ALDACTIDE 25 FILM-COATED TABLETS

Main information

  • Trade name:
  • ALDACTIDE 25 FILM-COATED TABLETS
  • Dosage:
  • 25mg Milligram
  • Pharmaceutical form:
  • Tablets
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug

Documents

Localization

  • Available in:
  • ALDACTIDE 25 FILM-COATED TABLETS
    Ireland
  • Language:
  • English

Status

  • Source:
  • HPRA - Health Products Regulatory Authority - Ireland
  • Authorization number:
  • PA0936/015/001
  • Authorization date:
  • 30-05-1998
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

IRISHMEDICINESBOARDACTS1995AND2006

MEDICINALPRODUCTS(CONTROLOFPLACINGONTHEMARKET)REGULATIONS,2007

(S.I.No.540of2007)

PA0936/015/001

CaseNo:2043911

TheIrishMedicinesBoardinexerciseofthepowersconferredonitbytheabovementionedRegulationsherebygrantsto

PharmaciaIrelandLimited

9Riverwalk,NationalDigitalPark,CitywestBusinessCampus,Dublin24,Ireland

anauthorisation,subjecttotheprovisionsofthesaidRegulations,inrespectoftheproduct

Aldactide25mg/25mgFilm-coatedtablets.

TheparticularsofwhicharesetoutinPartIandPartIIoftheattachedSchedule.Theauthorisationisalsosubjecttothegeneralconditionsas

maybespecifiedinthesaidRegulationsaslistedonthereverseofthisdocument.

Thisauthorisation,unlesspreviouslyrevoked,shallcontinueinforcefrom30/05/2008.

SignedonbehalfoftheIrishMedicinesBoardthis

________________

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PartII

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

Aldactide25mg/25mgFilm-coatedtablets.

2QUALITATIVEANDQUANTITATIVECOMPOSITION

Eachtabletcontains25mgspironolactoneand25mghydroflumethiazide.

Forafulllistofexcipients,seesection6.1.

3PHARMACEUTICALFORM

Film-coatedtablet.

Circular,biconvex,buffcoloured,film-coatedtabletwithapeppermintodour,engraved‘SEARLE101’ononesurface.

4CLINICALPARTICULARS

4.1TherapeuticIndications

Managementofhypertensionandforthecontrolofoedemaincongestivecardiacfailure.

4.2Posologyandmethodofadministration

AdministrationofAldactideoncedailywithamealisrecommended.

Adults

Essentialhypertension:OnetofourAldactide25tabletswithbreakfastorthefirstmainmealoftheday.Treatment

shouldbecontinuedforatleasttwoweekstoensureanadequateresponsetotherapy.Doseshouldbeindividually

determined.

Congestivecardiacfailure:MostpatientswillrequireaninitialdosageoffourAldactide25tabletsdaily.Thedosage

shouldbeadjustedasnecessaryandmayrangefromoneAldactide25tablettofourAldactide25tablets

daily.Treatmentshouldbecontinuedforatleasttwoweekstoensureanadequateresponsetotherapy.Maintenance

dailydoseshouldbeindividuallydetermined.

Elderly

Itisrecommendedthattreatmentisstartedwiththelowestdoseandtitratedupwardsasrequiredtoachievemaximum

benefit.Careshouldbetakenwithseverehepaticandrenalimpairmentwhichmayalterdrugmetabolismand

excretion.

Children

AlthoughclinicaltrialsusingAldactidehavenotbeencarriedoutinchildren,asaguide,adailydosageproviding1.5

to3mgofspironolactoneperkilogrambodyweightgivenindivideddoses,maybeemployed.Dosageshouldbe

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4.3Contraindications

Aldactideiscontraindicatedinneonatesandyounginfants,inpatientswithanuria,acuterenalinsufficiency,rapidly

deterioratingorsevereimpairmentofrenalfunction,hyperkalaemia,precomaassociatedwithsevereliverdisease,

Addison’sdisease,significanthypercalcemia,andinpatientswhoarehypersensitivetospironolactone,thiazide

diureticsortoothersulphonamidederiveddrugs.

Aldactideshouldnotbeadministeredwithotherpotassiumconservingdiureticssuchastriametereneoramiloride,and

potassiumsupplementsshouldnotbegivenroutinelywithAldactideashyperkalaemiamaybeinduced.

4.4Specialwarningsandprecautionsforuse

Concomitantuseofspironolactonewithangiotensinconvertingenzyme(ACE)inhibitors,angiotensinIIantagonists,

aldosteroneblockers,adietrichinpotassium,orsaltsubstitutescontainingpotassium,mayleadtosevere

hyperkalaemia.

Hyperkalaemiamayalsooccurinpatientswithimpairedrenalfunctionandcancausecardiacirregularitieswhichmay

befatal.ShouldhyperkalaemiadevelopAldactideshouldbediscontinued,andifnecessary,activemeasurestakento

reducetheserumpotassiumtonormal.

Sulphonamidederivativesincludingthiazideshavebeenreportedtoexacerbateoractivatesystemiclupus

erythematosus.

Patientswhoarebeingtreatedwiththispreparationrequireregularsupervisionwithmonitoringoffluidandelectrolyte

state.Periodicestimationofserumelectrolytesisrecommendedduetothepossibilityofhypokalaemiaor

hyperkalaemia,hypochloremicalkalosis,orhyponatremiaandpossibletransientBUNelevation,especiallyinthe

elderlyand/orinpatientswithpre-existingimpairedrenalorhepaticfunction,inpatientsreceivingdigoxinanddrugs

withpro-arrhythmiceffects,andinthosewithpotentialobstructionoftheurinarytract,orwithdisordersrendering

theirelectrolytebalanceprecarious.

Hypokalaemiamaydevelopasaresultofprofounddiuresis,particularlywhenAldactideisusedconcomitantlywith

loopdiuretics,glucocorticoidsorACTH.

HyponatraemiamaybeinducedespeciallywhenAldactideisadministeredincombinationwithotherdiuretics.

Thepreparationmayinducehyperglycaemiaparticularlyinpatientswithdiabetes,andmaynecessitateadjustmentof

controlbyhypoglycaemicagentsincasesofdiabetesmellitus.

Hepaticimpairment:Cautionshouldbeobservedinpatientswithacuteorsevereliverimpairmentasvigorous

diuretictherapymayprecipitateencephalopathyinsusceptiblepatients.Regularestimationofserumelectrolytesis

essentialinsuchpatients.

Reversiblehyperchloraemicmetabolicacidosis,usuallyinassociationwithhyperkalaemiahasbeenreportedtooccur

insomepatientswithdecompensatedhepaticcirrhosis,eveninthepresenceofnormalrenalfunction.

Ureaanduricacid:Reversibleincreasesinbloodureahavebeenreported,particularlyaccompanyingvigorous

diuresisorinthepresenceofimpairedrenalfunction.

Thiazidesmaycausehyperuricaemiaandprecipitateattacksofgoutinsomepatients.Dosageadjustmentofanti-gout

medicationsmaybenecessary.

Hyperlipidaemia:Cautionshouldbeobservedasincreasesincholesterolandtriglyceridelevelsmaybeassociated

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4.5Interactionwithothermedicinalproductsandotherformsofinteraction

Aldactidemayhaveanadditiveeffectwhengivenconcomitantlywithotherdiureticsandantihypertensiveagents.The

doseofsuchdrugsmayneedtobereducedwhenAldactideisaddedtothetreatmentregimeandthenadjustedas

necessary.

Concomitantuseofspironolactonewithangiotensinconvertingenzyme(ACE)inhibitors,angiotensinIIantagonists,

aldosteroneblockers,adietrichinpotassium,orsaltsubstitutescontainingpotassium,mayleadtosevere

hyperkalaemia.

Spironolactonehasbeenreportedtoincreaseserumdigoxinconcentrationandtointerferewithcertainserumdigoxin

assays.Inpatientsreceivingdigoxinandspironolactonethedigoxinresponseshouldbemonitoredbymeansotherthan

serumdigoxinconcentrations,unlessthedigoxinassayusedhasbeenprovennottobeaffectedbyspironolactone

therapy.

Ifitprovesnecessarytoadjustthedoseofdigoxinpatientsshouldbecarefullymonitoredforevidenceofenhancedor

reduceddigoxineffect.

Coadministrationofspironolactonewithcarbenoxolonemayresultindecreasedefficacyofeitheragent.

AscarbenoxolonemaycausesodiumretentionandthusdecreasetheeffectivenessofAldactideconcurrentuseshould

beavoided.

Spironolactoneandthiazidesmayreducevascularresponsivenesstonoradrenaline.Cautionshouldbeexercisedinthe

managementofpatientssubjectedtoregionalorgeneralanaesthesiawhiletheyarebeingtreatedwithAldactide.

Colestyramineandcolestipolreducetheabsorptionofthiazidesandmayreducetheirdiureticeffects.

Thiazidediureticagentsreducelithiumrenalclearanceandincreasetheriskoftoxicity.

Lithiumdoseadjustmentmayberequired.

Thiazidesmayincreaseresponsivenesstoskeletalmusclerelaxants(e.g.tubocurarine).

Non-steroidalanti-inflammatorydrugsmayattenuatethenatriureticefficacyofdiureticsduetoinhibitionofintrarenal

synthesisofprostaglandins.

Aspirin,indometacinandmefenamicacidhavebeenshowntoattenuatethediureticeffectofspironolactone.

Spironolactoneenhancesthemetabolismofantipyrine.

Hyperkalaemicmetabolicacidosishasbeenreportedinpatientsgivenspironolactoneconcurrentlywithammonium

chlorideorcolestyramine.

4.6Pregnancyandlactation

Pregnancy

Spironolactoneoritsmetabolitesmaycrosstheplacentalbarrier.Spironolactonewasdevoidofteratogeniceffectsin

mice.Rabbitsreceivingspironolactoneshowedreducedconceptionrate,increasedresorptionrate,andlowernumberof

livebirths.Noembryotoxiceffectswereseeninratsadministeredhighdosages,butlimited,dosage-related

hypoprolactinemiaanddecreasedventralprostateandseminalvesicleweightsinmales,andincreasedluteinizing

hormonesecretionandovariananduterineweightsinfemaleswerereported.Feminizationoftheexternalgenitaliaof

malefetuseswasreportedinanotherstudyinrats.

Thiazidescrosstheplacentalbarrier.Thiazidesmaydecreaseplacentalperfusion,increaseuterineinertia,andinhibit

labour.

Therearenostudiesinpregnantwomen.TheuseofAldactideinpregnantwomenrequiresthattheanticipatedbenefit

beweighedagainstthepossiblehazardstothemotherandfoetus.Thesehazardsincludefoetalorneonataljaundice,

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Lactation

Metabolitesofspironolactoneandhydroflumethiazide,havebeendetectedinbreastmilk.IfuseofAldactideis

consideredessential,analternativemethodofinfantfeedingshouldbeinstituted.

4.7Effectsonabilitytodriveandusemachines

Somnolenceanddizzinesshavebeenreportedtooccurinsomepatients.Cautionisadvisedwhendrivingoroperating

machineryuntiltheresponsetoinitialtreatmenthasbeendetermined.

4.8Undesirableeffects

AdverseEvents

Thefollowingadverseeventshavebeenreportedinassociationwithspironolactoneandspironolactone/thiazide

therapy:

BodyasaWhole:anaphylactoidreaction,asthenia,fever,malaise,orthostatichypotension

EndocrineDisorders:benignbreastneoplasm,breastpain

GastrointestinalDisorders:abdominalpain,diarrhoea,gastrointestinaldisturbance,nausea,vomiting

HematologicDisorders:blooddyscrasias,leukopenia(includingagranulocytosis),thrombocytopenia,purpura,aplastic

anaemia

LiverDisorders:hepaticfunctionabnormal,pancreatitis,jaundice

MetabolicandNutritionalDisorders:electrolytedisturbances,hyperkalemia,raisedserumlipids

MusculoskeletalDisorders:legcramps,musclecramps,necrotizingvasculitis

NervousSystemDisorders:dizziness,headache,paresthesia,drowsiness,lethargy,restlessness,xanthopsia

PsychiatricDisorders:changesinlibido,confusion,ataxia,impotence

ReproductiveDisorders:menstrualdisorders,mildandrogeniceffects

SkinandAppendages:alopecia,dermatitis,hypertrichosis,photosensitivity,pruritus,rash,urticaria

UrinarySystemDisorders:acuterenalfailure

Gynecomastiamaydevelopinassociationwiththeuseofspironolactone.Developmentofgynecomastiaisrelatedto

bothdoseanddurationoftherapy.Gynecomastiaisusuallyreversiblewhenspironolactoneisdiscontinued,althoughin

rareinstancessomebreastenlargementmaypersist.

Sulfonamidederivatives,includingthiazides,havebeenreportedtoexacerbateoractivatesystemiclupus

erythematosus.

Rarelyhypercalcaemiahasbeenreportedinassociationwiththiazides,usuallyinpatientswithpre-existingmetabolic

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4.9Overdose

Acuteoverdosagemaybemanifestedbydrowsiness,mentalconfusion,maculopapularorerythematousrash,nausea,

vomiting,dizzinessordiarrhoea.Electrolyteimbalanceanddehydrationmayoccur.Ifdigitalishasbeen

administered,hypokalaemiamayaccentuatecardiacarrythmias.Hyponatraemia,hypokalaemiaorhyperkalaemiamay

beinducedbuttheseeffectsareunlikelytobeassociatedwithacuteoverdosage.Symptomsofhyperkalaemiamay

manifestasparaesthesia,weakness,flaccidparalysisormusclespasmandmaybedifficulttodistinguishclinically

fromhypokalaemia.

Electro-cardiographicchangesaretheearliestspecificsignsofpotassiumdisturbances.Nospecificantidotehasbeen

identified.Aldactideuseshouldbediscontinuedandpotassiumintake(includingdietarysources)restricted.

Improvementmaybeexpectedafterwithdrawalofthedrug.Generalsupportivemeasuresincludingreplacementof

fluidsandelectrolytesmaybeindicated.

5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

Pharmacotherapeuticcode:AldosteroneAntagonistandThiazideDiuretic

ATCCode:C03DA01+C03AA02

Spironolactone,asacompetitivealdosteroneantagonist,increasessodiumexcretionwhilstreducingpotassiumlossat

thedistalrenaltubule.Ithasagradualandprolongedaction.

Therenalactionofasingledoseofspironolactonereachesitspeakafter7hours,andactivitypersistsforatleast24

hours.

Hydroflumethiazideisathiazidediuretic.Diuresisisinitiatedusuallywithin2hoursandlastsforabout12-18hours.

5.2Pharmacokineticproperties

Spironolactoneiswellabsorbedorallyandisprincipallymetabolisedtoactivemetabolites:sulphurcontaining

metabolites(80%)andpartlycanrenone(20%).Althoughtheplasmahalflifeofspironolactoneitselfisshort(1.3

hours)thehalflivesoftheactivemetabolitesarelonger(rangingfrom2.8to11.2hours).

Hydroflumethiazideisincompletelybutfairlyrapidlyabsorbedfromthegastro-intestinaltract.Itappearstohavea

biphasicbiologicalhalf-lifewithanestimatedalpha-phaseofabout2hoursandanestimatedbeta-phaseofabout17

hours;ithasametabolitewithalongerhalf-life,whichisextensivelyboundtotheredbloodcells.Hydroflumethiazide

isexcretedintheurine;itsmetabolitehasalsobeendetectedintheurine.

5.3Preclinicalsafetydata

Carcinogenicity:spironolactonehasbeenshowntoproducetumoursinratswhenadministeredathighdosesovera

longperiodoftime.Inmanandtheratspirolactoneismetabolisedtoaminorextenttocanrenone.Incontrast

canrenoneandcanrenoicacidarethemajormetabolitesofpotassiumcanrenoate.

Adoserelatedincidenceofmyelocyticleukaemiahasbeenobservedinratsadministeredpotassiumcanrenoateat

dosesabove20mg/kg/dayforaperiodofoneyear.Inonelongterm(twoyear)oralcarcinogenicitystudyofpotassium

canrenoateintherat,myelocyticleukaemiaandhepatic,thyroid,testicularandmammarytumourswereobserved.

Potassiumcanrenoatewasnotmutagenicintestsusingbacteriaandyeast,orinaninvivomammaliansystem.Itwas

mutagenicininvitrotestsinmammaliancellsfollowingmetabolicactivation.Anincreasedincidenceofleukaemiahas

notbeenobservedinchronicrattoxicitystudieswithspironolactoneatdosesupto500mg/kg/day,whichmaybedueto

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Theusualtherapeuticdoseofspironolactonerangesbetween0.35to5.7mg/kg/day(25-400mg/day).Thesignificance

oftheseanimalfindingswithrespecttoclinicaluseisnotcertain.However,thelongtermuseofspironolactonein

youngpatientsrequirescarefulconsiderationofthebenefitsandthepotentialhazardinvolved.

6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

Calciumsulphatedihydrate

Maizestarch

Povidone

Magnesiumstearate

Peppermintflavour

Hypromellose

Macrogol400

Opasprayyellowcontains:

Titaniumdioxide(E171)

Ironoxideyellow(E172)

Ironoxidered(E172)

Hypromellose5cP(E464)

6.2Incompatibilities

Notapplicable

6.3ShelfLife

5years.

6.4Specialprecautionsforstorage

Donotstoreabove30 o

Keepcontainerintheoutercarton.

6.5Natureandcontentsofcontainer

HDPEcontainersorPVC/foilblisterpackscontaining100and500tablets.

Notallpacksizesaremarketed.

6.6Specialprecautionsfordisposalofausedmedicinalproductorwastematerialsderivedfrom

suchmedicinalproductandotherhandlingoftheproduct

Nospecialrequirements.

7MARKETINGAUTHORISATIONHOLDER

PharmaciaIrelandLimited

9Riverwalk

NationalDigitalPark

CitywestBusinessCampus

Dublin24

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8MARKETINGAUTHORISATIONNUMBER

PA0936/015/001

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

Dateoffirstauthorisation:30May1978

Dateoflastrenewal:30May2008

10DATEOFREVISIONOFTHETEXT

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