BETALOC

Main information

  • Trade name:
  • BETALOC Tablets 50 Milligram
  • Dosage:
  • 50 Milligram
  • Pharmaceutical form:
  • Tablets
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug

Documents

Localization

  • Available in:
  • BETALOC Tablets 50 Milligram
    Ireland
  • Language:
  • English

Status

  • Source:
  • HPRA - Health Products Regulatory Authority - Ireland
  • Authorization number:
  • PA0970/032/002
  • Authorization date:
  • 26-05-2000
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

IRISHMEDICINESBOARDACT1995,asamended

MedicinalProducts(ControlofPlacingontheMarket)Regulations,2007,asamended

PA0970/032/002

CaseNo:2065373

TheIrishMedicinesBoardinexerciseofthepowersconferredonitbytheabovementionedRegulationsherebygrantsto

AstraZenecaUKLimited

600CapabilityGreen,Luton,LU13LU,UnitedKingdom

anauthorisation,subjecttotheprovisionsofthesaidRegulations,inrespectoftheproduct

Betaloc50mgTablets

theparticularsofwhicharesetoutintheattachedSchedule.Theauthorisationisalsosubjecttothegeneralconditionsasmaybespecifiedin

thesaidRegulationsaslistedonthereverseofthisdocument.

Thisauthorisation,unlesspreviouslyrevoked,shallcontinueinforcefrom26/05/2010.

SignedonbehalfoftheIrishMedicinesBoardthis

________________

Irish Medicines Board

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Date Printed 21/07/2010 CRN 2065373 page number: 1

PartII

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

Betaloc50mgTablets

2QUALITATIVEANDQUANTITATIVECOMPOSITION

EachtabletcontainsMetoprololtartrate50mg.

Excipients:Eachtabletcontains17.5mglactosemonohydrate

Forafulllistofexcipients,seesection6.1.

3PHARMACEUTICALFORM

Tablet.

Whitetooff-white,circular,biconvextablet,scoredandengraved‘A/BB’ononeside.

4CLINICALPARTICULARS

4.1TherapeuticIndications

Inthemanagementofhypertensionandanginapectoris.

Cardiacarrhythmias,especiallysupraventriculartachyarrhythmias.

Adjuncttothetreatmentofhyperthyroidism.

EarlyinterventionwithBetalocinacutemyocardialinfarctionreducesinfarctsizeandtheincidenceofventricular

fibrillation.Painreliefmayalsodecreasetheneedforopiateanalgesics.

Betalochasbeenshowntoreducemortalitywhenadministeredtopatientswithacutemyocardialinfarction.

Prophylaxisofmigraine.

4.2Posologyandmethodofadministration

Thetabletsshouldbetakenonanemptystomach.

Thedosemustalwaysbeadjustedtotheindividualrequirementsofthepatient.Thefollowingareguidelines:

Hypertension

Therecommendedmaintenancedosageinpatientswithhypertensionis100mg-200mgdaily,givenasasingledosein

themorningorindivideddoses(morningandevening).Beginwith50mgtwicedailyor100mgoncedaily.Dose

incrementsshouldbeatintervalsthereafteraccordingtoindividualpatientresponses.Maximumdose,usually200mg

daily.Dosesupto400mgdailyhavebeenused.Ifneeded,otherantihypertensiveagentsmaybeadded.

Long-termantihypertensivetreatmentwithmetoprololindailydosesof100-200mghasbeenshowntoreducetotal

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AnginaPectoris

Therecommendeddosageis100-200mgdaily,givenindivideddoses(morningandevening).Beginwith50mgtwice

daily.Doseincrementsshouldbeatintervalsthereafteraccordingtoindividualpatientresponses.Maximumdose,

usually200mgdaily(individeddoses).Dosesupto300mgdaily(individeddoses)havebeenused.Ifneeded,other

antianginalagentsmaybeadded.

CardiacArrhythmias

Therecommendeddosageis100-200mgdailygivenindivideddoses(morningandevening).Ifneeded,other

antiarrhythmicagentsmaybeadded.

Hyperthyroidism

Therecommendeddosageis50mgfourtimesaday.

MyocardialInfarction

Earlyintervention

ToachieveoptimalbenefitsfromintravenousBetalocsuitablepatientsshouldpresentwithin12hoursoftheonsetof

chestpain.Therapyshouldcommencewith5mgi.v.every2minutestoamaximumof15mgtotalasdeterminedby

bloodpressureandheartrate.Thesecondorthirddoseshouldnotbegivenifthesystolicbloodpressureis<90mmHg,

theheartrateis<40beats/minandtheP-Qtimeis>0.26seconds,orifthereisanyaggravationofdyspnoeaorcold

sweating.Oraltherapyshouldcommence15minutesafterthelastinjectionwith50mgevery6hoursfor48hours.

Patientswhofailtotoleratethefullintravenousdoseshouldbegivenhalfthesuggestedoraldose.

Maintenance

Theusualmaintenancedoseis200mgdaily,givenindivideddoses.

MigraineProphylaxis

Therecommendeddosageis100-200mgdaily,givenindivideddoses(morningandevening).

ImpairedRenalFunction

Doseadjustmentisgenerallynotneededinpatientswithimpairedrenalfunction.

ImpairedHepaticFunction

Doseadjustmentisnormallynotneededinpatientssufferingfromlivercirrhosisbecausemetoprololhasalowprotein

binding(5-10%).However,areductionindosagemaybenecessary,accordingtotheseverityofhepaticimpairment.

Elderly

Severalstudiesindicatethatage-relatedphysiologicalchangeshavenegligibleeffectsonthepharmacokineticsof

metoprolol.

Children

Thereislimitedexperiencewithmetoprololtreatmentinchildren.

4.3Contraindications

Betaloc,aswithotherbeta-blockers,shouldnotbeusedinpatientswithanyofthefollowing:

AVblockofsecond-orthird-degree,

Unstabledecompensatedcardiacfailure(pulmonaryoedema,hypoperfusionorhypotension),

Continuousorintermittentinotropictherapyactingthroughbeta-receptoragonism,

Bradycardia,(<45bpm),

Sicksinussyndrome,

Cardiogenicshock,

Severeperipheralarterialcirculatorydisorder,

Untreatedphaeochromocytoma,

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KnownhypersensitivitytoanycomponentofBetalocorotherbeta-blockers.

Betalocisalsocontra-indicatedwhensuspectedacutemyocardialinfarctioniscomplicatedbybradycardia(<45bpm),

firstdegreeheartblock(theP-Qintervalis>0.24sec)orsystolicbloodpressure<100mmHg.

4.4Specialwarningsandprecautionsforuse

Betalocaswithotherbeta-blockers:

Shouldnotbewithdrawnabruptly.Whenpossible,Betalocshouldbewithdrawngraduallyoveraperiodof

10-14days,indiminishingdosesto25mgdailyforthelast6days.Duringitswithdrawalpatientsshouldbe

keptunderclosesurveillance,especiallythosewithknownischaemicheartdisease.Theriskforcoronary

events,includingsuddendeath,mayincreaseduringthewithdrawalofbeta-blockade.

Mustbereportedtotheanaesthetistpriortogeneralanaesthesia.Itisnotgenerallyrecommendedtostop

Betaloctreatmentinpatientsundergoingsurgery.Acuteinitiationofhigh-dosemetoprololtopatients

undergoingnon-cardiacsurgeryshouldbeavoided,sinceithasbeenassociatedwithbradycardia,hypotension

andstrokeincludingfataloutcomeinpatientswithcardiovascularriskfactors.

Althoughcontra-indicatedinsevereperipheralarterialcirculatorydisturbances(seeSection4.3,

Contraindications),mayalsoaggravatelesssevereperipheralarterialcirculatorydisorders.

Maybeadministeredwhenheartfailurehasbeencontrolled.Digitalisationand/ordiuretictherapyshouldalso

beconsideredforpatientswithahistoryofheartfailure,orpatientsknowntohaveapoorcardiacreserve.

Maycausepatientstodevelopincreasingbradycardia,insuchcasestheBetalocdosageshouldbereducedor

graduallywithdrawn.

Duetothenegativeeffectonconductiontime,mayaggravatepre-existingconductiontimedisordersof

moderatedegree,whichmayleadtoAVblock,andshouldonlybegivenwithcautiontopatientswithfirst

degreeheartblock.

MayincreasethenumberanddurationofanginaattacksinpatientswithPrinzmetal’sangina,dueto

unopposedalpha-receptormediatedcoronaryarteryvasoconstriction.Betalocisabeta

-selectivebeta-blocker;

consequently,itsusemaybeconsideredalthoughutmostcautionmustbeexercised.

Maymasktheearlysignsofacutehypoglycaemia,inparticulartachycardia.DuringtreatmentwithBetaloc,

theriskofinterferingwithcarbohydratemetabolismormaskinghypoglycaemiaislessthanwithnon-selective

beta-blockers.

Maymaskthesymptomsofthyrotoxicosis.

Mayincreaseboththesensitivitytowardsallergensandtheseriousnessofanaphylacticreactions.

Althoughcardioselectivebeta-blockersmayhavelesseffectonlungfunctionthannon-selectivebeta-blockers,aswith

allbeta-blockers,theseshouldbeavoidedinpatientswithreversibleobstructiveairwaysdiseaseunlessthereare

compellingclinicalreasonsfortheiruse.Whenadministrationisnecessary,thesepatientsshouldbekeptunderclose

surveillance.Theuseofabeta

-bronchodilator(e.g.terbutaline)maybeadvisableinsomepatients.Thedosageofthe

beta

-agonistmayrequireanincreasewhentreatmentwithBetalociscommenced.

Aswithallbeta-blockers,carefulconsiderationshouldbegiventopatientswithpsoriasisbeforeBetalocis

administered.

InthepresenceoflivercirrhosisthebioavailabilityofBetalocmaybeincreased.

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Inlabileandinsulin-dependentdiabetesitmaybenecessarytoadjustthehypoglycaemictherapy.

Intravenousadministrationofcalciumantagonistsoftheverapamil-typeshouldnotbegiventopatientstreatedwith

beta-blockers.

Theinitialtreatmentofseveremalignanthypertensionshouldbesodesignedastoavoidsuddenreductionindiastolic

bloodpressurewithimpairmentofautoregulatorymechanisms.

Thisproductcontainslactose.Patientswithrarehereditaryproblemsofgalactoseintolerance,theLapplactase

deficiencyorglucose-galactosemalabsorptionshouldnottakethismedicine.

4.5Interactionwithothermedicinalproductsandotherformsofinteraction

Betaloccanreducemyocardialcontractilityandimpairintracardiacconduction.Careshouldbeexercisedwhendrugs

withsimilaractivity,e.g.antiarrhythmicagents(ofthequinidinetypeandamiodarone),orgeneralanaesthetics,are

givenconcurrently.

IncreasednegativeinotropicandchronotropiceffectsmayoccurwhenBetalocisgiventogetherwithcalcium

antagonistsoftheverapamilanddiltiazemtype,causingbradycardia,hypotensionandasystole.Inpatientstreatedwith

beta-blockersintravenousadministrationofcalciumantagonistsoftheverapamil-typeshouldnotbegivenin

combination.

Digitalisglycosides,inassociationwithbeta-blockers,mayincreaseatrioventricularconductiontimeandmayinduce

bradycardia.

Patientsreceivingconcomitanttreatmentwithsympatheticganglionblockingagents,otherbeta-blockers(i.e.eye

drops),orMonoAmineOxidase(MAO)inhibitorsshouldbekeptunderclosesurveillance.

Ifconcomitanttreatmentwithclonidineistobediscontinued,Betalocshouldbewithdrawnseveraldaysbefore

clonidine.

Betalocwillantagonisethebeta

-effectsofsympathomimeticagentsbutshouldhavelittleinfluenceonthe

bronchodilatoreffectsofbeta

-agonistsatnormaltherapeuticdoses.

Theadministrationofadrenaline(epinephrine)topatientsundergoingbeta-blockadecanresultinanincreaseinblood

pressureandbradycardiaalthoughthisislesslikelytooccurwithbeta

-selectivedrugs.

Betalocmayimpairtheeliminationoflidocaine.

MetoprololisametabolicsubstratefortheCytochromeP450isoenzymeCYP2D6.Drugsthatactasenzyme-inducing

andenzyme-inhibitingsubstancesmayexertaninfluenceontheplasmalevelofmetoprolol.Plasmalevelsof

metoprololmayberaisedbyco-administrationofcompoundsmetabolisedbyCYP2D6,e.g.antiarrhythmics,

antihistamines,histamine-2-receptorantagonists,antidepressants,antipsychotics,andCOX-2-inhibitors.Theplasma

concentrationofmetoprololisloweredbyrifampicinandmayberaisedbyalcoholandhydralazine.

Aswithotherbeta-blockers,concomitanttherapywithdihydropyridinese.g.nifedipine,mayincreasetheriskof

hypotension,andcardiacfailuremayoccurinpatientswithlatentcardiacinsufficiency.

Concomitanttreatmentwithindometacinorotherprostaglandinsynthetaseinhibitingdrugsmaydecreasethe

antihypertensiveeffectofbeta-blockers.

Thebeta-blockermaymasksomeofthesymptomsofthyrotoxicosisandofhypoglycaemiabyinhibitionof

sympatheticnervefunctions.Theeffectsofhypoglycaemicagentsmaybeincreased,particularlybythe

non-cardioselectivebeta-blockers.Thedosagesoforalantidiabeticsandalsoofinsulinmayhavetobereadjustedin

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Asbeta-blockersmayaffecttheperipheralcirculation,careshouldbeexercisedwhendrugswithsimilaractivitye.g.

ergotaminearegivenconcurrently.

TheeffectsofBetalocandotherantihypertensivedrugsonbloodpressureareusuallyadditive.Careshouldbetaken

whencombiningwithotherantihypertensivedrugsordrugsthatmightreducebloodpressure,suchastricyclic

antidepressants,barbituratesandphenothiazines.However,combinationsofantihypertensivedrugsmayoftenbeused

withbenefitstoimprovecontrolofhypertension.

4.6Pregnancyandlactation

Pregnancy

Betalocshouldnotbeusedinpregnancyornursingmothersunlessthephysicianconsidersthatthebenefitoutweighs

thepossiblehazardtothefoetus/infant.Beta-blockersreduceplacentalperfusion,whichmayresultinintrauterine

foetaldeath,immatureandprematuredeliveries.

Aswithallbeta-blockers,Betalocmaycauseside-effectsespeciallybradycardiaandhypoglycaemiainthefoetus,and

inthenewbornandbreastfedinfant.Betalochas,however,beenusedinpregnancyassociatedhypertensionunderclose

supervision,after20weeksgestation.AlthoughBetaloccrossestheplacentalbarrierandispresentinthecordblood,as

yetnoevidenceoffoetalabnormalitieshasbeenreported.

Lactation

Theamountofmetoprololingestedviabreastmilkshouldnotproducesignificantbeta-blockingeffectsintheneonate

ifthemotheristreatedwiththenormaltherapeuticdoses.

4.7Effectsonabilitytodriveandusemachines

PatientsshouldknowhowtheyreacttoBetalocbeforetheydriveorusemachinesbecauseoccasionallydizzinessor

fatiguemayoccur.

4.8Undesirableeffects

Betalociswelltoleratedandadversereactionshavegenerallybeenmildandreversible.Thefollowingeventshave

beenreportedasadverseeventsinclinicaltrialsorreportedfromroutineuse.Arelationshiptotreatmentwith

metoprololhasnotalwaysbeenestablished.

Thefollowingdefinitionsoffrequenciesareused:

Verycommon(>10%),common(1-9.9%),uncommon(0.1-0.9%),rare(0.01-0.09%)andveryrare(<0.01%).

Cardiovascularsystem

Common: Bradycardia,posturaldisorders(veryrarelywithsyncope),coldhandsandfeet,

palpitations.

Uncommon: Deteriorationofheartfailuresymptoms,cardiogenicshockinpatientswithacute

myocardialinfarction*,first-degreeheartblock,oedema,precordialpain.

Rare: Disturbancesofcardiacconduction,cardiacarrhythmias.

Veryrare: Gangreneinpatientswithpre-existingsevereperipheralcirculatorydisorders.

*Excessfrequencyof0.4%comparedwithplaceboinastudyof46,000patientswithacutemyocardialinfarction

wherethefrequencyofcardiogenicshockwas2.3%inthemetoprololgroupand1.9%intheplacebogroupinthe

subsetofpatientswithlowshockriskindex.Theshockriskindexwasbasedontheabsoluteriskofshockineach

individualpatientderivedfromage,sex,timedelay,Killipclass,bloodpressure,heartrate,ECGabnormality,andprior

historyofhypertension.Thepatientgroupwithlowshockriskindexcorrespondstothepatientsinwhichmetoprololis

recommendedforuseinacutemyocardialinfarction.

Centralnervoussystem

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Common: Dizziness,headache.

Uncommon: Paraesthesiae,musclecramps.

Gastrointestinal

Common: Nausea,abdominalpain,diarrhoea,constipation.

Uncommon: Vomiting.

Rare: Drymouth.

Haematologic

Veryrare: Thrombocytopenia.

Hepatic

Rare: Liverfunctiontestabnormalities.

Veryrare: Hepatitis.

Metabolism

Uncommon: Weightgain.

Musculoskeletal

Veryrare: Arthralgia.

Psychiatric

Uncommon: Depression,concentrationimpairment,somnolenceorinsomnia,nightmares.

Rare: Nervousness,anxiety,impotence/sexualdysfunction.

Veryrare: Amnesia/memoryimpairment,confusion,hallucinations.

Respiratory

Common: Dyspnoeaonexertion.

Uncommon: Bronchospasm.

Rare: Rhinitis.

Senseorgans

Rare: Disturbancesofvision,dryand/orirritatedeyes,conjunctivitis.

Veryrare: Tinnitus,tastedisturbances.

Skin

Uncommon: Rash(intheformofurticariapsoriasiformanddystrophicskinlesions),increased

sweating.

Rare: Lossofhair.

Veryrare: Photosensitivityreactions,aggravatedpsoriasis.

4.9Overdose

Thesymptomsofoverdosemayincludebradycardia,hypotension,acutecardiacinsufficiencyandbronchospasm.

Generaltreatmentshouldinclude:

Closesupervision,treatmentinanintensivecareward,theuseofgastriclavage,activatedcharcoalandalaxativeto

preventabsorptionofanydrugstillpresentinthegastrointestinaltract,theuseofplasmaorplasmasubstitutestotreat

hypotensionandshock.

Excessivebradycardiacanbecounteredwithatropine1-2mgintravenouslyand/oracardiacpacemaker.Ifnecessary,

thismaybefollowedbyabolusdoseofglucagon10mgintravenously.Ifrequired,thismayberepeatedorfollowedby

anintravenousinfusionofglucagon1-10mg/hourdependingonresponse.Ifnoresponsetoglucagonoccursorif

glucagonisunavailable,abetaadrenoceptorstimulantsuchasdobutamine2.5to10micrograms/kg/minuteby

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Dobutamine,becauseofitspositiveinotropiceffectcouldalsobeusedtotreathypotensionandacutecardiac

insufficiency.Itislikelythatthesedoseswouldbeinadequatetoreversethecardiaceffectsofbetablockadeifalarge

overdosehasbeentaken.Thedoseofdobutamineshouldthereforebeincreasedifnecessarytoachievetherequired

responseaccordingtotheclinicalconditionofthepatient.

Administrationofcalciumionsmayalsobeconsidered.Bronchospasmcanusuallybereversedbybronchodilators.

5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

Metoprololisacompetitive-adrenoceptorantagonist.Itactspreferentiallytoinhibit -adrenoceptors(conferring

somecardioselectivity),isdevoidofintrinsicsympathomimeticactivity(partialagonistactivity)andpossesses-

adrenoceptorblockingactivitycomparableinpotencywithpropranolol.

Anegativechronotropiceffectontheheartisaconsistentfeatureofmetoprololadministration.Thus,cardiacoutput

andsystolicbloodpressurerapidlydecreasefollowingacuteadministration.

5.2Pharmacokineticproperties

Metoprololtabletsdissolverapidlywhichresultsinarapidandcompleteabsorptionwitht

within2hoursand

consistentbioavailabilitydatabetweendifferentstudypopulations.

MetoprololundergoesoxidativemetabolismintheliverprimarilybytheCYP2D6isoenzyme.

Eliminationismainlyviahepaticmetabolism(>90%).Terminalhalflifeisabout3-4hours.

5.3Preclinicalsafetydata

Theacutetoxicityofmetoprololislowtomoderate.Signsoftoxicityarenon-specificanddonotindicateanytarget

organ.Signsinratsanddogsindicatethatmetoprololcanexertacardiopressiveactionathighplasmaconcentrations.

Acutetoxicityafteroraladministrationislowerinrodentsthanindogs.

Thereisnospecificgeneraltoxicityafterrepeatedadministrationtoratsordogs.Reproductionandmutagenicity

studieshaverevealednoevidenceofadverseeffects.

Carcinogenicitystudiesinratsandmicehaveshownnoincreasedincidenceofneoplasmsrelatedtometoprolol.

6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

Microcrystallinecellulose

Lactosemonohydrate

Sodiumstarchglycollate

Colloidalanhydroussilica

Povidone

Magnesiumstearate

6.2Incompatibilities

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6.3ShelfLife

5years.

6.4Specialprecautionsforstorage

Donotstoreabove25°C.

6.5Natureandcontentsofcontainer

Polypropylenesecuritainerwithpolyethylenecap-56,100and500tablets

ThermoformedPVC/aluminiumblisterpacks:

100(10x10blisters)

56(4x14blisters)

50(5x10blisters)

Notallpacksizesmaybemarketed.

6.6Specialprecautionsfordisposalofausedmedicinalproductorwastematerialsderivedfrom

suchmedicinalproductandotherhandlingoftheproduct

Nospecialrequirements.

7MARKETINGAUTHORISATIONHOLDER

AstraZenecaUKLtd.,

600CapabilityGreen,

Luton

LU13LU

UnitedKingdom

8MARKETINGAUTHORISATIONNUMBER

PA970/32/2

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

Dateoffirstauthorisation:04June1975

Dateoflastrenewal:26May2010

10DATEOFREVISIONOFTHETEXT

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