CARDURA XL

Main information

  • Trade name:
  • CARDURA XL
  • Dosage:
  • 8 Base Milligrams
  • Pharmaceutical form:
  • Tablet Prolonged Release
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug

Documents

Localization

  • Available in:
  • CARDURA XL
    Ireland
  • Language:
  • English

Status

  • Source:
  • HPRA - Health Products Regulatory Authority - Ireland
  • Authorization number:
  • PPA1500/001/002
  • Authorization date:
  • 15-05-2009
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

IRISHMEDICINESBOARDACT1995,asamended

MedicinalProducts(ControlofPlacingontheMarket)Regulations,2007,asamended

PPA1500/001/002

CaseNo:2083742

TheIrishMedicinesBoardinexerciseofthepowersconferredonitbytheabovementionedRegulationsherebygrantsto

ProfindWholesaleLtd.

Unit625,KilshaneAvenue,NorthwestBusinessPark,Dublin15,Ireland

anauthorisation,subjecttotheprovisionsofthesaidRegulations,inrespectoftheproduct

CarduraXL8mgProlonged-releaseTablets

theparticularsofwhicharesetoutintheattachedSchedule.Theauthorisationisalsosubjecttothegeneralconditionsasmaybespecifiedin

thesaidRegulationsaslistedonthereverseofthisdocument.

Thisauthorisation,unlesspreviouslyrevoked,shallcontinueinforcefrom28/07/2010.

SignedonbehalfoftheIrishMedicinesBoardthis

________________

Irish Medicines Board

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Date Printed 28/07/2010 CRN 2083742 page number: 1

PartII

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

CarduraXL8mgProlonged-releaseTablets

2QUALITATIVEANDQUANTITATIVECOMPOSITION

Eachtabletcontains8mgdoxazosin(asmesilate).

Forafulllistofexcipients,seeSection6.1.

3PHARMACEUTICALFORM

Prolonged-releasetablets.

ProductimportedfromtheUK:

White,round,biconvexshapedtabletswithanorificeononesidemarkedCXL8andplainonthereverse.

4CLINICALPARTICULARS

4.1TherapeuticIndications

CarduraXLisindicatedforthetreatmentofhypertensionandcanbeusedasasoleagenttocontrolbloodpressurein

hypertensivepatients.

Inpatientsinadequatelycontrolledonsingleantihypertensivetherapy,CarduraXLmaybeusedincombinationwitha

thiazidediuretic,beta-adrenoceptorblockingagent,calciumantagonistoranangiotensin-convertingenzymeinhibitor.

4.2Posologyandmethodofadministration

TheinitialdoseofCarduraXLis4mgoncedaily.Asignificantnumberofpatientswillbecontrolledonthisdose.If

necessary,thedosagemaybeincreasedto8mgoncedailyaccordingtopatientresponse.

Themaximumrecommendeddoseis8mgoncedaily.

CarduraXLcanbetakenwithorwithoutfood.

Thetabletsshouldbeswallowedwholewithasufficientamountofliquid.Theyshouldnotbecutorchewed.

Elderly:Incommonwithotherdrugsofthisclass,thedosageshouldbekeptaslowaspossibleandincrementsmade

underclosesupervision.

Useinrenallyimpairedpatients:Sincethepharmacokineticsofdoxazosinareunchangedinpatientswithrenal

insufficiency,andthereisnoevidencethatdoxazosinaggravatesexistingrenaldysfunction,theusualdosagesmaybe

usedinthesepatients.CarduraXLisnotdialysable.

Useinhepaticallyimpairedpatients:Thereareonlylimiteddatainpatientswithliverimpairmentandontheeffects

ofdrugsknowntoinfluencehepaticmetabolism(e.g.cimetidine).Aswithanydrugmetabolisedwhollybytheliver,

CarduraXLshouldbeusedwithcareinpatientswithsignificantexistinghepaticdysfunction.(seesection4.4Special

warningsandprecautionsforuse,andsection5.2Pharmacokineticproperties).

Useinchildren:ThereisinsufficientexperiencetorecommendtheuseofCarduraXLinchildrenunder12yearsof

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4.3Contraindications

CarduraXLiscontraindicatedinpatientswithaknownhypersensitivitytoquinazolines(e.g.doxazosin,prazosin,

terazosin),oranyoftheinertingredientsofCarduraXL.

CarduraXLiscontra-indicatedinpatientswithahistoryofgastro-intestinalobstruction,oesophagealobstruction,or

anydegreeofdecreasedlumendiameterofthegastro-intestinaltract.

Useduringlactation:Animalstudieshaveshownthatdoxazosinaccumulatesinbreastmilk.Theclinicalsafetyof

CarduraXLduringlactationhasnotbeenestablished,consequentlyCarduraXLiscontra-indicatedinnursingmothers.

4.4Specialwarningsandprecautionsforuse

Informationforthepatient:PatientsshouldbeinformedthatCarduraXLtabletsshouldbeswallowedwhole.

Patientsshouldnotchew,divideorcrushthetablets.

InCarduraXLthemedicationiscontainedwithinanon-absorbableshellthathasbeenspeciallydesignedtoslowly

releasethedrug.Whenthisprocessiscompletedtheemptytabletiseliminatedfromthebody.Patientsshouldbe

advisedthattheyshouldnotbeconcernediftheyoccasionallyobserveinthestoolssomethingthatlookslikeatablet.

UsewithPDE-5Inhibitors:ConcomitantadministrationofanalphablockerwithaPDE-5inhibitorshouldbeused

withcautionasitmayleadtosymptomatichypotensioninsomepatients.NostudieshavebeenconductedwithCardura

Impairedrenalfunction:ThereisnoevidencethatCarduraXLaggravatesrenaldysfunction.However,CarduraXL

dosageintroductionandadjustmentsshouldbecarriedoutwithgreatcare.

Impairedliverfunction:Aswithanydrugwhollymetabolisedbytheliver,CarduraXLshouldbeadministeredwith

cautiontopatientswithevidenceofimpairedhepaticfunction(seesection5.2Pharmacokineticproperties).

PosturalHypotension/Syncope:Aswithallalpha-blockers,averysmallpercentageofpatientshaveexperienced

posturalhypotensionevidencedbydizzinessandweaknessorrarelylossofconsciousness(syncope),particularlywith

thecommencementoftherapy.Wheninstitutingtherapywithanyeffectivealpha-blocker,thepatientshouldbeadvised

howtoavoidsymptomsresultingfromposturalhypotensionandwhatmeasurestotakeshouldtheydevelop.The

patientshouldbecautionedtoavoidsituationswhereinjurycouldresultshoulddizzinessorweaknessoccurduringthe

initiationofCarduraXLtherapy,suchasdrivingoroperationmachinery.

CataractSurgery:The'IntraoperativeFloppyIrisSyndrome'(IFIS,avariantofsmallpupilsyndrome)hasbeen

observedduringcataractsurgeryinsomepatientsonorpreviouslytreatedwithtamsulosin.Isolatedreportshavealso

beenreceivedwithotheralpha-blockersandthepossibilityofaclasseffectcannotbeexcluded.AsIFISmayleadto

increasedproceduralcomplicationsduringthecataractoperationcurrentorpastuseofalpha-1blockersshouldbemade

knowntotheophthalmicsurgeoninadvanceofsurgery

4.5Interactionwithothermedicinalproductsandotherformsofinteraction

Doxazosinishighlyboundtoplasmaproteins(98%).Invitrodatainhumanplasmaindicatesthatdoxazosinhasnoeffecton

proteinbindingofthedrugstested(digoxin,phenytoin,warfarinorindometacin).However,thetheoreticalpotentialfor

interactionwithotherproteinbounddrugsshouldbeborneinmind.Noadverseinteractionshavebeenobservedwiththiazide

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

uricosuricagents,oranticoagulants.

ConcomitantadministrationofanalphablockerwithaPDE-5inhibitormayleadtosymptomatichypotensioninsomepatients

(seesection4.4SpecialWarningsandSpecialPrecautionsforUse).NostudieshavebeenconductedwithCarduraXL.

Inanopen-label,randomized,placebo-controlledtrialin22healthymalevolunteers,theadministrationofasingle1mgdoseof

doxazosinonday1ofafour-dayregimenoforalcimetidine(400mgtwicedaily)resultedina10%increaseinmeanAUCof

doxazosin,andnostatisticallysignificantchangesinmeanCmaxandmeanhalf-lifeofdoxazosin.The10%increaseinthemean

AUCfordoxazosinwithcimetidineiswithinintersubjectvariation(27%)ofthemeanAUCfordoxazosinwithplacebo.

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4.6Pregnancyandlactation

Useduringpregnancy:Doxazosincrossestheplacenta.Althoughnoteratogeniceffectswereseeninanimaltesting,

reducedfoetalsurvivalwasobservedinanimalsatextremelyhighdoses.Thesedoseswereapproximately300times

themaximumrecommendedhumandose.Astherearenoadequateandwell-controlledstudiesinpregnantwomen,the

safetyofCarduraXLduringpregnancyhasnotyetbeenestablished.Accordingly,CarduraXLshouldbeusedonly

when,intheopinionofthephysician,thepotentialbenefitoutweighsthepotentialrisk.

Useduringlactation:Contraindicated.Seesection4.3Contraindicationsabove.

4.7Effectsonabilitytodriveandusemachines

Theabilitytodriveorusemachinerymaybeimpaired,especiallywheninitiatingtherapy.Thedrugmayalsoinduce

drowsiness.Patientsshouldnotdriveoroperatemachineryunlessithasbeenshownnottoaffecttheiralertnessor

dexterity.

4.8Undesirableeffects

Inclinicaltrials,themostcommonreactionsassociatedwithCarduraXLwereofaposturaltype(rarelyassociatedwith

fainting)ornon-specificandincluded:

Cardiacdisorders:palpitation,tachycardia

EarandLabyrinthDisorders:vertigo

GastrointestinalDisorders:abdominalpain,drymouth,nausea

GeneralDisordersandAdministrationSiteConditions:asthenia,chestpain,peripheraloedema

MusculoskeletalandConnectiveTissueDisorders:backpain,myalgia

NervousSystemDisorders:dizziness,headache

Respiratory,ThoracicandMediastinalDisorders:coughing,bronchitis

SkinandSubcutaneousTissueDisorders:pruritis

RenalandUrinaryDisorders:urinaryincontinence,cystitis

VascularDisorders:posturalhypotension

Inpost-marketingexperiencethefollowingadditionaladverseeventshavebeenreported:

BloodandLymphaticDisorders:leucopenia,thrombocytopenia

EarandLabyrinthDisorders:tinnitus

EyeDisorders:blurredvision

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

GeneralDisordersandAdministrationSiteConditions:fatigue,malaise,pain

HepatobiliaryDisorders:cholestasis,hepatitis,jaundice

ImmuneSystemDisorders:allergicreaction

Investigations:abnormalliverfunctiontests,weightincrease

MetabolismandNutrition:anorexia

MusculoskeletalandConnectiveTissueDisorders:arthralgia,musclecramps,muscleweakness

NervousSystemDisorders:posturaldizziness,hypoaesthesia,paraesthesia,syncope,tremor

PsychiatricDisorders:agitation,anxiety,depression,insomnia,nervousness

RenalandUrinaryDisorders:dysuria,haematuria,micturitiondisorder,micturitionfrequency,nocturia,polyuria,

urinaryincontinence

ReproductiveSystemandBreastDisorders:gynaecomastia,impotence,priapism,retrogradeejaculation

Respiratory,ThoracicandMediastinalDisorders:aggravatedbronchospasm,dyspnoea,epistaxis,coughing

SkinandSubcutaneousTissueDisorders:alopecia,purpura,skinrash,urticaria,pruritus

VascularDisorders:hotflushes,hypotension

Thefollowingadditionaladverseeventshavebeenreportedinmarketingexperienceamongpatientstreatedfor

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Ingeneral,thesearenotdistinguishablefromsymptomsthatmighthaveoccurredintheabsenceofexposureto

CarduraXL:bradycardia,tachycardia,palpitations,chestpain,anginapectoris,myocardialinfarction,cerebrovascular

accidentsandcardiacarrhythmias.

TheundesirableeffectsforCarduraXLaresimilartothosewithimmediatereleaseCarduratablets.

4.9Overdose

Shouldoverdosageleadtohypotension,thepatientshouldbeimmediatelyplacedinasupine,headdownposition.

Othersupportivemeasuresmaybeappropriateinindividualcases.Sincedoxazosinishighlyproteinbound,dialysisis

notindicated.

5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

Doxazosinisapotentandselectivepost-junctionalalpha1-adrenoceptorantagonist.

AdministrationofCarduraXLtohypertensivepatientscausesaclinicallysignificantreductioninbloodpressureasa

resultofareductioninsystemicvascularresistance.Thiseffectisthoughttoresultfromselectiveblockadeofthe

alpha-1-adrenoreceptorslocatedinthevasculature.Withoncedailydosing,clinicallysignificantreductionsinblood

pressurearepresentthroughoutthedayandat24hourspostdose.Themajorityofpatientsarecontrolledontheinitial

dose.Inpatientswithhypertension,bloodpressureduringtreatmentwithCarduraXLwassimilarinboththesupine

andstandingposition.

Responderdatafromthe2primaryhypertensionefficacystudies(includingatotalof630doxazosintreatedpatients)

indicatethatthosepatientscontrolledon1mg,2mgor4mgdoxazosinimmediatereleasetabletswouldbeequallywell

controlledon4mgCarduraXL.

Doxazosinhasbeenshowntobefreeofadversemetaboliceffectsandissuitableforuseinpatientswithcoexistent

diabetesmellitus,goutandinsulinresistance.

Doxazosinissuitableforuseinpatientswithcoexistentasthma,leftventricularhypertrophyandinelderlypatients.

Treatmentwithdoxazosinhasbeenshowntoresultinregressionofleftventricularhypertrophy,inhibitionofplatelet

aggregationandenhancedactivityoftissueplasminogenactivator.Additionally,doxazosinimprovesinsulinsensitivity

inpatientswithimpairment.

Doxazosinproducesfavourableeffectsonbloodlipids,withasignificantincreaseintheHDL/totalcholesterolratio

andtrendstoafavourablereductionintotaltriglycerides.Itthereforeconfersanadvantageoverdiureticsandbeta

adrenoceptorblockingagentswhichadverselyaffecttheseparameters.Basedontheestablishedassociationof

hypertensionandbloodlipidswithcoronaryheartdisease,thefavourableeffectsofdoxazosintherapyonbothblood

pressureandlipidsindicateareductioninriskofdevelopingcoronaryheartdisease.

5.2Pharmacokineticproperties

Absorption:Afteroraladministrationoftherapeuticdoses,CarduraXLiswellabsorbedwithpeakbloodlevels

graduallyreachedat8to9hoursafterdosing.Peakplasmalevelsareapproximatelyonethirdofthoseofthesamedose

ofimmediatereleaseCarduratablets.Troughlevelsat24hoursare,however,similar.

ThepharmacokineticcharacteristicsofCarduraXLwillleadtoasmootherplasmaprofile.

Peak/troughratioofCarduraXLislessthanhalfthatofimmediatereleaseCarduratablets.

Atsteady-state,therelativebioavailabilityofdoxazosinfromCarduraXLcomparedtotheimmediatereleaseformwas

54%atthe4mgdoseand59%atthe8mgdose.

PharmacokineticstudieswithCarduraXLintheelderlyhaveshownnosignificantalterationscomparedtoyounger

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Biotransformation/Elimination:Theplasmaeliminationisbiphasicwiththeterminaleliminationhalf-lifebeing22

hoursandhencethisprovidesthebasisforoncedailydosing.Doxazosinisextensivelymetabolisedwith<5%excreted

asunchangeddrug.

PharmacokineticstudieswithimmediatereleaseCardurainpatientswithrenalimpairmentalsoshowednosignificant

alterationscomparedtopatientswithnormalrenalfunction.

Thereareonlylimiteddatainpatientswithliverimpairmentandontheeffectsofdrugsknowntoinfluencehepatic

metabolism(e.g.cimetidine).Inaclinicalstudyin12patientswithmoderatehepaticimpairment,singledose

administrationofdoxazosinresultedinanincreaseinAUCof43%andadecreaseinapparentoralclearanceof30%.

(Seealso4.4Specialwarningsandspecialprecautionsforuse).

Approximately98%ofdoxazosinisprotein-boundinplasma.

DoxazosinisprimarilymetabolisedbyO-demethylationandhydroxylation.

5.3Preclinicalsafetydata

Preclinicaldatarevealnospecialhazardforhumansbasedonconventionalanimalstudiesinsafetypharmacology,

repeateddosetoxicity,genotoxicityandcarcinogenicity.Forfurtherinformationseesection4.6Pregnancyand

lactation.

6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

Polyethyleneoxide

Sodiumchloride

Hypromellose

Redferricoxide(E172)

Titaniumdioxide(E171)

Magnesiumstearate

Celluloseacetate

Macrogol

Pharmaceuticalglaze

Blackironoxide(E172)

Ammoniumhydroxide

Propyleneglycol

6.2Incompatibilities

Notapplicable

6.3ShelfLife

Theshelflifeexpirydateofthisproductisthedateshownontheblisterstripsandoutercartonoftheproductas

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6.4Specialprecautionsforstorage

Donotstoreabove30°C.

Storeintheoriginalpackage.

6.5Natureandcontentsofcontainer

Aluminiumfoilblisterstripsinanover-labelledcardboardcarton.Calendarpacksof28tablets.

6.6Specialprecautionsfordisposalofausedmedicinalproductorwastematerialsderivedfrom

suchmedicinalproductandotherhandlingoftheproduct

Nospecialrequirements

7PARALLELPRODUCTAUTHORISATIONHOLDER

ProfindWholesaleLtd

Unit625,KilshaneAvenue

NorthwestBusinessPark

Dublin15

Ireland

8PARALLELPRODUCTAUTHORISATIONNUMBER

PPA1500/1/2

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

DateofFirstAuthorisation:15thMay2009

10DATEOFREVISIONOFTHETEXT

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