FOSALEN ONCE WEEKLY

Main information

  • Trade name:
  • FOSALEN ONCE WEEKLY
  • Dosage:
  • 70 Milligram
  • Pharmaceutical form:
  • Tablets
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug

Documents

Localization

  • Available in:
  • FOSALEN ONCE WEEKLY
    Ireland
  • Language:
  • English

Status

  • Source:
  • HPRA - Health Products Regulatory Authority - Ireland
  • Authorization number:
  • PA0585/025/002
  • Authorization date:
  • 08-12-2006
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

IRISHMEDICINESBOARDACTS1995AND2006

MEDICINALPRODUCTS(CONTROLOFPLACINGONTHEMARKET)REGULATIONS,2007

(S.I.No.540of2007)

PA0585/025/002

CaseNo:2071003

TheIrishMedicinesBoardinexerciseofthepowersconferredonitbytheabovementionedRegulationsherebygrantsto

PlivaPharmaLimited

VisionHouse,BedfordRoad,Petersfield,HampshireGU323QB,UnitedKingdom

anauthorisation,subjecttotheprovisionsofthesaidRegulations,inrespectoftheproduct

FosalenOnceWeekly70mgTablets

TheparticularsofwhicharesetoutinPartIandPartIIoftheattachedSchedule.Theauthorisationisalsosubjecttothegeneralconditionsas

maybespecifiedinthesaidRegulationsaslistedonthereverseofthisdocument.

Thisauthorisation,unlesspreviouslyrevoked,shallcontinueinforcefrom11/02/2010until07/12/2011.

SignedonbehalfoftheIrishMedicinesBoardthis

________________

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Date Printed 13/02/2010 CRN 2071003 page number: 1

PartII

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

FosalenOnceWeekly70mgTablets

2QUALITATIVEANDQUANTITATIVECOMPOSITION

Eachtabletcontains70mgalendronicacid(assodiumalendronatetrihydrate)

Excipients:

Eachtabletcontains142.64mgoflactosemonohydrate.

Forafulllistofexcipientsseesection6.1.

3PHARMACEUTICALFORM

Tablet.

Whitetooff-white,ovaltablet,embossed"AN70"ononesideandtheArrowlogoontheother.

4CLINICALPARTICULARS

4.1TherapeuticIndications

Treatmentofpost-menopausalosteoporosis.

Alendronatereducestheriskofvertebralandhipfractures.

4.2Posologyandmethodofadministration

Fororaluse.

Therecommendeddoseisone70mgtabletperweek.

Toobtainsatisfactoryabsorptionofalendronate

FosalenOnceWeekly70mgtabletsmustbetakenonanemptystomachimmediatelyonrisinginthemorning,with

plainwateronly,atleast30minutesbeforethefirstfood,drinkorothermedicationoftheday.Otherdrinks(including

mineralwater),foodandsomemedicinesarelikelytoreducetheabsorptionofalendronate(seesection4.5).

Toassistdeliverytothestomachandthusreducetheriskofirritation/sideeffectslocallyandintheoesophagus(see

section4.4)

FosalenOnceWeekly70mgtabletsshouldonlybeswallowedonarisingforthedaywithawholeglassofwater

(notlessthan200mlor7fl.oz).

FosalenOnceWeeklytabletsshouldbeswallowedwhole.Thetabletsshouldnotbechewed,suckedorallowedto

dissolveinthemouthonaccountoftheriskoforopharyngealulceration.

Patientsshouldnotliedownuntilafterthefirstmealoftheday,whichmustbeatleast30minutesaftertakingthe

tablet.

Patientsshouldnotliedownwithin30minutesoftakingFosalenOnceWeekly70mgtablets.

FosalenOnceWeekly70mgtabletsshouldnotbetakenatbedtimeorbeforearisingfortheday.

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Useinelderlypatients:Inclinicaltrialstherewasnoage-relateddifferencewithregardtoefficacyorsafetyprofilesof

alendronate.Thereforenoadjustmentofthedoseisnecessaryforelderlypatients.

Useinimpairedrenalfunction:Nodoseadjustmentisnecessaryinpatientswithaglomerularfiltrationrate(GFR)

greaterthan35ml/min.AlendronateisnotrecommendedforpatientswithimpairedrenalfunctioniftheGFRisless

than35ml/min,asthereisnoexperienceofthis.

Useinimpairedhepaticfunction

Nodoseadjustmentisnecessary.

Useinchildren(under18years)

Alendronatehasbeenstudiedinasmallnumberofpatientswithosteogenesisimperfectaunder18yearsofage.Results

areinsufficienttosupportitsuseinchildren.

FosalenOnceWeekly70mgtabletshavenotbeeninvestigatedinthetreatmentofglucocorticoid-inducedosteoporosis.

4.3Contraindications

Oesophagealabnormalitiesandotherfactorsthatdelayoesophagealemptying,suchasstrictureorachalasia.

Inabilitytostandorsituprightforatleast30minutes.

Hypersensitivitytoalendronate,otherbisphosphonatesortoanyoftheexcipients.

Hypocalcaemia.

Alsoseesection4.4.

4.4Specialwarningsandprecautionsforuse

Alendronatecancauselocalirritationtotheuppergastrointestinalmucosa.Asthereisariskofworseningofthe

underlyingdisease,cautionshouldbeobservedifalendronateisgiventopatientswithactiveuppergastrointestinal

tractproblems,suchasdysphagia,oesophagealdisease,gastritis,duodenitisorulcers,orincasesofrecent(duringthe

lastyear)severegastrointestinaldiseasesuchasgastriculcer,activegastrointestinalbleedingorsurgeryintheupper

gastrointestinaltractotherthanpyloroplasty(seesection4.3).

Oesophagealsideeffects(insomecasessevereandrequiringhospitalisation)suchasoesophagitis,oesophagealulcers

oroesophagealerosions,inrarecasesfollowedbyoesophagealstricture,havebeenreportedinpatientsreceiving

treatmentwithalendronate.Thephysicianshouldthereforebealerttoanysignsorsymptomsofpossibleoesophageal

reaction.Thepatientsshouldbeinstructedtodiscontinuealendronateandseekmedicalattentioniftheydevelop

symptomsofoesophagealirritationsuchasdysphagia,painonswallowing,retrosternalpainornew/worsened

heartburn.

Theriskofsevereoesophagealsideeffectsisthoughttobegreaterinpatientswhodonottakealendronatecorrectly

and/orcontinuetotakealendronateafterdevelopingsymptomsindicativeofoesophagealirritation.Itisveryimportant

thatcompleteadministrationinstructionsaregivento,andunderstood,bythepatient(seesection4.2).Patientsshould

beinformedthattheriskofoesophagealproblemsmayincreaseiftheydonotfollowtheseinstructions.

Despitenoincreasedriskhavingbeenobservedinextensiveclinicaltrials,therehavebeenpost-marketingreportsof

rarecasesofgastricandduodenalulcers,someofthemsevereandwithcomplications.Acausalrelationshipcannotbe

excluded(seesection4.8).

IfpatientsforgettotakeadoseofFosalenOnceWeekly70mgtablets,theyshouldbeinstructedtotakethetabletthe

morningaftertheyremember.Theymustnottaketwotabletsonthesameday,butshouldreverttotakingonetablet

perweek,asoriginallyscheduledontheirchosenday.

AlendronateisnotrecommendedforpatientswithimpairedrenalfunctioniftheGFRislessthan35ml/min(see

section4.2).

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Hypocalcaemiamustbecorrectedbeforetreatmentwithalendronateisinitiated(seesection4.3).Otherdisordersof

mineralmetabolism(suchasvitaminDdeficiencyandhypoparathyroidism)shouldalsobeeffectivelytreatedbefore

startingalendronate.Inpatientswiththeseconditionsserumcalciumandsymptomsofhypocalcaemiashouldbe

monitoredduringtreatmentwithalendronate.

Onaccountofthepositiveeffectsofalendronateontheincreaseinbonemineralisation,reductionsinserumcalcium

andserumphosphatemayoccur.Theseareusuallyslightandasymptomatic.However,inrarecasessymptomatic

hypocalcaemiahasbeenreportedwhichoccasionallyhasbeensevereandoftenoccurredinpatientswithpredisposing

conditions(e.g.hypoparathyroidism,vitaminDdeficiencyandincasesofcalciummalabsorption).

Itisthereforeparticularlyimportanttoensurethatpatientstakingglucocorticoidshaveanadequatecalciumand

vitaminDintake.

FosalenOnceWeekly70mgtabletscontainlactose.Patientswithrarehereditaryproblemsofgalactoseintolerance,the

Lapplactasedeficiencyorglucose-galactosemalabsorptionshouldnottakethismedicine.

Osteonecrosisofthejaw,generallyassociatedwithtoothextractionand/orlocalinfection(includingosteomyelitis)has

beenreportedinpatientswithcancerreceivingtreatmentregimesincludingprimarilyintravenouslyadministered

bisphosphonates.Manyofthesepatientswerealsoreceivingchemotherapyandcorticosteroids.Osteonecrosisofthe

jawhasalsobeenreportedinpatientswithosteoporosisreceivingoralbisphosphonates.

Adentalexaminationwithappropriatepreventativedentistryshouldbeconsideredpriortotreatmentwith

bisphosphonatesinpatientswithconcomitantriskfactors(e.g.cancer,chemotherapy,radiotherapy,corticosteroids,

poororalhygiene).

Whileontreatment,thesepatientsshouldavoidinvasivedentalproceduresifpossible.Forpatientswhodevelop

osteonecrosisofthejawwhileonbisphosphonatetherapy,dentalsurgerymayexacerbatethecondition.Forpatients

requiringdentalprocedures,therearenodataavailabletosuggestwhetherdiscontinuationofbisphosphonatetreatment

reducestheriskofosteonecrosisofthejaw.

Clinicaljudgementofthetreatingphysicianshouldguidethemanagementplanofeachpatientbasedonindividual

benefit/riskassessment.

4.5Interactionwithothermedicinalproductsandotherformsofinteraction

Iftakenatthesametime,itislikelythatfoodsanddrinks(includingmineralwater),calciumsupplements,antacidsand

someoralmedicineswillaffecttheabsorptionofalendronate.Patientsmustthereforewaitforatleast30minutesafter

takingalendronatebeforetakinganyotheroralmedicine(seesection4.2).

Nootherclinicallysignificantdruginteractionsareexpected.Anumberofpatientsintheclinicaltrialsreceived

oestrogen(intravaginally,transdermallyororally)concomitantlywithalendronate.Noundesirableeffectscouldbe

relatedtothecombinationtreatment.

Nospecificinteractionstudieshavebeencarriedout,butalendronatewasusedinclinicaltrialsconcomitantlywitha

numberofothercommonlyprescribedmedicineswithoutanyevidenceofclinicallyunfavourableinteractions.

4.6Pregnancyandlactation

Useduringpregnancy

Thereareinsufficientdataregardingtheuseofalendronateinpregnantwomen.Animalstudiesrevealedeffectson

foetalboneformationathighdoses.Alendronategiventopregnantratscausedhypocalcaemia-relateddystocia(see

section5.3).Inviewoftheindication,alendronateshouldnotbeusedduringpregnancy.

Useduringlactation

Itisnotknownwhetheralendronateisexcretedintobreastmilkinhumans.Inviewoftheindication,alendronate

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4.7Effectsonabilitytodriveandusemachines

TherearenodatatosuggestthatFosalenOnceWeekly70mgtabletsaffecttheabilitytodriveorusemachines.

4.8Undesirableeffects

Inaone-yearstudyinpost-menopausalwomenwithosteoporosistheoverallsafetyprofilesforalendronateonce-

weeklytablets(n=519)andalendronate10mgdaily(n=370)weresimilar.

Intwothree-yearstudiesofalmostidenticaldesign,withpost-menopausalwomen(alendronate10mg:n=196;

placebo:n=397)theoverallsafetyprofilesforalendronate10mgdailyandplaceboweresimilar.

Undesirableeffectsreportedbytheinvestigatorsaspossibly,probablyordefinitelyrelatedtothedrugarepresented

belowiftheyoccurredin 1%ofanyinthetreatmentgroupsintheone-yearstudyorin 1%ofthepatientswho

weretreatedwithalendronate10mgperdayandwithanincidencehigherthaninpatientswhoweretreatedwith

placebointhree-yearstudies.

Thefollowingundesirableeffectshavealsobeenreportedinclinicaltrialsand/orpostmarketing:

Nervoussystemdisorders:

Common(1/100,<1/10):Headache

Eyedisorders:

Rare(1/10,000,<1/1000):Uveitis,scleritis,episcleritis

Gastrointestinaldisorders:

Common(1/100,<1/10):Abdominalpain,dyspepsia,constipation,diarrhoea,flatulence,oesophagealulcers*,

dysphagia*,abdominaldistension,acidregurgitation.

Theone-yearstudy Three-yearstudies

Alendronateonce-

weeklytablet

(n=519)

% Alendronate

10mgdaily

(n=370)

% Alendronate

10mgdaily

(n=196)

% Placebo

(n=397)

%

Gastrointestinal

Abdominalpain 3.7 3.0 6.6 4.8

Dyspepsia 2.7 2.2 3.6 3.5

Acidregurgitation 1.9 2.4 2.0 4.3

Nausea 1.9 2.4 3.6 4.0

Abdominaldistension 1.0 1.4 1.0 0.8

Constipation 0.8 1.6 3.1 1.8

Diarrhoea 0.6 0.5 3.1 1.8

Dysphagia 0.4 0.5 1.0 0.0

Flatulence 0.4 1.6 2.6 0.5

Gastritis 0.2 1.1 0.5 1.3

Gastriculcer 0.0 1.1 0.0 0.0

Oesophagealulcer 0.0 0.0 1.5 0.0

Musculoskeletal

Musculoskeletalpain

(bone,muscleorjoints) 2.9 3.2 4.1 2.5

Musclecramps 0.2 1.1 0.0 1.0

Neurological

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Rare(1/10,000,<1/1000):Oesophagealstricture*,oropharyngealulceration*,uppergastrointestinalPUB

(perforations,ulcers,bleeding),acausalrelationshipcannotberuledout.

Skinandsubcutaneoustissuedisorders:

Veryrare(1/10,000):IsolatedcasesofsevereskinreactionsincludingStevens-Johnsonsyndromeandtoxic

epidermalnecrolysishavebeenreported.

Musculoskeletal,connectivetissueandbonedisorders:

Common(1/100,<1/10):Musculoskeletalpain(bones,musclesorjoints)

Unknownfrequency:osteonecrosis

Generaldisordersandadministrationsiteconditions:

Uncommon(1/1000,<1/100):Rash,pruritus,erythema.

Rare(1/10,000,<1/1000):Hypersensitivityreactionsincludingurticariaandangioedema.Transientsymptomsasin

anacutephasereaction(myalgia,malaiseandinrarecasesfever)usuallyinconnectionwiththestartoftreatment.

Skinrashwithphotosensitivity.Symptomatichypocalcaemia,generallyinconnectionwithpredisposingconditions

(see.Section4.4).

*Seesection4.4andsection4.2.

Laboratoryvalues:Inclinicaltrials,asymptomatic,slightandtransientdecreasesinserumcalciumandserum

phosphatewereobservedinapprox.18and10%respectivelyofthepatientstakingalendronate10mg/dayversus12

and3%respectivelyofthosetakingplacebo.However,theincidenceofreductionsinserumcalciumto<2.0mmol/l

andserumphosphateto0.65mmol/lwascomparableinthetwogroups.

Osteonecrosisofthejawhasbeenreportedinpatientstreatedbybisphosphonates.Themajorityofthereportsreferto

cancerpatients,butsuchcaseshavealsobeenreportedinpatientstreatedforosteoporosis.Osteonecrosisofthejawis

generallyassociatedwithtoothextractionand/orlocalinfection(includingosteomyelitis).Diagnosisofcancer,

chemotherapy,radiotherapy,corticosteroidsandpoororalhygienearealsodeemedasriskfactors(sesection4.4).

4.9Overdose

Hypocalcaemia,hypophosphataemiaanduppergastrointestinalsideeffectssuchasupsetstomach,heartburn,

oesophagitis,gastritisorulcercanoccuronoraloverdosage.Thereisnospecificinformationavailablewithregardto

overdosagewithalendronate.Milkorantacidsshouldbegiveninordertobindalendronate.Onaccountoftheriskof

oesophagealirritation,vomitingshouldnotbeinducedandthepatientshouldbekeptinanuprightposition.

5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

Pharmacotherapeuticgroup:Drugsaffectingbonestructureandmineralisation,bisphosphonates.

ATCcode:M05BA04

TheactivesubstanceinFosalenOnceWeekly70mgtablets,sodiumalendronatetrihydrate,isabisphosphonatethat

inhibitsosteoclasticboneresorptionwithoutanydirecteffectonboneformation.Preclinicalstudieshavedemonstrated

apreferenceforlocalisationofalendronatetositeswhereactiveresorptiontakesplace.Osteoclasticactivityis

inhibitedbutformationandbindingoftheosteoclastsisnotaffected.Boneformedduringtreatmentwithalendronate

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Treatmentofpost-menopausalosteoporosis

Osteoporosisisdefinedasbonemineraldensity(BMD)ofthespineorhip2.5standarddeviationsbelowthe

meanvalueofanormalyoungpopulationorasapreviousfragilityfracture,irrespectiveofbonemineral

density.

Thetherapeuticequivalenceofalendronateonce-weeklytablets(n=519)andalendronate10mgdaily(n=370)was

demonstratedinaone-yearmulticentrestudyinpost-menopausalwomenwithosteoporosis.Themeanincreasefrom

baselineofBMDinthelumbarspineafteroneyearwas5.1%(95%confidenceinterval:4.8,5.4%)inthegroup

receiving70mgonceperweekand5.4%(95%confidenceinterval:5.0,5.8%)inthegroupreceiving10mgdaily.

TheaverageincreasesinBMDinthegroupreceiving70mgonceperweekandinthegroupreceiving10mgdaily

were2.3%and2.9%inthefemoralneckand2.9%and3.1%overthetotalhip.Thetwotreatmentgroupswerealso

similarwithregardtoincreasedbonedensityinotherpartsoftheskeleton.

TheeffectsofalendronateonBMDandfractureincidenceinpost-menopausalwomenwerestudiedintwoinitial

efficacystudiesofidenticaldesign(n=994),andintheFractureInterventionTrial(FIT:n=6459).

Intheinitialefficacystudies,theincreasesinBMDwithalendronate10mgdailyrelativetoplaceboafterthreeyears

were8.8%,5.9%and7.8%atthespine,femoralneckandtrochanterrespectively.TotalbodyBMDalsoincreased

significantly.Inthepatientstreatedwithalendronate,theproportionofpatientswhosufferedoneormorevertebral

fractureswasreducedby48%(alendronate3.2%versusplacebo6.2%).Inthetwo-yearextensionsofthesestudies

theBMDinthespineandtrochantercontinuedtoincrease.Inaddition,BMDatthefemoralneckandtotalbodywas

maintained.

TheFITstudyincludedtwoplacebo-controlledtrialsinwhichalendronatewasgivendaily(5mgdailyfortwoyears

and10mgdailyforafurtheroneortwoyears).

FIT1:Athree-yearstudywith2027patientswhohadhadatleastonebaselinevertebral(compression)fracture.In

thisstudyalendronatedailyreducedtheincidenceof1newvertebralfractureby47%(alendronate7.9%versus

placebo15.0%).Inaddition,astatisticallysignificantreductionintheincidenceofhipfractureswasconfirmed

(1.1%versus2.2%,areductionof51%).

FIT2:Afour-yearstudywith4432patientswhohadalowbonemassbuthadnothadanyvertebralfractureatthe

startofthestudy.Inthisstudy,inasubgroupanalysisofosteoporoticwomen(37%ofthetotalpopulationwho

fulfilledthedefinitionofosteoporosisgivenabove)asignificantdifferencewasseenintheincidenceofhip

fractures(alendronate1.0%versusplacebo2.2%,areductionof56%)andintheincidenceof1vertebral

fracture(2.9%versus5.8%,areductionof50%).

5.2Pharmacokineticproperties

Absorption

Comparedwithanintravenousreferencedose,themeanoralbioavailabilityofalendronateinwomenwas0.64%for

dosesrangingfrom5to70mggivenafteranovernightfastandtwohoursbeforeastandardisedbreakfast.

Bioavailabilitydecreasedtoanestimated0.46%and0.39%whenalendronatewasgivenanhourorhalfanhour

beforeastandardisedbreakfast.

Inosteoporosisstudiesalendronatewaseffectivewhenitwasgivenatleast30minutesbeforethefirstmealordrinkof

theday.Bioavailabilitywasnegligibleirrespectiveofwhetheralendronatewasgiventogetherwithoruptotwohours

afterastandardisedbreakfast.Concomitantadministrationofalendronatewithcoffeeororangejuicereduced

bioavailabilitybyapprox.60%.Inhealthypersons,oralprednisolone(20mgthreetimesdailyforfivedays)didnot

resultinanyclinicallymeaningfulchangeintheoralbioavailabilityofalendronate(ameanincreaserangingfrom20%

to44%).

Distribution

Studiesinratsshowthatalendronateisinitiallydistributedtosofttissuesafterintravenousadministrationof1mg/kg,

butisthenrapidlyredistributedtotheskeletonorexcretedintheurine.Themeansteady-statevolumeofdistribution,

exclusiveofbone,isatleast28litresinhumans.Concentrationsofdruginplasmafollowingtherapeuticoraldosesare

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Biotransformation

Thereisnoevidencethatalendronateismetabolisedinanimalsorhumans.

Elimination

Followingasingleintravenousdoseof( 14

C)alendronate,approximately50%oftheradioactivitywasexcretedinthe

urinewithin72hoursandlittleornoradioactivitywasrecoveredinthefaeces.Followingasingleintravenousdoseof

10mg,therenalclearanceofalendronatewas71ml/min,andsystemicclearancedidnotexceed200ml/min.Plasma

concentrationsfellbymorethan95%within6hoursfollowingintravenousadministration.Theterminalhalf-lifein

humansisestimatedtoexceedtenyears,reflectingreleaseofalendronatefromtheskeleton.Alendronateisnot

excretedthroughtheacidicorbasictransportsystemsofthekidneyinrats,andthusitisnotthoughttointerferewith

theexcretionofotherdrugsbythosesystemsinhumans.

Characteristicsinpatients

Preclinicalstudiesshowthatthedrugthatisnotdepositedinboneisrapidlyexcretedintheurine.Noevidenceof

saturationofboneuptakewasfoundafterchronicdosingwithcumulativeintravenousdosesupto35mg/kginanimals.

Althoughnoclinicalinformationisavailable,itislikelythat,asinanimals,eliminationofalendronateviathekidney

willbereducedinpatientswithimpairedrenalfunction.Therefore,somewhatgreateraccumulationofalendronatein

bonemightbeexpectedinpatientswithimpairedrenalfunction(seesection4.2).

5.3Preclinicalsafetydata

Conventionalstudiesofgeneraltoxicity,genotoxicityandcarcinogenicitydidnotrevealanyspecialrisksforhumans.

Studiesinfemaleratsshowedthattreatmentwithalendronateduringpregnancywasassociatedwithdystociaduring

parturition,whichwasrelatedtohypocalcaemia.Studiesinwhichratsweregivenhighdosesshowedanincreased

incidenceofincompletefoetalboneformation.Therelevanceforhumansisunknown.

6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

Microcrystallinecellulose

Lactosemonohydrate

Croscarmellosesodium

Magnesiumstearate

6.2Incompatibilities

Notapplicable

6.3ShelfLife

3years

6.4Specialprecautionsforstorage

Donotstoreabove25°C.Storeintheoriginalpackage.

6.5Natureandcontentsofcontainer

Thetabletsaresuppliedintriplexblister(PVC/PE/PVDC//Al)packscontaining2,4,8,12and40tablets.

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6.6Specialprecautionsfordisposalandotherhandling

Nospecialrequirements

7MARKETINGAUTHORISATIONHOLDER

PLIVAPharmaLtd.

VisionHouse

BedfordRoad

Petersfield

Hants,GU323QB

UnitedKingdom

8MARKETINGAUTHORISATIONNUMBER

PA585/25/2

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

December2006

10DATEOFREVISIONOFTHETEXT

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