FOSAMAX ONCE WEEKLY 70 MG TABLETS

Main information

  • Trade name:
  • FOSAMAX ONCE WEEKLY 70 MG TABLETS
  • Dosage:
  • 70 Milligram
  • 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:
  • PA0035/083/003
  • Authorization date:
  • 17-05-2001
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

FosamaxOnceWeekly70mgtablets.

2QUALITATIVEANDQUANTITATIVECOMPOSITION

Eachtabletcontainstheequivalentof70mgalendronicacidas91.37mgofalendronatesodiumtrihydrate.

Excipients:

Eachtabletcontains113.4mglactoseanhydrous.

Forafulllistofexcipients,see6.1.

3PHARMACEUTICALFORM

Tablet.

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(notlessthan200mlor

7fl.oz.).

Patientsshouldonlyswallow‘Fosamax’whole.Patientsshouldnotcrushorchewthetabletorallowthetabletto

dissolveintheirmouthsbecauseofapotentialfororopharyngealulceration.

Patientsshouldnotliedownuntilaftertheirfirstfoodofthedaywhichshouldbeatleast30minutesaftertakingthe

tablet.

Patientsshouldnotliedownforatleast30minutesaftertaking‘Fosamax’.

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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's

oesophagus,prescribersshouldconsiderthebenefitsandpotentialrisksofalendronateonanindividualpatientbasis.

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

bisphosphonates.Manyofthesepatientswerealsoreceivingchemotherapyandcorticosteroids.Osteonecrosisofthe

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Thefollowingriskfactorsshouldbeconsideredwhenevaluatinganindividual’sriskofdevelopingosteonecrosisofthe

jaw:

potencyofthebisphosphonate(highestforzoledronicacid),routeofadministration(seeabove)andcumulative

dose

cancer,chemotherapy,radiotherapy,corticosteroids,smoking

ahistoryofdentaldisease,poororalhygiene,periodontaldisease,invasivedentalproceduresandpoorlyfitting

dentures.

Adentalexaminationwithappropriatepreventivedentistryshouldbeconsideredpriortotreatmentwithoral

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,(see

section4.2).

Causesofosteoporosisotherthanoestrogendeficiencyandageingshouldbeconsidered.

Hypocalcaemiamustbecorrectedbeforeinitiatingtherapywithalendronate(seesection4.3).Otherdisordersaffecting

mineralmetabolism(suchasvitaminDdeficiencyandhypoparathyroidism)shouldalsobeeffectivelytreated.In

patientswiththeseconditions,serumcalciumandsymptomsofhypocalcemiashouldbemonitoredduringtherapywith

‘Fosamax’.

Duetothepositiveeffectsofalendronateinincreasingbonemineral,decreasesinserumcalciumandphosphatemay

occurespeciallyinpatientstakingglucocorticoidsinwhomcalciumabsorptionmaybedecreased.Theseareusually

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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.

Individualresponsesto‘Fosamax’mayvary(seesection4.8).

4.8Undesirableeffects

Inaone -yearstudyinpost-menopausalwomenwithosteoporosistheoverallsafetyprofilesof‘Fosamax’Once

Weekly70mg(n=519)andalendronate10mg/day(n=370)weresimilar.

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

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Adverseexperiencesreportedbytheinvestigatorsaspossibly,probablyordefinitelydrug-relatedarepresentedbelow

iftheyoccurredin1%ineithertreatmentgroupintheone -yearstudy,orin1%ofpatientstreatedwithalendronate

10mg/dayandatagreaterincidencethaninpatientsgivenplacebointhethree -yearstudies:

Thefollowingadverseexperienceshavealsobeenreportedduringclinicalstudiesand/orpost-marketinguse:

[Verycommon(1/10),Common(1/100,<1/10),Uncommon(1/1,000,<1/100),Rare(1/10,000,<1/1,000),Very

-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, 2.9 3.2 4.1 2.5

muscleorjoint)pain

musclecramp 0.2 1.1 0.0 1.0

Neurological

Headache 0.4 0.3 2.6 1.5

Immunesystemdisorders: Rare:hypersensitivityreactionsincludingurticariaandangioedema

Metabolismandnutrition

disorders: Rare:symptomatichypocalcaemia,ofteninassociationwith

predisposingconditions. §

Nervoussystemdisorders:

Common:headache,dizziness †

Uncommon:dysgeusia †

Eyedisorders: Uncommon:eyeinflammation(uveitis,scleritis,episcleritis)

Earandlabyrinthdisorders: Common:vertigo †

Gastrointestinaldisorders Common:abdominalpain,dyspepsia,constipation,diarrhoea,flatulence,

oesophagealulcer*,dysphagia*,abdominaldistension,acidregurgitation

Uncommon:nausea,vomiting,gastritis,oesophagitis*,oesophageal

erosions*,melena †

Rare:oesophagealstricture*,oropharyngealulceration*,upper

gastrointestinalPUBs(perforation,ulcers,bleeding) §

Skinandsubcutaneoustissue

disorders: Common:alopecia †

,pruritus †

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4.9Overdose

Hypocalcaemia,hypophosphataemiaanduppergastro-intestinaladverseevents,suchasupsetstomach,heartburn,

oesophagitis,gastritis,orulcer,mayresultfromoraloverdosage.

Nospecificinformationisavailableonthetreatmentofoverdosagewithalendronate.Milkorantacidsshouldbegiven

tobindalendronate.Owingtotheriskofoesophagealirritation,vomitingshouldnotbeinducedandthepatientshould

remainfullyupright.

5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

Pharmacotherapeuticgroup:Bisphosphonate,forthetreatmentofbonediseases

ATCCode:M05BA04

Theactiveingredientof‘Fosamax’,alendronatesodiumtrihydrate,isabisphosphonatethatinhibitsosteoclasticbone

resorptionwithnodirecteffectonboneformation.Preclinicalstudieshaveshownpreferentiallocalizationof

alendronatetositesofactiveresorption.Activityofosteoclastsisinhibited,butrecruitmentorattachmentof

osteoclastsisnotaffected.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

Rare:rashwithphotosensitivity,severeskinreactionsincluding

Stevens -Johnsonsyndromeandtoxicepidermalnecrolysis ‡

Musculoskeletaland

connectivetissuedisorders: Verycommon:musculoskeletal(bone,muscleorjoint)painwhichis

sometimessevere †§

Common:jointswelling †

Rare:Osteonecrosisofthejaw ‡§

;atypicalsubtrochantericanddiaphyseal

femoralfractures(bisphosphonateclassadversereaction)

Generaldisordersand

administrationsite

conditions: Common:asthenia †

,peripheraloedema †

Uncommon:transientsymptomsasinanacute-phaseresponse(myalgia,

malaiseandrarely,fever),typicallyinassociationwithinitiationof

treatment † .

Seesection4.4

FrequencyinClinicalTrialswassimilarinthedrugandplacebogroup.

*Seesections4.2and4.4

Thisadversereactionwasidentifiedthroughpost-marketingsurveillance.Thefrequencyofrarewasestimatedbasedonrelevant

clinicaltrials.

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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.In

thisstudyalendronatedailyreducedtheincidenceof1newvertebralfractureby47%(alendronate7.9%vs.

placebo15.0%).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%)andintheincidenceof1vertebralfracture(2.9%vs.

5.8%,areductionof50%).

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.

5.2Pharmacokineticproperties

Absorption

Relativetoanintravenousreferencedose,theoralmeanbioavailabilityofalendronateinwomenwas0.64%fordoses

rangingfrom5to70mgwhenadministeredafteranovernightfastandtwohoursbeforeastandardisedbreakfast.

Bioavailabilitywasdecreasedsimilarlytoanestimated0.46%and0.39%whenalendronatewasadministeredonehour

orhalfanhourbeforeastandardisedbreakfast.

Inosteoporosisstudies,alendronatewaseffectivewhenadministeredatleast30minutesbeforethefirstfoodor

beverageoftheday.

Bioavailabilitywasnegligiblewhetheralendronatewasadministeredwith,oruptotwohoursafter,astandardised

breakfast.Concomitantadministrationofalendronatewithcoffeeororangejuicereducedbioavailabilityby

approximately60%.

Inhealthysubjects,oralprednisone(20mgthreetimesdailyforfivedays)didnotproduceaclinicallymeaningful

changeinoralbioavailabilityofalendronate(ameanincreaserangingfrom20%to44%).

Distribution

Studiesinratsshowthatalendronatetransientlydistributestosofttissuesfollowing1mg/kgintravenousadministration

butisthenrapidlyredistributedtoboneorexcretedintheurine.Themeansteady-statevolumeofdistribution,

exclusiveofbone,isatleast28litresinhumans.Concentrationsofdruginplasmafollowingtherapeuticoraldosesare

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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

isunknown.

6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

Microcrystallinecellulose

Lactoseanhydrous

Croscarmellosesodium

Magnesiumstearate

6.2Incompatibilities

Notapplicable.

6.3Shelflife

3years.

6.4Specialprecautionsforstorage

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6.5Natureandcontentsofcontainer

Aluminum/aluminumblistersincartonscontaining2,4,8(2x4tablets),12(3x4tablets)or40(10x4tablets)tablets.

Notallpacksizesmaybemarketed.

6.6Specialprecautionsfordisposalofausedmedicinalproductorwastematerialsderivedfrom

suchmedicinalproductandotherhandlingoftheproduct

Nospecialrequirements.

7MARKETINGAUTHORISATIONHOLDER

MerckSharp&DohmeLimited

HertfordRoad

Hoddesdon

Hertfordshire

EN119BU

8MARKETINGAUTHORISATIONNUMBER

PA35/83/3

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

Dateoffirstauthorization:17May2001

Dateoflastrenewal:09November2005

9DATEOFFIRSTREGISTRATION/RENEWALOFTHEREGISTRATION

March2011

10DATEOFREVISIONOFTHETEXT

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