DURAGLAN

Main information

  • Trade name:
  • DURAGLAN Tablet Prolonged Release 4mg Base Milligrams
  • Dosage:
  • 4mg Base Milligrams
  • Pharmaceutical form:
  • Tablet Prolonged Release
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug

Documents

Localization

  • Available in:
  • DURAGLAN Tablet Prolonged Release 4mg Base Milligrams
    Ireland
  • Language:
  • English

Status

  • Source:
  • HPRA - Health Products Regulatory Authority - Ireland
  • Authorization number:
  • PA1035/001/001
  • Authorization date:
  • 23-11-2007
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

IRISHMEDICINESBOARDACTS1995AND2006

MEDICINALPRODUCTS(CONTROLOFPLACINGONTHEMARKET)REGULATIONS,2007

(S.I.No.540of2007)

PA1035/001/001

CaseNo:1025972

TheIrishMedicinesBoardinexerciseofthepowersconferredonitbytheabovementionedRegulationsherebygrantsto

JacobsenPharma

VemmingbundStrandvej111,DK-6310,Broadger,Denmark

anauthorisation,subjecttotheprovisionsofthesaidRegulations,inrespectoftheproduct

Duraglan4mgProlongedReleaseTablets

TheparticularsofwhicharesetoutinPartIandPartIIoftheattachedSchedule.Theauthorisationisalsosubjecttothegeneralconditionsas

maybespecifiedinthesaidRegulationsaslistedonthereverseofthisdocument.

Thisauthorisation,unlesspreviouslyrevoked,shallcontinueinforcefrom23/11/2007until22/11/2012.

SignedonbehalfoftheIrishMedicinesBoardthis

________________

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 30/11/2007 CRN 1025972 page number: 1

PartII

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

Duraglan4mgProlongedReleaseTablets

2QUALITATIVEANDQUANTITATIVECOMPOSITION

Eachtabletcontainsdoxazosin4mg(asmesilate)

Forafulllistofexcipients,see6.1

3PHARMACEUTICALFORM

Prolongedreleasetablets

Whiteround,biconvextabletswith‘DL’embossedononeside

4CLINICALPARTICULARS

4.1TherapeuticIndications

DuraglanXLisindicatedforthetreatmentofhypertensionandcanbeusedasasoleagenttocontrolbloodpressurein

hypertensivepatients.

Inpatientsinadequatelycontrolledonsingleantihypertensivetherapy,DuraglanXLtabletsmaybeusedin

combinationwithathiazidediuretic,beta-adrenoceptorblockingagent,calciumantagonistoranantiotensin-converting

enzymeinhibitor.

4.2Posologyandmethodofadministration

TheinitialdoseofDuraglanXLis4mgoncedaily.Asignificantnumberofpatientswillbecontrolledonthisdose.If

necessary,thedosagemaybeincreasedto8mgoncedailyaccordingtopatientresponse.

Themaximumrecommendeddoseis8mgoncedaily.

DuraglanXLcanbetakenwithorwithoutfood.

Thetabletsshouldbeswallowedwholewithasufficientamountofliquid.

Elderly:Incommonwithotherdrugsofthisclass,thedosageshouldbekeptalowaspossibleandincrementsmade

underclosesupervision.

UseinRenallyImpairedPatients:Sincethepharmacokineticsofdoxazosinareunchangedinpatientswithrenal

insufficiency,andthereisnoevidencethatdoxazosinaggravatesexistingrenaldysfunction,theusualdosagemaybe

usedinthesepatients.DuraglanXLisnotdialysable.

UseinHepaticallyImpairedPatients.DuraglanXLshouldbeusedwithcareinpatientswithsignificantexisting

hepaticdysfunction.(Seesection4.4Specialwarningsandspecialprecautionsforuse.)

UseinChildren:ThereisinsufficientexperiencetorecommendtheuseofDuraglanXLinChildrenunder12yearsof

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 30/11/2007 CRN 1025972 page number: 2

4.3Contraindications

DuraglanXLiscontra-indicatedinpatientswithaknownhypersensitivitytoquinazolines(e.g.doxazosin,prazosin,

terazosin)oranyconstituentsofDuraglanXL4mgTablets.

DuraglanXLiscontra-indicatedinpatientswithahistoryofgastro-intestinalobstruction,oesophagealobstruction,or

anydegreeofdecreasedlumendiameterofthegastro-intestinaltract.

Useduringlactation:Animalstudieshaveshownthatdoxazosinaccumulatesinbreastmilk.Theclinicalsafetyof

doxazosinduringlactationhasnotbeenestablished,consequentlyDuraglanXLiscontra-indicatedinnursingmothers.

4.4Specialwarningsandprecautionsforuse

InformationforthePatient:PatientswouldbeinformedthatDuraglanXLshouldbeswallowedwhole.Patientsshould

notchew,divideorcrushthetablets.

InDuraglanXL4mgTabletsthemedicationsiscontainedwithinanon-absorbableshellthathasbeenspecially

designedtoslowlyreleasethedrug.Whenthisprocessiscompletedtheemptytabletiseliminatedfromthebody.

Patientsshouldbeadvisedthattheyshouldnotbeconcernediftheyoccasionallyobserveinthestoolssomethingthat

lookslikeatablet.

UsewithPDE-5Inhibitors:ConcomitantadministrationofanalphablockerwithaPDE-5inhibitorshouldbeused

withcautionasitmayleadtosymptomatichypotensioninsomepatients.NostudieshavebeenconductedwithCardura

ImpairedRenalFunction:Thereisnoevidencethatdoxazosinaggravatesrenaldysfunction.However,DuraglanXL

dosageintroductionandadjustmentshouldbecarriedoutwithgreatcare.

ImpairedLiverfunction:Aswithanydrugwhollymetabolisedbytheliver,DuraglanXLshouldbeadministeredwith

cautioninpatientswithevidenceofimpairedhepaticfunction(see5.2PharmacokineticProperties)

Anexcessivehypotensiveeffectmayoccurinsomepatientsfollowingsoonafterinitialtreatmentofteninpersonswho

haveshownevidenceofoverreactionwithotherantihypertensivesandusuallywiththeinitialdose.Ifisrecommended

thattheinitialdosageshouldbegivenwhenthepatientisnotrequiredtoundertakeanyactivitysuchasdrivingor

operatingmachinery.

4.5Interactionwithothermedicinalproductsandotherformsofinteraction

Dozasosinishighlyboundtoplasmaproteins(98%).Invitrodatainhumanplasmaindicatesthatdoxazosinhasno

effectonproteinbindingofthedrugstested(digoxin,phenytoin,warfarinorindomethacin)however,thetheoretical

potentialforinteractionwithotherproteinbounddrugsshouldbeborneinmind.Noadverseinteractionshavebeen

observedwiththiazidediuretics,frusemide,beta-blockingagents,non-steroidalanti-inflammatorydrugs,antibiotics,

oralhypoglycaemicdrugs,uricosuricagents,oranticoagulants.

ConcomitantadministrationofanalphablockerwithaPDE-5inhibitormayleadtosymptomatichypotensioninsome

patients(seesection4.4SpecialWarningsandSpecialPrecautionsforUse).Nostudieshavebeenconductedwith

DuraglanXL.

Inanopen-label,randomized,placebo-controlledtrialin22healthymalevolunteers,theadministrationofasingle1

mgdoseofdoxazosinonday1ofafour-dayregimenoforalcimetidine(400mgtwicedaily)resultedina10%

increaseinmeanAUCofdoxazosin,andnostatisticallysignificantchangesinmeanCmaxandmeanhalf-lifeof

doxazosin.The10%increaseinthemeanAUCfordoxazosinwithcimetidineiswithinintersubjectvariation(27%)of

themeanAUCfordoxazosinwithplacebo.

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 30/11/2007 CRN 1025972 page number: 3

4.6Pregnancyandlactation

Useduringpregnancy:Doxazosincrossestheplacenta.Althoughnoteratogeniceffectswereseeninanimaltesting,

reducedfoetalsurvivalwasobservedinanimalsatextremelyhighdoses.Thesedoseswereapproximately300times

themaximumrecommendedhumandose.Astherearenoadequateandwellcontrolledstudiesinpregnantwomen,

thesafetyofdoxazosinuseduringpregnancyhasnotyetbeenestablished.Accordingly,DuraglanXLshouldbeused

onlywhen,intheopinionofthephysician,potentialbenefitoutweighspotentialrisk.

Useduringlactation:Contra-indicated.See4.3above.

4.7Effectsonabilitytodriveandusemachines

Theabilitytodriveorusemachinerymaybeimpaired,especiallywheninitiatingtherapy.Thedrugmayalsoinduce

drowsiness.Patientsshouldnotdriveoroperatemachineryunlessithasbeenshownnottoaffecttheiralertnessor

dexterity.

4.8Undesirableeffects

Inclinicaltrials,themostcommonreactionsassociatedwithdoxazosinmodified-releaseformulationswereofa

posturaltype(rarelyassociatedwithfainting)ornon-specificandincluded:

Cardiacdisorders:palpitation,tachycardia

EarandLabyrinthDisorders:vertigo

GastrointestinalDisorders:abdominalpain,drymouth,nausea

GeneralDisordersandAdministrationSiteConditions:asthenia,chestpain,

peripheraloedema

MusculoskeletalandConnectiveTissueDisorders:backpain,myalgia

NervousSystemDisorders:dizziness,headache

Respiratory,ThoracicandMediastinalDisorders:coughing,bronchitis

SkinandSubcutaneousTissueDisorders:pruritis

RenalandUrinaryDisorders:urinaryincontinence,cystitis

VascularDisorders:posturalhypotension

Inpost-marketingexperiencewithimmediatereleasedoxazosinformulations,thefollowingadditionaladverseevents

havebeenreported:

BloodandLymphaticDisorders:leucopenia,thrombocytopenia

EarandLabyrinthDisorders:tinnitus

EyeDisorders:blurredvision

GastrointestinalDisorders:constipation,diarrhoea,dyspepsia,flatulence,vomiting,drymouth

GeneralDisordersandAdministrationSiteConditions:fatigue,malaise,pain

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 30/11/2007 CRN 1025972 page number: 4

ImmuneSystemDisorders:allergicreaction

Investigations:abnormalliverfunctiontests,weightincrease

MetabolismandNutrition:anorexia

MusculoskeletalandConnectiveTissueDisorders:arthralgia,musclecramps,muscleweakness

NervousSystemDisorders:posturaldizziness,hypoaesthesia,paraesthesia,syncope,tremor

PsychiatricDisorders:agitation,anxiety,depression,insomnia,nervousness

RenalandUrinaryDisorders:dysuria,haematuria,micturitiondisorder,micturitionfrequency,nocturia,polyuria,

urinaryincontinence

ReproductiveSystemandBreastDisorders:gynaecomastia,impotence,priapism

Respiratory,ThoracicandMediastinalDisorders:aggravatedbronchospasm,dyspnoea,epistaxis,coughing

SkinandSubcutaneousTissueDisorders:alopecia,purpura,skinrash,urticaria,pruritus

VascularDisorders:hotflushes,hypotension

Analysisofhaematologicdatafromhypertensivepatientsreceivingdoxazosinincontrolledhypertensionclinicaltrials

showedthatthemeanWBCandmeanneutrophilcountsweredecreasedby2.4%and1.0%respectively,comparedto

placebo,aphenomenonseenwithotheralphablockingdrugs.

Thefollowingadditionaladverseeventshavebeenreportedinmarketingexperienceamongpatientstreatedfor

hypertensionwithimmediatereleasedoxazosintablets.Ingeneral,thesearenotdistinguishablefromsymptomsthat

mighthaveoccurredintheabsenceofexposuretodoxazosin:tachycardia,palpitations,chestpain,anginapectoris,

myocardialinfarction,cerebrovascularaccidents,cardiacarrhythmiasandblurredvision.

Theundesirableeffectsfordoxazosinmodified-releaseformulationsaresimilartothosewithimmediaterelease

Doxazosintablets.

4.9Overdose

Shouldoverdosageleadtohypotension,thepatientshouldbeimmediatelyplacedinasupine,headdownposition.

Othersupportivemeasuresmaybeappropriateinindividualcases.Sincedoxazosinishighlyproteinbound,dialysisis

notindicated.

5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

Doxazosinisapotentandselectivepost-junctionalalpha1-adrenoceptorantagonist,

ATCCodeC02CA04 .

Administrationofdoxazosinmodified-releaseformulationstohypertensivepatientscausesaclinicallysignificant

reductioninbloodpressureasaresultofareductioninsystemicvascularresistance.Thiseffectisthoughttoresult

fromselectiveblockadeofthealpha-1-adrenoreceptorslocatedinthevasculature.Withoncedailydosing,clinically

significantreductionsinbloodpressurearepresentthroughoutthedayandat24hourspostdose.Themajorityof

patientsarecontrolledontheinitialdose.Inpatientswithhypertension,bloodpressureduringtreatmentwith

doxazosinmodified-releaseformulationswassimilarinboththesupineandstandingposition.

Responderdatafromthe2primaryhypertensionefficacystudies(includingatotalof630doxazosintreatedpatients)

indicatethatthosepatientscontrolledon1mg,2mg,or4mgdoxazosinimmediatereleasetabletswouldbeequallywell

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 30/11/2007 CRN 1025972 page number: 5

Doxazosinhasbeenshowntobefreeofadversemetaboliceffectsandissuitableforuseinpatientswithcoexistent

diabetesmellitus,goutandinsulinresistance.

Doxazosinissuitableforuseinpatientswithcoexistentasthma,leftventricularhypertrophyandinelderlypatients.

Treatmentwithdoxazosinhasbeenshowntoresultinregressionofleftventricularhypertrophy,inhibitionofplatelet

aggregationandenhancedactivityoftissueplasminogenactivator.

Additionally,doxazosinimprovesinsulinsensitivityinpatientswithimpairment.Doxazosinproducesfavourable

effectsonbloodlipids,withasignificantincreaseintheHDL/totalcholesterolratioandtrendstoafavourable

reductionintotaltriglycerides.

Itthereforeconfersanadvantageoverdiureticsandbetaadrenoceptorblockingagents

Whichadverselyaffecttheseparameters.

Basedontheestablishedassociationofhypertensionandbloodlipidswithcoronaryheartdisease,thefavourable

effectsofdoxazosintherapyonbothbloodpressureandlipidsindicateareductioninriskofdevelopingcoronaryheart

disease.

5.2Pharmacokineticproperties

Absorption

Afteroraladministrationoftherapeuticdoses,doxazosinmodified-releaseformulationsarewellabsorbedwithpeak

bloodlevelsgraduallyreachedat8to9hoursafterdosing.Peakplasmalevelsareapproximatelyonethirdofthoseof

thesamedoseofimmediatereleaseDoxazosintablets.Troughlevelsat24hoursare,however,similar.

Thepharmacokineticcharacteristicsofdoxazosinmodified-releaseformulationswillleadtoasmootherplasmaprofile.

Peak/troughratioofdoxazosinmodified-releaseformulationsislessthanhalfthatofimmediatereleasedoxazosin

tablets.

Atsteady-state,therelativebioavailabilityofdoxazosinfromdoxazosinmodified-releaseformulationscomparedtothe

immediatereleaseformwas54%atthe4mgdoseand59%atthe8mgdose.

Pharmacokineticstudieswithdoxazosinmodified-releaseformulationsintheelderlyhaveshownnosignificant

alterationscomparedtoyoungerpatients.

Biotransformation/Elimination

Theplasmaeliminationisbiphasicwiththeterminaleliminationhalf-lifebeing22hoursandhencethisprovidesthe

basisforoncedailydosing.Doxazosinisextensivelymetabolisedwith<5%excreatedasunchangeddrug.

Pharmacokineticstudieswithimmediatereleasedoxazosininpatientswithrenalimpairmentalsoshowedno

significantalterationscomparedtopatientswithnormalrenalfunction.

Thereareonlylimiteddatainpatientswithliverimpairmentandontheeffectsofdrugsknowntoinfluencehepatic

metabolism(e.g.cimetidine).Inaclinicalstudyin12patientswithmoderatehepaticimpairment,singledose

administrationofdoxazosinresultedinanincreaseinAUCof43%andadecreaseinapparentoralclearanceof30%

(seealso4.4SpecialWarningsandSpecialprecautionsforUse)

Approximately98%ofdoxazosinisprotein-boundinplasma.

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 30/11/2007 CRN 1025972 page number: 6

5.3Preclinicalsafetydata

Preclinicaldatarevealnospecialhazardforhumansbasedonconventionalanimalstudiesinsafetypharmacology,

repeateddosetoxicity,genotoxicityandcarcinogenicity.Forfurtherinformationseesection4.6Pregnancyand

lactation.

6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

TabletCore

Polyethyleneoxide,

Microcrystallinecellulose(E460(i)),

Povidone,

-Tocopherol(E307),

Silica,colloidalanhydrous

Sodiumstearylfumarate

Butylhydroxytoluene(E321)

Coating

Methacrylicacidcopolymer

Macrogol

Titaniumdioxide(E171)

6.2Incompatibilities

Notapplicable

6.3ShelfLife

3years

6.4Specialprecautionsforstorage

Thismedicinalproductdoesnotrequireanyspecialstorageprecautions

6.5Natureandcontentsofcontainer

Duraglanprolongedreleasetabletsareavailableinpacksof28,30and100tablets.

Aluminium/PVdC/PVCblisterstripswithaluminiumfoil.

6.6Specialprecautionsfordisposalofausedmedicinalproductorwastematerialsderivedfrom

suchmedicinalproductandotherhandlingoftheproduct

Nospecialrequirements.

7MARKETINGAUTHORISATIONHOLDER

JacobsenPharma,

Vemmingbund,

Strandvej111,DK6310,Broadger,

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 30/11/2007 CRN 1025972 page number: 7

8MARKETINGAUTHORISATIONNUMBER

PA1035/1/1

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

DateofFirstAuthorisation:23rdNovember2007

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 30/11/2007 CRN 1025972 page number: 8