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:
  • PPA1562/056/001
  • Authorization date:
  • 26-08-2011
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

Betagan0.5%w/vEyeDrops,Solution

2QUALITATIVEANDQUANTITATIVECOMPOSITION

Onemlsolutioncontains5.0mglevobunololhydrochloride,equivalentto4.4mglevobunolol.

Excipient(s):Containsbenzalkoniumchloride0.04mg/ml.

Forafulllistofexcipients,seesection6.1

3PHARMACEUTICALFORM

EyeDrops,Solution

ProductimportedfromtheUK:

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.

IfBetaganistoreplaceacombinationofanti-glaucomaproducts,onlyasingleproductshouldberemovedatatime.

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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

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Aswithsystemicbeta-blockers,ifdiscontinuationoftreatmentisneededinpatientswithcoronaryheartdisease,

therapyshouldbewithdrawngraduallytoavoidrhythmdisorders,myocardialinfarctionorsuddendeath.

Choroidaldetachmentafterfiltrationprocedureshasbeenreportedwithadministrationofaqueoussuppressanttherapy

(e.g.timolol,acetazolamide).

InpatientswithchroniceyeinflammationandcornealdystropyBetaganshouldonlybeappliedintheeventofstringent

diagnosis&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

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CautionmustbeexercisedifBetaganisusedconcomitantlywithiodinecontrastproductsorintravenously

administeredlidocaine.

Cimetidinemayincreasetheplasmaconcentrationsoflevobunolol.

NodataonthelevelofcirculatingcatecholaminesafterBetaganadministeredareavailable.Caution,however,is

advisedinpatientstakingmedicationwhichcaneffectthemetabolismanduptakeofcirculatingaminese.g.

chlorpromazine,methylphenidate,reserpinebecauseofpossibleadditiveeffectsandtheproductionofhypotension

and/ormarkedbradycardia,whichmayproducevertigo,syncopeorposturalhypotension.

AlthoughspecificdruginteractionsstudieshavenotbeenconductedwithBetagan,knownadditiveIOPloweringeffect

withprostamides,prostaglandins,alpha-agonists,carbonicanhydraseinhibitorsandpilocarpineshouldbeconsidered.

4.6Fertility,pregnancyandlactation

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

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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

maybenecessary.

5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

SafetyandeffectivenessofBetaganinpaediatricpatientshavenotbeenestablished.

Levobunololisanon-cardioselectivebeta-adrenoceptorblockingagent,equipotentatbothbetaandbetareceptors.

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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

Sodiumphosphatedibasicheptahydrate

Potassiumdihydrogenphosphate

Sodiumhydroxide(toadjustph)or

Hydrochloricacid(toadjustph)

Purifiedwater

6.2Incompatibilities

Notapplicable.

6.3Shelflife

TheshelflifeexpirydateforthisproductshallbethedateshownontheBottleandouterpackageoftheproductonthe

marketinthecountryoforigin.

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6.4Specialprecautionsforstorage

Donotstoreabove25 o

C.Keepthebottleintheoutercartoninordertoprotectfromlight.

6.5Natureandcontentsofcontainer

Bottleanddroppertipmadeoflowdensitypolyethylene.Thecapiseithera''traditional'',highimpact,polystyrenecap

orahighimpact,polystyrenecompliancecap(C-Cap)withanexternalrotatingsleeveindicatingdailydosagestatus.

Bothhaveasafetysealtoensureintegrity.

5mlBottles.

6.6Specialprecautionsfordisposalofausedmedicinalproductorwastematerialsderivedfrom

suchmedicinalproductandotherhandlingoftheproduct

Nospecialrequirements.

7PARALLELPRODUCTAUTHORISATIONHOLDER

LTTPharmaLimited

Unit18,OxleasowRoad

EastMoonsMoat

Redditch

WorcestershireB980RE

UnitedKingdom

8PARALLELPRODUCTAUTHORISATIONNUMBER

PPA1562/056/001

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

Thedateoffirstauthorisation:26 th

August2011

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