FOSTEPOR 10MG TABLETS

Main information

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

Documents

Localization

  • Available in:
  • FOSTEPOR 10MG TABLETS
    Ireland
  • Language:
  • English

Status

  • Source:
  • HPRA - Health Products Regulatory Authority - Ireland
  • Authorization number:
  • PA0577/086/001
  • Authorization date:
  • 13-10-2006
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

Fostepor10mgTablets

2QUALITATIVEANDQUANTITATIVECOMPOSITION

Eachtabletcontains10mgalendronicacid,assodiumalendronate

Excipient:Lactosemonohydrate.

Forafulllistofexcipientsseesection6.1.

3PHARMACEUTICALFORM

Tablet.

White,ovalshapedtabletembossed"AD10"ononesideand"G"onthereverse;

4CLINICALPARTICULARS

4.1TherapeuticIndications

Treatmentofosteoporosisinpostmenopausalwomen.

Treatmentofosteoporosisinmentoreducetheriskofvertebralfractures(seesection5.1)

4.2Posologyandmethodofadministration

Treatmentofosteoporosisinpost-menopausalwomen:

Therecommendeddosageis10mgonceaday

Treatmentofosteoporosisinmen:

Therecommendeddosageis10mgonceaday

Prophylaxisofglucocorticoid-inducedosteoporosis

Forpost-menopausalwomenwhoarenotreceivingoestrogentreatmenttherecommendeddoseisone10mgtablet

daily.

Topermitadequateabsorptionofalendronate:

Fostepormustbetakenatleast30minutesbeforethefirstfood,beverage,ormedicinalproductofthedaywithplain

wateronly.Otherbeverages(includingmineralwater),foodandsomemedicinalproductsarelikelytoreducethe

absorptionofalendronate(seesection4.5).

Tofacilitatedeliverytothestomachandthusreducethepotentialforlocalandoesophagealirritation/adverse

experiences(seesection4.4):

Fosteporshouldonlybeswalloweduponarisingforthedaywithafullglassofwater(notlessthan200mlor7

fl.oz.).

PatientsshouldonlyswallowFosteporwhole.Patientsshouldnotcrushorchewthetabletorallowthetabletto

dissolveintheirmouthsbecauseofapotentialfororopharyngealulceration.

Patientsshouldnotliedownuntilaftertheirfirstfoodofthedaywhichshouldbeatleast30minutesaftertakingthe

tablet.

Patientsshouldnotliedownforatleast30minutesaftertakingFostepor.

Fosteporshouldnotbetakenatbedtimeorbeforearisingfortheday.

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Useintheelderly:Inclinicalstudiestherewasnoage-relateddifferenceintheefficacyorsafetyprofilesof

alendronate.Thereforenodosageadjustmentisnecessaryfortheelderly.

Paediatricpatients:Alendronatesodiumisnotrecommendedforuseinchildrenundertheageof18yearsdueto

insufficientdataonsafetyandefficacyinconditionsassociatedwithpaediatricosteoporosis(alsoseesection5.1).

Useinrenalimpairment:NodosageadjustmentisnecessaryforpatientswithGFRgreaterthan35ml/min.

AlendronateisnotrecommendedforpatientswithrenalimpairmentwhereGFRislessthan35ml/min,duetolackof

experience.

Fosteporhasnotbeeninvestigatedinthetreatmentofglucocorticoid-inducedosteoporosis.

Theoptimaldurationofbisphosphonatetreatmentforosteoporosishasnotbeenestablished.Theneedforcontinued

treatmentshouldbere-evaluatedperiodicallybasedonthebenefitsandpotentialrisksofFostepor10mgTabletsonan

individualpatientbasis,particularlyafter5ormoreyearsofuse.

4.3Contraindications

Abnormalitiesoftheoesophagusandotherfactorswhichdelayoesophagealemptyingsuchasstrictureorachalasia.

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

surgeryoftheuppergastrointestinaltractotherthanpyloroplasty(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

beenreportedinpatientswithcancerwhoarereceivingtreatmentregimensincludingprimarilyintravenously

administeredbisphosphonates.Manyofthesepatientswerealsoreceivingchemotherapyandcorticosteroids.

Osteonecrosisofthejawhasalsobeenreportedinpatientswithosteoporosisreceivingoralbisphosphonates.

Thefollowingriskfactorsshouldbeconsideredwhenevaluatinganindividual’sriskofdevelopingosteonecrosisofthe

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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.

Atypicalfracturesofthefemur

Atypicalsubtrochantericanddiaphysealfemoralfractureshavebeenreportedwithbisphosphonatetherapy,primarily

inpatientsreceivinglong-termtreatmentforosteoporosis.Thesetransverseorshortoblique,fracturescanoccur

anywherealongthefemurfromjustbelowthelessertrochantertojustabovethesupracondylarflare.Thesefractures

occurafterminimalornotraumaandsomepatientsexperiencethighorgroinpain,oftenassociatedwithimaging

featuresofstressfractures,weekstomonthsbeforepresentingwithacompletedfemoralfracture.Fracturesareoften

bilateral;thereforethecontralateralfemurshouldbeexaminedinbisphosphonate-treatedpatientswhohavesustaineda

femoralshaftfracture.Poorhealingofthesefractureshasalsobeenreported.

Discontinuationofbisphosphonatetherapyinpatientssuspectedtohaveanatypicalfemurfractureshouldbe

consideredpendingevaluationofthepatient,basedonanindividualbenefitriskassessment.Duringbisphosphonate

treatmentpatientsshouldbeadvisedtoreportanythigh,hiporgroinpainandanypatientpresentingwithsuch

symptomsshouldbeevaluatedforanincompletefemurfracture.

PatientsshouldbeinstructedthatiftheymissadoseofFostepor,theyshouldtakeonetabletonthemorningafterthey

remember.Theyshouldnottaketwotabletsonthesamedaybutshouldreturntotakingonetabletperday,as

originallyscheduled.

AlendronateisnotrecommendedforpatientswithrenalimpairmentwhereGFRislessthan35ml/min,(seesection

4.2).

Causesofosteoporosisotherthanoestrogendeficiencyandageingshouldbeconsidered.

Hypocalcaemiamustbecorrectedbeforeinitiatingtherapywithalendronate(seesection4.3).Otherdisordersaffecting

mineralmetabolism(suchasvitaminDdeficiencyandhypoparathyroidism)shouldalsobeeffectivelytreated.In

patientswiththeseconditions,serumcalciumandsymptomsofhypocalcaemiashouldbemonitoredduringtherapy

withFostepor.

Duetothepositiveeffectsofalendronateinincreasingbonemineral,decreasesinserumcalciumandphosphatemay

occurespeciallyinpatientstakingglucocorticoidsinwhomcalciumabsorptionmaybedecreased.Theseareusually

smallandasymptomatic.However,therehavebeenrarereportsofsymptomatichypocalcaemia,whichhave

occasionallybeensevereandoftenoccurredinpatientswithpredisposingconditions(e.g.hypoparathyroidism,vitamin

Ddeficiencyandcalciummalabsorption).

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Excipients

Thismedicinalproductcontainslactose.Patientswithrarehereditaryproblemsofgalactoseintolerance,theLapp

lactasedeficiencyorglucose-galactosemalabsorptionshouldnottakethismedicinalproduct.

4.5Interactionwithothermedicinalproductsandotherformsofinteraction

Iftakenatthesametime,itislikelythatfoodandbeverages(includingmineralwater),calciumsupplements,antacids,

andsomeoralmedicinalproductswillinterferewithabsorptionofalendronate.Therefore,patientsmustwaitatleast30

minutesaftertakingalendronatebeforetakinganyotheroralmedicinalproduct(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.Alendronategivenduringpregnancyinratscauseddystociarelatedtohypocalcaemia.Animalstudiesrevealed

effectsonfoetalboneformation(incompleteossification)athighdoses(seesection5.3).

Useduringlactation

Itisnotknownwhetheralendronateisexcretedintohumanbreastmilk.Alendronateshouldnotbeusedbybreast-

feedingwomen.

4.7Effectsonabilitytodriveandusemachines

Nostudiesontheeffectsontheabilitytodriveandusemachineshavebeenperformed.However,certainadverse

reactionsthathavebeenreportedwithFostepormayaffectsomepatients'abilitytodriveoroperatemachinery.

IndividualresponsestoFostepormayvary.(Seesection4.8).

4.8Undesirableeffects

Inaone-yearstudyinpost-menopausalwomenwithosteoporosistheoverallsafetyprofilesofAlendronatesodium

OnceWeekly70mg(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:

-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

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Thefollowingadverseexperienceshavealsobeenreportedduringclinicalstudiesand/orpost-marketinguse:

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

Nausea 1.9 2.4 3.6 4.0

abdominaldistension 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:hypersensitivityreactionsincluding

urticariaandangioedema

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,diarrhoea,flatulence,oesophageal

ulcer*,dysphagia*,abdominaldistension,acid

regurgitation

Uncommon:nausea,vomiting,gastritis,

oesophagitis*,oesophagealerosions*,melena †

Rare:oesophagealstricture*,oropharyngeal

ulceration*,uppergastrointestinalPUBs

(perforation,ulcers,bleeding) §

Skinandsubcutaneoustissuedisorders:

Common:alopecia †

,pruritus †

Uncommon:rash,,erythema

Rare:rashwithphotosensitivity,severeskin

reactionsincludingStevens-Johnsonsyndrome

andtoxicepidermalnecrolysis ‡

Musculoskeletalandconnectivetissue

disorders: Verycommon:musculoskeletal(bone,muscle

orjoint)painwhichissometimessevere †§

Common:jointswelling †

Rare:Osteonecrosisofthejaw ‡§

,atypical

subtrochantericanddiaphysealfemoral

fractures(bisphosphonateclassadverse

reaction) ‡§

Generaldisordersandadministrationsite

Common:asthenia †

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§

Seesection4.4

FrequencyinClinicalTrialswassimilarinthedrugandplacebogroup.

*Seesections4.2and4.4

Thisadversereactionwasidentifiedthroughpost-marketingsurveillance.Thefrequencyofrarewasestimated

basedonrelevantclinicaltrials

4.9Overdose

Hypocalcaemia,hypophosphataemiaanduppergastro-intestinaladverseevents,suchasupsetstomach,heartburn,

oesophagitis,gastritis,orulcer,mayresultfromoraloverdosage.

Nospecificinformationisavailableonthetreatmentofoverdosagewithalendronate.Milkorantacidsshouldbegiven

tobindalendronate.Owingtotheriskofoesophagealirritation,vomitingshouldnotbeinducedandthepatientshould

remainfullyupright.

5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

ATCCode:M05BA04.

Pharmacotherapeuticgroup:Bisphosphonates.Osteoclastinhibitingagentforthetreatmentofbonediseases.

Alendronateisabisphosphonatewhichinanimalstudiesisdepositedbelowosteoclastsinareaswithboneresorption.It

inhibitstheboneresorptionwithnodirecteffectontheboneformation.Asbothboneresorptionandboneformation

arelinked,theformationoftheboneisalsoreduced,buttoalessextentthantheresorption,resultinginaprogressive

increaseofthebonemasswithnormalbonestructure.Alendronateisdepositedinbonematrixwhereitis

pharmacologicallyinactive.

Inratsthelowestdoseofalendronateinfluencingthebonemineralisation(leadingtoosteomalacia)was6000times

higherthantheantiresorptivedose.Thecorrespondingrelationforetidronatewasonetoone.Thesedataindicatethat

alendronateadministeredintherapeuticdosesmostprobablydonotinduceosteomalacia.

Osteoporosisinpostmenopausalwomen

Treatmentwithalendronateinpostmenopausalwomencausesbiochemicalchangesindicatingdose-dependent

inhibitionoftheboneresorption.Suchbiochemicalchangesreturnedtothestartingpointassoonasthreeweeksafter

discontinuationofthealendronatetherapydespitethelongretentionofalendronateinthebones.

Instudiesofuptofiveyearsalendronate10mg/dayreducedthebiochemicalmarkersforboneresorptionduringthree

tosixmonthsbyapproximately50-70%toalevelcorrespondingtothelevelinhealthy,premenopausalwomen.

Likewise,themarkersforboneformationwerereducedby25-50%aftersixtotwelvemonths.Thenewlevelofbone

resorptionandboneformationwasmaintainedfortherestofthealendronatetreatmentperiod.

Effectonbonemineralisationdensity

Inclinicaltrialsalendronate10mgoncedailyforthreeyearsresultedinincreasedbonemineralisationdensity(BMD)

inpostmenopausalwomenwithosteoporosis.Followingtreatmentforthreeyearswithalendronate10mg/daythe

BMDincrease(versusplacebo)wasapproximately8.8%incolumnalumbalis,5.9%incollumfemoris,7.8%in

trochanter,2.25intheforearmand2.5%inthewholebody.Inthetwo-yearprolongationofthesetrials,treatmentwith

alendronate10mg/dayresultedinfurtherincreaseofBMDincolumnaspinalsandtrochanter(absolutefurtherincrease

betweenyear3and5:Columniaspinalis0.94%,trochanter0.88%).BMDincollumfemoris,intheforearmandinthe

conditions: Uncommon:transientsymptomsasinanacute-

phaseresponse(myalgia,malaiseandrarely,

fever),typicallyinassociationwithinitiationof

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Theeffectofalendronatewasthesameregardlessofage,race,initialbonemetabolismrate,renalfunctionanduse

togetherwithawiderangeofotherdrugs.

Followingdiscontinuationofalendronateafter1-2yearsoftreatment,neitherafurtherincreaseofthebonemass,nor

anacceleratedbonelosswereobserved.ThesedataindicatethatdailytreatmentwithFostepormustcontinuetoobtain

aprogressiveincreaseofthebonemass.

Effectonfractureincidence

Alendronategivesthesamereductionofincidenceofbothvertebralandnon-vertebralfracturesinpatientswhohave

nothadfracturesandinpatientswhohadprevioushadavertebralfracture.

Thefollowingresultswerereportedfromananalysisofpooledthree-yeardatafromthetwomaintreatmenttrialswith

varyingdosesofalendronatetopostmenopausalwomen:48%reductionofthenumberofpatientsdevelopingoneor

morevertebralfractures(alendronate3.2%versusplacebo6.2%).Inpatientswhodevelopedvertebralfractures,the

lossofheightwassmallerinthosetreatedwithalendronate(5.9mmversus23.3mm).Pooleddatafromfivetrialsof2-

3yearsdurationshoweda29%reductioninthenumberofnon-vertebralfractures(alendronate9.0%versusplacebo

12.6%).

Threeyearsoftreatmentwithalendronate(5mg/dayforthefirsttwoyearsand10mg/dayinthethirdyear)in

menopausalwomenwithosteoporosis(whohavehadatleastonevertebralcompressionfracture)resultedina

reductionofthefollowingfractureincidences:Theproportionofpatientswhoexperiencedatleastonenewvertebral

fracture(alendronate8.0%versusplacebo15.0%-areductionof47%);patientswithatleasttwonewvertebral

fractures(0.5%versus4.9%–areductionof90%);anyclinical(i.e.painful)fracture(13.7%versus18.3%-a

reductionof28%;hipfracture(1.1%versus2.2%-areductionof51%);wrist(forearm)fracture(2.2%versus4.1%-a

reductionof48%).

Bonehistology

Thebonehistologyin270postmenopausalpatientswithosteoporosistreatedwithalendronateinadosageof1-20

mg/dayfor1-3years,showednormalmineralisationandstructureaswellasanexpectedreductioninthebone

metabolismascomparedwithplacebo.Long-termtreatmentwithalendronateinratsandbaboonsshowednormalbone

histologyandincreasedbonestrength.

Co-therapywithoestrogen/hormonesubstitution(HRT):

TheeffectonBMDofalendronate10mgoncedailyandconjugatedoestrogen(0.625mg/day)eitheraloneorin

combinationwasassessedinatwo-yearstudyofpostmenopausalwomenwithosteoporosisandhysterectomy.After

twoyearstheincreaseincolumnalumbalisBMDfrombaselinewassignificantlylargerwiththecombination(8.3%)

thanwitheitheroestrogenoralendronatetreatmentalone(both6%).

TheeffectonBMDwhenalendronatewasaddedtolong-termtherapy(atleastoneyear)withHRT(oestrogen+/-

gestagen)wasassessedinaone-yearstudyofpostmenopausalwomenwithosteoporosis.Theadditionofalendronate

10mgatleastoncedailytoHRTafteroneyearresultedinasignificantlargerincreaseofcolumnalumbalisBMD

(3.7%)comparedwithHRTalone(1.1%).

ThesestudiesshowedasignificantlymorefavourabletrendinBMDwithcombinedtreatmentthanwithHRTalone,for

thewholehip,collumfemorisandtrochanter.ThestudyshowednosignificanteffectontheoverallbodyBMD.

Treatmentofosteoporosisinmen

Theefficacyofalendronateinmenwithosteoporosiswasdemonstratedinaclinicaltrial.

Inatwoyearsstudy10mgofalendronatewasadministeredoncedailytomen(agegroup31to87years,average66

years).AftertwoyearstheaveragesignificantincreaseinBMDcomparedtotreatmentwithplacebowasthefollowing:

columnalumbalis,5.3%;collumfemoris,2.6%;trochanter,3.1%andtotalBDM1.6%.

In127menreceiving10mgalendronatetheincidenceofnewvertebralfractures(measuredwithquantitative

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reducedtheloweringofheight(-0.6versus2.4mm-respectively).Thisisinlinewithotheressentiallargerstudiesin

postmenopausalwomen.

Thereisnodocumentedreductionoftheincidenceofclinicalfracturesinvertebrae.

Thereisnodocumentedreductionoftheincidenceofnon-vertebralfracturesinmen.

Paediatricpatients

Alendronatesodiumhasbeenstudiedinasmallnumberofpatientswithosteogenesisimperfectaundertheageof18

years.Resultsareinsufficienttosupporttheuseofalendronatesodiuminpaediatricpatientswithosteogenesis

imperfecta.

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:

Oralbioavailabilityforalendronateinwomenis0.7%fordosesfrom5-40mgwhenadministeredonanemptystomach

andtwohourspriortoastandardbreakfast.Oralbioavailabilityinmen(0.6%)wasapproximatelythesameasin

women.Bioavailabilitywasreducedwithapproximately40%whenalendronatewasgivenhalftoonehourbeforea

standardbreakfast.

Bioavailabilitywasnegligibleregardlessofwhetheralendronatewastakenwithoruptotwohoursafterastandard

breakfast.Coffeeandorangejuicereducebioavailabilitywithapproximately60%(SeeSection4.2Posologyand

methodofadministration).

Inhealthyvolunteersoralprednisone(20mgthricedailyforfivedays)didnotchangethebioavailabilityof

alendronatesignificantly(averageincreasefrom20-44%).

Distribution:

Proteinbindingisapproximately78%.Preclinicalstudiesshowadistributionofalendronatetosofttissueandthena

fastredistributiontotheboneswhereitisboundorexcretedwithurine.Steadystatedistributionvolumeinthebody’s

softtissueisatleast28litres(22-35litres).Theplasmaconcentrationsofthemedicinalproductfollowing

administrationofanoraltherapeuticdoseisbelowdetectionlimit(<5ng/ml).

Biotransformation:

Alendronatehasnoknownmetabolites.

Elimination:

Approximately50%of 14

Clabelledalendronateisexcretedviaurinewithin72hours.Verylittleornoradioactivityis

recoveredinfaeces.Therestisdepositedinbonetissuewhereitisinactive.Renalclearanceis71ml/minuteaftera

singledoseof10mgIV.Withinsixhourstheplasmaconcentrationdeclineswithmorethan95%followingIV

administration.Thenalendronateisslowlyreleasedfromtheskeleton.Estimatedhalflifeisthus>10years.

Patientcharacteristics:

Preclinicalinvestigationsshowthatthemedicinalproductwhichisnotdepositedinthebone,isexcretedfastinthe

urine.FollowingchronicdosageofcumulativeIVdosesofupto35mg/kginanimalsnosaturationofboneuptakehas

beendemonstrated.Inanimalstheeliminationofalendronateviathekidneysisreducedwithreducedrenalfunction.

Nocorrespondinginformationisavailableforhumanbeings,butalargeraccumulationofalendronateinbonesmustbe

expectedinhumansincaseofreducedrenalfunction(seeSection4.2Dosage).

5.3Preclinicalsafetydata

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toxicity,genotoxicityandcarcinogenicpotential.Studiesinratshaveshownthattreatmentwithalendronateduring

pregnancywasassociatedwithdystociaindamsduringparturitionwhichwasrelatedtohypocalcaemia.Instudies,rats

givenhighdosesshowedanincreasedincidenceofincompletefoetalossification.Therelevancetohumansis

unknown.

6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

Microcrystallinecellulose(E460).

Lactosemonohydrate.

Croscarmellosesodium.

Magnesiumstearate(E572).

Povidone.

6.2Incompatibilities

Notapplicable.

6.3Shelflife

3years.

6.4Specialprecautionsforstorage

Keepintheoriginalpackage.Nospecialprecautionforstorage.

6.5Natureandcontentsofcontainer

Greenopaquealuminium/PVCblisterpacks.

Polypropylenecontainerwithpolyethylenecap.

Packsizes:

Blisters:10,14,28,30and98tablets*

Containers:28,30,50,98,100,112and250tablets*

*Notallpacksizesmaybemarketed.

6.6Specialprecautionsfordisposal

Nospecialrequirements.

7MARKETINGAUTHORISATIONHOLDER

McDermottLaboratoriesLtd.t/aGerardLaboratories

35/36BaldoyleIndustrialEstate,GrangeRoad,

Dublin13

8MARKETINGAUTHORISATIONNUMBER

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 24/11/2011 CRN 2104779 page number: 9

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

Dateoffirstauthorisation:13October2006

Dateoflastrenewal:19May2010

10DATEOFREVISIONOFTHETEXT

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 24/11/2011 CRN 2104779 page number: 10