BRIMON 2MG/ML EYE DROPS SOLUTION

Main information

  • Trade name:
  • BRIMON 2MG/ML EYE DROPS SOLUTION
  • Dosage:
  • 0.2 Per Cent
  • Pharmaceutical form:
  • Eye Drops Solution
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug

Documents

Localization

  • Available in:
  • BRIMON 2MG/ML EYE DROPS SOLUTION
    Ireland
  • Language:
  • English

Status

  • Source:
  • HPRA - Health Products Regulatory Authority - Ireland
  • Authorization number:
  • PA0711/119/001
  • Authorization date:
  • 12-10-2007
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

IRISHMEDICINESBOARDACTS1995AND2006

MEDICINALPRODUCTS(CONTROLOFPLACINGONTHEMARKET)REGULATIONS,2007

(S.I.No.540of2007)

PA0711/119/001

CaseNo:2073375

TheIrishMedicinesBoardinexerciseofthepowersconferredonitbytheabovementionedRegulationsherebygrantsto

RowexLtd

Bantry,Co.Cork,Ireland

anauthorisation,subjecttotheprovisionsofthesaidRegulations,inrespectoftheproduct

Brimon2mg/mlEyeDrops,Solution

TheparticularsofwhicharesetoutinPartIandPartIIoftheattachedSchedule.Theauthorisationisalsosubjecttothegeneralconditionsas

maybespecifiedinthesaidRegulationsaslistedonthereverseofthisdocument.

Thisauthorisation,unlesspreviouslyrevoked,shallcontinueinforcefrom20/05/2010until11/10/2012.

SignedonbehalfoftheIrishMedicinesBoardthis

________________

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PartII

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

Brimon2mg/mlEyeDrops,Solution

2QUALITATIVEANDQUANTITATIVECOMPOSITION

Eachmlcontains2mgbrimonidinetartrate(equivalenttobrimonidinebase1.3mg/ml).

Excipient(s):Benzalkoniumchloride0.05mg/ml.

Forafulllistofexcipients,seesection6.1.

3PHARMACEUTICALFORM

Eyedrops,solution.

Clear,colourlesstoyellowishsolution.

4CLINICALPARTICULARS

4.1TherapeuticIndications

Reductionofelevatedintraocularpressure(IOP)inpatientswithopenangleglaucomaorocularhypertension.

Asmonotherapyinpatientsinwhomtopicalbeta-blockertherapyiscontraindicated.

AsadjunctivetherapytootherintraocularpressureloweringmedicationswhenthetargetIOPisnotachievedwith

asingleagent(seesection5.1).

4.2Posologyandmethodofadministration

TherecommendeddoseisonedropofBrimonintheaffectedeye(s)twicedaily,approximately12hoursapart.No

dosageadjustmentisrequiredfortheuseinelderlypatients.

Aswithanyeyedrops,toreducepossiblesystemicabsorption,itisrecommendedthatthelachrymalsacbecompressed

atthemedialcanthus(punctalocclusion)foroneminute.Thisshouldbeperformedimmediatelyfollowingthe

instillationofeachdrop.

Ifmorethanonetopicalophthalmicdrugistobeused,thedifferentdrugsshouldbeinstilled5-15minutesapart.

Brimonidinehasnotbeenstudiedinpatientswithhepaticorrenalimpairment(seesection4.4).

Useinpaediatricsubjects

Noclinicalstudieshavebeenperformedinadolescents(12to17years).

Brimonidineisnotrecommendedforuseinchildrenbelow12yearsandiscontraindicatedinneonatesandinfants(less

than2yearsofage)(seesection4.3,section4.4andsection4.9).Itisknownthatsevereadversereactionscanoccurin

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4.3Contraindications

Neonatesandinfants

Hypersensitivitytobrimonidinetartrateortoanyoftheexcipients

Concomitanttreatmentwithmonoamineoxidase(MAO)inhibitortherapy

Concomitanttreatmentwithantidepressantswhichaffectnoradrenergictransmission(e.g.tricyclicantidepressants

andmianserin).

4.4Specialwarningsandprecautionsforuse

Cautionshouldbeexercisedintreatingpatientswithsevereorunstableanduncontrolledcardiovasculardisease.

Some(12.7%)patientsinclinicaltrialsexperiencedanocularallergictypereaction(seesection4.8fordetails).If

allergicreactionsareobserved,treatmentwithBrimonshouldbediscontinued.

Brimonshouldbeusedwithcautioninpatientswithdepression,cerebralorcoronaryinsufficiency,Raynaud's

phenomenon,orthostatichypotensionorthromboangiitisobliterans.

Brimonidinehasnotbeenstudiedinpatientswithhepaticorrenalimpairment;suchpatientsshouldbetreatedwith

caution.

Childrenof2yearsofageandabove,especiallythoseinthe2-7agerangeand/or

weighing<20kg,shouldbetreatedwithcautionandcloselymonitoredduetothehighincidenceofsomnolence(see

section4.8).

Contactlensesshouldberemovedpriortoapplication.Ithastobewaitedatleast15minutesbeforereinsertion.Known

todiscoloursoftcontactlenses.

ThepreservativeinBrimon,benzalkoniumchloride,maycauseeyeirritation.

4.5Interactionwithothermedicinalproductsandotherformsofinteraction

Althoughspecificdruginteractionsstudieshavenotbeenconductedwithbrimonidine,thepossibilityofanadditiveor

potentiatingeffectwithCNSdepressants(alcohol,barbiturates,opiates,sedatives,oranaesthetics)shouldbe

considered.

Nodataonthelevelofcirculatingcatecholaminesafterbrimonidineadministrationareavailable.Caution,however,is

advisedinpatientstakingmedicationswhichcanaffectthemetabolismanduptakeofcirculatingaminese.g.

chlorpromazine,methylphenidate,reserpine.

Aftertheapplicationofbrimonidine,clinicallyinsignificantdecreasesinbloodpressurewerenotedinsomepatients.

Cautionisadvisedwhenusingdrugssuchasantihypertensivesand/orcardiacglycosidesconcomitantlywith

brimonidine.

Cautionisadvisedwheninitiating(orchangingthedoseof)aconcomitantsystemicagent(irrespectiveof

pharmaceuticalform)whichmayinteractwith-adrenergicagonistsorinterferewiththeiractivityi.e.agonistsor

antagonistsoftheadrenergicreceptore.g.(isoprenaline,prazosin).

4.6Pregnancyandlactation

Pregnancy

Thesafetyofuseduringhumanpregnancyhasnotbeenestablished.Inanimalstudies,brimonidinetartratedidnot

causeanyteratogeniceffects.Inrabbits,brimonidinetartrate,atplasmalevelshigherthanareachievedduringtherapy

inhumans,hasbeenshowntocauseincreasedpreimplantationlossandpostnatalgrowthreduction.Brimonidine

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Breastfeeding

Itisunknownwhetherbrimonidineisexcretedinhumanmilk.Animalstudieshaveshownexcretionofbrimonidinein

rat’sbreastmilk.Brimonshouldnotbeusedbywomannursinginfants.

4.7Effectsonabilitytodriveandusemachines

Brimonidinemaycausefatigueand/ordrowsiness,whichmayimpairtheabilitytodriveoroperatemachinery.Itmay

causeblurredand/orabnormalvision,whichmayimpairtheabilitytodriveortousemachinesespeciallyatnightorin

reducedlighting.Thepatientshouldwaituntilthesesymptomshaveclearedbeforedrivingorusingmachinery.

4.8Undesirableeffects

ThemostcommonlyreportedADRsareoraldryness,ocularhyperaemiaandburning/stinging,alloccurringin22to

25%ofpatients.Theyareusuallytransientandnotcommonlyofaseverityrequiringdiscontinuationoftreatment.

Symptomsofocularallergicreactionsoccurredin12.7%ofsubjects(causingwithdrawalin11.5%ofsubjects)in

clinicaltrialswiththeonsetbetween3and9monthsinthemajorityofpatients.

Withineachfrequencygrouping,undesirableeffectsarepresentedinorderofdecreasingseriousness.Thefollowing

terminologieshavebeenusedinordertoclassifytheoccurrenceofundesirableeffects: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).

Immunesystem

disorders Uncommon:

(1/1,000,<1/100) - Systemicallergicreactions

Psychiatricdisorders Uncommon:

(>1/1,000,<1/100) - Depression

VeryRare:

(<1/10,000) - Insomnia

Nervoussystem

disorders VeryCommon:

(>1/10) - Headache

-drowsiness

Common:

(>1/100,<1/10) - Dizziness

Abnormaltaste

VeryRare:

(<1/10,000) - syncope

Eyedisorders VeryCommon:

(>1/10) - ocularirritationincluding

allergicreactions(hyperaemia,

burningandstinging,pruritis,

foreignbodysensation,

conjunctivalfollicles).

blurredvision.

Common:

(>1/100,<1/10) - localirritation(eyelid

hyperaemiaandoedema,

blepharitis,conjunctival

oedemaanddischarge,ocular

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Incaseswherebrimonidinehasbeenusedaspartofthemedicaltreatmentofcongenitalglaucoma,symptomsof

brimonidineoverdosesuchaslossofconsciousness,hypotension,hypotonia,bradycardia,hypothermia,cyanosisand

apnoeahavebeenreportedinneonatesandinfantsreceivingbrimonidine(seesection4.3).Ina3-month,phase3study

inchildrenaged2-7yearswithglaucoma,inadequatelycontrolledbybeta-blockers,ahighprevalenceofsomnolence

(55%)wasreportedwithbrimonidineasadjunctivetreatment.In8%ofchildren,thiswassevereandledto

discontinuationoftreatmentin13%.Theincidenceofsomnolencedecreasedwithincreasingage,beingleastinthe7-

year-oldagegroup(25%),butwasmoreaffectedbyweight,occurringmorefrequentlyinthosechildrenweighing<20

kg(63%)comparedtothoseweighing>20kg(25%)(seesection4.4).

4.9Overdose

Ophthalmicoverdose:

Thereisnoexperienceinadultswiththeunlikelycaseofanoverdosageviatheophthalmicroute.However,symptoms

ofbrimonidineoverdose(includinglossofconsciousness,hypotension,hypotonia,bradycardia,hypothermia,cyanosis

andapnoea)havebeenreportedinneonatesandinfantsreceivingbrimonidineeyedropsaspartofmedicaltreatmentof

photophobia

cornealerosionandstaining

oculardryness

conjunctivalblanching

abnormalvision

conjunctivitis.

VeryRare:

(<1/10,000) - Iritis(anterioruveitis)

Miosis

Cardiacdisorders Uncommon:

(>1/1,000,<1/100) - Palpitations/arrythmias

(includingbradycardiaand

tachycardia)

Vasculardisorders VeryRare:

(<1/10,000) - Hypertension

Hypotension

Respiratory,thoracic

andmediastinal

disorders Common:

(>1/100,<1/10) - Upperrespiratorysymptoms

Uncommon:

(>1/1,000,<1/100) - Nasaldryness

Rare:

(>1/10,000,<1/1,000) - Dyspnoea

Gastrointestinal

disorders VeryCommon:

(>1/10) - Oraldryness

Common:

(>1/100,<1/10) - Gastrointestinalsymptoms

Generaldisordersand

administrativesite

condition VeryCommon:

(>1/10) Fatiguer

Common:

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Systemicoverdoseresultingfromaccidentalingestion:

Onereportofaccidentalhumanadultingestionofbrimonidineeyedropshasbeenreceived.Thepatientingestedabout

10drops.Heexperiencedahypotensiveepisodeafewhoursaftertheingestionandthenareboundhypertension

approximately8hoursafteringestion.

ReportsofseriousadverseeffectsfollowinginadvertentingestionofBrimonidinebypaediatricsubjectshavebeen

publishedorreported.ThesubjectsexperiencedsymptomsofCNSdepression,typicallytemporarycomaorlowlevel

ofconsciousness,hypotonia,bradycardia,hypothermiaandapnoea,andrequiredadmissiontointensivecarewith

intubationifindicated.Allsubjectswerereportedtohavemadeafullrecovery,usuallywithin6-24hours.

Oraloverdosesofotheralpha-2-agonistshavebeenreportedtocausesymptomssuchashypotension,asthenia,

vomiting,lethargy,sedation,bradycardia,arrhythmias,miosis,apnoea,hypotonia,hypothermia,respiratorydepression

andseizure.

5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

Pharmacotherapeuticgroup:Sympathomimeticsinglaucomatherapy,ATCcode:S01EA05

Brimonidineisanalpha-2adrenergicreceptoragonistthatis1000-foldmoreselectiveforthealpha-2adrenoceptor

thanthealpha-1adrenoreceptor.Thisselectivityresultsinnomydriasisandtheabsenceofvasoconstrictionin

microvesselsassociatedwithhumanretinalxenografts.

Topicaladministrationofbrimonidinetartratedecreasesintraocularpressure(IOP)inhumanswithminimaleffecton

cardiovascularorpulmonaryparameters.

Limiteddataareavailableforpatientswithbronchialasthmashowingnoadverseeffects.

Brimonidineeyedropshasarapidonsetofaction,withpeakocularhypotensiveeffectseenattwohourspost-dosing.

Intwo1yearstudies,thesedropsloweredIOPbymeanvaluesofapproximately4-6mmHg.

Fluorophotometricstudiesinanimalsandhumanssuggestthatbrimonidinetartratehasadualmechanismofaction.It

isthoughtthatbrimonidinemaylowerIOPbyreducingaqueoushumourformationandenhancinguveoscleraloutflow.

Clinicaltrialsshowthatbrimonidineeyedropsareeffectiveincombinationwithtopicalbeta-blockers.Shorterterm

studiesalsosuggestthatthesedropshasaclinicallyrelevantadditiveeffectincombinationwithtravoprost(6weeks)

andlatanoprost(3months).

5.2Pharmacokineticproperties

Generalcharacteristics

Afterocularadministrationofa0.2%solutiontwicedailyfor10days,plasmaconcentrationswerelow(meanC

was0.06ng/ml).Therewasaslightaccumulationinthebloodaftermultiple(2timesdailyfor10days)instillations.

Theareaundertheplasmaconcentration-timecurveover12hoursatsteadystate(AUC

0-12h )was0.31ng·hr/ml,as

comparedto0.23ng·hr/mlafterthefirstdose.Themeanapparenthalf-lifeinthesystemiccirculationwas

approximately3hoursinhumansaftertopicaldosing.

Theplasmaproteinbindingofbrimonidineaftertopicaldosinginhumansisapproximately29%.

Brimonidinebindsreversiblytomelanininoculartissues,invitroandinvivo.Following2weeksofocularinstillation,

theconcentrationsofbrimonidineiniris,ciliarybodyandchoroid-retinawere3-to17-foldhigherthanthoseaftera

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Thesignificanceofmelaninbindinginhumansisunclear.However,nosignificantocularadversereactionwasfound

duringbiomicroscopicexaminationofeyesinpatientstreatedwithbrimonidinetartrateforuptooneyear,norwas

significantoculartoxicityfoundduringaoneyearocularsafetystudyinmonkeysgivenapproximatelyfourtimesthe

recommendeddoseofbrimonidinetartrate.

Followingoraladministrationtoman,brimonidineiswellabsorbedandrapidlyeliminated.Themajorpartofthedose

(around75%ofthedose)wasexcretedasmetabolitesinurinewithinfivedays;nounchangeddrugwasdetectedin

urine.Invitrostudies,usinganimalandhumanliver,indicatethatthemetabolismismediatedlargelybyaldehyde

oxidaseandcytochromeP450.Hence,thesystemiceliminationseemstobeprimarilyhepaticmetabolism.

NogreatdeviationfromdoseproportionalityforplasmaC

andAUCwasobservedfollowingasingletopicaldose

of0.08%,0.2%and0.5%.

Characteristicsinpatients

Characteristicsinelderlypatients:

TheC

,AUC,andapparenthalf-lifeofbrimonidinearesimilarintheelderly(subjects65yearsorolder)aftera

singledosecomparedwithyoungadults,indicatingthatitssystemicabsorptionandeliminationarenotaffectedbyage.

Basedondatafroma3monthclinicalstudy,whichincludedelderlypatients,systemicexposuretobrimonidinewas

verylow.

5.3Preclinicalsafetydata

Non-clinicaldatarevealnospecialhazardforhumansbasedonconventionalstudiesofsafetypharmacology,repeated

dosetoxicity,genotoxicity,carcinogenicpotential,toxicitytoreproduction.

6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

Benzalkoniumchloride

Polyvinylalcohol

Sodiumchloride

Sodiumcitrate,dihydrate

Citricacid,monohydrate

Waterforinjection

HydrochloricacidandsodiumhydroxidetoadjustpH.

6.2Incompatibilities

Notapplicable.

6.3ShelfLife

Unopened:2years.

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6.4Specialprecautionsforstorage

Thismedicinalproductdoesnotrequireanyspecialstorageconditions

6.5Natureandcontentsofcontainer

White,opaque,sterile,plasticbottleforophthalmicmadeofpolyethylenewithsterileplasticdropperandsterilecap

madeofpolyethylene:5mlx1,5mlx2,5mlx3and5mlx6.

Notallpacksizesmaybemarketed.

6.6Specialprecautionsfordisposalandotherhandling

Nospecialrequirements.

7MARKETINGAUTHORISATIONHOLDER

RowexLtd

Newtown

Bantry

CountyCork

8MARKETINGAUTHORISATIONNUMBER

PA711/119/1

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

DateofFirstAuthorisation:12thOctober2007

10DATEOFREVISIONOFTHETEXT

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