FOSAMAX ONCE WEEKLY

Main information

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

Documents

Localization

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

Status

  • Source:
  • HPRA - Health Products Regulatory Authority - Ireland
  • Authorization number:
  • PPA1463/036/001
  • Authorization date:
  • 18-06-2010
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

FosamaxOnceWeekly70mgtablets

2QUALITATIVEANDQUANTITATIVECOMPOSITION

Eachtabletcontainstheequivalentof70mgalendronicacidas91.37mgofalendronatesodiumtrihydrate.

Excipients:lactoseanhydrous

Forafulllistofexcipients,seesection6.1.

3PHARMACEUTICALFORM

Tablet

ProductimportedfromItaly

Ovalwhitetablets,markedwithanoutlineofaboneimageononeside,and’31’ontheother.

4CLINICALPARTICULARS

4.1TherapeuticIndications

Treatmentofpostmenopausalosteoporosis.‘Fosamax’reducestheriskofvertebralandhipfractures.

4.2Posologyandmethodofadministration

Therecommendeddosageisone70mgtabletonceweekly.Theoptimaldurationofbisphosphonatetreatmentfor

osteoporosishasnotbeenestablished.Theneedforcontinuedtreatmentshouldbere-evaluatedperiodicallybasedon

thebenefitsandpotentialrisksof‘Fosamax’onanindividualpatientbasis,particularlyafter5ormoreyearsofuse.

Topermitadequateabsorptionofalendronate:

'Fosamax'mustbetakenatleast30minutesbeforethefirstfood,beverage,ormedicinalproductofthedaywithplain

wateronly.Otherbeverages(includingmineralwater),foodandsomemedicinalproductsarelikelytoreducethe

absorptionofalendronate(seesection4.5).

Tofacilitatedeliverytothestomachandthusreducethepotentialforlocalandoesophagealirritation/adverse

experiences(seesection4.4):

'Fosamax'shouldonlybeswalloweduponarisingforthedaywithafullglassofwater(notlessthan200mlor7

fl.oz.).

Patientsshouldonlyswallow'Fosamax'whole.Patientsshouldnotcrushorchewthetabletorallowthetabletto

dissolveintheirmouthsbecauseofapotentialfororopharyngealulceration.

Patientsshouldnotliedownuntilaftertheirfirstfoodofthedaywhichshouldbeatleast30minutesaftertakingthe

tablet.

Patientsshouldnotliedownforatleast30minutesaftertaking'Fosamax'.

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 02/02/2012 CRN 2104747 page number: 1

PatientsshouldreceivesupplementalcalciumandvitaminDifdietaryintakeisinadequate(seesection4.4).

Useintheelderly:Inclinicalstudiestherewasnoage-relateddifferenceintheefficacyorsafetyprofilesof

alendronate.Thereforenodosageadjustmentisnecessaryfortheelderly.

Useinrenalimpairment:NodosageadjustmentisnecessaryforpatientswithGFRgreaterthan35ml/min.

AlendronateisnotrecommendedforpatientswithrenalimpairmentwhereGFRislessthan35ml/min,duetolackof

experience.

Useinchildren(under18years):Alendronatehasbeenstudiedinasmallnumberofpatientswithosteogenesis

imperfectaunder18yearsofage.Resultsareinsufficienttosupportitsuseinchildren.

'Fosamax'OnceWeekly70mghasnotbeeninvestigatedinthetreatmentofglucocorticoid-inducedosteoporosis.

4.3Contraindications

Abnormalitiesoftheoesophagusandotherfactorswhichdelayoesophagealemptyingsuchasstrictureor

achalasia.

Inabilitytostandorsituprightforatleast30minutes.

Hypersensitivitytoalendronateortoanyoftheexcipients.

Hypocalcaemia.

Seealsosection4.4.

4.4Specialwarningsandprecautionsforuse

Alendronatecancauselocalirritationoftheuppergastro-intestinalmucosa.Becausethereisapotentialforworsening

oftheunderlyingdisease,cautionshouldbeusedwhenalendronateisgiventopatientswithactiveuppergastro-

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

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

surgeryoftheuppergastro-intestinaltractotherthanpyloroplasty(seesection4.3).

InpatientswithknownBarrett'soesophagus,prescribersshouldconsiderthebenefitsandpotentialrisksofalendronate

onanindividualpatientbasis.

Oesophagealreactions(sometimessevereandrequiringhospitalisation),suchasoesophagitis,oesophagealulcersand

oesophagealerosions,rarelyfollowedbyoesophagealstricture,havebeenreportedinpatientsreceivingalendronate.

Physiciansshouldthereforebealerttoanysignsorsymptomssignallingapossibleoesophagealreactionandpatients

shouldbeinstructedtodiscontinuealendronateandseekmedicalattentioniftheydevelopsymptomsofoesophageal

irritationsuchasdysphagia,painonswallowingorretrosternalpain,neworworseningheartburn.

Theriskofsevereoesophagealadverseexperiencesappearstobegreaterinpatientswhofailtotakealendronate

properlyand/orwhocontinuetotakealendronateafterdevelopingsymptomssuggestiveofoesophagealirritation.Itis

veryimportantthatthefulldosinginstructionsareprovidedto,andunderstoodbythepatient(seesection4.2).Patients

shouldbeinformedthatfailuretofollowtheseinstructionsmayincreasetheirriskofoesophagealproblems.

Whilenoincreasedriskwasobservedinextensiveclinicaltrials,therehavebeenrare(post-marketing)reportsof

gastricandduodenalulcers,somesevereandwithcomplications.

Osteonecrosisofthejaw,generallyassociatedwithtoothextractionand/orlocalinfection(includingosteomyelitis)has

beenreportedinpatientswithcancerreceivingtreatmentregimensincludingprimarilyintravenouslyadministered

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 02/02/2012 CRN 2104747 page number: 2

jawhasalsobeenreportedinpatientswithosteoporosisreceivingoralbisphosphonates.

Thefollowingriskfactorsshouldbeconsideredwhenevaluatinganindividual’sriskofdevelopingosteonecrosisofthe

jaw.

Potencyofthebisphosphonate(highestforzoledronicacid),routeofadministration(seeabove)andcumulativedose

Cancer,chemotherapy,radiotherapy,corticosteroids,smoking.

Ahistoryofdentaldisease,poororalhygiene,periodontaldisease,invasivedentalproceduresandpoorlyfitting

dentures.

Adentalexaminationwithappropriatepreventivedentistryshouldbeconsideredpriortotreatmentwith

bisphosphonatesinpatientswithpoordentalstatus.

Whileontreatment,thesepatientsshouldavoidinvasivedentalproceduresifpossible.Forpatientswhodevelop

osteonecrosisofthejawwhileonbisphosphonatetherapy,dentalsurgerymayexacerbatethecondition.Forpatients

requiringdentalprocedures,therearenodataavailabletosuggestwhetherdiscontinuationofbisphosphonatetreatment

reducestheriskofosteonecrosisofthejaw.Clinicaljudgementofthetreatingphysicianshouldguidethemanagement

planofeachpatientbasedonindividualbenefit/riskassessment.

Duringbisphosphonatetreatment,allpatientsshouldbeencouragedtomaintaingoodoralhygiene,receiveroutine

dentalcheck-ups,andreportanyoralsymptomssuchasdentalmobility,pain,orswelling.

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

thesesymptomshaverarelybeensevereand/orincapacitating(seesection4.8).Thetimetoonsetofsymptomsvaried

fromonedaytoseveralmonthsafterstartingtreatment.Mostpatientshadreliefofsymptomsafterstopping.Asubset

hadrecurrenceofsymptomswhenrechallengedwiththesamedrugoranotherbisphosphonate.

Atypicalsubtrochantericanddiaphysealfemoralfractureshavebeenreportedwithbisphosphonatetherapy,primarily

inpatientsreceivinglong-termtreatmentforosteoporosis.Thesetransverseorshortoblique,fracturescanoccur

anywherealongthefemurfromjustbelowthelessertrochantertojustabovethesupracondylarflare.Thesefractures

occurafterminimalornotraumaandsomepatientsexperiencethighorgroinpain,oftenassociatedwithimaging

featuresofstressfractures,weekstomonthsbeforepresentingwithacompletedfemoralfracture.Fracturesareoften

bilateral;thereforethecontralateralfemurshouldbeexaminedinbisphosphonate-treatedpatientswhohavesustaineda

femoralshaftfracture.Poorhealingofthesefractureshasalsobeenreported.Discontinuationofbisphosphonate

therapyinpatientssuspectedtohaveanatypicalfemurfractureshouldbeconsideredpendingevaluationofthepatient,

basedonanindividualbenefitriskassessment.

Duringbisphosphonatetreatmentpatientsshouldbeadvisedtoreportanythigh,hiporgroinpainandanypatient

presentingwithsuchsymptomsshouldbeevaluatedforanincompletefemurfracture.

Patientsshouldbeinstructedthatiftheymissadoseof'Fosamax'OnceWeekly,theyshouldtakeonetabletonthe

morningaftertheyremember.Theyshouldnottaketwotabletsonthesamedaybutshouldreturntotakingonetablet

onceaweek,asoriginallyscheduledontheirchosenday.

AlendronateisnotrecommendedforpatientswithrenalimpairmentwhereGFRislessthan35ml/min,(seesection

4.2).

Causesofosteoporosisotherthanoestrogendeficiencyandageingshouldbeconsidered.

Hypocalcaemiamustbecorrectedbeforeinitiatingtherapywithalendronate(seesection4.3).Otherdisordersaffecting

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 02/02/2012 CRN 2104747 page number: 3

patientswiththeseconditions,serumcalciumandsymptomsofhypocalcemiashouldbemonitoredduringtherapywith

'Fosamax'.

Duetothepositiveeffectsofalendronateinincreasingbonemineral,decreasesinserumcalciumandphosphatemay

occurespeciallyinpatientstakingglucocorticoidsinwhomcalciumabsorptionmaybedecreased.Theseareusually

smallandasymptomatic.However,therehavebeenrarereportsofsymptomatichypocalcemia,whichhave

occasionallybeensevereandoftenoccurredinpatientswithpredisposingconditions(e.g.hypoparathyroidism,vitamin

Ddeficiencyandcalciummalabsorption).

EnsuringadequatecalciumandvitaminDintakeisparticularlyimportantinpatientsreceivingglucocorticoids.

Excipients

Thismedicinalproductcontainslactose.Patientswithrarehereditaryproblemsofgalactoseintolerance,theLapp

lactasedeficiencyorglucose-galactosemalabsorptionshouldnottakethismedicinalproduct.

4.5Interactionwithothermedicinalproductsandotherformsofinteraction

Iftakenatthesametime,itislikelythatfoodandbeverages(includingmineralwater),calciumsupplements,antacids,

andsomeoralmedicinalproductswillinterferewithabsorptionofalendronate.Therefore,patientsmustwaitatleast

30minutesaftertakingalendronatebeforetakinganyotheroralmedicinalproduct(seesections4.2and5.2).

Nootherinteractionswithmedicinalproductsofclinicalsignificanceareanticipated.Anumberofpatientsinthe

clinicaltrialsreceivedoestrogen(intravaginal,transdermal,ororal)whiletakingalendronate.Noadverseexperiences

attributabletotheirconcomitantusewereidentified.

SinceNSAIDuseisassociatedwithgastrointestinalirritation,cautionshouldbeusedduringconcomitantusewith

alendronate.

Althoughspecificinteractionstudieswerenotperformed,inclinicalstudiesalendronatewasusedconcomitantlywitha

widerangeofcommonlyprescribedmedicinalproductswithoutevidenceofclinicaladverseinteractions.

4.6Fertility,pregnancyandlactation

Useduringpregnancy

Alendronateshouldnotbeusedduringpregnancy.Therearenoadequatedatafromtheuseofalendronateinpregnant

women.Animalstudiesdonotindicatedirectharmfuleffectswithrespecttopregnancy,embryonal/fetaldevelopment,

orpostnataldevelopment.Alendronategivenduringpregnancyinratscauseddystociarelatedtohypocalcemia(see

section5.3).

Useduringlactation

Itisnotknownwhetheralendronateisexcretedintohumanbreastmilk.Giventheindication,alendronateshouldnot

beusedbybreast-feedingwomen.

4.7Effectsonabilitytodriveandusemachines

Nostudiesontheeffectsontheabilitytodriveandusemachineshavebeenperformed.However,certainadverse

reactionsthathavebeenreportedwith‘Fosamax’mayaffectsomepatients'abilitytodriveoroperatemachinery.

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 02/02/2012 CRN 2104747 page number: 4

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

iftheyoccurredin1%ineithertreatmentgroupintheone-yearstudy,orin1%ofpatientstreatedwithalendronate

10mg/dayandatagreaterincidencethaninpatientsgivenplacebointhethree-yearstudies:

One-YearStudy Three-YearStudies

'Fosamax'

OnceWeekly70mg

(n=519)

alendronate

10mg/day

(n=370)

alendronate

10mg/day

(n=196)

Placebo

(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

Musculoskeletal

musculoskeletal(bone,muscle

orjoint)pain 2.9 3.2 4.1 2.5

musclecramp 0.2 1.1 0.0 1.0

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 02/02/2012 CRN 2104747 page number: 5

Thefollowingadverseexperienceshavealsobeenreportedduringclinicalstudiesand/orpost-marketinguse:

[Verycommon(1/10),Common(1/100,<1/10),Uncommon(1/1000,<1/100),Rare(1/10000,<1/1000),Veryrare

(<1/10000includingisolatedcases)]

4.9Overdose

Hypocalcaemia,hypophosphataemiaanduppergastro-intestinaladverseevents,suchasupsetstomach,heartburn,

Headache 0.4 0.3 2.6 1.5

Immunesystemdisorders: Rare:hypersensitivityreactionsincluding

urticariaandangiodema

Metabolismandnutritiondisorders: Rare:symptomatichypocalcaemia,oftenin

associationwithpredisposingconditions.§

Nervoussystemdisorders: Common:headache,dizziness†

Uncommon:dysgeusia†

EyeDisorders: Uncommon:eyeinflammation(uveitis,

scleritis,episcleritis)

Earandlabyrinthdisorders: Common:vertigo†

Gastrointestinaldisorders Common:abdominalpain,dyspepsia,

constipation,diarrhea,flatulence,

oesophagealulcer*,dysphagia*,abdominal

distension,acidregurgitation

Uncommon:nausea,vomiting,gastritis,

oesophagitis*,oesophagelerosions*,melena†

Rare:oesophagelstricture*.Oropharyngeal

ulceration*,uppergastrointestinalPUBs

(perforation,ulcers,bleeding)§

Skinandsubcutaneoustissuedisorders: Common:alopecia†,pruritus†

Uncommon:rash,erythema

Rare:rashwithphotosensitivity,severeskin

reactionsincludingStevens-Johnson

syndromeandtoxicepidermalnecrolysis‡

Musculoskeletalandconnectivetissue

disorders: Verycommon:musculoskeletal(bone,muscle

orjoint)painwhichissometimessevere†§

Common:jointswelling†

Rare:Osteonecrosisofthejaw‡§,atypical

subtrochantericanddiaphysealfemoral

fractures(bisphosphonateclassadverse

reaction)

Generaldisordersandadministrationsite

conditions: Common:asthenia†,peripheraloedema†

Uncommon:transientsymptomsasinan

acute-phaseresponse(myalgia,malaiseand

rarely,fever),typicallyinassociationwith

initiationoftreatment†.

§Seesection4.4

FrequencyinClinicalTrialswassimilarinthedrugandplacebogroup.

*Seesections4.2and4.4

‡Thisadversereactionwasidentifiedthroughpost-marketingsurveillance.Thefrequencyof

rarewasestimatedbasedonrelevantclinicaltrials.

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 02/02/2012 CRN 2104747 page number: 6

Nospecificinformationisavailableonthetreatmentofoverdosagewithalendronate.Milkorantacidsshouldbegiven

tobindalendronate.Owingtotheriskofoesophagealirritation,vomitingshouldnotbeinducedandthepatientshould

remainfullyupright.

5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

Pharmacotherapeuticgroup:Bisphosphonate,forthetreatmentofbonediseases

ATCCode:M05BA04

Theactiveingredientof'Fosamax',alendronatesodiumtrihydrate,isabisphosphonatethatinhibitsosteoclasticbone

resorptionwithnodirecteffectonboneformation.Preclinicalstudieshaveshownpreferentiallocalizationof

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

groupswerealsosimilarwithregardtoBMDincreasesatotherskeletalsites.

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

studyalendronatedailyreducedtheincidenceof1newvertebralfractureby47%(alendronate7.9%vs.placebo

15.0%).Inaddition,astatisticallysignificantreductionwasfoundintheincidenceofhipfractures(1.1%vs.2.2%,a

reductionof51%).

FIT2:Afour-yearstudyof4,432patientswithlowbonemassbutwithoutabaselinevertebralfracture.Inthisstudy,

asignificantdifferencewasobservedintheanalysisofthesubgroupofosteoporoticwomen(37%oftheglobal

populationwhocorrespondwiththeabovedefinitionofosteoporosis)intheincidenceofhipfractures(alendronate

1.0%vs.placebo2.2%,areductionof56%)andintheincidenceof1vertebralfracture(2.9%vs.5.8%,areductionof

50%).

Laboratorytestfindings

Inclinicalstudies,asymptomatic,mildandtransientdecreasesinserumcalciumandphosphatewereobservedin

approximately18and10%,respectively,ofpatientstakingalendronate10mg/dayversus12and3%ofthosetaking

placebo.However,theincidencesofdecreasesinserumcalciumto<8.0mg/dl(2.0mmol/l)andserumphosphateto

2.0mg/dl(0.65mmol/l)weresimilarinbothtreatmentgroups.

5.2Pharmacokineticproperties

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 02/02/2012 CRN 2104747 page number: 7

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.Concentrationsofdruginplasmafollowingtherapeuticoraldosesare

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

Biotransformation

Thereisnoevidencethatalendronateismetabolisedinanimalsorhumans.

Elimination

Followingasingleintravenousdoseof[ 14

C]alendronate,approximately50%oftheradioactivitywasexcretedinthe

urinewithin72hoursandlittleornoradioactivitywasrecoveredinthefaeces.Followingasingle10mgintravenous

dose,therenalclearanceofalendronatewas71ml/min,andsystemicclearancedidnotexceed200ml/min.Plasma

concentrationsfellbymorethan95%withinsixhoursfollowingintravenousadministration.Theterminalhalf-lifein

humansisestimatedtoexceedtenyears,reflectingreleaseofalendronatefromtheskeleton.Alendronateisnot

excretedthroughtheacidicorbasictransportsystemsofthekidneyinrats,andthusitisnotanticipatedtointerfere

withtheexcretionofothermedicinalproductsbythosesystemsinhumans.

Characteristicsinpatients

Preclinicalstudiesshowthatthedrugthatisnotdepositedinboneisrapidlyexcretedintheurine.Noevidenceof

saturationofboneuptakewasfoundafterchronicdosingwithcumulativeintravenousdosesupto35mg/kgin

animals.Althoughnoclinicalinformationisavailable,itislikelythat,asinanimals,eliminationofalendronateviathe

kidneywillbereducedinpatientswithimpairedrenalfunction.Therefore,somewhatgreateraccumulationof

alendronateinbonemightbeexpectedinpatientswithimpairedrenalfunction(seesection4.2).

5.3Preclinicalsafetydata

Non-clinicaldatarevealnospecialhazardforhumansbasedonconventionalstudiesofsafetypharmacology,repeated

dosetoxicity,genotoxicityandcarcinogenicpotential.Studiesinratshaveshownthattreatmentwithalendronate

duringpregnancywasassociatedwithdystociaindamsduringparturitionwhichwasrelatedtohypocalcaemia.In

studies,ratsgivenhighdosesshowedanincreasedincidenceofincompletefetalossification.Therelevancetohumans

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 02/02/2012 CRN 2104747 page number: 8

6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

Microcrystallinecellulose

Lactoseanhydrous

Croscarmellosesodium

MagnesiumStearate

6.2Incompatibilities

Notapplicable.

6.3Shelflife

Theshelf-lifeexpirydateofthisproductisthedateshownonthecontainerandouterpackageoftheproductonthe

marketinthecountryoforigin.

6.4Specialprecautionsforstorage

Nospecialprecautionsforstorage

6.5Natureandcontentsofcontainer

Aluminium/aluminiumblistersinanoverlabelledcardboardcartoncontaining4tablets

6.6Specialprecautionsfordisposalofausedmedicinalproductorwastematerialsderivedfrom

suchmedicinalproductandotherhandlingoftheproduct

Nospecialrequirements.

7PARALLELPRODUCTAUTHORISATIONHOLDER

IMEDHealthcareLtd.

NewRoad

Buncrana

Co.Donegal

8PARALLELPRODUCTAUTHORISATIONNUMBER

PPA1463/36/1

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

Dateoffirstauthorisation:18thJune2010.

10DATEOFREVISIONOFTHETEXT

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 02/02/2012 CRN 2104747 page number: 9