ALENDRONIC ACID 70MG 'ONCE WEEKLY'

Main information

  • Trade name:
  • ALENDRONIC ACID 70MG 'ONCE WEEKLY'
  • Dosage:
  • 70 Milligram
  • Pharmaceutical form:
  • Film Coated Tablet
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug

Documents

Localization

  • Available in:
  • ALENDRONIC ACID 70MG 'ONCE WEEKLY'
    Ireland
  • Language:
  • English

Status

  • Source:
  • HPRA - Health Products Regulatory Authority - Ireland
  • Authorization number:
  • PA1330/002/001
  • Authorization date:
  • 19-12-2007
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

IRISHMEDICINESBOARDACTS1995AND2006

MEDICINALPRODUCTS(CONTROLOFPLACINGONTHEMARKET)REGULATIONS,2007

(S.I.No.540of2007)

PA1330/002/001

CaseNo:2040878

TheIrishMedicinesBoardinexerciseofthepowersconferredonitbytheabovementionedRegulationsherebygrantsto

GedeonRichterLtd

H-1103Budapest,Gyomroiut19-21,Hungary

anauthorisation,subjecttotheprovisionsofthesaidRegulations,inrespectoftheproduct

AlendronicAcid70mg"onceweekly"film-coatedtablets

TheparticularsofwhicharesetoutinPartIandPartIIoftheattachedSchedule.Theauthorisationisalsosubjecttothegeneralconditionsas

maybespecifiedinthesaidRegulationsaslistedonthereverseofthisdocument.

Thisauthorisation,unlesspreviouslyrevoked,shallcontinueinforcefrom22/01/2008until18/12/2012.

SignedonbehalfoftheIrishMedicinesBoardthis

________________

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Date Printed 23/01/2008 CRN 2040878 page number: 1

PartII

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

AlendronicAcid70mg"onceweekly"film-coatedtablets

2QUALITATIVEANDQUANTITATIVECOMPOSITION

Eachfilm-coatedtabletcontains70mgalendronicacid(equivalentto91.35mgsodiumalendronatetrihydrate).

Forafulllistofexcipients,seesection6.1.

3PHARMACEUTICALFORM

Filmcoatedtablet.

White,round,biconvexfilm-coatedtabletwithengraving“M14”.

4CLINICALPARTICULARS

4.1TherapeuticIndications

Treatmentofpostmenopausalosteoporosis.Alendronatereducestheriskofvertebralandhipfractures.

4.2Posologyandmethodofadministration

Therecommendeddosageisone70mgfilm-coatedtabletonceweeklyfororaluse.

Topermitadequateabsorptionofalendronate:

AlendronicAcid70mg„onceweekly”mustbetakenonanemptystomachatleast30minutesbeforethefirstfood,

drinkormedicinalproductofthedaywithplainwateronly.Otherbeverages(includingmineralwatereitherstillor

sparkling),foodandsomemedicinalproductsarelikelytoreducetheabsorptionofalendronate(seesection4.5).

Inordertoreducethepotentialforlocalandoesophagealirritation/adverseexperiencesthefollowingshouldbedone:

AlendronicAcid70mg„onceweekly”shouldbeswalloweduponarisingforthedaywithafullglassofwater

(notlessthan200ml).

Patientsshouldnotchewthetabletorallowthetabletodissolveintheirmouths.

Patientsshouldnotliedownuntilaftertheirfirstfoodofthedaywhichshouldbeatleast30minutesaftertaking

thetablet.

Patientsshouldnotliedownforatleast30minutesaftertakingAlendronicAcid70mg„onceweekly”.

AlendronicAcid70mg„onceweekly”shouldnotbetakenatbedtimeorbeforearisingfortheday.

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Useintheelderly:Nodosageadjustmentisnecessaryfortheelderly.

Useinrenalimpairment:Nodosageadjustmentisnecessaryforpatientswithglomerularfiltrationrate(GFR)greater

than35ml/min.Duetolackofexperiencealendronateisnotrecommendedforpatientswithrenalimpairmentwhere

GFRislessthan35ml/min.

Useinchildren:ThereisnorelevantindicationforuseofAlendronicAcid70mg„onceweekly”inchildren.

4.3Contraindications

Abnormalitiesoftheoesophagusandotherfactorswhichdelayoesophagealemptyingsuchasstrictureor

achalasia.

Inabilitytostandorsituprightforatleast30minutes.

Hypersensitivitytotheactivesubstanceortoanyoftheexcipients.

Hypocalcaemia

Seealsosection4.4.

4.4Specialwarningsandprecautionsforuse

Alendronatecancauselocalirritationoftheuppergastrointestinalmucosa.Becausethereisapotentialforworsening

oftheunderlyingdisease,cautionshouldbeusedwhenalendronateisgiventopatientswithactiveuppergastro-

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

(withinthepreviousyear)ofmajorgastrointestinaldiseasesuchaspepticulcer,oractivegastro-intestinalbleeding,or

surgeryoftheuppergastrointestinaltractotherthanpyloroplasty(see4.3‘Contraindications’).

Oesophagealreactions(sometimessevereandrequiringhospitalisation),suchasoesophagitis,oesophagealulcersand

oesophagealerosions,rarelyfollowedbyoesophagealstricture,havebeenreportedinpatientsreceivingalendronate.

Physiciansshouldthereforebealerttoanysignsorsymptomssignalingapossibleoesophagealreactionandpatients

shouldbeinstructedtodiscontinuealendronateandseekmedicalattentioniftheydevelopsymptomsofoesophageal

irritationsuchasdysphagia,painonswallowingorretrosternalpain,neworworseningheartburn.

Theriskofsevereoesophagealadverseexperiencesappearstobegreaterinpatientswhofailtotakealendronate

properlyand/orwhocontinuetotakealendronateafterdevelopingsymptomssuggestiveofoesophagealirritation.Itis

veryimportantthatthefulldosinginstructionsareprovidedto,andunderstoodbythepatient(see4.2‘Posologyand

methodofadministration’).Patientsshouldbeinformedthatfailuretofollowtheseinstructionsmayincreasetheirrisk

ofoesophagealproblems.

Whilenoincreasedriskwasobservedinextensiveclinicaltrials,therehavebeenrare(postmarketing)reportsofgastric

andduodenalulcers,somesevereandwithcomplications.Acausalrelationshipcannotberuledout.

Osteonecrosisofthejaw,generallyassociatedwithtoothextractionand/orlocalinfection(includingosteomyelitis)has

beenreportedinpatientswithcancerreceivingtreatmentregimensincludingprimarilyintravenouslyadministered

bisphosphonates.Manyofthesepatientswerealsoreceivingchemotherapyandcorticosteroids.Osteonecrosisofthe

jawhasalsobeenreportedinpatientswithosteoporosisreceivingoralbisphosphonates.

Adentalexaminationwithappropriatepreventivedentistryshouldbeconsideredpriortotreatmentwith

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

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Whileontreatment,thesepatientsshouldavoidinvasivedentalproceduresifpossible.Forpatientswhodevelop

osteonecrosisofthejawwhileonbisphosphonatetherapy,dentalsurgerymayexacerbatethecondition.Forpatients

requiringdentalprocedures,therearenodataavailabletosuggestwhetherdiscontinuationofbisphosphonatetreatment

reducestheriskofosteonecrosisofthejaw.Clinicaljudgementofthetreatingphysicianshouldguidethemanagement

planofeachpatientbasedonindividualbenefit/riskassessment.

Bone,joint,and/ormusclepainhasbeenreportedinpatientstakingbisphosphonates.Inpostmarketingexperience,

thesesymptomshaverarelybeensevereand/orincapacitating(see‘4.8Undesirableeffects’).Thetimetoonsetof

symptomsvariedfromonedaytoseveralmonthsafterstartingtreatment.Mostpatientshadreliefofsymptomsafter

stopping.Asubsethadrecurrenceofsymptomswhenrechallengedwiththesamedrugoranotherbisphosphonate.

PatientsshouldbeinstructedthatiftheymissadoseofAlendronicAcid70mg„onceweekly”theyshouldtakeone

tabletonthemorningaftertheyremember.Theyshouldnottaketwotabletsonthesamedaybutshouldreturnto

takingonetabletonceaweek,asoriginallyscheduledontheirchosenday.

AlendronateisnotrecommendedforpatientswithrenalimpairmentwhereGFRislessthan35ml/min,(see4.2

‘Posologyandmethodofadministration’).

Causesofosteoporosisotherthanoestrogendeficiencyandageingshouldbeconsidered.

Hypocalcaemiamustbecorrectedbeforeinitiatingtherapywithalendronate(see4.3‘Contraindications’).Other

disordersaffectingmineralmetabolism(suchasvitaminDdeficiencyandhypoparathyroidism)shouldalsobe

effectivelytreated.Inpatientswiththeseconditions,serumcalciumandsymptomsofhypocalcemiashouldbe

monitoredduringtherapywithAlendronicAcid70mg„onceweekly”.

Duetothepositiveeffectsofalendronateinincreasingbonemineral,decreasesinserumcalciumandphosphatemay

occur.Theseareusuallysmallandasymptomatic.However,therehavebeenrarereportsofsymptomatic

hypocalcemia,whichhaveoccasionallybeensevereandoftenoccurredinpatientswithpredisposingconditions

(e.g.hypoparathyroidism,vitaminDdeficiencyandcalciummalabsorption).

EnsuringadequatecalciumandvitaminDintakeisparticularlyimportantinpatientsreceivingglucocorticoids.

4.5Interactionwithothermedicinalproductsandotherformsofinteraction

Iftakenatthesametime,itislikelythatfoodandbeverages(includingmineralwater),calciumsupplements,antacids,

andsomeoralmedicinalproductswillinterferewithabsorptionofalendronate.Therefore,patientsmustwaitatleast

30minutesaftertakingalendronatebeforetakinganyotheroralmedicinalproduct.

Nointeractionstudieshavebeenperformed.However,inclinicalstudiesalendronatewasusedconcomitantlywitha

widerangeofcommonlyprescribedmedicinalproductswithoutevidenceofclinicaladverseinteractions.

4.6Pregnancyandlactation

Useduringpregnancy

Therearenoadequatedatafromtheuseofalendronicacidinpregnantwomen.Animalstudiesdonotindicatedirect

harmfuleffectswithrespecttopregnancy,embryonal/fetaldevelopment,orpostnataldevelopment.Alendronicacid

givenduringpregnancyinratscauseddystociarelatedtohypocalcaemia(seesection5.3).Giventheindication,

alendronicacidshouldnotbeusedduringpregnancy.

Useduringlactation

Itisnotknownwhetheralendronicacidisexcretedintohumanbreastmilk.Giventheindication,alendronicacid

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4.7Effectsonabilitytodriveandusemachines

Noeffectsonabilitytodriveandusemachineshavebeenobserved.

4.8Undesirableeffects

InaoneyearstudyinpostmenopausalwomenwithosteoporosistheoverallsafetyprofilesofAlendronicacid

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

design,inpostmenopausalwomen(alendronate10mg:n=196,placebo:n=397)theoverallsafetyprofilesof

alendronate10mg/dayandplaceboweresimilar.

Adverseexperiencesreportedbytheinvestigatorsaspossibly,probablyordefinitelydrugrelatedarepresentedbelowif

theyoccurredin ≥1%ineithertreatmentgroupintheoneyearstudy,orin≥1%ofpatientstreatedwithalendronate

10mg/dayandatagreaterincidencethaninpatientsgivenplacebointhethreeyearstudies:

Thefollowingadverseexperienceshavealsobeenreportedduringclinicalstudiesand/orpostmarketinguse:

[Common( ≥1/100,<1/10),Uncommon(≥1/1000,<1/100),Rare(≥1/10,000,<1/1000),Veryrare(<1/10,000including

isolatedcases)]

Immunesystemdisorders:

Rare:hypersensitivityreactionsincludingurticariaandangioedema

Metabolismandnutritiondisorders:

Rare:symptomatichypocalcaemia,ofteninassociationwithpredisposingconditions.(seesection4.4)

Nervoussystemdisorders:

One-YearStudy Three-YearStudy

Alendronicacid

70mg(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

diarrheoa 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,muscleor

joint)pain 2.9 3.2 4.1 2.5

musclecramp 0.2 1.1 0.0 1.0

Neurological

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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:rashwithphotosensitivityVeryrareandisolatedcases:isolatedcasesofsevereskinreactionsincludingStevens

Johnsonsyndromeandtoxicepidermalnecrolysis

Musculoskeletal,connectivetissueandbonedisorders:

Common:musculoskeletal(bone,muscleorjoint)pain

Rare:Osteonecrosisofthejawhasbeenreportedinpatientstreatedbybisphosphonates.Themajorityofthereports

refertocancerpatients,butsuchcaseshavealsobeenreportedinpatientstreatedforosteoporosis.Osteonecrosisofthe

jawisgenerallyassociatedwithtoothextractionand/orlocalinfection(includingosteomyelitis).Diagnosisofcancer,

chemotherapy,radiotherapy,corticosteroidsandpoororalhygienearealsodeemedasriskfactors;severe

musculoskeletal(bone,muscleorjoint)pain(see4.4‘Specialwarningsandprecautionsforuse’).

Generaldisordersandadministrationsiteconditions:

Rare:transientsymptomsasinanacutephaseresponse(myalgia,malaiseandrarely,fever),typicallyinassociation

withinitiationoftreatment.

Laboratorytestfindings

Inclinicalstudies,asymptomatic,mildandtransientdecreasesinserumcalciumandphosphatewereobservedin

approximately18and10%,respectively,ofpatientstakingalendronate10mg/dayversusapproximately12and3%of

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

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

4.9Overdose

Hypocalcaemia,hypophosphataemiaanduppergastrointestinaladverseevents,suchasupsetstomach,heartburn,

oesophagitis,gastritis,orulcer,mayresultfromoraloverdosage.

Nospecificinformationisavailableonthetreatmentofoverdosagewithalendronate.Milkorantacidsshouldbe

giventobindalendronate.Owingtotheriskofoesophagealirritation,vomitingshouldnotbeinducedandthepatient

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5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

Pharmacotherapeuticgroup:Drugsaffectingbonestructureandmineralization,bisphosphonateATCCode:

M05BA04

Theactivesubstancealendronicacid,isabisphosphonatethatinhibitsosteoclasticboneresorptionwithnodirect

effectonboneformation.Preclinicalstudieshavedemonstratedapreferenceforlocalizationofalendronatetosites

whereactiveresorptiontakesplace.Activityofosteoclastsisinhibited,butrecruitmentorattachmentofosteoclastsis

notaffected.Theboneformedduringtreatmentwithalendronateisofnormalquality.

5.2Pharmacokineticproperties

Absorption:

Theoralmeanbioavailabilityofalendronateinwomenwas0.64%fordosesrangingfrom5to70mgwhen

administeredafteranovernightfastandtwohoursbeforeastandardizedbreakfast.Bioavailabilitywasdecreased

similarlytoanestimated0.46%and0.39%whenalendronatewasadministeredonehourorhalfanhourbeforea

standardizedbreakfast.

Concomitantadministrationofalendronatewithcoffeeororangejuicereducedbioavailabilitybyapproximately60%.

Inhealthysubjects,oralprednisone(20mgthreetimesdailyforfivedays)didnotproduceaclinicallysignificant

changeinoralbioavailabilityofalendronate(ameanincreaserangingfrom20%to44%).

Distribution:

Alendronatetransientlydistributestosofttissuesfollowingadministrationbutisthenrapidlyredistributedtoboneor

excretedintheurine.Proteinbindinginhumanplasmaisapproximately78%.

Metabolism:

Thereisnoevidencethatalendronateismetabolizedinanimalsorhumans.

Elimination:

Followingasingleintravenousdoseof[ 14

C]alendronateintravenousadministration,approximately50%ofthedose

wasexcretedintheurinewithin72hours.Noactivesubstancewasrecoveredinthefaeces.Followingasingle10mg

intravenousdose,therenalclearanceofalendronatewas71ml/min,andsystemicclearancedidnotexceed200ml/min.

Plasmaconcentrationsfellbymorethan95%withinsixhoursfollowingintravenousadministration.Theterminalhalf-

lifeinhumansisestimatedtoexceedtenyears,reflectingreleaseofalendronatefromtheskeleton.Alendronateisnot

excretedthroughtheacidicorbasictransportsystemsofthekidney,andthusitisnotanticipatedtointerferewiththe

excretionofothermedicinalproductsbythosesystemsinhumans.

Characteristicsinpatients:

Thedrugthatisabsorbedbutnotdepositedinboneisrapidlyexcretedintheurine.Noevidenceofsaturationofbone

uptakewasfoundafterchronicdosingwithcumulativeintravenousdosesupto35mg/kginanimals.Althoughno

clinicalinformationisavailable,itislikelythat,asinanimals,eliminationofalendronateviathekidneywillbe

reducedinpatientswithimpairedrenalfunction.Therefore,somewhatgreateraccumulationofalendronateinbone

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5.3Preclinicalsafetydata

Nonclinicaldatarevealnospecialhazardforhumansbasedonconventionalstudiesofsafetypharmacology,repeated

dosetoxicity,genotoxicity,carcinogenicpotential,toxicitytoreproduction.

Studiesinratshaveshownthattreatmentwithalendronateduringpregnancywasassociatedwithdystociaindams

duringparturitionwhichwasrelatedtohypocalcaemia.Instudies,ratsgivenhighdosesshowedanincreasedincidence

ofincompletefetalossification.Therelevancetohumansisunknown.

6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

Tabletcore:

Cellulosemicrocrystalline(E460)

Colloidalanhydroussilica

Croascarmellosesodium(E468)

Magnesiumstearate(E572)

Film-coating:

LustreClearLC103:

Cellulosemicrocrystalline(E460)

Carrageenan(E407)

Macrogol8000

6.2Incompatibilities

Notapplicable.

6.3ShelfLife

2years.

6.4Specialprecautionsforstorage

Storebelow25ºC.

6.5Natureandcontentsofcontainer

2film-coatedtabletsarepackedintoOPA/Al/PVC/Alblisterandfoldedcarton.

4filmcoatedtabletsarepackedintoOPA/Al/PVC/Alblisterandfoldedcarton.

12(3x4)filmcoatedtabletsarepackedintoOPA/Al/PVC/Alblistersandfoldedcarton.

Notallpacksizesmaybemarketed.

6.6Specialprecautionsfordisposalofausedmedicinalproductorwastematerialsderivedfrom

suchmedicinalproductandotherhandlingoftheproduct

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7MARKETINGAUTHORISATIONHOLDER

GedeonRichterLtd.

H-1103Budapest

Gyömriút1921

Hungary

8MARKETINGAUTHORISATIONNUMBER

PA1330/2/1

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

19thDecember2007

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