CAMCOLIT 250 MG, FILM COATED TABLETS

Main information

  • Trade name:
  • CAMCOLIT 250 MG, FILM COATED TABLETS
  • Dosage:
  • 250 mg Milligram
  • Pharmaceutical form:
  • Film Coated Tablet
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug

Documents

Localization

  • Available in:
  • CAMCOLIT 250 MG, FILM COATED TABLETS
    Ireland
  • Language:
  • English

Status

  • Source:
  • HPRA - Health Products Regulatory Authority - Ireland
  • Authorization number:
  • PA0102/003/001
  • Authorization date:
  • 01-04-1978
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

CAMCOLIT250mg,filmcoatedtablets

2QUALITATIVEANDQUANTITATIVECOMPOSITION

Eachtabletcontains250mgLithiumCarbonate.

Forafulllistofexcipients,seesection6.1.

3PHARMACEUTICALFORM

Filmcoatedtablet

Thetabletsareengraved"CAMCOLIT"aroundonefaceandhavingabreaklineonthereverse.

Thescorelineisonlytofacilitatebreakingforeaseofswallowingandnotintoequaldoses.

4CLINICALPARTICULARS

4.1TherapeuticIndications

Thetreatmentandprophylaxisofmania,bipolaraffectivedisordersandrecurrentdepression,andthetreatmentof

aggressiveorselfmutilatingbehaviour.

4.2Posologyandmethodofadministration

Fororaladministration.

CAMCOLIT250mgfilmcoatedtabletsareusuallyadministeredaccordingtoatwicedailyregimen.

4.2.1Dosage

Lithiumcarbonatehasanarrowtherapeuticwindow.Thedoserequiredfortreatmentmustbetitratedandadjustedon

thebasisofregularmonitoringoftheserumconcentrationoflithium(SeeSection4.4.1).Lithiumtherapyshouldnotbe

initiatedunlessadequatefacilitiesforroutinemonitoringofplasmaconcentrationsareavailable.

Toxicsymptomsareusuallyassociatedwithlithiumconcentrationsexceeding1.5mmol/l.

Levelsofmorethan1.5mmol/lmustbeavoided.

Withdrawal

Iflithiumistobediscontinued,particularlyincasesofhighdoses,thedoseshouldbereducedgradually.

Acutemania:

Adults:Treatmentshouldbeinitiatedinhospitalwhereregularmonitoringofplasmalithiumlevelscanbeconducted.

ThedosageofCamcolitshouldbeadjustedtoproduceaplasmalithiumlevelbetween0.6and1.0mmol/l12hours

afterthelastdose.Therequiredplasmalithiumlevelmaybeachievedinoneoftwowaysbut,whicheverisadopted,

regularestimationsmustbecarriedouttoensuremaintenanceoflevelswithinthetherapeuticrange.Forconsistent

resultsitisessentialthatthebloodsamplesforplasmalithiumestimationsaretaken12hoursafterthelastdoseof

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1.1,000-1,500mgoflithiumcarbonateareadministereddailyforthefirstfivedays.Abloodsampleforplasmalithium

estimationistaken12hoursafterthelastdoseonthefifthday,andthedosageofCamcolitisadjustedtokeepthe

plasmalithiumlevelwithinthetherapeuticrange.Subsequently,regularplasmalithiumestimationsmustbecarriedout

and,wherenecessary,thedosageofCamcolitadjustedaccordingly.Thepreciseinitialdoseoflithiumshouldbe

decidedinthelightoftheageandweightofthepatient;youngpatientsoftenrequireadosehigherthanaverageand

olderpatientsalowerdose.

2.Alithiumclearancetestiscarriedoutandtheinitialdosagecalculatedfromtheresults.Evenwhentheinitialdosage

iscalculatedinthisway,itisstilldesirablethatplasmalithiumlevelsshouldbedeterminedatweeklyintervalsduring

thefirstthreeweeksoftreatment,andanynecessaryadjustmentstodosagemadeasaresultofthelevelsactually

obtained.

Mostoftheaboveappliesinthetreatmentofhypomaniaaswellasmania,butthepatient(ifnottooill)canbestarted

ontreatmentasanoutpatientprovidedthatfacilitiesforregularplasmalithiummonitoringareavailable,andassaysare

initiatedwithinoneweek.

Prophylaxisofrecurrentaffectivedisorders:

Adults:(Includingunipolarmania&unipolardepressionsandbipolarmanic-depressiveillness):Alowdoseof300-

400mgoflithiumcarbonatecanbeadministereddailyforthefirstsevendays.Abloodsampleforplasmalithium

estimationisthentaken12hoursafterthelastdose,andthedosageofCamcolitisadjustedtokeeptheplasmalithium

levelwithintherangeof0.4-0.8mmol/l.Toxicsymptomsareusuallyassociatedwithconcentrationsexceeding1.5

mmol/l.

Aggressiveandselfmutilatingbehaviour

Adults:Thedosageisatthelowerendoftherangeforthetreatmentformanicdepressiveillness.

4.2.2Specialpopulations

Elderly:

Starttreatmentwithalowdose.

Toxicsymptomsaremorelikelyatlowerconcentrationsthaninthegeneralpopulation.

Elderlypatientsoftenrequirealowerlithiumdosagetoachievetherapeuticserumlevels.

Children:

Donotuseinchildren.

4.3Contraindications

Ahistoryofhypersensitivitytolithiumoranyoftheexcipients.

Severelyimpairedrenalfunction

Untreatedoruntreatablehypothyroidism.

Cardiacdiseaseassociatedwithrhythmdisorder.

Lowbodysodiumlevelsforexampledehydratedpatients,thoseonlowsodiumdiets,orthosewithAddison’s

disease

Breastfeeding.

4.4Specialwarningsandprecautionsforuse

Lithiumcarbonatehasanarrowtherapeuticwindow.Thedoserequiredfortreatmentmustbetitratedandadjustedon

thebasisofregularmonitoringofserumconcentrationoflithium.Lithiumtherapyshouldnotbeinitiatedunless

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Elderlypatientsareparticularlyliabletolithiumtoxicity.Usewithcareaslithiumexcretionmayalsobereduced.They

mayalsoexhibitadversereactionsatserumlevelsordinarilytoleratedbyyoungerpatients(seesection4.2).

Beforebeginningalithiumtreatment:

Itisimportanttoensurethatrenalfunctionisevaluated(seesections4.3and4.4.2).

Cardiacfunctionshouldbeassessedespeciallyinpatientswithcardiovasculardisease.

Thyroidfunctionshouldbeevaluated.Patientsshouldbeeuthyroidbeforeinitiationoflithiumtherapy.

Renal,cardiacandthyroidfunctionsshouldbere-assessedperiodically.

Concomitantadministrationofantipsychoticsshouldbeavoided.

4.4.1Monitoringofbloodlithiumlevels

Serumconcentrationoflithiumshouldbemeasuredonasampletakenjustpriortothetimewhenadoseoflithiumis

duetobetaken(i.e.attroughlevel12hoursfollowingthelastdose).

Toxiceffectsmaybeexpectedatserum-lithiumconcentrationsofapproximately1.5mmol/litre,althoughtheycan

appearatlowerconcentrations.Theycallforimmediatewithdrawaloftreatmentandshouldalwaysbeconsideredvery

seriously.

Serumconcentrationoflithiumshouldbemeasuredevery5to7daysfrominitiationuntilstabilisationisachievedand

atregularintervalsforthedurationoftreatment.

Serumlithiumconcentrationsshouldbemonitoredmorefrequently(reverttoweeklymonitoring)inthefollowing

circumstances:

Dosagealterationorchangeoflithiumformulation(bioavailabilitymaydiffer)

Significantintercurrentdisease

Intercurrentinfection

Significantchangeinsodiumintake

Significantchangeinfluidintake

Treatmentwithdrugsalteringrenalclearanceoflithium

Treatmentwithdrugslikelytoupsetelectrolytebalance.

Patientsshouldalsobewarnedtoreportifpolyuriaorpolydipsiadevelops(seesection4.4.2).Episodesofnauseaand

vomitingorotherconditionsleadingtosalt/waterdepletion(includingseveredieting)shouldalsobereported.Patients

shouldbeadvisedtomaintaintheirusualsaltandfluidintake.

Lithiumshouldbestopped24hoursbeforemajorsurgery,butthenormaldosecanbecontinuedforminorsurgeryif

fluidsandelectrolytesarecarefullymonitored.

4.4.2Renalimpairment

Lithiumexcretionisreducedinthepresenceofrenalimpairment.Thisincreasestheriskoftoxicity.Lithiumiscontra-

indicatedinpatientswithsevererenalimpairment(seesection4.3).Ifpatientswithmildormoderaterenalimpairment

arebeingtreatedwithlithium,serumlithiumlevelsshouldbecloselymonitored.

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4.4.3Warningstobegiventopatientsaboutsignsandsymptomsoftoxicity

Clearinstructionsregardingthesymptomsofimpendingtoxicityshouldbegivenbythedoctortoallpatientsreceiving

long-termlithiumtherapy(seeSection4.9forsymptomsofintoxication)andadvicegivenfortheneedforurgencyin

seekingmedicalassistanceifthesesymptomsappear.

4.5Interactionwithothermedicinalproductsandotherformsofinteraction

Interactionsmayoccurasaresultofincreasedordecreasedlithiumlevels,orthroughothermechanisms,themost

importantbeingneurotoxicitywhichmayoccurattherapeuticlevelswhenotherdrugswhichactcentrallyontheCNS

aretakenconcurrently.

Interactionswhichincreaselithiumconcentrations:

Co-administrationofthefollowingdrugswithlithiummayleadtoincreasedlithiumconcentrationsandariskof

toxicity:

anydrugwhichmaycauserenalimpairmenthasthepotentialtocauselithiumlevelstorise,therebycausing

toxicity.Iftheuseofthedrugisunavoidable,carefullymonitorlithiumbloodlevelandadaptdosageasnecessary.

antibiotics(metronidazole,tetracyclines,co-trimoxazole,trimethoprim), N.B.Toxicsymptomsmayalsooccur

atlowornormallevelswhenusedinconjunctionwithco-trimoxazoleortrimethoprim.Lithiumtoxicityhasbeen

reportedonisolatedoccasionsinpatientsreceivingspectinomycin.

non-steroidalanti-inflammatorydrugs(includingselectivecyclo-oxygenase(COX)IIinhibitors;monitorserum

lithiumconcentrationsmorefrequentlyifNSAIDtherapyisinitiatedordiscontinued.

drugsaffectingthereninangiotensinsystem(ACEinhibitors,AngiotensinIIreceptorantagonists)

diuretics(includingherbalpreparations).Inadditiontotheeffectsnotedabove,thiazidediureticsshowa

paradoxicalantidiureticeffectresultinginpossiblewaterretentionandlithiumintoxication.Loopdiuretics(e.g.

furosemide,bumetanideandetacrynicacid)seemlesslikelytocauselithiumretention,althoughcautioniswarranted.

otherdrugsaffectingelectrolytebalance,e.g.steroids,mayalterlithiumexcretionandshouldthereforebe

avoided.

Interactionswhichdecreaseserumlithiumconcentrations:

Co-administrationofthefollowingdrugswithlithiummayleadtodecreasedlithiumconcentrationsandariskofloss

ofefficacy:

xanthinederivatives(e.g.theophylline,caffeine)

productscontaininglargequantitiesofsodiume.g.sodiumbicarbonate

carbonicanhydraseinhibitors.

urea

Interactionswhichmaynotbeassociatedwithincreasedorreducedlithiumlevels:

Concomitantuseofthefollowingdrugsmayprecipitatesymptomsoftoxicitywhenthelithiumleveliswithinnormal

range:

antipsychotics,includingtheatypicalantipsychoticsolanzapineandclozapineandhaloperidolathighdoses.

carbamazepine

phenytoin

methyldopa

clonazepam

selectiveserotoninre-uptakeinhibitors(SSRIs)Concurrentusewithlithiummayprecipitateaserotonergic

syndrome.

tricyclicandtetracyclicantidepressants

calciumchannelblockers.

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Triptans:lithiumtoxicityreportedsuggestiveofserotoninsyndrome.

DrugswhichprolongtheQTinterval:

LithiumcancauseanincreaseintheQTcinterval,particularlyathigherbloodlevels.Thereforeconcurrentuseof

drugswhichhaveariskofprolongingtheQTcintervalshouldbeavoided,andconsiderationbemadeofotherpotential

riskfactorssuchasincreasingage,femalesex,congenitallongQTsyndrome,cardiacandthyroiddiseaseandthe

followingmetabolicdisturbances:hypocalcaemia,hypokalaemia,hypomagnesaemia.

ThefollowingproductshaveahighriskofcausingQTprolongationandtorsadedepointes:amisulpride;ClassIa

antiarrhythmics(disopyramide,procainamide,quinidine),ClassIIIantiarrhythmics(amiodarone,sotalol),arsenic

trioxide,artemisininderivatives,dolasetronmesylate,mefloquine,

astemizole,intravenouserythromycin,amisulpride,haloperidol,pimozide,ranolazine,sertindole,terfenadine,

thioridazine.

ECGshouldbeperformedafterinitiationoftreatmentandatanypointwherethepatientbecomessymptomaticor

whentherearechangesindiseaseortreatmentwhichmayincreasetheriskofinteractionorarrhythmia.

NonDrugInteractions:

Lowsodiumdiet.Rapidreductionofsodiumintakemaycauseraisedlithiumlevels.

Intercurrentillnessmaycauselithiumtoxicity.

4.6Fertility,pregnancyandlactation

Lithiumtherapyshouldnotbeusedduringpregnancy,especiallyduringthefirsttrimesterunlessconsideredessential.

Thereisepidemiologicalevidencethatitmaybeharmfultothefoetusinhumanpregnancy.Lithiumcrossesthe

placentalbarrier.

Inanimalstudieslithiumhasbeenreportedtointerferewithfertility,gestationandfoetaldevelopment.Anincreasein

cardiacandotherabnormalities,especiallyEbsteinanomaly,arereported.Therefore,apre-nataldiagnosissuchas

ultrasoundandelectrocardiogramexaminationisstronglyrecommended.Incertaincaseswereasevererisktothe

patientcouldexistiftreatmentwerestopped,lithiumhasbeencontinuedduringpregnancy.

Ifitisconsideredessentialtomaintainlithiumtreatmentduringpregnancy,serumlithiumlevelsshouldbeclosely

monitoredandmeasuredfrequentlysincerenalfunctionchangesgraduallyduringpregnancyandsuddenlyat

parturition.Dosageadjustmentsarerequired.Itisrecommendedthatlithiumbediscontinuedshortlybeforedelivery

andreinitiatedafewdayspost-partum.

Hyperemesisgravidarummayreducelithiumabsorptionifemesisoccursshortlyaftertheadministrationoflithium.

Fluidlossesandprofusevomitingmaycausedehydrationandelectrolytedisturbanceswhichincreaselithium

concentration.

Polyhydramnioscanbeaconsequenceoffoetaldiabetesinsipidus.Foetaldiabetesinsipiduscanpersistforaweekor

longerafterdelivery.

Pre-eclampsia.Moderatetoseverepre-eclampsiadecreasestheglomerularfiltrationrate,whichcanelevatelithium

concentrationsbyreducinglithiumclearance.Somecommontreatmentstrategies(thiazidediuretics,aspirin,sodium

restriction)canalsoincreaselithiumconcentration.

Morefrequentmonitoringisrequiredincludingatthetimeofparturition.

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Reviewandtitratelithiumdoseafterdelivery.

Neonatesmayshowsignsoflithiumtoxicitynecessitatingfluidtherapyintheneonatalperiod.Neonatesbornwithlow

serumconcentrationsmayhaveaflaccidappearancethatreturnstonormalwithoutanytreatment.

4.6.2 Womenofchild-bearingpotential

Itisadvisablethatwomentreatedwithlithiumshouldadoptadequatecontraceptivemethods.Incaseofaplanned

pregnancy,itisstronglyrecommendedtodiscontinuelithiumtherapy.

4.6.3 Lactation

Sinceadequatehumandataonuseduringlactationandadequatehumanreproductionstudiesarenotavailable,andas

lithiumissecretedinbreastmilk,bottlefeedingisrecommended(seesection4.3Contra-indications).

4.7Effectsonabilitytodriveandusemachines

AslithiummaycausedisturbancesoftheCNS,patientsshouldbewarnedofthepossiblehazardswhendrivingor

operatingmachinery.

4.8Undesirableeffects

Sideeffectsareusuallyrelatedtoserumlithiumconcentrationsandarelesscommoninpatientswithplasmalithium

concentrationsbelow1.0mmol/l.

Initialtherapy:finetremorofthehands,polyuriaandthirstmayoccur.

Bloodandlymphaticsystemdisorders:leucocytosis.

Immunesystemdisorders:increaseinantinuclearantibody.

Endocrinedisorders:disturbancesofthyroidfunctionincluding(euthyroid)goitre,hypothyroidismand

hyperthyroidism,hyperparathyroidism,parathyroidadenoma.

Metabolismandnutritiondisorders:hypercalcaemia,hypermagnesaemia,hyperglycaemia,anorexia,weightgain.

Nervoussystemdisorders:coma,pseudotumorcerebri,syndromeofirreversiblelithiumeffectuatedneurotoxicity

(SILENT),encephalopathy,stupor,seizures,neurolepticmalignantsyndrome,myastheniagravis,serotoninsyndrome,

Parkinsonism,extrapyramidalsymptoms,ataxia,dizziness,memoryimpairment,mildcognitiveimpairment,giddiness,

nystagmus,slurredspeech,vertigo,hyperactivedeeptendonreflexes,dysgeusia,dazedfeeling,finehandtremors.

Eyedisorders:scotomataandblurredvision.

Cardiacdisorders:cardiacarrest,arrhythmiasincludingventricularfibrillation,ventriculartachycardia,ventricular

arrhythmias,Torsadedepointes,QTintervalprolongation,bradycardia,cardiomyopathy,sinusnodedysfunction,ECG

changes.

Vasculardisorders:peripheralcirculatorycollapse,hypotension,Raynaud’sphenomena

Gastrointestinaldisorders:gastritis,nausea,diarrhoea,vomiting,drymouth,excessivesalivation.

Skinandsubcutaneoustissuedisorders:allergicrash,exacerbationofpsoriasis,acneiformeruptions,alopecia,acne,

papularskindisorder,folliculitis,pruritus,rash.

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Renalandurinarydisorders:symptomsofnephrogenicdiabetesinsipidus,impairmentofrenalfunction,permanent

changesinthekidney,nephroticsyndrome,histologicalrenalchangeswithinterstitialfibrosisafterlongterm

treatment,polyuria,polydipsia.

Reproductivesystemandbreastdisorders:sexualdysfunction.

Generaldisordersandadministrationsiteconditions:suddenunexplaineddeath,oedema,asthenia,lethargy,thirst,

fatigue,andmalaisecanoccurduetolithiumtoxicity.

Other:

SomeadverseeventswillbeseenwhenLithiumlevelsareraised–forsymptomsseesection4.9Overdose.

4.9Overdose

Lithiumcarbonatehasanarrowtherapeuticwindow.Symptomsoflithiumoverdose(lithiumintoxication)canoccur

duetointercurrentillness,iatrogeniccauses,andselfpoisoning.

Inpatientswitharaisedlithiumconcentration,theriskoftoxicityisgreaterinthosewiththefollowingunderlying

medicalconditions:hypertension;diabetes;congestiveheartfailure;chronicrenalfailure;schizophrenia;Addison's

disease.

Anyoverdoseinapatientwhohasbeentakingchroniclithiumtherapyshouldberegardedaspotentiallyserious.

Acuteoverdosage

Asingleacuteoverdoseusuallycarrieslowriskandpatientstendtoshowmildsymptomsonly,irrespectiveoftheir

serumlithiumconcentration.Howevermoreseveresymptomsmayoccurafteradelayiflithiumeliminationisreduced

becauseofrenalimpairment,particularlyifaslow-releasepreparationhasbeentaken.Thefataldose,inasingle

overdose,isprobablyover5g.

Acuteoverdosageinapatientonchroniclithiumtherapy

Ifanacuteoverdosehasbeentakenbyapatientonchroniclithiumtherapy,thiscanleadtoserioustoxicityoccurring

evenafteramodestoverdoseastheextravasculartissuesarealreadysaturatedwithlithium.

Symptoms

Theonsetofsymptomsmaybedelayed,withpeakeffectsnotoccurringforaslongas24hours,especiallyinpatients

whoarenotreceivingchroniclithiumtherapyorfollowingtheuseofasustainedreleasepreparation.

Mild:Nausea,diarrhoea,blurredvision,polyuria,lightheadedness,finerestingtremor,muscularweaknessand

drowsiness.

Moderate:Increasingconfusion,blackouts,fasciculationandincreaseddeeptendonreflexes,myoclonictwitchesand

jerks,choreoathetoidmovements,urinaryorfaecalincontinence,increasingrestlessnessfollowedbystupor.

Hypernatraemia.

Severe:Coma,convulsions,cerebellarsigns,cardiacdysrhythmiasincludingsinoatrialblock,sinusandjunctional

bradycardiaandfirstdegreeheartblock.Hypotensionorrarelyhypertension,circulatorycollapseandrenalfailure.

Management

Thereisnoknownantidotetolithiumpoisoning.

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Adequatehydrationshouldbeensuredandanyelectrolyteimbalancecorrectedbecauseoftheriskofhypernatraemia.

Forceddiuresisordiureticsarecontra-indicated.Appropriatesupportivecaremayincludemeasurestocontrol

hypotensionandconvulsions.

Allpatientsshouldbemonitoredforaminimumof24hours.TheECGshouldbemonitoredinsymptomaticpatients.

Stepsshouldbetakentocorrecthypotension.

Considergastriclavagefornon-sustained-releasepreparationsifmorethan4ghasbeeningestedbyanadultwithinone

hourordefiniteingestionofasignificantamountbyachild.Slow-releasetabletsdonotdisintegrateinthestomachand

mostaretoolargetopassupalavagetube.Gutdecontaminationisnotusefulforchronicaccumulation.Wholebowel

irrigationmaybehelpfulinpatientsingestinglargequantitiesofaslow-releasepreparation.

Note:Activatedcharcoaldoesnotadsorblithium.

Haemodialysisisthetreatmentofchoiceforseverepoisoningandshouldbeconsideredinallpatientswithmarked

neurologicalfeatures.

Itisthemostefficientmethodofloweringlithiumconcentrationsrapidlybutsubstantialreboundincreasescanbe

expectedwhendialysisisstopped,andprolonged,orrepeatedtreatmentsmayberequired.

Itshouldbeconsideredalsoinacute,acuteonchronicorchronicoverdoseinpatientswithseveresymptomsregardless

ofserumlithiumconcentration;discusswithyourlocalpoisonsservice.

Note:Clinicalimprovementgenerallytakeslongerthanreductionofserumlithiumconcentrationsregardlessofthe

methodused.

5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

Theprecisemechanismofactionoflithiumasamood-stabilisingagentremainsunknown,althoughmanycellular

actionsoflithiumhavebeencharacterised.

5.2Pharmacokineticproperties

Lithiumisexcretedalmostexclusivelyintheurinebythekidneys.

Thepharmacokineticsoflithiumareextremelywelldocumented.AsingleoraldoseofCAMCOLIT250givesapeak

plasmalevelapproximately2-3hourslater,withthelevelat24hoursbeingapproximately40%ofpeaklevels.The

half-lifeoflithiumvariesconsiderablybetweenformulations,butgenerallyisconsideredtobeabout12to24hours

followingasingledose.

Half-livesofupto36hourshavebeenreportedforelderlypatientsand40to50hoursforpatientswithrenal

impairment.Steady-stateconcentrationsmaynot,therefore,beattaineduntil4to7daysafterstartingtreatment

5.3Preclinicalsafetydata

Inanimalstudies,lithiumhasbeenreportedtointerferewithfertility,gestationandfoetaldevelopment.

6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

TabletCore

MaizeStarch

MagnesiumStearate

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FilmCoating

Hypromellose

Macrogol400

6.2Incompatibilities

Notapplicable.

6.3ShelfLife

5years.

6.4Specialprecautionsforstorage

Donotstoreabove25ºC.

Keepcontainertightlyclosed.

6.5Natureandcontentsofcontainer

Polypropylenetabletcontainer,containing100or1000tablets.

Notallpacksizesmaybemarketed.

6.6Specialprecautionsfordisposalofausedmedicinalproductorwastematerialsderivedfrom

suchmedicinalproductandotherhandlingoftheproduct

Nospecialrequirements.

7MARKETINGAUTHORISATIONHOLDER

NorgineLimited

NorgineHouse

WidewaterPlace

MoorhallRoad

Harefield

UXBRIDGE

Middlesex,UB96NS

UnitedKingdom

8MARKETINGAUTHORISATIONNUMBER

PA102/3/1

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

Dateoffirstauthorisation:1 st

April1978

Dateoflastrenewal:1 st

April2008

10DATEOFREVISIONOFTHETEXT

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