ALDACTONE

Main information

  • Trade name:
  • ALDACTONE Tablets 50 Milligram
  • Dosage:
  • 50 Milligram
  • Pharmaceutical form:
  • Tablets
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug

Documents

Localization

  • Available in:
  • ALDACTONE Tablets 50 Milligram
    Ireland
  • Language:
  • English

Status

  • Source:
  • HPRA - Health Products Regulatory Authority - Ireland
  • Authorization number:
  • PA0936/016/002
  • Authorization date:
  • 12-12-1999
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

Aldactone50mgFilm-coatedtablets

2QUALITATIVEANDQUANTITATIVECOMPOSITION

Eachtabletcontains50mgofSpironolactone.

Forafulllistofexcipients,seesection6.1.

3PHARMACEUTICALFORM

Film-coatedtablet(Tablets)

Round,whitecoloured,biconvextabletwithapeppermintodourembossed‘SEARLEover916’ononesideandthe

othersideplain.

4CLINICALPARTICULARS

4.1TherapeuticIndications

Inthemanagementofrefractoryoedemaassociatedwithcongestivecardiacfailure,hepaticcirrhosiswithascitesand

oedema,malignantascites,nephriticsyndrome,diagnosisandtreatmentofprimaryaldosteronism,essential

hypertension.

4.2Posologyandmethodofadministration

AdministrationofAldactoneoncedailywithamealisrecommended.

Adults

Congestiveheartfailure:Usualdose-100mg/day.Indifficultorseverecasesthedosagemaybegraduallyincreased

upto200mg/day.Whenoedemaiscontrolled,theusualmaintenancelevelis75-200mg/day.

Forsevereheartfailureinconjunctionwithstandardtherapy(NYHAClassIIIIV):

BasedontheRandomizedAldactoneEvaluationStudy(RALES),treatmentinconjunctionwithstandardtherapy

shouldbeinitiatedatadoseofspironolactone25mgoncedailyinpatientswithaserumpotassium 5.0mEq/Land

serumcreatinine 2.5mg/dL.Patientswhotolerate25mgoncedailymayhavetheirdoseincreasedto50mgonce

dailyasclinicallyindicated.Patientswhodonottolerate25mgoncedailymayhavetheirdosereducedto25mgevery

otherday.Seesection4.4Specialwarningsandprecautionsforuse:HyperkalemiainPatientswithSevereHeart

Failureforadviceonmonitoringserumpotassiumandserumcreatinine.

Hepaticcirrhosiswithascitesandoedema:IfurinaryNa+/K+ratioisgreaterthan1.0,100mgperday.Iftheratiois

lessthan1.0,200-400mg/day.Maintenancedosageshouldbeindividuallydetermined.

Malignantascites:Initialdoseusually100-200mg/day.Inseverecasesthedosagemaybegraduallyincreasedupto

400mg/day.Whenoedemaiscontrolled,maintenancedosageshouldbeindividuallydetermined.

Nephroticsyndrome:Usualdose-100-200mg/day.Spironolactonehasnotbeenshowntobeanti-inflammatory,nor

toaffectthebasicpathologicalprocess.Itsuseisonlyadvisedifglucocorticoidsbythemselvesareinsufficiently

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Diagnosisandtreatmentofprimaryaldosteronism:Aldactonemaybeemployedasaninitialdiagnosticmeasureto

providepresumptiveevidenceofprimaryhyperaldosteronismwhilepatientsareonnormaldiets.

Longtest:Aldactoneisadministeredatadailydosageof400mgforthreetofourweeks.Correctionofhypokalaemia

andofhypertensionprovidespresumptiveevidenceforthediagnosisofprimaryhyperaldosteronism.

Shorttest:Aldactoneisadministeredatadailydosageof400mgforfourdays.Ifserumpotassiumincreasesduring

AldactoneadministrationbutdropswhenAldactoneisdiscontinued,apresumptivediagnosisofprimary

hyperaldosteronismshouldbeconsidered.

Afterthediagnosisofhyperaldosteronismhasbeenestablishedbymoredefinitivetestingprocedures,Aldactonemay

beadministeredindosesof100mgto400mgdailyinpreparationforsurgery.Forpatientswhoareconsidered

unsuitableforsurgery,Aldactonemaybeemployedforlongtermmaintenancetherapyatthelowesteffectivedosage

determinedfortheindividualpatient.

Essentialhypertension:Usualdose-50-100mgperday,whichfordifficultorseverecasesmaybegradually

increasedattwoweeklyintervalsupto200mg/day.Treatmentshouldbecontinuedfortwoweeksorlongersincean

adequateresponsemaynotoccurbeforethistime.Dosageshouldsubsequentlybeadjustedaccordingtotheresponseof

thepatient.

Elderly

Itisrecommendedthattreatmentisstartedwiththelowestdoseandtitratedupwardsasrequiredtoachievemaximum

benefit.Careshouldbetakeninseverehepaticandrenalimpairmentwhichmayalterdrugmetabolismandexcretion.

Children

Initialdailydosageshouldprovide3mgofspironolactoneperkilogrambodyweight,givenindivideddoses.Dosage

shouldbeadjustedonthebasisofresponseandtolerance.Ifnecessaryasuspensionmaybepreparedbycrushing

Aldactonetablets.

4.3Contraindications

Spironolactoneiscontraindicatedinpatientswiththefollowing:

acuterenalinsufficiency,significantrenalcompromise,anuria

Addison’sdisease

hyperkalemia

hypersensitivitytospironolactone

concomitantuseofeplerenone

Aldactoneshouldnotbeadministeredconcurrentlywithotherpotassium-conservingdiureticsandpotassium

supplementsshouldnotbegivenroutinelywithAldactoneashyperkalaemiamaybeinduced.

4.4Specialwarningsandprecautionsforuse

Concomitantuseofspironolactonewithotherpotassiumsparingdiuretics,ACEinhibitors,angiotensinIIantagonists,

aldosteroneblockers,heparin,lowmolecularweightheparin,orpotassiumsupplements,adietrichinpotassium,orsalt

substitutescontainingpotassium,mayleadtoseverehyperkalemia.Hyperkalemiamayalsooccurinpatientswith

impairedrenalfunction.Cardiacdysrhythmias,occasionallyfatal,mayresult.

Theconcomitantadministrationofthispreparationwithcardiacglycosidesorhypotensiveagentsmaynecessitate

adjustmentofthosedrugs.

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function.

Dilutionhyponatraemiamayoccurincombinationwithotherdiuretics.

Patientswhoarebeingtreatedwiththispreparationrequireregularsupervisionwithmonitoringoffluidandelectrolyte

state.Periodicestimationofserumelectrolytesisrecommendedduetothepossibilityofhyperkalemia,hyponatremia

andpossibletransientBUNelevation,especiallyintheelderlyand/orinpatientswithpre-existingimpairedrenalor

hepaticfunction.

Thepreparationshouldonlybeusedwithparticularcautioninelderlypatientsorthosewithpotentialobstructionofthe

urinarytract,orwithdisordersrenderingtheirelectrolytebalanceprecarious.

Spironolactonemayinducegynaecomastiaandmenstrualirregularities.

Reversiblehyperchloremicmetabolicacidosis,usuallyinassociationwithhyperkalemia,hasbeenreportedtooccurin

somepatientswithdecompensatedhepaticcirrhosis,evenwhenrenalfunctionisnormal.

Carcinogenicity:seeSection5.3(Pre-clinicalSafetyData)

HyperkalemiainPatientswithSevereHeartFailure.Hyperkalemiamaybefatal.Itiscriticaltomonitorandmanage

serumpotassiuminpatientswithsevereheartfailurereceivingspironolactone.Avoidusingotherpotassium-sparing

diuretics.Avoidusingoralpotassiumsupplementsinpatientswithserumpotassium>3.5mEq/L.Therecommended

monitoringforpotassiumandcreatinineisoneweekafterinitiationorincreaseindoseofspironolactone,monthlyfor

thefirst3months,thenquarterlyforayear,andthenevery6months.Discontinueorinterrupttreatmentforserum

potassium>5mEq/Lorforserumcreatinine>4mg/dL.(Seesection4.2Posologyandmethodofadministration;

Severeheartfailure).

4.5Interactionwithothermedicinalproductsandotherformsofinteraction

Spironolactonehasbeenreportedtoincreaseserumdigoxinconcentrationandtointerferewithcertainserumdigoxin

assays.Inpatientsreceivingdigoxinandspironolactonethedigoxinresponseshouldbemonitoredbymeansotherthan

serumdigoxinconcentrations,unlessthedigoxinassayusedhasbeenprovennottobeaffectedbyspironolactonetherapy.

Ifitprovesnecessarytoadjustthedoseofdigoxin,patientsshouldbecarefullymonitoredforevidenceofenhancedor

reduceddigoxineffect.

Concurrentusewithcarbenoxoloneorlithiumsaltsshouldbeavoided.

Hyperkalemicmetabolicacidosishasbeenreportedinpatientsgivenspironolactoneconcurrentlywithammoniumchloride

orcolestyramine.

Potentiationoftheeffectofotherdiureticsandantihypertensivedrugsoccursandtheirdosagemayneedtobereducedby

about50%whenAldactoneisaddedtothetreatmentregime,andthenadjustedasnecessary.Concomitantadministration

withcardiacglycosidesmaynecessitateadjustmentofthedosagesofthesedrugs.

SinceACEinhibitorsdecreasealdosteroneproductiontheyshouldnotroutinelybeusedwithAldactone,particularlyin

patientswithmarkedrenalimpairment.

Non-steroidalanti-inflammatorydrugsmayattenuatethenatriureticefficacyofdiureticsduetotheinhibitionofintra-renal

synthesisofprostaglandins.

Spironolactonereducesvascularresponsivenesstonoradrenaline.

Cautionshouldbeexercisedinthemanagementofpatientssubjectedtoregionalorgeneralanaesthesiawhiletheyare

beingtreatedwithAldactone.

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Spironolactonecaninterferewithassaysforplasmadigoxinconcentrations.

Aspirin,indometacinandmefenamicacidhavebeenshowntoattenuatethediureticeffectofspironolactone.

Spironolactoneenhancesthemetabolismofantipyrine.

Influorimetricassays,spironolactonemayinterferewiththeestimationofcompoundswithsimilarfluorescence

characteristics.

4.6Fertility,pregnancyandlactation

Pregnancy

Spironolactonewasdevoidofteratogeniceffectsinmice.Rabbitsreceivingspironolactoneshowedreducedconception

rate,increasedresorptionrate,andlowernumbersoflivebirths.Noembryotoxiceffectswereseeninratsadministered

highdosages,butlimited,dosage-relatedhyprolactinemiaanddecreasedventralprostateandseminalvesicleweightsin

males,andincreasingluteinizinghormonesecretionandovariananduterineweightsinfemaleswerereported.

Feminizationoftheexternalgenitaliaofmalefoetuseswasreportedinanotherstudyinrats.

Therearenostudiesinpregnantwomen.Spironolactoneshouldbeusedduringpregnancyonlyifthepotentialbenefit

justifiesthepotentialrisktothefoetus.

Lactation

Themetabolitecanrenoneisdetectedinbreastmilk,sothatbreastfeedingofinfantsshouldbeavoidedduringtherapywith

thedrug.

4.7Effectsonabilitytodriveandusemachines

Somnolenceanddizzinesshavebeenreportedtooccurinsomepatients.Cautionisadvisedwhendrivingoroperating

machineryuntiltheresponsetoinitialtreatmenthasbeendetermined.

4.8Undesirableeffects

Thefollowingadverseeventshavebeenreportedinassociationwithspironolactonetherapy:

Bodyasawhole:Malaise,drugfever,lethargy.

EndocrineDisorders:benignbreastneoplasm,breastpain.

GastrointestinalDisorders:gastrointestinaldisturbances,nausea.

HaematologicalDisorders:leucopenia(includingagranulocytosis),thrombocytopenia,anaemia,purpura,eosinophilia.

LiverDisorders:hepaticfunctionabnormal.

MetabolicandNutritionalDisorders:electrolytedisturbances,hyperkalemia.

MusculoskeletalDisorders:legcramps.

NervousSystemDisorders:dizziness,headache,drowsiness,ataxia.

PsychiatricDisorders:changesinlibido,confusion.

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SkinandAppendages:alopecia,hypertrichosis,pruritus,rash,urticaria,StevensJohnsonSyndrome.

UrinarySystemDisorders:acuterenalfailure.

Gynaecomastiamaydevelopinassociationwiththeuseofspironolactone.Developmentappearstoberelatedtoboth

dosagelevelanddurationoftherapyandisnormallyreversiblewhenspironolactoneisdiscontinued.Inrareinstances

somebreastenlargementmaypersist.

4.9Overdose

Acuteoverdosagemaybemanifestedbydrowsiness,mentalconfusion,nausea,vomiting,dizziness,diarrhoea,or

maculopapularorerythematousrash.Dehydrationmayoccur.

Hyponatraemiaorhyperkalaemiamaybeinducedbuttheseeffectsareunlikelytobeassociatedwithacuteoverdosage.

Symptomsofhyperkalaemiamaymanifestasparaesthesia,weakness,flaccidparalysisormusclespasmandmaybe

difficulttodistinguishclinicallyfromhypokalaemia.Electrocardiographicchangesaretheearliestspecificsignsof

potassiumdisturbance.Nospecificantidotehasbeenidentified.Spironolactoneuseshouldbediscontinued.Improvement

maybeexpectedafterwithdrawalofthedrug.Generalsupportivemeasuresincludingreplacementoffluidsand

electrolytesmaybeindicated.Forhyperkalaemia,reducepotassiumintake,administerpotassium-excretingdiuretics,

intravenousglucosewithregularinsulin,ororalion-exchangeresins.

5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

Aldactone,asacompetitivealdosteroneantagonist,increasessodiumexcretionwhilstreducingpotassiumlossatthe

distalrenaltubule.Ithasagradualandprolongedaction,maximumresponsebeingusuallyattainedafter2-3days

treatment.CombinationofAldactonewithaconventional,moreproximallyactingdiureticusuallyenhancesdiuresis

withoutexcessivepotassiumloss.

Severeheartfailure:TheRandomizedAldactoneEvaluationStudy(RALES)wasamultinational,double-blindstudy

in1663patientswithanejectionfractionof 35%,ahistoryofNewYorkHeartAssociation(NYHA)classIVheart

failurewithin6months,andclassIII-IVheartfailureatthetimeofrandomization.Allpatientswererequiredtobe

takingaloopdiureticand,iftolerated,anACEinhibitor.Patientswithabaselineserumcreatinineof>2.5mg/dLora

recentincreaseof25%orwithabaselineserumpotassiumof>5.0mEq/Lwereexcluded.Patientswererandomized

1:1tospironolactone25mgorallyoncedailyormatchingplacebo.Patientswhotolerated25mgoncedailyhadtheir

doseincreasedto50mgoncedailyasclinicallyindicated.Patientswhodidnottolerate25mgoncedailyhadtheir

dosagereducedto25mgeveryotherday.TheprimaryendpointforRALESwastimetoall-causemortality.RALES

wasterminatedearly,afterameanfollow-upof24months,becauseofsignificantmortalitybenefitdetectedona

plannedinterimanalysis.Spironolactonereducedtheriskofdeathby30%comparedtoplacebo(p<0.001;95%

confidenceinterval18%to40%).Spironolactonereducedtheriskofcardiacdeath,primarilysuddendeathanddeath

fromprogressiveheartfailureby31%comparedtoplacebo(p<0.001;95%confidenceinterval18%to42%).

Spironolactonealsoreducedtheriskofhospitalizationforcardiaccauses(definedasworseningheartfailure,angina,

ventriculararrhythmiasormyocardialinfarction)by30%(p<0.00195%confidenceinterval18%to41%).Changesin

NYHAclassweremorefavorablewithspironolactone:Inthespironolactonegroup,NYHAclassattheendofthe

studyimprovedin41%ofpatientsandworsenedin38%comparedtoimprovedin33%andworsenedin48%inthe

placebogroup(P<0.001).

5.2Pharmacokineticproperties

Spironolactoneiswellabsorbedorallyandisprincipallymetabolisedtoactivemetabolites:sulphurcontaining

metabolites(80%)andpartlycanrenone(20%).

Althoughtheplasmahalf-lifeofspironolactoneitselfisshort(1.3hours)thehalf-livesofactivemetabolitesarelonger

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5.3Preclinicalsafetydata

Carcinogenicity:spironolactonehasbeenshowntoproducttumoursinratswhenadministeredathighdosesovera

longperiodoftime.Inmanandtheratspironolactoneismetabolisedtoaminorextenttocanrenone.Incontrast

canrenoneandcanrenoicacidarethemajormetabolitesofpotassiumcanrenoate.

Adoserelatedincidenceofmyelocyticleukaemiahasbeenobservedinratsadministeredpotassiumcanrenoateat

dosesabove20mg/kg/dayforaperiodofoneyear.

Inonelongterm(twoyear)oralcarcinogenicitystudyofpotassiumcanrenoateintherat,myelocyticleukaemiaand

hepatic,thyroid,testicularandmammarytumourswereobserved.Potassiumcanrenoatewasnotmutagenicintests

usingbacteriaandyeast,orinaninvivomammaliansystem.Itwasmutagenicinvitrotestsinmammaliancells

followingmetabolicactivation.Anincreasedincidenceofleukaemiahasnotbeenobservedinchronicrattoxicity

studieswithspironolactoneatdosesupto500mg/kg/day,whichmaybeduetodifferencesinmetabolismbetween

spironolactoneandpotassiumcanrenoateinrats.

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

oftheseanimalfindingswithrespecttoclinicaluseisnotcertain.

However,thelongtermuseofspironolactoneinyoungpatientsrequirescarefulconsiderationofthebenefitsandthe

potentialhazardinvolved.

6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

CalciumSulphateDihydrate

MaizeStarch

Povidone

MagnesiumStearate

FelcofixpeppermintNo.16433

Hypromellose

Macrogol400

OpasprayWhiteM-1-7111B(ContainsHypromelloseandTitaniumDioxide(E171))

6.2Incompatibilities

Notapplicable.

6.3Shelflife

5years.

6.4Specialprecautionsforstorage

Donotstoreabove30 º C.Keeptheblistersintheoutercarton.

6.5Natureandcontentsofcontainer

Thefollowingpresentationsareregistered:

PVC/foilblisterpacksof50,100tablets.

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6.6Specialprecautionsfordisposalofausedmedicinalproductorwastematerialsderivedfrom

suchmedicinalproductandotherhandlingoftheproduct

Nospecialrequirements.

7MARKETINGAUTHORISATIONHOLDER

PharmaciaIreland

9Riverwalk

NationalDigitalPark

CitywestBusinessCampus

Dublin24

8MARKETINGAUTHORISATIONNUMBER

PA936/16/2

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

Dateoffirstauthorisation:12December1984

Dateoflastrenewal:1April2008

10DATEOFREVISIONOFTHETEXT

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