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:
  • PPA0465/200/001
  • Authorization date:
  • 13-07-2007
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

IRISHMEDICINESBOARDACTS1995AND2006

MEDICINALPRODUCTS(CONTROLOFPLACINGONTHEMARKET)REGULATIONS,2007

(S.I.No.540of2007)

PPA0465/200/001

CaseNo:2054664

TheIrishMedicinesBoardinexerciseofthepowersconferredonitbytheabovementionedRegulationsherebygrantsto

PCOManufacturingLimited

Unit10,AshbourneBusinessPark,Rath,Ashbourne,Co.Meath,Ireland

anauthorisation,subjecttotheprovisionsofthesaidRegulations,inrespectoftheproduct

BetalocTablets50mg

TheparticularsofwhicharesetoutinPartIandPartIIoftheattachedSchedule.Theauthorisationisalsosubjecttothegeneralconditionsas

maybespecifiedinthesaidRegulationsaslistedonthereverseofthisdocument.

Thisauthorisation,unlesspreviouslyrevoked,shallcontinueinforcefrom20/10/2008until12/07/2012.

SignedonbehalfoftheIrishMedicinesBoardthis

________________

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PartII

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

BetalocTablets50mg

2QUALITATIVEANDQUANTITATIVECOMPOSITION

EachtabletcontainsMetoprololtartrate50mg.

Excipient:Lactosemonohydrate

Forafulllistofexcipients,seesection6.1.

3PHARMACEUTICALFORM

Tablet.

ProductimportedfromtheUK:

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

4CLINICALPARTICULARS

4.1TherapeuticIndications

Inthemanagementofhypertensionandanginapectoris.Cardiacarrhythmias,especiallysupraventricular

tachyarrhythmias.

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),

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-Bradycardia,(<45bpm),

-Sicksinussyndrome,

-Cardiogenicshock,

-Severeperipheralarterialcirculatorydisorder,

-Untreatedphaeochromocytoma,

-Metabolicacidosis.

KnownhypersensitivitytoanycomponentofBetalocorotherbeta-blockers.

Betalocisalsocontra-indicatedwhensuspectedacutemyocardialinfarctioniscomplicatedbybradycardia(<45bpm),

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

4.4Specialwarningsandprecautionsforuse

Betalocaswithotherbeta-blockers:

shouldnotbewithdrawnabruptly.Whenpossible,Betalocshouldbewithdrawngraduallyoveraperiodof10-14

days,indiminishingdosesto25mgdailyforthelast6days.Duringitswithdrawalpatientsshouldbekeptunderclose

surveillance,especiallythosewithknownischaemicheartdisease.Theriskforcoronaryevents,includingsudden

death,mayincreaseduringthewithdrawalofbeta-blockade.

mustbereportedtotheanaesthetistpriortogeneralanaesthesia.ItisnotgenerallyrecommendedtostopBetaloc

treatmentinpatientsundergoingsurgery.

althoughcontra-indicatedinsevereperipheralarterialcirculatorydisturbances(seeSection4.3),mayalsoaggravate

lesssevereperipheralarterialcirculatorydisorders.

maybeadministeredwhenheartfailurehasbeencontrolled.Digitalisationand/ordiuretictherapyshouldalsobe

consideredforpatientswithahistoryofheartfailure,orpatientsknowntohaveapoorcardiacreserve.

maycausepatientstodevelopincreasingbradycardia,insuchcasestheBetalocdosageshouldbereducedor

graduallywithdrawn.

duetothenegativeeffectonconductiontime,mayaggravatepre-existingconductiontimedisordersofmoderate

degree,whichmayleadtoAVblock,andshouldonlybegivenwithcautiontopatientswithfirstdegreeheartblock.

mayincreasethenumberanddurationofanginaattacksinpatientswithPrinzmetal'sangina,duetounopposedalpha-

receptormediatedcoronaryarteryvasoconstriction.Betalocisabeta1-selectivebeta-blocker;consequently,itsusemay

beconsideredalthoughutmostcautionmustbeexercised.

maymasktheearlysignsofacutehypoglycaemia,inparticulartachycardia.DuringtreatmentwithBetaloc,theriskof

interferingwithcarbohydratemetabolismormaskinghypoglycaemiaislessthanwithnon-selectivebeta-blockers.

maymaskthesymptomsofthyrotoxicosis.

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Althoughcardioselectivebeta-blockersmayhavelesseffectonlungfunctionthannon-selectivebeta-blockers,aswith

allbeta-blockers,theseshouldbeavoidedinpatientswithreversibleobstructiveairwaysdiseaseunlessthereare

compellingclinicalreasonsfortheiruse.Whenadministrationisnecessary,thesepatientsshouldbekeptunderclose

surveillance.Theuseofabeta2-bronchodilator(e.g.terbutaline)maybeadvisableinsomepatients.Thedosageofthe

beta2-agonistmayrequireanincreasewhentreatmentwithBetalociscommenced.

Aswithallbeta-blockers,carefulconsiderationshouldbegiventopatientswithpsoriasisbeforeBetalocis

administered.

InthepresenceoflivercirrhosisthebioavailabilityofBetalocmaybeincreased.

Inpatientswithaphaeochromocytoma,analpha-blockershouldbegivenconcomitantly.

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.

Betalocwillantagonisethebeta1-effectsofsympathomimeticagentsbutshouldhavelittleinfluenceonthe

bronchodilatoreffectsofbeta2-agonistsatnormaltherapeuticdoses.

Theadministrationofadrenaline(epinephrine)topatientsundergoingbeta-blockadecanresultinanincreaseinblood

pressureandbradycardiaalthoughthisislesslikelytooccurwithbeta1-selectivedrugs.

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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,particularlybythenon-

cardioselectivebeta-blockers.Thedosagesoforalantidiabeticsandalsoofinsulinmayhavetobereadjustedinpatients

receivingbeta-blockers.Thetachycardiaofhypoglycaemiamaybemodified.

Asbeta-blockersmayaffecttheperipheralcirculation,careshouldbeexercisedwhendrugswithsimilaractivitye.g.

ergotaminearegivenconcurrently.

TheeffectsofBetalocandotherantihypertensivedrugsonbloodpressureareusuallyadditive.Careshouldbetaken

whencombiningwithotherantihypertensivedrugsordrugsthatmightreducebloodpressure,suchas

tricyclicantidepressants,barbituratesandphenothiazines.However,combinationsofantihypertensivedrugsmayoften

beusedwithbenefitstoimprovecontrolofhypertension.

4.6Pregnancyandlactation

Pregnancy

Betalocshouldnotbeusedinpregnancyornursingmothersunlessthephysicianconsidersthatthebenefitoutweighs

thepossiblehazardtothefoetus/infant.Beta-blockersreduceplacentalperfusion,whichmayresultinintrauterine

foetaldeath,immatureandprematuredeliveries.

Aswithallbeta-blockers,Betalocmaycauseside-effectsespeciallybradycardiaandhypoglycaemiainthefoetus,and

inthenewbornandbreastfedinfant.

Betalochas,however,beenusedinpregnancyassociatedhypertensionunderclosesupervision,after20weeks

gestation.AlthoughBetaloccrossestheplacentalbarrierandispresentinthecordblood,asyetnoevidenceoffoetal

abnormalitieshasbeenreported.

Lactation

Theamountofmetoprololingestedviabreastmilkshouldnotproducesignificantbeta-blockingeffectsintheneonate

ifthemotheristreatedwiththenormaltherapeuticdoses.

4.7Effectsonabilitytodriveandusemachines

PatientsshouldknowhowtheyreacttoBetalocbeforetheydriveorusemachinesbecauseoccasionallydizzinessor

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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,cardiogenicshockinpatientswithacutemyocardialinfarction*,first-degree

heartblock,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

Verycommon:

Fatigue

Common:

Dizziness,headache

Uncommon:

Paraesthesiae,musclecramps.

Gastrointestinal

Common:

Nausea,abdominalpain,diarrhoea,constipation.

Uncommon:

Vomiting.

Rare:

Drymouth.

Haematologic

Veryrare:

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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),increasedsweating.

Rare:

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Veryrare:

Photosensitivityreactions,aggravatedpsoriasis.

4.9Overdose

Symptoms

PoisoningduetoanoverdoseofBetalocmayleadtoseverehypotension,sinusbradycardia,atrioventricularblock,

heartfailure,cardiogenicshock,cardiacarrest,bronchospasm,impairmentofconsciousness,coma,nausea,vomiting,

cyanosis,hypoglycaemiaand,occasionally,hyperkalaemia.

Concomitantingestionofalcohol,antihypertensives,quinidineorbarbituratesmayaggravatethepatient'scondition.

Thefirstmanifestationsusuallyappear20minutesto2hoursafterdrugingestion.

Management

Treatmentshouldincludeclosemonitoringofcardiovascular,respiratoryandrenalfunction,andbloodglucoseand

electrolytes.Furtherabsorptionmaybepreventedbyinductionofvomiting,gastriclavageoradministrationof

activatedcharcoalifingestionisrecent.Cardiovascularcomplicationsshouldbetreatedsymptomatically.Inthe

presenceofseverehypotension,bradycardia,andimpendingheartfailure,administerabeta1-agonistuntilthedesired

effectisachieved.Whereaselectivebeta1-agonistisnotavailable,dopaminemaybeused;oratropinesulphateivmay

beusedinordertoblockthevagusnerve.Ifasatisfactoryeffectisnotachieved,othersympathomimeticagents(e.g.

noradrenaline[norepinephrine],metaraminol),orinotropicagents(e.g.dobutamine)maybeused.Temporarypacing

mayberequiredforAVblock.

Glucagoncanreversetheeffectsofexcessivebeta-blockade,giveninadoseof1-10mgintravenously.

Intravenousbeta2-stimulantse.g.terbutalinemayberequiredtorelievebronchospasm.

Itshouldbenotedthatthedosagesofdrugs(antidotes)neededtotreatoverdoseofbeta-blockadearemuchhigherthan

normallyrecommendedtherapeuticdosages.Thisisbecausethebeta-receptorsareoccupiedbythebeta-blocker.

Betaloccannotbeeffectivelyremovedbyhaemodialysis.

5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

Metoprololisacompetitive-adrenoceptorantagonist.Itactspreferentiallytoinhibit1-adrenoceptors(conferring

somecardioselectivity),isdevoidofintrinsicsympathomimeticactivity(partialagonistactivity)andpossesses-

adrenoceptorblockingactivitycomparableinpotencywithpropranolol.

Anegativechronotropiceffectontheheartisaconsistentfeatureofmetoprololadministration.Thus,cardiacoutput

andsystolicbloodpressurerapidlydecreasefollowingacuteadministration.

5.2Pharmacokineticproperties

Metoprololtabletsdissolverapidlywhichresultsinarapidandcompleteabsorptionwithtmaxwithin2hoursand

consistentbioavailabilitydatabetweendifferentstudypopulations.

MetoprololundergoesoxidativemetabolismintheliverprimarilybytheCYP2D6isoenzyme.

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5.3Preclinicalsafetydata

Theacutetoxicityofmetoprololislowtomoderate.Signsoftoxicityarenon-specificanddonotindicateanytarget

organ.Signsinratsanddogsindicatethatmetoprololcanexertacardiopressiveactionathighplasmaconcentrations.

Acutetoxicityafteroraladministrationislowerinrodentsthanindogs.

Thereisnospecificgeneraltoxicityafterrepeatedadministrationtoratsordogs.Reproductionandmutagenicity

studieshaverevealednoevidenceofadverseeffects.Carcinogenicitystudiesinratsandmicehaveshownnoincreased

incidenceofneoplasmsrelatedtometoprolol.

6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

Microcrystallinecellulose

Lactosemonohydrate

Sodiumstarchglycollate

Colloidalanhydroussilica

Povidone

Magnesiumstearate

6.2Incompatibilities

Notapplicable.

6.3ShelfLife

Theshelf-lifeexpirydateofthisproductshallbethedateshownonthecontainerandouterpackageoftheproducton

themarketinthecountryoforigin.

6.4Specialprecautionsforstorage

Donotstoreabove25C.

6.5Natureandcontentsofcontainer

Aluminiumblisterfoilpacks:

100tablets(10x10blisters)

6.6Specialprecautionsfordisposalandotherhandling

Nospecialrequirements.

7ParallelProductAuthorisationHolder

PCOManufacturingLtd

Unit10,AshbourneBusinessPark

Rath

Ashbourne

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8ParallelProductAuthorisationNumber

PPA465/200/1

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

DateofFirstAuthorisation:13thJuly2007

10DATEOFREVISIONOFTHETEXT

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