FOSAMAX ONCE WEEKLY 70 MG TABLETS

Main information

  • Trade name:
  • FOSAMAX ONCE WEEKLY 70 MG TABLETS
  • Dosage:
  • 70 Base Milligrams
  • Pharmaceutical form:
  • Tablets
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug

Documents

Localization

  • Available in:
  • FOSAMAX ONCE WEEKLY 70 MG TABLETS
    Ireland
  • Language:
  • English

Status

  • Source:
  • HPRA - Health Products Regulatory Authority - Ireland
  • Authorization number:
  • PPA0465/115/001A
  • Authorization date:
  • 14-05-2004
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

FosamaxOnceWeekly70mgTablets

2QUALITATIVEANDQUANTITATIVECOMPOSITION

Eachtabletcontains70mgofalendronicacid(asaledronatesodiumtrihydrate).

Excipients:Lactose

Forafulllistofexcipients,seesection6.1.

3PHARMACEUTICALFORM

Tablets.

ProductimportedfromBelgium,Italy,UK,theNetherlands,HungaryandTheCzechRepublic.

Ovalwhitetablets,markedwithanoutlineofaboneimageononeside,and‘31’ontheother.

4CLINICALPARTICULARS

4.1TherapeuticIndications

Treatmentofpostmenopausalosteoporosis.'Fosamax'reducestheriskofvertebralandhipfractures.

4.2Posologyandmethodofadministration

Therecommendeddosageisone70mgtabletonceweekly.

Topermitadequateabsorptionofalendronate:

'Fosamax'mustbetakenatleast30minutesbeforethefirstfood,beverage,ormedicinalproductofthedaywithplain

wateronly.Otherbeverages(includingmineralwater),foodandsomemedicinalproductsarelikelytoreducethe

absorptionofalendronate(see4.5'Interactionwithothermedicinalproductsandotherformsofinteraction').

Tofacilitatedeliverytothestomachandthusreducethepotentialforlocalandoesophagealirritation/adverse

experiences(see4.4'Specialwarningsandprecautionsforuse'):

'Fosamax'shouldonlybeswalloweduponarisingforthedaywithafullglassofwater(notlessthan200mlor7

fl.oz.).

Patientsshouldonlyswallow'Fosamax'whole.Patientsshouldnotcrushorchewthetabletorallowthetabletto

dissolveintheirmouthsbecauseofapotentialfororopharyngealulceration.

Patientsshouldnotliedownuntilaftertheirfirstfoodofthedaywhichshouldbeatleast30minutesaftertakingthe

tablet.

Patientsshouldnotliedownforatleast30minutesaftertaking'Fosamax'.

'Fosamax'shouldnotbetakenatbedtimeorbeforearisingfortheday.

PatientsshouldreceivesupplementalcalciumandvitaminDifdietaryintakeisinadequate(see4.4'Specialwarnings

andprecautionsforuse').

Useintheelderly:Inclinicalstudiestherewasnoage-relateddifferenceintheefficacyorsafetyprofilesof

alendronate.Thereforenodosageadjustmentisnecessaryfortheelderly.

Useinrenalimpairment:NodosageadjustmentisnecessaryforpatientswithGFRgreaterthan35ml/min.

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experience.

Useinchildren(under18years):Alendronatehasbeenstudiedinasmallnumberofpatientswithosteogenesis

imperfectaunder18yearsofage.Resultsareinsufficienttosupportitsuseinchildren

'Fosamax'OnceWeekly70mghasnotbeeninvestigatedinthetreatmentofglucocorticoid-inducedosteoporosis.

4.3Contraindications

Abnormalitiesoftheoesophagusandotherfactorswhichdelayoesophagealemptyingsuchasstrictureor

achalasia.

Inabilitytostandorsituprightforatleast30minutes.

Hypersensitivitytoalendronateortoanyoftheexcipients.

Hypocalcaemia.

Seealso4.4'Specialwarningsandprecautionsforuse'.

4.4Specialwarningsandprecautionsforuse

Alendronatecancauselocalirritationoftheuppergastro-intestinalmucosa.Becausethereisapotentialforworsening

oftheunderlyingdisease,cautionshouldbeusedwhenalendronateisgiventopatientswithactiveuppergastro-

intestinalproblems,suchasdysphagia,oesophagealdisease,gastritis,duodenitis,ulcers,orwitharecenthistory

(withinthepreviousyear)ofmajorgastro-intestinaldiseasesuchaspepticulcer,oractivegastro-intestinalbleeding,or

surgeryoftheuppergastro-intestinaltractotherthanpyloroplasty(see4.3'Contraindications').Inpatientswithknown

Barrett'soesophagus,prescribersshouldconsiderthebenefitsandpotentialrisksofalendronateonanindividualpatient

basis.

Oesophagealreactions(sometimessevereandrequiringhospitalisation),suchasoesophagitis,oesophagealulcersand

oesophagealerosions,rarelyfollowedbyoesophagealstricture,havebeenreportedinpatientsreceivingalendronate.

Physiciansshouldthereforebealerttoanysignsorsymptomssignallingapossibleoesophagealreactionandpatients

shouldbeinstructedtodiscontinuealendronateandseekmedicalattentioniftheydevelopsymptomsofoesophageal

irritationsuchasdysphagia,painonswallowingorretrosternalpain,neworworseningheartburn.

Theriskofsevereoesophagealadverseexperiencesappearstobegreaterinpatientswhofailtotakealendronate

properlyand/orwhocontinuetotakealendronateafterdevelopingsymptomssuggestiveofoesophagealirritation.Itis

veryimportantthatthefulldosinginstructionsareprovidedto,andunderstoodbythepatient(see4.2'Posologyand

methodofadministration').Patientsshouldbeinformedthatfailuretofollowtheseinstructionsmayincreasetheirrisk

ofoesophagealproblems.

Whilenoincreasedriskwasobservedinextensiveclinicaltrials,therehavebeenrare(post-marketing)reportsof

gastricandduodenalulcers,somesevereandwithcomplications.

Osteonecrosisofthejaw,generallyassociatedwithtoothextractionand/orlocalinfection(includingosteomyelitis)has

beenreportedinpatientswithcancerreceivingtreatmentregimensincludingprimarilyintravenouslyadministered

bisphosphonates.Manyofthesepatientswerealsoreceivingchemotherapyandcorticosteroids.Osteonecrosisofthe

jawhasalsobeenreportedinpatientswithosteoporosisreceivingoralbisphosphonates.

Adentalexaminationwithappropriatepreventivedentistryshouldbeconsideredpriortotreatmentwith

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

poororalhygiene,periodontaldisease).

Whileontreatment,thesepatientsshouldavoidinvasivedentalproceduresifpossible.Forpatientswhodevelop

osteonecrosisofthejawwhileonbisphosphonatetherapy,dentalsurgerymayexacerbatethecondition.Forpatients

requiringdentalprocedures,therearenodataavailabletosuggestwhetherdiscontinuationofbisphosphonatetreatment

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Clinicaljudgementofthetreatingphysicianshouldguidethemanagementplanofeachpatientbasedonindividual

benefit/riskassessment.

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

thesesymptomshaverarelybeensevereand/orincapacitating(see'4.8Undesirableeffects').Thetimetoonsetof

symptomsvariedfromonedaytoseveralmonthsafterstartingtreatment.Mostpatientshadreliefofsymptomsafter

stopping.Asubsethadrecurrenceofsymptomswhenrechallengedwiththesamedrugoranotherbisphosphonate.

Stressfractures(alsoknownasinsufficiencyfractures)oftheproximalfemoralshafthavebeenreportedinpatients

treatedlong-termwithalendronicacid(timetoonsetinthemajorityofcasesrangedfrom18monthsto10years).The

fracturesoccurredafterminimalornotraumaandsomepatientsexperiencedthighpain,oftenassociatedwithimaging

featuresofstressfractures,weekstomonthsbeforepresentingwithacompletedfemoralfracture.Fractureswereoften

bilateral;thereforethecontralateralfemurshouldbeexaminedinbisphosphonate-treatedpatientswhohavesustaineda

femoralshaftfracture.Poorhealingofthesefractureswasalsoreported.Discontinuationofbisphosphonatetherapyin

patientswithstressfractureisadvisablependingevaluationofthepatient,basedonanindividualbenefitrisk

assessment.

Patientsshouldbeinstructedthatiftheymissadoseof'Fosamax'OnceWeekly,theyshouldtakeonetabletonthe

morningaftertheyremember.Theyshouldnottaketwotabletsonthesamedaybutshouldreturntotakingonetablet

onceaweek,asoriginallyscheduledontheirchosenday.

AlendronateisnotrecommendedforpatientswithrenalimpairmentwhereGFRislessthan35ml/min,(see4.2

'Posologyandmethodofadministration').

Causesofosteoporosisotherthanoestrogendeficiencyandageingshouldbeconsidered.

Hypocalcaemiamustbecorrectedbeforeinitiatingtherapywithalendronate(see4.3'Contraindications').Other

disordersaffectingmineralmetabolism(suchasvitaminDdeficiencyandhypoparathyroidism)shouldalsobe

effectivelytreated.Inpatientswiththeseconditions,serumcalciumandsymptomsofhypocalcemiashouldbe

monitoredduringtherapywith'Fosamax'.

Duetothepositiveeffectsofalendronateinincreasingbonemineral,decreasesinserumcalciumandphosphatemay

occurespeciallyinpatientstakingglucocorticoidsinwhomcalciumabsorptionmaybedecreased.Theseareusually

smallandasymptomatic.However,therehavebeenrarereportsofsymptomatichypocalcemia,whichhave

occasionallybeensevereandoftenoccurredinpatientswithpredisposingconditions(e.g.hypoparathyroidism,vitamin

Ddeficiencyandcalciummalabsorption).

EnsuringadequatecalciumandvitaminDintakeisparticularlyimportantinpatientsreceivingglucocorticoids.

Thismedicinalproductcontainslactose.Patientswithrarehereditaryproblemsofgalactoseintolerance,theLapp

lactasedeficiencyorglucose-galactosemalabsorptionshouldnottakethismedicinalproduct.

4.5Interactionwithothermedicinalproductsandotherformsofinteraction

Iftakenatthesametime,itislikelythatfoodandbeverages(includingmineralwater),calciumsupplements,antacids,

andsomeoralmedicinalproductswillinterferewithabsorptionofalendronate.Therefore,patientsmustwaitatleast30

minutesaftertakingalendronatebeforetakinganyotheroralmedicinalproduct(see4.2'Posologyandmethodof

administration'and5.2'Pharmacokineticproperties').

Nootherinteractionswithmedicinalproductsofclinicalsignificanceareanticipated.Anumberofpatientsinthe

clinicaltrialsreceivedoestrogen(intravaginal,transdermal,ororal)whiletakingalendronate.Noadverseexperiences

attributabletotheirconcomitantusewereidentified.

SinceNSAIDuseisassociatedwithgastrointestinalirritation,cautionshouldbeusedduringconcomitantusewith

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Althoughspecificinteractionstudieswerenotperformed,inclinicalstudiesalendronatewasusedconcomitantlywitha

widerangeofcommonlyprescribedmedicinalproductswithoutevidenceofclinicaladverseinteractions.

4.6Fertility,pregnancyandlactation

Useduringpregnancy

Alendronateshouldnotbeusedduringpregnancy.Therearenoadequatedatafromtheuseofalendronateinpregnant

women.Animalstudiesdonotindicatedirectharmfuleffectswithrespecttopregnancy,embryonal/foetal

development,orpostnataldevelopment.Alendronategivenduringpregnancyinratscauseddystociarelatedto

hypocalcemia(see5.3'Preclinicalsafetydata').Giventheindication,alendronateshouldnotbeusedduringpregnancy.

Useduringlactation

Itisnotknownwhetheralendronateisexcretedintohumanbreastmilk.Giventheindication,alendronateshouldnotbe

usedbybreast-feedingwomen.

4.7Effectsonabilitytodriveandusemachines

Nostudiesontheeffectsontheabilitytodriveandusemachineshavebeenperformed.

However,certainadversereactionsthathavebeenreportedwith'Fosamax'mayaffectsomepatients'abilitytodriveor

operatemachinery.Individualresponsesto'Fosamax'mayvary(seesection4.8)

4.8Undesirableeffects

Inaone-yearstudyinpost-menopausalwomenwithosteoporosistheoverallsafetyprofilesof'Fosamax'OnceWeekly

70mg(n=519)andalendronate10mg/day(n=370)weresimilar.

Intwothree-yearstudiesofvirtuallyidenticaldesign,inpost-menopausalwomen(alendronate10mg:n=196,placebo:

n=397)theoverallsafetyprofilesofalendronate10mg/dayandplaceboweresimilar.

Adverseexperiencesreportedbytheinvestigatorsaspossibly,probablyordefinitelydrug-relatedarepresentedbelow

iftheyoccurredin ≥1%ineithertreatmentgroupintheone-yearstudy,orin≥1%ofpatientstreatedwithalendronate

10mg/dayandatagreaterincidencethaninpatientsgivenplacebointhethree-yearstudies:

One-YearStudy Three-YearStudies

'Fosamax' Alendronate Alendronate Placebo

OnceWeekly

70mg 10mg/day 10mg/day

(n=519) (n=370) (n=196) (n=397)

Gastro-intestinal

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

abdominaldistention 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

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Thefollowingadverseexperienceshavealsobeenreportedduringclinicalstudiesand/orpost-marketinguse:

[Common( ≥1/100,<1/10),Uncommon(≥1/1000,<1/100),Rare(≥1/10,000,<1/1000),Veryrare(<1/10,000

includingisolatedcases)]

Immunesystemdisorders:

Rare:hypersensitivityreactionsincludingurticariaandangioedema

Metabolismandnutritiondisorders:

Rare:symptomatichypocalcaemia,ofteninassociationwithpredisposingconditions.(seesection4.4)

Nervoussystemdisorders:

Common:headache

Eyedisorders:

Rare:uveitis,scleritis,episcleritis

Gastrointestinaldisorders:

Common:abdominalpain,dyspepsia,constipation,diarrhoea,flatulence,oesophagealulcer*,dysphagia*,abdominal

distension,acidregurgitation

Uncommon:nausea,vomiting,gastritis,oesophagitis*,oesophagealerosions*,melena

Rare:oesophagealstricture*,oropharyngealulceration*,uppergastrointestinalPUBs(perforation,ulcers,bleeding)(see

section4.4)

*Seesections4.2and4.4

Skinandsubcutaneoustissuedisorders:

Uncommon:rash,pruritus,erythema

Rare:rashwithphotosensitivity

Veryrareandisolatedcases:isolatedcasesofsevereskinreactionsincludingStevens-Johnsonsyndromeandtoxic

epidermalnecrolysis

Musculoskeletal,connectivetissueandbonedisorders:

Common:musculoskeletal(bone,muscleorjoint)pain

Rare:Osteonecrosisofthejawhasbeenreportedinpatientstreatedbybisphosphonates.Themajorityofthereports

refertocancerpatients,butsuchcaseshavealsobeenreportedinpatientstreatedforosteoporosis.Osteonecrosisofthe

jawisgenerallyassociatedwithtoothextractionand/orlocalinfection(includingosteomyelitis).Diagnosisofcancer,

chemotherapy,radiotherapy,corticosteroidsandpoororalhygienearealsodeemedasriskfactors;severe

musculoskeletal(bone,

muscleorjoint)pain 2.9 3.2 4.1 2.5

musclecramp 0.2 1.1 0.0 1.0

Neurological

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Generaldisordersandadministrationsiteconditions:

Rare:transientsymptomsasinanacute-phaseresponse(myalgia,malaiseandrarely,fever),typicallyinassociation

withinitiationoftreatment.

Duringpost-marketingexperiencethefollowingreactionshavebeenreported(frequencyunknown):

Nervoussystemdisorders:dizzinessdysgeusia

Earandlabyrinthdisorders:vertigo

Skinandsubcutaneoustissuedisorders:alopecia

Musculoskeletal,connectivetissueandbonedisorders:

jointswelling,stressfracturesoftheproximalfemoralshaft(seesection4.4).

Generaldisordersandadministrationsiteconditions:

asthenia,peripheraloedema

Laboratorytestfindings

Inclinicalstudies,asymptomatic,mildandtransientdecreasesinserumcalciumandphosphatewereobservedin

approximately18and10%,respectively,ofpatientstakingalendronate10mg/dayversusapproximately12and3%of

thosetakingplacebo.However,theincidencesofdecreasesinserumcalciumto<8.0mg/dl(2.0mmol/l)andserum

phosphateto2.0mg/dl(0.65mmol/l)weresimilarinbothtreatmentgroups.

4.9Overdose

Hypocalcaemia,hypophosphataemiaanduppergastro-intestinaladverseevents,suchasupsetstomach,heartburn,

oesophagitis,gastritis,orulcer,mayresultfromoraloverdosage.

Nospecificinformationisavailableonthetreatmentofoverdosagewithalendronate.Milkorantacidsshouldbegiven

tobindalendronate.

Owingtotheriskofoesophagealirritation,vomitingshouldnotbeinducedandthepatientshouldremainfullyupright.

5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

Pharmacotherapeuticgroup:Bisphosphonate,forthetreatmentofbonediseases.

ATCCode:M05BA04

Theactiveingredientof'Fosamax',alendronatesodiumtrihydrate,isabisphosphonatethatinhibitsosteoclasticbone

resorptionwithnodirecteffectonboneformation.Preclinicalstudieshaveshownpreferentiallocalisationof

alendronatetositesofactiveresorption.Activityofosteoclastsisinhibited,butrecruitmentorattachmentofosteoclasts

isnotaffected.Theboneformedduringtreatmentwithalendronateisofnormalquality.

Treatmentofpost-menopausalosteoporosis

OsteoporosisisdefinedasBMDofthespineorhip2.5SDbelowthemeanvalueofanormalyoungpopulation

orasapreviousfragilityfracture,irrespectiveofBMD.

Thetherapeuticequivalenceof'Fosamax'OnceWeekly70mg(n=519)andalendronate10mgdaily(n=370)was

demonstratedinaone-yearmulticentrestudyofpost-menopausalwomenwithosteoporosis.Themeanincreasesfrom

baselineinlumbarspineBMDatoneyearwere5.1%(95%CI:4.8,5.4%)inthe70mgonce-weeklygroupand5.4%

(95%CI:5.0,5.8%)inthe10mgdailygroup.ThemeanBMDincreaseswere2.3%and2.9%atthefemoralneckand

2.9%and3.1%atthetotalhipinthe70mgonceweeklyand10mgdailygroups,respectively.Thetwotreatment

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Theeffectsofalendronateonbonemassandfractureincidenceinpost-menopausalwomenwereexaminedintwo

initialefficacystudiesofidenticaldesign(n=994)aswellasintheFractureInterventionTrial(FIT:n=6,459).

Intheinitialefficacystudies,themeanbonemineraldensity(BMD)increaseswithalendronate10mg/dayrelativeto

placeboatthreeyearswere8.8%,5.9%and7.8%atthespine,femoralneckandtrochanter,respectively.Totalbody

BMDalsoincreasedsignificantly.Therewasa48%reduction(alendronate3.2%vsplacebo6.2%)intheproportionof

patientstreatedwithalendronateexperiencingoneormorevertebralfracturesrelativetothosetreatedwithplacebo.In

thetwo-yearextensionofthesestudiesBMDatthespineandtrochantercontinuedtoincreaseandBMDatthefemoral

neckandtotalbodyweremaintained.

FITconsistedoftwoplacebo-controlledstudiesusingalendronatedaily(5mgdailyfortwoyearsand10mgdailyfor

eitheroneortwoadditionalyears):

FIT1:Athree-yearstudyof2,027patientswhohadatleastonebaselinevertebral(compression)fracture.Inthis

studyalendronatedailyreducedtheincidenceof ≥1newvertebralfractureby47%(alendronate7.9%vs.placebo

15.0%).Inaddition,astatisticallysignificantreductionwasfoundintheincidenceofhipfractures(1.1%vs.

2.2%,areductionof51%).

FIT2:Afour-yearstudyof4,432patientswithlowbonemassbutwithoutabaselinevertebralfracture.Inthis

study,asignificantdifferencewasobservedintheanalysisofthesubgroupofosteoporoticwomen(37%ofthe

globalpopulationwhocorrespondwiththeabovedefinitionofosteoporosis)intheincidenceofhipfractures

(alendronate1.0%vs.placebo2.2%,areductionof56%)andintheincidenceof ≥1vertebralfracture(2.9%vs.

5.8%,areductionof50%).

5.2Pharmacokineticproperties

Absorption

Relativetoanintravenousreferencedose,theoralmeanbioavailabilityofalendronateinwomenwas0.64%fordoses

rangingfrom5to70mgwhenadministeredafteranovernightfastandtwohoursbeforeastandardisedbreakfast.

Bioavailabilitywasdecreasedsimilarlytoanestimated0.46%and0.39%whenalendronatewasadministeredonehour

orhalfanhourbeforeastandardisedbreakfast.Inosteoporosisstudies,alendronatewaseffectivewhenadministeredat

least30minutesbeforethefirstfoodorbeverageoftheday.

Bioavailabilitywasnegligiblewhetheralendronatewasadministeredwith,oruptotwohoursafter,astandardised

breakfast.Concomitantadministrationofalendronatewithcoffeeororangejuicereducedbioavailabilityby

approximately60%.

Inhealthysubjects,oralprednisone(20mgthreetimesdailyforfivedays)didnotproduceaclinicallymeaningful

changeinoralbioavailabilityofalendronate(ameanincreaserangingfrom20%to44%).

Distribution

Studiesinratsshowthatalendronatetransientlydistributestosofttissuesfollowing1mg/kgintravenousadministration

butisthenrapidlyredistributedtoboneorexcretedintheurine.

Themeansteady-statevolumeofdistribution,exclusiveofbone,isatleast28litresinhumans.Concentrationsofdrug

inplasmafollowingtherapeuticoraldosesaretoolowforanalyticaldetection(<5ng/ml).Proteinbindinginhuman

plasmaisapproximately78%.

Biotransformation

Thereisnoevidencethatalendronateismetabolisedinanimalsorhumans.

Elimination

Followingasingleintravenousdoseof[ 14

C]alendronate,approximately50%oftheradioactivitywasexcretedinthe

urinewithin72hoursandlittleornoradioactivitywasrecoveredinthefaeces.

Followingasingle10mgintravenousdose,therenalclearanceofalendronatewas71ml/min,andsystemicclearance

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Plasmaconcentrationsfellbymorethan95%withinsixhoursfollowingintravenousadministration.Theterminalhalf-

lifeinhumansisestimatedtoexceedtenyears,reflectingreleaseofalendronatefromtheskeleton.Alendronateisnot

excretedthroughtheacidicorbasictransportsystemsofthekidneyinrats,andthusitisnotanticipatedtointerfere

withtheexcretionofothermedicinalproductsbythosesystemsinhumans.

Characteristicsinpatients

Preclinicalstudiesshowthatthedrugthatisnotdepositedinboneisrapidlyexcretedintheurine.Noevidenceof

saturationofboneuptakewasfoundafterchronicdosingwithcumulativeintravenousdosesupto35mg/kginanimals.

Althoughnoclinicalinformationisavailable,itislikelythat,asinanimals,eliminationofalendronateviathekidney

willbereducedinpatientswithimpairedrenalfunction.Therefore,somewhatgreateraccumulationofalendronatein

bonemightbeexpectedinpatientswithimpairedrenalfunction(see4.2'Posologyandmethodofadministration').

5.3Preclinicalsafetydata

Non-clinicaldatarevealnospecialhazardforhumansbasedonconventionalstudiesofsafetypharmacology,repeated

dosetoxicity,genotoxicityandcarcinogenicpotential.Studiesinratshaveshownthattreatmentwithalendronate

duringpregnancywasassociatedwithdystociaindamsduringparturitionwhichwasrelatedtohypocalcaemia.In

studies,ratsgivenhighdosesshowedanincreasedincidenceofincompletefoetalossification.Therelevancetohumans

isunknown.

6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

Microcrystallinecellulose

Lactoseanhydrous

Croscarmellosesodium

Magnesiumstearate

6.2Incompatibilities

Notapplicable.

6.3Shelflife

Theshelf-lifeexpirydateofthisproductisthedateshownonthecontainerandouterpackageoftheproductonthe

marketinthecountryoforigin.

6.4Specialprecautionsforstorage

ProductimportedfromBelgium,TheUK,TheNetherlands,Hungary,andTheCzechRepublic:

Therearenospecialprecautionsforstorage.

ProductimportedfromItaly:

Donotstoreabove30 o

6.5Natureandcontentsofcontainer

Blisterpackcontaining4tabletsinanoutercardboardcartonoranoverlabelledoutercardboardcarton.

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6.6Specialprecautionsfordisposalofausedmedicinalproductorwastematerialsderivedfrom

suchmedicinalproductandotherhandlingoftheproduct

Nospecialrequirements.

7PARALLELPRODUCTAUTHORISATIONHOLDER

PCOManufacturing

Unit10,AshbourneBusinessPark

Rath

Ashbourne

Co.Meath

Ireland

8PARALLELPRODUCTAUTHORISATIONNUMBER

PPA465/115/1

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

Dateoffirstauthorizations: 14 th

May2004

Dateoflastrenewal: 14 th

May2009

10DATEOFREVISIONOFTHETEXT

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