ADALAT LA

Main information

  • Trade name:
  • ADALAT LA
  • Dosage:
  • 20 Milligram
  • Pharmaceutical form:
  • Film Coated Tablet
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug

Documents

Localization

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

Status

  • Source:
  • HPRA - Health Products Regulatory Authority - Ireland
  • Authorization number:
  • PPA1328/047/001
  • Authorization date:
  • 13-10-2006
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

IRISHMEDICINESBOARDACT1995

MEDICINALPRODUCTS(LICENSINGANDSALE)REGULATIONS,1998

(S.I.No.142of1998)

PPA1328/047/001

CaseNo:2034068

TheIrishMedicinesBoardinexerciseofthepowersconferredonitbytheabovementionedRegulationsherebygrants

B&SHealthcare

Unit4,BradfieldRoad,Ruislip,Middlesex,HA40NU,UnitedKingdom

anauthorisation,subjecttotheprovisionsofthesaidRegulations,inrespectoftheproduct

AdalatLA20mgFilm-CoatedTablets

TheparticularsofwhicharesetoutinPartIandPartIIoftheattachedSchedule.Theauthorisationisalsosubjectto

thegeneralconditionsasmaybespecifiedinthesaidRegulationsaslistedonthereverseofthisdocument.

Thisauthorisation,unlesspreviouslyrevoked,shallcontinueinforcefrom26/03/2007until12/10/2011.

SignedonbehalfoftheIrishMedicinesBoardthis

________________

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Date Printed 12/04/2007 CRN 2034068 page number: 1

PartII

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

AdalatLA20mgFilm-CoatedTablets

2QUALITATIVEANDQUANTITATIVECOMPOSITION

Eachprolonged-releaseFilm-coatedtabletcontains20mgnifedipine.

Excipients:Sodium

Forafulllistofexcipients,seesection6.1.

3PHARMACEUTICALFORM

Prolonged-release,film-coatedtablet.

ProductimportedfromItalyandtheUK:

Pink,circularbiconvextabletswith“Adalat20”,printedwithblackinkononeside.

4CLINICALPARTICULARS

4.1TherapeuticIndications

AdalatLA20:Forthetreatmentofmildtomoderatehypertension.

Forthemanagementofchronicstableanginapectoriseitherasmonotherapyorincombinationwithabeta-blocker.

4.2Posologyandmethodofadministration

Fororaladministration,thetabletsshouldbeswallowedwholewithaglassofwater.Thetablets

shouldbetakenatapproximately24-hourintervals,i.e.atthesametimeeachday,preferablyduring

themorning.AdalatLAtabletsmustbeswallowedwhole;undernocircumstancesshouldtheybe

bitten,chewedorbrokenup.

Inmildtomoderatehypertension,therecommendedinitialdoseisone20mgtabletonce-daily.In

severehypertension,therecommendedinitialdoseisone30mgtabletonce-daily.Ifnecessary,the

dosagecanbeincreasedaccordingtoindividualrequirementsuptoamaximumof90mgonce-daily.

Forthemanagementofanginapectoris,therecommendedinitialdoseisone30mgtabletonce-daily.

Thedosagecanbeincreasedaccordingtoindividualrequirementsuptoamaximumof90mgonce-

daily.

PatientsinwhomhypertensionoranginalsymptomsarecontrolledonAdalatcapsulesorAdalat

retardmaybesafelyswitchedtoAdalatLA.Prophylacticanti-anginalefficacyismaintainedwhen

patientsareswitchedfromothercalciumantagonistssuchasdiltiazemorverapamiltoAdalatLA.

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doseof30mgAdalatLAonce-daily.Subsequenttitrationtoahigherdosemaybeinitiatedas

warrantedclinically.

Thepharmacokineticsofnifedipinearealteredintheelderlysothatlowermaintenancedosesof

nifedipinemayberequiredcomparedtoyoungerpatients.

Patientswithrenalimpairmentshouldnotrequireadjustmentofdosage.

Treatmentmaybecontinuedindefinitely.

Nifedipineisnotrecommendedforuseinchildren.

AdalatLAshouldnotbetakenwithgrapefruitjuice(seeSection4.5).

4.3Contraindications

AdalatLAshouldnotbeadministeredtopatientswithknownhypersensitivitytonifedipineorother

dihydropyridinesbecauseofthetheoreticalriskofcross-reactivity.

AdalatLAshouldnotbeadministeredtowomencapableofchild-bearingortonursingmothers.

AdalatLAshouldnotbeusedincardiogenicshock,clinicallysignificantaorticstenosis,unstable

anginapectoris,orduringorwithinonemonthofamyocardialinfarction.

AdalatLAshouldnotbeusedforthetreatmentofacuteattacksofangina.

ThesafetyofAdalatLAinmalignanthypertensionhasnotbeenestablished.

AdalatLAshouldnotbeusedforsecondarypreventionofmyocardialinfarction.

Owingtothedurationofactionoftheformulation,AdalatLAshouldnotbeadministeredtopatients

withhepaticimpairment.

AdalatLAshouldnotbeadministeredtopatientswithahistoryofgastro-intestinalobstruction,

oesophagealobstruction,oranydegreeofdecreasedlumendiameterofthegastro-intestinaltract.

AdalatLAiscontra-indicatedinpatientswithinflammatoryboweldiseaseorCrohn'sdisease.

AdalatLAshouldnotbeadministeredconcomitantlywithrifampicinsinceeffectiveplasmalevelsofnifedipinemay

notbeachievedowingtoenzymeinduction(seeSection4.5).

4.4Specialwarningsandprecautionsforuse

AdalatLAtabletsmustbeswallowedwhole;undernocircumstancesshouldtheybebitten,chewedor

brokenup.

TheoutermembraneoftheAdalatLAtabletisnotdigestedand,therefore,whatappearstobethe

completetabletmaybeseeninthetoiletorassociatedwiththepatient'sstools.

Cautionshouldbeexercisedinpatientswithhypotensionasthereisariskoffurtherreductionin

bloodpressure.

AdalatLAmaybeusedincombinationwithbeta-blockingdrugsandotherantihypertensiveagents

butthepossibilityofanadditiveeffectresultinginposturalhypotensionshouldbeborneinmind.

AdalatLAwillnotpreventpossiblereboundeffectsaftercessationofotherantihypertensivetherapy.

AdalatLAshouldbeusedwithcautioninpatientswhosecardiacreserveispoor.Deteriorationof

heartfailurehasoccasionallybeenobservedwithnifedipine.

Ischaemicpainhasbeenreportedinasmallproportionofpatientsfollowingtheintroductionof

nifedipinetherapy.Althougha'steal'effecthasnotbeendemonstrated,patientsexperiencingthis

effectshoulddiscontinuenifedipinetherapy.

DiabeticpatientstakingAdalatLAmayrequireadjustmentoftheircontrol.

Indialysispatientswithmalignanthypertensionandhypovolaemia,amarkeddecreaseinblood

pressurecanoccur.

Whilstnifedipineiscontra-indicatedinpregnancy,particularcaremustbeexercisedwhen

administeringnifedipineincombinationwithi.v.magnesiumsulphatetopregnantwomen.

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fluoxetine,indinavir,nelfinavir,ritonavir,amprenavirandsaquinavir,maytheoreticallyresultinan

increaseinnifedipineplasmaconcentrations.Uponco-administrationwithanyofthesecytochrome

P4503A4inhibitors,bloodpressureshouldbemonitoredand,ifnecessary,areductioninthe

nifedipinedoseconsidered(seeSection4.5).

AstheoutermembraneoftheAdalatLAtabletisnotdigested,careshouldbeexercisedasobstructive

symptomsmayoccur,particularlyinpatientswithpre-existingseveregastrointestinalnarrowing.

Bezoarscanoccurinveryrarecasesandmayrequiresurgicalintervention.

AdalatLAmustnotbeadministeredtopatientswithKockpouch(ileostomyafterproctocolectomy).

Afalsepositiveeffectmaybeexperiencedwhenperformingabariumcontrastx-ray.

4.5Interactionwithothermedicinalproductsandotherformsofinteraction

KnownInteractions

Aswithotherdihydropyridines,nifedipineshouldnotbetakenwithgrapefruitjuiceaselevated

plasmaconcentrationsoccur,duetoadecreasedfirstpassmetabolism.Asaconsequence,theblood

pressureloweringeffectofnifedipinemaybeincreased.Afterregularintakeofgrapefruitjuice,this

effectmaylastforatleastthreedaysafterthelastingestionofgrapefruitjuice(seeSection4.2).

TheantihypertensiveeffectofAdalatLAmaybepotentiatedbysimultaneousadministrationof

cimetidine.

Whenusedincombinationwithnifedipine,serumquinidinelevelshavebeenshowntobesuppressed

regardlessofdosageofquinidine.Therefore,monitoringofquinidineplasmalevelsandifnecessary

adjustmentofthequinidinedosagearerecommended.Thepharmacokineticsofnifedipinemayalso

bealteredwhenusedincombinationwithquinidine.Itisthereforerecommendedtomonitorblood

pressure,andifnecessaryreducethenifedipinedosage.

Thesimultaneousadministrationofnifedipineanddigoxinmayleadtoreduceddigoxinclearanceand,

hence,anincreaseintheplasmadigoxinlevel.Plasmadigoxinlevelsshouldbemonitoredand,if

necessary,thedigoxindosereduced.

PhenytoininducesthecytochromeP4503A4system.Uponco-administrationwithphenytoin,the

bioavailabilityofnifedipineisreducedandthusitsefficacyweakened.Whenbothdrugsare

concomitantlyadministered,theclinicalresponsetonifedipineshouldbemonitoredand,ifnecessary,

anincreaseofthenifedipinedoseconsidered.Ifthedoseofnifedipineisincreasedduringco-

administrationofbothdrugs,areductionofthenifedipinedoseshouldbeconsideredwhenthe

treatmentwithphenytoinisdiscontinued.

Diltiazemdecreasestheclearanceofnifedipineand,hence,increasesplasmanifedipinelevels.

Therefore,cautionshouldbetakenwhenbothdrugsareusedincombinationandareductionofthe

nifedipinedosemaybenecessary.

Nifedipinemayincreasethespectrophotometricvaluesofurinaryvanillylmandelicacidfalsely.

However,HPLCmeasurementsareunaffected.

AdalatLAshouldnotbeadministeredconcomitantlywithrifampicinsinceeffectiveplasmalevelsof

nifedipinemaynotbeachievedowingtoenzymeinduction(seeSection4.3).

Simultaneousadministrationofcisaprideandnifedipineorquinupristin/dalfopristinandnifedipine

mayleadtoincreasedplasmaconcentrationsofnifedipine.Consequently,thebloodpressureshould

bemonitoredand,ifnecessary,thenifedipinedosereduced.

TheoreticalInteractions

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interactionsfordrugswhichareknowntoinhibitthisenzymesystem(e.g.erythromycin,

ketoconazole,itraconazole,fluconazole,fluoxetine,indinavir,nelfinavir,ritonavir,amprenavirand

saquinavir).Althoughnoformalinvivointeractionstudieshavebeenperformedwiththesedrugs,co-

administrationcanbeexpectedtoleadtoanincreaseinplasmaconcentrationsofnifedipine.Blood

pressureshouldthereforebemonitoredand,ifnecessary,areductioninthenifedipinedoseconsidered

(seeSection4.4).

TacrolimushasbeenshowntobemetabolisedviathecytochromeP4503A4system.Uponco-

administrationofbothdrugs,thetacrolimusplasmaconcentrationsshouldbemonitoredand,if

necessary,areductioninthetacrolimusdoseconsidered.

Aclinicalstudyinvestigatingthepotentialofadruginteractionbetweennifedipineandnefazodone

hasnotyetbeenperformed.NefazodoneisknowntoinhibitthecytochromeP4503A4mediated

metabolismofotherdrugs.Thereforeanincreaseinnifedipineplasmaconcentrationsuponco-

administrationofbothdrugscannotbeexcluded.Whennefazodoneisgiventogetherwithnifedipine,

thebloodpressureshouldbemonitoredand,ifnecessary,areductioninthenifedipinedose

considered.

Althoughnoformalinteractionstudieshavebeenperformedbetweennifedipineandcarbamazipine,

phenobarbitoneorvalproicacid,thesedrugshavebeenshowntoaltertheplasmaconcentrationsofa

structurallysimilarcalciumchannelblocker.Achangeinnifedipineplasmaconcentrationsandhence

analterationinefficacycannotbeexcluded.

Drugsshownnottointeractwithnifedipine

Thefollowingdrugshavebeenshowntohavenoeffectonthepharmacokineticsofnifedipinewhenadministered

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

orlistat,pantoprazole,ranitidine,rosiglitazone,talinololandtriamterenehydrochlorothiazide.

4.6Pregnancyandlactation

AdalatLAiscontra-indicatedinwomencapableofchildbearing.

ThesafetyofAdalatLAforuseinhumanpregnancyhasnotbeenestablished.Evaluationof

experimentalanimalstudieshasshownreproductivetoxicityconsistingofembryotoxicityand

teratogeniceffectsatmaternallytoxicdoses.

AdalatLAiscontra-indicatedinnursingmothersasnifedipinemaybepresentinbreastmilk.

Insinglecasesofinvitrofertilisationcalciumantagonistslikenifedipinehavebeenassociatedwithreversible

biochemicalchangesinthespermatozoa'sheadsectionthatmayresultinimpairedspermfunction.

Inthosemenwhoarerepeatedlyunsuccessfulinfatheringachildbyinvitrofertilisation,andwherenoother

explanationcanbefound,calciumantagonistslikenifedipineshouldbeconsideredaspossiblecauses.

4.7Effectsonabilitytodriveandusemachines

Reactionstothedrug,whichvaryinintensityfromindividualtoindividual,mayimpairtheabilitytodriveorto

operatemachinery.Thisappliesparticularlyatthestartoftreatment,onchangingthemedicationandincombination

withalcohol.

4.8Undesirableeffects

Mostundesirableeffectsareconsequencesofthevasodilatoryeffectsofnifedipineandusuallyregress

uponwithdrawaloftherapy.

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reported(>1%<10%incidence):headache,palpitationsandvasodilatationwhichoccurmost

frequentlyintheearlystagesoftreatment,lethargy,asthenia,constipation,dizzinessandoedema

particularlyperipheraloedemanotassociatedwithheartfailureorweightgain.

Additionally,uncommonandrareundesirableeffectswerealsoreported:

Uncommon(>0.1%<1%)

Rare(>0.01%<0.1%)

Aswithothersustainedreleasedihydropyridines,exacerbationofanginapectorismayoccurrarelyat

Bodyasawhole: abdominalpain;chestpain;legpain;pain;

malaise

Cardiovascular: hypotension;posturalhypotension;syncope;

tachycardia

Digestive: diarrhoea;drymouth;dyspepsia;flatulence;

nausea

Musculo-skeletal: legcramps

Nervous: insomnia;nervousness;paraesthesia;

somnolence;vertigo

Respiratory: dyspnoea

Skin: pruritus;rash

Urogenital: nocturia;polyuria

Bodyasawhole: allergicreaction;chestpainsubsternal;chills;

facialoedema;fever;hypersensitivity-type

jaundice

Cardiovascular: cardiovasculardisorder

Digestive: anorexia;eructation;gastrointestinaldisorder;

gingivitis;gingivalhyperplasia;GGT

increased;liverfunctiontestabnormalities;

vomiting

Musculo-skeletal: arthralgia;jointdisorder;myalgia

Nervous: hyperaesthesia;sleepdisorder;tremor;mood

changes

Respiratory: epistaxis

Skin: angioedema;maculopapular,pustularand

vesiculobullousrash;sweating;urticaria

Specialsenses: abnormalvision;eyedisorder;eyepain

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infarctionhasbeendescribedalthoughitisnotpossibletodistinguishsuchaneventfromthenatural

courseofischaemicheartdisease.

Forspontaneousreports(n=2886)thefollowingundesirableeffectswerereportedveryrarelyworldwide(<0.01%):

anaphylacticreaction,bezoar,dysphagia,oesophagitis,gumdisorder,intestinalobstruction,intestinalulcer,jaundice,

increaseinALT,leucopenia,purpura,hyperglycaemia,weightloss,musclecramps,exfoliativedermatitis,

photosensitivedermatitisandblurredvision.Therehavealsobeenreportsofgynaecomastiainoldermenonlong-term

therapy,butthisusuallyregressesuponwithdrawaloftherapy.

4.9Overdose

TherearenoreportsofoverdosagewithAdalatLA.

Clinicaleffects

Reportsofnifedipineoverdosagearelimitedandsymptomsarenotnecessarilydose-related.Severe

hypotensionduetovasodilatation,andtachycardiaorbradycardiaarethemostlikelymanifestations

ofoverdose.

Metabolicdisturbancesincludehyperglycaemia,metabolicacidosisandhypo-orhyperkalaemia.

Cardiaceffectsmayincludeheartblock,AVdissociationandasystole,andcardiogenicshockwith

pulmonaryoedema.

Othertoxiceffectsincludenausea,vomiting,drowsiness,dizziness,confusion,lethargy,flushing,

hypoxiaandunconsciousnesstothepointofcoma.

Treatment

Asfarastreatmentisconcerned,eliminationofnifedipineandtherestorationofstablecardiovascular

conditionshavepriority.

Afteroralingestion,gastriclavageisindicated,ifnecessaryincombinationwithirrigationofthe

smallintestine.Ipecacuanhashouldbegiventochildren.

Eliminationmustbeascompleteaspossible,includingthesmallintestine,topreventtheotherwise

inevitablesubsequentabsorptionoftheactivesubstance.

Activatedcharcoalshouldbegivenin4-hourlydosesof25gforadults,10gforchildren.

Bloodpressure,ECG,centralarterialpressure,pulmonarywedgepressure,ureaandelectrolytes

shouldbemonitored.

Hypotensionasaresultofcardiogenicshockandarterialvasodilatationshouldbetreatedwith

elevationofthefeetandplasmaexpanders.Ifthesemeasuresareineffective,hypotensionmaybe

treatedwith10%calciumgluconate10-20mlintravenouslyover5-10minutes.Iftheeffectsare

inadequate,thetreatmentcanbecontinued,withECGmonitoring.Inaddition,beta-

sympathomimeticsmaybegiven,e.g.isoprenaline0.2mgslowlyi.v.orasacontinuousinfusionof5

µg/min.Ifaninsufficientincreaseinbloodpressureisachievedwithcalciumandisoprenaline,

vasoconstrictingsympathomimeticssuchasdopamineornoradrenalineshouldbeadministered.The

dosageofthesedrugsshouldbedeterminedbythepatient'sresponse.

Bradycardiamaybetreatedwithatropine,beta-sympathomimeticsoratemporarycardiacpacemaker,

asrequired.

Additionalfluidsshouldbeadministeredwithcautiontoavoidcardiacoverload.

5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

ATCcode:C08CA05

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Asaspecificandpotentcalciumantagonist,themainactionofnifedipineistorelaxarterialsmooth

muscle,bothinthecoronaryandperipheralcirculation.TheAdalatLAtabletisformulatedtoachieve

controlleddeliveryofnifedipineinareleaseprofilesufficienttoenableonce-dailyadministrationto

beeffectiveinclinicaluse.

Inhypertension,themainactionofnifedipineistocauseperipheralvasodilatationandthusreduce

peripheralresistance.Nifedipineadministeredonce-dailyprovides24-hourcontrolofraisedblood

pressure.Nifedipinecausesreductioninbloodpressuresuchthatthepercentageloweringis

proportionaltoitsinitiallevel.

Innormotensiveindividuals,nifedipinehaslittleornoeffectonbloodpressure.

Inangina,AdalatLAreducesperipheralandcoronaryvascularresistance,leadingtoanincreasein

coronarybloodflow,cardiacoutputandstrokevolume,whilstdecreasingafter-load.Additionally,

nifedipinedilatessubmaximallybothclearandatheroscleroticcoronaryarteries,thusprotectingthe

heartagainstcoronaryarteryspasmandimprovingperfusiontotheischaemicmyocardium.

NifedipinereducesthefrequencyofpainfulattacksandtheischaemicECGchangesirrespectiveofthe

relativecontributionfromcoronaryarteryspasmoratherosclerosis.

Inamulti-national,randomised,double-blind,prospectivestudyinvolving6321hypertensivepatientswithatleastone

additionalriskfactorfollowedover3to4.8years,AdalatLA30and60(nifedipineGITS)wereshowntoreduce

cardiovascularandcerebrovasculareventstoacomparabledegreeasastandarddiureticcombination.

5.2Pharmacokineticproperties

Generalcharacteristics:

Orallyadministerednifedipineisalmostcompletelyabsorbedinthegastro-intestinaltract.Nifedipine

undergoesfirst-passmetabolismintheliver,givingasystemicavailabilityof45-68%followingoral

administration.Atsteady-state,thebioavailabilityofAdalatLAtabletsrangesfrom68-86%relative

toAdalatcapsules.Administrationinthepresenceoffoodslightlyalterstheearlyrateofabsorption

butdoesnotinfluencetheextentofdrugavailability.

Nifedipineisalmostcompletelymetabolisedintheliver.Nifedipineiseliminatedintheformofits

metabolites,predominantlyviathekidneys,withapproximately5-15%beingexcretedviathebilein

thefaeces.Non-metabolisednifedipinecanbedetectedonlyintraces(below1.0%)intheurine.

Nifedipineisapproximately95%boundtoplasmaprotein.

TheAdalatLAtabletisformulatedtoreleasenifedipineinacontrolledwaytoenableonce-daily

administration.

Thepharmacokineticprofileofthisformulationischaracterisedbylowpeak-troughfluctuation.0-24

hourplasmaconcentrationversustimeprofilesatsteady-stateareplateau-like,renderingtheAdalat

LAtabletappropriateforonce-a-dayadministration.

Characteristicsinpatients:

Therearenosignificantdifferencesinthepharmacokineticsofnifedipinebetweenhealthysubjects

andsubjectswithrenalimpairment.Therefore,dosageadjustmentisnotneededinthesepatients.

Inpatientswithhepaticimpairment,theeliminationhalf-lifeisdistinctlyprolongedandthetotalclearanceisreduced.

Owingtothedurationofactionoftheformulation,AdalatLAshouldnotbeadministeredinthesepatients.

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Followingacuteoralandintravenousadministrationofnifedipineinvariousanimalspecies,thefollowingLD

(mg/kg)valueswereobtained:

Mouse:Oral:454(401-572)*;i.v.:4.2(3.8-4.6)*.

Rat:Oral:1022(950-1087)*;i.v.:15.5(13.7-17.5)*.

Rabbit:Oral:250-500;i.v.:2-3.

Cat:Oral:~100;i.v.:0.5-8.

Dog:Oral:>250;i.v.:2-3.

*95%confidenceinterval.

Insubacuteandsubchronictoxicitystudiesinratsanddogs,nifedipinewastoleratedwithoutdamageatdosesofupto

50mg/kg(rats)and100mg/kg(dogs)p.o.overperiodsofthirteenandfourweeks,respectively.Followingintravenous

administration,dogstoleratedupto0.1mg/kgnifedipineforsixdayswithoutdamage.Ratstolerateddailyintravenous

administrationof2.5mg/kgnifedipineoveraperiodofthreeweekswithoutdamage.

Inchronictoxicitystudiesindogswithtreatmentlastinguptooneyear,nifedipinewastoleratedwithoutdamageat

dosesuptoandincluding100mg/kgp.o..Inrats,toxiceffectsoccurredatconcentrationsabove100ppminthefeed

(approximately5-7mg/kgbodyweight).

Inacarcinogenicitystudyinrats(twoyears),therewasnoevidenceofacarcinogeniceffectofnifedipine.

Instudiesinmice,ratsandrabbits,adosewhichwasmaternallytoxicinducedteratogeniceffectsinsomecasesand

embryotoxicity.Ininvitroandinvivotests,nifedipinehasnotbeenassociatedwithmutagenicproperties.

6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

Propyleneglycol

Celluloseacetate

Hypromellose

Hyprolose

Polyethyleneoxide

Macrogol

Magnesiumstearate

Sodiumchloride

Titaniumdioxide(E171)

Ironoxide,red(E172)

ThetabletsfromtheUKalsocontain:

Shellac

6.2Incompatibilities

Notapplicable.

6.3ShelfLife

Theshelf-lifeexpirydateofthisproductshallbethedateshownonthecontainerandouterpackageoftheproducton

themarketinthecountryoforigin.

6.4Specialprecautionsforstorage

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6.5Natureandcontentsofcontainer

BlisterpackscomposedofPPbackedwithaluminiumfoil,eachcontaining14or28tablets.

6.6Specialprecautionsfordisposalofausedmedicinalproductorwastematerials

derivedfromsuchmedicinalproductandotherhandlingoftheproduct

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7ParallelProductAuthorisationHolder

B&SHealthcare

Unit4

BradfieldRoad

Ruislip

Middlesex

HA40NU

UnitedKingdom

8ParallelProductAuthorisationNumber

PPA1328/47/1

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

DateofFirstAuthorisation:13thOctober2006

10DATEOFREVISIONOFTHETEXT

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