DORTIM

Main information

  • Trade name:
  • DORTIM Eye Drops Solution 20 + 5
  • Dosage:
  • 20 + 5
  • Pharmaceutical form:
  • Eye Drops Solution
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug

Documents

Localization

  • Available in:
  • DORTIM Eye Drops Solution 20 + 5
    Ireland
  • Language:
  • English

Status

  • Source:
  • HPRA - Health Products Regulatory Authority - Ireland
  • Authorization number:
  • PA0749/079/001
  • Authorization date:
  • 02-07-2010
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

Dortim20mg/ml+5mg/mlEyeDropsSolution

2QUALITATIVEANDQUANTITATIVECOMPOSITION

Eachmillilitrecontains20mgofdorzolamideasdorzolamidehydrochlorideand5mgoftimololastimololmaleate.

Excipients

Eachmlcontains0.075mgbenzalkoniumchloride.

Forafulllistofexcipients,seesection6.1.

3PHARMACEUTICALFORM

Eyedrops,solution.

Colourless,clear,viscoussolution,freefromvisibleparticles.

4CLINICALPARTICULARS

4.1TherapeuticIndications

Thismedicinalproductisindicatedinthetreatmentofelevatedintra-ocularpressure(IOP)inpatientswithopen-angle

glaucomaorpseudo-exfoliativeglaucomawhentopicalbeta-blockermonotherapyisnotsufficient.

4.2Posologyandmethodofadministration

ThedoseisonedropofDortiminthe(conjunctivalsacofthe)affectedeye(s)twotimesdaily.

Ifanothertopicalophthalmicagentisbeingused,Dortimandtheotheragentshouldbeadministeredatleastten

minutesapart.

Patientsshouldbeinstructedtowashtheirhandsbeforeuseandavoidallowingthetipofthedispensingcontainerto

comeintocontactwiththeeyeorsurroundingstructures.

Patientsshouldalsobeinstructedthatocularsolutions,ifhandledimproperly,canbecomecontaminatedbycommon

bacteriaknowntocauseocularinfections.Seriousdamagetotheeyeandsubsequentlossofvisionmayresultfrom

usingcontaminatedsolutions.

Usageinstructions

1.Beforeusingthemedicationforthefirsttime,besurethetampersealisunbroken.

2.Toopenthebottle,unscrewthecap.

3.Tiltyourheadbackandpullyourlowereyeliddownslightlytoformapocketbetweenyoureyelid

andeye.

4.Invertthebottle,andpresslightlyonthesidesofthebottleuntilasingledropisdispensedintothe

eyeasdirectedbyyourdoctor.DONOTTOUCHYOUREYEOREYELIDWITHTHEDROPPERTIP.

5.Repeatsteps3&4withtheothereyeifinstructedtodosobyyourdoctor.

6.Replacethecapbyturninguntilitisfirmlytouchingthebottle.

7.Thedispensertipisdesignedtoprovideapre-measureddrop;therefore,donotenlargetheholeof

thedispensertip.

Paediatricuse

Efficacyinpaediatricpatientshasnotbeenestablished.

Safetyinpaediatricpatientsbelowtheageoftwoyearshasnotbeenestablished.(Forinformation

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4.3Contraindications

Thismedicinalproductiscontra-indicatedinpatientswith:

hypersensitivitytooneorbothactivesubstancesortoanyoftheexcipients

reactiveairwaydisease,includingbronchialasthmaorahistoryofbronchialasthma,orseverechronic

obstructivepulmonary

sinusbradycardia,second-orthird-degreeatrioventricularblock,overtcardiacfailure,cardiogenic

shock

severerenalimpairment(CrCl<30ml/min)orhyperchloraemicacidosis

Theabovearebasedonthecomponentsandarenotuniquetothecombination.

4.4Specialwarningsandprecautionsforuse

Cardiovascular/respiratoryreactions

Aswithothertopically-appliedophthalmicagents,theactivesubstancesmaybeabsorbedsystemically.Thetimolol

componentisabeta-blocker.Therefore,thesametypesofadversereactionsfoundwithsystemicadministrationof

beta-blockersmayoccurwithtopicaladministration,includingworseningofPrinzmetal'sangina,worseningofsevere

peripheralandcentralcirculatorydisorders,andhypotension.

Becauseofthetimololmaleatecomponent,cardiacfailureshouldbeadequatelycontrolledbeforebeginningtherapy

withDortim.Inpatientswithahistoryofseverecardiacdisease,signsofcardiacfailureshouldbewatchedforand

pulseratesshouldbechecked.

Respiratoryreactionsandcardiacreactions,includingdeathduetobronchospasminpatientswithasthmaandrarely

deathinassociationwithcardiacfailure,havebeenreportedfollowingadministrationoftimololmaleate.

Hepaticimpairment

Dortimhasnotbeenstudiedinpatientswithhepaticimpairmentandthereforeshouldbeusedwithcautioninsuch

patients.

Immunologyandhypersensitivity

Aswithothertopically-appliedophthalmicagents,theactivesubstancesmaybeabsorbedsystemically.Dorzolamide

containsasulphonamidogroup,whichalsooccursinsulphonamides.Thereforethesametypesofadversereactions

foundwithsystemicadministrationofsulphonamidesmayoccurwithtopicaladministration.Ifsignsofserious

reactionsorhypersensitivityoccur,discontinueuseofthispreparation.

Localocularadverseeffects,similartothoseobservedwithdorzolamidehydrochlorideeyedrops,havebeenseenwith

Dortim.Ifsuchreactionsoccur,discontinuationofDortimshouldbeconsidered.

Whiletaking-blockers,patientswithahistoryofatopyorahistoryofsevereanaphylacticreactiontoavarietyof

allergensmaybemorereactivetoaccidental,diagnostic,ortherapeuticrepeatedchallengewithsuchallergens.Such

patientsmaybeunresponsivetotheusualdosesofepinephrineusedtotreatanaphylacticreactions.

Concomitanttherapy

Thefollowingconcomitantmedicationisnotrecommended:

−dorzolamideandoralcarbonicanhydraseinhibitors

−topicalbeta-adrenergicblockingagents.

Withdrawaloftherapy

Aswithsystemicbeta-blockers,ifdiscontinuationofophthalmictimololisneededinpatientswithcoronaryheart

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Additionaleffectsofbeta-blockade

Therapywithbeta-blockersmaymaskcertainsymptomsofhypoglycaemiainpatientswithdiabetesmellitusor

hypoglycaemia.

Therapywithbeta-blockersmaymaskcertainsymptomsofhyperthyroidism.Abruptwithdrawalofbeta-blocker

therapymayprecipitateaworseningofsymptoms.

Therapywithbeta-blockersmayaggravatesymptomsofmyastheniagravis.

Additionaleffectsofcarbonicanhydraseinhibition

Therapywithoralcarbonicanhydraseinhibitorshasbeenassociatedwithurolithiasisasaresultofacid-base

disturbances,especiallyinpatientswithapriorhistoryofrenalcalculi.Althoughnoacid-basedisturbanceshavebeen

observedwithDortim,urolithiasishasbeenreportedinfrequently.BecauseDortimcontainsatopicalcarbonic

anhydraseinhibitorthatisabsorbedsystemically,patientswithapriorhistoryofrenalcalculimaybeatincreasedrisk

ofurolithiasiswhileusingDortim.

Other

Themanagementofpatientswithacuteangle-closureglaucomarequirestherapeuticinterventionsinadditiontoocular

hypotensiveagents.Dortimhasnotbeenstudiedinpatientswithacuteangle-closureglaucoma.

Cornealoedemaandirreversiblecornealdecompensationhavebeenreportedinpatientswithpre-existingchronic

cornealdefectsand/orahistoryofintra-ocularsurgerywhileusingdorzolamide.Topicaldorzolamideshouldbeused

withcautioninsuchpatients.

Choroidaldetachmentconcomitantwithocularhypotonyhavebeenreportedafterfiltrationprocedureswith

administrationofaqueoussuppressanttherapies.

Aswiththeuseofotherantiglaucomaagents,diminishedresponsivenesstoophthalmictimololmaleateafterprolonged

therapyhasbeenreportedinsomepatients.However,inclinicalstudiesinwhich164patientshavebeenfollowedfor

atleastthreeyears,nosignificantdifferenceinmeanintra-ocularpressurehasbeenobservedafterinitialstabilisation.

Contactlensuse

Dortimcontainsthepreservativebenzalkoniumchloride,whichmaycauseeyeirritation.Avoidcontactwithsoft

contactlenses.Removecontactlensespriortoapplicationandwaitatleast15minutesbeforereinsertion.

Benzalkoniumchlorideisknowntodiscoloursoftcontactlenses.

Paediatricuse

Seesection5.1.

4.5Interactionwithothermedicinalproductsandotherformsofinteraction

SpecificinteractionstudieshavenotbeenperformedwithDortim.

However,thepotentialexistsforadditiveeffectsandproductionofhypotensionand/ormarkedbradycardiawhen

timololmaleateophthalmicsolutionisadministeredtogetherwithoralcalciumchannelblockers,catecholamine-

depletingorbeta-adrenergicblockingagents,antiarrhythmics(includingamiodarone),digitalisglycosides,

parasympathomimetics,narcotics,andmonoamineoxidase(MAO)inhibitors.

Potentiatedsystemicbeta-blockade(e.g.,decreasedheartrate,depression)hasbeenreportedduringcombined

treatmentwithCYP2D6inhibitors(e.g.quinidine,SSRIs)andtimolol.

AlthoughDortimalonehaslittleornoeffectonpupilsize,mydriasisresultingfromconcomitantuseofophthalmic

timololmaleateandepinephrine(adrenaline)hasbeenreportedoccasionally.

Beta-blockersmayincreasethehypoglycaemiceffectofantidiabeticagents.

Oralbeta-adrenergicblockingagentsmayexacerbatethereboundhypertensionwhichcanfollowthewithdrawalof

clonidine.

Inclinicalstudies,Dortimwasusedconcomitantlywiththefollowingsystemicmedicationswithoutevidenceof

adverseinteractions:ACE-inhibitors,calciumchannelblockers,diuretics,non-steroidalanti-inflammatorydrugs

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4.6Fertility,pregnancyandlactation

Useduringpregnancy

Dortimshouldnotbeusedduringpregnancy.

Dorzolamide

Noadequateclinicaldatainexposedpregnanciesareavailable.Inrabbits,dorzolamideproducedteratogeniceffectsat

maternotoxicdoses(seesection5.3).

Timolol

Well-controlledepidemiologicalstudieswithsystemicbeta-blockersshowednoevidenceofteratogeniceffects,but

somepharmacologicaleffectssuchasbradycardiawereobservedinfetusesorneonates.IfDortimisadministereduntil

delivery,theneonateshouldbecarefullymonitoredduringthefirstdaysoflife.

Useduringlactation

Itisnotknownwhetherdorzolamideisexcretedinhumanmilk.Inlactatingratsreceivingdorzolamide,decreasesin

thebodyweightgainofoffspringwereobserved.Timololdoesappearinhumanmilk.IftreatmentwithDortimis

required,thenlactationisnotrecommended.

4.7Effectsonabilitytodriveandusemachines

Nostudiesontheeffectsontheabilitytodriveandusemachineshavebeenperformed.Possiblesideeffectssuchas

blurredvisionmayaffectsomepatients'abilitytodriveand/oroperatemachinery.

4.8Undesirableeffects

InclinicalstudiesnoadverseexperiencesspecifictoDortimhavebeenobserved;adverseexperienceshavebeen

limitedtothosethatwerereportedpreviouslywithdorzolamidehydrochlorideand/ortimololmaleate.

Duringclinicalstudies,1,035patientsweretreatedwithDortim.Approximately2.4%ofallpatientsdiscontinued

therapywithDortimbecauseoflocalocularadversereactions,approximately1.2%ofallpatientsdiscontinuedbecause

oflocaladversereactionssuggestiveofallergyorhypersensitivity(suchaslidinflammationandconjunctivitis).

ThefollowingadversereactionshavebeenreportedwithDortimoroneofitscomponentseitherduringclinicaltrialsor

duringpost-marketingexperience:

[VeryCommon:( ≥1/10),Common:(≥1/100to<1/10),Uncommon:(≥1/1000to<1/100),andRare:(≥1/10,000to

<1/1000)]

Nervoussystemdisorders:

Dorzolamidehydrochlorideeyedrops,solution:

Common: headache*

Rare: dizziness*,paresthesia*

Timololmaleateeyedrops,solution:

Common: headache*

Uncommon: dizziness*,depression*

Rare: insomnia*,nightmares*,memoryloss,

paraesthesia*,increaseinsignsand

symptomsofmyastheniagravis,decreased

libido*,cerebrovascularaccident*

Eyedisorders:

Dortim:

VeryCommon: burningandstinging

Common: conjunctivalinjection,blurredvision,corneal

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Dorzolamidehydrochlorideeyedrops,solution:

Common: eyelidinflammation*,eyelidirritation*

Uncommon: iridocyclitis*

Rare: irritationincludingredness*,pain*,eyelid

crusting*,transientmyopia(whichresolved

upondiscontinuationoftherapy),corneal

oedema*,ocularhypotony*,choroidal

detachment(followingfiltrationsurgery)*

Timololmaleateeyedrops,solution:

Common: signsandsymptomsofocularirritation

includingblepharitis*,keratitis*,decreased

cornealsensitivity,anddryeyes*

Uncommon: visualdisturbancesincludingrefractivechanges

(duetowithdrawalofmiotictherapyinsome

cases)*

Rare: ptosis,diplopia,choroidaldetachment

(followingfiltrationsurgery)*

Earandlabyrinthdisorders:

Timololmaleateeyedrops,solution:

Rare: tinnitus*

Cardiacandvasculardisorders:

Timololmaleateeyedrops,solution:

Uncommon: bradycardia*,syncope*

Rare: hypotension*,chestpain*,palpitation*,

oedema*,arrhythmia*,congestiveheart

failure*,heartblock*,cardiacarrest*,cerebral

ischaemia,claudication,Raynaud's

phenomenon*,coldhandsandfeet*

Respiratory,thoracic,andmediastinaldisorders:

Dortim:

Common: sinusitis

Rare: shortnessofbreath,respiratoryfailure,

rhinitis

Dorzolamidehydrochlorideeyedrops,solution:

Rare: epistaxis*

Timololmaleateeyedrops,solution:

Uncommon: dyspnoea*

Rare: bronchospasm(predominantlyinpatients

withpre-existingbronchospasticdisease)*,

cough*

Gastro-intestinaldisorders:

Dortim:

VeryCommon: tasteperversion

Dorzolamidehydrochlorideeyedrops,solution:

Common: nausea*

Rare: throatirritation,drymouth*

Timololmaleateeyedrops,solution:

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*TheseadversereactionswerealsoobservedwithDortimduringpost-marketingexperience.

Laboratoryfindings

Dortimwasnotassociatedwithclinicallymeaningfulelectrolytedisturbancesinclinicalstudies.

4.9Overdose

NodataareavailableinhumansinregardtooverdosebyaccidentalordeliberateingestionofDortim.

Therehavebeenreportsofinadvertentoverdoseswithtimololmaleateophthalmicsolutionresultinginsystemiceffects

similartothoseseenwithsystemicbeta-adrenergicblockingagentssuchasdizziness,headache,shortnessofbreath,

bradycardia,bronchospasm,andcardiacarrest.Themostcommonsignsandsymptomstobeexpectedwithoverdoses

ofdorzolamideareelectrolyteimbalance,developmentofanacidoticstate,andpossiblycentralnervoussystemeffects.

Onlylimitedinformationisavailablewithregardtohumanoverdosebyaccidentalordeliberateingestionof

dorzolamidehydrochloride.Withoralingestion,somnolencehasbeenreported.Withtopicalapplicationthefollowing

havebeenreported:nausea,dizziness,headache,fatigue,abnormaldreams,anddysphagia.

Treatment

Treatmentshouldbesymptomaticandsupportive.Serumelectrolytelevels(particularlypotassium)andbloodpH

Rare: diarrhoea,drymouth*

Skinandsubcutaneoustissuedisorders:

Dortim:

Rare: contactdermatitis

Dorzolamidehydrochlorideeyedrops,solution:

Rare: rash*

Timololmaleateeyedrops,solution:

Rare: alopecia*,psoriasiformrashorexacerbationof

psoriasis*

Renalandurinarydisorders:

Dortim:

Uncommon: urolithiasis

Reproductivesystemandbreastdisorders:

Timololmaleateeyedrops,solution:

Rare: Peyronie'sdisease*

Generaldisordersandadministrationsitedisorders:

Dortim:

Rare: signsandsymptomsofsystemic

allergicreactions,including

angioedema,urticaria,pruritus,rash,

anaphylaxis,rarelybronchospasm

Dorzolamidehydrochlorideeyedrops,solution:

Common: asthenia/fatigue*

Timololmaleateophthalmicsolution:

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5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

Pharmacotherapeuticgroup:

(Antiglaucomapreparationsandmiotics-Beta-BlockingAgents)

ATCcode:S01ED51

Mechanismofaction

Dortimiscomprisedoftwocomponents:dorzolamidehydrochlorideandtimololmaleate.Eachofthesetwo

componentsdecreaseselevatedintra-ocularpressurebyreducingaqueoushumorsecretion,butdoessobyadifferent

mechanismofaction.

DorzolamidehydrochlorideisapotentinhibitorofhumancarbonicanhydraseII.Inhibitionofcarbonicanhydrasein

theciliaryprocessesoftheeyedecreasesaqueoushumorsecretion,presumablybyslowingtheformationof

bicarbonateionswithsubsequentreductioninsodiumandfluidtransport.Timololmaleateisanon-selectivebeta-

adrenergicreceptorblockingagent.Theprecisemechanismofactionoftimololmaleateinloweringintra-ocular

pressureisnotclearlyestablishedatthistime,althoughafluoresceinstudyandtonographystudiesindicatethatthe

predominantactionmayberelatedtoreducedaqueousformation.However,insomestudiesaslightincreaseinoutflow

facilitywasalsoobserved.Thecombinedeffectofthesetwoagentsresultsinadditionalintra-ocularpressurereduction

comparedtoeithercomponentadministeredalone.

Followingtopicaladministration,Dortimreduceselevatedintra-ocularpressure,whetherornotassociatedwith

glaucoma.Elevatedintra-ocularpressureisamajorriskfactorinthepathogenesisofopticnervedamageand

glaucomatousvisualfieldloss.Dortimreducesintra-ocularpressurewithoutthecommonsideeffectsofmioticssuch

asnightblindness,accommodativespasmandpupillaryconstriction.

Pharmacodynamiceffects

Clinicaleffects:

Clinicalstudiesofupto15monthsdurationwereconductedtocomparetheIOP-loweringeffectofDortimb.i.d.

(dosedmorningandbedtime)toindividually-andconcomitantly-administered0.5%timololand2.0%dorzolamidein

patientswithglaucomaorocularhypertensionforwhomconcomitanttherapywasconsideredappropriateinthetrials.

Thisincludedbothuntreatedpatientsandpatientsinadequatelycontrolledwithtimololmonotherapy.Themajorityof

patientsweretreatedwithtopicalbeta-blockermonotherapypriortostudyenrollment.Inananalysisofthecombined

studies,theIOP-loweringeffectofDortimb.i.d.wasgreaterthanthatofmonotherapywitheither2%dorzolamidet.i.d.

or0.5%timololb.i.d.TheIOP-loweringeffectofDortimb.i.d.wasequivalenttothatofconcomitanttherapywith

dorzolamideb.i.d.andtimololb.i.d.TheIOP-loweringeffectofDortimb.i.d.wasdemonstratedwhenmeasuredat

varioustimepointsthroughoutthedayandthiseffectwasmaintainedduringlong-termadministration.

Paediatricuse

Athreemonthcontrolledstudy,withtheprimaryobjectiveofdocumentingthesafetyof2%dorzolamide

hydrochlorideophthalmicsolutioninchildrenundertheageof6yearshasbeenconducted.Inthisstudy,30patients

undersixandgreaterthanorequaltotwoyearsofagewhoseIOPwasnotadequatelycontrolledwithmonotherapyby

dorzolamideortimololreceivedDortiminanopenlabelphase.Efficacyinthosepatientshasnotbeenestablished.In

thissmallgroupofpatients,twicedailyadministrationofDortimwasgenerallywelltoleratedwith19patients

completingthetreatmentperiodand11patientsdiscontinuingforsurgery,achangeinmedication,orotherreasons.

5.2Pharmacokineticproperties

Dorzolamidehydrochloride:

Unlikeoralcarbonicanhydraseinhibitors,topicaladministrationofdorzolamidehydrochlorideallowsfortheactive

substancetoexertitseffectsdirectlyintheeyeatsubstantiallylowerdosesandthereforewithlesssystemicexposure.

Inclinicaltrials,thisresultedinareductioninIOPwithouttheacid-basedisturbancesoralterationsinelectrolytes

characteristicoforalcarbonicanhydraseinhibitors.

Whentopicallyapplied,dorzolamidereachesthesystemiccirculation.Toassessthepotentialforsystemiccarbonic

anhydraseinhibitionfollowingtopicaladministration,activesubstanceandmetaboliteconcentrationsinredbloodcells

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DorzolamideaccumulatesinRBCsduringchronicdosingasaresultofselectivebindingtoCA-IIwhileextremelylow

concentrationsoffreeactivesubstanceinplasmaaremaintained.TheparentactivesubstanceformsasingleN-desethyl

metabolitethatinhibitsCA-IIlesspotentlythantheparentactivesubstancebutalsoinhibitsalessactiveisoenzyme

(CA-I).ThemetabolitealsoaccumulatesinRBCswhereitbindsprimarilytoCA-I.Dorzolamidebindsmoderatelyto

plasmaproteins(approximately33%).Dorzolamideisprimarilyexcretedunchangedintheurine;themetaboliteisalso

excretedinurine.Afterdosingends,dorzolamidewashesoutofRBCsnon-linearly,resultinginarapiddeclineof

activesubstanceconcentrationinitially,followedbyaslowereliminationphasewithahalf-lifeofaboutfourmonths.

Whendorzolamidewasgivenorallytosimulatethemaximumsystemicexposureafterlong-termtopicalocular

administration,steadystatewasreachedwithin13weeks.Atsteadystate,therewasvirtuallynofreeactivesubstance

ormetaboliteinplasma;CAinhibitioninRBCswaslessthanthatanticipatedtobenecessaryforapharmacological

effectonrenalfunctionorrespiration.Similarpharmacokineticresultswereobservedafterchronic,topical

administrationofdorzolamidehydrochloride.However,someelderlypatientswithrenalimpairment(estimatedCrCl

30-60ml/min)hadhighermetaboliteconcentrationsinRBCs,butnomeaningfuldifferencesincarbonicanhydrase

inhibitionandnoclinicallysignificantsystemicsideeffectsweredirectlyattributabletothisfinding.

Timololmaleate:

Inastudyofplasmaactivesubstanceconcentrationinsixsubjects,thesystemicexposuretotimololwasdetermined

followingtwicedailytopicaladministrationoftimololmaleateophthalmicsolution0.5%.Themeanpeakplasma

concentrationfollowingmorningdosingwas0.46ng/mlandfollowingafternoondosingwas0.35ng/ml.

5.3Preclinicalsafetydata

Theocularandsystemicsafetyprofileoftheindividualcomponentsiswellestablished.

Dorzolamide

Inrabbitsgivenmaternotoxicdosesofdorzolamideassociatedwithmetabolicacidosis,malformationsofthevertebral

bodieswereobserved.

Timolol

Animalstudieshavenotshownteratogeniceffect.

Furthermore,noadverseoculareffectswereseeninanimalstreatedtopicallywithdorzolamidehydrochlorideand

timololmaleateophthalmicsolutionorwithconcomitantly-administereddorzolamidehydrochlorideandtimolol

maleate.Invitroandinvivostudieswitheachofthecomponentsdidnotrevealamutagenicpotential.Therefore,no

significantriskforhumansafetyisexpectedwiththerapeuticdosesofDortim.

6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

Hydroxyethylcellulose

Mannitol

Sodiumcitrate

Sodiumhydroxide(toadjustpH)

Benzalkoniumchloride

Waterforinjections

6.2Incompatibilities

Notapplicable.

6.3ShelfLife

2years

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6.4Specialprecautionsforstorage

Storebelow30°C.

Donotrefrigerateorfreeze.

6.5Natureandcontentsofcontainer

Dortim20mg/ml+5mg/mlEyeDropsSolutionisfilledintoa5mlfillvolumecapacitywhiteLDPEbottleequipped

withawhiteLDPEdropperapplicatorandclosedwithayellowHDPEtamperproofcap.

Packsizes:

1x5ml(asingle5mlbottle)

2x5ml(two5mlbottles)

3x5ml(three5mlbottles)

6x5ml(six5mlbottles)

Notallpacksizesmaybemarketed.

6.6Specialprecautionsfordisposalandotherhandling

Nospecialrequirements.

7MARKETINGAUTHORISATIONHOLDER

TevaPharmaB.V.

Computerweg10

3542DRUtrecht

TheNetherlands

8MARKETINGAUTHORISATIONNUMBER

PA749/79/1

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

Dateoffirstauthorisation:2ndJuly2010

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