FOSALEN

Main information

  • Trade name:
  • FOSALEN Tablets 10 Milligram
  • Dosage:
  • 10 Milligram
  • Pharmaceutical form:
  • Tablets
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug

Documents

Localization

  • Available in:
  • FOSALEN Tablets 10 Milligram
    Ireland
  • Language:
  • English

Status

  • Source:
  • HPRA - Health Products Regulatory Authority - Ireland
  • Authorization number:
  • PA0585/025/001
  • Authorization date:
  • 08-12-2006
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

Fosalen10mgTablets

2QUALITATIVEANDQUANTITATIVECOMPOSITION

Eachtabletcontains10mgalendronicacid(assodiumalendronatetrihydrate).

Excipients:

Eachtabletcontains103.95mgoflactosemonohydrate.

Forafulllistofexcipientsseesection6.1.

3PHARMACEUTICALFORM

Tablet

Whitetooff-white,capsule-shapedtablet,embossed"AN10"ononesideand"Arrowlogo"ontheother.

4CLINICALPARTICULARS

4.1TherapeuticIndications

Treatmentofpost-menopausalosteoporosis.

Alendronatereducestheriskofvertebralandhipfractures.

4.2Posologyandmethodofadministration

Fororaluseonly.

Therecommendeddosageis10mgoncedaily.

Toobtainsatisfactoryabsorptionofalendronate

Fosalentabletsmustbetakenonanemptystomachimmediatelyonrisinginthemorning,withplainwateronly,atleast

30minutesbeforethefirstfood,drinkorothermedicationoftheday.Otherdrinks(includingmineralwater),foodand

somemedicinesarelikelytoreducetheabsorptionofalendronate(seesection4.5).

Toassistdeliverytothestomachandthusreducetheriskofirritation/sideeffectslocallyandintheoesophagus(see

section4.4)

Fosalentabletsshouldonlybeswallowedonarisingforthedaywithawholeglassofwater(notlessthan200ml

or7fl.oz).

Fosalentabletsshouldbeswallowedwhole.Thetabletsshouldnotbecrushed,chewed,orallowedtodissolvein

themouthonaccountoftheriskoforopharyngealulceration.

Patientsshouldnotliedownuntilafterthefirstmealoftheday,whichmustbeatleast30minutesaftertakingthe

tablet.

Patientsshouldnotliedownwithin30minutesoftakingFosalen10mgtablets.

Fosalen10mgtabletsshouldnotbetakenatbedtimeorbeforearisingfortheday.

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Useinelderlypatients:

Inclinicaltrialstherewasnoage-relateddifferencewithregardtoefficacyorsafetyprofilesofalendronate.Therefore

noadjustmentofthedoseisnecessaryforelderlypatients.

Useinimpairedrenalfunction

Nodoseadjustmentisnecessaryinpatientswithaglomerularfiltrationrate(GFR)greaterthan35ml/min.Alendronate

isnotrecommendedforpatientswithimpairedrenalfunctioniftheGFRislessthan35ml/min,asthereisno

experienceofthis.

Useinimpairedhepaticfunction

Nodoseadjustmentisnecessary.

Useinchildren(under18years)

Alendronatehasbeenstudiedinasmallnumberofpatientswithosteogenesisimperfectunder18yearsofage.Results

areinsufficienttosupportitsuseinchildren.

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,followingmarketingoftheoriginal

preparationtherehavebeenreportsofrarecasesofgastricandduodenalulcers,someofthemsevereandwith

complications.Acausalrelationshipcannotbeexcluded(seesection4.8).

PatientsshouldbeinstructedthatiftheymissadoseofFosalen,theyshouldtakeonetabletonthemorningafterthey

remember.Theyshouldnottaketwotabletsonthesameday,butshouldreturntotakingonetabletonceaday,as

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AlendronateisnotrecommendedforpatientswithimpairedrenalfunctioniftheGFRislessthan35ml/min(see

section4.2).

Causesofosteoporosisotherthanoestrogendeficiencyandageingshouldbeconsidered.

Hypocalcaemiamustbecorrectedbeforetreatmentwithalendronateisinitiated(seesection4.3).Otherdisordersof

mineralmetabolism(suchasvitaminDdeficiencyandhypoparathyroidism)shouldalsobeeffectivelytreatedbefore

startingalendronate.Inpatientswiththeseconditions,serumcalciumandsymptomsofhypocalcaemiashouldbe

monitoredduringtreatmentwithalendronate.

Onaccountofthepositiveeffectsofalendronateontheincreaseinbonemineralisation,reductionsinserumcalcium

andserumphosphatemayoccur.Theseareusuallyslightandasymptomatic.However,inrarecases,symptomatic

hypocalcaemiahasbeenreportedwhichoccasionallyhasbeensevereandoftenoccurredinpatientswithpredisposing

conditions(e.g.hypoparathyroidism,vitaminDdeficiencyandincasesofcalciummalabsorption).

Itisthereforeparticularlyimportanttoensurethatpatientstakingglucocorticoidshaveanadequatecalciumand

vitaminDintake.

Fosalen10mgtabletscontainlactose.Patientswithrarehereditaryproblemsofgalactoseintolerance,theLapplactase

deficiencyorglucose-galactosemalabsorptionshouldnottakethismedicine.

Osteonecrosisofthejaw,generallyassociatedwithtoothextractionand/orlocalinfection(includingosteomyelitis)has

beenreportedinpatientswithcancerreceivingtreatmentregimesincludingprimarilyintravenouslyadministered

bisphosphonates.Manyofthesepatientswerealsoreceivingchemotherapyandcorticosteroids.Osteonecrosisofthe

jawhasalsobeenreportedinpatientswithosteoporosisreceivingoralbisphosphonates.

Adentalexaminationwithappropriatepreventativedentistryshouldbeconsideredpriortotreatmentwith

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

poororalhygiene,periodentaldisease,smoking).

Whileontreatment,thesepatientsshouldavoidinvasivedentalproceduresifpossible.Forpatientswhodevelop

osteonecrosisofthejawwhileonbisphosphonatetherapy,dentalsurgerymayexacerbatethecondition.Forpatients

requiringdentalprocedures,therearenodataavailabletosuggestwhetherdiscontinuationofbisphosphonatetreatment

reducestheriskofosteonecrosisofthejaw.

Clinicaljudgementofthetreatingphysicianshouldguidethemanagementplanofeachpatientbasedonindividual

benefit/riskassessment.

Bone,joint,and/ormusclepainhasbeenreportedinpatientstakingbisphosphonates.Inpost-marketingexperience,

thesesymptomshaverarelybeensevereand/orincapacitating(seesection4.8).Thetimetoonsetofsymptomsvaried

fromonedaytoseveralmonthsafterstartingtreatment.Mostpatientshadreliefofsymptomsafterstopping.Asubset

hadrecurrenceofsymptomswhenrechallengedwiththesamedrugoranotherbisphosphonate.

Atypicalstressfractures

Stressfractures(alsoknownasinsufficiencyfractures)oftheproximalfemoralshafthavebeenreportedinpatients

treatedlong-termwithalendronicacid(timetoonsetinthemajorityofcasesrangedfrom18monthsto10years.The

fracturesoccurredafterminimalornotraumaandsomepatientsexperiencedthighpain,weekstomonthsbefore

presentingwithacompletedfemoralfracture.Fractureswereoftenbilateral;thereforethecontralateralfemurshouldbe

examinedinbisphosphonate-treatedpatientswhohavesustainedafemoralshaftfracture.Poorhealingothesefractures

wasalsoreported.Discontinuationofbisphosphonatetherapyinpatientswithstressfractureisadvisablepending

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4.5Interactionwithothermedicinalproductsandotherformsofinteraction

Iftakenatthesametime,itislikelythatfoodsanddrinks(includingmineralwater),calciumsupplements,antacidsand

someoralmedicineswillaffecttheabsorptionofalendronate.Patientsmustthereforewaitforatleast30minutesafter

takingalendronatebeforetakinganyotheroralmedicine(seesection4.2).

Nootherclinicallysignificantdruginteractionsareexpected.Anumberofpatientsintheclinicaltrialsreceived

oestrogen(intravaginally,transdermallyororally)concomitantlywithalendronate.Noundesirableeffectscouldbe

relatedtothecombinationtreatment.

SinceNSAIDuseisassociatedwithgastrointestinalirritation,cautionshouldbeusedduringconcomitantusewith

alendronate.

Nospecificinteractionstudieshavebeencarriedout,butalendronatewasusedinclinicaltrialsconcomitantlywitha

numberofothercommonlyprescribedmedicineswithoutanyevidenceofclinicallyunfavourableinteractions.

4.6Pregnancyandlactation

Useduringpregnancy

Thereareinsufficientdataregardingtheuseofalendronateinpregnantwomen.Animalstudiesrevealedeffectson

foetalboneformationathighdoses.Alendronategiventopregnantratscausedhypocalcaemia-relateddystocia(see

section5.3).Inviewoftheindication,alendronateshouldnotbeusedduringpregnancy.

Useduringlactation

Itisnotknownwhetheralendronateisexcretedintobreastmilkinhumans.Inviewoftheindication,alendronate

shouldnotbeusedbybreast-feedingwomen.

4.7Effectsonabilitytodriveandusemachines

Nostudiesontheeffectsontheabilitytodriveandusemachineshavebeenperformed.However,certainadverse

reactionsthathavebeenreportedwithFosalenmayaffectsomepatients'abilitytodriveoroperatemachinery.

IndividualresponsestoFosalenmayvary(seesection4.8).

4.8Undesirableeffects

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

placebo:n=397)theoverallsafetyprofilesforalendronate10mgdailyandplaceboweresimilar.

Undesirableeffectsreportedbytheinvestigatorsaspossibly,probablyordefinitelyrelatedtothedrugarepresented

belowiftheyoccurredin 1%ofanyinthetreatmentgroupsintheone-yearstudyorin 1%ofthepatientswho

weretreatedwithalendronate10mgperdayandwithanincidencehigherthaninpatientswhoweretreatedwith

placebointhree-yearstudies.

Theone-yearstudy Three-yearstudies

Alendronate

once-weekly

tablet

(n=519)

% Alendronate

10mgdaily

(n=370)

% Alendronate10mg

daily

(n=196)

% Placebo

(n=397)

%

Gastrointestinal

Abdominalpain 3.7 3.0 6.6 4.8

Dyspepsia 2.7 2.2 3.6 3.5

Acid

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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.

Uncommon(1/1000,<1/100):Nausea,vomiting,gastritis,oesophagitis*oesophagealerosions*,melaena.

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

(perforations,ulcers,bleeding),acausalrelationshipcannotberuledout.

Skinandsubcutaneoustissuedisorders:

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

Rare(1/10,000,<1/1000:Rashwithphotosensitivity,urticaria,angioedema,alopecia

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

epidermalnecrolysishavebeenreported.

Musculoskeletal,connectivetissueandbonedisorders:

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

Rare(1/10,000,<1/1000:Osteonecrosisofthejawhasbeenreportedinpatientstreatedbybisphosphonates.The

majorityofthereportsrefertocancerpatients,butsuchcaseshavealsobeenreportedinpatientstreatedfor

osteoporosis.Osteonecrosisofthejawisgenerallyassociatedwithtoothextractionand/orlocalinfection(including

osteomyelitis).Diagnosisofcancer,chemotherapy,radiotherapy,corticosteroidsandpoororalhygienearealsodeemed

asriskfactors;severemusculoskeletal(bone,muscleorjoint)pain(seesection4.4)

Unknownfrequency:Stressfracturesoftheproximalfemoralshaft(seesection4.4)

Generaldisordersandadministrationsiteconditions:

Rare(1/10,000,<1/1000):Transientsymptomsasinanacutephasereaction(myalgia,malaiseandinrarecases

Nausea 1.9 2.4 3.6 4.0

Abdominal

distension 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

Oesophageal

ulcer 0.0 0.0 1.5 0.0

Musculoskeletal

Musculoskeletal

pain

(bone,muscleor

joints) 2.9 3.2 4.1 2.5

Musclecramps 0.2 1.1 0.0 1.0

Neurological

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Metabolismandnutririondisorders:

Rare(1/10,000,<1/1000):Symptomatichypocalcaemia,generallyinconnectionwithpredisposingconditions(see.

section4.4).

Immunesystemdisorders:

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

*Seesection4.4andsection4.2.

Duringpost-marketingexperiencethefollowingreactionshavebeenreported(frequencyunknown):

Nervoussystemdisorders:Dizziness,dysgeusia

Earandlabyrinthdisorders:Vertigo

Musculoskeletal,connectivetissueandbonedisorders:Jointswelling,stressfracturesoftheproximalfemoralshaft

(seesection4.4)

Generaldisordersandadministrationsiteconditions:Asthenia,peripheraloedema

Laboratoryvalues:Inclinicaltrials,asymptomatic,slightandtransientdecreasesinserumcalciumandserum

phosphatewereobservedinapprox.18and10%respectivelyofthepatientstakingalendronate10mg/dayversus12

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

andserumphosphateto0.65mmol/lwascomparableinthetwogroups.

4.9Overdose

Hypocalcaemia,hypophosphataemiaanduppergastrointestinalsideeffectssuchasupsetstomach,heartburn,

oesophagitis,gastritisorulcercanoccuronoraloverdosage.Thereisnospecificinformationavailablewithregardto

overdosagewithalendronate.Milkorantacidsshouldbegiveninordertobindalendronate.Onaccountoftheriskof

oesophagealirritation,vomitingshouldnotbeinducedandthepatientshouldbekeptinanuprightposition.

5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

Pharmacotherapeuticgroup:Drugsaffectingbonestructureandmineralisation,bisphosphonates.

ATCcode:M05BA04

TheactivesubstanceinFosalen10mgtablets,sodiumalendronatetrihydrate,isabisphosphonatethatinhibits

osteoclasticboneresorptionwithoutanydirecteffectonboneformation.Preclinicalstudieshavedemonstrateda

preferenceforlocalisationofalendronatetositeswhereactiveresorptiontakesplace.Osteoclasticactivityisinhibited,

butformationandbindingoftheosteoclastsisnotaffected.Boneformedduringtreatmentwithalendronateisof

normalquality.

Treatmentofpost-menopausalosteoporosis

Osteoporosisisdefinedasbonemineraldensity(BMD)ofthespineorhip2.5standarddeviationsbelowthe

meanvalueofanormalyoungpopulationorasapreviousfragilityfracture,irrespectiveofbonemineral

density.

TheeffectsofalendronateonBMDandfractureincidenceinpost-menopausalwomenwerestudiedintwoinitial

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Intheinitialefficacystudies,theincreasesinBMDwithalendronate10mgdailyrelativetoplaceboafterthreeyears

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

significantly.Inthepatientstreatedwithalendronate,theproportionofpatientswhosufferedoneormorevertebral

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

theBMDinthespineandtrochantercontinuedtoincrease.Inaddition,BMDatthefemoralneckandtotalbodywas

maintained.

TheFITstudyincludedtwoplacebo-controlledtrialsinwhichalendronatewasgivendaily(5mgdailyfortwoyears

and10mgdailyforafurtheroneortwoyears).

FIT1:Athree-yearstudywith2027patientswhohadhadatleastonebaselinevertebral(compression)fracture.

Inthisstudyalendronatedailyreducedtheincidenceof1newvertebralfractureby47%(alendronate7.9%

versusplacebo15.0%).Inaddition,astatisticallysignificantreductionintheincidenceofhipfractureswas

confirmed(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%).

Concomitantusewithoestrogen/hormonereplacementtherapy(HRT)

TheeffectsonBMDoftreatmentwithalendronate10mgonce-dailyandconjugatedoestrogen(0.625mg/day)either

aloneorincombinationwereassessedinatwo-yearstudyofhysterectomised,post-menopausal,osteoporoticwomen.

Attwoyears,theincreasesinlumbarspineBMDfrombaselineweresignificantlygreaterwiththecombination(8.3%)

thanwitheitheroestrogenoralendronatealone(both6.0%).

TheeffectsonBMDwhen'Fosamax'wasaddedtostabledoses(foratleastoneyear)ofHRT(oestrogen±progestin)

wereassessedinaone-yearstudyinpost-menopausal,osteoporoticwomen.Theadditionof'Fosamax'10mgonce-

dailytoHRTproduced,atoneyear,significantlygreaterincreasesinlumbarspineBMD(3.7%)vs.HRTalone(1.1%).

Inthesestudies,significantincreasesorfavourabletrendsinBMDforcombinedtherapycomparedwithHRTalone

wereseenatthetotalhip,femoralneckandtrochanter.NosignificanteffectwasseenfortotalbodyBMD.

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

toolowforanalyticaldetection(<5ng/ml).Proteinbindinginhumanplasmaisapproximately78%.

Biotransformation

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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

2years

6.4Specialprecautionsforstorage

Donotstoreabove25°C.

6.5Natureandcontentsofcontainer

Thetabletsaresuppliedintriplexblister(PVC/PE/PVDC/AL)packaging.

14,28,56,98,112and50x1(unitdose).

Notallpacksizesmaybemarketed.

6.6Specialprecautionsfordisposalandotherhandling

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7MARKETINGAUTHORISATIONHOLDER

PLIVAPharmaLtd.

VisionHouse,

BedfordRoad,

Petersfield,

Hants,GU323QB,

UnitedKingdom

8MARKETINGAUTHORISATIONNUMBER

PA585/25/1

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

Dateoffirstauthorisation:.8 th

December2006

Dateoflastrenewal:3 rd

December2009

10DATEOFREVISIONOFTHETEXT

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