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:
  • PPA1596/019/001
  • Authorization date:
  • 08-10-2010
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

FosamaxOnceWeekly70mgTablets

2QUALITATIVEANDQUANTITATIVECOMPOSITION

Eachtabletcontainstheequivalentof70mgalendronicacidas91.37mgofalendronatesodiumtrihydrate.

Excipients:Eachtabletcontainslactoseanhydrous.

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.

Patientsshouldnotliedownuntilaftertheirfirstfoodofthedaywhichshouldbeatleast30minutesaftertaking

thetablet.

Patientsshouldnotliedownforatleast30minutesaftertaking'Fosamax'.

'Fosamax'shouldnotbetakenatbedtimeorbeforearisingfortheday.

PatientsshouldreceivesupplementalcalciumandvitaminDifdietaryintakeisinadequate(seesection4.4).

Useintheelderly:Inclinicalstudiestherewasnoage-relateddifferenceintheefficacyorsafetyprofilesof

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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,oractivegastrointestinalbleeding,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

jawhasalsobeenreportedinpatientswithosteoporosisreceivingoralbisphosphonates.

Thefollowingriskfactorsshouldbeconsideredwhenevaluatinganindividual'sriskofdevelopingosteonecrosisofthe

jaw:

potencyofthebisphosphonate(highestforzoledronicacid),routeofadministration(seeabove)andcumulative

dose

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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.

Theyshouldnottaketwotabletsonthesamedaybutshouldreturntotakingonetabletonceaweek,asoriginally

scheduledontheirchosenday.

AlendronateisnotrecommendedforpatientswithrenalimpairmentwhereGFRislessthan35ml/min,(seesection

4.2).

Causesofosteoporosisotherthanoestrogendeficiencyandageingshouldbeconsidered.

Hypocalcaemiamustbecorrectedbeforeinitiatingtherapywithalendronate(seesection4.3).Otherdisordersaffecting

mineralmetabolism(suchasvitaminDdeficiencyandhypoparathyroidism)shouldalsobeeffectivelytreated.In

patientswiththeseconditions,serumcalciumandsymptomsofhypocalcemiashouldbemonitoredduringtherapywith

'Fosamax'.

Duetothepositiveeffectsofalendronateinincreasingbonemineral,decreasesinserumcalciumandphosphatemay

occurespeciallyinpatientstakingglucocorticoidsinwhomcalciumabsorptionmaybedecreased.Theseareusually

smallandasymptomatic.However,therehavebeenrarereportsofsymptomatichypocalcemia,whichhave

occasionallybeensevereandoftenoccurredinpatientswithpredisposingconditions(e.g.hypoparathyroidism,vitamin

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EnsuringadequatecalciumandvitaminDintakeisparticularlyimportantinpatientsreceivingglucocorticoids.

Excipients

Thismedicinalproductcontainslactose.Patientswithrarehereditaryproblemsofgalactoseintolerance,theLapp

lactasedeficiencyorglucosegalactosemalabsorptionshouldnottakethismedicinalproduct.

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

Inaoneyearstudyinpost-menopausalwomenwithosteoporosistheoverallsafetyprofilesof'Fosamax'OnceWeekly

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

Intwothreeyearstudiesofvirtuallyidenticaldesign,inpost-menopausalwomen(alendronate10mg:n=196,placebo:

n=397)theoverallsafetyprofilesofalendronate10mg/dayandplaceboweresimilar.

Adverseexperiencesreportedbytheinvestigatorsaspossibly,probablyordefinitelydrug-relatedarepresentedbelow

iftheyoccurredin1%ineithertreatmentgroupintheoneyearstudy,orin1%ofpatientstreatedwithalendronate

10mg/dayandatagreaterincidencethaninpatientsgivenplacebointhethreeyearstudies:

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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

‘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:hypersensitivityreactionsincludingurticaria

andangioedema

Metabolismandnutritiondisorders: Rare:symptomatichypocalcaemia,oftenin

associationwithpredisposingconditions. §

Nervoussystemdisorders:

Common:headache,dizziness †

Uncommon:dysegeusia †

Eyedisorders: Uncommon:eyeinflammation(uvetis,scleritis,

episcleritis)

Earandlabyrinthdisorders:

Common:vertigo †

Gastrointestinaldisorders: Common:abdominalpain,dyspepsia,constipation,

diarrhoea,flatulence,oesophagealulcer*,dysphagia*,

abdominaldistension,acidregurgitation

Uncommon:nausea,vomiting,gastritis,

oesophagitis*,oesophagealerosions*,melena †

Rare:oesophagealstricture*,oropharyngeal

ulceration*,uppergastrointestinalPUBs(perforation

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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,butrecruitmentorattachmentofosteoclasts

isnotaffected.Theboneformedduringtreatmentwithalendronateisofnormalquality.

Treatmentofpost-menopausalosteoporosis

Skinandsubcutaneoustissue

disorders: Common:alopecia †

,pruritus †

Uncommon:rash,erythemas

Rare:rashwithphotosensitivity,severeskinreactions

includingStevens-Johnstonsyndromeandtoxic

epidermalnecrolysis ‡

Musculoskeletalandconnective

tissuedisorders: Verycommon:musculoskeletal(bone,muscleor

joint)painwhichissometimessevere †§

Common:jointswelling †

Rare:Osteonecrosisofthejaw ‡§

;atypical

subtrochantericanddiaphysealfemoralfractures

(bisphosphonateclassadversereaction)

Generaldisordersand

administrationsiteconditions: Common:asthenia †

,peripheraloedema †

Uncommon:transientsymptomsasinanacute-phase

response(myalgia,malaiseandrarely,fever),

typicallyinassociationwithinitiationoftreatment †

Seesection4.4

FrequencyinClinicalTrialswassimilarinthedrugandplacebogroup.

*Seesections4.2and4.4

‡Thisadversereactionwasidentifiedthroughpost-marketingsurveillance.Thefrequency

ofrarewasestimatedbasedonrelevantclinicaltrials.

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orasapreviousfragilityfracture,irrespectiveofBMD.

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

demonstratedinaoneyearmulticentrestudyofpostmenopausalwomenwithosteoporosis.Themeanincreasesfrom

baselineinlumbarspineBMDatoneyearwere5.1%(95%CI:4.8,5.4%)inthe70mgonceweeklygroupand5.4%

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

2.9%and3.1%atthetotalhipinthe70mgonceweeklyand10mgdailygroups,respectively.Thetwotreatment

groupswerealsosimilarwithregardtoBMDincreasesatotherskeletalsites.Theeffectsofalendronateonbonemass

andfractureincidenceinpostmenopausalwomenwereexaminedintwoinitialefficacystudiesofidenticaldesign

(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

thetwoyearextensionofthesestudiesBMDatthespineandtrochantercontinuedtoincreaseandBMDatthefemoral

neckandtotalbodyweremaintained.

FITconsistedoftwoplacebo-controlledstudiesusingalendronatedaily(5mgdailyfortwoyearsand10mgdailyfor

eitheroneortwoadditionalyears):

FIT1:Athreeyearstudyof2,027patientswhohadatleastonebaselinevertebral(compression)fracture.Inthis

studyalendronatedailyreducedtheincidenceof1newvertebralfractureby47%(alendronate7.9%vs.placebo

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

2.2%,areductionof51%).

FIT2:Afouryearstudyof4,432patientswithlowbonemassbutwithoutabaselinevertebralfracture.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

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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

isunknown.

6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

Microcrystallinecellulose(E460)

Lactoseanhydrous

Croscarmellosesodium

Magnesiumstearate(E572)

6.2Incompatibilities

Notapplicable.

6.3Shelflife

Theshelf-lifeexpirydateofthisproductshallbethedateshownonthecontainerandouterpackagingoftheproducton

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6.4Specialprecautionsforstorage

Thismedicinalproductdoesnotrequireanyspecialstorageconditions.

6.5Natureandcontentsofcontainer

Aluminum/aluminumblistersinpackscontaining4tablets.

6.6Specialprecautionsfordisposalofausedmedicinalproductorwastematerialsderivedfrom

suchmedicinalproductandotherhandlingoftheproduct

Nospecialrequirements.

7PARALLELPRODUCTAUTHORISATIONHOLDER

ClearPharmacy

157-173RodenStreet

BelfastBT125QA

UnitedKingdom

8PARALLELPRODUCTAUTHORISATIONNUMBER

PPA1596/19/1

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

Dateoffirstauthorisation:8 th

October2010

10DATEOFREVISIONOFTHETEXT

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