CARDURA

Main information

  • Trade name:
  • CARDURA Tablets 2 Milligram
  • Dosage:
  • 2 Milligram
  • Pharmaceutical form:
  • Tablets
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug

Documents

Localization

  • Available in:
  • CARDURA Tablets 2 Milligram
    Ireland
  • Language:
  • English

Status

  • Source:
  • HPRA - Health Products Regulatory Authority - Ireland
  • Authorization number:
  • PPA1328/079/003
  • Authorization date:
  • 20-11-2009
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

IRISHMEDICINESBOARDACTS1995AND2006

MEDICINALPRODUCTS(CONTROLOFPLACINGONTHEMARKET)REGULATIONS,2007

(S.I.No.540of2007)

PPA1328/079/003

CaseNo:2071979

TheIrishMedicinesBoardinexerciseofthepowersconferredonitbytheabovementionedRegulationsherebygrantsto

B&SHealthcare

Unit4,BradfieldRoad,Ruislip,Middlesex,HA40NU,UnitedKingdom

anauthorisation,subjecttotheprovisionsofthesaidRegulations,inrespectoftheproduct

Cardura2mgTablets

TheparticularsofwhicharesetoutinPartIandPartIIoftheattachedSchedule.Theauthorisationisalsosubjecttothegeneralconditionsas

maybespecifiedinthesaidRegulationsaslistedonthereverseofthisdocument.

Thisauthorisation,unlesspreviouslyrevoked,shallcontinueinforcefrom20/11/2009.

SignedonbehalfoftheIrishMedicinesBoardthis

________________

Irish Medicines Board

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Date Printed 27/11/2009 CRN 2071979 page number: 1

PartII

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

Cardura2mgTablets

2QUALITATIVEANDQUANTITATIVECOMPOSITION

Doxazosinmesilate2.43mgequivalentto2mgdoxazosin

Eachtabletcontainslactose

Forafulllistofexcipients,seesection6.1

3PHARMACEUTICALFORM

Tablets

ProductimportedfromItaly

Whiteoblongbiconvextablets:marked“CN2”andscoredononesideandmarkedwiththePfizerlogoontheother.

4CLINICALPARTICULARS

4.1TherapeuticIndications

Hypertension:Carduraisindicatedforthetreatmentofhypertensionandcanbeusedasasoleagenttocontrolblood

pressureinhypertensivepatients.

Inpatientsinadequatelycontrolledonsingleantihypertensivetherapy,Carduramaybeusedincombinationwitha

thiazidediuretic,beta-adrenoceptorblockingagent,calciumantagonistoranangiotensin-convertingenzymeinhibitor.

BenignProstaticHyperplasia:Carduraisindicatedasanadjunctinthetreatmentofurinaryoutflowobstructionand

symptomsassociatedwithbenignprostatichyperplasia(BPH).Itmaythereforebeofvalueinpatientsawaiting

prostaticsurgeryorforwhomsurgeryisnotpossible.

CarduramaybeusedinBPHpatientswhoareeitherhypertensiveornormotensive.

4.2Posologyandmethodofadministration

Adults:Carduraisusedinaoncedailyregimenandmaybeadministeredinthemorningorevening.

Hypertension:Itisrecommendedthattherapybeinitiatedat1mggivenoncedailyforoneortwoweekstominimise

thepotentialforposturalhypotensionand/orsyncope(seesection4.4Specialwarningsandspecialprecautionsforuse)

Thedosagemaythenbeincreasedto2mgoncedailyforanadditionaloneortwoweeks.Ifnecessarythedailydosage

shouldthenbeincreasedgraduallyatsimilarintervalsto4mg,8mg,andl6mgasdeterminedbypatientresponseto

achievethedesiredreductioninbloodpressure.Theusualdoseis2-4mgoncedaily.

Themaximumdailydoseshouldnotexceed16mg.

Diuretictherapymaybeintroduced,ifrequired.

BenignProstaticHyperplasia:TherecommendedinitialdosageofCardurais1mggivenoncedailytominimisethe

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Dependingontheindividualpatient’surodynamicsandBPHsymptomatology,dosagemaythenbeincreasedto2mg

andthereafterto4mganduptothemaximumrecommendeddoseof8mg.Therecommendedtitrationintervalis1-2

weeks.Theusualrecommendeddoseis2-4mgoncedaily.

Children:ThereisinsufficientexperiencetorecommendtheuseofCardurainchildrenunder12yearsofage.

Elderly:Normaladultdosage.Incommonwithotherdrugsofthisclass,dosageshouldbekeptaslowaspossibleand

incrementsmadeunderclosesupervision.

Patientswithrenalimpairment:Sincethereisnochangeinpharmacokineticsinpatientswithimpairedrenalfunction

theusualadultdoseofCarduraisrecommended.Carduraisnotdialysable.

Patientswithhepaticimpairment:Thereareonlylimiteddatainpatientswithliverimpairmentandontheeffectof

drugsknowntoinfluencehepaticmetabolism(e.g.cimetidine).Aswithanydrugwhollymetabolisedbytheliver,

Cardurashouldbeusedwithcareinpatientswithsignificantexistinghepaticdysfunction(seeSection4.4.Special

warningsandprecautionsforuse,andsection5.2Pharmacokineticproperties).

4.3Contraindications

Doxazosiniscontraindicatedin:

Patientswithaknownhypersensitivitytoquinazolines(e.g.prazosin,terazosin,doxazosin),oranyofthe

excipients

Patientswithahistoryoforthostatichypotension

Patientswithbenignprostatichyperplasiaandconcomitantcongestionoftheupperurinarytract,chronicurinary

tractinfectionorbladderstones.

Duringlactation(pleaseseesection4.6)

Patientswithhypotension(forbenignprostatichyperplasiaindicationonly)

Doxazosiniscontraindicatedasmonotherapyinpatientswitheitheroverflowbladderoranuriawithorwithout

progressiverenalinsufficiency.

4.4Specialwarningsandprecautionsforuse

PosturalHypotension/Syncope:

InitiationofTherapy-Aswithallalpha-blockers,averysmallpercentageofpatientshaveexperiencedpostural

hypotensionevidencedbydizzinessandweakness,orrarelylossofconsciousness(syncope),particularlywiththe

commencementoftherapy(seesection4.2Posologyandmethodofadministration).Therefore,itisprudentmedical

practicetomonitorbloodpressureoninitiationoftherapytominimisethepotentialforposturaleffects.

Wheninstitutingtherapywithanyeffectivealpha-blocker,thepatientshouldbeadvisedhowtoavoidsymptoms

resultingfromposturalhypotensionandwhatmeasurestotakeshouldtheydevelop.Thepatientshouldbecautionedto

avoidsituationswhereinjurycouldresult,shoulddizzinessorweaknessoccurduringtheinitiationofCarduratherapy,

suchasdrivingoroperatingmachinery.

UseinpatientswithAcuteCardiacConditions:

Aswithanyothervasodilatoryanti-hypertensiveagentitisprudentmedicalpracticetoadvisecautionwhen

administeringdoxazosintopatientswiththefollowingacutecardiacconditions:

-pulmonaryoedemaduetoaorticormitralstenosis

-heartfailureathighoutput

-right-sidedheartfailureduetopulmonaryembolismorpericardialeffusion

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UseinHepaticallyImpairedPatients:

Thereareonlylimiteddatainpatientswithliverimpairmentandontheeffectofdrugsknowntoinfluencehepatic

metabolism(e.g.cimetidine).Aswithanydrugwhollymetabolisedbytheliver,Cardurashouldbeadministeredwith

particularcautiontopatientswithevidenceofimpairedhepaticfunction(seesection4.2Posologyandmethodof

administration,andsection5.2Pharmacokineticproperties).

Sincethereisnoclinicalexperienceinpatientswithseverehepaticimpairmentuseinthesepatientsisnot

recommended.

UsewithPDE-5Inhibitors:

Concomitantadministrationofdoxazosinwithphosphodiesterase-5-inhibitors(egsildenafil,tadalafil,andvardenafil)

shouldbedonewithcautionasbothdrugshavevasodilatingeffectsandmayleadtosymptomatichypotensioninsome

patients.Toreducetheriskoforthostatichypotensionitisrecommendedtoinitiatethetreatmentwith

phosphodiesterase-5-inhibitorsonlyifthepatientishemodynamicallystabilizedonalpha-blockertherapy.

Furthermore,itisrecommendedtoinitiatephosphodiesterase-5-inhibitortreatmentwiththelowestpossibledoseandto

respecta6-hourtimeintervalfromintakeofdoxazosin.Nostudieshavebeenconductedwithdoxazosinprolonged

releaseformulations.

UseinpatientswithRenalImpairment:

ThereisnoevidencethatCarduraaggravatesrenaldysfunction.However,Carduradosageintroductionandadjustment

shouldbecarriedoutwithgreatcare.

Useinpatientsundergoingcataractsurgery:

The‘IntraoperativeFloppyIrisSyndrome’(IFIS,avariantofsmallpupilsyndrome)hasbeenobservedduringcataract

surgeryinsomepatientsonorpreviouslytreatedwithtamsulosin.Isolatedreportshavealsobeenreceivedwithother

alpha-1blockersandthepossibilityofaclasseffectcannotbeexcluded.AsIFISmayleadtoincreasedprocedural

complicationsduringthecataractoperationcurrentorpastuseofalpha-1blockersshouldbemadeknowntothe

ophthalmicsurgeoninadvanceofsurgery.

Themeanterminalhalf-lifeofdoxazosinis22hours.Thismaybeprolongedinpatientswithcongestiveheartfailure.

Therateofdoseadjustmentmayneedtobeslowed.

Insomepatientswithleftventricularfailure,thedecreaseinleftventricularfillingassociatedwithvigoroustherapy

mayresultinasignificantfallincardiacoutputandsystemicbloodpressureafteradministrationofdoxazosin.These

effectsshouldbekeptinmindwhenintroducingtherapyandcontinuousadjustmentofdoseused.

Patientswithrarehereditaryproblemsofgalactoseintolerance,theLapplactosedeficiencyorglucose-galactose

malabsorptionshouldnottakethismedicine.

4.5Interactionwithothermedicinalproductsandotherformsofinteraction

ConcomitantadministrationofanalphablockerwithaPDE-5inhibitormayleadtosymptomatichypotensioninsome

patients(seesection4.4SpecialWarningsandSpecialPrecautionsforUse).Nostudieshavebeenconductedwith

doxazosinprolongedreleaseformulations.

Doxazosinishighlyboundtoplasmaproteins(98%).Invitrodatainhumanplasmaindicatesthatdoxazosinhasno

effectonproteinbindingofthedrugstested(digoxin,phenytoin,warfarinorindometacin),however,thetheoretical

potentialforinteractionwithotherproteinbounddrugsshouldbeborneinmind.

Conventionaldoxazosinhasbeenadministeredwithoutanyadversedruginteractioninclinicalexperiencewiththiazide

diuretics,furosemide,beta-blockers,non-steroidalanti-inflammatorydrugs,antibiotics,oralhypoglycaemicdrugs,

uricosuricagents,andanticoagulants.However,datafromformaldrug/druginteractionstudiesarenotpresent.

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Inanopen-label,randomized,placebo-controlledtrialin22healthymalevolunteers,theadministrationofasingle1

mgdoseofdoxazosinonday1ofafour-dayregimenoforalcimetidine(400mgtwicedaily)resultedina10%

increaseinmeanAUCofdoxazosin,andnostatisticallysignificantchangesinmeanCmaxandmeanhalf-lifeof

doxazosin.The10%increaseinthemeanAUCfordoxazosinwithcimetidineiswithinintersubjectvariation(27%)of

themeanAUCfordoxazosinwithplacebo.

4.6Pregnancyandlactation

Forthehypertensionindication:

Useduringpregnancy:Doxazosincrossestheplacenta.

Astherearenoadequateandwell-controlledstudiesinpregnantwomen,thesafetyofCarduraduringpregnancyhas

notyetbeenestablished.Accordingly,Cardurashouldbeusedonlywhen,intheopinionofthephysician,thepotential

benefitoutweighsthepotentialrisk.Althoughnoteratogeniceffectswereseeninanimaltesting,reducedfoetal

survivalwasobservedinanimalsatextremelyhighdoses(seeSection5.3:PreclinicalSafetyData).Thesedoseswere

approximately300timesthemaximumrecommendedhumandose.

Useduringlactation:

Doxazosiniscontraindicatedduringlactationasanimalstudieshaveshownthatdoxazosinaccumulatesinmilkof

lactatingrats,andthereisnoinformationabouttheexcretionofthedrugintothemilkoflactatingwomen.Theclinical

safetyofCarduraduringlactationhasnotbeenestablished,consequentlyCarduraiscontra-indicatedinnursing

mothers.

Alternatively,mothersshouldstopbreast-feedingwhentreatmentwithdoxazosinisnecessary(Pleaseseesection5.3:

PreclinicalSafetyData).

Forthebenignprostatichyperplasiaindication:Thissectionisnotapplicable.

4.7Effectsonabilitytodriveandusemachines

Theabilitytoengageinactivitiessuchasoperatingmachineryoroperatingamotorvehiclemaybeimpaired,

especiallywheninitiatingtherapy.Thedrugmayalsoinducedrowsiness.Patientsshouldnotdriveoroperate

machineryunlessithasbeenshownnottoaffecttheiralertnessordexterity.

4.8Undesirableeffects

Hypertension:Inclinicaltrialsinvolvingpatientswithhypertension,themostcommonreactionsassociatedwith

Carduratherapywereofaposturaltype(rarelyassociatedwithfainting)ornon-specific.

Benignprostatichyperplasia:ExperienceincontrolledclinicaltrialsinBPHindicatesasimilaradverseeventprofile

tothatseeninhypertension.

Frequenciesusedareasfollows:Verycommon 1/10,Common 1/100and <

1/10,Uncommon 1/1,000and <

1/100,Rare 1/10,000and <

1/1,000,Veryrare <

1/10,000.

MedDRA

SystemOrganClass Frequency UndesirableEffects

Infectionsandinfestations Common Respiratorytractinfection,urinarytractinfection

Bloodandlymphaticsystem

disorders VeryRare Leukopenia,thrombocytopenia

ImmuneSystemDisorders Uncommon Allergicdrugreaction

MetabolismandNutrition

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PsychiatricDisorders Uncommon Agitation,depressionAnxiety,insomnia,

nervousness

NervousSystemDisorders Common somnolenceDizziness,headache

Uncommon Cerebrovascularaccident,hypoesthesia,syncope,

tremor

VeryRare Dizzinesspostural,paresthesia,

EyeDisorders VeryRare Blurredvision

Unknown Introperativefloppyirissyndrome(seeSection

4.4)

EarandLabyrinthDisorders Common Vertigo

Uncommon Tinnitus

CardiacDisorders Common Palpitation,tachycardia

Uncommon Anginapectoris,myocardialinfarction,

VeryRare Bradycardiacardiacarrhythmias

VascularDisorders Common Hypotension,posturalhypotension

VeryRare Hotflushes

Respiratory,Thoracicand

MediastinalDisorders Common Bronchitis,cough,dyspnea,rhinitis

Uncommon Epistaxis

VeryRare Bronchospasm

GastrointestinalDisorders Common Abdominalpain,dyspepsia,drymouth,nausea,

Uncommon Constipation,flatulence,vomiting,gastroenteritis

diarrhoea

HepatobiliaryDisorders Uncommon Abnormalliverfunctiontests

VeryRare Cholestasis,hepatitis,jaundice

SkinandSubcutaneousTissue

Disorders Common Pruritus

Uncommon Skinrash,

VeryRare urticariaalopecia,purpura

MusculoskeletalandConnective

TissueDisorders Common Backpain,myalgia

Uncommon Arthralgia,

Rare musclecramps,muscleweakness

RenalandUrinaryDisorders Common Cystitis,urinaryincontinence

Uncommon Dysuria,micturitionfrequency,hematuria

Rare polyuria

VeryRare Increaseddiuresis,micturitiondisorder,nocturia

ReproductiveSystemandBreast

Disorders Uncommon Impotence

VeryRare Gynecomastia,priapism

Unknown Retrogradeejaculation

GeneralDisordersand

AdministrationSiteConditions Common Asthenia,chestpain,influenza-likesymptoms,

peripheraloedema,

Uncommon Pain,facialoedema

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4.9Overdose

Shouldoverdosageleadtohypotension,thepatientshouldbeimmediatelyplacedinasupine,headdownposition.

Othersupportivemeasuresmaybeappropriateinindividualcases.

Ifthismeasureisinadequate,shockshouldfirstbetreatedwithvolumeexpanders.Ifnecessary,vasopressorshould

thenbeused.Renalfunctionshouldbemonitoredandsupportedasneeded.

Sincedoxazosinishighlyproteinbound,dialysisisnotindicated.

5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

AdministrationofCardurareducesbloodpressureduetoadecreaseinsystemicvascularresistance.Withoncedaily

dosing,clinicallysignificantreductionsinbloodpressurearemaintainedthroughoutthedayandat24hourspost-dose.

Duringtheonsetoftherapy,agradualreductioninbloodpressureoccurs,andorthostaticeffectsarecomparablewith

thoseofotherantihypertensives.

Cardurahasbeenshowntobefreeofadversemetaboliceffectsandissuitableforuseinpatientswithco-existent

diabetesmellitus,insulinresistanceandgout.

Carduraissuitabletouseinpatientswithco-existentasthma,leftventricularhypertrophyandinelderlypatients.

TreatmentwithCardurahasbeenshowntoresultinregressionofleftventricularhypertrophy,inhibitionofplatelet

aggregationandenhancedactivityoftissueplasminogenactivator.Additionally,Carduraimprovesinsulinsensitivity

inpatientswhohaveimpairment.

Carduraproducesfavourableeffectsonbloodlipids,withasignificantincreaseinthehighdensitylipoprotein

(HDL)/totalcholesterolratioandtrendstoafavourablereductionintotaltriglycerides.

AdministrationofCarduratopatientswithsymptomaticBPHresultsinasignificantimprovementinurodynamicsand

symptoms.TheeffectinBPHisthoughttoresultfromselectiveblockadeofthealpha-adrenoceptorslocatedinthe

muscularstromaandcapsuleoftheprostate,andinthebladderneck.

Doxazosinhasbeenshowntobeaneffectiveblockerofthe1Asubtypeofthealpha-1-adrenoceptorwhichaccountsfor

over70%ofthesubtypesintheprostate.ThisaccountsfortheactioninBPHpatients.

CardurahasdemonstratedsustainedefficacyandsafetyinthelongtermtreatmentofBPH.

5.2Pharmacokineticproperties

Absorption:Followingoraladministrationinhumans(youngmaleadultsortheelderlyofeithersex),doxazosiniswell

absorbedandapproximatelytwothirdsofthedoseisbioavailable.

Biotransformation/Elimination:Approximately98%ofdoxazosinisprotein-boundinplasma.

DoxazosininprimarilymetabolisedbyO-demethylationandhydroxylation.

Doxazosinisextensivelymetabolisedinmanandintheanimalspeciestested,withthefaecesbeingthepredominant

routeofexcretion.

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Afteroraladministrationofdoxazosintheplasmaconcentrationsofthemetabolitesarelow.Themostactive(6'

hydroxy)metaboliteispresentinmanatonefortiethoftheplasmaconcentrationoftheparentcompoundwhich

suggeststhattheantihypertensiveactivityisinthemainduetodoxazosin.

Pharmacokineticstudiesintheelderlyandpatientswithrenalinsufficiencyhaveshownnosignificantalterations

comparedtoyoungerpatientswithnormalrenalfunction.

Thereareonlylimiteddatainpatientswithliverimpairmentandontheeffectsofdrugsknowntoinfluencehepatic

metabolism(e.g.,cimetidine).Inaclinicalstudyin12subjectswithmoderatehepaticimpairment,singledose

administrationofdoxazosinresultedinanincreaseinAUCof43%andadecreaseinapparentoralclearanceof40%.

Aswithanydrugwhollymetabolizedbytheliver,useofCardurainpatientswithimpairedliverfunctionshouldbe

undertakenwithcaution.(seesection4.4SpecialWarningsandSpecialPrecautionsforUse).

5.3Preclinicalsafetydata

Preclinicalsafetydatarevealnospecialhazardforhumansbasedonconventionalanimalstudiesinsafety

pharmacology,repeateddosetoxicity,genotoxicityandcarcinogenicity.Forfurtherinformationseesection4.6

Pregnancyandlactation.

6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

Lactose

Magnesiumstearate

Microcrystallinecellulose

Sodiumlaurilsulfate

Sodiumstarchglycollate

6.2Incompatibilities

Notapplicable.

6.3ShelfLife

Theshelf-lifeexpirydateofthisproductshallbethedateshownonthecontainerandtheouterpackageoftheproduct

inthecountryoforigin.

6.4Specialprecautionsforstorage

Donotstoreabove30°C

6.5Natureandcontentsofcontainer

Cardura2mgTabletsareavailableinpacksof30tablets.Blisterstrips,10tablets/strip,3stripsinanoverlabelledouter

container.

6.6Specialprecautionsfordisposalandotherhandling

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7ParallelProductAuthorisationHolder

B&SHealthcare

Unit4,BradfieldRoad

Ruislip

MiddlesexHA40NU

UnitedKingdom

8ParallelProductAuthorisationNumber

PPA1328/079/003

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

Dateoffirstauthorisation:20 th

November2009

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