FARMADURA XL

Main information

  • Trade name:
  • FARMADURA XL
  • Dosage:
  • 4 Milligram
  • Pharmaceutical form:
  • Tablet Prolonged Release
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug

Documents

Localization

  • Available in:
  • FARMADURA XL
    Ireland
  • Language:
  • English

Status

  • Source:
  • HPRA - Health Products Regulatory Authority - Ireland
  • Authorization number:
  • PA0822/023/001
  • Authorization date:
  • 11-03-2011
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

FarmaduraXL4mgProlonged–releasetablets.

2QUALITATIVEANDQUANTITATIVECOMPOSITION

Eachtabletcontains4mgdoxazosin(asmesilate).

Forfulllistofexcipients,seesection6.1

3PHARMACEUTICALFORM

Prolonged-releasetablet.

FarmaduraXL4mgprolonged-releasetabletsarewhiteround,biconvexshapedtabletwithanorificeononeside,

marked‘CXL4’.

4CLINICALPARTICULARS

4.1TherapeuticIndications

FarmaduraXLisindicatedforthetreatmentofhypertensionandcanbeusedasasoleagenttocontrolbloodpressure

inhypertensivepatients.

Inpatientsinadequatelycontrolledonsingleantihypertensivetherapy,FarmaduraXLmaybeusedincombinationwith

athiazidediuretic,beta-adrenoceptorblockingagent,calciumantagonistoranangiotensin-convertingenzyme

inhibitor.

4.2Posologyandmethodofadministration

TheinitialdoseofFarmaduraXLis4mgoncedaily.Asignificantnumberofpatientswillbecontrolledonthisdose.If

necessary,thedosagemaybeincreasedto8mgoncedailyaccordingtopatientresponse.

Themaximumrecommendeddoseis8mgoncedaily.

FarmaduraXLcanbetakenwithorwithoutfood.

Thetabletsshouldbeswallowedwholewithasufficientamountofliquid.Theyshouldnotbecutorchewed.

Elderly:Incommonwithotherdrugsofthisclass,thedosageshouldbekeptaslowaspossibleandincrementsmade

underclosesupervision.

Useinrenallyimpairedpatients:Sincethepharmacokineticsofdoxazosinareunchangedinpatientswithrenal

insufficiency,andthereisnoevidencethatdoxazosinaggravatesexisting

renaldysfunction,theusualdosagesmaybeusedinthesepatients.FarmaduraXLisnotdialysable.

Useinhepaticallyimpairedpatients:Thereareonlylimiteddatainpatientswithliverimpairmentandontheeffectsof

drugsknowntoinfluencehepaticmetabolism(e.g.cimetidine).Aswithanydrugmetabolisedwhollybytheliver,

FarmaduraXLshouldbeusedwithcareinpatientswithsignificantexistinghepaticdysfunction.(seesection4.4

Specialwarningsandprecautionsforuse,andsection5.2Pharmacokineticproperties).

Useinchildren:ThereisinsufficientexperiencetorecommendtheuseofFarmaduraXLinchildrenunder12yearsof

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4.3Contraindications

FarmaduraXLiscontraindicatedin:

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

excipients.

Patientswithahistoryoforthostatichypotension.

Patientswithbenignprostatichyperplasiaandconcomitantcongestionoftheupperurinarytract,chronicurinary

tractinfectionorbladderstones.

Patientswithahistoryofgastro-intestinalobstruction,oesophagealobstruction,oranydegreeofdecreasedlumen

diameterofthegastro-intestinaltract.

Duringlactation(pleaseseesection4.6).

Doxazosiniscontraindicatedinhypertensivepatientswithconcomitantbenignprostatichyperplasiawitheither

overflowbladderoranuriawithorwithoutprogressiverenalinsufficiency.

4.4Specialwarningsandprecautionsforuse

Informationtobegiventothepatient:PatientsshouldbeinformedthatFarmaduraXLtabletsshouldbeswallowed

whole.Patientsshouldnotchew,divideorcrushthetablets.

InFarmaduraXL,theactivecompoundissurroundedbyaninert,non-absorbableshellthathasbeenspeciallydesigned

tocontrolthereleaseofthedrugoveraprolongedperiod.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

resultingfromposturalhypotensionandwhatmeasurestotakeshould

theydevelop.Thepatientshouldbecautionedtoavoidsituationswhereinjurycouldresultshoulddizzinessor

weaknessoccurduringtheinitiationofFarmaduraXLtherapy,suchasdrivingoroperatingmachinery.

UseinpatientswithAcuteCardiacConditions:

Aswithanyothervasodilatoryanti-hypertensiveagentitisprudentmedicalpracticetoadvisecautionwhen

administeringdoxazosintopatientswiththefollowingacutecardiacconditions:

pulmonaryoedemaduetoaorticormitralstenosis

heartfailureathighoutput

right-sidedheartfailureduetopulmonaryembolismorpericardialeffusion

leftventricularheartfailurewithlowfillingpressure.

UseinHepaticallyImpairedPatients:Aswithanydrugwhollymetabolisedbytheliver,FarmaduraXLshouldbe

administeredwithparticularcautiontopatientswithevidenceofimpairedhepaticfunction(seesection5.2

Pharmacokineticproperties).Sincethereisnoclinicalexperienceinpatientswithseverehepaticimpairmentusein

thesepatientsisnotrecommended.

UseinpatientswithImpairedrenalfunction:ThereisnoevidencethatFarmaduraXLaggravatesrenaldysfunction.

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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

FarmaduraXL.

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,thesafetyof

FarmaduraXLduringpregnancyhasnotyetbeenestablished.Accordingly,FarmaduraXLshouldbeusedonlywhen,

intheopinionofthephysician,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,themostcommonreactionsassociatedwithFarmaduraXLwereofaposturaltype(rarelyassociated

withfainting)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

Uncommon Epistaxis

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TheundesirableeffectsforFarmaduraXLaresimilartothosewithimmediatereleaseCarduratablets.

4.9Overdose

Shouldoverdosageleadtohypotension,thepatientshouldbeimmediatelyplacedinasupine,headdownposition.

Othersupportivemeasuresmaybeappropriateinindividualcases.Sincedoxazosinishighlyproteinbound,dialysisis

notindicated.

5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

Doxazosinisapotentandselectivepost-junctionalalpha1-adrenoceptorantagonist.

AdministrationofFarmaduraXLtohypertensivepatientscausesaclinicallysignificantreductioninbloodpressureasa

resultofareductioninsystemicvascularresistance.Thiseffectisthoughttoresultfromselectiveblockadeofthe

alpha-1-adrenoreceptorslocatedinthevasculature.Withoncedailydosing,clinicallysignificantreductionsinblood

pressurearepresentthroughoutthedayandat24hourspostdose.Themajorityofpatientsarecontrolledontheinitial

dose.Inpatientswithhypertension,bloodpressureduringtreatmentwithFarmaduraXLwassimilarinboththesupine

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,

increaseddieresis

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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Responderdatafromthe2primaryhypertensionefficacystudies(includingatotalof630doxazosintreatedpatients)

indicatethatthosepatientscontrolledon1mg,2mgor4mgdoxazosinimmediatereleasetabletswouldbeequallywell

controlledon4mgFarmaduraXL.

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,FarmaduraXLiswellabsorbedwithpeakbloodlevelsgradually

reachedat8to9hoursafterdosing.Peakplasmalevelsareapproximatelyonethirdofthoseofthesamedoseof

immediatereleaseCarduratablets.Troughlevelsat24hoursare,however,similar.

ThepharmacokineticcharacteristicsofFarmaduraXLwillleadtoasmootherplasmaprofile.

Peak/troughratioofFarmaduraXLislessthanhalfthatofimmediatereleaseCarduratablets.

Atsteady-state,therelativebioavailabilityofdoxazosinfromFarmaduraXLcomparedtotheimmediatereleaseform

was54%atthe4mgdoseand59%atthe8mgdose.

PharmacokineticstudieswithFarmaduraXLintheelderlyhaveshownnosignificantalterationscomparedtoyounger

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.

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5.3Preclinicalsafetydata

Preclinicaldatarevealnospecialhazardforhumansbasedonconventionalanimalstudiesinsafetypharmacology,

repeateddosetoxicity,genotoxicityandcarcinogency.ForfurtherinformationseeSection4.6Pregnancyand

Lactation.

6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

Polyethyleneoxide

Sodiumchloride

Hypromellose

Redferricoxide(E172)

Titaniumdioxide(E171)

Magnesiumstearate

Celluloseacetate

Macrogol

Pharmaceuticalglaze

Blackironoxide(E172)

Ammoniumhydroxide

Propyleneglycol

6.2Incompatibilities

Notapplicable.

6.3ShelfLife

2years.

6.4Specialprecautionsforstorage

Donotstoreabove30 o

Storeintheoriginalpackageinordertoprotectfrommoisture.

6.5Natureandcontentsofcontainer

FarmaduraXL4mgProlongedReleaseTabletsareavailableascalendarpacksof28tablets.

Aluminiumfoil/aluminiumfoilblisterstripsinacarton.

6.6Specialprecautionsfordisposalofausedmedicinalproductorwastematerialsderivedfrom

suchmedicinalproductandotherhandlingoftheproduct

Nospecialrequirements.

7MARKETINGAUTHORISATIONHOLDER

PfizerHealthcareIreland

9Riverwalk

NationalDigitalPark

CitywestBusinessCampus

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8MARKETINGAUTHORISATIONNUMBER

PA822/23/1

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

Dateoffirstauthorisation:11thMarch2011

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