CARDURA XL

Main information

  • Trade name:
  • CARDURA XL
  • Dosage:
  • 8 Milligram
  • Pharmaceutical form:
  • Tablets
  • 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:
  • PPA1473/006/002
  • Authorization date:
  • 20-02-2009
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

IRISHMEDICINESBOARDACTS1995AND2006

MEDICINALPRODUCTS(CONTROLOFPLACINGONTHEMARKET)REGULATIONS,2007

(S.I.No.540of2007)

PPA1473/006/002

CaseNo:2066413

TheIrishMedicinesBoardinexerciseofthepowersconferredonitbytheabovementionedRegulationsherebygrantsto

McDowellPharmaceuticals

4AltonaRoad,Lisburn,N.Ireland,BT275QB

anauthorisation,subjecttotheprovisionsofthesaidRegulations,inrespectoftheproduct

CarduraXL8mgProlonged-releasetablets

TheparticularsofwhicharesetoutinPartIandPartIIoftheattachedSchedule.Theauthorisationisalsosubjecttothegeneralconditionsas

maybespecifiedinthesaidRegulationsaslistedonthereverseofthisdocument.

Thisauthorisation,unlesspreviouslyrevoked,shallcontinueinforcefrom08/12/2009.

SignedonbehalfoftheIrishMedicinesBoardthis

________________

Irish Medicines Board

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Date Printed 08/12/2009 CRN 2066413 page number: 1

PartII

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

CarduraXL8mgProlonged-releasetablets

2QUALITATIVEANDQUANTITATIVECOMPOSITION

Eachtabletcontains8mgdoxazosin(asmesilate).

Forafulllistofexcipients,seesection6.1.

3PHARMACEUTICALFORM

Prolonged-releasetablets.

ProductimportedfromtheUK;

CarduraXL8mgarewhite,round,biconvexshapedtabletswithanorificeononesidemarked‘CXL8’andplainon

theother.

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

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Useinhepaticallyimpairedpatients:Thereareonlylimiteddatainpatientswithliverimpairmentandontheeffectsof

drugsknowntoinfluencehepaticmetabolism(e.g.cimetidine).Aswithanydrugmetabolisedwhollybytheliver,

CarduraXLshouldbeusedwithcareinpatientswithsignificantexistinghepaticdysfunction.(seesection4.4Special

warningsandprecautionsforuse,andsection5.2Pharmacokineticproperties).

Useinchildren:ThereisinsufficientexperiencetorecommendtheuseofCarduraXLinchildrenunder12yearsof

age.

4.3Contraindications

CarduraXLiscontraindicatedin:

1)Patientswithaknownhypersensitivitytoquinazolines(e.g.doxazosin,prazosin,terazosin),oranyof

theexcipients.

2)Patientswithahistoryoforthostatichypotension.

3)Patientswithbenignprostatichyperplasiaandconcomitantcongestionoftheupperurinarytract,

chronicurinarytractinfectionorbladderstones.

4)Patientswithahistoryofgastro-intestinalobstruction,oesophagealobstruction,oranydegreeof

decreasedlumendiameterofthegastro-intestinaltract.

5)Duringlactation(pleaseseesection4.6).

Doxazosiniscontraindicatedinhypertensivepatientswithconcomitantbenignprostatichyperplasiawitheither

overflowbladderoranuriawithorwithoutprogressiverenalinsufficiency.

4.4Specialwarningsandprecautionsforuse

Informationtobegiventothepatient:PatientsshouldbeinformedthatCarduraXLtabletsshouldbeswallowed

whole.Patientsshouldnotchew,divideorcrushthetablets.

InCarduraXL,theactivecompoundissurroundedbyaninert,non-absorbableshellthathasbeenspeciallydesignedto

controlthereleaseofthedrugoveraprolongedperiod.Aftertransitthroughthegastrointestinaltract,whenthis

processiscompletedtheemptytabletshelliseliminatedfromthebody.Patientsshouldbeadvisedthattheyshouldnot

beconcernediftheyoccasionallyobserveremainsintheirstoolsthatlooklikeatablet.

Abnormallyshorttransittimesthroughthegastrointestinaltract(e.g.followingsurgicalresection)couldresultin

incompleteabsorption.Inviewofthelonghalflifeofdoxazosintheclinicalsignificanceofthisisunclear.

PosturalHypotension/Syncope:

Initiationoftherapy-Aswithallalpha-blockers,averysmallpercentageofpatientshaveexperiencedpostural

hypotensionevidencedbydizzinessandweakness,orrarelylossofconsciousness(syncope),particularlywiththe

commencementoftherapy.Therefore,itisprudentmedicalpracticetomonitorbloodpressureoninitiationoftherapy

tominimisethepotentialforposturaleffects.

Wheninstitutingtherapywithanyeffectivealpha-blocker,thepatientshouldbeadvisedhowtoavoidsymptoms

resultingfromposturalhypotensionandwhatmeasurestotakeshouldtheydevelop.Thepatientshouldbecautionedto

avoidsituationswhereinjurycouldresultshoulddizzinessorweaknessoccurduringtheinitiationofCarduraXL

therapy,suchasdrivingoroperatingmachinery.

UseinpatientswithAcuteCardiacConditions:

Aswithanyothervasodilatoryanti-hypertensiveagentitisprudentmedicalpracticetoadvisecautionwhen

administeringdoxazosintopatientswiththefollowingacutecardiacconditions:

-pulmonaryoedemaduetoaorticormitralstenosis

-heartfailureathighoutput

-right-sidedheartfailureduetopulmonaryembolismorpericardialeffusion

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UseinHepaticallyImpairedPatients:Aswithanydrugwhollymetabolisedbytheliver,CarduraXLshouldbe

administeredwithparticularcautiontopatientswithevidenceofimpairedhepaticfunction(seesection5.2

Pharmacokineticproperties).Sincethereisnoclinicalexperienceinpatientswithseverehepaticimpairmentusein

thesepatientsisnotrecommended.

UseinpatientswithImpairedrenalfunction:ThereisnoevidencethatCarduraXLaggravatesrenaldysfunction.

However,CarduraXLdosageintroductionandadjustmentsshouldbecarriedoutwithgreatcare.

UsewithPDE-5Inhibitors:Concomitantadministrationofdoxazosinwithphosphodiesterase-5-inhibitors(e.g.

sildenafil,tadalafil,andvardenafil)shouldbeusedwithcautionasbothdrugshavevasodilatingeffectsandmayleadto

symptomatichypotensioninsomepatients.Toreducetheriskoforthostatichypotensionitisrecommendedtoinitiate

thetreatmentwithphosphodiesterase-5-inhibitorsonlyifthepatientishemodynamicallystabilizedonalpha-blocker

therapy.Furthermore,itisrecommendedtoinitiatephosphodiesterase-5-inhibitortreatmentwiththelowestpossible

doseandtorespecta6-hourtimeintervalfromintakeofdoxazosin.Nostudieshavebeenconductedwithdoxazosin

prolongedreleaseformulations.

UseinpatientsundergoingCataractSurgery:The‘IntraoperativeFloppyIrisSyndrome’(IFIS,avariantofsmall

pupilsyndrome)hasbeenobservedduringcataractsurgeryinsomepatientsonorpreviouslytreatedwithtamsulosin.

Isolatedreportshavealsobeenreceivedwithotheralpha-1blockersandthepossibilityofaclasseffectcannotbe

excluded.AsIFISmayleadtoincreasedproceduralcomplicationsduringthecataractoperationcurrentorpastuseof

alpha-1blockersshouldbemadeknowntotheophthalmicsurgeoninadvanceofsurgery

4.5Interactionwithothermedicinalproductsandotherformsofinteraction

ConcomitantadministrationofanalphablockerwithaPDE-5inhibitormayleadtosymptomatichypotensioninsome

patients(seesection4.4SpecialWarningsandSpecialPrecautionsforUse).Nostudieshavebeenconductedwith

CarduraXL.

Doxazosinishighlyboundtoplasmaproteins(98%).Invitrodatainhumanplasmaindicatesthatdoxazosinhasno

effectonproteinbindingofthedrugstested(digoxin,phenytoin,warfarinorindometacin).However,thetheoretical

potentialforinteractionwithotherproteinbounddrugsshouldbeborneinmind.

Conventionaldoxazosinhasbeenadministeredwithoutanyadversedruginteractionsinclinicalexperiencewith

thiazidediuretics,furosemide,beta-blockingagents,non-steroidalanti-inflammatorydrugs,antibiotics,oral

hypoglycaemicdrugs,uricosuricagents,oranticoagulants.However,datafromformaldrug/druginteractionstudiesare

notpresent.

Doxazosincanpotentiatethebloodpressureloweringactivityofotheralpha-blockersandotherantihypertensives.

Inanopen-label,randomized,placebo-controlledtrialin22healthymalevolunteers,theadministrationofasingle1

mgdoseofdoxazosinonday1ofafour-dayregimenoforalcimetidine(400mgtwicedaily)resultedina10%

increaseinmeanAUCofdoxazosin,andnostatisticallysignificantchangesinmeanCmaxandmeanhalf-lifeof

doxazosin.The10%increaseinthemeanAUCfordoxazosinwithcimetidineiswithinintersubjectvariation(27%)of

themeanAUCfordoxazosinwithplacebo.

4.6Pregnancyandlactation

Forthehypertensionindication:

Useduringpregnancy:Astherearenoadequateandwell-controlledstudiesinpregnantwomen,thesafetyofCardura

XLduringpregnancyhasnotyetbeenestablished.Accordingly,CarduraXLshouldbeusedonlywhen,intheopinion

ofthephysician,thepotentialbenefitoutweighsthepotentialrisk.

Doxazosincrossestheplacenta.Althoughnoteratogeniceffectswereseeninanimaltesting,reducedfoetalsurvival

wasobservedinanimalsatextremelyhighdoses(seeSection5.3:PreclinicalSafetyData).Thesedoseswere

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Useduringlactation:Doxazosiniscontraindicatedduringlactationasanimalstudieshaveshownthatdoxazosin

accumulatesinmilkoflactatingrats,andthereisnoinformationabouttheexcretionofthedrugintothemilkof

lactatingwomen.TheclinicalsafetyofCarduraduringlactationhasnotbeenestablished,consequentlyCardurais

contra-indicatedinnursingmothers.

Alternatively,mothersshouldstopbreast-feedingwhentreatmentwithdoxazosinisnecessary(Pleaseseesection5.3:

PreclinicalSafetyData).

4.7Effectsonabilitytodriveandusemachines

Theabilitytoengageinactivitiessuchasoperatingmachineryoroperatingamotorvehiclemaybeimpaired,

especiallywheninitiatingtherapy.Thedrugmayalsoinducedrowsiness.Patientsshouldnotdriveoroperate

machineryunlessithasbeenshownnottoaffecttheiralertnessordexterity.

4.8Undesirableeffects

Inclinicaltrials,themostcommonreactionsassociatedwithCarduraXLwereofaposturaltype(rarelyassociatedwith

fainting)ornon-specific.

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,urinarytract

infection

Bloodandlymphaticsystem

disorders VeryRare Leukopenia,thrombocytopenia

ImmuneSystemDisorders Uncommon Allergicdrugreaction

MetabolismandNutrition

Disorders Uncommon Anorexia,gout,increasedappetite

PsychiatricDisorders Uncommon Anxiety,depression,insomnia

VeryRare Agitation,nervousness

NervousSystemDisorders Common Dizziness,headache,somnolence

Uncommon Cerebrovascularaccident,hypoesthesia,

syncope,tremor

VeryRare Dizzinesspostural,paresthesia

EyeDisorders VeryRare Blurredvision

Unknown Introperativefloppyirissyndrome(see

Section4.4)

EarandLabyrinthDisorders Common Vertigo

Uncommon Tinnitus

CardiacDisorders Common Palpitation,tachycardia

Uncommon Anginapectoris,myocardialinfarction

VeryRare Bradycardia,cardiacarrhythmias

VascularDisorders Common Hypotension,posturalhypotension

VeryRare HotFlush

Respiratory,Thoracicand

MediastinalDisorders Common Bronchitis,cough,dyspnea,rhinitis

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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

VeryRare AggravatedBronchospasm

GastrointestinalDisorders Common Abdominalpain,dyspepsia,drymouth,

nausea

Uncommon Constipation,diarrhoea,flatulence,

vomiting,gastroenteritis

HepatobiliaryDisorders Uncommon Abnormalliverfunctiontests

VeryRare Cholestasis,hepatitis,jaundice

SkinandSubcutaneousTissue

Disorders Common Pruritus

Uncommon Skinrash

VeryRare Alopecia,purpura,urticaria

Musculoskeletaland

ConnectiveTissueDisorders Common Backpain,myalgia

Uncommon Arthralgia

VeryRare Musclecramps,muscleweakness

RenalandUrinaryDisorders Common Cystitis,urinaryincontinence

Uncommon Dysuria,hematuria,micturitionfrequency

VeryRare Micturitiondisorder,nocturia,polyuria,

increaseddiuresis

ReproductiveSystemand

BreastDisorders Uncommon Impotence

VeryRare Gynecomastia,priapism

Unknown Retrogradeejaculation

GeneralDisordersand

AdministrationSiteConditions Common Asthenia,chestpain,influenza-like

symptoms,peripheraledema

Uncommon Pain,facialoedema

VeryRare Fatigue,malaise,

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Doxazosinhasbeenshowntobefreeofadversemetaboliceffectsandissuitableforuseinpatientswithcoexistent

diabetesmellitus,goutandinsulinresistance.

Doxazosinissuitableforuseinpatientswithcoexistentasthma,leftventricularhypertrophyandinelderlypatients.

Treatmentwithdoxazosinhasbeenshowntoresultinregressionofleftventricularhypertrophy,inhibitionofplatelet

aggregationandenhancedactivityoftissueplasminogenactivator.Additionally,doxazosinimprovesinsulin

sensitivityinpatientswithimpairment.

Doxazosinproducesfavourableeffectsonbloodlipids,withasignificantincreaseintheHDL/totalcholesterolratio

andtrendstoafavourablereductionintotaltriglycerides.Itthereforeconfersanadvantageoverdiureticsandbeta

adrenoceptorblockingagentswhichadverselyaffecttheseparameters.Basedontheestablishedassociationof

hypertensionandbloodlipidswithcoronaryheartdisease,thefavourableeffectsofdoxazosintherapyonbothblood

pressureandlipidsindicateareductioninriskofdevelopingcoronaryheartdisease.

5.2Pharmacokineticproperties

Absorption

Afteroraladministrationoftherapeuticdoses,CarduraXLiswellabsorbedwithpeakbloodlevelsgraduallyreachedat

8to9hoursafterdosing.Peakplasmalevelsareapproximatelyonethirdofthoseofthesamedoseofimmediate

releaseCarduratablets.Troughlevelsat24hoursare,however,similar.

ThepharmacokineticcharacteristicsofCarduraXLwillleadtoasmootherplasmaprofile.

Peak/troughratioofCarduraXLislessthanhalfthatofimmediatereleaseCarduratablets.

Atsteady-state,therelativebioavailabilityofdoxazosinfromCarduraXLcomparedtotheimmediatereleaseformwas

54%atthe4mgdoseand59%atthe8mgdose.

PharmacokineticstudieswithCarduraXLintheelderlyhaveshownnosignificantalterationscomparedtoyounger

patients.

Biotransformation/Elimination

Theplasmaeliminationisbiphasicwiththeterminaleliminationhalf-lifebeing22hoursandhencethisprovidesthe

basisforoncedailydosing.Doxazosinisextensivelymetabolisedwith<5%excretedasunchangeddrug.

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

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6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

Polyethyleneoxide

Sodiumchloride

Hypromellose

Redferricoxide(E172)

Titaniumdioxide(E171)

Magnesiumstearate

Celluloseacetate

Macrogol

Pharmaceuticalglaze

Blackironoxide(E172)

Ammoniumhydroxide

PropyleneGlycol

6.2Incompatibilities

Notapplicable

6.3ShelfLife

Theshelflifeexpirydateofthisproductshallbethedateshownonthecontainerandouterpackageoftheproducton

themarketinthecountryoforigin.

6.4Specialprecautionsforstorage

Donotstoreabove30°C.

Storeintheoriginalpackage.

6.5Natureandcontentsofcontainer

Aluminiumfoilblisterstripsinacardboardcarton.Calendarpacksof28tablets.

6.6Specialprecautionsfordisposalofausedmedicinalproductorwastematerialsderivedfrom

suchmedicinalproductandotherhandlingoftheproduct

Nospecialrequirements.

7ParallelProductAuthorisationHolder

McDowellPharmaceuticals

4AltonaRoad,

Lisburn

NIrelandBT275QB

8ParallelProductAuthorisationNumber

PPA1473/6/2

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

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10DATEOFREVISIONOFTHETEXT

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