DIDRONEL PMO

Main information

  • Trade name:
  • DIDRONEL PMO
  • Dosage:
  • 400 Milligram
  • Pharmaceutical form:
  • Tablets
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug

Documents

Localization

  • Available in:
  • DIDRONEL PMO
    Ireland
  • Language:
  • English

Status

  • Source:
  • HPRA - Health Products Regulatory Authority - Ireland
  • Authorization number:
  • PA0170/017/001
  • Authorization date:
  • 01-05-1996
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

PartII

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

DidronelPMO.

2QUALITATIVEANDQUANTITATIVECOMPOSITION

Atwocomponenttherapyconsistingof14Didronel400mgtabletsand76Cacit500mgeffervescenttablets

(equivalentto500mgelementalcalcium).EachDidroneltabletcontains400mgofEtidronateDisodium.EachCacit

500mgeffervescenttabletcontains1250mgofCalciumCarbonatewhichwhendispersedinwaterprovides500mgof

elementalcalciumascalciumcitrate.

Excipients:

EachCacittabletcontains2mgSunsetyellowFCF(E110)

Forfulllistofexcipients,seesection6.1.

3PHARMACEUTICALFORM

Didronel400mg:Tablet

Cacit:Effervescenttablet

EachDidronel400mgtabletiswhite,capsule-shapedandmarkedwith‘NE’ononefaceand‘406’ontheother.Each

Cacit500mgeffervescenttabletisround,flat,whitewithpinkspecklesandhasadistinctiveorangeflavour.

4CLINICALPARTICULARS

4.1TherapeuticIndications

Treatmentofosteoporosisandpreventionofbonelossinpostmenopausalwomenconsideredatriskofdeveloping

osteoporosis.DidronelPMOisparticularlyindicatedinpatientswhoareunableorunwillingtotakeoestrogen

replacementtherapy.DidronelPMOisalsoindicatedforthepreventionandtreatmentofcorticosteroid-induced

osteoporosis

4.2Posologyandmethodofadministration

DidronelPMOtherapyisalong-termcyclicalregimenadministeredin90-daycycles.EachcycleconsistsofDidronel

400mgtabletsforthefirst14days,followedbyCacit500mgtabletsfortheremaining76days.

*Didronel400mgcomponent:

Onetabletshouldbetakeneachdayfor14consecutivedaysonanemptystomach.Itisrecommendedthatpatients

takethetabletwithwateratthemidpointofafourhourfast(i.e.twohoursbeforeandtwohoursafterfood).

*Cacit500mgcomponent:

Following14daystreatmentwithDidronel400mgtablets,oneCacittabletshouldbedissolveddailyinwaterand

drunkimmediatelyaftercompletedissolution.

AdultsandElderly

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Children

Nodataexistsintheuseofthistherapyinjuvenileosteoporosis.

4.3Contraindications

Knownhypersensitivitytoanyoftheingredients.Treatmentofpatientswithsevererenalimpairment.Patientswith

hypercalcaemia(e.g.duetohyperparathyroidism,hypervitaminosisD,decalcifyingtumours,severerenalfailure,bone

metastases),hypercalciuriaorrenalcalculi.Clinicallyovertosteomalacia.Useinpregnancyandlactation.

4.4Specialwarningsandprecautionsforuse

Cliniciansshouldadvisepatientstoadheretotherecommendedtreatmentregimen,andcompliancepack.

Themajorityofpatientshavebeentreatedforthreeyears.Theoptimumdurationoftreatmentbeyondthishasnotbeen

established,althoughalimitednumberofpatientshavebeentreateduptosevenyears.

Inclinicaltrialsforosteoporosis,noclinicalosteomalaciawasobservedwithcyclicaletidronatetherapy.Insmall

groupsofpatientsthesetrialshavecontinuedoversevenyears.

Continuousadministrationofetidronateshouldbeavoided.

Patientswithsignificantchronicdiarrhoealdiseasemayexperienceincreasedfrequencyofbowelmovementsand

diarrhoea.

DidronelPMOtherapyshouldbewithheldfrompatientswithenterocolitisbecauseofincreasedfrequencyofbowel

movements.

Cautionshouldbetakeninpatientswithimpairedrenalfunction,orahistoryofrenalstoneformation.Inthesepatients

serumandurinarycalciumshouldbemonitoredregularly.

Etidronatedisodiumdoesnotadverselyaffectserumlevelsofparathyroidhormoneorcalcium.

Hyperphosphataemiahasbeenobservedinpatientsreceivingetidronatedisodium,usuallyinassociationwithdosesof

10-20mg/kg/day.Noadverseeffectshavebeentracedtothis,anditdoesnotconstitutegroundsfordiscontinuing

therapy.Itisapparentlyduetoadrug-relatedincreaseinrenaltubularreabsorptionofphosphate.Serumphosphate

levelsgenerallyreturntonormal2-4weeksposttherapy.

Osteonecrosisofthejaw,generallyassociatedwithtoothextractionand/orlocalinfection(includingosteomyelitis)has

beenreportedinpatientswithcancerreceivingtreatmentregimensincludingprimarilyintravenouslyadministered

bisphosphonates.Manyofthesepatientswerealsoreceivingchemotherapyandcorticosteroids.Osteonecrosisofthe

jawhasalsobeenreportedinpatientswithosteoporosisreceivingoralbisphosphonates.

Adentalexaminationwithappropriatepreventivedentistryshouldbeconsideredpriortotreatmentwith

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

poororalhygiene).

Whileontreatment,thesepatientsshouldavoidinvasivedentalproceduresifpossible.Forpatientswhodevelop

osteonecrosisofthejawwhileonbisphosphonatetherapy,dentalsurgerymayexacerbatethecondition.Forpatients

requiringdentalprocedures,therearenodataavailabletosuggestwhetherdiscontinuationofbisphosphonatetreament

reducesriskofosteonecrosisofthejaw.

Clinicaljudgementofthetreatingphysicianshouldguidethemanagementplanofeachpatientbasedonindividual

benefit/riskassessment.

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4.5Interactionwithothermedicinalproductsandotherformsofinteraction

Foodinthestomachoruppergastrointestinaltract,particularlymaterialswithahighcalciumcontentsuchasmilk,

mayreduceabsorptionofetidronatedisodium.Vitaminswithmineralsupplementssuchasiron,calciumsupplements,

laxativescontainingmagnesium,orantacidscontainingcalciumoraluminiumshouldnotbetakenwithintwohoursof

dosingetidronatedisodium.

Asmallnumberofpatientsinclinicaltrials(involvingmorethan600patients)receivedeitherthiazidediureticsor

intravaginaloestrogenwhileontheDidronelPMOregimen.Theconcomitantuseofeitheroftheseagentsdidnot

interferewiththepositiveeffectsoftheDidronelPMOtherapyonvertebralbonemassorfracturerates.

Calciumsaltsmayreducetheabsorptionofsomedrugs,e.g.tetracyclines.Itisthereforesuggestedthatadministration

ofCacittabletsbeseparatedfromtheseproductsbyatleastthreehours.

VitaminDcausesanincreaseincalciumabsorptionandplasmacalciumlevelsmaycontinuetoriseafterstopping

vitaminDtherapy.ConcomitantadministrationofCacittabletsandvitaminDshouldthereforebecarriedoutwith

caution.

Theeffectsofdigoxinandothercardiacglycosidesmaybeaccentuatedbycalciumandtoxicitymaybeproduced,

especiallyincombinationwithvitaminDtherapy.

Therehavebeenisolatedreportsofpatientsexperiencingchangesintheirprothrombintimeswhenetidronatewas

addedtowarfarintherapy.Themajorityofthesereportsconcernedvariableelevationsinprothrombintimeswithout

clinicallysignificantsequelae.Althoughtherelevanceofthesereportsandanymechanismofcoagulationalterationsis

unclear,patientsonwarfarinshouldhavetheirprothrombintimemonitored.

4.6Pregnancyandlactation

Contra-indicated.

4.7Effectsonabilitytodriveandusemachines

Etidronatedisodiumdoesnotinterferewiththeabilitytodriveorusemachines.

4.8Undesirableeffects

Gastro-intestinal

Inclinicalstudiesof2-3yearsduration,theincidenceoftheseeventswerecomparabletoplacebo.Themostcommon

effectsreportedinorderofincidencewerediarrhoea,nausea,flatulence,dyspepsia,abdominalpain,gastritis,

constipationandvomiting.Reportsofexacerbationofpepticulcerwithcomplicationsinafewpatients.

Dermatological/hypersensitivity

Hypersensitivityreactionsincludingangio-oedema,urticaria,rashand/orpruritushavebeenreportedrarely.The

colouringagentE110cancauseallergic-typereactionsincludingasthma.Allergyismorecommoninthosepeoplewho

areallergictoaspirin.

NervousSystem

Headache,andrarelyparesthesia,peripheralneuropathyandconfusion.

Haematological

Therehavebeenrarereportsofleucopenia,agranulocytosisandpancytopenia.

Other

Lesscommoneffectsbelievedtoberelatedtotherapyincludearthopathies(arthralgiaandarthritis),andrarelyburning

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Occasionalmildlegcrampshavebeenreportedinlessthan5%ofpatientsontheDidronelPMOregimen.These

crampsweretransient,oftennocturnalandgenerallyassociatedwithotherunderlyingconditions

4.9Overdose

Clinicalexperienceofacuteoverdosagewithetidronateislimitedandunlikelywiththiscompliancekit.Theoretically

itwouldbemanifestedasthesignsandsymptomsofhypocalcaemiaandpossiblyparesthesiaofthefingers.Treatment

wouldconsistofgastriclavagetoremoveunabsorbeddrugalongwithcorrectionofhypocalcaemiawithadministration

ofCa intravenously.

Prolongedcontinuoustreatment(chronicoverdose)hasbeenreportedtocausenephroticsyndromeandfractures.

5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

Etidronateinanintermittentcyclicalregimen,worksindirectlytoincreasebonemass.Bytimingdeliveryand

withdrawal,theetidronatedisodiumcomponentactstomodulateosteoclastsandreducethemeanresorptiondepthof

theaffectedbasicmulticellularunits(BMU).Calciumisanessentialelement,whichhasbeenshowntohelpprevent

boneloss.

5.2Pharmacokineticproperties

Within24hours,aboutonehalfoftheabsorbeddoseofetidronateisexcretedintheurine.Theremainderis

chemicallyabsorbedonboneandisslowlyeliminated.Unabsorbeddrugisexcretedinthefaeces.Etidronate

disodiumisnotmetabolised.Afteroraldosesofupto1600mgofthedisodiumsalt,theamountofdrugabsorbedis

approximately3-4%.Innormalsubjects,plasmahalflife(t½)ofetidronate,basedonnon-compartmental

pharmacokineticsis1-6hours.

Calciumcarbonateisconvertedintosolublecalciumsaltsinthestomachundertheinfluenceofhydrochloricacid.30-

80%oforallyingestedcalciumisabsorbedbothbyactivetransport(primarilyintheuppersmallintestine)andby

passivediffusion.Thedistributionofcalciuminthebodyissubjecttothemechanismofphysiologicalregulation

controlledbyparathyroidhormone,calcitonin,calciferolandotherhormones.

5.3Preclinicalsafetydata

Inlong-termstudiesinmiceandrats,therewasnoevidenceofcarcinogenicitywithetidronatedisodium.Allinvitro

andinvivoassaysconductedtoassessthemutagenicpotentialofetidronatedisodiumhavebeennegative.

6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

Etidronatedisodiumtablets:

Microcrystallinecellulose

Pregelatinisedmaizestarch

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Cacittablets:

Anhydrouscitricacid

Saccharinsodium

Sodiumcyclamate

SunsetyellowFCF(E110)

Orangeflavouring.

6.2Incompatibilities

Notapplicable.

6.3ShelfLife

3years.

6.4Specialprecautionsforstorage

Donotstoreabove30 °

C.Keepthetubetightlyclosed.

6.5Natureandcontentsofcontainer

14Didronel400mgtabletsinanopaquePVdC/foilblisterplusfourpolypropylenetubes,eachcontaining19Cacit500

mgtablets,allpackagedinacompliancekit.

6.6Specialprecautionsfordisposalofausedmedicinalproductorwastematerialsderivedfrom

suchmedicinalproductandotherhandlingoftheproduct

Nospecialrequirements.

7MARKETINGAUTHORISATIONHOLDER

Procter&GamblePharmaceuticalsUKLtd

RushamPark

WhitehallLane

Egham

SurreyTW209NW

UnitedKingdom

8MARKETINGAUTHORISATIONNUMBER

PA0170/017/001

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

Dateoffirstauthorisation:01May1996

Dateoflastrenewal:01May2006

10DATEOFREVISIONOFTHETEXT

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Date Printed 15/08/2008 CRN 2054440 page number: 5