ALENDRONIC ACID PFIZER 70 MG TABLETS

Main information

  • Trade name:
  • ALENDRONIC ACID PFIZER 70 MG TABLETS
  • Dosage:
  • 70 Milligram
  • Pharmaceutical form:
  • Tablets
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug

Documents

Localization

  • Available in:
  • ALENDRONIC ACID PFIZER 70 MG TABLETS
    Ireland
  • Language:
  • English

Status

  • Source:
  • HPRA - Health Products Regulatory Authority - Ireland
  • Authorization number:
  • PA0822/079/001
  • Authorization date:
  • 23-06-2011
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

AlendronicAcidPfizer70mgTablets

2QUALITATIVEANDQUANTITATIVECOMPOSITION

Eachtabletcontains70mgalendronicacid(equivalentto91.363mgofsodiumalendronatetrihydrate).

Forthefulllistofexcipients,seesection6.1.

3PHARMACEUTICALFORM

Tablet.

Whitetooff-white,oval,biconvex,uncoatedtabletsdebossedwith‘F’ononesideand‘21’ontheotherside.

4CLINICALPARTICULARS

4.1TherapeuticIndications

Treatmentofpostmenopausalosteoporosis.Alendronicacidreducestheriskofvertebralandhipfractures.

4.2Posologyandmethodofadministration

Therecommendeddosageisone70mgtabletonceweekly.

Topermitadequateabsorptionofalendronicacid:

Alendronicacidmustbetakenatleast30minutesbeforethefirstfood,beverage,ormedicinalproductofthedaywith

plainwateronly.Otherbeverages(includingmineralwater),foodandsomemedicinalproductsarelikelytoreducethe

absorptionofalendronicacid(seesection4.5).

Tofacilitatedeliverytothestomachandthusreducethepotentialforlocalandoesophagealirritation/adverse

experiences(seesection4.4):

Alendronicacidshouldonlybeswalloweduponarisingforthedaywithafullglassofwater(notlessthan200ml

or7fl.oz.).

PatientsshouldonlyswallowAlendronicacidwhole.Patientsshouldnotcrushorchewthetabletorallowthe

tablettodissolveintheirmouthsbecauseofapotentialfororopharyngealulceration.

Patientsshouldnotliedownuntilaftertheirfirstfoodofthedaywhichshouldbeatleast30minutesaftertaking

thetablet.

Patientsshouldnotliedownforatleast30minutesaftertakingalendronicacid.

Alendronicacidshouldnotbetakenatbedtimeorbeforearisingfortheday.

PatientsshouldreceivesupplementalcalciumandvitaminDifdietaryintakeisinadequate(seesection4.4).

Useintheelderly:Inclinicalstudiestherewasnoage-relateddifferenceintheefficacyorsafetyprofilesofalendronic

acid.Thereforenodosageadjustmentisnecessaryfortheelderly.

Useinrenalimpairment:NodosageadjustmentisnecessaryforpatientswithGFRgreaterthan35ml/min.Alendronic

acidisnotrecommendedforpatientswithrenalimpairmentwhereGFRislessthan35ml/min,duetolackof

experience.

Paediatricpatients:Alendronatesodiumisnotrecommendedforuseinchildrenundertheageof18yearsdueto

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AlendronicAcid70mg,tabletshasnotbeeninvestigatedinthetreatmentofglucocorticoid-inducedosteoporosis.

Theoptimaldurationofbisphosphonatetreatmentforosteoporosishasnotbeenestablished.Theneedforcontinued

treatmentshouldbere-evaluatedperiodicallybasedonthebenefitsandpotentialrisksofAlendronicAcid70mgonan

individualpatientbasis,particularlyafter5ormoreyearsofuse.

4.3Contraindications

Hypersensitivitytoalendronicacidortoanyoftheexcipientslistedinsection6.1

Abnormalitiesoftheoesophagusandotherfactorswhichdelayoesophagealemptyingsuchasstrictureor

achalasia.

Inabilitytostandorsituprightforatleast30minutes.

Hypocalcaemia.

Seealsosection4.4.

4.4Specialwarningsandprecautionsforuse

Alendronicacidcancauselocalirritationoftheuppergastro-intestinalmucosa.Becausethereisapotentialfor

worseningoftheunderlyingdisease,cautionshouldbeusedwhenalendronicacidisgiventopatientswithactiveupper

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

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

surgeryoftheuppergastro-intestinaltractotherthanpyloroplasty(seesection4.3).InpatientswithknownBarrett’s

oesophagous,prescribersshouldconsiderthebenefitsandpotentialrisksofalendronicacidonanindividualpatient

basis.

Oesophagealreactions(sometimessevereandrequiringhospitalisation),suchasoesophagitis,oesophagealulcersand

oesophagealerosions,rarelyfollowedbyoesophagealstricture,havebeenreportedinpatientsreceivingalendronic

acid.Physiciansshouldthereforebealerttoanysignsorsymptomssignallingapossibleoesophagealreactionand

patientsshouldbeinstructedtodiscontinuealendronicacidandseekmedicalattentioniftheydevelopsymptomsof

oesophagealirritationsuchasdysphagia,painonswallowingorretrosternalpain,neworworseningheartburn.

Theriskofsevereoesophagealadverseexperiencesappearstobegreaterinpatientswhofailtotakealendronicacid

properlyand/orwhocontinuetotakealendronicacidafterdevelopingsymptomssuggestiveofoesophagealirritation.It

isveryimportantthatthefulldosinginstructionsareprovidedto,andunderstoodbythepatient(seesection4.2).

Patientsshouldbeinformedthatfailuretofollowtheseinstructionsmayincreasetheirriskofoesophagealproblems.

Whilenoincreasedriskwasobservedinextensiveclinicaltrials,therehavebeenrare(post-marketing)reportsof

gastricandduodenalulcers,somesevereandwithcomplications.

PatientsshouldbeinstructedthatiftheymissadoseofAlendronicAcid,theyshouldtakeonetabletonthemorning

aftertheyremember.Theyshouldnottaketwotabletsonthesamedaybutshouldreturntotakingonetabletoncea

week,asoriginallyscheduledontheirchosenday.

AlendronicacidisnotrecommendedforpatientswithrenalimpairmentwhereGFRislessthan35ml/min,(seesection

4.2).

Causesofosteoporosisotherthanoestrogendeficiencyandageingshouldbeconsidered.

Hypocalcaemiamustbecorrectedbeforeinitiatingtherapywithalendronicacid(seesection4.3).Otherdisorders

affectingmineralmetabolism(suchasvitaminDdeficiencyandhypoparathyroidism)shouldalsobeeffectivelytreated.

Inpatientswiththeseconditions,serumcalciumandsymptomsofhypocalcaemiashouldbemonitoredduringtherapy

withalendronicacid.

Duetopositiveeffectsofalendronicacidinincreasingbonemineral,decreasesinserumcalciumandphosphatemay

occurespeciallyinpatientstakingglucocorticoidsinwhomcalciumabsorptionmaybedecreased.Theseareusually

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occasionallybeensevereandoftenoccurredinpatientswithpredisposingconditions(e.g.hypoparathyroidism,vitamin

Ddeficiencyandcalciummalabsorption).

EnsuringadequatecalciumandvitaminDintakeisparticularlyimportantinpatientsreceivingglucocorticoids.

Osteonecrosisofthejaw,generallyassociatedwithtoothextractionand/orlocalinfection(includingosteomyelitis)has

beenreportedinpatientswithcancerreceivingtreatmentregimensincludingprimarilyintravenouslyadministered

bisphosphonates.Manyofthesepatientswerealsoreceivingchemotherapyandcorticosteroids.Osteonecrosisofthe

jawhasalsobeenreportedinpatientswithosteoporosisreceivingoralbisphosphonates.

Adentalexaminationwithappropriatepreventivedentistryshouldbeconsideredpriortotreatmentwith

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

poororalhygiene,periodontaldisease,smoking).

Whileontreatment,thesepatientsshouldavoidinvasivedentalproceduresifpossible.Forpatientswhodevelop

osteonecrosisofthejawwhileonbisphosphonatetherapy,dentalsurgerymayexacerbatethecondition.Forpatients

requiringdentalprocedures,therearenodataavailabletosuggestwhetherdiscontinuationofbisphosphonatetreatment

reducestheriskofosteonecrosisofthejaw.

Clinicaljudgementofthetreatingphysicianshouldguidethemanagementplanofeachpatientbasedonindividual

benefit/riskassessment.

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

thesesymptomshaverarelybeensevereand/orincapacitating(seesection4.8).Thetimetoonsetofsymptomsvaried

fromonedaytoseveralmonthsafterstartingtreatment.Mostpatientshadreliefofsymptomsafterstopping.Asubset

hadrecurrenceofsymptomswhenrechallengedwiththesamedrugoranotherbisphosphonate.

Atypicalfracturesofthefemur

Atypicalsubtrochantericanddiaphysealfemoralfractureshavebeenreportedwithbisphosphonatetherapy,primarily

inpatientsreceivinglong-termtreatmentforosteoporosis.Thesetransverseorshortobliquefracturescanoccur

anywherealongthefemurfromjustbelowthelessertrochantertojustabovethesupracondylarflare.Thesefractures

occurafterminimalornotraumaandsomepatientsexperiencethighorgroinpain,oftenassociatedwithimaging

featuresofstressfractures,weekstomonthsbeforepresentingwithacompletedfemoralfracture.Fracturesareoften

bilateral;thereforethecontralateralfemurshouldbeexaminedinbisphosphonate-treatedpatientswhohavesustaineda

femoralshaftfracture.Poorhealingofthesefractureshasalsobeenreported.Discontinuationofbisphosphonate

therapyinpatientssuspectedtohaveanatypicalfemurfractureshouldbeconsideredpendingevaluationofthepatient,

basedonanindividualbenefitriskassessment.

Duringbisphosphonatetreatmentpatientsshouldbeadvisedtoreportanythigh,hiporgroinpainandanypatient

presentingwithsuchsymptomsshouldbeevaluatedforanincompletefemurfracture.

4.5Interactionwithothermedicinalproductsandotherformsofinteraction

Iftakenatthesametime,itislikelythatfoodandbeverages(includingmineralwater),calciumsupplements,antacids,

andsomeoralmedicinalproductswillinterferewithabsorptionofalendronicacid.Therefore,patientsmustwaitat

least30minutesaftertakingalendronicacidbeforetakinganyotheroralmedicinalproduct(seesection4.2andsection

5.2).

Nootherinteractionswithmedicinalproductsofclinicalsignificanceareanticipated.Anumberofpatientsinthe

clinicaltrialsreceivedoestrogen(intravaginal,transdermal,ororal)whiletakingalendronicacid.Noadverse

experiencesattributabletotheirconcomitantusewereidentified.

SinceNSAIDuseisassociatedwithgastrointestinalirritation,cautionshouldbeusedduringconcomitantusewith

alendronicacid.

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withawiderangeofcommonlyprescribedmedicinalproductswithoutevidenceofclinicaladverseinteractions.

4.6Fertility,pregnancyandlactation

Pregnancy

Therearenoadequatedatafromtheuseofalendronicacidinpregnantwomen.Animalstudiesdonotindicatedirect

harmfuleffectswithrespecttopregnancy,embryonal/foetaldevelopment,orpostnataldevelopment.Alendronicacid

givenduringpregnancyinratscauseddystociarelatedtohypocalcemia(seesection5.3).Giventheindication,

alendronicacidshouldnotbeusedduringpregnancy.

Lactation

Itisnotknownwhetheralendronicacidisexcretedintohumanbreastmilk.Giventheindication,alendronicacid

shouldnotbeusedbybreast-feedingwomen.

4.7Effectsonabilitytodriveandusemachines

Nostudiesontheeffectsontheabilitytodriveandusemachineshavebeenperformed.However,certainadverse

reactionsthathavebeenreportedwithAlendronicacidmayaffectsomepatientsabilitytodriveoroperatemachinery.

IndividualresponsestoAlendronicacidmayvary(seesection4.8).

4.8Undesirableeffects

Inaone-yearstudyinpost-menopausalwomenwithosteoporosistheoverallsafetyprofilesofAlendronicacidOnce

Weekly70mg(n=519)andalendronicacid10mg/day(n=370)weresimilar.

Intwothree-yearstudiesofvirtuallyidenticaldesign,inpost-menopausalwomen(alendronicacid10mg:n=196,

placebo:n=397)theoverallsafetyprofilesofalendronicacid10mg/dayandplaceboweresimilar.

Adverseexperiencesreportedbytheinvestigatorsaspossibly,probablyordefinitelydrug-relatedarepresentedbelow

iftheyoccurredin 1%ineithertreatmentgroupintheone-yearstudy,orin 1%ofpatientstreatedwithalendronic

acid10mg/dayandatagreaterincidencethaninpatientsgivenplacebointhethree-yearstudies:

One-YearStudy Three-YearStudies

AlendronicacidOnce

Weekly70mg

(n=519) Alendronicacid

10mg/day

(n=370) Alendronicacid10

mg/day

(n=196) Placebo

(n=397)

Gastrointestinaldisorders

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,connectivetissueandbonedisorders

musculoskeletal(bone,muscle

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Thefollowingadverseexperienceshavealsobeenreportedduringclinicalstudiesand/orpost-marketinguse:

[Common(1/100,<1/10),Uncommon(1/1000,<1/100),Rare(1/10,000,<1/1000),Veryrare(<1/10,000)not

known(cannotbeestimatedfromtheavailabledata)]

Immunesystemdisorders:

Rare:hypersensitivityreactionsincludingurticariaandangioedema

Metabolismandnutritiondisorders:

Rare:symptomatichypocalcaemia,ofteninassociationwithpredisposingconditions.(seesection4.4)

Nervoussystemdisorders:

Common:headache

Eyedisorders:

Rare:uveitis,scleritis,episcleritis

Gastrointestinaldisorders:

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

distension,acidregurgitation

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

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

(seesection4.4)

*Seesections4.2and4.4

Skinandsubcutaneoustissuedisorders:

Uncommon:rash,pruritus,erythema

Rare:rashwithphotosensitivity

Veryrareandisolatedcases:isolatedcasesofsevereskinreactionsincludingStevens-Johnsonsyndromeandtoxic

epidermalnecrolysis

Musculoskeletal,connectivetissueandbonedisorders:

Common:musculoskeletal(bone,muscleorjoint)pain

Rare:Osteonecrosisofthejawhasbeenreportedinpatientstreatedbybisphosphonates.Themajorityofthereports

refertocancerpatients,butsuchcaseshavealsobeenreportedinpatientstreatedforosteoporosis.Osteonecrosisofthe

jawisgenerallyassociatedwithtoothextractionand/orlocalinfection(includingosteomyelitis).Diagnosisofcancer,

chemotherapy,radiotherapy,corticosteroidsandpoororalhygieneandsmokingarealsodeemedasriskfactors;severe

musculoskeletal(bone,muscleorjoint)pain(seesection4.4).Atypicalsubtrochantericanddiaphysealfemoral

fractures(adversereactionforthebisphosphonateclassofsubstances).

Generaldisordersandadministrationsiteconditions:

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

withinitiationoftreatment.

Duringpost-marketingexperiencethefollowingreactionshavebeenreported(frequencyunknown):

Nervoussystemdisorders:dizziness,dysgeusia

Earandlabyrinthdisorders:vertigo

Skinandsubcutaneoustissuedisorders:alopecia

Musculoskeletal,connectivetissueandbonedisorders:jointswelling,(seesection4.4)

Generaldisordersandadministrationsiteconditions:asthenia,peripheraloedema

Investigations

musclecramp 0.2 1.1 0.0 1.0

Nervoussystemdisorders

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approximately18and10%,respectively,ofpatientstakingalendronicacid10mg/dayversusapproximately12and3%

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

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

4.9Overdose

Hypocalcaemia,hypophosphataemiaanduppergastro-intestinaladverseevents,suchasupsetstomach,heartburn,

oesophagitis,gastritis,orulcer,mayresultfromoraloverdosage.

Nospecificinformationisavailableonthetreatmentofoverdosagewithalendronicacid.Milkorantacidsshouldbe

giventobindalendronicacid.Owingtotheriskofoesophagealirritation,vomitingshouldnotbeinducedandthe

patientshouldremainfullyupright.

5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

Pharmacotherapeuticgroup:Drugsaffectingbonestructureandmineralization,biphosphonate.

ATCCode:M05BA04

TheactiveingredientofAlendronicAcidtabletAlendronicAcid(assodiumalendronate)isabisphosphonatethat

inhibitsosteoclasticboneresorptionwithnodirecteffectonboneformation.Preclinicalstudieshaveshown

preferentiallocalisationofalendronicacidtositesofactiveresorption.Activityofosteoclastsisinhibited,but

recruitmentorattachmentofosteoclastsisnotaffected.Theboneformedduringtreatmentwithalendronicacidisof

normalquality.

Treatmentofpost-menopausalosteoporosis

OsteoporosisisdefinedasBMDofthespineorhip2.5SDbelowthemeanvalueofanormalyoungpopulation

orasapreviousfragilityfracture,irrespectiveofBMD.

Thetherapeuticequivalenceofalendronicacidonceweekly70mg(n=519)andalendronicacid10mgdaily(n=370)

wasdemonstratedinaone-yearmulticentrestudyofpost-menopausalwomenwithosteoporosis.Themeanincreases

frombaselineinlumbarspineBMDatoneyearwere5.1%(95%CI:4.8,5.4%)inthe70mgonce-weeklygroupand

5.4%(95%CI:5.0,5.8%)inthe10mgdailygroup.ThemeanBMDincreaseswere2.3%and2.9%atthefemoralneck

and2.9%and3.1%atthetotalhipinthe70mgonceweeklyand10mgdailygroups,respectively.Thetwotreatment

groupswerealsosimilarwithregardtoBMDincreasesatotherskeletalsites.

Theeffectsofalendronicacidonbonemassandfractureincidenceinpost-menopausalwomenwereexaminedintwo

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

Intheinitialefficacystudies,themeanbonemineraldensity(BMD)increaseswithalendronicacid10mg/dayrelative

toplaceboatthreeyearswere8.8%,5.9%and7.8%atthespine,femoralneckandtrochanter,respectively.Totalbody

BMDalsoincreasedsignificantly.Therewasa48%reduction(alendronicacid3.2%vsplacebo6.2%)inthe

proportionofpatientstreatedwithalendronicacidexperiencingoneormorevertebralfracturesrelativetothosetreated

withplacebo.Inthetwo-yearextensionofthesestudiesBMDatthespineandtrochantercontinuedtoincreaseand

BMDatthefemoralneckandtotalbodyweremaintained.

FITconsistedoftwoplacebo-controlledstudiesusingalendronicaciddaily(5mgdailyfortwoyearsand10mgdaily

foreitheroneortwoadditionalyears):

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

studyalendronicaciddailyreducedtheincidenceof 1newvertebralfractureby47%(alendronicacid7.9%vs.

placebo15.0%).Inaddition,astatisticallysignificantreductionwasfoundintheincidenceofhipfractures(1.1%

vs.2.2%,areductionof51%).

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study,asignificantdifferencewasobservedintheanalysisofthesubgroupofosteoporoticwomen(37%oftheglobal

populationwhocorrespondwiththeabovedefinitionofosteoporosis)intheincidenceofhipfractures(alendronic

acid1.0%vs.placebo2.2%,areductionof56%)andintheincidenceof 1vertebralfracture(2.9%vs.5.8%,a

reductionof50%).

Paediatricpatients:Alendronatesodiumhasbeenstudiedinasmallnumberofpatientswithosteogenesisimperfecta

undertheageof18years.Resultsareinsufficienttosupporttheuseofalendronatesodiuminpaediatricpatientswith

osteogenesisimperfecta.

5.2Pharmacokineticproperties

Absorption

Relativetoanintravenousreferencedose,theoralmeanbioavailabilityofalendronicacidinwomenwas0.64%for

dosesrangingfrom5to70mgwhenadministeredafteranovernightfastandtwohoursbeforeastandardisedbreakfast.

Bioavailabilitywasdecreasedsimilarlytoanestimated0.46%and0.39%whenalendronicacidwasadministeredone

hourorhalfanhourbeforeastandardisedbreakfast.Inosteoporosisstudies,alendronicacidwaseffectivewhen

administeredatleast30minutesbeforethefirstfoodorbeverageoftheday.

Bioavailabilitywasnegligiblewhetheralendronicacidwasadministeredwith,oruptotwohoursafter,astandardised

breakfast.Concomitantadministrationofalendronicacidwithcoffeeororangejuicereducedbioavailabilityby

approximately60%.

Inhealthysubjects,oralprednisone(20mgthreetimesdailyforfivedays)didnotproduceaclinicallymeaningful

changeinoralbioavailabilityofalendronicacid(ameanincreaserangingfrom20%to44%).

Distribution

Studiesinratsshowthatalendronicacidtransientlydistributestosofttissuesfollowing1mg/kgintravenous

administrationbutisthenrapidlyredistributedtoboneorexcretedintheurine.Themeansteady-statevolumeof

distribution,exclusiveofbone,isatleast28litresinhumans.Concentrationsofdruginplasmafollowingtherapeutic

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

Biotransformation

Thereisnoevidencethatalendronicacidismetabolisedinanimalsorhumans.

Elimination

Followingasingleintravenousdoseof[ 14

C]alendronicacid,approximately50%oftheradioactivitywasexcretedin

theurinewithin72hoursandlittleornoradioactivitywasrecoveredinthefaeces.Followingasingle10mg

intravenousdose,therenalclearanceofalendronicacidwas71ml/min,andsystemicclearancedidnotexceed200

ml/min.Plasmaconcentrationsfellbymorethan95%withinsixhoursfollowingintravenousadministration.The

terminalhalf-lifeinhumansisestimatedtoexceedtenyears,reflectingreleaseofalendronicacidfromtheskeleton.

Alendronicacidisnotexcretedthroughtheacidicorbasictransportsystemsofthekidneyinrats,andthusitisnot

anticipatedtointerferewiththeexcretionofothermedicinalproductsbythosesystemsinhumans.

Characteristicsinpatients

Preclinicalstudiesshowthatthedrugthatisnotdepositedinboneisrapidlyexcretedintheurine.Noevidenceof

saturationofboneuptakewasfoundafterchronicdosingwithcumulativeintravenousdosesupto35mg/kginanimals.

Althoughnoclinicalinformationisavailable,itislikelythat,asinanimals,eliminationofalendronicacidviathe

kidneywillbereducedinpatientswithimpairedrenalfunction.Therefore,somewhatgreateraccumulationof

alendronicacidinbonemightbeexpectedinpatientswithimpairedrenalfunction(seesection4.2).

5.3Preclinicalsafetydata

Non-clinicaldatarevealnospecialhazardforhumansbasedonconventionalstudiesofsafetypharmacology,repeated

dosetoxicity,genotoxicityandcarcinogenicpotential.Studiesinratshaveshownthattreatmentwithalendronicacid

duringpregnancywasassociatedwithdystociaindamsduringparturitionwhichwasrelatedtohypocalcaemia.In

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Therelevancetohumansisunknown.

6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

Cellulose,Microcrystalline

MaizeStarch

SodiumStarchGlycolate(TypeA)

Povidone(Kollidon30)

Magnesiumstearate

6.2Incompatibilities

Notapplicable.

6.3Shelflife

2years.

6.4Specialprecautionsforstorage

Thismedicinalproductdoesnotrequireanyspecialstoragecondition.

6.5Natureandcontentsofcontainer

ThetabletsaresuppliedinblisterpackscomprisingofPVC/Aclar–Aluminium.

Packsize:2,4,8,12,20,30,40,50or60tablets.

Notallpacksizesmaybemarketed.

6.6Specialprecautionsfordisposal

Nospecialrequirementsfordisposal

Anyunusedmedicinalproductorwastematerialshouldbedisposedofinaccordancewithlocalrequirements.

6.6Specialprecautionsfordisposalandotherhandling

Nospecialrequirements.

7MARKETINGAUTHORISATIONHOLDER

PfizerHealthcareIreland

9Riverwalk

NationalDigitalPark

CitywestBusinessCampus

Dublin24

8MARKETINGAUTHORISATIONNUMBER

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9DATEOFFIRSTREGISTRATION/RENEWALOFTHEREGISTRATION

DateofFirstAuthorisation:23rdJune2011

10DATEOFREVISIONOFTHETEXT

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