EVEROSE

Main information

  • Trade name:
  • EVEROSE Film Coated Tablet 660 Milligram
  • Dosage:
  • 660 Milligram
  • Pharmaceutical form:
  • Film Coated Tablet
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug

Documents

Localization

  • Available in:
  • EVEROSE Film Coated Tablet 660 Milligram
    Ireland
  • Language:
  • English

Status

  • Source:
  • HPRA - Health Products Regulatory Authority - Ireland
  • Authorization number:
  • PA1350/003/001
  • Authorization date:
  • 29-02-2008
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

IRISHMEDICINESBOARDACTS1995AND2006

MEDICINALPRODUCTS(CONTROLOFPLACINGONTHEMARKET)REGULATIONS,2007

(S.I.No.540of2007)

PA1350/003/001

CaseNo:2032366

TheIrishMedicinesBoardinexerciseofthepowersconferredonitbytheabovementionedRegulationsherebygrantsto

FreseniusMedicalCareNephrologicaDeutschlandGmbH

61346BadHomburgv.d.H.,Germany

anauthorisation,subjecttotheprovisionsofthesaidRegulations,inrespectoftheproduct

Everose660mgfilm-coatedtablets

TheparticularsofwhicharesetoutinPartIandPartIIoftheattachedSchedule.Theauthorisationisalsosubjecttothegeneralconditionsas

maybespecifiedinthesaidRegulationsaslistedonthereverseofthisdocument.

Thisauthorisation,unlesspreviouslyrevoked,shallcontinueinforcefrom29/02/2008until28/02/2013.

SignedonbehalfoftheIrishMedicinesBoardthis

________________

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PartII

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

Everose660mgfilm-coatedtablets

2QUALITATIVEANDQUANTITATIVECOMPOSITION

Onefilm-coatedtabletcontains660mgcalciumacetate,equivalentto167mgcalcium.

Excipients:

Eachfilm-coatedtabletcontains68.3mgsucrose.

Forafulllistofexcipients,seesection6.1.

3PHARMACEUTICALFORM

Film-coatedtablet.

Whitetoyellowish,oblong-shapedtabletwithascore-line.

Thescorelineisonlytofacilitatebreakingforeaseofswallowingandnottodivideintoequaldoses.

4CLINICALPARTICULARS

4.1TherapeuticIndications

Hyperphosphataemiainpatientswithchronicrenalinsufficiencyundergoingdialysis.

4.2Posologyandmethodofadministration

Everoseshouldalwaysbeusedwithclosemonitoring(seesection4.4).

Inadults

Therecommendedstartingdoseistwotablets(334mgcalcium)threetimesdaily.Thedoseisgraduallyincreaseduntil

thedesiredserumphosphoruslevelisreached,providedthathypercalcaemiadoesnotoccur.Mostpatientsrequire3to

4tabletswitheachmeal.

Thedosemayneedtobeadjustedeitherupwardsordownwards,dependingonphosphateintakeandeliminationof

phosphatebydialysis.

Inchildrenandadolescent(lessthan18yearsofage)

Nosufficientinformationisavailableontherelationshipofagetotheeffectsofcalciumacetateinpaediatricpatients.

Therefore,Everosecannotberecommendedinthesepatients.

Intheelderly

Normaldosageregimenisrecommendedintheelderly.

Thetabletsshouldonlybetakentogetherwithmealstoachievethemaximum-phosphatebindingeffect.Preferablythe

tabletsshouldbeswallowedwhole.Whenapatienthasdifficultyswallowingthetabletduetoitssize,thetabletcanbe

brokeninhalfonthescorelineifnecessary,sohalfatabletcanbetakentwicedirectlyaftereachother.

Inthatcasethetabletsneedtobedividedintohalvesjustbeforeingestiontoavoidthedevelopmentoftasteofacetic

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Incaseofamisseddose,thenextdoseshouldbetakenatthenormaltime(noattemptshouldbemadetomakeupfor

themisseddose).

4.3Contraindications

Hypophosphataemia

Hypercalcaemia

Hypersensitivitytocalciumacetateortoanyoftheexcipients

4.4Specialwarningsandprecautionsforuse

Patientsshouldbeadvisednottotakeanyotheroralmedicationwithin1-2hbeforeandafterEverose(seesection4.5).

Chronicoverdoseofcalciumpreparationsinuraemicpatientscancausesofttissuecalcifications.Theriskof

hypercalcaemiaisincreasedincasesofconcomitanttreatmentwithvitaminD-preparations.

Increasedamountsofcalciumsaltsinthegastrointestinaltractmayresultintheprecipitationoffattyacidsandbile

acidsascalciumsalt.Thismayleadtoconstipation.

Theapplicationofadrenaline(epinephrine)inpatientswithincreasedserumcalciumlevelmayleadtoseverecardiac

arrhythmias.

Serumphosphorusandcalciumlevelsshouldbecloselymonitoredatregularintervals.Thecalciumphosphateproduct

shouldnotexceed5.25mmol 2

,sincetheincidenceofsofttissuecalcificationsincreasesbyexceedingthisvalue.

Monitoringshouldbemorefrequentafterinitiationofthetherapye.g.inweeklyintervalsorevery2weeksfor3

months.Afterthismonthlyintervalsaresufficient,dependentonthemedicalconditionofthepatient.Ingeneralthe

monitoringfrequencyisuptothedecisionofthedoctoranddependsonthemedicalprofileofthepatient.The

prolongedexceedingofacalciumphosphateproductof5.25mmol 2

shouldpromptatherapychange.

Toavoidanincreaseofserumcalciumabovenormallevels,incaseofaprevioustherapywithcalciumsupplementsthe

amountofcalciumthatisadministeredwithEveroseshouldbeconsidered.

Incaseofhypercalcaemiathedoseshouldbereducedorthetreatmentdiscontinued,dependingonthedegreeof

hypercalcaemia.Forthesymptomsofhypercalcaemiaseesection4.8.

Calciumsaltsshouldgenerallybeavoidedinpatientswithcalciumrenalcalculi,orahistoryofrenalcalculi.Calcium

saltsshouldbegivencautiouslytopatientswithdiseasesassociatedwithhypercalcaemiasuchassarcoidosisandsome

malignancies.

Patientsshouldbewarnedforthepossiblesymptomsofhypercalcaemia.

Inpatientswherethereisdifficultycontrollingserumphosphorousconcentrationse.g.withseverehyperphosphataemia

(serumlevels>2.26mmol/L),aluminiumbasedphosphatebindersmaybeusedasashorttermtherapy(4weeks).

Theuseofphosphatebindersshouldbeprecededbyadietaryconsultationwiththepatientconcerningphosphate

uptake,andmaydependonthekindofdialysistreatmentthepatientisreceiving.

Thisproductcontainssucrose.Duetothecontentofsucrosepatientswithrarehereditaryproblemsoffructose

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4.5Interactionwithothermedicinalproductsandotherformsofinteraction

EffectsofothermedicinalproductsonEverose

Onconcomitantadministrationofthiazidediuretics(bendroflumethiazide)orvitaminD-preparationsthereisan

increasedriskofhypercalcaemia.Ifthesedrugsareprescribedsimultaneously,additionalserumcalciummonitoring,

eg,weeklymaybenecessary,abovetheregularmonitoringintervalsasgiveninsection4.4.

Concurrentuseofoestrogens(estradiol)orvitaminApreparationswithcalciumsaltsmayincreasecalciumabsorption.

EffectsofEveroseonothermedicinalproducts

Becausetherateand/orextentofabsorptionofotheroralmedicationsmayvarywhenusedconcurrentlywithEverose,

patientsshouldbeadvisednottotakeanyotheroralmedicationwithin1-2hbeforeandafterEverose.

Calciumsaltscanformcomplexeswithcitrates,phosphates,carbonates/bicarbonates,oxalates,tartrates,phytatesor

sulphates.Calciumsaltsaffect,likeothermultivalentcations,theabsorptionofnumerousanionicactivesubstancesby

formingpoorlysolublesalts.Thus,theconcurrentuseofcalciumcontainingdrugswithtetracyclines,bisphosphonates,

fluorides,somefluoroquinolones(ciprofloxacin,ofloxacin),somecephalosporins(cefpodoxime,cefuroxime),

ketoconazole,estramustin-preparationsandanticholinergicsmayreducetheintestinalabsorptionofthesesubstances.

Alsotheintestinalabsorptionofzincandironmaybereduced.

Increasedamountsofcalciumsaltsinthegastrointestinaltractmayreducetheabsorptionoftherapeutically

administeredurso-andchenodesoxycholicacidduetoprecipitationascalciumsoap.

Calciumincreasestheeffectofdigitalisglycosides(digoxin),whichmayresultindigitalisintoxicationincludingthe

riskofarrhythmia.IndigitalisedpatientscareshouldbetakenwhenadministeringEverose,e.g.ECGmonitoringis

warranted.

Calciumcanreducethepharmacologicaleffectsofverapamilandprobablyofothercalciumchannelblockers.

4.6Pregnancyandlactation

Forcalciumacetatenoclinicaldataonexposedpregnanciesareavailable.Preclinicalstudieswithrespecttoaffect

pregnancy,embryonal/foetaldevelopment,parturitionand/orpostnataldevelopmenthavenotbeenperformedwith

Everose.Cautionshouldbeexercisedwhenprescribingtopregnantwomen.Duringpregnancy,serumcalciumlevels

shouldbecloselymonitoredatregularintervals.

Itisnotknownwhethercalciumacetateisdistributedinbreastmilk.Breast-feedingisnotrecommendedwhenwomen

needEveroseinthattime.

4.7Effectsonabilitytodriveandusemachines

Everosehasnoinfluenceontheabilitytodriveandusemachines.

4.8Undesirableeffects

Verycommon ( ≥1/10)

Common ( ≥1/100to<1/10)

Uncommon ( ≥1/1000to<1/100)

Rare ( ≥1/10000to<1/1000)

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Metabolismandnutritiondisorders:

Common:

MildHypercalcaemia

Mildhypercalcaemia(Ca>2.6mmol/l)mayoccurinabout1%ofpatientsandmaybeasymptomaticormanifest

itselfasconstipation,anorexia,nauseaandvomiting.

Uncommon:

MoreSevereHypercalcaemia

Moreseverehypercalcaemia(Ca>3.0mmol/l)mayoccurinabout0.1%ofpatientsandcanbeassociatedwith

cardiacrhythmdisorders,confusion,lethargy,delirium,stuporandinveryseverecasescoma.Patientsshould

beadvisedtoconsulttheirdoctorifanyofthesesymptomsoccur.

Gastrointestinaldisorders:

Common:

nausea

vomiting

bloatedfeeling

belching

constipation

diarrhoea

4.9Overdose

Overdosemayresultinhypercalcaemia.Chronicoverdoseinuraemicpatientsmayresultinsofttissuecalcification.

Emergencytreatment,antidotes

Incaseofhypercalcaemia(serumcalciumlevel>2.5mmol/l)boththedialysatecalcium(to1.25mmol/l)and/orthe

dosageofEverosehastobereduced.Ifaserumcalciumlevelof2.75mmol/lisexceeded,theadministration

ofEverosemustbetemporarilyinterruptedandifnecessarycalcium-freephosphatebinderhastobeapplied.A

hypercalcaemiccrisis(serumcalciumlevel>3.5mmol/l)requiresatherapywithacalciumfreedialysate.

5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

Pharmacotherapeuticgroup:Mineralsupplements,Calcium

ATCcode:A12AA12

Everosecontainscalciumacetate,andisprimarilyintendedinpatientswithchronicrenalfailure.Theycannotexcrete

phosphateviathekidneystothenormaldegree,andthisleadstohyperphosphataemia.Dietoreliminationofphosphate

isinsufficient,andphosphate-bindingsubstancesmustbeusedtoreducephosphateabsorptioninthegastrointestinal

tract.Calciumacetatetakenwithmeals,togetherwithphosphateinthefoodformspoorlysolublecalciumphosphate,

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5.2Pharmacokineticproperties

Absorption

Althoughthisproductisintendedtoactlocallytobindphosphateinthegut,theamountofcalciuminvolvedinthe

bindingofphosphateisvariableandanyunboundcalciummaybeabsorbedinthegastrointestinaltractbyactive

transportandpassivediffusion.Calciumisactivelyabsorbedintheduodenumandproximaljejunum,andtoalesser

extent,inthemoredistalsegmentofthesmallintestine.Afteroraladministrationofcalciumacetate,approximately

40%isabsorbedinthefastingstateandapproximately30%isabsorbedinthenon-fastingstate.Calciumabsorptionis

decreasedinpatientswithchronicrenalinsufficiency,inotherdiseasestatesandifcalciumbindstophosphate.Any

boundcalciumcannotbeabsorbed.

Distribution

Bonecontains99%ofthebodycalcium,theremaining1%isdistributedequallybetweentheintra-andextracellular

fluids.Ofthetotalserumcalciumconcentration,50%isintheionicformand5%iscomplexedbyphosphates,citrates

andotheranions.Approximately45%oftheserumcalciumisboundtoplasmaproteins.

Metabolism

Theanionofcalciumacetate(acetateion)isametaboliteofglucosemetabolism.Boundtothesulfydrylgroupof

coenzymeAitcanbecatabolisedinthecitratecycleandaswellinmanyothermetabolicpathways.Absorbedacetate

israpidlymetabolisedtobicarbonate.

Excretion

Underphysiologicconditionsabout90%ofthedailyintakeofcalciumisexcretedinthefaeces,approximately10%of

theingestedcalciumisexcretedintheurine.Urinarycalciumexcretiondecreasesduringdevelopmentofrenalfailure.

5.3Preclinicalsafetydata

Preclinicalstudieswithcalciumacetateareverylimitedandrevealnospecialadditionalriskstothosealready

mentionedinothersectionsoftheSPC.Preclinicaleffectswereobservedonlyatdosesconsideredsufficientlyin

excessofthemaximumhumandose,thusbeingnotrelevanttoclinicaluse.

6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

Inthetabletcore:

Sucrose

Gelatin(E441)

Croscarmellosesodium(E468)

Magnesiumstearate(E470b)

Inthefilmcoating:

Refinedcastoroil

Saccharinsodium(E954)

Hypromellose(E464)

6.2Incompatibilities

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6.3ShelfLife

2years.

5weeksafterfirstopening.

6.4Specialprecautionsforstorage

Storebelow30°C.

6.5Natureandcontentsofcontainer

HDPEcontainerwithLDPEcap.

Packsizes:

100,200film-coatedtablets.

Notallpacksizesmaybemarketed.

6.6Specialprecautionsfordisposal

Nospecialrequirements.

7MARKETINGAUTHORISATIONHOLDER

FreseniusMedicalCareNephrologicaDeutschlandGmbH

61346BadHomburgv.d.H.

Germany

8MARKETINGAUTHORISATIONNUMBER

PA1350/3/1

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

Dateoffirstauthorisation:29thFebruary2008.

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