypertensionisnotclearbutitisknownthatbisoprolol

markedlydepressesplasmareninlevels.

Inpatientswithangina,theblockadeof1-receptorsreducesheartactionandthusreducesoxygendemand.Hence

bisoprololiseffectiveineliminatingorreducingthesymptoms.

5.2Pharmacokineticproperties

Followingoraladministrationofbisoprololfumarate,90%ofbisoprololisabsorbedfromthegastrointestinaltract.

Peakplasmaconcentrationsareachievedafter3hours,40µg/laftera10mgdose,andappearnottobeaffectedby

concomitantfoodintakeorfasting.Thesystemicbioavailabilityofbisoprolol,givenasfumarate,is90%,andhence

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 22/09/2007 CRN 2039842 page number: 6

Thereareonlysmallintra-andinterindividualvariationsintheplasmalevelsofthedrug.Themeanplasmahalf-life

of10to20hoursislongcomparedtothatofother-blockers.About50%ofbisoprololisexcretedunchangedinthe

urine,andother50%isbiotransformedintheliverwithsubsequenteliminationofpharmacologicallyinactive

metabolitesviathekidneys.Therenalclearanceis160ml/minandthenon-renalclearance150ml/min.The

pharmacokineticpropertiesofbisoprololarenotdependentonageordoseintherange2.5-100mg.

Thepharmacokineticsofbisoprololisnotalteredinpatientswithfebrileinfectiousdiseases.Bisoprololisslowly

distributedthroughoutthebody,withanapparentdistributionvolumeof3l/kg.

Inanimalexperimentbisoprololhasbeenfoundinthelung,kidneys,brainandtheheartafteroralandintravenous

administration.Inplasmaabout30%ofbisoprololisproteinbound.Informationaboutconcentrationsofbisoprololin

thecerebrospinalfluid,thecerebrospinalfluid/plasmaratio,theconcentrationinthebreastmilk,anditsplacental

transfer,inmanisnotavailable.

5.3Preclinicalsafetydata

Notapplicable

6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

Cellulosemicrocrystalline

Mannitol(E421)

Croscarmellosesodium

Magnesiumstearate

FilmCoating

Hypromellose(E464)

Titaniumdioxide(E171)

Macrogol400

Ironoxideyellow(E172)

6.2Incompatibilities

Notapplicable

6.3ShelfLife

2years

6.4Specialprecautionsforstorage

Forblisterpacks: Donotstoreabove25°C.

Storeinoriginalpackage.

Forplasticcontainer: Donotstoreabove30°C.

Storeinoriginalcontainer.

6.5Natureandcontentsofcontainer

Whiteroundhighdensitypolyethylenetamperproofcontainerwithpolyethylenecapandtamperevidentring.

ThermoformedtransparentPVC/PVdC–aluminiumblisterstrips(PVCfoil250µmthick,PVdCcoating23µm,and

aluminiumfoil20µmthick)

Packsizes-14,20,28,30,50,56,98,100,105tablets

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 22/09/2007 CRN 2039842 page number: 7

6.6Specialprecautionsfordisposalofausedmedicinalproductorwastematerialsderivedfrom

suchmedicinalproductandotherhandlingoftheproduct

Nospecialrequirements.

7MARKETINGAUTHORISATIONHOLDER

PinewoodLaboratoriesLtd.,Tradingas:PinewoodHealthcare

Ballymacarbry

Clonmel

CountyTipperary

8MARKETINGAUTHORISATIONNUMBER

PA0281/095/001

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

DateofFirstAuthorisation:08February2001

DateofLastRenewal:08February2006

10DATEOFREVISIONOFTHETEXT

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 22/09/2007 CRN 2039842 page number: 8