BETAGAN

Main information

  • Trade name:
  • BETAGAN Eye Drops Solution 0.5 %w/ v
  • Dosage:
  • 0.5 %w/ v
  • Pharmaceutical form:
  • Eye Drops Solution
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug

Documents

Localization

  • Available in:
  • BETAGAN Eye Drops Solution 0.5 %w/v
    Ireland
  • Language:
  • English

Status

  • Source:
  • HPRA - Health Products Regulatory Authority - Ireland
  • Authorization number:
  • PPA1328/137/001
  • Authorization date:
  • 03-09-2010
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

IRISHMEDICINESBOARDACT1995,asamended

MedicinalProducts(ControlofPlacingontheMarket)Regulations,2007,asamended

PPA1328/137/001

CaseNo:2083500

TheIrishMedicinesBoardinexerciseofthepowersconferredonitbytheabovementionedRegulationsherebygrantsto

B&SHealthcare

Unit4,BradfieldRoad,Ruislip,Middlesex,HA40NU,UnitedKingdom

anauthorisation,subjecttotheprovisionsofthesaidRegulations,inrespectoftheproduct

Betagan0.5%w/vEyeDrops,Solution

theparticularsofwhicharesetoutintheattachedSchedule.Theauthorisationisalsosubjecttothegeneralconditionsasmaybespecifiedin

thesaidRegulationsaslistedonthereverseofthisdocument.

Thisauthorisation,unlesspreviouslyrevoked,shallcontinueinforcefrom03/09/2010.

SignedonbehalfoftheIrishMedicinesBoardthis

________________

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 06/09/2010 CRN 2083500 page number: 1

PartII

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

Betagan0.5%w/vEyeDrops,Solution

2QUALITATIVEANDQUANTITATIVECOMPOSITION

Onemlsolutioncontains5mglevobunololhydrochloride.

Excipient(s):Containsbenzalkoniumchloride.

Forafulllistofexcipients,seesection6.1.

3PHARMACEUTICALFORM

Eyedrops,solution.

ProductimportedfromUK

Aclear,colourlesstolightyellowsolution.

4CLINICALPARTICULARS

4.1TherapeuticIndications

Forthecontrolofintraocularpressureinchronicopenangleglaucomaandocularhypertension.

4.2Posologyandmethodofadministration

Adults(includingtheelderly):TherecommendeddosageisonedropofBetaganintheaffectedeye(s)onceortwice

daily.

Betaganisnotrecommendedforuseinchildrenduetolackofsafetyandefficacydata(seesection5.1).

Methodofadministration:topicalintotheconjunctivalsac.

Ifrequired,Betaganmaybeusedwithotheragentstolowerintra-ocularpressure.Theuseoftwotopicalbeta-

adrenergicblockingagentsisnotrecommended(seesection4.4).

IntraocularpressureshouldbemeasuredapproximatelyfourweeksafterstartingtreatmentwithBetaganasareturnto

normalocularpressurecantakeafewweeks.

Aswithanyeyedrops,toreducepossiblesystemicabsorption,itisrecommendedthatthelachrymalsaciscompressed

atthemedialcanthus(punctualocclusion)foroneminute.Thisshouldbeperformedimmediatelyfollowingthe

instillationofeachdrop.

Transferfromotherbeta-blockingtreatment

Whenanotherbetablockingagentisbeingusedtreatmentmustbediscontinuedafterafulldayoftherapy.Start

treatmentwithBetaganthenextdaywithonedropofBetagantopicallyappliedintotheconjunctivalsacintheaffected

eye(s)onceortwiceaday.

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 06/09/2010 CRN 2083500 page number: 2

Useinrenalandhepaticimpairment

Levobunololhydrochloridehasnotbeenstudiedinpatientswithhepaticorrenalimpairment.Therefore,caution

shouldbeusedintreatingsuchpatients(seesection4.4).

4.3Contraindications

Hypersensitivitytotheactivesubstanceortoanyoftheexcipients.

Reactiveairwaydiseaseincludingbronchialasthmaorahistoryofbronchialasthmaseverechronicobstructive

pulmonarydisease.

Sinusbradycardia,secondandthird-degreeatrioventricularblocknotcontrolledwithapacemaker,overtcardiac

failureorcardiogenicshock.

4.4Specialwarningsandprecautionsforuse

Likeothertopicallyappliedopthalmicagents,Betaganmaybeabsorbedsystemicallysothesametypesof

cardiovascularandpulmonaryadversereactionsasseenwithsystemicbeta-blockersmayoccur.

Cautionshouldbeexercisedintreatingpatientswithsevereorunstableanduncontrolledcardiovasculardisease

includingfirstdegreeatrioventricularblock.Cardiacfailureshouldbeadequatelycontrolledbeforebeginningtherapy.

Patientswithahistoryofseverecardiacdiseaseshouldbewatchedforsignsofcardiacfailureandhavetheirpulserates

checked.

Cardiacandrespiratoryreactions,includingdeathduetobronchospasminpatientswithasthmas,and,rarelydeathin

associationwithcardiacfailureshavebeenreportedfollowingadministrationoflevobunolol.

Theeffectonintra-ocularpressureortheknowneffectsofsystemicbeta-blockademaybeexaggeratedwhenBetagan

isgiventopatientsalreadyreceivingasystemicbetablockingagent.Theresponseofthesepatientsshouldbeclosely

observed.Theuseoftwotopicalbeta-adrenergicblockingagentsisnotrecommended.

Inpatientswithangleclosureglaucoma,theimmediateobjectiveoftreatmentistoreopentheangle.Thisrequires

constrictingthepupilwithamiotic.Betaganhaslittleornoeffectonthepupil.WhenBetaganisusedtoreduce

elevatedintra-ocularpressureinangle-closureglaucomaitshouldbeusedwithamioticandnotalone.

Inpatientswithsevererenalimpairmentondialysis,treatmentwithlevobunololhasbeenassociatedwithpronounced

hypotension.

Levobunololmayimpaircompensatorytachycardiaandincreaseriskofhypotensionwhenusedinconjunctionwith

anaesthetics.TheanaesthetistmustbeinformedifthepatientisusingBetagan.

Beta-blockersmayalsomaskthesignsofhyperthyroidismandcausesworseningogPrinzmetalangina,severe

peripheralandcentralcirculatorydisordersandhypotension.Betaganmustbeusedincautioninpatientswith

metabolicacidosisanduntreatedphaeochromocytoma.

Beta-adrenergicblockingagentsshouldbeadministeredwithcautioninpatientssubjecttospontaneoushypoglycaemia

ortouncontrolleddiabeticpatients(especiallythosewithlabilediabetes)asbeta-blockersmaymaskthesignsand

symptomsofacutehypoglycaemia.Theindicatorysignsofacutehypoglycaemiamaybemasked,inparticular

tachycardia,palpitationsandsweating.

Betaganshouldbeusedwithcautioninpatientswithdepression,cerebralorcoronaryinsufficiency.Raynaud's

phenomenon,orthostatichypotensionorthromboangiitisobliterans.

Whiletakingbeta-blockers,patientswithahistoryofatopyorahistoryofsevereanaphylacticreactiontoavarietyof

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 06/09/2010 CRN 2083500 page number: 3

Aswithsystemicbeta-blockers,ifdiscontinuationoftreatmentisneededinpatientswithcoronaryheartdisease,

therapyshouldbewithdrawngraduallytoavoidrhythmdisorders,myocardialinfarctionorsuddendeath.

Choroidaldetachmentafterfiltrationprocedureshasbeenreportedwithadministrationofaqueoussuppressanttherapy

(e.g.timolol,acetazolamide).

InpatientswithchroniceyeinflammationandcornealdystropyBetaganshouldonlybeappliedintheeventof

stringentdiagnosis&undercontinuousmonitoringatshortintervals.

Skinrashesand/ordryeyesassociatedwiththeuseofbeta-blockershavebeenreported.Theincidenceissmalland

symptomshavestoppedonwithdrawalofthebeta-blockers.Discontinuationoftheuseofbeta-blockersshouldbe

consideredifthesesymptomsarereportedbutcessationoftreatmentshouldbegradual.

ThepreservativeinBetagan,benzalkoniumchloride,maycauseeyeirritation.Removecontactlensespriorto

applicationandwaitatleast15minutesbeforereinsertion.Benzalkoniumchlorideisknowntodiscoloursoftcontact

lenses.Avoidcontactwithsoftcontactlenses.

Betagancontainssodiummetabisulphitewhichmayrarelycauseseverehypersensitivityreactionsandbronchospasm.

AthletesshouldbeawarethatBetagancontainslevonbunololthatmayinduceapositiveresultinanti-dopingcontrols.

4.5Interactionwithothermedicinalproductsandotherformsofinteraction

Nointeractionstudieshavebeenperformed.

AlthoughspecificdruginteractionsstudieshavenotbeenconductedwithBetagan,thetheoreticalpossibilityofan

additiveorpotentiatingeffectwithCNSdepressants(alcohol,barbiturates,opiates,sedatives,oranaesthetics)should

beconsidered.

Thereispotentialforadditiveeffectsresultinginhypotension,and/ormarkedbradycardiawheneyedropswith

levobunololareadministeredconcomitantlywithoralcalciumchannelblocker.Rauwolfiaalkaloids,guanethidine,

beta-blockingagents,anti-arrhythmics,digitalisglycosidesorparasympthomimetics.

CautionshouldbeexercisedandpatientsmustbemonitoredwhenBetaganisusedconcomitantlywithoralbeta-

adrenergicblockagents,becauseofthepotentialforadditiveeffectsonsystemicblockade.

Enhancedhypotensiveeffectisseenwhenbaclofenisgivenwithbeta-blockers.Sincesomesystemicabsorptionmay

followtopicalapplicationofbeta-blockers,regularbloodpressuremonitoringisadvised.

Althoughlevonbunololhaslittleeffectonthesizeofthepupil,mydriasishasoccasionallybeenreportedwhen

levobunololhasbeenusedwithmydriaticagentssuchasadrenaline.

Beta-blockersmayincreasethehypoglycaemiceffectofantidiabeticagents.Beta-blockerscanmaskthesignsand

symptomsofhypoglycaemia(seesection4.4)

Thehypertensivereactiontosuddenwithdrawalofclonidinecanbepotentiatedwhentakingbeta-blockers.

Potentiatedsystemicbeta-blockade(e.g.decreasedheartrate)hasbeenreportedduringcombinedtreatmentwith

quinidineandlevobunolol,possibilybecausequinidineinhibitsthemetabolismoflevonbunololviatheP450enzyme,

CYP2D6.

Concomitantuseofabeta-blockerwithanaestheticdrugsmayattenuatecompensatorytachycardiaandincreasetherisk

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 06/09/2010 CRN 2083500 page number: 4

CautionmustbeexercisedifBetaganisusedconcomitantlywithiodinecontrastproductsorintravenously

administeredlidocaine.

Cimetidinemayincreasetheplasmaconcentrationsoflevobunolol.

NodataonthelevelofcirculatingcatecholaminesafterBetaganadministeredareavailable.Caution,however,is

advisedinpatientstakingmedicationwhichcaneffectthemetabolismanduptakeofcirculatingaminese.g.

chlorpromazine,methylphenidate,reserpinebecauseofpossibleadditiveeffectsandtheproductionofhypertension

and/ormarkedbradycardia,whichmayproductvertigo,syncopeorposturalhypotension.

AlthoughspecificdruginteractionsstudieshavenotbeenconductedwithBetagan,knownadditiveIOPloweringeffect

withprostamides,prostaglandins,alpha-agonists,carbonicanhydraseinhibitorsandpilocarpineshouldbeconsidered.

4.6Pregnancyandlactation

Pregnancy

TherearenoadequatedatafortheuseofBetaganinpregnantwomen.betaganshouldnotbeusedduringpregnancy

unlessclearlynecessary.

Epidemiologicalstudieshavenotrevealedmalformativeeffectsbutshowariskforintrauterinegrowthretardation

whenbeta-blockersareadministeredbytheoralroute.Inaddition,signsandsymptomsofbeta-blockade(e.g.

bradycardia,hypotension,respiratorydistressandhypoglycaemia)havebeenobservedintheneonatewhenbeta-

blockershavebeenadministereduntildelivery.IfBetaganisadministereduntildelivery,theneonateshouldbe

carefullymonitoredduringthefirstdaysoflife.Animalstudieswithlevonbunololhaveshownreproductivetoxicityat

dosessignificantlyhigherthenwouldbeusedinclinicalpractice.

Lactation

Levonbunololisexcretedinbreastmilk.Betaganshouldnotbeusedbybreast-feedingwomen.

4.7Effectsonabilitytodriveandusemachines

Betaganhasminorinfluenceontheabilitytodriveandusemachines.Betaganmaycausetransientblurringofvision,

fatigueand/ordrowsinesswhichmayimpairtheabilitytodriveoroperatemachines.Thepatientshouldwaituntil

thesesymptomshaveclearedbeforedrivingorusingmachinery.

4.8Undesirableeffects

Withineachfrequencygrouping,undesirableeffectsarepresentedinorderofdecreasingseriousness.

Thefollowingterminologieshavebeenusedinordertoclassifytheoccurrenceofundesirableeffects:VeryCommon

≥1/10);Common(≥1/100to<1/10);Uncommon(≥1/1,000to<1/100);Rare(≥1/10,000to<1/1,000);Veryrare

(<1/10,000),notknown(cannotbeestimatedfromtheavailabledata).

PsychiatricDisorders

Notknown:Depression

NervousSystemDisorders

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 06/09/2010 CRN 2083500 page number: 5

EyeDisorders

VeryCommon:Eyeirritation,Conjunctivalirritation

Common:Blepharitis,Conjunctivitis

Notknown:Cornealreflexdecreased,Iridocyclitis,Keratitis,Visualdisturbance,Eye/Eyelidspruritus,Eye/Eyelid

oedema,Eyedischarge,Lacrimationincreased,dryeye.

CardiacDisorders

Notknown:Syncope,Bradycardia,Atrioventricularblock,Palpitations

VascularDisorders

Notknown:Hypotension

Respiratory,Thoracic,andMediastinalDisorders

Notknown:Asthma,Dyspnoea,Throatirritation,Nasaldiscomfort

GastrointestinalDisorders

Notknown:Nausea

SkinandSubcutaneousTissueDisorders

Notknown:Urticaria,Dermatitis,Rash,Erythema,Skinexfoliation,Lichenoidkeratosis,Pruritus

GeneralDisordersandAdministrationSiteConditions

Notknown:Faceoedema,Fatigue.

Thefollowingeventshavebeenreportedwithsystemicbeta-blockerformulationsandmayoccurwiththetopical

formulation:

NervousSystemDisorders:Sleepdisturbance

Psychiatricdisorders:Impotence,hallucinations,nightmares

CardiacDisorders:Cardiacfailure

VascularDisorders:Coldextremities,Raynaud'sphenomenon,worseningintermittentclaudication

GastrointestinalDisorders:Abdominalpainupper,vomiting,diarrhea

Respiratory,ThoracicandMediastinalDisorders:Bronchospasm

EndocrineDisorders:Hypoglycaemia

SkinandsubcutaneousTissueDisorders:Angioedema(Quincke'soedema),cutaneous(seesection4.4)andpsoriasis-

likesymptoms.

4.9Overdose

TherearenodataavailableonhumanoverdosagewithBetagan,whichisunlikelytooccurviatheocularroute.Should

accidentalocularoverdosageoccur,flushtheeye(s)withwaterornormalsaline.Ifaccidentallyingested,systemic

symptomsmayresultandeffortstodecreasefurtherabsorptionmaybeappropriate.Thesymptomsassociatedwith

systemicoverdosagearemostlikelytobebradycardia,hypotension,bronchospasmandcardiacfailure.Therapyfor

overdosageofabeta-adrenergicagentshouldbeinstituted,suchasintravenousadministrationofatropinesulphate0.25

to2mgtoinducevagalblockade.Conventionaltherapyforhypotension,bronchospasm,heartblockandcardiacfailure

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 06/09/2010 CRN 2083500 page number: 6

5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

SafetyandeffectivenessofBetaganinpaediatricpatientshavenotbeenestablished.

Levobunololisanon-cardioselectivebeta-adrenoceptorblockingagent,equipotentatbothbetaandbetareceptors.

Levobunololisgreaterthan60timesmorepotentthanitsdextroisomerinitsbeta-blockingactivity.

Inordertoobtainthehighestdegreeofbeta-blockingpotentialwithoutincreasingthepotentialfordirectmyocardial

depression,thelevoisomer,levobunolol,isused.Levobunololdoesnothavesignificantlocalanaesthetic(membrane-

stabilising)orintrinsicsympathomimeticactivity.BetaganhasshowntobeaseffectiveasTimololinlowering

intraocularpressure.

Betaganwheninstilledintheeyewilllowerelevatedintraocularpressureaswellasnormalintraocularpressure,

whetherornotaccompaniedbyglaucoma.Elevatedintraocularpressurepresentsamajorriskfactorinthepathogenesis

ofglaucomatousfieldloss.Thehigherthelevelofintraocularpressure,thelikelihoodofopticnervedamageandvisual

fieldloss.

Theprimarymechanismofactionoflevobunololinreducingintraocularpressureismostlikelyadecreaseinaqueous

humourproduction.Betaganreducesintraocularpressurewithlittleornoeffectonpupilsizeincontrasttothemiosis

whichcholinergicagentsareknowntoproduce.

TheblurredvisionandnightblindnessoftenassociatedwithmioticswouldnotbeexpectedwiththeuseofBetagan.

Patientswithcataractsavoidtheinabilitytoseearoundlenticularopacitiescausedbypupilconstriction.

5.2Pharmacokineticproperties

TheonsetofactionwithonedropofBetagancanbedetectedwithinonehourafterinstillation,withmaximumeffect

seenbetweentwoandsixhours.Asignificantdecreasecanbemaintainedforupto24hoursfollowingasingledose.

5.3Preclinicalsafetydata

Notapplicable.

6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

Poly(vinylalcohol)

Benzalkoniumchloride

Sodiummetabisulphite(E223)

Sodiumchloride

Disodiumedetate

Sodiumphosphate,dibasic,heptahydrate

Potassiumdihydrogenphosphate

Sodiumhydroxide(toadjustpH)or

Hydrochloricacid(toadjustpH)

Purifiedwater

6.2Incompatibilities

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 06/09/2010 CRN 2083500 page number: 7

6.3ShelfLife

Theshelf-lifeexpirydateofthisproductshallbethedateshownonthebottleandouterpackageoftheproductonthe

marketinthecountryoforigin.

6.4Specialprecautionsforstorage

Donotstoreabove25°C.

Keepthebottleintheoutercartoninordertoprotectfromlight.

6.5Natureandcontentsofcontainer

Whitebottleanddroppertipmadeoflowdensitypolyethylene.Thecapiseitheragreenorwhitepolystyrenecapora

white,polystyrenecompliancecap(C-Cap®)withanexternalrotatingsleeveindicatingdailydosagestatus.Eachhave

asafetysealtoensureintegrity.

Thebottlecontains5mlofsolution.

6.6Specialprecautionsfordisposalandotherhandling

Nospecialrequirements.

7PARALLELPRODUCTAUTHORISATIONHOLDER

B&SHealthcare

Unit4,BradfieldRoad

MiddlesexHA40NU

UnitedKingdom

8PARALLELPRODUCTAUTHORISATIONNUMBER

PPA1328/137/1

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

Dateoffirstauthorisation:3 rd

September2010

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 06/09/2010 CRN 2083500 page number: 8