ADALAT RETARD

Main information

  • Trade name:
  • ADALAT RETARD
  • Dosage:
  • 10 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:
  • PPA1562/036/004
  • Authorization date:
  • 12-11-2010
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

AdalatRetard10mgProlonged-Releasetablets

2QUALITATIVEANDQUANTITATIVECOMPOSITION

Onefilm-coated,prolonged-releasetabletcontains10mgnifedipine.

Excipients:containslactose.

Forafulllistofexcipients,seesection6.1.

3PHARMACEUTICALFORM

Film-coated,prolonged-releasetablets

ProductimportedfromtheUK:

Grey-pink,circulartabletsmarkedwithA10ononesideandaBayercrossonthereverse.

4CLINICALPARTICULARS

4.1TherapeuticIndications

Forthemanagementofchronicstableanginapectorisandthetreatmentofmildtomoderatehypertension.

4.2Posologyandmethodofadministration

Asarule,tabletsareswallowedwholewithalittleliquid,independentlyofmeals.Therecommendedstartingdoseof

Adalatretard10mgis10mgevery12hoursswallowedwithwaterwithsubsequenttitrationofdosageaccordingto

response.Thedosemaybeadjustedto40mgevery12hours.

Adalatretard10mgpermitstitrationofinitialdosage.TherecommendeddoseisoneAdalatretard10mgtabletevery

12hours.TherecommendeddosageintervalforAdalatretard10mgtabletsorretard20mgtabletsisabout12hours

andshouldnotbelessthen4hours.

Co-administrationwithCYP3A4inhibitorsorCYP3A4inducersmayresultintherecommendationtoadaptthe

nifedipinedoseornottousenifedipineatall(seeSection4.5).

Thepharmacokineticsofnifedipinearealteredintheelderlysothatlowermaintenancedosesofnifedipinemaybe

requiredcomparedtoyoungerpatients.

Nifedipineismetabolisedprimarilybytheliverandthereforepatientswithliverdysfunctionshouldbecarefully

monitored,andinseverecases,adosereductionmaybenecessary.

Patientswithrenalimpairmentshouldnotrequireadjustmentofdosage.

Treatmentmaybecontinuedindefinitely.

Nifedipineisnotrecommendedforuseinchildren.

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4.3Contraindications

Adalatretard10mgshouldnotbeadministeredtopatientswithknownhypersensitivitytonifedipineortoother

dihydropyridinesbecauseofthetheoreticalriskofcross-reactivity.

Adalatretard10mgshouldnotbeadministeredduringpregnancyortonursingmothers.

Adalatretard10mgshouldnotbeusedincaseofcardiogenicshock,clinicallysignificantaorticstenosis,unstable

anginapectoris,orduringorwithinonemonthofamyocardialinfarction.

Adalatretard10mgshouldnotbeusedforthetreatmentofacuteattacksofangina.

ThesafetyofAdalatretard10mginmalignanthypertensionhasnotbeenestablished.

Adalatretard10mgshouldnotbeusedforsecondarypreventionofmyocardialinfarction.

Adalatretard10mgshouldnotbeadministeredconcomitantlywithrifampicinsinceeffectiveplasmalevelsof

nifedipinemaynotbeachievedowingtoenzymeinduction(seeSection4.5).

4.4Specialwarningsandprecautionsforuse

Adalatretard10mgisnotabeta-blockerandthereforegivesnoprotectionagainstthedangersofabruptbeta-blocker

withdrawal;anysuchwithdrawalshouldbeagradualreductionofthedoseofbeta-blockerpreferablyover8-10days.

Adalatretard10mgmaybeusedincombinationwithbeta-blockingdrugsandotherantihypertensiveagentsbutthe

possibilityofanadditiveeffectresultinginposturalhypotensionshouldbeborneinmind.Adalatretard10mgwillnot

preventpossiblereboundeffectsaftercessationofotherantihypertensivetherapy.

Adalatretard10mgshouldbeusedwithcautioninpatientswhosecardiacreserveispoor.Deteriorationofheartfailure

hasoccasionallybeenobservedwithnifedipine.

Cautionshouldbeexercisedinpatientswithseverehypotension.

Ischaemicpainhasbeenreportedinasmallproportionofpatientswithinonetofourhoursoftheintroductionof

Adalatretard10mgtherapy.Althougha"steal"effecthasnotbeendemonstrated,patientsexperiencingthiseffect

shoulddiscontinueAdalatretard10mg.

DiabeticpatientstakingAdalatretard10mgmayrequireadjustmentoftheircontrol.

Indialysispatientswithmalignanthypertensionandhypovoleamia,amarkeddecreasein

bloodpressurecanoccur.

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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Patientswithrarehereditaryproblemsofgalactoseintolerance,theLapplactasedeficiencyorglucose-galactose

malabsorptionshouldnottakethismedicine.

4.5Interactionwithothermedicinalproductsandotherformsofinteraction

Drugsthataffectnifedipine.

NifedipineismetabolisedviathecytochromeP4503A4system,locatedbothintheintestinalmucosaandintheliver.

Drugsthatareknowntoeitherinhibitortoinducethisenzymesystemmaythereforealterthefirstpass(afteroral

administration)ortheclearanceofnifedipine(seeSection4.4).

Theextentaswellasthedurationofinteractionsshouldbetakenintoaccountwhenadministeringnifedipinetogether

withthefollowingdrugs:

Rifampicin:RifampicinstronglyinducesthecytochromeP4503A4system.Uponco-administrationwithrifampicin,

thebioavailabilityofnifedipineisdistinctlyreducedandthusitsefficacyweakened.Theuseofnifedipinein

combinationwithrifampicinisthereforecontraindicated(seeSection4.3).

Uponco-administrationofweaktomoderateinhibitorsofthecytochromeP4503A4system(listedimmediately

below),thebloodpressureshouldbemonitoredand,ifnecessary,areductioninthenifedipinedoseconsidered(see

Sections4.2and4.4).Inthemajorityofthesecases,noformalstudiestoassessthepotentialforadruginteraction

betweennifedipineandthedrug(s)listedhavebeenundertaken,thusfar.

Macrolideantibiotics(e.g.,erythromycin):CertainmacrolideantibioticsareknowntoinhibitthecytochromeP450

3A4mediatedmetabolismofotherdrugs.Thereforethepotentialforanincreaseofnifedipineplasmaconcentrations

uponco-administrationofbothdrugscannotbeexcluded(seeSection4.4).

Azithromycin,althoughstructurallyrelatedtotheclassofmacrolideantibioticsisvoidofCYP3A4inhibition.

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

P4503A4mediatedmetabolismofnifedipine.Whenadministeredtogetherwithnifedipine,asubstantialincreasein

plasmaconcentrationsofnifedipineduetoadecreasedfirstpassmetabolismandadecreasedeliminationcannotbe

excluded(seeSection4.4).

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

Whenadministeredorallytogetherwithnifedipine,asubstantialincreaseinsystemicbioavailabilityofnifedipinedue

toadecreasedfirstpassmetabolismcannotbeexcluded(seeSection4.4).

Fluoxetine:FluoxetinehasbeenshowntoinhibitinvitrothecytochromeP4503A4mediatedmetabolismofnifedipine.

Thereforeanincreaseofnifedipineplasmaconcentrationsuponco-administrationofbothdrugscannotbeexcluded

(seeSection4.4).

Nefazodone:NefazodoneisknowntoinhibitthecytochromeP4503A4mediatedmetabolismofotherdrugs.Therefore

anincreaseinnifedipineplasmaconcentrationsuponco-administrationofbothdrugscannotbeexcluded(seeSection

4.4).

Quinupristin/dalfopristinandcisapride:Simultaneousadministrationofquinupristin/dalfopristinandnifedipine,or

cisaprideandnifedipine,mayleadtoincreasedplasmaconcentrationsofnifedipine(seeSection4.4).

Valproicacid:Asvalproicacidhasbeenshowntoincreasetheplasmaconcentrationsofthestructurallysimilar

calciumchannelblocker,nimodipine,duetoenzymeinhibition,anincreaseinnifedipineplasmaconcentrationsand

mhenceanincreaseinefficacycannotbeexcluded(seeSection4.4).

Cimetidine:DuetoitsinhibitionofcytochromeP4503A4,cimetidineelevatestheplasmaconcentrationsofnifedipine

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Furtherstudies

CytochromeP4503A4system-inducinganti-epilepticdrugs,suchasphenytoin,carbamazepineandphenobarbital:

phenytoininducesthecytochromeP4503A4system.Uponco-administrationwithphenytoin,thebioavailabilityof

nifedipineisreducedandthusitsefficacyweakened.Whenbothdrugsareadministeredconcomitantly,theclinical

responsetonifedipineshouldbemonitoredand,ifnecessary,anincreaseofthenifedipinedoseconsidered.Ifthedose

ofnifedipineisincreasedduringco-administrationofbothdrugs,areductionofthenifedipinedoseshouldbe

consideredwhenthetreatmentwithphenytoinisdiscontinued.

Noformalstudieshavebeenperformedtoinvestigatethepotentialinteractionbetweennifedipineandcarbamazepine

orphenobarbital.Asbothdrugshavebeenshowntoreducetheplasmaconcentrationsofthestructurallysimilar

calciumchannelblocker,nimodipine,duetoenzymeinduction,adecreaseinnifedipineplasmaconcentrationsand

henceadecreaseinefficacycannotbeexcluded.

Effectsofnifedipineonotherdrugs

Nifedipinemayincreasethebloodpressureloweringeffectofconcomitantappliedantihypertensives,suchas:

diuretics

beta-blockers

ACE-inhibitors

AT-1antagonists

othercalciumantagonists

alpha-adrenergicblockingagents

PDE5inhibitors

alpha-methyldopa

Whennifedipineisadministeredsimultaneouslywithbeta-receptorblockersthepatientshouldbecarefullymonitored,

sincedeteriorationofheartfailureisalsoknowntodevelopinisolatedcases.

Digoxin:Thesimultaneousadministrationofnifedipineanddigoxinmayleadtoreduceddigoxinclearanceand,hence,

anincreaseintheplasmadigoxinlevel.Thepatientshouldthereforebecheckedforsymptomsofdigoxinoverdosage

asaprecautionand,ifnecessary,theglycosidedoseshouldbereducedtakingaccountoftheplasmaconcentrationof

digoxin.

Quinidine:Whennifedipineandquinidinehavebeenadministeredsimultaneously,loweredquinidinelevels,orafter

discontinuationofnifedipine,adistinctincreaseinplasmaconcentrationsofquinidine,havebeenobservedin

individualcases.Forthisreason,whennifedipineiseitheradditionallyadministeredordiscontinued,monitoringofthe

quinidineplasmaconcentration,andifnecessary,adjustmentofthequinidinedosearerecommended.Someauthors

reportedincreasedplasmaconcentrationsofnifedipineuponco-administrationofbothdrugs,whileothersdidnot

observeanalterationinthepharmacokineticsofnifedipine.

Thereforethebloodpressureshouldbecarefullymonitored,ifquinidineisaddedtoanexistingtherapywithnifedipine.

Ifnecessary,thedoseofnifedipineshouldbedecreased.

Tacrolimus:TacrolimushasbeenshowntobemetabolisedviathecytochromeP4503A4system.Datarecently

publishedindicatesthatthedoseoftacrolimusadministeredsimultaneouslywithnifedipinemaybereducedin

individualcases.Uponco-administrationofbothdrugs,thetacrolimusplasmaconcentrationsshouldbemonitoredand,

ifnecessary,areductioninthetacrolimusdoseconsidered.

Drugfoodinteractions

GrapefruitjuiceinhibitsthecytochromeP4503A4system.Administrationofnifedipinetogetherwithgrapefruitjuice

thusresultsinelevatedplasmaconcentrationsandprolongedactionofnifedipineduetoadecreasedfirstpass

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Afterregularintakeofgrapefruitjuice,thiseffectmaylastforatleastthreedaysafterthelastingestionofgrapefruit

juice.

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

Adalatretard10mgiscontra-indicatedduringpregnancy.

Adalatretard10mgshouldnotbeusedbywomenwhointendtogetpregnantinthenearfuture.

ThesafetyofAdalatretard10mgforuseinhumanpregnancyhasnotbeenestablished.Evaluationofexperimental

animalstudieshasshownreproductivetoxicityconsistingofembryotoxicityandteratogeniceffectsatmaternallytoxic

doses.

AdalatRetard10mgiscontra-indicatedinbreastfeeding.Nifedipinepassesintothebreastmilk.Asthereisno

experienceofpossibleeffectsoninfants,breastfeedingshouldfirstbestoppedifnifedipinetreatmentbecomes

necessaryduringthebreastfeedingperiod.

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.larynx

oedema*) 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

vascular

symptoms 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:Disturbancesofconsciousnesstothe

pointofcoma,adropinbloodpressure,tachycardiac/bradycardiacheartrhythmdisturbances,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,theserumcalciumcan

reachtheuppernormalrangetoslightlyelevatedlevels.Ifaninsufficientincreaseinbloodpressureisachievedwith

calcium,vasoconstrictingsympathomimeticssuchasdopamineornoradrenalineshouldbeadministered.Thedosage

ofthesedrugsshouldbedeterminedbythepatient'sresponse.

Symptomaticbradycardiamaybetreatedwithbeta-sympathomimetics,andinlife-threateningbradycardiac

disturbancesofheartrhythm,temporarypacemakertherapymaybeadvisable.

Additionalliquidorvolumemustbeadministeredwithcautionbecauseofthedangerofoverloadingtheheart.

5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

ATCcode:C08CA05

Nifedipineisaspecificandpotentcalciumantagonistofthe1,4-dihydropyridinetype.Calciumantagonistsreducethe

transmembranalinfluxofcalciumionsthroughtheslowcalciumchannelintothecell.Nifedipineactsparticularlyon

RenalandUrinaryDisorders

Urinarydisorders Polyuria

Dysuria

ReproductiveSystemandBreastDisorders

Sexual

dysfunction Erectiledysfunction

GeneralDisordersandAdministrationSiteConditions

Generalfeelingof

illness Feelingunwell Unspecificpain

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Inhypertension,themainactionofAdalatretard10mgistocauseperipheralvasodilatationandthusreduceperipheral

resistance.Inangina,Adalatretard10mgreducesperipheralandcoronaryvascularresistance,leadingtoanincrease

incoronarybloodflow,cardiacoutputandstrokevolume,whilstdecreasingafter-load.

Additionally,nifedipinedilatessubmaximallybothclearandatheroscleroticcoronaryarteries,thusprotectingtheheart

againstcoronaryarteryspasmandimprovingperfusiontotheischaemicmyocardium.

NifedipinereducesthefrequencyofpainfulattacksandtheischaemicECGchangesirrespectiveoftherelative

contributionfromcoronaryarteryspasmoratherosclerosis.

Adalatretard10mgadministeredtwice-dailyprovides24-hourcontrolofraisedbloodpressure.

Adalatretard10mgcausesreductioninbloodpressuresuchthatthepercentageloweringisdirectlyrelatedtoitsinitial

level.Innormotensiveindividuals,Adalatretard10mghaslittleornoeffectonbloodpressure.

5.2Pharmacokineticproperties

Absorption

Afteroraladministrationnifedipineisrapidlyandalmostcompletelyabsorbed.Thesystemicavailabilityoforally

administerednifedipineis45-56%owingtoafirstpasseffect.Maximumplasmaandserumconcentrationarereached

at1.5to4.2hourswithAdalatretard20mgtablets.Simultaneousfoodintakeleadstodelayed,butnotreduced

absorption.

Distribution

Nifedipineisabout95%boundtoplasmaprotein(albumin).Thedistributionhalf-lifeafterintravenousadministration

wasdeterminedtobe5to6minutes.

Biotransformation

Afteroraladministrationnifedipineismetabolizedinthegutwallandintheliver,primarilybyoxidativeprocesses.

Thesemetabolitesshownopharmacodynamicactivity.Nifedipineisexcretedintheformofitsmetabolites

predominantlyviathekidneysandabout5-15%viathebileinthefaeces.Theunchangedsubstanceisrecoveredonly

intraces(below0.1%)intheurine.

Elimination

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

thesubstanceaftertheusualdosewasreportedduringlong-termtreatment.Incasesofimpairedkidneyfunctionno

substantialchangeshavebeendetectedincomparisonwithhealthyvolunteers.Incasesofimpairedliverfunctionthe

eliminationhalf-lifeisdistinctlyprolongedandthetotalclearanceisreduced.Adosereductionmaybenecessaryin

severecases.

5.3Preclinicalsafetydata

Preclinicaldatarevealnospecialhazardforhumansbasedonconventionalstudiesofsingleandrepeateddosetoxicity,

genotoxicityandcarcinogenicpotential.

Reproductiontoxicology

Nifedipinehasbeenshowntoproduceteratogenicfindingsinrats,miceandrabbits,includingdigitalanomalies,

malformationoftheextremities,cleftpalatescleftsternum,andmalformationoftheribs.Digitalanomaliesand

malformationoftheextremitiesarepossiblyaresultofcompromiseduterinebloodflow,buthavealsobeenobserved

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Nifedipineadministrationwasassociatedwithavarietyofembryotoxic,placentotoxicandfetotoxiceffects,including

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

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

Allofthedosesassociatedwiththeteratogenic,embryotoxicorfetotoxiceffectsinanimalswerematernallytoxicand

severaltimestherecommendedmaximumdoseforhumans(seesection4.6).

6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

Microcrystallinecellulose

Polysorbate80

Hypromellose

Lactose

Maizestarch

Macrogol

Magnesiumstearate

Titaniumdioxide(E171)

Ironoxide(E172)

6.2Incompatibilities

Notapplicable.

6.3ShelfLife

Theshelflifeexpirydateforthisproductshallbethedateshownontheblisterandouterpackageoftheproductonthe

marketinthecountryoforigin.

6.4Specialprecautionsforstorage

Storeintheoriginalcontainerinordertoprotectfromlight.

6.5Natureandcontentsofcontainer

Blisterstripsoftabletsinacardboardoutercontainer,inpacksof56tablets.

6.6Specialprecautionsfordisposalofausedmedicinalproductorwastematerialsderivedfrom

suchmedicinalproductandotherhandlingoftheproduct

Nospecialrequirements.

7PARALLELPRODUCTAUTHORISATIONHOLDER

LTTPharmaLimited

Unit18OxleasowRoad

EastMoonMoat

Redditch

WorcestershireB980RE

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8PARALLELPRODUCTAUTHORISATIONNUMBER

PPA1562/36/4

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

Dateoffirstauthorisation:12 th

November2010

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