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:
  • PPA0465/063/002A
  • Authorization date:
  • 18-08-2000
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

IRISHMEDICINESBOARDACT1995,asamended

MedicinalProducts(ControlofPlacingontheMarket)Regulations,2007,asamended

PPA0465/063/002A

CaseNo:2086852

TheIrishMedicinesBoardinexerciseofthepowersconferredonitbytheabovementionedRegulationsherebygrantsto

PCOManufacturingLimited

Unit10,AshbourneBusinessPark,Rath,Ashbourne,Co.Meath,Ireland

anauthorisation,subjecttotheprovisionsofthesaidRegulations,inrespectoftheproduct

Cardura2mgTablet

theparticularsofwhicharesetoutintheattachedSchedule.Theauthorisationisalsosubjecttothegeneralconditionsasmaybespecifiedin

thesaidRegulationsaslistedonthereverseofthisdocument.

Thisauthorisation,unlesspreviouslyrevoked,shallcontinueinforcefrom10/08/2010until17/09/2010.

SignedonbehalfoftheIrishMedicinesBoardthis

________________

Irish Medicines Board

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Date Printed 10/08/2010 CRN 2086852 page number: 1

PartII

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

Cardura2mgTablet

2QUALITATIVEANDQUANTITATIVECOMPOSITION

Eachtabletcontainsdoxazosinmesilateequivalentto2mgdoxazosin.

Excipients:includesLactose

Forafulllistofexcipients,seesection6.1

3PHARMACEUTICALFORM

Tablet

ProductimportedfromtheUK:

Whiteovaltabletsmarked‘DXP2’ononesideand‘PFIZER’ontheother.

ProductimportedfromGreece,ItalyandHungary:

White,flatbevellededgedtabletswith‘CN2’andabreaklineononesideand‘PFIZER’ontheother.

4CLINICALPARTICULARS

4.1TherapeuticIndications

Hypertension:Carduraisindicatedfortreatmentofhypertensionandcanbeusedasasoleagenttocontrolblood

pressureinhypertensionpatients.

Inpatientsinadequatelycontrolledonsingleantihypertensivetherapy,Carduramaybeusedincombinationwitha

thiazidediuretic,beta-adrenoceptorblockingagent,calciumantagonistorangiotensinconvertingenzymeinhibitor.

Benignprostatichyperplasia:Carduraisindicatedasanadjunctinthetreatmentofurinaryoutflowobstructionand

symptomsassociatedwithbenignprostatichyperplasia(BPH).Itmaythereforebeofvalueinpatientsawaiting

prostaticsurgeryorforwhomsurgeryisnotpossible.

Carduramaybeusedinpatientswhoareeitherhypertensiveornormotensive.

4.2Posologyandmethodofadministration

Adults:Carduraisusedinaoncedailyregimenandmaybeadministeredinthemorningorevening.

Hypertension:Itisrecommendedthattherapybeinitiatedat1mggivenoncedailyforoneortwoweekstominimise

thepotentialforposturalhypotensionand/orsyncope(seesection4.4Specialwarningsandspecialprecautionsfor

use).Thedosagemaythenbeincreasedto2mgoncedailyforanadditionaloneortwoweeks.Ifnecessarythedaily

dosageshouldthenbeincreasedgraduallyatsimilarintervalsto4mg,8mg,and16mgasdeterminedbypatient

responsetoachievethedesiredreductioninbloodpressure.Theusualdoseis2-4mgoncedaily.

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Diuretictherapymaybeintroduced,ifrequired.

Benignprostatichyperplasia:TherecommendedinitialdosageofCardurais1mggivenoncedailytominimisethe

potentialforposturalhypotensionand/orsyncope(seesections4.4Specialwarningsandspecialprecautionsforuse).

Dependingontheindividualpatient’surodynamicsandBPHsymptomatology,dosagemaythenbeincreasedto2mg

andthereafterto4mganduptothemaximumrecommendeddoseof8mg.Therecommendedtitrationintervalis1-2

weeks.Theusualrecommendeddoseis2-4mgoncedaily.

Children:ThereisinsufficientexperiencetorecommendtheuseofCardurainchildrenundertheageof12years.

Elderly:Normaladultdosage.Incommonwithotherdrugsinthisclass,thedosageshouldbekeptaslowaspossible

andincrementsmadeunderclosesupervision.

Pateintswithrenalimpairment:Sincethereisnochangeinpharmacokineticsinpatientswithimpairedfunction,the

usualadultdoseofCarduraisrecommended.Carduraisnotdialyzable.

Patientswithhepaticimpairment:Thereareonlylimiteddatainpatientswithliverimpairmentandontheeffectof

drugsknowntoinfluencehepaticmetabolism(e.g.cimetidine).Aswithanydrugwhollymetabolisedbytheliver,

Cardurashouldbeusedwithcareinpatientswithsignificantexistinghepaticdysfunction(seesection4.4Special

warningsandspecialprecautionsforuse,andsection5.2Pharmacokineticsproperties).

4.3Contraindications

Carduraiscontra-indicatedinpatientswithaknownhypersensitivitytoquinazolines,doxazosin,oranyoftheinert

ingredients.

Useduringlactation

Animalstudieshaveshownthatdoxazosinaccumulatesinbreastmilk.TheclinicalsafetyofCarduraduringlactation

hasnotbeenestablished,consequentlyCarduraiscontra-indicatedinnursingmothers.

4.4Specialwarningsandprecautionsforuse

PosturalHypotension/Syncope:Aswithallalpha-blockers,averysmallpercentageofpatientshaveexperienced

posturalhypotensionevidencedbydizzinessandweakness,orrarelylossofconsciousness(syncope),particularlywith

thecommencementoftherapy(seesection4.2Posologyandmethodofadministation).Wheninstitutingtherapywith

anyeffectivealpha-blocker,thepatientshouldbeadvisedhowtoavoidsymptomsresultingfromposturalhypotension

andwhatmeasurestotakeshouldtheydevelop.Thepatientsshouldbecautionedtoavoidsituationswhereinjury

couldresult,shoulddizzinessorweaknessoccurduringtheinitiationofCarduratherapy,suchasdrivingoroperating

machinery.

UsewithPDE-5Inhibitors:ConcomitantadministrationofanalphablockerwithaPDE-5inhibitorshouldbeused

withcautionasitmayleadtosymptomatichypotensioninsomepatients.

Patientswithrenalimpairment:ThereisnoevidencethatCarduraaggravatesrenaldysfunction.Carduradosage

introductionandadjustmentshouldbecarriedoutwithgreatcare.

Patientswithhepaticimpairment:

Thereisonlylimiteddatainpatientswithliverimpairmentandontheeffectsofdrugsknowntoinfluencehepatic

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

patientswithsignificantexistinghepaticdysfunction(seesection4.2Posologyandmethodofadministration,and

section5.2Pharmacokineticproperties).

Themeanterminalhalf-lifeofdoxazosinis22hours.Thismaybeprolongedinpatientswithcongestiveheartfailure.

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Insomepatientswithleftventricularfailure,thedecreaseinleftventricularfillingassociatedwithvigoroustherapy

mayresultinasignificantfallincardiacoutputandsystemicbloodpressureafteradministrationofdoxazosin.These

effectsshouldbekeptinmindwhenintroducingtherapyandcontinuousadjustmentofdoseused.

Thisproductincludeslactose:Patientswithrarehereditaryproblemsofgalactoseintolerance,theLapplactose

deficiencyorglucose-galactosemalabsorptionshouldnottakethismedicine.

The‘IntraoperativeFloppyIrisSyndrome’(IFIS,avariantofsmallpupilsyndrome)hasbeenobservedduringcataract

surgeryinsomepatientsonorpreviouslytreatedwithtamsulosin.Isolatedreportshavealsobeenreceivedwithother

alpha-1blockersandthepossibilityofaclasseffectcannotbeexcluded.AsIFISmayleadtoincreasedprocedural

complicationsduringthecataractoperationcurrentorpastuseofalpha-1blockersshouldbemadeknowntothe

ophthalmicsurgeoninadvanceofsurgery.

4.5Interactionwithothermedicinalproductsandotherformsofinteraction

Doxazosinishighlyboundtoplasmaproteins(98%).Invitrodatainhumanplasmaindicatesthatdoxazosinhasno

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

potentialforinteractionwithotherproteinbounddrugsshouldbeborneinmind.

Noadversedrugreactionshavebeenobservedwiththiazidediuretics,frusemide,beta-blockingagents,non-steroidal

anti-inflammatorydrugs,antibiotics,oralhypoglycaemicdrugs,uricosuricagents,oranticoagulants.

ConcomitantadministrationofanalphablockerwithaPDE-5inhibitormayleadtosymptomatichypotensioninsome

patients(seesection4.4SpecialWarningsandSpecialPrecautionsforUse).

Inanopen-label,randomized,placebo-controlledtrialin22healthymalevolunteers,theadministrationofasingle1mg

doseofdoxazosinonday1ofafour-dayregimenoforalcimetidine(400mgtwicedaily)resultedina10%increasein

meanAUCofdoxazosin,andnostatisticallysignificantchangesinmeanCmaxandmeanhalf-lifeofdoxazosin.The

10%increaseinthemeanAUCofdoxazosinwithcimetidineiswithinintersubjectvariation(27%)ofthemeanAUC

fordoxazosinwithplacebo.

Doxazosincanpotentiatethebloodpressureloweringactivityoftheotherhypertensives.

4.6Pregnancyandlactation

Useduringpregnancy:Doxazosincrossestheplacenta.Althoughnoteratogeniceffectswereseeninanimaltesting,

reducedfoetalsurvivalwasobservedatextremelyhighdoses.Thesedoseswereapproximately300timesthe

maximumrecommendedhumandose.Astherearenoadequateandwellcontrolledstudiesinpregnantwomen,the

safetyofCardura’suseduringpregnancyhasnotyetbeenestablished.Accordingly,Cardurashouldbeusedonly

when,intheopinionofthephysician,potentialbenefitsoutweighthepotentialrisks.

Useduringlactation:Contraindicated.Seesection4.3Contraindicationsabove.

4.7Effectsonabilitytodriveandusemachines

Theabilitytodriveorusemachinerymaybeimpaired,especiallywheninitiatingtherapy.Thedrugmayalsocause

drowsiness.Patientsshouldnotdriveoroperatemachineryunlessithasbeenshownnottoaffecttheiralertnessor

dexterity.

4.8Undesirableeffects

Hypertension:Inclinicalstudiesinvolvingpatientswithhypertension,themostcommonreactionsassociatedwith

Carduratherapywereofaposturaltype(rarelyassociatedwithfainting),ornon-specificandincluded:

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GastrointestinalDisorders:Nausea

GeneralDisordersandAdministrationSiteConditions:asthenia,oedema,fatigue,malaise

Nervoussystemdisorders:dizziness,headache,posturaldizziness,somnolence,syncope

Respiratory,ThoracicandMediastinalDisorders:rhinitis

Benignprostatichyperplasia:ExperienceincontrolledclinicaltrialsinBPHindicatesasimilaradverseeventprofile

tothatseeninhypertension.

Inpostmarketingexperience,thefollowingadditionaladverseeventshavebeenreported:

BloodandlymphaticDisorders:Leucopenia,thrombocytopenia

EarandLabyrinthDisorders:tinnitus

EyeDisorders:blurredvision

GastrointestinalDisorders:abdominalpain,constipation,diarrhoea,dyspepsia,flatulence,drymouth,vomiting

GeneralDisordersandAdministrationSiteConditions:pain

HepatobiliaryDisorders:cholestasis,hepatitis,jaundice

ImmuneSystemDisorders:allergicreaction

Investigations:abnormalliverfunctiontests,weightincrease

MetabolismandNutrition:anorexia

MusculoskeletalandConnectiveTissueDisorders:arthralgia,backpain,musclecramps,muscleweakness,myalgia.

NervousSystemDisorders:hypoaesthesia,paraesthesia,tremor

PsychiatricDisorders:agitation,anxiety,depression,insomnia,nervousness

RenalandUrinarySystemDisorders:dysuria,haematuria,micturitiondisorder,micturitionfrequency,nocturia,

polyuria,urinaryincontinence

ReproductiveSystemandBreastDisorder:gynaecomastia,impotence,priapism

Respiratory,ThoracicandMediastinalDisorders:aggravatedbronchospasm,coughing,dyspnoea,epistaxis

SkinandSubcutaneousTissueDisorders:alopecia,pruritus,purpura,skinrash,urticaria

VascularDisorders:Hotflushes,hypotension,posturalhypotension.

Thefollowingadditionaladverseeventshavebeenreportedinmarketingexperienceamongpatientstreatedfor

hypertension.Ingeneral,thesearenotdistinguishablefromsymptomsthatmighthaveoccurredintheabsenceof

exposuretoCardura:bradycardia,tachycardia,palpitations,chestpain,anginapectoris,myocardialinfarction,

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4.9Overdose

Shouldoverdoseleadtohypotension,thepatientshouldbeimmediatelyplacedinasupine,headdownposition.Other

supportivemeasuresmaybeappropriateinindividualcases.Sincedoxazosinishighlyproteinbound,dialysisisnot

indicated.

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,withasignificantincreaseintheHDL/totalcholesterolratioand

trendstoafavourablereductionintotaltriglycerides.

AdministrationofCarduratopatientswithsymptomaticBPHresultsinasignificantimprovementinurodynamicsand

symptoms.TheeffectinBPHisthoughttoresultfromselectiveblockadeofthealpha-adrenoceptorslocatedinthe

muscularstromaandcapsuleoftheprostate,andinthebladderneck.

Doxazosinhasbeenshowntobeaneffectiveblockerofthe1Asubtypeofthealpha-1-adrenoceptorwhichaccountsfor

over70%ofthesubtypesintheprostate.ThisaccountsfortheactioninBPHpatients.

Cardurahasdemonstratedsustainedefficacyandsafetyinthelong-termtreatmentofBPH.

5.2Pharmacokineticproperties

Absorption:followingoraladministrationinhumans(youngmaleadultsortheelderlyofeithersex),doxazosinis

wellabsorbedandapproximatelytwothirdsofthedoseisbioavailable.

Biotransformation/Elimination:Approximately98%ofdoxazosinisprotein-boundinplasma.

DoxazosinisprimarilymetabolizedbyO-demethylationandhydroxylation.

Doxazosinisextensivelymetabolizedinmanandintheanimalspeciestested,withthefaecesbeingthepredominant

routeofexcretion.

Themeanplasmaeliminationhalf-lifeis22hoursthusmakingthedrugsuitableforoncedailyadministration.

Afteroraladministrationofdoxazosintheplasmaconcentrationsofthemetabolitesarelow.Themostactive(6’

hydroxy)metaboliteispresentinmanatonefortiethoftheplasmaconcentrationoftheparentcompoundwhich

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Pharmacokineticstudiesintheelderlyandpatientswithrenalinsufficiencyhaveshownnosignificantalterations

comparedtoyoungerpatientswithnormalrenalfunction.

Thereareonlylimiteddatainpatientswithliverimpairmentandontheeffectsofdrugsknowntoinfluencehepatic

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

administrationofdoxazosinresultedinanincreaseinAUCof43%andadecreaseinapparentoralclearanceof40%.

Aswithanydrugwhollymetabolizedbytheliver,useofCardurainpatientswithimpairedliverfunctionshouldbe

undertakenwithcaution(seesection4.4Specialwarningsandspecialprecautionsforuse).

5.3Preclinicalsafetydata

Preclinicaldatarevealnospecialhazardforhumansbasedonconventionalanimalstudiesinsafetypharmacology,

repeateddosetoxicity,genotoxicityandcarcinogenicity.Forfurtherinformationseesection4.6Pregnancyand

lactation.

6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

Lactose

Microcrystallinecellulose

Sodiumlaurilsulfate

Sodiumstarchglycolate

Magnesiumstearate

6.2Incompatibilities

Notapplicable.

6.3ShelfLife

Theshelf-lifeexpirydateofthisproductshallbethedateshownonthecontainerandouterpackageoftheproducton

themarketinthecountryoforigin.

6.4Specialprecautionsforstorage

Donotstoreabove30 o

6.5Natureandcontentsofcontainer

Blisterpacksof14,28and30tabletscontainedinanoutercardboardcarton.

6.6Specialprecautionsfordisposalofausedmedicinalproductorwastematerialsderivedfrom

suchmedicinalproductandotherhandlingoftheproduct

Thetabletsshouldnotbebroken.

7MARKETINGAUTHORISATIONHOLDER

PCOManufacturingLimited

Unit10,AshbourneBusinessPark

Rath

Ashbourne

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7PARALLELPRODUCTAUTHORISATIONHOLDER

PCOManufacturingLimited

Unit10,AshbourneBusinessPark

Rath

Ashbourne

Co.Meath

8PARALLELPRODUCTAUTHORISATIONNUMBER

PPA0465/063/002

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

Dateoffirstauthorisation:18August2000

Dateoflastrenewal:18August2005

10DATEOFREVISIONOFTHETEXT

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