CARDURA

Main information

  • Trade name:
  • CARDURA Tablets 2 Milligram
  • Dosage:
  • 2 Milligram
  • Pharmaceutical form:
  • Tablets
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug

Documents

Localization

  • Available in:
  • CARDURA Tablets 2 Milligram
    Ireland
  • Language:
  • English

Status

  • Source:
  • HPRA - Health Products Regulatory Authority - Ireland
  • Authorization number:
  • PPA1447/035/001
  • Authorization date:
  • 22-07-2010
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

Cardura2mgTablets

2QUALITATIVEANDQUANTITATIVECOMPOSITION

Eachtabletcontains2.43mgdoxazosinmesilateequivalentto2mgdoxazosin.

Excipients:Containslactosemonohydrate.

Forafulllistofexcipients,seesection6.1.

3PHARMACEUTICALFORM

Tablets

ProductimportedfromItaly:

Whiteoblongbiconvextablets:marked‘CN2’andscoredononesideandmarkedwiththePfizerlogoontheother.

4CLINICALPARTICULARS

4.1TherapeuticIndications

Hypertension:Carduraisindicatedforthetreatmentofhypertensionandcanbeusedasasoleagenttocontrolblood

pressureinhypertensivepatients.

Inpatientsinadequatelycontrolledonsingleantihypertensivetherapy,Carduramaybeusedincombinationwitha

thiazidediuretic,beta-adrenoceptorblockingagent,calciumantagonistoranangiotensin-convertingenzymeinhibitor.

BenignProstaticHyperplasia:Carduraisindicatedasanadjunctinthetreatmentofurinaryoutflowobstructionand

symptomsassociatedwithbenignprostatichyperplasia(BPH).Itmaythereforebeofvalueinpatientsawaitingprostatic

surgeryorforwhomsurgeryisnotpossible.

CarduramaybeusedinBPHpatientswhoareeitherhypertensiveornormotensive.

4.2Posologyandmethodofadministration

Adults:Carduraisusedinaoncedailyregimenandmaybeadministeredinthemorningorevening.

Hypertension:Itisrecommendedthattherapybeinitiatedat1mggivenoncedailyforoneortwoweekstominimise

thepotentialforposturalhypotensionand/orsyncope(seesection4.4Specialwarningsandspecialprecautionsforuse)

Thedosagemaythenbeincreasedto2mgoncedailyforanadditionaloneortwoweeks.Ifnecessarythedailydosage

shouldthenbeincreasedgraduallyatsimilarintervalsto4mg,8mg,andl6mgasdeterminedbypatientresponseto

achievethedesiredreductioninbloodpressure.Theusualdoseis2-4mgoncedaily.

Themaximumdailydoseshouldnotexceed16mg.

Diuretictherapymaybeintroduced,ifrequired.

BenignProstaticHyperplasia:TherecommendedinitialdosageofCardurais1mggivenoncedailytominimisethe

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Dependingontheindividualpatient’surodynamicsandBPHsymptomatology,dosagemaythenbeincreasedto2mgand

thereafterto4mganduptothemaximumrecommendeddoseof8mg.Therecommendedtitrationintervalis1-2weeks.

Theusualrecommendeddoseis2-4mgoncedaily.

Children:ThereisinsufficientexperiencetorecommendtheuseofCardurainchildrenunder12yearsofage.

Elderly:Normaladultdosage.Incommonwithotherdrugsofthisclass,dosageshouldbekeptaslowaspossibleand

incrementsmadeunderclosesupervision.

Patientswithrenalimpairment:Sincethereisnochangeinpharmacokineticsinpatientswithimpairedrenalfunctionthe

usualadultdoseofCarduraisrecommended.Carduraisnotdialysable.

Patientswithhepaticimpairment:Thereareonlylimiteddatainpatientswithliverimpairmentandontheeffectofdrugs

knowntoinfluencehepaticmetabolism(e.g.cimetidine).Aswithanydrugwhollymetabolisedbytheliver,Cardura

shouldbeusedwithcareinpatientswithsignificantexistinghepaticdysfunction(seeSection4.4.Specialwarningsand

precautionsforuse,andsection5.2Pharmacokineticproperties).

4.3Contraindications

Doxazosiniscontraindicatedin:

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

excipients

2)Patientswithahistoryoforthostatichypotension

3)Patientswithbenignprostatichyperplasiaandconcomitantcongestionoftheupperurinarytract,chronicurinary

tractinfectionorbladderstones.

4)Duringlactation(pleaseseesection4.6)

5)Patientswithhypotension(forbenignprostatichyperplasiaindicationonly)

Doxazosiniscontraindicatedasmonotherapyinpatientswitheitheroverflowbladderoranuriawithorwithout

progressiverenalinsufficiency.

4.4Specialwarningsandprecautionsforuse

PosturalHypotension/Syncope:

InitiationofTherapy-Aswithallalpha-blockers,averysmallpercentageofpatientshaveexperiencedpostural

hypotensionevidencedbydizzinessandweakness,orrarelylossofconsciousness(syncope),particularlywiththe

commencementoftherapy(seesection4.2Posologyandmethodofadministration).Therefore,itisprudentmedical

practicetomonitorbloodpressureoninitiationoftherapytominimisethepotentialforposturaleffects.

Wheninstitutingtherapywithanyeffectivealpha-blocker,thepatientshouldbeadvisedhowtoavoidsymptoms

resultingfromposturalhypotensionandwhatmeasurestotakeshouldtheydevelop.Thepatientshouldbecautionedto

avoidsituationswhereinjurycouldresult,shoulddizzinessorweaknessoccurduringtheinitiationofCarduratherapy,

suchasdrivingoroperatingmachinery.

UseinpatientswithAcuteCardiacConditions:

Aswithanyothervasodilatoryanti-hypertensiveagentitisprudentmedicalpracticetoadvisecautionwhen

administeringdoxazosintopatientswiththefollowingacutecardiacconditions:

-pulmonaryoedemaduetoaorticormitralstenosis

-heartfailureathighoutput

-right-sidedheartfailureduetopulmonaryembolismorpericardialeffusion

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UseinHepaticallyImpairedPatients:

Thereareonlylimiteddatainpatientswithliverimpairmentandontheeffectofdrugsknowntoinfluencehepatic

metabolism(e.g.cimetidine).Aswithanydrugwhollymetabolisedbytheliver,Cardurashouldbeadministeredwith

particularcautiontopatientswithevidenceofimpairedhepaticfunction(seesection4.2Posologyandmethodof

administration,andsection5.2Pharmacokineticproperties).

Sincethereisnoclinicalexperienceinpatientswithseverehepaticimpairmentuseinthesepatientsisnot

recommended.

UsewithPDE-5Inhibitors:

Concomitantadministrationofdoxazosinwithphosphodiesterase-5-inhibitors(egsildenafil,tadalafil,andvardenafil)

shouldbedonewithcautionasbothdrugshavevasodilatingeffectsandmayleadtosymptomatichypotensioninsome

patients.Toreducetheriskoforthostatichypotensionitisrecommendedtoinitiatethetreatmentwith

phosphodiesterase-5-inhibitorsonlyifthepatientishemodynamicallystabilizedonalpha-blockertherapy.

Furthermore,itisrecommendedtoinitiatephosphodiesterase-5-inhibitortreatmentwiththelowestpossibledoseandto

respecta6-hourtimeintervalfromintakeofdoxazosin.Nostudieshavebeenconductedwithdoxazosinprolonged

releaseformulations.

UseinpatientswithRenalImpairment:

ThereisnoevidencethatCarduraaggravatesrenaldysfunction.However,Carduradosageintroductionandadjustment

shouldbecarriedoutwithgreatcare.

Useinpatientsundergoingcataractsurgery:

The‘IntraoperativeFloppyIrisSyndrome’(IFIS,avariantofsmallpupilsyndrome)hasbeenobservedduringcataract

surgeryinsomepatientsonorpreviouslytreatedwithtamsulosin.Isolatedreportshavealsobeenreceivedwithother

alpha-1blockersandthepossibilityofaclasseffectcannotbeexcluded.AsIFISmayleadtoincreasedprocedural

complicationsduringthecataractoperationcurrentorpastuseofalpha-1blockersshouldbemadeknowntothe

ophthalmicsurgeoninadvanceofsurgery.

Themeanterminalhalf-lifeofdoxazosinis22hours.Thismaybeprolongedinpatientswithcongestiveheartfailure.

Therateofdoseadjustmentmayneedtobeslowed.

Insomepatientswithleftventricularfailure,thedecreaseinleftventricularfillingassociatedwithvigoroustherapy

mayresultinasignificantfallincardiacoutputandsystemicbloodpressureafteradministrationofdoxazosin.These

effectsshouldbekeptinmindwhenintroducingtherapyandcontinuousadjustmentofdoseused.

Patientswithrarehereditaryproblemsofgalactoseintolerance,theLapplactosedeficiencyorglucose-galactose

malabsorptionshouldnottakethismedicine.

4.5Interactionwithothermedicinalproductsandotherformsofinteraction

ConcomitantadministrationofanalphablockerwithaPDE-5inhibitormayleadtosymptomatichypotensioninsome

patients(seesection4.4SpecialWarningsandSpecialPrecautionsforUse).Nostudieshavebeenconductedwith

doxazosinprolongedreleaseformulations.

Doxazosinishighlyboundtoplasmaproteins(98%).Invitrodatainhumanplasmaindicatesthatdoxazosinhasno

effectonproteinbindingofthedrugstested(digoxin,phenytoin,warfarinorindometacin),however,thetheoretical

potentialforinteractionwithotherproteinbounddrugsshouldbeborneinmind.

Conventionaldoxazosinhasbeenadministeredwithoutanyadversedruginteractioninclinicalexperiencewiththiazide

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

uricosuricagents,andanticoagulants.However,datafromformaldrug/druginteractionstudiesarenotpresent.

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Inanopen-label,randomized,placebo-controlledtrialin22healthymalevolunteers,theadministrationofasingle1

mgdoseofdoxazosinonday1ofafour-dayregimenoforalcimetidine(400mgtwicedaily)resultedina10%

increaseinmeanAUCofdoxazosin,andnostatisticallysignificantchangesinmeanCmaxandmeanhalf-lifeof

doxazosin.The10%increaseinthemeanAUCfordoxazosinwithcimetidineiswithinintersubjectvariation(27%)of

themeanAUCfordoxazosinwithplacebo.

4.6Fertility,pregnancyandlactation

Forthehypertensionindication:

Useduringpregnancy:Doxazosincrossestheplacenta.

Astherearenoadequateandwell-controlledstudiesinpregnantwomen,thesafetyofCarduraduringpregnancyhas

notyetbeenestablished.Accordingly,Cardurashouldbeusedonlywhen,intheopinionofthephysician,thepotential

benefitoutweighsthepotentialrisk.Althoughnoteratogeniceffectswereseeninanimaltesting,reducedfoetal

survivalwasobservedinanimalsatextremelyhighdoses(seeSection5.3:PreclinicalSafetyData).Thesedoseswere

approximately300timesthemaximumrecommendedhumandose.

Useduringlactation:

Doxazosiniscontraindicatedduringlactationasanimalstudieshaveshownthatdoxazosinaccumulatesinmilkof

lactatingrats,andthereisnoinformationabouttheexcretionofthedrugintothemilkoflactatingwomen.Theclinical

safetyofCarduraduringlactationhasnotbeenestablished,consequentlyCarduraiscontra-indicatedinnursing

mothers.

Alternatively,mothersshouldstopbreast-feedingwhentreatmentwithdoxazosinisnecessary(Pleaseseesection5.3:

PreclinicalSafetyData).

Forthebenignprostatichyperplasiaindication:Thissectionisnotapplicable.

4.7Effectsonabilitytodriveandusemachines

Theabilitytodriveorusemachinerymaybeimpaired,especiallywheninitiatingtherapy.Thedrugmayalsoinduce

drowsiness.Patientsshouldnotdriveoroperatemachineryunlessithasbeenshownnottoaffecttheiralertnessor

dexterity.

4.8Undesirableeffects

Hypertension:Inclinicaltrialsinvolvingpatientswithhypertension,themostcommonreactionsassociatedwith

Carduratherapywereofaposturaltype(rarelyassociatedwithfainting)ornon-specific.

Benignprostatichyperplasia:ExperienceincontrolledclinicaltrialsinBPHindicatesasimilaradverseeventprofile

tothatseeninhypertension.

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

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MetabolismandNutrition

Disorders Uncommon gout,increasedappetiteAnorexia

PsychiatricDisorders Uncommon Agitation,depressionAnxiety,insomnia,

nervousness

NervousSystemDisorders Common somnolenceDizziness,headache

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 Bradycardiacardiacarrhythmias

VascularDisorders Common Hypotension,posturalhypotension

VeryRare Hotflushes

Respiratory,Thoracicand

MediastinalDisorders Common Bronchitis,cough,dyspnea,rhinitis

Uncommon Epistaxis

VeryRare Bronchospasm

GastrointestinalDisorders Common Abdominalpain,dyspepsia,drymouth,

nausea,

Uncommon Constipation,flatulence,vomiting,

gastroenteritisdiarrhoea

HepatobiliaryDisorders Uncommon Abnormalliverfunctiontests

VeryRare Cholestasis,hepatitis,jaundice

SkinandSubcutaneousTissue

Disorders Common Pruritus

Uncommon Skinrash,

VeryRare urticariaalopecia,purpura

Musculoskeletaland

ConnectiveTissueDisorders Common Backpain,myalgia

Uncommon Arthralgia,

Rare musclecramps,muscleweakness

RenalandUrinaryDisorders Common Cystitis,urinaryincontinence

Uncommon Dysuria,micturitionfrequency,hematuria

Rare polyuria

VeryRare Increaseddiuresis,micturitiondisorder,

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4.9Overdose

Shouldoverdosageleadtohypotension,thepatientshouldbeimmediatelyplacedinasupine,headdownposition.

Othersupportivemeasuresmaybeappropriateinindividualcases.

Ifthismeasureisinadequate,shockshouldfirstbetreatedwithvolumeexpanders.Ifnecessary,vasopressorshould

thenbeused.Renalfunctionshouldbemonitoredandsupportedasneeded.

Sincedoxazosinishighlyproteinbound,dialysisisnotindicated.

5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

AdministrationofCardurareducesbloodpressureduetoadecreaseinsystemicvascularresistance.Withoncedaily

dosing,clinicallysignificantreductionsinbloodpressurearemaintainedthroughoutthedayandat24hourspost-dose.

Duringtheonsetoftherapy,agradualreductioninbloodpressureoccurs,andorthostaticeffectsarecomparablewith

thoseofotherantihypertensives.

Cardurahasbeenshowntobefreeofadversemetaboliceffectsandissuitableforuseinpatientswithco-existent

diabetesmellitus,insulinresistanceandgout.

Carduraissuitabletouseinpatientswithco-existentasthma,leftventricularhypertrophyandinelderlypatients.

TreatmentwithCardurahasbeenshowntoresultinregressionofleftventricularhypertrophy,inhibitionofplatelet

aggregationandenhancedactivityoftissueplasminogenactivator.Additionally,Carduraimprovesinsulinsensitivity

inpatientswhohaveimpairment.

Carduraproducesfavourableeffectsonbloodlipids,withasignificantincreaseinthehighdensitylipoprotein

(HDL)/totalcholesterolratioandtrendstoafavourablereductionintotaltriglycerides.

AdministrationofCarduratopatientswithsymptomaticBPHresultsinasignificantimprovementinurodynamicsand

symptoms.TheeffectinBPHisthoughttoresultfromselectiveblockadeofthealpha-adrenoceptorslocatedinthe

muscularstromaandcapsuleoftheprostate,andinthebladderneck.

Doxazosinhasbeenshowntobeaneffectiveblockerofthe1Asubtypeofthealpha-1-adrenoceptorwhichaccountsfor

over70%ofthesubtypesintheprostate.ThisaccountsfortheactioninBPHpatients.

ReproductiveSystemand

BreastDisorders Uncommon Impotence

VeryRare Gynecomastia,priapism

Unknown Retrogradeejaculation

GeneralDisordersand

AdministrationSiteConditions Common Asthenia,chestpain,influenza-like

symptoms,peripheraloedema,

Uncommon Pain,facialoedema

VeryRare fatigue,malaise

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5.2Pharmacokineticproperties

Absorption:Followingoraladministrationinhumans(youngmaleadultsortheelderlyofeithersex),doxazosiniswell

absorbedandapproximatelytwothirdsofthedoseisbioavailable.

Biotransformation/Elimination:Approximately98%ofdoxazosinisprotein-boundinplasma.

DoxazosininprimarilymetabolisedbyO-demethylationandhydroxylation.

Doxazosinisextensivelymetabolisedinmanandintheanimalspeciestested,withthefaecesbeingthepredominant

routeofexcretion.

Themeanplasmaeliminationhalflifeis22hoursthusmakingthedrugsuitableforoncedailyadministration.

Afteroraladministrationofdoxazosintheplasmaconcentrationsofthemetabolitesarelow.Themostactive(6'

hydroxy)metaboliteispresentinmanatonefortiethoftheplasmaconcentrationoftheparentcompoundwhich

suggeststhattheantihypertensiveactivityisinthemainduetodoxazosin.

Pharmacokineticstudiesintheelderlyandpatientswithrenalinsufficiencyhaveshownnosignificantalterations

comparedtoyoungerpatientswithnormalrenalfunction.

Thereareonlylimiteddatainpatientswithliverimpairmentandontheeffectsofdrugsknowntoinfluencehepatic

metabolism(e.g.,cimetidine).Inaclinicalstudyin12subjectswithmoderatehepaticimpairment,singledose

administrationofdoxazosinresultedinanincreaseinAUCof43%andadecreaseinapparentoralclearanceof40%.

Aswithanydrugwhollymetabolizedbytheliver,useofCardurainpatientswithimpairedliverfunctionshouldbe

undertakenwithcaution(seesection4.4SpecialWarningsandSpecialPrecautionsforUse).

5.3Preclinicalsafetydata

Preclinicalsafetydatarevealnospecialhazardforhumansbasedonconventionalanimalstudiesinsafety

pharmacology,repeateddosetoxicity,genotoxicityandcarcinogenicity.Forfurtherinformationseesection4.6

Pregnancyandlactation.

6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

Lactosemonohydrate

Magnesiumstearate

Microcrystallinecellulose

Sodiumlaurilsulfate

Sodiumstarchglycolate

6.2Incompatibilities

Notapplicable

6.3Shelflife

Theshelf-lifeexpirydateofthisproductisthedateshownontheblisterstripandoutercartonoftheproductas

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6.4Specialprecautionsforstorage

Donotstoreabove30 °

6.5Natureandcontentsofcontainer

Over-labelledcardboardcartoncontaining3blisterstrips(10tabletsperstrip)

Packsizeof30tablets

6.6Specialprecautionsfordisposalofausedmedicinalproductorwastematerialsderivedfrom

suchmedicinalproductandotherhandlingoftheproduct

Nospecialrequirements.

7PARALLELPRODUCTAUTHORISATIONHOLDER

G&ALicensingLtd

Ballymurray

Co.Roscommon

Ireland

8PARALLELPRODUCTAUTHORISATIONNUMBER

PPA1447/35/1

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

Dateoffirstauthorisation:22 nd

July2010

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