ADALAT RETARD

Main information

  • Trade name:
  • ADALAT RETARD
  • Dosage:
  • 20 Milligram
  • Pharmaceutical form:
  • Tablet Prolonged Release
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug

Documents

Localization

  • Available in:
  • ADALAT RETARD
    Ireland
  • Language:
  • English

Status

  • Source:
  • HPRA - Health Products Regulatory Authority - Ireland
  • Authorization number:
  • PPA1447/058/001
  • Authorization date:
  • 05-02-2010
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

AdalatRetard20mgProlongedReleaseTablets

2QUALITATIVEANDQUANTITATIVECOMPOSITION

Onefilm-coated,prolonged-releasetabletcontains20mgnifedipine.

Excipient:Lactosemonohydrate

Forafulllistofexcipients,seesection6.1.

3PHARMACEUTICALFORM

Film-coated,prolonged-releasetablet

ProductimportedfromGreece:

Grey-pink,circulartabletsmarkedwith'1U'ononesideandaBayercrossonthereverse

4CLINICALPARTICULARS

4.1TherapeuticIndications

Forthemanagementofchronicstableanginapectorisandthetreatmentofmildtomoderatehypertension.

4.2Posologyandmethodofadministration

Asarule,tabletsareswallowedwholewithalittleliquid,independentlyofmeals.Therecommendedstartingdoseof

Adalatretard20mgis10mgevery12hoursswallowedwithwaterwithsubsequenttitrationofdosageaccordingto

response.Thedosemaybeadjustedto40mgevery12hours.

Adalatretard10mgpermitstitrationofinitialdosage.TherecommendeddoseisoneAdalatretard10mgtabletevery12

hours.TherecommendeddosageintervalforAdalatretard10mgtabletsorretard20mgtabletsisabout12hoursand

shouldnotbelessthan4hours.

Co-administrationwithCYP3A4inhibitorsorCYP3A4inducersmayresultintherecommendationtoadaptthe

nifedipinedoseornottousenifedipineatall(seeSection4.5).

Thepharmacokineticsofnifedipinearealteredintheelderlysothatlowermaintenancedosesofnifedipinemaybe

requiredcomparedtoyoungerpatients.

Nifedipineismetabolisedprimarilybytheliverandthereforepatientswithliverdysfunctionshouldbecarefully

monitored,andinseverecases,adosereductionmaybenecessary.

Patientswithrenalimpairmentshouldnotrequireadjustmentofdosage.

Treatmentmaybecontinuedindefinitely.

Nifedipineisnotrecommendedforuseinchildren.

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4.3Contraindications

Adalatretard20mgshouldnotbeadministeredtopatientswithknownhypersensitivitytonifedipineorother

dihydropyridinesbecauseofthetheoreticalriskofcross-reactivity.

Adalatretard20mgshouldnotbeadministeredduringpregnancyortonursingmothers.

Adalatretard20mgshouldnotbeusedincardiogenicshock,clinicallysignificantaorticstenosis,unstableangina

pectoris,orduringorwithinonemonthofamyocardialinfarction.

Adalatretard20mgshouldnotbeusedforthetreatmentofacuteattacksofangina.

ThesafetyofAdalatretard20mginmalignanthypertensionhasnotbeenestablished.

Adalatretard20mgshouldnotbeusedforsecondarypreventionofmyocardialinfarction.

Adalatretard20mgshouldnotbeadministeredconcomitantlywithrifampicinsinceeffectiveplasmalevelsof

nifedipinemaynotbeachievedowingtoenzymeinduction(seeSection4.5).

4.4Specialwarningsandprecautionsforuse

Adalatretard20mgisnotabeta-blockerandthereforegivesnoprotectionagainstthedangersofabruptbeta-blocker

withdrawal;anysuchwithdrawalshouldbeagradualreductionofthedoseofbeta-blockerpreferablyover8–10days.

Adalatretard20mgmaybeusedincombinationwithbeta-blockingdrugsandotherantihypertensiveagentsbutthe

possibilityofanadditiveeffectresultinginposturalhypotensionshouldbeborneinmind.Adalatretard20mgwillnot

preventpossiblereboundeffectsaftercessationofotherantihypertensivetherapy.

Cautionshouldbeexercisedinpatientswithseverehypotension.

Adalatretard20mgshouldbeusedwithcautioninpatientswhosecardiacreserveispoor.Deteriorationofheart

failurehasoccasionallybeenobservedwithnifedipine.

IschaemicpainhasbeenreportedinasmallproportionofpatientswithinonetofourhoursoftheintroductionofAdalat

retard20mgtherapy.Althougha"steal"effecthasnotbeendemonstrated,patientsexperiencingthiseffectshould

discontinueAdalatretard20mg.

DiabeticpatientstakingAdalatretard20mgmayrequireadjustmentoftheircontrol.

Indialysispatientswithmalignanthypertensionandhypovolaemia,amarkeddecreaseinbloodpressurecanoccur.

Therearenosafetyandefficacydatafromwell-controlledstudiesinpregnantwomen(seesection4.6).

Animalstudieshaveshownavarietyofembryotoxic,placentotoxicandfetotoxiceffects(seeSection5.3)when

administeredduringandaftertheperiodoforganogenesis.

Whilstnifedipineiscontra-indicatedinpregnancy,particularcaremustbeexercisedwhenadministeringnifedipinein

combinationwithi.v.magnesiumsulphatetopregnantwomen.

Co-administrationofnifedipinewitherythromycin,ketoconazole,itraconazole,fluconazole,fluoxetine,indinavir,

nelfinavir,ritonavir,amprenavirandsaquinavirmaytheoreticallyresultinanincreaseinnifedipineplasma

concentrations.Uponco-administrationwithanyofthesecytochromeP4503A4inhibitors,bloodpressureshouldbe

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4.5Interactionwithothermedicinalproductsandotherformsofinteraction

Drugsthataffectnifedipine

NifedipineismetabolisedviathecytochromeP4503A4system,locatedbothintheintestinalmucosaandintheliver.

Drugsthatareknowntoeitherinhibitortoinducethisenzymesystemmaythereforealterthefirstpass(afteroral

administration)ortheclearanceofnifedipine(seeSection4.4).

Theextentaswellasthedurationofinteractionsshouldbetakenintoaccountwhenadministeringnifedipinetogetherwith

thefollowingdrugs:

Rifampicin:RifampicinstronglyinducesthecytochromeP4503A4system.Uponco-administrationwithrifampicin,the

bioavailabilityofnifedipineisdistinctlyreducedandthusitsefficacyweakened.Theuseofnifedipineincombinationwith

rifampicinisthereforecontraindicated(seeSection4.3).

Uponco-administrationofweaktomoderateinhibitorsofthecytochromeP4503A4system(listedimmediatelybelow),

thebloodpressureshouldbemonitoredand,ifnecessary,areductioninthenifedipinedoseconsidered(seeSections4.2

and4.4).Inthemajorityofthesecases,noformalstudiestoassessthepotentialforadruginteractionbetweennifedipine

andthedrug(s)listedhavebeenundertaken,thusfar.

Macrolideantibiotics(e.g.,erythromycin):CertainmacrolideantibioticsareknowntoinhibitthecytochromeP4503A4

mediatedmetabolismofotherdrugs.Thereforethepotentialforanincreaseofnifedipineplasmaconcentrationsuponco-

administrationofbothdrugscannotbeexcluded(seeSection4.4).

Azithromycin,althoughstructurallyrelatedtotheclassofmacrolideantibioticsisvoidofCYP3A4inhibition.

Anti-HIVproteaseinhibitors(e.g.,ritonavir):DrugsofthisclasshavebeenshowntoinhibitinvitrothecytochromeP450

3A4mediatedmetabolismofnifedipine.Whenadministeredtogetherwithnifedipine,asubstantialincreaseinplasma

concentrationsofnifedipineduetoadecreasedfirstpassmetabolismandadecreasedeliminationcannotbeexcluded(see

Section4.4).

Azoleanti-mycotics(e.g.,ketoconazole):DrugsofthisclassareknowntoinhibitthecytochromeP4503A4system.When

administeredorallytogetherwithnifedipine,asubstantialincreaseinsystemicbioavailabilityofnifedipineduetoa

decreasedfirstpassmetabolismcannotbeexcluded(seeSection4.4).

Fluoxetine:FluoxetinehasbeenshowntoinhibitinvitrothecytochromeP4503A4mediatedmetabolismofnifedipine.

Thereforeanincreaseofnifedipineplasmaconcentrationsuponco-administrationofbothdrugscannotbeexcluded(see

Section4.4).

Nefazodone:NefazodoneisknowntoinhibitthecytochromeP4503A4mediatedmetabolismofotherdrugs.Thereforean

increaseinnifedipineplasmaconcentrationsuponco-administrationofbothdrugscannotbeexcluded(seeSection4.4).

Quinupristin/dalfopristinandcisapride:Simultaneousadministrationofquinupristin/dalfopristinandnifedipine,or

cisaprideandnifedipine,mayleadtoincreasedplasmaconcentrationsofnifedipine(seeSection4.4).

Valproicacid:Asvalproicacidhasbeenshowntoincreasetheplasmaconcentrationsofthestructurallysimilarcalcium

channelblocker,nimodipine,duetoenzymeinhibition,anincreaseinnifedipineplasmaconcentrationsandhencean

increaseinefficacycannotbeexcluded(seeSection4.4).

Cimetidine:DuetoitsinhibitionofcytochromeP4503A4,cimetidineelevatestheplasmaconcentrationsofnifedipineand

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Furtherstudies

CytochromeP4503A4system-inducinganti-epilepticdrugs,suchasphenytoin,carbamazepineandphenobarbital:

phenytoininducesthecytochromeP4503A4system.Uponco-administrationwithphenytoin,thebioavailabilityof

nifedipineisreducedandthusitsefficacyweakened.Whenbothdrugsareadministeredconcomitantly,theclinical

responsetonifedipineshouldbemonitoredand,ifnecessary,anincreaseofthenifedipinedoseconsidered.Ifthedoseof

nifedipineisincreasedduringco-administrationofbothdrugs,areductionofthenifedipinedoseshouldbeconsidered

whenthetreatmentwithphenytoinisdiscontinued.

Noformalstudieshavebeenperformedtoinvestigatethepotentialinteractionbetweennifedipineandcarbamazepineor

phenobarbital.Asbothdrugshavebeenshowntoreducetheplasmaconcentrationsofthestructurallysimilarcalcium

channelblocker,nimodipine,duetoenzymeinduction,adecreaseinnifedipineplasmaconcentrationsandhencea

decreaseinefficacycannotbeexcluded.

Effectsofnifedipineonotherdrugs

Nifedipinemayincreasethebloodpressureloweringeffectofconcomitantappliedantihypertensives,suchas:

diuretics

beta-blockers

ACE-inhibitors

AT-1antagonists

othercalciumantagonists

alpha-adrenergicblockingagents

PDE5inhibitors

alpha-methyldopa

Whennifedipineisadministeredsimultaneouslywithbeta-receptorblockersthepatientshouldbecarefullymonitored,

sincedeteriorationofheartfailureisalsoknowntodevelopinisolatedcases.

Digoxin:Thesimultaneousadministrationofnifedipineanddigoxinmayleadtoreduceddigoxinclearanceand,hence,an

increaseintheplasmadigoxinlevel.Thepatientshouldthereforebecheckedforsymptomsofdigoxinoverdosageasa

precautionand,ifnecessary,theglycosidedoseshouldbereducedtakingaccountoftheplasmaconcentrationofdigoxin.

Quinidine:Whennifedipineandquinidinehavebeenadministeredsimultaneously,loweredquinidinelevels,orafter

discontinuationofnifedipine,adistinctincreaseinplasmaconcentrationsofquinidine,havebeenobservedinindividual

cases.Forthisreason,whennifedipineiseitheradditionallyadministeredordiscontinued,monitoringofthequinidine

plasmaconcentration,andifnecessary,adjustmentofthequinidinedosearerecommended.Someauthorsreported

increasedplasmaconcentrationsofnifedipineuponco-administrationofbothdrugs,whileothersdidnotobservean

alterationinthepharmacokineticsofnifedipine.

Thereforethebloodpressureshouldbecarefullymonitored,ifquinidineisaddedtoanexistingtherapywithnifedipine.If

necessary,thedoseofnifedipineshouldbedecreased.

Tacrolimus:TacrolimushasbeenshowntobemetabolisedviathecytochromeP4503A4system.Datarecentlypublished

indicatethatthedoseoftacrolimusadministeredsimultaneouslywithnifedipinemaybereducedinindividualcases.Upon

co-administrationofbothdrugs,thetacrolimusplasmaconcentrationsshouldbemonitoredand,ifnecessary,areductionin

thetacrolimusdoseconsidered.

Drugfoodinteractions

GrapefruitjuiceinhibitsthecytochromeP4503A4system.Administrationofnifedipinetogetherwithgrapefruitjuicethus

resultsinelevatedplasmaconcentrationsandprolongedactionofnifedipineduetoadecreasedfirstpassmetabolismor

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Afterregularintakeofgrapefruitjuice,thiseffectmaylastforatleastthreedaysafterthelastingestionofgrapefruitjuice.

Ingestionofgrapefruit/grapefruitjuiceisthereforetobeavoidedwhiletakingnifedipine(seeSection4.2).

Drugsshownnottointeractwithnifedipine

Thefollowingdrugshavebeenshowntohavenoeffectonthepharmacokineticsofnifedipinewhenadministered

concomitantly:ajmaline,aspirin,benazepril,candesartancilexetil,debrisoquine,doxazosin,irbesartan,omeprazole,

orlistat,pantoprazole,ranitidine,rosiglitazone,talinololandtriamterenehydrochlorothiazide.

Otherformsofinteraction

Nifedipinemayincreasethespectrophotometricvaluesofurinaryvanillylmandelicacidfalsely.However,HPLC

measurementsareunaffected.

4.6Fertility,pregnancyandlactation

Adalatretard20mgiscontra-indicatedduringpregnancy.

Adalatretard20mgshouldnotbeusedbywomenwhointendtogetpregnantinthenearfuture.

ThesafetyofAdalatretard20mgforuseinhumanpregnancyhasnotbeenestablished.Evaluationofexperimental

animalstudieshasshownreproductivetoxicityconsistingofembryotoxicityandteratogeniceffectsatmaternallytoxic

doses.

AdalatRetard20mgiscontra-indicatedinbreastfeeding.Nifedipinepassesintothebreastmilk.Asthereisnoexperience

ofpossibleeffectsoninfants,breastfeedingshouldfirstbestoppedifnifedipinetreatmentbecomesnecessaryduringthe

breastfeedingperiod.

Insinglecasesofinvitrofertilisationcalciumantagonistslikenifedipinehavebeenassociatedwithreversible

biochemicalchangesinthespermatozoa’sheadsectionthatmayresultinimpairedspermfunction.Inthosemenwho

arerepeatedlyunsuccessfulinfatheringachildbyinvitrofertilisation,andwherenootherexplanationcanbefound,

calciumantagonistslikenifedipineshouldbeconsideredaspossiblecauses.

4.7Effectsonabilitytodriveandusemachines

Reactionstothedrug,whichvaryinintensityfromindividualtoindividual,mayimpairtheabilitytodriveorto

operatemachinery.Thisappliesparticularlyatthestartoftreatment,onchangingthemedicationandincombination

withalcohol.

4.8Undesirableeffects

Adversedrugreactions(ADRs)basedonplacebo-controlledstudieswithnifedipinesortedbyCIOMSIIIcategoriesof

frequency(clinicaltrialdatabase:nifedipinen=2,661;placebon=1,486;status:22Feb2006andtheACTIONstudy:

nifedipinen=3,825;placebon=3,840)arelistedbelow:ADRslistedunder“common”wereobservedwitha

frequencybelow3%withtheexceptionofoedema(9.9%)andheadache(3.9%).ADRsderivedfrompostmarketing

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Clinical

Description Common

1%to<10% Uncommon

0.1%to<1% Rare

0.01%to<0.1% VeryRare

<0.01%

ImmuneSystemDisorders

Acute

hypersensitivity

reactions Allergicreaction

Allergic

oedema/angioedema

(incl.larynxoedema*) Pruritus

Urticaria

Rash Anaphylactic/

anaphylactoid

reaction

PsychiatricDisorders

Behavioural

disturbancesand

sleepdisorders Anxietyreactions

Sleepdisorders

NervousSystemDisorders

Unspecific

cerebrovascular

symptoms Headache Vertigo

Migraine

Unspecific

neurological

symptoms Dizziness

Tremor

Unspecificaltered

peripheral

perception Par-dysaesthesia

EyeDisorders

Unspecificeye

disorders Visualdisturbances

CardiacDisorders

Unspecific

arrhythmias Tachycardia

Palpitations

VascularDisorders

Unspecific

vascularsymptoms Oedema

Vasodilatation Hypotension

Syncope

Respiratory,ThoracicandMediastinalDisorders

Upperrespiratory

tractsymptoms Nasalcongestion

Nosebleed Dyspnoea

GastrointestinalDisorders

Gastro-intestinal

symptoms Constipation Gastrointestinaland

abdominalpain

Nausea

Dyspepsia

Flatulence

Drymouth Gingival

hyperplasia Vomiting

HepatobiliaryDisorders

Mildtomoderate

hepaticreactions Transientincreasein

liverenzymes

SkinandSubcutaneousTissuedisorders

Unspecificskin

reactions Erythema

Musculoskeletal,ConnectiveTissueandBoneDisorders

Unspecificjoint

andmuscular

disorders Musclecramps

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*=Mayresultinlifethreateningoutcome.

Indialysispatientswithmalignanthypertensionandhypovolaemiaadistinctfallinbloodpressurecanoccurasaresult

ofvasodilation.

4.9Overdose

Symptoms

Thefollowingsymptomsareobservedincasesofseverenifedipineintoxication:

Disturbancesofconsciousnesstothepointofcoma,adropinbloodpressure,tachycardiac/bradycardiacheartrhythm

disturbances,hyperglycaemia,metabolicacidosis,hypoxia,cardiogenicshockwithpulmonaryoedema.

Treatment

Asfarastreatmentisconcerned,eliminationoftheactivesubstanceandtherestorationofstablecardiovascular

conditionshavepriority.

Afteroralingestion,thoroughgastriclavageisindicated,ifnecessaryincombinationwithirrigationofthesmall

intestine.Particularlyincasesofintoxicationwithslow-releasenifedipineformulations,suchasAdalatretard10mg

and20mg,eliminationmustbeascompleteaspossible,includingthesmallintestine,topreventtheotherwise

inevitablesubsequentabsorptionoftheactivesubstance.

Haemodialysisservesnopurpose,asnifedipineisnotdialysable,butplasmapheresisisadvisable(highplasmaprotein

binding,relativelylowvolumeofdistribution).

Hypotensionasaresultofcardiogenicshockandarterialvasodilatationcanbetreatedwithcalcium(10-20mlofa10%

calciumgluconatesolutionadministeredslowlyi.v.andrepeatedifnecessary).Asaresult,theserumcalciumcanreach

theuppernormalrangetoslightlyelevatedlevels.Ifaninsufficientincreaseinbloodpressureisachievedwithcalcium,

vasoconstrictingsympathomimeticssuchasdopamineornoradrenalineshouldbeadministered.Thedosageofthese

drugsshouldbedeterminedbythepatient'sresponse.

Symptomaticbradycardiamaybetreatedwithbeta-sympathomimetics,andinlife-threateningbradycardicdisturbancesof

heartrhythm,temporarypacemakertherapymaybeadvisable.

Additionalliquidorvolumemustbeadministeredwithcautionbecauseofthedangerofoverloadingtheheart.

5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

ATCcode:C08CA05

Nifedipineisaspecificandpotentcalciumantagonistofthe1,4-dihydropyridinetype.Calciumantagonistsreducethe

transmembranalinfluxofcalciumionsthroughtheslowcalciumchannelintothecell.

Nifedipineactsparticularlyonthecellsofthemyocardiumandthesmoothmusclecellsofthecoronaryarteriesandthe

RenalandUrinaryDisorders

Urinarydisorders Polyuria

Dysuria

ReproductiveSystemandBreastDisorders

Sexualdysfunction Erectiledysfunction

GeneralDisordersandAdministrationSiteConditions

Generalfeelingof

illness Feelingunwell Unspecificpain

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Inhypertension,themainactionofAdalatretard20mgistocauseperipheralvasodilatationandthusreduceperipheral

resistance.Inangina,Adalatretard 20mgreducesperipheralandcoronaryvascularresistance,leadingtoanincreasein

coronarybloodflow,cardiacoutputandstrokevolume,whilstdecreasingafter-load.

Additionally,nifedipinedilatessubmaximallybothclearandatheroscleroticcoronaryarteries,thusprotectingtheheart

againstcoronaryarteryspasmandimprovingperfusiontotheischaemicmyocardium.

NifedipinereducesthefrequencyofpainfulattacksandtheischaemicECGchangesirrespectiveoftherelativecontribution

fromcoronaryarteryspasmoratherosclerosis.

Adalatretard20mgadministeredtwice-dailyprovides24-hourcontrolofraisedbloodpressure.Adalatretard20mg

causesreductioninbloodpressuresuchthatthepercentageloweringisdirectlyrelatedtoitsinitiallevel.Innormotensive

individuals,Adalatretard20mghaslittleornoeffectonbloodpressure.

5.2Pharmacokineticproperties

Absorption

Afteroraladministrationnifedipineisrapidlyandalmostcompletelyabsorbed.Thesystemicavailabilityoforally

administerednifedipineis45-56%owingtoafirstpasseffect.Maximumplasmaandserumconcentrationarereachedat

1.5to4.2hourswithAdalatretard20mgtablets.Simultaneousfoodintakeleadstodelayed,butnotreducedabsorption.

Distribution

Nifedipineisabout95%boundtoplasmaprotein(albumin).Thedistributionhalf-lifeafterintravenousadministrationwas

determinedtobe5to6minutes.

Biotransformation

Afteroraladministrationnifedipineismetabolizedinthegutwallandintheliver,primarilybyoxidativeprocesses.These

metabolitesshownopharmacodynamicactivity.Nifedipineisexcretedintheformofitsmetabolitespredominantlyviathe

kidneysandabout5-15%viathebileinthefaeces.Theunchangedsubstanceisrecoveredonlyintraces(below0.1%)in

theurine.

Elimination

Theterminaleliminationhalf-lifeis6-11hours(Adalatretard),becauseofdelayedabsorption.Noaccumulationofthe

substanceaftertheusualdosewasreportedduringlong-termtreatment.Incasesofimpairedkidneyfunctionnosubstantial

changeshavebeendetectedincomparisonwithhealthyvolunteers.Incasesofimpairedliverfunctiontheeliminationhalf-

lifeisdistinctlyprolongedandthetotalclearanceisreduced.Adosereductionmaybenecessaryinseverecases.

5.3Preclinicalsafetydata

Preclinicaldatarevealnospecialhazardforhumansbasedonconventionalstudiesofsingleandrepeateddosetoxicity,

genotoxicityandcarcinogenicpotential.

Reproductiontoxicology

Nifedipinehasbeenshowntoproduceteratogenicfindingsinrats,miceandrabbits,includingdigitalanomalies,

malformationoftheextremities,cleftpalates,cleftsternum,andmalformationoftheribs.Digitalanomaliesand

malformationoftheextremitiesarepossiblyaresultofcompromiseduterinebloodflow,buthavealsobeenobservedin

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Nifedipineadministrationwasassociatedwithavarietyofembryotoxic,placentotoxicandfetotoxiceffects,including

stuntedfetuses(rats,mice,rabbits),smallplacentasandunderdevelopedchorionicvilli(monkeys),embryonicandfetal

deaths(rats,mice,rabbits)andprolongedpregnancy/decreasedneonatalsurvival(rats;notevaluatedinotherspecies).All

ofthedosesassociatedwiththeteratogenic,embryotoxicorfetotoxiceffectsinanimalswerematernallytoxicandseveral

timestherecommendedmaximumdoseforhumans(seeSection4.6).

6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

Microcrystallinecellulose

Polysorbate80

Hypromellose

Lactosemonohydrate

Maizestarch

Macrogol4000

Magnesiumstearate

Titaniumdioxide(E171)

Redironoxide(E172)

6.2Incompatibilities

Notapplicable

6.3Shelflife

Theshelflifeexpirydateforthisproductshallbethedateshownonthecontainerandouterpackageoftheproducton

themarketinthecountryoforigin

6.4Specialprecautionsforstorage

Donotstoreabove25 o

Keeptheblistersintheoutercartoninordertoprotectfromlight.

6.5Natureandcontentsofcontainer

Over-labelledcardboardcartonscontaining3blisterstrips(10tabletsperstrip)

Packsize30tablets.

6.6Specialprecautionsfordisposalofausedmedicinalproductorwastematerialsderivedfrom

suchmedicinalproductandotherhandlingoftheproduct

Nospecialrequirements.

7PARALLELPRODUCTAUTHORISATIONHOLDER

G&ALicensingLimited

Ballymurray

Co.Roscommon

8PARALLELPRODUCTAUTHORISATIONNUMBER

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9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

Dateoffirstauthorisation:5 th

February2010

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