AFFEX

Main information

  • Trade name:
  • AFFEX Capsules Hard 20 Base Milligrams
  • Dosage:
  • 20 Base Milligrams
  • Pharmaceutical form:
  • Capsules Hard
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug

Documents

Localization

  • Available in:
  • AFFEX Capsules Hard 20 Base Milligrams
    Ireland
  • Language:
  • English

Status

  • Source:
  • HPRA - Health Products Regulatory Authority - Ireland
  • Authorization number:
  • PA1241/011/001
  • Authorization date:
  • 30-09-2005
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

Affex20mgHardCapsules

2QUALITATIVEANDQUANTITATIVECOMPOSITION

EachcapsulecontainsFluoxetine20mg(asFluoxetineHydrochloride).

Excipients:ContainsSoyaLecithin

Forafulllistofexcipients,seesection6.1.

3PHARMACEUTICALFORM

Capsule,hard

Ahard,gelatincapsulewithalight-greenopaquecapandayellowopaquebody.Thecapsuleismarked‘F20’.

4CLINICALPARTICULARS

4.1TherapeuticIndications

Majordepressiveepisodes.

Obsessive-compulsivedisorder.

Bulimianervosa:Affexisindicatedasacomplementofpsychotherapyforthereductionofbinge-eatingandpurging

activity.

4.2Posologyandmethodofadministration

Fororaladministrationtoadultsonly.

Majordepressiveepisodes:

Adultsandtheelderly:20mg/dayto60mg/day.Adoseof20mg/dayisrecommendedastheinitialdose.Althoughthere

maybeanincreasedpotentialforundesirableeffectsathigherdoses,adoseincreasemaybeconsideredafterthree

weeksifthereisnoresponse.

InagreementwiththeconsensusstatementoftheWHO,antidepressantmedicationshouldbecontinuedforatleastsix

months.

Obsessive-compulsivedisorder(OCD):

Adultsandtheelderly:20mg/dayto60mg/day.Adoseof20mg/dayisrecommendedastheinitialdose.Although

theremaybeanincreasedpotentialforsideeffectsathigherdoses,adoseincreasemaybeconsideredaftertwoweeks

ifthereisnoresponse.Ifnoimprovementisobservedwithintenweeks,treatmentwithfluoxetineshouldbe

reconsidered.Ifagoodtherapeuticresponsehasbeenobtained,treatmentcanbecontinuedatadosageadjustedonan

individualbasis.Whiletherearenosystematicstudiestoanswerthequestionofhowlongtocontinuefluoxetine

treatment,OCDisachronicconditionanditisreasonabletoconsidercontinuationbeyondtenweeksinresponding

patients.Dosageadjustmentsshouldbemadecarefully,onanindividualpatientbasis,tomaintainthepatientatthe

lowesteffectivedose.Theneedfortreatmentshouldbereassessedperiodically.Somecliniciansadvocateconcomitant

behaviouralpsychotherapyforpatientswhohavedonewellonpharmacotherapy.

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Bulimianervosa:

Adultsandtheelderly:Adoseof60mg/dayisrecommended.Long-termefficacy(morethanthreemonths)hasnot

beendemonstratedinbulimianervosa.

Allindications:Therecommendeddosemaybeincreasedordecreased.Dosesabove80mg/dayhavenotbeen

systematicallyevaluated.

Fluoxetinemaybeadministeredasasingleordivideddose,duringorbetweenmeals.

Whendosingisstopped,activedrugsubstanceswillpersistinthebodyforweeks.Thisshouldbeborneinmindwhen

startingorstoppingtreatment.Dosagetaperingisunnecessaryinmostpatients.

Children:Theuseoffluoxetineinchildrenandadolescents(undertheageof18)isnotrecommended,assafetyand

efficacyhavenotbeenestablished.

Elderly:Cautionisrecommendedwhenincreasingthedose,andthedailydoseshouldgenerallynotexceed40mg.

Maximumrecommendeddoseis60mg/day.

Alowerorlessfrequentdose(e.g.,20mgeverysecondday)shouldbeconsideredinpatientswithhepaticimpairment

(seesection5.2),orinpatientswhereconcomitantmedicationhasthepotentialforinteractionwithAffex(seesection

4.5).

4.3Contraindications

Hypersensitivitytofluoxetineortoanyofitsexcipients.

Monoamineoxidaseinhibitors:Casesofseriousandsometimesfatalreactionshavebeenreportedinpatientsreceiving

anselectiveserotoninreuptakeinhibitor(SSRI)incombinationwithamonoamineoxidaseinhibitor(MAOI),andin

patientswhohaverecentlydiscontinuedanSSRIandhavebeenstartedonaMAOI.Treatmentoffluoxetineshould

onlybestartedtwoweeksafterdiscontinuationofanirreversibleMAOIandthefollowingdayafterdiscontinuationof

areversibleMAOI-A.

Somecasespresentedwithfeaturesresemblingserotoninsyndrome(whichmayresemble,andbediagnosedas,

neurolepticmalignantsyndrome).Cyproheptadineordantrolenemaybenefitpatientsexperiencingsuchreactions.

SymptomsofadruginteractionwithaMAOIinclude:hyperthermia,rigidity,myoclonus,autonomicinstabilitywith

possiblerapidfluctuationsofvitalsigns,mentalstatuschangesthatincludeconfusion,irritability,andextreme

agitation,progressingtodeliriumandcoma.

Therefore,fluoxetineiscontra-indicatedincombinationwithanon-selectiveMAOI.Similarly,atleastfiveweeks

shouldelapseafterdiscontinuingfluoxetinetreatmentbeforestartingaMAOI.Iffluoxetinehasbeenprescribed

chronicallyand/oratahighdose,alongerintervalshouldbeconsidered.

ThecombinationoffluoxetinewithareversibleMAOI(e.g.,moclobemide)isnotrecommended.Treatmentwith

fluoxetinecanbeinitiatedthefollowingdayafterdiscontinuationofareversibleMAOI.

Affex20mgHardCapsulescontainsoyalecithin.Ifyouareallergictosoyaorpeanut,donotusethismedicinal

product.

4.4Specialwarningsandprecautionsforuse

Warnings

Suicide/suicidalthoughtsorclinicalworsening

Depressionisassociatedwithanincreasedriskofsuicidalthoughts,selfharmandsuicide(suicide-relatedevents).This

riskpersistsuntilsignificantremissionoccurs.Asimprovementmaynotoccurduringthefirstfewweeksormoreof

treatment,patientsshouldbecloselymonitoreduntilsuchimprovementoccurs.Itisgeneralclinicalexperiencethatthe

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OtherpsychiatricconditionsforwhichAffex20mgHardCapsulesisprescribedcanalsobeassociatedwithan

increasedriskofsuicide-relatedevents.Inaddition,theseconditionsmaybeco-morbidwithmajordepressivedisorder.

Thesameprecautionsobservedwhentreatingpatientswithmajordepressivedisordershouldthereforebeobserved

whentreatingpatientswithotherpsychiatricdisorders.

Patientswithahistoryofsuiciderelatedevents,orthoseexhibitingasignificantdegreeofsuicidalideationpriorto

commencementoftreatment,areknowntobeatgreaterriskofsuicidalthoughtsorsuicideattempts,andshould

receivecarefulmonitoringduringtreatment.Ametaanalysisofplacebo-controlledclinicaltrialsofantidepressant

drugsinadultpatientswithpsychiatricdisordersshowedanincreasedriskofsuicidalbehaviourwithantidepressants

comparedtoplaceboinpatientslessthan25yearsold.

Closesupervisionofpatientsandinparticularthoseathighriskshouldaccompanydrugtherapyespeciallyinearly

treatmentandfollowingdosechanges.Patients,(andcaregiversofpatients)shouldbealertedabouttheneedtomonitor

foranyclinicalworsening,suicidalbehaviourorthoughtsandunusualchangesinbehaviourandtoseekmedicaladvice

immediatelyifthesesymptomspresent.

Rashandallergicreactions:Rash,anaphylactoidevents,andprogressivesystemicevents,sometimesserious

(involvingskin,kidney,liver,orlung),havebeenreported.Upontheappearanceofrashorofotherallergicphenomena

forwhichanalternativeaetiologycannotbeidentified,fluoxetineshouldbediscontinued.

Precautions

Seizures:Seizuresareapotentialriskwithantidepressantdrugs.Therefore,aswithotherantidepressants,fluoxetine

shouldbeintroducedcautiouslyinpatientswhohaveahistoryofseizures.Treatmentshouldbediscontinuedinany

patientwhodevelopsseizuresorwherethereisanincreaseinseizurefrequency.Fluoxetineshouldbeavoidedin

patientswithunstableseizuredisorders/epilepsy,andpatientswithcontrolledepilepsyshouldbecarefullymonitored.

Mania:Antidepressantsshouldbeusedwithcautioninpatientswithahistoryofmania/hypomania.Aswithall

antidepressants,fluoxetineshouldbediscontinuedinanypatiententeringamanicphase.

Hepatic/renalfunction:Fluoxetineisextensivelymetabolisedbytheliverandexcretedbythekidneys.Alowerdose,

eg,alternatedaydosing,isrecommendedinpatientswithsignificanthepaticdysfunction.Whengivenfluoxetine

20mg/dayfortwomonths,patientswithsevererenalfailure(GFR<10ml/min)requiringdialysisshowednodifference

inplasmalevelsoffluoxetineornorfluoxetinecomparedtocontrolswithnormalrenalfunction.

Cardiacdisease:NoconductionabnormalitiesthatresultedinheartblockwereobservedintheECGof312patients

whoreceivedfluoxetineindouble-blindclinicaltrials.However,clinicalexperienceinacutecardiacdiseaseislimited;

therefore,cautionisadvisable.

Weightloss:Weightlossmayoccurinpatientstakingfluoxetinebutitisusuallyproportionaltobaselinebodyweight.

Half-life:Thelongeliminationhalf-livesofbothfluoxetineandnorfluoxetineshouldbeborneinmind(seesection5.2)

whenconsideringpharmacodynamicorpharmacokineticdruginteractions(e.g.,whenswitchingfromfluoxetineto

otherantidepressants).

Monoamineoxidaseinhibitors:Seesection4.3.

Notrecommendedcombinations:MAOI-A(seesection4.3).

Combinationsrequiringprecautionsforuse:MAOI-B(selegiline):Riskofserotoninsyndrome.Clinicalmonitoringis

recommended.

Phenytoin:Changesinbloodlevelshavebeenobservedwhencombinedwithfluoxetine.Insomecasesmanifestations

oftoxicityhaveoccurred.Considerationshouldbegiventousingconservativetitrationschedulesoftheconcomitant

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Serotonergicdrugs:Co-administrationwithserotonergicdrugs(e.g.,tramadol,triptans)mayincreasetheriskof

serotoninsyndrome.Usewithtriptanscarriestheadditionalriskofcoronaryvasoconstrictionandhypertension.

Lithiumandtryptophan:TherehavebeenreportsofserotoninsyndromewhenSSRIshavebeengivenwithlithiumor

tryptophanand,therefore,theconcomitantuseoffluoxetinewiththesedrugsshouldbeundertakenwithcaution.When

fluoxetineisusedincombinationwithlithium,closerandmorefrequentclinicalmonitoringisrequired.

CYP2D6isoenzyme:Becausefluoxetine'smetabolism(liketricyclicantidepressantsandotherselectiveserotonin

antidepressants)involvesthehepaticcytochromeCYP2D6isoenzymesystem,concomitanttherapywithdrugsalso

metabolisedbythisenzymesystemmayleadtodruginteractions.Concomitanttherapywithdrugspredominantly

metabolisedbythisisoenzyme,andwhichhaveanarrowtherapeuticindex(suchasflecainide,encainide,

carbamazepine,andtricyclicantidepressants),shouldbeinitiatedatoradjustedtothelowendoftheirdoserange.This

willalsoapplyiffluoxetinehasbeentakeninthepreviousfiveweeks.

Oralanticoagulants:Alteredanticoagulanteffects(laboratoryvaluesand/orclinicalsignsandsymptoms),withno

consistentpattern,butincludingincreasedbleeding,havebeenreporteduncommonlywhenfluoxetineisco-

administeredwithoralanticoagulants.Patientsreceivingwarfarintherapyshouldreceivecarefulcoagulation

monitoringwhenfluoxetineisinitiatedorstopped(seesection4.4).

Electroconvulsivetherapy(ECT):Therehavebeenrarereportsofprolongedseizuresinpatientsonfluoxetinereceiving

ECTtreatment,thereforecautionisadvisable.

Alcohol:Informaltesting,fluoxetinedidnotraisebloodalcohollevelsorenhancetheeffectsofalcohol.However,the

combinationofSSRItreatmentandalcoholisnotadvisable.

StJohn'sWort:IncommonwithotherSSRIs,pharmacodynamicinteractionsbetweenfluoxetineandtheherbalremedy

StJohn'sWort(Hypericumperforatum)mayoccur,whichmayresultinanincreaseofundesirableeffects.

4.6Fertility,pregnancyandlactation

Pregnancy:Dataonalargenumberofexposedpregnanciesdonotindicateateratogeniceffectoffluoxetine.

Fluoxetinecanbeusedduringpregnancy,butcautionshouldbeexercised,especiallyduringlatepregnancyorjust

priortotheonsetoflabour,sincethefollowingeffectshavebeenreportedinneonates:irritability,tremor,hypotonia,

persistentcrying,difficultyinsuckingorinsleeping.Thesesymptomsmayindicateeitherserotonergiceffectsora

withdrawalsyndrome.Thetimetooccurandthedurationofthesesymptomsmayberelatedtothelonghalf-lifeof

fluoxetine(4-6days)anditsactivemetabolite,norfluoxetine(4-16days).

Lactation:Fluoxetineanditsmetabolite,norfluoxetine,areknowntobeexcretedinhumanbreastmilk.Adverseevents

havebeenreportedinbreast-feedinginfants.Iftreatmentwithfluoxetineisconsiderednecessary,discontinuationof

breast-feedingshouldbeconsidered;however,ifbreast-feedingiscontinued,thelowesteffectivedoseoffluoxetine

shouldbeprescribed.

Someepidemiologicalstudiessuggestanincreasedriskofcardiovasculardefectsassociatedwiththeuseoffluoxetine

duringthefirsttrimester.Themechanismisunknown.Overallthedatasuggestthattheriskofhavinganinfantwitha

cardiovasculardefectfollowingmaternalfluoxetineexposureisintheregionof2/100comparedwithanexpectedrate

forsuchdefectsofapproximately1/100inthegeneralpopulation.

EpidemiologicaldatahavesuggestedthattheuseofSSRIsinpregnancy,particularinlatepregnancy,mayincreasethe

riskofpersistentpulmonaryhypertensioninthenewborn(PPHN).Theobservedriskwasapproximately5casesper

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4.7Effectsonabilitytodriveandusemachines

Althoughfluoxetinehasbeenshownnottoaffectpsychomotorperformanceinhealthyvolunteers,anypsychoactive

drugmayimpairjudgementorskills.Patientsshouldbeadvisedtoavoiddrivingacaroroperatinghazardous

machineryuntiltheyarereasonablycertainthattheirperformanceisnotaffected.

4.8Undesirableeffects

Undesirableeffectsmaydecreaseinintensityandfrequencywithcontinuedtreatmentanddonotgenerallyleadto

cessationoftherapy.

IncommonwithotherSSRIs,thefollowingundesirableeffectshavebeenseen:

Bodyasawhole:Hypersensitivity(e.g.,pruritus,rash,urticaria,anaphylactoidreaction,vasculitis,serumsickness-like

reaction,angioedema)(seesection4.3andsection4.4),chills,serotoninsyndrome,photosensitivity,and,veryrarely,

toxicepidermalnecrolysis(Lyellsyndrome).

Digestivesystem:Gastro-intestinaldisorders(eg,diarrhoea,nausea,vomiting,dyspepsia,dysphagia,tasteperversion),

drymouth.Abnormalliverfunctiontestshavebeenreportedrarely.Veryrarecasesofidiosyncratichepatitis.

Suicidalideationandbehaviour:CasesofsuicidalideationandsuicidalbehaviourshavebeenreportedduringAffex

20mgHardCapsulestherapyorearlyaftertreatmentdiscontinuation(seesection4.4).

Nervoussystem:Headache,sleepabnormalities(e.g.,abnormaldreams,insomnia),dizziness,anorexia,fatigue(e.g.,

somnolence,drowsiness),euphoria,transientabnormalmovement(e.g.,twitching,ataxia,tremor,myoclonus),

seizures,andpsychomotorrestlessness.Hallucinations,manicreaction,confusion,agitation,anxietyandassociated

symptoms(e.g.,nervousness),impairedconcentrationandthoughtprocess(e.g.,depersonalisation),panicattacks

(thesesymptomsmaybeduetotheunderlyingdisease),and,veryrarely,serotoninsyndrome.

Urogenitalsystem:Urinaryretention,urinaryfrequency.

Reproductivedisorders:Sexualdysfunction(delayedorabsentejaculation,anorgasmia),priapism,galactorrhoea.

Miscellaneous:Alopecia,yawn,abnormalvision(e.g.,blurredvision,mydriasis),sweating,vasodilatation,arthralgia,

myalgia,posturalhypotension,ecchymosis.Otherhaemorrhagicmanifestations(e.g.,gynaecologicalhaemorrhages,

gastro-intestinalbleedings,andothercutaneousormucousbleedings)havebeenreportedrarely(seesection4.4).

Hyponatraemia:Hyponatraemia(includingserumsodiumbelow110mmol/l)hasbeenrarelyreportedandappearedto

bereversiblewhenfluoxetinewasdiscontinued.Somecaseswerepossiblyduetothesyndromeofinappropriate

antidiuretichormonesecretion.Themajorityofreportswereassociatedwitholderpatients,andpatientstaking

diureticsorotherwisevolumedepleted.

Respiratorysystem:Pharyngitis,dyspnoea.Pulmonaryevents(includinginflammatoryprocessesofvarying

histopathologyand/orfibrosis)havebeenreportedrarely.Dyspnoeamaybetheonlyprecedingsymptom.

ClassEffects:Epidemiologicalstudies,mainlyinpatients50yearsofageorolder,showanincreasedriskofbone

fracturesinpatientsreceivingSSRIsandTCAs.Themechanismleadingtothisriskisunknown.

Whenstoppingtreatment,withdrawalsymptomshavebeenreportedinassociationwithSSRIs,althoughtheavailable

evidencedoesnotsuggestthisisduetodependence.Commonsymptomsincludedizziness,paraesthesia,headache,

anxiety,andnausea,themajorityofwhicharemildandself-limiting.Fluoxetinehasbeenonlyrarelyassociatedwith

suchsymptoms.Plasmafluoxetineandnorfluoxetineconcentrationsdecreasegraduallyattheconclusionoftherapy,

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4.9Overdose

Casesofoverdoseoffluoxetinealoneusuallyhaveamildcourse.Symptomsofoverdosehaveincludednausea,

vomiting,seizures,cardiovasculardysfunctionrangingfromasymptomaticarrhythmiastocardiacarrest,pulmonary

dysfunction,andsignsofalteredCNSstatusrangingfromexcitationtocoma.Fatalityattributedtooverdoseof

fluoxetinealonehasbeenextremelyrare.Cardiacandvitalsignsmonitoringarerecommended,alongwithgeneral

symptomaticandsupportivemeasures.Nospecificantidoteisknown.

Forceddiuresis,dialysis,haemoperfusion,andexchangetransfusionareunlikelytobeofbenefit.Activatedcharcoal,

whichmaybeusedwithsorbitol,maybeasormoreeffectivethanemesisorlavage.Inmanagingoverdosage,consider

thepossibilityofmultipledruginvolvement.Anextendedtimeforclosemedicalobservationmaybeneededinpatients

whohavetakenexcessivequantitiesofatricyclicantidepressantiftheyarealsotaking,orhaverecentlytaken,

fluoxetine.

5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

Fluoxetineisaselectiveinhibitorofserotoninreuptake,andthisprobablyaccountsforthemechanismofaction.

Fluoxetinehaspracticallynoaffinitytootherreceptorssuchasalfa1-,alfa2-,andbeta-adrenergic;serotonergic;

dopaminergic;histaminergic1;muscarinic;andGABAreceptors.

Majordepressiveepisodes:Clinicaltrialsinpatientswithmajordepressiveepisodeshavebeenconductedversus

placeboandactivecontrols.Fluoxetinehasbeenshowntobesignificantlymoreeffectivethanplacebo,asmeasuredby

theHamiltonDepressionRatingScale(HAM-D).Inthesestudies,Fluoxetineproducedasignificantlyhigherrateof

response(definedbya50%decreaseintheHAM-Dscore)andremissioncomparedtoplacebo.

Obsessive-compulsivedisorder:Inshort-termtrials(under24weeks),fluoxetinewasshowntobesignificantlymore

effectivethanplacebo.Therewasatherapeuticeffectat20mg/day,buthigherdoses(40or60mg/day)showedahigher

responserate.Inlong-termstudies(threeshort-termstudiesextensionphaseandarelapsepreventionstudy)efficacy

hasnotbeenshown.

Bulimianervosa:Inshort-termtrials(under16weeks),inout-patientsfulfillingDSM-III-R-criteriaforbulimia

nervosa,fluoxetine60mg/daywasshowntobesignificantlymoreeffectivethanplaceboforthereductionofbingeing

andpurgingactivities.However,forlong-termefficacynoconclusioncanbedrawn.

Twoplacebo-controlledstudieswereconductedinpatientsmeetingpre-menstrualdysphoricdisorder(PMDD)

diagnosticcriteriaaccordingtoDSM-IV.Patientswereincludediftheyhadsymptomsofsufficientseveritytoimpair

socialandoccupationalfunctionandrelationshipswithothers.

Patientsusingoralcontraceptiveswereexcluded.Inthefirststudyofcontinuous20mgdailydosingforsixcycles,

improvementwasobservedintheprimaryefficacyparameter(irritability,anxiety,anddysphoria).Inthesecondstudy,

withintermittentlutealphasedosing(20mgdailyfor14days)forthreecycles,improvementwasobservedinthe

primaryefficacyparameter(DailyRecordofSeverityofProblemsscore).However,definitiveconclusionsonefficacy

anddurationoftreatmentcannotbedrawnfromthesestudies.

5.2Pharmacokineticproperties

Absorption:Fluoxetineiswellabsorbedfromthegastro-intestinaltractafteroraladministration.Thebioavailabilityis

notaffectedbyfoodintake.

Distribution:Fluoxetineisextensivelyboundtoplasmaproteins(about95%)anditiswidelydistributed(volumeof

distribution:20-40l/kg).Steady-stateplasmaconcentrationsareachievedafterdosingforseveralweeks.Steady-state

concentrationsafterprolongeddosingaresimilartoconcentrationsseenatfourtofiveweeks.

Metabolism:Fluoxetinehasanon-linearpharmacokineticprofilewithfirstpasslivereffect.Maximumplasma

concentrationisgenerallyachievedsixtoeighthoursafteradministration.Fluoxetineisextensivelymetabolisedbythe

polymorphicenzymeCYP2D6.Fluoxetineisprimarilymetabolisedbythelivertotheactivemetabolitenorfluoxetine

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Elimination:Theeliminationhalf-lifeoffluoxetineis4to6daysandfornorfluoxetine4to16days.Theselonghalf-

livesareresponsibleforpersistenceofthedrugfor5-6weeksafterdiscontinuation.Excretionismainly(about60%)

viathekidney.Fluoxetineissecretedintobreastmilk.

At-RiskPopulations

Elderly:Kineticparametersarenotalteredinhealthyelderlywhencomparedtoyoungersubjects.

Hepaticinsufficiency:Incaseofhepaticinsufficiency(alcoholiccirrhosis),fluoxetineandnorfluoxetinehalf-livesare

increasedto7and12days,respectively.Alowerorlessfrequentdoseshouldbeconsidered.

Renalinsufficiency:Aftersingle-doseadministrationoffluoxetineinpatientswithmild,moderate,orcomplete(anuria)

renalinsufficiency,kineticparametershavenotbeenalteredwhencomparedtohealthyvolunteers.However,after

repeatedadministration,anincreaseinsteady-stateplateauofplasmaconcentrationsmaybeobserved.

5.3Preclinicalsafetydata

Thereisnoevidenceofcarcinogenicity,mutagenicity,orimpairmentoffertilityfrominvitrooranimalstudies.

6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

CapsuleContents

Pregelatinisedmaizestarch

Colloidalanhydroussilica

Magnesiumstearate

Talc

CapsuleShell

Quinolineyellow(E104)

Indigocarmine(E132)

Titaniumdioxide(E171)

Gelatin

Erythrosine(E127)

PrintingInk

Shellac

Blackironoxide(E172)

Soyalecithin

AntifoamDC1510(includesdimethylsiloxane)

6.2Incompatibilities

Notapplicable.

6.3Shelflife

3years.

6.4Specialprecautionsforstorage

Donotstoreabove25 o

C.Storeintheoriginalpackageinordertoprotectfrommoisture.

6.5Natureandcontentsofcontainer

Al/PVCblisters;

7,14,28,30,56,60,100,120capsulesperpack.

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6.6Specialprecautionsfordisposalofausedmedicinalproductorwastematerialsderivedfrom

suchmedicinalproductandotherhandlingoftheproduct

Nospecialrequirements.

7MARKETINGAUTHORISATIONHOLDER

AstellasPharmaCo.Ltd.

25TheCourtyard

KilcarberyBusinessPark

Clondalkin

Dublin22

Ireland

8MARKETINGAUTHORISATIONNUMBER

PA1241/11/1

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

Dateoffirstauthorisation:26November1999

Dateoflastrenewal:26November2009

10DATEOFREVISIONOFTHETEXT

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