BELLIMCOR

Main information

  • Trade name:
  • BELLIMCOR Tablets 5 Milligram
  • Dosage:
  • 5 Milligram
  • Pharmaceutical form:
  • Tablets
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug

Documents

Localization

  • Available in:
  • BELLIMCOR Tablets 5 Milligram
    Ireland
  • Language:
  • English

Status

  • Source:
  • HPRA - Health Products Regulatory Authority - Ireland
  • Authorization number:
  • PA0408/054/001
  • Authorization date:
  • 29-06-2001
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

Bellimcor5mgTablets

2QUALITATIVEANDQUANTITATIVECOMPOSITION

Eachtabletcontains5mgofbisoprololfumarate.

Excipients:alsoincludeslactosemonohydrate65.6mgpertablet.

Forafulllistofexcipients,seesection6.1.

3PHARMACEUTICALFORM

Tablet.

Thetabletsarepaleyellowmottledincolour,roundandconvexwiththefollowingidentificationmarkings:

"BI"centrallyaboveabreak-linewith"5"below.Thescorelineisonlytofacilitatebreakingforeaseofswallowing

andnottodivideintoequaldoses.

4CLINICALPARTICULARS

4.1TherapeuticIndications

Hypertension

Chronicstableanginapectoris

4.2Posologyandmethodofadministration

Bellimcor5mgtabletsarefororaladministration.

Thedosageshouldbeindividuallyadjusted.Itisrecommendedtostartwiththelowestpossibledose.Insomepatients,

5mgperdaymaybeadequate.Theusualdoseis10mgoncedailywithamaximumrecommendeddoseof20mgper

day.

Patientswithkidneyimpairment

Inpatientswithsevererenalimpairment,(creatinineclearance<20ml/min)thedoseshouldnotexceed10mgonce

daily.Thisdosagemayeventuallybedividedintohalves.

Patientswithsevereliverimpairment

Nodosageadjustmentisrequired,howevercarefulmonitoringisadvised.

Elderly:

Nodosageadjustmentisnormallyrequired.Itisrecommendedtostartwiththelowestpossibledose.

Childrenunder12yearsandadolescents:

Thereisnopaediatricexperiencewiththismedicine,thereforeitsusecannotberecommended.

Discontinuationoftreatment

Treatmentshouldnotbestoppedabruptly(seesection4.4Specialwarningsandprecautionsforuse).Thedosage

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4.3Contraindications

Acuteheartfailureorduringepisodesofheartfailuredecompensationrequiringi.v.inotropictherapy

Cardiogenicshock

AVblockofsecondorthirddegree(withoutapacemaker)

Sicksinussyndrome

Sinoatrialblock

Symptomaticbradycardiawithlessthan60beats/minbeforestartoftherapy

Symptomatichypotension(systolicbloodpressurelessthan100mmHg)

Severebronchialasthmaorseverechronicobstructivepulmonarydisease

SevereformsofperipheralarterialocclusivediseaseorsevereformsofRaynaud'ssyndrome

Metabolicacidosis

Hypersensitivitytobisoprololfumarateortoanyoftheexcipientslisted

Untreatedphaeochromocytoma(see4.4)

Combinationswithfloctafenineandsultopride(seealsosection4.5)

4.4Specialwarningsandprecautionsforuse

Otherformulationsofbisoprololfumaratecontainingmedicinalproductsareusedinthetreatmentofchronicheart

failure.Theuseof-blockingagentsinthisindicationneedsaverycautiousapproachandshouldbestartedwithavery

stricttitrationphase.Inthisphaseincrementsarenecessaryallofwhicharenotpossiblewiththecurrentmedicinal

product.Thisproductshouldthereforenotbeusedinthetreatmentofchronicheartfailure.

Thecessationoftherapywithbisoprololfumarateshouldnotbedoneabruptlyunlessclearlyindicated.Thereisarisk

ofmyocardialinfarctionandsuddendeathifthetreatmentissuddenlydiscontinuedinpatientswithischaemicheart

disease.Formoreinformationpleaserefertosection4.2.

Bisoprololfumaratemustbeusedwithcautioninpatientswithhypertensionoranginapectorisandaccompanyingheart

failure.

Bisoprololfumaratemustbeusedwithcautionin:

Diabetesmellitusshowinglargefluctuationsinbloodglucosevalues;symptomsofhypoglycaemia(e.g.

tachycardia,palpitationsorsweating)maybemasked.Bloodglucoselevelsshouldbemonitoredduringtreatmentwith

bisoprololfumarate

Strictfasting

Ongoingdesensitisationtherapy.Aswithotherß-blockingagentsbisoprololfumaratemayincreaseboththe

sensitivitytowardsallergensandtheseverityofanaphylacticreactions.Epinephrinetreatmentdoesnotalwaysgivethe

expectedtherapeuticeffect.

AVblockoffirstdegree

Printzmetal’sangina:ß-blockingagentsmayincreasethenumberanddurationofanginalattacksinpatientswith

Printzmetal’sangina.Theuseofß-1selectiveadrenoceptorblockingagentsispossibleincasesofmildformsandonly

incombinationwithavasodilatingagent.

Peripheralcirculatorydisorders,suchasRaynaud’sphenomenaandintermittentclaudication:intensificationof

complaintsmighthappenespeciallyduringstartoftherapy.

Inpatientswithphaeochromocytoma(seesection4.3),bisoprololfumaratemustnotbeadministereduntilafter-

receptorblockade.

Patientswithpsoriasisorwithahistoryofpsoriasisshouldonlybegivenbeta-blockers(e.g.bisoprololfumarate)after

acarefulbalancingofbenefitsagainstrisks.

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Inpatientsundergoinggeneralanaesthesiabeta-blockadereducestheincidenceofarrhythmiasandmyocardial

ischemiaduringinductionandintubation,andthepost-operativeperiod.Itiscurrentlyrecommendedthatmaintenance

ofbeta-blockadebecontinuedperi-operatively.Theanaesthetistmustbeawareofbeta-blockadebecauseofthe

potentialforinteractionswithotherdrugs,resultinginbradyarrhythmias,attenuationofreflextachycardia,and

decreasedreflexabilitytocompensateforbloodloss.Ifitisthoughtnecessarytowithdrawbeta-blockertherapybefore

surgery,thisshouldbedonegraduallyandcompletedabout48hoursbeforeanaesthesia.

Theinitiationoftreatmentwithbisoprololfumaratenecessitatesregularmonitoring,especiallywhentreatingelderly

patients.

Bronchospasm(bronchialasthma,obstructiveairwaysdisease):Inbronchialasthmaorotherchronicobstructiveairway

diseases,whichmaycausesymptoms,bronchodilatingtherapyshouldbegivenconcomitantly.Occasionallyan

increaseoftheairwayresistancemayoccurinpatientswithasthma,thereforethedoseofß

-stimulantsmayhavetobe

increased.Itisrecommendedtohaveafunctionalrespiratorytestdonebeforetheinitiatingoftreatment.

Thecombinationwithamiodaroneisnotrecommendedconsideringtheriskofcontractilityautomatismandconduction

disorders(suppressionofcompensatorysympatheticreactions).

Thismedicinalproductcontains65.6mglactosemonohydrate.

Patientswithrarehereditaryconditionssuchasgalactoseintolerance,Lapplactasedeficiencyorglucose-galactose

malabsorptionshouldnotusethismedicinalproduct.

4.5Interactionwithothermedicinalproductsandotherformsofinteraction

Combinationscontra-indicated

Floctafenine:betablockersmayimpedethecompensatorycardiovascularreactionsassociatedwithhypotensionor

shockthatmaybeinducedbyfloctafenine.

Sultopride:bisoprololfumarateshouldnotbeconcomitantlyadministeredwithsultopridesincethereisanincreaserisk

ofventriculararrhythmia.

Combinationsnotrecommended

Calciumantagonistsoftheverapamiltypeandtoalesserextendofthediltiazemtype(bepridil):negativeinfluence

oncontractilityandatrio-ventricularconductionandbloodpressure.Intravenousadministrationofverapamilinpatients

onbeta-blockertreatmentmayleadtoprofoundhypotensionandatrio-ventricularblock

Centrally-actingantihypertensivedrugs(e.g.Clonidine,methyldopa,moxonodine,rilmenidine):Concomitantuse

ofcentrally-actingantihypertensivedrugsmayfurtherdecreasethecentralsympathetictonusandmaythusleadto

reductionofheartrateandcardiacoutputandtovasodilatation.Abruptwithdrawal,particularlyifpriortobeta-blocker

discontinuation,mayincreasetheriskof'reboundhypertension'.

Combinationstobeusedwithcaution:

ClassIantiarrhythmicdrugs(e.g.quinidine,disopyramide,lidocaine,phenytoin,flecainide,propafenone):effect

onatrio-ventricularconductiontimemaybepotentiatedandnegativeinotropiceffectincreased.

ClassIIIantiarrhythmicdrugs(e.g.amiodarone):effectonatrialconductiontimemaybepotentiated.

Calciumantagonistsofthedihydropyridinederivatives(e.g.felodipineandamlodipine):Concomitantusemay

increasetheriskofhypotensionandanincreaseintheriskofafurtherdeteriorationoftheventricularpumpfunctionin

patientswithheartfailurecannotbeexcluded.

Parasympathomimeticdrugs(includingtacrine):atrio-ventricularconductiontimeandtheriskofbradycardiamay

beincreased.

Topicalbeta-blockers(e.g.eyedropsforglaucomatreatment)mayaddtothesystemiceffectsofbisoprolol

fumarate.

Insulinandoralanti-diabeticdrugs:intensificationofbloodsugarloweringeffect.Blockadeofß-adrenoreceptor

maymasksymptomsofhypoglycaemia.

Anaestheticagents:attentuationofthereflextachycardiaandincreaseoftheriskofhypotension.Continuationof

ß-blockadereducestheriskofarrhythmiaduringinductionandintubation.Theanaesthesiologistshouldbeinformed

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Digitalisglycosides:reductionofheartrate,increaseofatrio-ventricularconductiontime.

Non-steroidalanti-inflammatorydrugs(NSAIDs):decreasedhypotensiveeffectofbisoprololfumarate.

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

Combinationwithbisoprololfumaratemayunmaskthealpha-adrenoceptor-mediatedvasoconstrictoreffectsofthese

agentsleadingtobloodpressureincreaseandexacerbatedintermittentclaudication.Suchinteractionsareconsideredto

bemorelikelywithnonselectivebeta-blockers

Concomitantusewithantihypertensiveagentsaswellaswithotherdrugswithbloodpressureloweringpotential

(e.g.Tricyclicantidepressants,barbiturates,phenothiazinesaswellasotherantihypertensiveagents:increasedblood

pressureloweringeffect.

Baclofene:increasedantihypertensiveactivity.

Iodatedcontrastproducts:Beta-blockersmayimpedethecompensatorycardiovascularreactionsassociatedwith

hypotensionorshockinducedbyiodatedcontrastproducts.

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

effectofbothagents.

Combinationstobeconsidered

Mefloquine:increasedriskofbradycardia.

Monoamineoxidaseinhibitors(exceptMAO-Binhibitors):Enhancedhypotensiveeffectofthebetablockersbut

alsoriskofhypertensivecrisis.

Corticosteroids:decreaseofantihypertensiveeffectduetowaterandsodiumretention.

Ergotaminederivatives:exacerbationofperipheralcirculatorydisturbances.

Rifampicin:slightreductionofthehalflifeofbisoprololfumaratepossibleduetotheinductionofhepaticdrug-

metabolisingenzymes.Normallynodosageadjustmentisnecessary.

4.6Fertility,pregnancyandlactation

Pregnancy:

Bisoprololfumaratehaspharmacologicaleffectsthatmaycauseharmfuleffectsonpregnancyand/orthe

fetus/newborn.Ingeneral,-adrenoceptorblockingagentsreduceplacentalperfusion,whichhasbeenassociatedwith

growthretardation,intrauterinedeath,abortionorearlylabour.Adversereactions(e.g.hypoglycaemia,bradycardia)

mayoccurinthefetusandnewborninfant.Iftreatmentwith -adrenoceptorblockingagentsisnecessary, -

adrenoceptorblockingagentsarepreferable.

Bisoprololfumarateshouldnotbeusedduringpregnancyunlessclearlynecessary.Iftreatmentwithbisoprolol

fumarateisconsiderednecessary,theuteroplacentalbloodflowandfetalgrowthshouldbemonitored.Incaseof

harmfuleffectsonpregnancyorthefetusalternativetreatmentshouldbeconsidered.Thenewborninfantmustbe

closelymonitored.Symptomsofhypoglycaemiaandbradycardiaaregenerallytobeexpectedwithinthefirst3days.

Lactation:

Therearenodataontheexcretionofbisoprololfumarateinhumanbreastmilkorthesafetyofbisoprololfumarate

exposureininfants.Thereforebreastfeedingisnotrecommendedduringadministrationofbisoprololfumarate.

4.7Effectsonabilitytodriveandusemachines

Inastudywithcoronaryheartdiseasepatient’sbisoprololfumaratedidnotimpairdrivingperformance.However,due

toindividualvariationsinreactionstothemedicinalproduct,theabilitytodriveavehicleortooperatemachinerymay

beimpaired.Thisshouldbeconsideredparticularlyatstartofthetreatmentanduponchangeofmedicationaswellas

inconjunctionwithalcohol.

4.8Undesirableeffects

Theadversereactionsconsideredatleastpossiblyrelatedtotreatmentarelistedbelowbybodysystemorganclassand

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Frequenciesaredefinedas:Verycommon(10%),common(1%and<10%),uncommon(0.1%and<1%),rare

(0.01%and<0.1%),veryrare(<0.01%))

Psychiatricdisorders

Uncommon:depression,sleepdisorders

Rare:nightmares,hallucinations

Nervoussystemdisorders

Common:dizziness*,headache*

Rare:syncope

Eyedisorders

Rare:reducedtearflow(tobeconsideredifthepatientusescontactlenses)

Veryrare:conjunctivitis

Earandlabyrinthdisorders

Rare:hearingdisorders

Cardiacdisorders

Uncommon:AV-conductiondisturbances;worseningofpre-existingheartfailure;bradycardia

Vasculardisorders

Common:feelingofcoldnessornumbnessintheextremities,hypotensionespeciallyinpatientswithheartfailure

Respiratory,thoracicandmediastinaldisorders

Uncommon:bronchospasminpatientswithbronchialasthmaorahistoryofobstructiveairwaysdisease

Rare:allergicrhinitis

Gastrointestinaldisorders

Common:gastrointestinalcomplaintssuchasnausea,vomiting,diarrhoea,constipation

Hepatobilarydisorders

Rare:hepatitis

Skinandsubcutaneoustissuedisorders

Rare:hypersensitivityreactionssuchasitching,flush,rash

Veryrare:alopecia.Beta-blockersmayprovokeorworsenpsoriasisorinducepsoriasis-likerash.

Musculoskeletalandconnectivetissuedisorders

Uncommon:muscleweakness,musclecramps

Reproductivesystemandbreastdisorders

Rare:potencydisorders

Generaldisordersandadministrativesiteconditions

Common:fatigue*

Uncommon:asthenia

Investigations

Rare:increasedtriglycerides,increasedliverenzymes(ALAT,ASAT)

Appliesonlytohypertensionoranginapectoris:

*Thesesymptomsespeciallyoccuratthebeginningofthetherapy.Theyaregenerallymildandusuallydisappear

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4.9Overdose

Themostcommonsignsexpectedwithoverdosageofbisoprololfumaratearebradycardia,hypotension,bronchospasm,

acutecardiacinsufficiencyandhypoglycaemia.

Thereislimitedexperiencewithoverdoseofbisoprololfumarate,onlyafewcasesofoverdosewithbisoprolol

fumaratehavebeenreported.Bradycardiaand/orhypotensionwerenoted.Allpatientsrecovered.Thereisawideinter-

individualvariationinsensitivitytoonesinglehighdoseofbisoprololfumarateandpatientswithheartfailureare

probablyverysensitive.

Ingeneral,ifoverdoseoccurs,discontinuationofbisoprololfumaratetreatmentandsupportiveandsymptomatic

treatmentisrecommended.

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/oraminophylline.

Hypoglycaemia:Administeri.v.glucose.

Limiteddatasuggestthatbisoprololfumarateishardlydialysable.

5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

Pharmacotherapeuticgroup:selective -blockingagents,ATCcode:C07AB07

Bisoprololfumarateisapotent,highly -selective-adrenoceptorblockingagentdevoidofintrinsicsympathomimetic

activity.Aswithother -blockingagents,themodeofactioninhypertensionisunclear.However,itisknownthat

bisoprololfumaratemarkedlydepressesplasmareninactivity.

Inpatientswithangina,theblockadeof-receptorsreducesheartactionandthusreducesoxygendemand.

Bisoprololfumaratepossessessimilarlocalanaestheticpropertiestopropranolol.

5.2Pharmacokineticproperties

Bisoprololfumarateisabsorbedalmostcompletelyfromthegastrointestinaltract.Togetherwiththeverysmallfirst

passeffectintheliver,thisresultsinahighbioavailabilityofapproximately90%.Theplasmaproteinbindingof

bisoprololisabout30%.Thedistributionvolumeis3.5l/kg.Thetotalclearanceisapproximately15l/h.

Theplasmaeliminationhalf-life(10-12hours)provides24hoursefficacyfollowingaoncedailydosage.

Bisoprololfumarateisexcretedfromthebodybytworoutes,50%ismetabolisedbythelivertoinactivemetabolites

whicharethenexcretedbythekidneys.Theremaining50%isexcretedbythekidneysinanunmetabolisedform.Since

eliminationtakesplaceinthekidneysandthelivertothesameextentadosageadjustmentisnotrequiredforpatients

withimpairedliverfunctionorrenalinsufficiency.

Thekineticsofbisoprololfumaratearelinearandindependentofage.

Inpatientswithchronicheartfailure(NYHAstageIII)theplasmalevelsofbisoprololfumaratearehigherandthehalf

lifeisprolongedcomparedtohealthyvolunteers.Maximumplasmaconcentrationatsteadystateis64+/-21ng/mlata

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5.3Preclinicalsafetydata

Preclinicaldatarevealnospecialhazardforhumansbasedonconventionalstudiesofsafetypharmacology,repeated

dosetoxicity,genotoxicityorcarcinogenicity.Likeother -blockingagents,bisoprololfumaratecausedmaternal

toxicity(decreasedfoodintakeanddecreasedbodyweight)andembryo/fetaltoxicity(increasedincidenceof

resorptions,reducedbirthweightoftheoffspring,retardedphysicaldevelopment)athighdosesbutwasnot

teratogenic.

6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

Lactosemonohydrate

Cellulose,microcrystalline(E460)

Magnesiumstearate(E572)

Crospovidone

PigmentBlend:YellowPB22812(lactosemonohydrateandironoxideyellow(E172))

6.2Incompatibilities

Notapplicable.

6.3Shelflife

2years.

6.4Specialprecautionsforstorage

Thismedicinalproductdoesnotrequireanyspecialstorageconditions.

6.5Natureandcontentsofcontainer

Bellimcor5mgtabletsarepresentedin:

BlisterscomprisingofPVC/PVdC/aluminiumfoil,containedwithinaprintedcartonbox.Eachcartonwillcontain

either:20,28,30,50,56,60or100tablets.

Notallpacksizesmaybemarketed.

6.6Specialprecautionsfordisposalofausedmedicinalproductorwastematerialsderivedfrom

suchmedicinalproductandotherhandlingoftheproduct

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7MARKETINGAUTHORISATIONHOLDER

RanbaxyIrelandLtd.

Spafield

CorkRoad

Cashel

Co.Tipperary

Ireland

8MARKETINGAUTHORISATIONNUMBER

PA408/54/1

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

Dateoffirstauthorisation:29 th

June2001

Dateoflastrenewal:13 th

September2010

10DATEOFREVISIONOFTHETEXT

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