CARDURA XL

Main information

  • Trade name:
  • CARDURA XL
  • Dosage:
  • 4 Milligram
  • 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:
  • PPA1328/079/001
  • Authorization date:
  • 20-03-2009
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

CarduraXL4mgProlonged-releaseTablets

2QUALITATIVEANDQUANTITATIVECOMPOSITION

Eachtabletcontains4mgdoxazosin(asmesilate).

Forafulllistofexcipients,seesection6.1

3PHARMACEUTICALFORM

Prolonged-releaseTablet.

ProductimportedfromtheUK,PolandandSpain:

White,round,biconvexshapedtabletswithanorificeononesidemarked‘CXL4’andplainontheother.

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:Thereareonlylimiteddatainpatientswithliverimpairmentandontheeffectsof

drugsknowntoinfluencehepaticmetabolism(e.g.cimetidine).Aswithanydrugmetabolisedwhollybytheliver,

CarduraXLshouldbeusedwithcareinpatientswithsignificantexistinghepaticdysfunction.(seesection4.4Special

warningsandprecautionsforuse,andsection5.2Pharmacokineticproperties).

Useinchildren:ThereisinsufficientexperiencetorecommendtheuseofCarduraXLinchildrenunder12yearsof

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4.3Contraindications

CarduraXLiscontraindicatedin:

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

excipients.

2)Patientswithahistoryoforthostatichypotension

3)Patientswithbenignprostatichyperplasiaandconcomitantcongestionoftheupperurinarytract,chronicurinary

tractinfectionorbladderstones.

4)Patientswithahistoryofgastro-intestinalobstruction,oesophagealobstruction,oranydegreeofdecreasedlumen

diameterofthegastro-intestinaltract.

5)Duringlactation(pleaseseesection4.6)

Doxazosiniscontraindicatedinhypertensivepatientswithconcomitantbenignprostatichyperplasiawitheither

overflowbladderoranuriawithorwithoutprogressiverenalinsufficiency.

4.4Specialwarningsandprecautionsforuse

Informationtobegiventothepatient:PatientsshouldbeinformedthatCarduraXLtabletsshouldbeswallowedwhole.

Patientsshouldnotchew,divideorcrushthetablets.

InCarduraXL,theactivecompoundissurroundedbyaninert,non-absorbableshellthathasbeenspeciallydesignedto

controlthereleaseofthedrugoveraprolongedperiod.

Aftertransitthroughthegastrointestinaltract,whenthisprocessiscompletedtheemptytabletshelliseliminatedfrom

thebody.Patientsshouldbeadvisedthattheyshouldnotbeconcernediftheyoccasionallyobserveremainsintheir

stoolsthatlooklikeatablet.

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

-leftventricularheartfailurewithlowfillingpressure.

UseinHepaticallyImpairedPatients:Aswithanydrugwhollymetabolisedbytheliver,CarduraXLshouldbe

administeredwithparticularcautiontopatientswithevidenceofimpairedhepaticfunction(seesection5.2

Pharmacokineticproperties).Sincethereisnoclinicalexperienceinpatientswithseverehepaticimpairmentusein

thesepatientsisnotrecommended.

UseinpatientswithImpairedRenalFunction:ThereisnoevidencethatCarduraXLaggravatesrenaldysfunction.

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UsewithPDE-5Inhibitors:Concomitantadministrationofdoxazosinwithphosphodiesterase-5-inhibitors(eg

sildenafil,tadalafil,andvardenafil)shouldbeusedwithcautionasbothdrugshavevasodilatingeffectsandmayleadto

symptomatichypotensioninsomepatients.Toreducetheriskoforthostatichypotensionitisrecommendedtoinitiate

thetreatmentwithphosphodiesterase-5-inhibitorsonlyifthepatientishemodynamicallystabilizedonalpha-blocker

therapy.Furthermore,itisrecommendedtoinitiatephosphodiesterase-5-inhibitortreatmentwiththelowestpossible

doseandtorespecta6-hourtimeintervalfromintakeofdoxazosin.Nostudieshavebeenconductedwithdoxazosin

prolongedreleaseformulations.

UseinpatientsundergoingCataractSurgery:The'IntraoperativeFloppyIrisSyndrome'(IFIS,avariantofsmallpupil

syndrome)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.

4.6Fertility,pregnancyandlactation

Forthehypertensionindication:

Useduringpregnancy:Astherearenoadequateandwell-controlledstudiesinpregnantwomen,thesafetyofCardura

XLduringpregnancyhasnotyetbeenestablished.Accordingly,CarduraXLshouldbeusedonlywhen,intheopinion

ofthephysician,thepotentialbenefitoutweighsthepotentialrisk.

Doxazosincrossestheplacenta.Althoughnoteratogeniceffectswereseeninanimaltesting,reducedfoetalsurvival

wasobservedinanimalsatextremelyhighdoses(seeSection5.3:PreclinicalSafetyData).Thesedoseswere

approximately300timesthemaximumrecommendedhumandose.

Useduringlactation:Doxazosiniscontraindicatedduringlactationasanimalstudieshaveshownthatdoxazosin

accumulatesinmilkoflactatingrats,andthereisnoinformationabouttheexcretionofthedrugintothemilkof

lactatingwomen.TheclinicalsafetyofCarduraduringlactationhasnotbeenestablished;consequentlyCardurais

contra-indicatedinnursingmothers.

Alternatively,mothersshouldstopbreast-feedingwhentreatmentwithdoxazosinisnecessary(Pleaseseesection5.3:

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4.7Effectsonabilitytodriveandusemachines

Theabilitytoengageinactivitiessuchasoperatingmachineryoroperatingamotorvehiclemaybeimpaired,

especiallywheninitiatingtherapy.Thedrugmayalsoinducedrowsiness.Patientsshouldnotdriveoroperate

machineryunlessithasbeenshownnottoaffecttheiralertnessordexterity.

4.8Undesirableeffects

Inclinicaltrials,themostcommonreactionsassociatedwithCarduraXLwereofaposturaltype(rarelyassociatedwith

fainting)ornon-specific.

Frequenciesusedareasfollows:Verycommon1/10,Common1/100and<1/10,Uncommon1/1,000and<1/100,

Rare1/10,000and<1/1,000,Veryrare<1/10,000

MedDRA

SystemOrganClass Frequency UndesirableEffects

Infectionsandinfestations Common Respiratorytractinfection,urinarytractinfection

Bloodandlymphaticsystemdisorders VeryRare Leukopenia,thrombocytopenia

ImmuneSystemDisorders Uncommon Allergicdrugreaction

MetabolismandNutritionDisorders 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(seeSection4.4)

EarandLabyrinthDisorders Common Vertigo

Uncommon Tinnitus

CardiacDisorders Common Palpitation,tachycardia

Uncommon Anginapectoris,myocardialinfarction

VeryRare Bradycardia,cardiacarrhythmias

VascularDisorders Common Hypotension,posturalhypotension

VeryRare HotFlush

Respiratory,ThoracicandMediastinal

Disorders Common Bronchitis,cough,dyspnea,rhinitis

Uncommon Epistaxis

VeryRare AggravatedBronchospasm

GastrointestinalDisorders Common Abdominalpain,dyspepsia,drymouth,nausea

Uncommon Constipation,diarrhoea,flatulence,vomiting,gastroenteritis

HepatobiliaryDisorders Uncommon Abnormalliverfunctiontests

VeryRare Cholestasis,hepatitis,jaundice

SkinandSubcutaneousTissueDisorders Common Pruritus

Uncommon Skinrash

VeryRare Alopecia,purpura,urticaria

MusculoskeletalandConnectiveTissue

Disorders Common Backpain,myalgia

Uncommon Arthralgia

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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,clinicallysignificantreductionsinbloodpressurearepresentthroughoutthedayandat24

hourspostdose.Themajorityofpatientsarecontrolledontheinitialdose.Inpatientswithhypertension,blood

pressureduringtreatmentwithCarduraXLwassimilarinboththesupineandstandingposition.

Responderdatafromthe2primaryhypertensionefficacystudies(includingatotalof630doxazosintreatedpatients)

indicatethatthosepatientscontrolledon1mg,2mgor4mgdoxazosinimmediatereleasetabletswouldbeequallywell

controlledon4mgCarduraXL.

Doxazosinhasbeenshowntobefreeofadversemetaboliceffectsandissuitableforuseinpatientswithcoexistent

diabetesmellitus,goutandinsulinresistance.

Doxazosinissuitableforuseinpatientswithcoexistentasthma,leftventricularhypertrophyandinelderlypatients.

Treatmentwithdoxazosinhasbeenshowntoresultinregressionofleftventricularhypertrophy,inhibitionofplatelet

aggregationandenhancedactivityoftissueplasminogenactivator.Additionally,doxazosinimprovesinsulinsensitivity

inpatientswithimpairment.

Doxazosinproducesfavourableeffectsonbloodlipids,withasignificantincreaseintheHDL/totalcholesterolratio

andtrendstoafavourablereductionintotaltriglycerides.Itthereforeconfersanadvantageoverdiureticsandbeta

RenalandUrinaryDisorders Common Cystitis,urinaryincontinence

Uncommon Dysuria,hematuria,micturitionfrequency

VeryRare Micturitiondisorder,nocturia,polyuria,increaseddiuresis

ReproductiveSystemandBreast

Disorders Uncommon Impotence

VeryRare Gynecomastia,priapism

Unknown Retrogradeejaculation

GeneralDisordersandAdministration

SiteConditions Common Asthenia,chestpain,influenza-likesymptoms,peripheral

oedema

Uncommon Pain,facialoedema

VeryRare Fatigue,malaise,

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Basedontheestablishedassociationofhypertensionandbloodlipidswithcoronaryheartdisease,thefavourable

effectsofdoxazosintherapyonbothbloodpressureandlipidsindicateareductioninriskofdevelopingcoronaryheart

disease.

5.2Pharmacokineticproperties

Absorption:Afteroraladministrationoftherapeuticdoses,CarduraXLiswellabsorbedwithpeakbloodlevels

graduallyreachedat8to9hoursafterdosing.Peakplasmalevelsareapproximatelyonethirdofthoseofthesamedose

ofimmediatereleaseCarduratablets.Troughlevelsat24hoursare,however,similar.

ThepharmacokineticcharacteristicsofCarduraXLwillleadtoasmootherplasmaprofile.

Peak/troughratioofCarduraXLislessthanhalfthatofimmediatereleaseCarduratablets.

Atsteady-state,therelativebioavailabilityofdoxazosinfromCarduraXLcomparedtotheimmediatereleaseformwas

54%atthe4mgdoseand59%atthe8mgdose.

PharmacokineticstudieswithCarduraXLintheelderlyhaveshownnosignificantalterationscomparedtoyounger

patients.

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

Macrogol3350

Shellac

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Blackironoxide(E172)

AmmoniumHydroxide(E527)

PropyleneGlycol

n-butylalcohol

Isopropylalcohol

6.2Incompatibilities

Notapplicable.

6.3Shelflife

Theshelf-lifeexpirydateofthisproductisthedateshownontheblisterandouterpackageoftheproductonthemarket

inthecountryoforigin.

6.4Specialprecautionsforstorage

UKproduct

Donotstoreabove30°C.

Storeintheoriginalpackage.

Polishproduct

Donotstoreabove30°C.

Storeintheoriginalpackageinordertoprotectfrommoisture.

6.5Natureandcontentsofcontainer

UKproduct

Overlabelledblisterpackscontaining28tablets.

Polishproduct

Overlabelledblisterpackscontaining30tablets.

6.6Specialprecautionsfordisposalofausedmedicinalproductorwastematerialsderivedfrom

suchmedicinalproductandotherhandlingoftheproduct

Nospecialrequirements

7PARALLELPRODUCTAUTHORISATIONHOLDER

B&SHealthcare

Unit4

BradfieldRoad

Ruislip

MiddlesexHA40NU

UnitedKingdom

8PARALLELPRODUCTAUTHORISATIONNUMBER

PPA1328/79/1

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

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10DATEOFREVISIONOFTHETEXT

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