BETALOC

Main information

  • Trade name:
  • BETALOC Tablet Prolonged Release 200 Milligram
  • Dosage:
  • 200 Milligram
  • Pharmaceutical form:
  • Tablet Prolonged Release
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug

Documents

Localization

  • Available in:
  • BETALOC Tablet Prolonged Release 200 Milligram
    Ireland
  • Language:
  • English

Status

  • Source:
  • HPRA - Health Products Regulatory Authority - Ireland
  • Authorization number:
  • PPA1328/053/001
  • Authorization date:
  • 29-09-2006
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

IRISHMEDICINESBOARDACT1995

MEDICINALPRODUCTS(LICENSINGANDSALE)REGULATIONS,1998

(S.I.No.142of1998)

PPA1328/053/001

CaseNo:2034068

TheIrishMedicinesBoardinexerciseofthepowersconferredonitbytheabovementionedRegulationsherebygrants

B&SHealthcare

Unit4,BradfieldRoad,Ruislip,Middlesex,HA40NU,UnitedKingdom

anauthorisation,subjecttotheprovisionsofthesaidRegulations,inrespectoftheproduct

Betaloc200mgProlonged-ReleaseTablets

TheparticularsofwhicharesetoutinPartIandPartIIoftheattachedSchedule.Theauthorisationisalsosubjectto

thegeneralconditionsasmaybespecifiedinthesaidRegulationsaslistedonthereverseofthisdocument.

Thisauthorisation,unlesspreviouslyrevoked,shallcontinueinforcefrom26/03/2007until28/09/2011.

SignedonbehalfoftheIrishMedicinesBoardthis

________________

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PartII

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

Betaloc200mgProlonged-releaseTablets

2QUALITATIVEANDQUANTITATIVECOMPOSITION

Eachtabletcontains200mgmetoprololtartrate.

Forafulllistofexcipients,seesection6.1.

3PHARMACEUTICALFORM

Prolonged-releasetablet

ProductimportedfromtheUK:

Round,whitetabletsimpressedwith“A/MD”.

4CLINICALPARTICULARS

4.1TherapeuticIndications

Inthemanagementofanginapectorisandhypertension.

Prophylaxisofmigraine.

4.2Posologyandmethodofadministration

Thetabletsshouldbetakenonanemptystomach.

Betaloc200mgProlongedReleaseTabletsmaybedividedinhalf.

Betaloc200mgProlongedReleaseTabletsshouldbeswallowedwithliquid.Betaloc200mg

ProlongedReleaseTablets(orthedividedtablets)shouldnotbechewedorcrushed.

Thedosemustalwaysbeadjustedtotheindividualrequirementsofthepatient.Thefollowingare

guidelines:

Hypertension

Therecommendedmaintenancedosageinpatientswithhypertensionis100-200mgdaily,givenas

Betaloc200mgProlongedReleaseTabletsoncedaily.Ifneeded,otherantihypertensiveagentsmaybe

added.

Long-termantihypertensivetreatmentwithmetoprololindailydosesof100-200mghasbeenshownto

reducetotalmortality,includingsuddencardiovasculardeath,strokeandcoronaryeventsin

hypertensivepatients.

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Therecommendedmaintenancedosageis100-200mgdaily,givenasBetaloc200mgProlonged

ReleaseTabletsoncedaily.Ifneeded,otheranti-anginalagentsmaybeadded.

MigraineProphylaxis

Therecommendeddosageis100-200mgdaily,givenasBetaloc200mgProlongedReleaseTablets

oncedaily.

ImpairedRenalFunction

Doseadjustmentisgenerallynotneededinpatientswithimpairedrenalfunction.

ImpairedHepaticFunction

Doseadjustmentisnormallynotneededinpatientssufferingfromlivercirrhosisbecausemetoprolol

hasalowproteinbinding(5-10%).However,areductionindosagemaybenecessary,accordingto

theseverityofhepaticimpairment.

Elderly

Severalstudiesindicatethatage-relatedphysiologicalchangeshavenegligibleeffectsonthe

pharmacokineticsofmetoprolol.

Children

Thereislimitedexperiencewithmetoprololtreatmentinchildren.

4.3Contraindications

Betaloc200mgProlongedReleaseTablets,aswithotherbeta-blockers,shouldnotbeusedinpatients

withanyofthefollowing:

-AVblockofsecond-orthird-degree,

-Unstabledecompensatedcardiacfailure(pulmonaryoedema,hypoperfusionorhypotension),

-Continuousorintermittentinotropictherapyactingthroughbeta-receptoragonism,

-Bradycardia,(<45bpm),

-Sicksinussyndrome,

-Cardiogenicshock,

-Severeperipheralarterialcirculatorydisorder,

-Untreatedphaeochromocytoma,

-Metabolicacidosis.

KnownhypersensitivitytoanycomponentofBetaloc200mgProlongedReleaseTabletsorotherbeta-

blockers.

Betaloc200mgProlongedReleaseTabletsisalsocontra-indicatedwhensuspectedacutemyocardialinfarctionis

complicatedbybradycardia(<45bpm),firstdegreeheartblock(theP-Qintervalis>0.24sec)orsystolicbloodpressure

<100mmHg.

4.4Specialwarningsandprecautionsforuse

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shouldnotbewithdrawnabruptly.Whenpossible,Betaloc200mgProlongedReleaseTabletsshould

bewithdrawngraduallyoveraperiodof10-14days,indiminishingdosesto25mgdailyforthelast6

days.Duringwithdrawalpatientsshouldbekeptunderclosesurveillance,especiallythosewithknown

ischaemicheartdisease.Theriskforcoronaryevents,includingsuddendeath,mayincreaseduringthe

withdrawalofbeta-blockade.

mustbereportedtotheanaesthetistpriortogeneralanaesthesia.Itisnotgenerallyrecommendedto

stopBetaloc200mgProlongedReleaseTabletstreatmentinpatientsundergoingsurgery.

althoughcontra-indicatedinsevereperipheralarterialcirculatorydisturbances(seeSection4.3),may

alsoaggravatelesssevereperipheralarterialcirculatorydisorders.

maybeadministeredwhenheartfailurehasbeencontrolled.Digitalisationand/ordiuretictherapy

shouldalsobeconsideredforpatientswithahistoryofheartfailure,orpatientsknowntohaveapoor

cardiacreserve.

maycausepatientstodevelopincreasingbradycardia,insuchcasestheBetaloc200mgProlonged

ReleaseTabletsdosageshouldbereducedorgraduallywithdrawn.

duetothenegativeeffectonconductiontime,mayaggravatepre-existingconductiontimedisorders

ofmoderatedegree,whichmayleadtoAVblock,andshouldonlybegivenwithcautiontopatients

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mayincreasethenumberanddurationofanginaattacksinpatientswithPrinzmetal'sangina,dueto

unopposedalpha-receptormediatedcoronaryarteryvasoconstriction.Betaloc200mgProlonged

ReleaseTabletsisabeta

-selectivebeta-blocker;consequently,itsusemaybeconsideredalthough

utmostcautionmustbeexercised.

maymasktheearlysignsofacutehypoglycaemia,inparticulartachycardia.Duringtreatmentwith

Betaloc200mgProlongedReleaseTablets,theriskofinterferingwithcarbohydratemetabolismor

maskinghypoglycaemiaislessthanwithnon-selectivebeta-blockers.

maymaskthesymptomsofthyrotoxicosis.

mayincreaseboththesensitivitytowardsallergensandtheseriousnessofanaphylacticreactions.

Althoughcardioselectivebeta-blockersmayhavelesseffectonlungfunctionthannon-selectivebeta-

blockers,aswithallbeta-blockers,theseshouldbeavoidedinpatientswithreversibleobstructive

airwaysdiseaseunlesstherearecompellingclinicalreasonsfortheiruse.Whenadministrationis

necessary,thesepatientsshouldbekeptunderclosesurveillance.Theuseofabeta

-bronchodilator

(e.g.terbutaline)maybeadvisableinsomepatients.Thedosageofthebeta

-agonistmayrequirean

increasewhentreatmentwithBetaloc200mgProlongedReleaseTabletsiscommenced.

Aswithallbeta-blockers,carefulconsiderationshouldbegiventopatientswithpsoriasisbefore

Betaloc200mgProlongedReleaseTabletsareadministered.

InthepresenceoflivercirrhosisthebioavailabilityofBetaloc200mgProlongedReleaseTabletsmay

beincreased.

Inpatientswithaphaeochromocytoma,analpha-blockershouldbegivenconcomitantly.

Inlabileandinsulin-dependentdiabetesitmaybenecessarytoadjustthehypoglycaemictherapy.

Intravenousadministrationofcalciumantagonistsoftheverapamil-typeshouldnotbegivento

patientstreatedwithbeta-blockers.

Theinitialtreatmentofseveremalignanthypertensionshouldbesodesignedastoavoidsuddenreductionindiastolic

bloodpressurewithimpairmentofautoregulatorymechanisms.

4.5Interactionwithothermedicinalproductsandotherformsofinteraction

Betaloc200mgProlongedReleaseTabletscanreducemyocardialcontractilityandimpairintracardiac

conduction.Careshouldbeexercisedwhendrugswithsimilaractivity,e.g.antiarrhythmicagents(of

thequinidinetypeandamiodarone),orgeneralanaesthetics,aregivenconcurrently.

IncreasednegativeinotropicandchronotropiceffectsmayoccurwhenBetaloc200mgProlonged

ReleaseTabletsaregiventogetherwithcalciumantagonistsoftheverapamilanddiltiazemtype,

causingbradycardia,hypotensionandasystole.Inpatientstreatedwithbeta-blockers,intravenous

administrationofcalciumantagonistsoftheverapamil-typeshouldnotbegivenincombination.

Patientsreceivingconcomitanttreatmentwithsympatheticganglionblockingagents,otherbeta-

blockers(i.e.eyedrops),orMonoAmineOxidase(MAO)inhibitorsshouldbekeptunderclose

surveillance.

Ifconcomitanttreatmentwithclonidineistobediscontinued,Betaloc200mgProlongedRelease

Tabletsshouldbewithdrawnseveraldaysbeforeclonidine.

Betaloc200mgProlongedReleaseTabletswillantagonisethebeta

-effectsofsympathomimetic

agentsbutshouldhavelittleinfluenceonthebronchodilatoreffectsofbeta

-agonistsatnormal

therapeuticdoses.

Theadministrationofadrenalinetopatientsundergoingbeta-blockadecanresultinanincreasein

bloodpressureandbradycardiaalthoughthisislesslikelytooccurwithbeta

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Betaloc200mgProlongedReleaseTabletsmayimpairtheeliminationoflignocaine.

MetoprololisametabolicsubstratefortheCytochromeP450isoenzymeCYP2D6.Drugsthatactas

enzyme-inducingandenzyme-inhibitingsubstancesmayexertaninfluenceontheplasmalevelof

metoprolol.Plasmalevelsofmetoprololmayberaisedbyco-administrationofcompounds

metabolisedbyCYP2D6,e.g.antiarrhythmics,antihistamines,histamine-2-receptorantagonists,

antidepressants,antipsychotics,andCOX-2-inhibitors.Theplasmaconcentrationofmetoprololis

loweredbyrifampicinandmayberaisedbyalcoholandhydralazine.

Aswithotherbeta-blockers,concomitanttherapywithdihydropyridinese.g.nifedipine,mayincrease

theriskofhypotension,andcardiacfailuremayoccurinpatientswithlatentcardiacinsufficiency.

Concomitanttreatmentwithindomethacinorotherprostaglandinsynthetaseinhibitingdrugsmay

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Thebeta-blockermaymasksomeofthesymptomsofthyrotoxicosisandofhypoglycaemiaby

inhibitionofsympatheticnervefunctions.Theeffectsofhypoglycaemicagentsmaybeincreased

particularly,bythenon-cardioselectivebeta-blockers.Thedosagesoforalantidiabeticsandalsoof

insulinmayhavetobereadjustedinpatientsreceivingbeta-blockers.Thetachycardiaof

hypoglycaemiamaybemodified.

Asbeta-blockersmayaffecttheperipheralcirculation,careshouldbeexercisedwhendrugswith

similaractivitye.g.ergotaminearegivenconcurrently.

TheeffectsofBetaloc200mgProlongedReleaseTabletsandotherantihypertensivedrugsonbloodpressureare

usuallyadditive.Careshouldbetakenwhencombiningwithotherhypertensivedrugsordrugsthatmightreduceblood

pressure,suchastricyclicantidepressants,barbituratesandphenothiazines.However,combinationsofantihypertensive

drugsmayoftenbeusedwithbenefittoimprovecontrolofhypertension.

4.6Pregnancyandlactation

Pregnancy

Betaloc200mgProlongedReleaseTabletsshouldnotbeusedinpregnancyornursingmothersunless

thephysicianconsidersthatthebenefitoutweighsthepossiblehazardtothefoetus/infant.Beta-

blockersreduceplacentalperfusion,whichmayresultinintrauterinefoetaldeath,immatureand

prematuredeliveries.

Aswithallbeta-blockers,Betaloc200mgProlongedReleaseTabletsmaycauseside-effects,

especiallybradycardiaandhypoglycaemiainthefoetus,andinthenewbornandbreastfedinfant.

Betaloc200mgProlongedReleaseTabletshave,however,beenusedinpregnancyassociated

hypertensionunderclosesupervision,after20weeksgestation.AlthoughBetaloc200mgProlonged

ReleaseTabletscrossestheplacentalbarrierandispresentinthecordblood,asyetnoevidenceof

foetalabnormalitieshasbeenreported.

Lactation

TheamountofBetaloc200mgProlongedReleaseTabletsingestedviabreastmilkshouldnotproducesignificantbeta-

blockingeffectsintheneonateifthemotheristreatedwiththenormaltherapeuticdoses.

4.7Effectsonabilitytodriveandusemachines

PatientsshouldknowhowtheyreacttoBetaloc200mgProlongedReleaseTabletsbeforetheydriveorusemachines

becauseoccasionallydizzinessorfatiguemayoccur.

4.8Undesirableeffects

Betaloc200mgProlongedReleaseTabletsarewelltoleratedandadversereactionshavegenerally

beenmildandreversible.Thefollowingeventshavebeenreportedasadverseeventsinclinicaltrials

orreportedfromroutineuse.Arelationshiptotreatmentwithmetoprololhasnotalwaysbeen

established.

Thefollowingdefinitionsoffrequenciesareused:

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

(<0.01%).

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Centralnervoussystem

Gastrointestinal

Haematologic

Hepatic

Metabolism

Musculoskeletal

Common: Bradycardia,posturaldisorders(veryrarelywith

syncope),coldhandsandfeet,palpitations.

Uncommon: Deteriorationofheartfailuresymptoms,first-degreeheart

block,oedema,pericordialpain.

Rare: Disturbancesofcardiacconduction,cardiacarrhythmias.

Veryrare: Gangreneinpatientswithpre-existingsevereperipheral

circulatorydisorders.

Verycommon: Fatigue.

Common: Dizziness,headache.

Uncommon: Paraesthesiae,musclecramps.

Common: Nausea,abdominalpain,diarrhoea,constipation.

Uncommon: Vomiting.

Rare: Drymouth.

Veryrare: Thrombocytopenia.

Rare: Liverfunctiontestabnormalities.

Veryrare: Hepatitis.

Uncommon: Weightgain.

Veryrare: Arthralgia.

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Respiratory

Senseorgans

Skin

4.9Overdose

Symptoms

PoisoningduetoanoverdoseofBetaloc200mgProlongedReleaseTabletsmayleadtosevere

hypotension,sinusbradycardia,atrioventricularblock,heartfailure,cardiogenicshock,cardiacarrest,

bronchospasm,impairmentofconsciousness,coma,nausea,vomiting,cyanosis,hypoglycaemiaand,

occasionally,hyperkalaemia.

Concomitantingestionofalcohol,antihypertensives,quinidineorbarbituratesmayaggravatethe

patient'scondition.

Thefirstmanifestationsusuallyappear20minutesto2hoursafterdrugingestion.

Management

Treatmentshouldincludeclosemonitoringofcardiovascular,respiratoryandrenalfunction,and

bloodglucoseandelectrolytes.Furtherabsorptionmaybepreventedbyinductionofvomiting,gastric

lavageoradministrationofactivatedcharcoalifingestionisrecent.Cardiovascularcomplications

shouldbetreatedsymptomatically.Inthepresenceofseverehypotension,bradycardia,andimpending

heartfailure,administerabeta

-agonistuntilthedesiredeffectisachieved.Whereaselectivebeta

agonistisnotavailable,dopaminemaybeused;oratropinesulphatei.v.maybeusedinordertoblock

insomnia,nightmares.

Rare: Nervousness,anxiety,impotence/sexualdysfunction.

Veryrare: Amnesia/memoryimpairment,confusion,hallucinations.

Common: Dyspnoeaonexertion.

Uncommon: Bronchospasm.

Rare: Rhinitis.

Rare: Disturbancesofvision,dryand/orirritatedeyes,

conjunctivitis.

Veryrare: Tinnitus,tastedisturbances.

Uncommon: Rash(intheformofurticariapsoriasiformanddystrophic

skinlesions),increasedsweating.

Rare: Lossofhair.

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

mayberequiredforAVblock.Glucagoncanreversetheeffectsofexcessivebeta-blockade,givenina

doseof1-10mgintravenously.

Intravenousbeta

-stimulantse.g.terbutalinemayberequiredtorelievebronchospasm.

Itshouldbenotedthatthedosagesofdrugs(antidotes)neededtotreatoverdoseofbeta-blockadeare

muchhigherthannormallyrecommendedtherapeuticdosages.Thisisbecausethebeta-receptorsare

occupiedbythebeta-blocker.

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5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

ATCCode:C07AB02

Metoprololisacompetitive-adrenoceptorantagonist.Itactspreferentiallytoinhibit

adrenoceptors(conferringsomecardioselectivity),isdevoidofintrinsicsympathomimeticactivity

(partialagonistactivity)andpossesses-adrenoceptorblockingactivitycomparableinpotencywith

propranolol.

Anegativechronotropiceffectontheheartisaconsistentfeatureofmetoprololadministration.Thuscardiacoutputand

systolicbloodpressurerapidlydecreasefollowingacuteadministration.

5.2Pharmacokineticproperties

Metoprololisalmostcompletelyabsorbedoveralargepartofthegastrointestinaltract,but

bioavailabilityafteroraladministrationis40-50%ofthatafteri.v.injection,becauseofhepaticfirst

passmetabolism.ThebioavailabilityofmetoprololafterCRtabletadministrationisabout70%ofthat

afterplaintablets.

ThesteadystateV

ofmetoprololis3.2L/kgandproteinbindingisabout12%.

MetoprololundergoesoxidativemetabolismintheliverprimarilybytheCYP2D6isoenzyme.

Eliminationhalflifeofmetoprololisusuallybetweenabout3and5hours.Eliminationisbyliver

metabolismandmetabolitesarelargelyinactive.WithmetoprololCRT

isprolongedtoabout8

hours.MeanC

afterBetaloc200mgProlongedReleaseTabletswas519nmol/L,achievedafter4

hours.Plasmalevelsat24hourswereabout85nmol/LafterBetaloc200mgProlongedRelease

Tablets.

InitialabsorptionofmetoprololCRwasmorerapidandAUCincreasedwhengiventogetherwith

food.

Urinerecoveryofunchangeddrugwasabout4%aftermetoprololCRandmetoprololplaintablets.

Thepharmacokineticsand-blockingeffectofmetoprololarenotsignificantlyalteredinpatientswith

renalfailure.

Inhealthyelderlyvolunteerstherewasnosignificantdifferenceinthevolumeofdistribution,

eliminationhalflife,totalbodyclearanceorbioavailabilityofmetoprololcomparedwithyoung

volunteers.

Inpatientswithcirrhosisoftheliverthebioavailabilityofmetoprololwasincreasedandtotalbodyclearancereduced.

5.3Preclinicalsafetydata

Thereisnotoxicitydatathatwouldindicatethatmetoprololtartrateisunsafeforuseintheindicationsgiven.Signsin

ratsanddogsindicatethatmetoprololcanexertacardiopressiveactionathighplasmalevels.

6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

Sodiumaluminiumsilicate

Paraffin

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Ethylcellulose

Hypromellose

Macrogol

Titaniumdioxide(E171)

6.2Incompatibilities

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6.3ShelfLife

Theshelf-lifeexpirydateofthisproductshallbethedateshownonthecontainerandouterpackageof

theproductonthemarketinthecountryoforigin.

6.4Specialprecautionsforstorage

Donotstoreabove25 0

6.5Natureandcontentsofcontainer

Blisterstrips(pressthroughpacksofthermoformedPVCwithAlfoilasenclosureweb).7tabletsper

calendarstrip-packsize28.

6.6Specialprecautionsfordisposalofausedmedicinalproductorwastematerials

derivedfromsuchmedicinalproductandotherhandlingoftheproduct

Nospecialrequirements.

7ParallelProductAuthorisationHolder

B&SHealthcare

Unit4

BradfieldRoad

Ruislip

Middlesex

HA40NU

UnitedKingdom

8ParallelProductAuthorisationNumber

PPA1328/53/1

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

DateofFirstAuthorisation:29thSeptember2006

10DATEOFREVISIONOFTHETEXT

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