EMVASC

Main information

  • Trade name:
  • EMVASC Film Coated Tablet 10 Milligram
  • Dosage:
  • 10 Milligram
  • Pharmaceutical form:
  • Film Coated Tablet
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug

Documents

Localization

  • Available in:
  • EMVASC Film Coated Tablet 10 Milligram
    Ireland
  • Language:
  • English

Status

  • Source:
  • HPRA - Health Products Regulatory Authority - Ireland
  • Authorization number:
  • PA0282/081/002
  • Authorization date:
  • 24-01-2003
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

PartII

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

Emvasc10mgTablets.

2QUALITATIVEANDQUANTITATIVECOMPOSITION

Eachtabletcontainsbisoprololfumarate10mg.

Forexcipients,seesection6.1.

3PHARMACEUTICALFORM

Film-coatedTablets.

White,roundbiconvexfilmcoatedtablets,embossedwithBPL10ononeface.

4CLINICALPARTICULARS

4.1TherapeuticIndications

Hypertension

Chronicstableanginapectoris

4.2Posologyandmethodofadministration

Bisoprolol10mgTabletsarefororaladministration.

Thedosageshouldbeindividuallyadjusted.Itisrecommendedtostartwiththelowestpossibledose.Insomepatients,

5mgperdaymaybeadequate.Theusualdoseis10mgoncedailywithamaximumrecommendeddoseof20mgper

day.

Patientswithkidneyimpairment

Inpatientswithsevererenalimpairment(creatinineclearance<20ml/min),thedoseshouldnotexceed10mg

bisoprololoncedaily.Thisdosagemayeventuallybehalvedto5mgperday.

Patientswithsevereliverimpairment

Nodosageadjustmentisrequired,howevercarefulmonitoringisadvised.

Elderly:

Nodosageadjustmentisnormallyrequired.Itisrecommendedtostartwiththelowestpossibledose.

Childrenunder12yearsandadolescents:

Thereisnopaediatricexperiencewiththismedicine,thereforeitsusecannotberecommended.

Discontinuationoftreatment

Treatmentshouldnotbestoppedabruptly(seesection4.4,Specialwarningsandprecautionsforuse).Thedosage

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4.3Contraindications

acuteheartfailureorduringepisodesofheartfailuredecompensationrequiringi.v.inotropictherapy

cardiogenicshock

AVblockofsecondorthirddegree(withoutapacemaker)

sicksinussyndrome

sinoatrialblock

bradycardia(lessthan45-50beatsperminuteduringtherapy,orlessthan60beatsperminutebeforestartof

therapy

hypotension(systolicbloodpressurelessthan100mmHg)

severebronchialasthmaorseverechronicobstructivepulmonarydisease

latestagesofperipheralarterialocclusivediseaseandRaynaud'ssyndrome

metabolicacidosis

hypersensitivitytobisoprololortooneoftheexcipientslisted.

untreatedphaeochromocytoma(seesection4.4,Specialwarningsandprecautionsforuse).

combinationswithfloctafenineandsultopride(Seesection4.5,Interactionwithothermedicinalproductsand

otherformsofinteractions).

withanaestheticswhichdepressmyocardialactivity(e.g.cyclopropaneandtrichlorethylene)(Seesection4.5,

Interactionwithothermedicinalproductsandotherformsofinteractions).

4.4Specialwarningsandprecautionsforuse

Otherformulationsofbisoprololcontainingmedicinalproductsareusedinthetreatmentofchronicheartfailure.The

useof -blockingagentsinthisindicationneedsaverycautiousapproachandshouldbestartedwithaverystrict

titrationphase.Inthisphaseincrementsarenecessaryallofwhicharenotpossiblewiththecurrentmedicinalproduct.

Thisproductshouldthereforenotbeusedinthetreatmentofchronicheartfailure.

Combinationofbisoprololwithcalciumantagonistsoftheverapamilanddiltiazemtype,withcentrally-acting

antihypertensivedrugsandwithClassIantiarrhythmicdrugsisgenerallynotrecommended,(Seesection4.5,

Interactionwithothermedicinalproductsandotherformsofinteractions).

Bisoprololmustbeusedwithcautionin:

concomitanttreatmentwithamiodarone:riskofcontractilityautomatismandconductiondisorders(suppression

ofcompensatorysympatheticreactions),(Seesection4.5,Interactionwithothermedicinalproductsandother

formsofinteractions).

bronchospasm(bronchialasthma,obstructiveairwaysdisease):Inbronchialasthmaorotherchronicobstructive

airwaydiseases,whichmaycausesymptoms,bronchodilatingtherapyshouldbegivenconcomitantly.

Occasionallyanincreaseoftheairwayresistancemayoccurinpatientswithasthma,thereforethedoseof 2-

stimulantsmayhavetobeincreased.Itisrecommendedtohaveafunctionalrespiratorytestdonebeforethe

initiationoftreatment.

concomitanttreatmentwithanticholinesterasedrugs(includingtacrine):atrio-ventricularconductiontimeand/or

bradycardiamaybeincreased(Seesection4.5,Interactionwithothermedicinalproductsandotherformsof

interactions).

concomitanttreatmentwithanaesthetics:Attenuationofthereflextachycardiaandincreaseoftheriskof

hypotension(Seesection4.3,Contraindication,andseesection4.5,Interactionwithothermedicinalproducts

andotherformsofinteractions)Continuationof-blockadereducestheriskofarrhythmiaduringinductionand

intubation.Theanaesthesiologistshouldbeinformedwhenthepatientisreceivingbisoprolol.

Iodinatedcontrastproducts:Beta-blockersmayimpedethecompensatorycardiovascularreactionsassociated

withhypotensionorshockinducedbyiodatedcontrastproducts.

diabetesmellituswithlargefluctuationsinbloodglucosevalues;symptomsofhypoglycaemiamaybemasked.

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thyrotoxicosis,symptomsandclinicalsignsofthyrotoxicosismaybemasked

strictfasting

ongoingdesensitisationtherapy

Aswithother-blockingagentsbisoprololmayincreaseboththesensitivitytowardsallergensandtheseverityof

anaphylacticreactions.Adrenalinetreatmentdoesnotalwaysgivetheexpectedtherapeuticeffect.Higherdoses

ofepinephrine(adrenaline)maybenecessary.

AVblockoffirstdegree

Printzmetal'sangina:-blockingagentsmayincreasethenumberanddurationofanginalattacksinpatientswith

Printzmetal'sangina.

peripheralcirculatorydisorders,suchasRaynaud'sphenomenaandintermittentclaudication:intensificationof

complaintsmighthappenespeciallyduringstartoftherapy.

Inpatientswithphaeochromocytoma(Seesection4.3,Contraindications)bisoprololmustnotbeadministered

untilafter-receptorblockadehasbeensuccessfullyestablished

pre-existingorexistingpsoriasis,bisoprololshouldonlybegivenafterathoroughrisk/benefitassessment

Theinitiationoftreatmentwithbisoprololnecessitatesregularmonitoring,especiallywhentreatingelderlypatients.

Thecessationoftherapywithbisoprololshouldnotbedoneabruptlyunlessclearlyindicated.Thereisariskof

myocardialinfarctionandsuddendeathifthetreatmentissuddenlydiscontinuedinpatientswithischaemicheart

disease.Formoreinformationpleaserefertosection4.2,Posologyandmethodofadministration.

Thismedicinalproductcontainsanactivesubstance,whichresultsinapositivetestduringantidopingcontrols.

4.5Interactionwithothermedicinalproductsandotherformsofinteraction

Combinationscontra-indicated

Floctafenine:betablockersmayimpedethecompensatorycardiovascularreactionsassociatedwithhypotensionor

shockthatmaybeinducedbyfloctafenine.

Sultopride:bisoprololshouldnotbeconcomitantlyadministeredwithsultopridesincethereisanincreasedriskof

ventriculararrhythmias.

Anaestheticswhichdepressmyocardialactivity.

Combinationsnotrecommended

Calciumantagonists(verapamil,diltiazem,bepridil):negativeinfluenceoncontractility,atrio-ventricular

conductionandbloodpressure(seesection4.4,Specialwarningsandprecautionsforuse).

ClassIantiarrhythmicdrugs(e.g.disopyramide,quinidine):effectonatrioventricularconductiontimemaybe

potentiatedandnegativeinotropiceffectmaybeincreased.StrictclinicalandECGmonitoringisrequired(seesection

4.4,Specialwarningsandprecautionsforuse).

Clonidineandothercentrally-actingantihypertensivedrugs,i.e.methyldopa,guanfacin,moxonidine,rilmenidine:

Increasedriskof"reboundhypertension"aswellasexaggerateddecreaseinheartrateandcardiacconduction,

includingworseningthecardiacinsufficiency.

Monoamineoxidaseinhibitors(exceptMAO-Binhibitors):Enhancedhypotensiveeffectofthebeta-blockersbut

alsoriskforhypertensivecrisis.

Combinationstobeusedwithcaution

ClassIIIantiarrhythmicdrugs(e.g.amiodarone):effectonatrialconductiontimemaybepotentiated(seesection

4.4,Specialwarningsandprecautionsforuse).

Calciumantagonists(,dihydropyridinederivatives):increasedriskofhypotension.Insomepatientswithlatent

heartfailureconcomitantuseof-blockingagentscanleadtoheartfailure.

Anticholinesterasedrugs(includingtacrine):atrio-ventricularconductiontimeand/orbradycardiamaybeincreased

(seesection4.4,Specialwarningsandprecautionsforuse).

Other-blockingagents,includingineye-drops,haveadditionaleffects.

Insulinandoralanti-diabeticdrugs:intensificationofbloodsugarloweringeffect.Blockadeof -adrenoreceptor

maymasksymptomsofhypoglycaemia.

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Anaestheticagents:attenuationofthereflextachycardiaandincreasedriskofhypotension(forfurtherinformationon

anaesthesiaseesection4.4,Specialwarningsandprecautionsforuse).

NSAIDs:decreaseoftheantihypertensiveeffect(inhibitionofvasodilatativeprostaglandinbyNSAIandwaterand

sodiumretentionwithpyrazoloneNSAI).

Ergotaminederivatives:exacerbationofperipheralcirculatorydisturbances.

Beta-sympathomimeticagents(e.g.isoprenaline,dobutamine):combinationwithbisoprololmayreduceeffectsof

bothagents.

Sympathomimeticsthatactivateboth -and -adrenoceptors(e.g.noradrenaline,adrenaline):Combinationwith

bisoprololmayunmaskthe -adrenoceptor-mediatedvasoconstrictoreffectsoftheseagentsleadingtobloodpressure

increaseandexacerbatedintermittentclaudication.Suchinteractionsareconsideredtobemorelikelywithnon

selective-blockers.

Tricyclicantidepressants,barbiturates,phenothiazinesaswellasotherantihypertensiveagent:increasedblood

pressureloweringeffect.

Baclofen:increasedantihypertensiveactivity.

Amifostine:increasedhypotensiveactivity.

Combinationstobeconsidered

Mefloquine:increasedriskofbradycardia.

Corticosteroids:decreaseofantihypertensiveeffectduetowaterandsodiumretention.

4.6Pregnancyandlactation

Pregnancy:

Bisoprololhaspharmacologicaleffectsthatmaycauseharmfuleffectsonpregnancyand/orthefetus/newborn.In

general,-adrenoceptorblockingagentsreduceplacentalperfusion.whichhasbeenassociatedwithgrowthretardation,

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

andnewborninfant.Iftreatmentwith -adrenoceptorblockingagentsisnecessary,

-adrenoceptorblockingagents

arepreferred.

Bisoprololshouldnotbeusedduringpregnancyunlessclearlynecessary.Iftreatmentwithbisoprololisconsidered

necessary,theuteroplacentalbloodflowandfetalgrowthshouldbemonitored.Incaseofharmfuleffectsonpregnancy

orthefetusalternativetreatmentshouldbeconsidered.Thenewborninfantmustbecloselymonitored.Symptomsof

hypoglycaemiaandbradycardiaaregenerallytobeexpectedwithinthefirst3days.

Lactation:

Itisnotknownwhetherbisoprololisexcretedinhumanmilk.Thereforebreastfeedingisnotrecommendedduring

administrationofbisoprolol.

4.7Effectsonabilitytodriveandusemachines

Inastudywithcoronaryheartdiseasepatient’sbisoprololdidnotimpairdrivingperformance.However,dueto

individualvariationsinreactionstothemedicinalproduct,theabilitytodriveavehicleortooperatemachinerymaybe

impairedasbisoprololcancausedizzinessandfatigue.Thisshouldbeconsideredparticularlyatstartofthetreatment

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4.8Undesirableeffects

Thereportedsideeffectsaregenerallyattributabletothepharmacologicalpropertiesof-blockingagents.

Thefollowingundesirableeffectshavebeenobservedduringtreatmentwithbisoprololwiththefollowingfrequencies:

Verycommon( ≥10%),

common( ≥1%and<10%),

uncommon( ≥0.1%and<1%),

rare( ≥0.01%and<0.1%),

veryrare(<0.01%)includingisolatedreports

Immunesystemdisorders

Rare: Allergicrhinitis,theappearanceofantinuclearantibodieswithexceptionalclinicalsymptoms

suchaslupussyndrome,whichdisappearuponcessationoftreatment

Metabolismandnutritiondisorders

Rare: Increasedtriglycerides,hypoglycaemia

Psychiatricdisorders

Uncommon: Sleepdisturbances,depression

Rare: Nightmare,hallucinations

Nervoussystemdisorders

Common: Tiredness,exhaustion,dizziness,headache(especiallyatthebeginningofthetherapy,theyare

generallymildandoftendisappearwithin1-2weeks)

Eyedisorders

Rare: Reducedtearflow(tobeconsideredifthepatientuseslenses)

Veryrare: Conjunctivitis

Earandlabyrinthdisorders

Rare: Hearingimpairment

Cardiacdisorders

Uncommon: Bradycardia,AV-stimulusdisturbances(slowedAV-conductionorincreaseofexistingAV-

block),worseningofheartfailure

Vasculardisorders

Common: Feelingofcoldnessornumbnessoftheextremities,Raynaud’sdisease,increaseofexisting

intermittentclaudication

Uncommon: orthostatichypotension

Respiratory,thoracicandmediastinaldisorders

Uncommon: Bronchospasminpatientswithbronchialasthmaorahistoryofobstructiveairwaydisease

Gastrointestinaldisorders

Common: Nausea,vomiting,diarrhoea,abdominalpain,andconstipation

Hepato-biliarydisorders

Rare: Increasedliverenzymes(ALAT,ASAT),hepatitis

Skinandsubcutaneoustissuedisorders

Rare: Hypersensitivityreactions(itching,flush,rash)

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Musculoskeletalandconnectivetissuedisorders

Uncommon: Muscularweaknessandcramps,arthropathy

Reproductivesystemandbreastdisorders

Rare: Potencydisorders

4.9Overdose

Themostcommonsignsexpectedwithoverdosageofbisoprololarebradycardia,hypotension,bronchospasm,acute

cardiacinsufficiencyandhypoglycaemia.

Inthecaseofoverdosage,bisoprololtreatmentshouldbestoppedandsupportiveandsymptomatictreatmentshouldbe

provided.Resorptionofbisoprololinthegastrointestinaltractmustbeavoided;gastriclavage,oradministrationof

adsorbents(i.e.activatedcharcoal),andalaxativeagent(i.e.sodiumsulphate)maybeused.Respirationmustbe

monitoredandifnecessary,artificialrespirationshouldbeinitiated.Bronchospasmshouldbecounteractedwith

bronchodilatortherapysuchasisoprenalineor

-sympathicomimeticdrugs.Cardiovascularcomplicationsshouldbe

treatedsymptomatically:AV-block(secondorthirddegree)needscarefulmonitoringandshouldbetreatedwith

isoprenalineinfusionortransvenouscardiacpacemakerinsertion.Bradycardiashouldbetreatedwithintravenous

atropine(orM-methyl-atropine).Fallinbloodpressureorshockshouldbetreatedwithplasmasubstitutingagentsand

vasopressors.Hypoglycaemiacanbetreatedwithi.v.-glucose.

5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

Pharmacotherapeuticgroup:selective

-blockingagents,ATCcode:C07AB07

Bisoprololisapotent,highly

-selective-adrenoceptorblockingagentdevoidofintrinsicsympathomimeticactivity.

Aswithother

-blockingagents,themodeofactioninhypertensionisunclear.However,itisknownthatbisoprolol

markedlydepressesplasmareninactivity.

Inpatientswithangina,theblockadeof-receptorsreducesheartactionandthusreducesoxygendemand.

Bisoprololpossessessimilarlocalanaestheticpropertiestopropranolol.

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

withimpairedliverfunctionorrenalinsufficiency.

Thekineticsofbisoprololarelinearandindependentofage.

Inpatientswithchronicheartfailure(NYHAstageIII)theplasmalevelsofbisoprololarehigherandthehalf-lifeis

prolongedcomparedtohealthyvolunteers.Maximumplasmaconcentrationatsteadystateis64 ±

21ng/mlatadaily

doseof10mgandthehalflifeis17 ±

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5.3Preclinicalsafetydata

Preclinicaldatarevealnospecialhazardforhumansbasedonconventionalstudiesofsafetypharmacology,repeated

dosetoxicity,genotoxicityorcarcinogenicity.Likeother -blockingagents,bisoprololcausedmaternal(decreased

foodintakeanddecreasedbodyweight)andembryo/fetaltoxicity(increasedincidenceofresorptions,reducedbirth

weightoftheoffspring,retardedphysicaldevelopment)athighdoseswasnotteratogenic.

6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

CalciumHydrogenPhosphateDihydrate

MicrocrystallineCellulose

PregelatinisedStarch

CroscarmelloseSodium

Silica,Colloidalanhydrous

MagnesiumStearate

FilmCoat

Hypromellose(HPMC,E464)

Titaniumdioxide(E171)

Macrogol400

6.2Incompatibilities

Notapplicable.

6.3ShelfLife

2years.

6.4Specialprecautionsforstorage

Donotstoreabove25°C.

Storeintheoriginalpackagetoprotectfrommoisture.

6.5Natureandcontentsofcontainer

ThetabletsareplacedinthermoformedPVCfoillaminatedwithaluminium.

Theblisterpackisthenplacedinaprintedboxboardcartonwithpacksizeof7,14,21,28,30,50,56,60,84,90,98,

100,112,120,250and500.

Notallpacksizeswillbemarketed.

6.6Specialprecautionsfordisposalofausedmedicinalproductorwastematerialsderivedfrom

suchmedicinalproductandotherhandlingoftheproduct

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7MARKETINGAUTHORISATIONHOLDER

NortonHealthcareLimited

T/AIVAXPharmaceuticalsUK

AlbertBasin

RoyalDocks

LondonE162QJ

UnitedKingdom

8MARKETINGAUTHORISATIONNUMBER

PA0282/081/002

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

Dateoffirstauthorisation: 24January2003

Dateoflastrenewal: 02February2006

10DATEOFREVISIONOFTHETEXT

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