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:
  • PPA0465/095/002A
  • Authorization date:
  • 17-10-2003
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

CarduraXL8mgProlonged-releaseTablets.

2QUALITATIVEANDQUANTITATIVECOMPOSITION

Eachprolonged-releasetabletcontains8mgdoxazosin(asmesilate).

Forafulllistofexcipients,seesection6.1.

3PHARMACEUTICALFORM

Prolonged-releasetablet.

ProductimportedfromtheNetherlandsandtheUK:

White,round,biconvexshapedtabletswithanorificeinoneside,marked‘CXL8’ononeside,plainontheother.

4CLINICALPARTICULARS

4.1TherapeuticIndications

CarduraXLisindicatedforthetreatmentofhypertensionandcanbeusedasthesoleagenttocontrolbloodpressurein

hypertensivepatients.

Inpatientsinadequatelycontrolledonsingleantihypertensivetherapy,CarduraXLmaybeusedincombinationwitha

thiazidediuretic,beta-adrenoceptorblockingagent,calciumantagonistoranangiotensin-convertingenzymeinhibitor.

4.2Posologyandmethodofadministration

TheinitialdoseofCarduraXLis4mgoncedaily.Asignificantnumberofpatientswillbecontrolledonthisdose.If

necessary,thedosagemaybeincreasedto8mgoncedailyaccordingtopatientresponse.

ThemaximumrecommendeddoseofCarduraXLis8mgoncedaily.

CarduraXLcanbetakenwithorwithoutfood.

Thetabletsshouldbeswallowedwholewithasufficientamountofliquid.Theyshouldnotbecutorchewed.

Elderly:Incommonwithotherdrugsofthisclass,thedosageshouldbekeptaslowaspossibleandincrementsmade

underclosesupervision.

Useinrenally-impairedPatients:Sincethepharmacokineticsofdoxazosinareunchangedinpatientswithrenal

insufficiency,andthereisnoevidencethatdoxazosinaggravatesexistingrenaldysfunction,theusualdosagesmaybe

usedinthesepatients.CarduraXLisnotdialysable.

Useinhepaticallyimpairedpatients:

Thereareonlylimiteddatainpatientswihtliverimpairmentandontheeffectsofdrugsknowntoinfluencehepatic

metabolism(e.g.cimetidine).Aswithanydrugmetabolisedwhollybytheliver,CarduraXLsholdbeusedwithcarein

patientswithsignificantexistinghepaticdysfunction.(seesection4.4Specialwarningsandspecialprecautionsforuse,

andsection5.2Pharmacokineticproperties).

Useinchildren:

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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

InformationforthePatient:PatientsshouldbeinformedthatCarduraXLtabletsshouldbeswallowedwhole.Patients

shouldnotchew,divideorcrushthetablets.

InCarduraXL,themedicationiscontainedwithinanon-absorbableshellthathasbeenspeciallydesignedtoslowly

releasethedrug.Whenthisprocessiscompletedtheemptytabletiseliminatedfromthebody.Patientsshouldbe

advisedthattheyshouldnotbeconcernediftheyoccasionallyobserveinthestoolssomethingthatlookslikeatablet.

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

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UseinpatientswithImpairedrenalfunction:ThereisnoevidencethatCarduraXLaggravatesrenaldysfunction.

However,CarduraXLdosageintroductionandadjustmentsshouldbecarriedoutwithgreatcare.

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(seesection4.4).NostudieshavebeenconductedwithCarduraXL.

Doxazosinishighlyboundtoplasmaproteins(98%).Invitrodatainhumanplasmaindicatesthatdoxazosinhasno

effectonproteinbindingofthedrugstested(digoxin,phenytoin,warfarinorindomethacin)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

Theabilitytodriveorusemachinerymaybeimpaired,especiallywheninitiatingtherapy.Thedrugmayalsoinduce

drowsiness.Patientsshouldnotdriveoroperatemachineryunlessithasbeenshownnottoaffecttheiralertnessor

dexterity.

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

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(seeSection

4.4)

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

Uncommon Epistaxis

VeryRare AggravatedBronchospasm

GastrointestinalDisorders Common Abdominalpain,dyspepsia,drymouth,nausea

Uncommon Constipation,diarrhoea,flatulence,vomiting,

gastroenteritis

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TheundesirableeffectsforCarduraXLaresimilartothosewithimmediatereleaseCarduratablets.

4.9Overdose

Shouldoverdosageleadtohypotension,thepatientshouldbeimmediatelyplacedinasupine,headdownposition.

Othersupportivemeasuresmaybeappropriateinindividualcases.Sincedoxazosinishighlyproteinbound,dialysisis

notindicated.

5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

Doxazosinisapotentandselectivepost-junctionalalpha1-adrenoreceptorantagonist.

AdministrationofCarduraXLtohypertensivepatientscausesaclinicallysignificantreductioninbloodpressureasa

resultofareductioninsystemicvascularresistance.Thiseffectisthoughttoresultfromselectiveblockadeofthe

alpha-1-adrenoreceptorslocatedinthevasculature.Withoncedailydosing,clinicallysignificantreductionsinblood

pressurearepresentthroughoutthedayandat24hourspostdose.Themajorityofpatientsarecontrolledontheinitial

dose.Inpatientswithhypertension,thedecreaseinbloodpressureduringtreatmentwithCarduraXLwassimilarin

boththesittingandstandingposition.

Responderdatafromthe2primaryhypertensionefficacystudies(includingatotalof630doxazosintreatedpatients)

indicatethatthosepatientscontrolledon1mg,2mgor4mgdoxazosinimmediatereleasetabletswouldbeequallywell

controlledonCarduraXL4mgTablets.

Doxazosinhasbeenshowntobefreeofadversemetaboliceffectsandissuitableforuseinpatientswithcoexistent

diabetesmellitus,goutandinsulinresistance.

VeryRare Cholestasis,hepatitis,jaundice

SkinandSubcutaneousTissue

Disorders Common Pruritus

Uncommon Skinrash

VeryRare Alopecia,purpura,urticaria

MusculoskeletalandConnective

TissueDisorders Common Backpain,myalgia

Uncommon Arthralgia

VeryRare Musclecramps,muscleweakness

RenalandUrinaryDisorders Common Cystitis,urinaryincontinence

Uncommon Dysuria,hematuria,micturitionfrequency

VeryRare Micturitiondisorder,nocturia,polyuria,increased

diuresis

ReproductiveSystemandBreast

Disorders Uncommon Impotence

VeryRare Gynecomastia,priapism

Unknown Retrogradeejaculation

GeneralDisordersand

AdministrationSiteConditions Common Asthenia,chestpain,influenza-likesymptoms,

peripheraledema

Uncommon Pain,facialoedema

VeryRare Fatigue,malaise,

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Treatmentwithdoxazosinhasbeenshowntoresultinregressionofleftventricularhypertrophy,inhibitionofplatelet

aggregationandenhancedactivityoftissueplasminogenactivator.Additionally,doxazosinimprovesinsulinsensitivity

inpatientswithimpairment.

Doxazosinproducesfavourableeffectsonbloodlipids,withasignificantincreaseintheHDL/totalcholesterolratio

andtrendstoafavourablereductionintotaltriglycerides.Itthereforeconfersanadvantageoverdiureticsandbeta

adrenoreceptorblockingagentswhichadverselyaffecttheseparameters.Basedontheestablishedassociationof

hypertensionandbloodlipidswithcoronaryheartdisease,thefavourableeffectsofdoxazosintherapyonbothblood

pressureandlipidsindicateareductioninriskofdevelopingcoronaryheartdisease.

5.2Pharmacokineticproperties

Absorption

Afteroraladministrationoftherapeuticdoses,CarduraXLiswellabsorbedwithpeakblodlevelsgraduallyreachedat

8to9hoursafterdosing.Peakplasmalevelsareapproximatelyonethirdofthoseofthesamedoseofimmediate

releaseCarduratablets.Troughlevelsat24hoursare,however,similar.

ThepharmacokineticcharacteristicsofCarduraXLwillleadtoasmootherplasmaprofile.

Peak/troughratioofCarduraXLislessthanhalfthatofimmediatereleaseCarduratablets.

Atsteadystate,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%.

(Seealso4.4SpecialWarningsandPrecautionsforUse).

Approximately98%ofdoxazosinisprotein-boundinplasma.

DoxazosinisprimarilymetabolisedbyO-demethylationandhydroxylation.

5.3Preclinicalsafetydata

Preclinicaldatarevealnospecialhazardforhumansbasedonconventionalanimalstudiesinsafetypharmacology,

repeateddosetoxicity,genotoxicityandcarcinogenicity.Forfurtherinformationseesection4.6Pregnancyand

lactation.

6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

ListofexcipientsforproductsimportedfromtheNetherlandsandtheUK

PropyleneGlycol

Polyethyleneoxide

Sodiumchloride

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Redferricoxide(E172)

Titaniumdioxide(E171)

Magnesiumstearate

Cellacefate

Macrogol

Pharmaceuticalglaze

Blackironoxide(E172)

AmmoniumHydroxide(E527)

6.2Incompatibilities

Notapplicable.

6.3Shelflife

Theshelf-lifeexpirydateofthisproductisthedateshownonthecontainerandouterpackageoftheproductonthe

marketinthecountryoforigin.

6.4Specialprecautionsforstorage

Donotstoreabove30°C.

Storeintheoriginalpackageinordertoprotectfrommoisture.

6.5Natureandcontentsofcontainer

Blisterpackscontaining28or30tablets.

6.6Specialprecautionsfordisposalofausedmedicinalproductorwastematerialsderivedfrom

suchmedicinalproductandotherhandlingoftheproduct

Nospecialrequirements.

7PARALLELPRODUCTAUTHORISATIONHOLDER

PCOManufacturing

Unit10,AshbourneBusinessPark

Rath

Ashbourne

Co.Meath

8PARALLELPRODUCTAUTHORISATIONNUMBER

PPA0465/095/002

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

Dateoffirstauthorizations:17October2003

Dateoflastrenewal:17October2008

10DATEOFREVISIONOFTHETEXT

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