ALENDRONIC ACID CEFT ONCE WEEKLY

Main information

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

Documents

Localization

  • Available in:
  • ALENDRONIC ACID CEFT ONCE WEEKLY
    Ireland
  • Language:
  • English

Status

  • Source:
  • HPRA - Health Products Regulatory Authority - Ireland
  • Authorization number:
  • PA1524/002/002
  • Authorization date:
  • 07-10-2011
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

AlendronicAcidCeftOnceWeekly70mgTablets

2QUALITATIVEANDQUANTITATIVECOMPOSITION

Eachtabletcontains70mgalendronicacid(assodiumalendronate).

Forafulllistofexcipients,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.).

Patientsshouldonlyswallow'AlendronicAcid'whole.Patientsshouldnotcrushorchewthetabletorallowthe

tablettodissolveintheirmouthsbecauseofapotentialfororopharyngealulceration.

Patientsshouldnotliedownuntilaftertheirfirstfoodofthedaywhichshouldbeatleast30minutesaftertaking

thetablet.

Patientsshouldnotliedownforatleast30minutesaftertakingalendronicacid.

Alendronicacidshouldnotbetakenatbedtimeorbeforearisingfortheday.

PatientsshouldreceivesupplementalcalciumandvitaminDifdietaryintakeisinadequate(seesection4.4).

Useintheelderly:Inclinicalstudiestherewasnoage-relateddifferenceintheefficacyorsafetyprofilesofalendronic

acid.Thereforenodosageadjustmentisnecessaryfortheelderly.

Useinrenalimpairment:NodosageadjustmentisnecessaryforpatientswithGFRgreaterthan35ml/min.Alendronic

acidisnotrecommendedforpatientswithrenalimpairmentwhereGFRislessthan35ml/min,duetolackof

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 10/10/2011 CRN 2058435 page number: 1

Paediatricpatients:Alendronatesodiumisnotrecommendedforuseinchildrenundertheageof18yearsdueto

insufficientdataonsafetyandefficacyinconditionsassociatedwithpaediatricosteoporosis(alsoseesection5.1).

AlendronicAcidCeftOnceWeekly70mg,tabletstenhasnotbeeninvestigatedinthetreatmentofglucocorticoid-

inducedosteoporosis.

Theoptimaldurationofbisphosphonatetreatmentforosteoporosishasnotbeenestablished.Theneedforcontinued

treatmentshouldbere-evaluatedperiodicallybasedonthebenefitsandpotentialrisksofalendronicacidonan

individualpatientbasis,particularlyafter5ormoreyearsofuse.

4.3Contraindications

Hypersensitivitytoalendronicacidortoanyoftheexcipients.

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.

Osteonecrosisofthejaw,generallyassociatedwithtoothextractionand/orlocalinfection(includingosteomyelitis)has

beenreportedinpatientswithcancerreceivingtreatmentregimensincludingprimarilyintravenouslyadministered

bisphosphonates.Manyofthesepatientswerealsoreceivingchemotherapyandcorticosteroids.Osteonecrosisofthe

jawhasalsobeenreportedinpatientswithosteoporosisreceivingoralbisphosphonates.

Thefollowingriskfactorsshouldbeconsideredwhenevaluatinganindividual'sriskofdevelopingosteonecrosisofthe

jaw:

potencyofthebisphosphonate(highestforzoledronicacid),routeofadministration(seeabove)andcumulative

dose

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 10/10/2011 CRN 2058435 page number: 2

ahistoryofdentaldisease,poororalhygiene,periodontaldisease,invasivedentalproceduresandpoorlyfitting

dentures.

Adentalexaminationwithappropriatepreventivedentistryshouldbeconsideredpriortotreatmentwithoral

bisphosphonatesinpatientswithpoordentalstatus.

Whileontreatment,thesepatientsshouldavoidinvasivedentalproceduresifpossible.Forpatientswhodevelop

osteonecrosisofthejawwhileonbisphosphonatetherapy,dentalsurgerymayexacerbatethecondition.Forpatients

requiringdentalprocedures,therearenodataavailabletosuggestwhetherdiscontinuationofbisphosphonatetreatment

reducestheriskofosteonecrosisofthejaw.

Clinicaljudgementofthetreatingphysicianshouldguidethemanagementplanofeachpatientbasedonindividual

benefit/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.Thesetransverseorshortobliquefracturescanoccur

anywherealongthefemurfromjustbelowthelessertrochantertojustabovethesupracondylarflare.Thesefractures

occurafterminimalornotraumaandsomepatientsexperiencethighorgroinpain,oftenassociatedwithimaging

featuresofstressfractures,weekstomonthsbeforepresentingwithacompletedfemoralfracture.Fracturesareoften

bilateral;thereforethecontralateralfemurshouldbeexaminedinbisphosphonate-treatedpatientswhohavesustaineda

femoralshaftfracture.Poorhealingofthesefractureshasalsobeenreported.Discontinuationofbisphosphonate

therapyinpatientssuspectedtohaveanatypicalfemurfractureshouldbeconsideredpendingevaluationofthepatient,

basedonanindividualbenefitriskassessment.

Duringbisphosphonatetreatmentpatientsshouldbeadvisedtoreportanythigh,hiporgroinpainandanypatient

presentingwithsuchsymptomsshouldbeevaluatedforanincompletefemurfracture.

PatientsshouldbeinstructedthatiftheymissadoseofAlendronicAcidCeftOnceWeekly,theyshouldtakeonetablet

onthemorningaftertheyremember.Theyshouldnottaketwotabletsonthesamedaybutshouldreturntotakingone

tabletonceaweek,asoriginallyscheduledontheirchosenday.

AlendronicacidisnotrecommendedforpatientswithrenalimpairmentwhereGFRislessthan35ml/min,(seesection

4.2).

Causesofosteoporosisotherthanoestrogendeficiencyandageingshouldbeconsidered.

Hypocalcaemiamustbecorrectedbeforeinitiatingtherapywithalendronicacid(seesection4.3).Otherdisorders

affectingmineralmetabolism(suchasvitaminDdeficiencyandhypoparathyroidism)shouldalsobeeffectivelytreated.

Inpatientswiththeseconditions,serumcalciumandsymptomsofhypocalcaemiashouldbemonitoredduringtherapy

withalendronicacid.

Duetopositiveeffectsofalendronicacidinincreasingbonemineral,decreasesinserumcalciumandphosphatemay

occur.Theseareusuallysmallandasymptomatic.However,therehavebeenreportsofsymptomatichypocalcaemia,

whichoccasionallyhavebeensevereandoftenoccurredinpatientswithpredisposingconditions(e.g.

hypoparathyroidism,vitaminDdeficiencyandcalciummalabsorption).EnsuringadequatecalciumandvitaminD

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 10/10/2011 CRN 2058435 page number: 3

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

alendronate.

Althoughspecificinteractionstudieswerenotperformed,inclinicalstudiesalendronicacidwasusedconcomitantly

withawiderangeofcommonlyprescribedmedicinalproductswithoutevidenceofclinicaladverseinteractions.

4.6Fertility,pregnancyandlactation

Useduringpregnancy

Alendronateshouldnotbeusedduringpregnancy.Therearenoadequatedatafromtheuseofalendronateinpregnant

women.Animalstudiesdonotindicatedirectharmfuleffectswithrespecttopregnancy,embryonal/fetaldevelopment,

orpostnataldevelopment.Alendronategivenduringpregnancyinratscauseddystociarelatedtohypocalcemia(see

section5.3).

Useduringlactation

Itisnotknownwhetheralendronateisexcretedintohumanbreastmilk.Giventheindication,alendronateshouldnotbe

usedbybreast-feedingwomen.

4.7Effectsonabilitytodriveandusemachines

Nostudiesontheeffectsontheabilitytodriveandusemachineshavebeenperformed.However,certainadverse

reactionsthathavebeenreportedwithalendronicacidmayaffectsomepatients'abilitytodriveoroperatemachinery.

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

iftheyoccurredin1%ineithertreatmentgroupintheone-yearstudy,orin1%ofpatientstreatedwithalendronicacid

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 10/10/2011 CRN 2058435 page number: 4

Thefollowingadverseexperienceshavealsobeenreportedduringclinicalstudiesand/orpost-marketinguse:

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

One-YearStudy Three-YearStudies

Alendronicacid

OnceWeekly

70mg

(n=519) Alendronic

acid10

mg/day

(n=370) Alendronicacid

10mg/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,

muscleorjoint)pain 2.9 3.2 4.1 2.5

musclecramp 0.2 1.1 0.0 1.0

Nervoussystem

disorders

headache 0.4 0.3 2.6 1.5

Immunesystemdisorders: Rare:hypersensitivityreactionsincludingurticariaandangioedema

Metabolismandnutrition

disorders: Rare:symptomatichypocalcaemia,ofteninassociationwithpredisposing

conditions. §

Nervoussystemdisorders: Common:headache,dizziness †

Uncommon:dysgeusia †

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

Earandlabyrinth

disorders: Common:vertigo †

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

oesophagealulcer*,dysphagia*,abdominaldistension,acidregurgitation

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

melena †

Rare:oesophagealstricture*,oropharyngealulceration*,uppergastrointestinal

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 10/10/2011 CRN 2058435 page number: 5

Duringpost-marketingexperiencethefollowingreactionshavebeenreported(frequencyrare):

Atypicalsubtrochantericanddiaphysealfemoralfractures(bisphosphonateclassadversereaction)

4.9Overdose

Hypocalcaemia,hypophosphataemiaanduppergastro-intestinaladverseevents,suchasupsetstomach,heartburn,

oesophagitis,gastritis,orulcer,mayresultfromoraloverdosage.

Nospecificinformationisavailableonthetreatmentofoverdosagewithalendronicacid.Milkorantacidsshouldbe

giventobindalendronicacid.Owingtotheriskofoesophagealirritation,vomitingshouldnotbeinducedandthe

patientshouldremainfullyupright.

5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

Pharmacotherapeuticgroup:Bisphosphonate,forthetreatmentofbonediseasesATCCode:M05BA04

TheactiveingredientofAlendronicAcidCeftOnceWeekly,alendronicacid,isabisphosphonatethatinhibits

osteoclasticboneresorptionwithnodirecteffectonboneformation.Preclinicalstudieshaveshownpreferential

localisationofalendronicacidtositesofactiveresorption.Activityofosteoclastsisinhibited,butrecruitmentor

attachmentofosteoclastsisnotaffected.Theboneformedduringtreatmentwithalendronicacidisofnormalquality.

Treatmentofpost-menopausalosteoporosis

OsteoporosisisdefinedasBMDofthespineorhip2.5SDbelowthemeanvalueofanormalyoungpopulation

Skinandsubcutaneous

tissuedisorders: Common:alopecia †

,pruritus †

Uncommon:rash,erythema

Rare:rashwithphotosensitivity,severeskinreactionsincludingStevens-

Johnsonsyndromeandtoxicepidermalnecrolysis ‡

Musculoskeletaland

connectivetissuedisorders: Verycommon:musculoskeletal(bone,muscleorjoint)painwhichissometimes

severe †§

Common:jointswelling †

Rare:Osteonecrosisofthejaw ‡§

;stressfracturesoftheproximalfemoral

shaft ‡§

Generaldisordersand

administrationsite

conditions: Common:asthenia †

,peripheraloedema †

Uncommon:transientsymptomsasinanacute-phaseresponse(myalgia,

malaiseandrarely,fever),typicallyinassociationwithinitiationoftreatment †

Seesection4.4

FrequencyinClinicalTrialswassimilarinthedrugandplacebogroup.

*Seesections4.2and4.4

Thisadversereactionwasidentifiedthroughpost-marketingsurveillance.Thefrequencyofrarewas

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 10/10/2011 CRN 2058435 page number: 6

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

studyalendronicaciddailyreducedtheincidenceof1newvertebralfractureby47%(alendronicacid7.9%vs.

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

vs.2.2%,areductionof51%).

FIT2:Afour-yearstudyof4,432patientswithlowbonemassbutwithoutabaselinevertebralfracture.Inthis

study,asignificantdifferencewasobservedintheanalysisofthesubgroupofosteoporoticwomen(37%ofthe

globalpopulationwhocorrespondwiththeabovedefinitionofosteoporosis)intheincidenceofhipfractures

(alendronicacid1.0%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.

Paediatricpatients:

Alendronatesodiumhasbeenstudiedinasmallnumberofpatientswithosteogenesisimperfectaundertheageof18

years.Resultsareinsufficienttosupporttheuseofalendronatesodiuminpaediatricpatientswithosteogenesis

imperfecta.

5.2Pharmacokineticproperties

Absorption

Relativetoanintravenousreferencedose,theoralmeanbioavailabilityofalendronicacidinwomenwas0.64%for

dosesrangingfrom5to70mgwhenadministeredafteranovernightfastandtwohoursbeforeastandardisedbreakfast.

Bioavailabilitywasdecreasedsimilarlytoanestimated0.46%and0.39%whenalendronicacidwasadministeredone

hourorhalfanhourbeforeastandardisedbreakfast.Inosteoporosisstudies,alendronicacidwaseffectivewhen

administeredatleast30minutesbeforethefirstfoodorbeverageoftheday.

Bioavailabilitywasnegligiblewhetheralendronicacidwasadministeredwith,oruptotwohoursafter,astandardised

breakfast.Concomitantadministrationofalendronicacidwithcoffeeororangejuicereducedbioavailabilityby

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 10/10/2011 CRN 2058435 page number: 7

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[C]alendronicacid,approximately50%oftheradioactivitywasexcretedin

theurinewithin72hoursandlittleornoradioactivitywasrecoveredinthefaeces.Followingasingle10mg

intravenousdose,therenalclearanceofalendronicacidwas71ml/min,andsystemicclearancedidnotexceed200

ml/min.Plasmaconcentrationsfellbymorethan95%withinsixhoursfollowingintravenousadministration.The

terminalhalf-lifeinhumansisestimatedtoexceedtenyears,reflectingreleaseofalendronicacidfromtheskeleton.

Alendronicacidisnotexcretedthroughtheacidicorbasictransportsystemsofthekidneyinrats,andthusitisnot

anticipatedtointerferewiththeexcretionofothermedicinalproductsbythosesystemsinhumans.

Characteristicsinpatients

Non-clinicalstudiesshowthatthedrugthatisnotdepositedinboneisrapidlyexcretedintheurine.Noevidenceof

saturationofboneuptakewasfoundafterchronicdosingwithcumulativeintravenousdosesupto35mg/kginanimals.

Althoughnoclinicalinformationisavailable,itislikelythat,asinanimals,eliminationofalendronicacidviathe

kidneywillbereducedinpatientswithimpairedrenalfunction.Therefore,somewhatgreateraccumulationof

alendronicacidinbonemightbeexpectedinpatientswithimpairedrenalfunction(seesection4.2).

5.3Preclinicalsafetydata

Non-clinicaldatarevealnospecialhazardforhumansbasedonconventionalstudiesofsafetypharmacology,repeated

dosetoxicity,genotoxicityandcarcinogenicpotential.Studiesinratshaveshownthattreatmentwithalendronicacid

duringpregnancywasassociatedwithdystociaindamsduringparturitionwhichwasrelatedtohypocalcaemia.In

studies,ratsgivenhighdosesshowedanincreasedincidenceofincompletefoetalossification.Therelevancetohumans

isunknown.

6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

Cellulose,Microcrystalline

MaizeStarch

SodiumStarchGlycolate(TypeA)

Povidone(K-30)

Magnesiumstearate

6.2Incompatibilities

Notapplicable.

6.3Shelflife

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 10/10/2011 CRN 2058435 page number: 8

6.4Specialprecautionsforstorage

Thismedicinalproductdoesnotrequireanyspecialstorageconditions.

6.5Natureandcontentsofcontainer

ThetabletsaresuppliedinblisterpackscomprisingofPVC/Aclar–Aluminium.

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

Notallpacksizesmaybemarketed.

6.6Specialprecautionsfordisposal

Nospecialrequirements.

7MARKETINGAUTHORISATIONHOLDER

CeftLimited

65DelamereRoad,Hayes

MiddlesexUB40NN

UnitedKingdom

8MARKETINGAUTHORISATIONNUMBER

PA1524/2/2

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

Dateoffirstauthorisation:7 th

October2011

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 10/10/2011 CRN 2058435 page number: 9