CARDURA XL

Main information

  • Trade name:
  • CARDURA XL
  • Dosage:
  • 8 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:
  • PPA1562/003/002
  • Authorization date:
  • 31-07-2009
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

CarduraXL8mgProlonged-releasetablets.

2QUALITATIVEANDQUANTITATIVECOMPOSITION

Eachtabletcontains8mgdoxazosin(asmesilate)

Forafulllistofexcipients,seesection6.1.

3PHARMACEUTICALFORM

Prolonged-ReleaseTablet.

ProductimportedfromtheUK

CarduraXL8mgprolonged-releasetabletsarewhiteround,biconvexshapedtabletswithanorificeononeside,

marked‘CXL8’.

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,CarduraXLshouldbeusedwithcareinpatientswithsignificant

existinghepaticdysfunction.(seesection4.4Specialwarningsandprecautionsforuse,andsection5.2

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Useinchildren:ThereisinsufficientexperiencetorecommendtheuseofCarduraXLinchildrenunder12yearsof

age.

4.3Contraindications

CarduraXLiscontraindicatedinpatientswithaknownhypersensitivitytoquinazolines(e.g.doxazosin,prazosin,

terazosin),oranyoftheinertingredientsofCarduraXL.

CarduraXLiscontra-indicatedinpatientswithahistoryofgastro-intestinalobstruction,oesophagealobstruction,or

anydegreeofdecreasedlumendiameterofthegastrointestinaltract.

Useduringlactation:Animalstudieshaveshownthatdoxazosinaccumulatesinbreastmilk.

TheclinicalsafetyofCarduraXLduringlactationhasnotbeenestablished,consequentlyCarduraXLiscontra-

indicatedinnursingmothers.

4.4Specialwarningsandprecautionsforuse

Informationtobegiventothepatient:PatientsshouldbeinformedthatCarduraXLtabletsshouldbeswallowed

whole.Patientsshouldnotchew,divideorcrushthetablets.

InCarduraXL,theactivecompoundissurroundedbyaninert,non-absorbableshellthathasbeenspeciallydesignedto

controlthereleaseofthedrugoveraprolongedperiod.Aftertransitthroughthegastrointestinaltract,whenthisprocess

iscompletedtheemptytabletshelliseliminatedfromthebody.Patientsshouldbeadvisedthattheyshouldnotbe

concernediftheyoccasionallyobserveremainsintheirstoolsthatlooklikeatablet.

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,suchasdrivingoroperationmachinery.

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,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,theadministrationofasingle1mg

doseofdoxazosinonday1ofafour-dayregimenoforalcimetidine(400mgtwicedaily)resultedina10%increasein

meanAUCofdoxazosin,andnostatisticallysignificantchangesinmeanCmaxandmeanhalf-lifeofdoxazosin.The

10%increaseinthemeanAUCfordoxazosinwithcimetidineiswithinintersubjectvariation(27%)ofthemeanAUC

fordoxazosinwithplacebo.

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(Pleaseseesection

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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 Frequency UndesirableEffects

SystemOrganClass

Infectionsandinfestations Common Respiratorytractinfection,urinary

tractinfection

Bloodandlymphaticsystem VeryRare Leukopenia,thrombocytopenia

Disorders

ImmuneSystemDisorders Uncommon Allergicdrugreaction

MetabolismandNutrition Uncommon Anorexia,gout,increasedappetite

Disorders

PsychiatricDisorders Uncommon Anxiety,depression,insomnia

VeryRare Agitation,nervousness

NervousSystemDisorders Common Dizziness,headache,somnolence

Uncommon Cerebrovascularaccident,

hypoesthesia,syncope,tremor

VeryRare Dizzinesspostural,paraesthesia

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,Thoracicand Common Bronchitis,cough,dyspnea,rhinitis

MediastinalDisorders

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VeryRare AggravatedBronchospasm

GastrointestinalDisorders Common Abdominalpain,dyspepsia,drymouth,

nausea

Uncommon Constipation,diarrhoea,flatulence,

vomiting,gastroenteritis

HepatobiliaryDisorders Uncommon Abnormalliverfunctiontests

VeryRare Cholestasis,hepatitis,jaundice

SkinandSubcutaneousTissue Common Pruritus

Disorders

Uncommon Skinrash

VeryRare Alopecia,purpura,urticaria

Musculoskeletaland Common Backpain,myalgia

ConnectiveTissueDisorders

Uncommon Arthralgia

VeryRare Musclecramps,muscleweakness

RenalandUrinaryDisorders Common Cystitis,urinaryincontinence

Uncommon Dysuria,hematuria,micturition

frequency

VeryRare Micturitiondisorder,nocturia,

polyuria,increaseddieresis

ReproductiveSystemand Uncommon Impotence

BreastDisorders

VeryRare Gynecomastia,priapism

Unknown Retrogradeejaculation

GeneralDisordersand Common Asthenia,chestpain,influenza-like

AdministrationSiteConditions symptoms,peripheraledema

Uncommon Pain,facialoedema

VeryRare Fatigue,malaise,

Investigations Uncommon Weightincrease

TheundesirableeffectsforCarduraXLaresimilartothosewithimmediatereleaseCarduratablets.

4.9Overdose

Shouldoverdosageleadtohypotension,thepatientshouldbeimmediatelyplacedinasupine,headdownposition.

Othersupportivemeasuresmaybeappropriateinindividualcases.Sincedoxazosinishighlyproteinbound,dialysisis

notindicated.

5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

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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,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%.

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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

Propyleneglycol.

Blackironoxide(E172)

Ammoniumhydroxide

6.2Incompatibilities

Notapplicable

6.3Shelflife

Theshelflifeexpirydateforthisproductshallbethedateshownonthecontainerandouterpackageoftheproducton

themarketinthecountryoforigin.

6.4Specialprecautionsforstorage

Donotstoreabove30°C.

Storeintheoriginalpackageinordertoprotectfrommoisture.

6.5Natureandcontentsofcontainer

CarduraXL8mgProlongedReleaseTabletsareavailableinoverlabelledcalendarpacksof28tablets.

Aluminiumfoil/aluminiumfoilblisterinacarton.

6.6Specialprecautionsfordisposalofausedmedicinalproductorwastematerialsderivedfrom

suchmedicinalproductandotherhandlingoftheproduct

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7PARALLELPRODUCTAUTHORISATIONHOLDER

LTTPharmaLimited

Unit18

OxleasowRoad

EastMoonMoat

Redditch

Worcestershire

B980RE

UnitedKingdom

8PARALLELPRODUCTAUTHORISATIONNUMBER

PPA1562/3/2

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

Dateoffirstauthorisation:31 st

July2009

10DATEOFREVISIONOFTHETEXT

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