DOXAZOSIN DISPHAR

Main information

  • Trade name:
  • DOXAZOSIN DISPHAR
  • Dosage:
  • 4mg Milligram
  • Pharmaceutical form:
  • Tablets
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug

Documents

Localization

  • Available in:
  • DOXAZOSIN DISPHAR
    Ireland
  • Language:
  • English

Status

  • Source:
  • HPRA - Health Products Regulatory Authority - Ireland
  • Authorization number:
  • PA0915/012/003
  • Authorization date:
  • 27-05-2005
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

IRISHMEDICINESBOARDACT1995

MEDICINALPRODUCTS(LICENSINGANDSALE)REGULATIONS,1998

(S.I.No.142of1998)

PA0915/012/003

CaseNo:2021543

TheIrishMedicinesBoardinexerciseofthepowersconferredonitbytheabovementionedRegulationsherebygrantsto

HelsinnBirexTherapeuticsLtd

Damastown,Mulhuddart,Dublin15,Ireland

anauthorisation,subjecttotheprovisionsofthesaidRegulations,inrespectoftheproduct

DOXAZOSINDISPHAR4mgTablets

TheparticularsofwhicharesetoutinPartIandPartIIoftheattachedSchedule.Theauthorisationisalsosubjecttothegeneralconditionsas

maybespecifiedinthesaidRegulationsaslistedonthereverseofthisdocument.

Thisauthorisation,unlesspreviouslyrevoked,shallcontinueinforcefrom25/06/2007until21/04/2010.

SignedonbehalfoftheIrishMedicinesBoardthis

________________

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 27/06/2007 CRN 2021543 page number: 1

PartII

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

DoxazosinDisphar4mgTablets

2QUALITATIVEANDQUANTITATIVECOMPOSITION

EachtabletcontainsDoxazosin4mg(asmesilate).

Forexcipients,see6.1.

3PHARMACEUTICALFORM

Tablet

White,oblongtabletswith'D4'embossedononeside.

4CLINICALPARTICULARS

4.1TherapeuticIndications

Doxazosinisindicatedforfirst-linetreatmentofhypertensionandcanbeusedasmonotherapytocontrolblood

pressureinthesepatients.Thedrugcanalsobeusedincombinationwithathiazidediuretic,beta-blockingagent,

calciumantagonistsorACEinhibitorswhentreatmentwithdiureticsorbeta-blockersalonehasnotgiventhedesired

effectorisunsuitable.

4.2Posologyandmethodofadministration

Hypertension:

Doxazosinisusedinaoncedailyregimen.Theinitialdosageis1mg,andmaybetakeninthemorningorevening.

Thisdoseismaintainedfor1or2weeks.Thedosecanthenbeincreasedto2mgonceadayforanother1or2weeks.

Ifnecessarythedailydosecanthenbegraduallyincreased,observingequalintervals,to4,8and16mgonceaday,

dependingonthepatient'sresponse.Themaximumrecommendeddoseis16mgdaily.Theusualmaintenancedoseis

2-4mgoncedaily.

Useinelderlypatients:

Aswithalldrugsofthisclassdosageshouldbekeptaslowaspossibleandincreasesonlyunderclosesupervision.

Useinrenallyimpairedpatients:

Becausethepharmacokineticsofdoxazosinremainunchangedinpatientswithrenalinsufficiency,andnoevidence

existsthatdoxazosinwillexacerbateanexistingrenalinsufficiency,theapplicationoftheusualdosagesisgenerally

advised.Asinrarecasesanincreasedsensitivitycannotberuledout,amorecautiousapproachwithrespectto

initiatingthetreatmentinsuchpatientsmaybecalledfor.Asdoxazosinishighlyproteinbound,itisnotremovedby

dialysis.

Useinpatientswithhepaticinsufficiency:

Thedoxazosindoseshouldbetitratedparticularlycarefullyinpatientswithimpairedliverfunction.Noclinical

experienceisavailableinpatientswithserioushepaticdysfunction(cf.4.4‘Warningsandprecautionsforuse’).

Useinchildren:

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 27/06/2007 CRN 2021543 page number: 2

recommended.

4.3Contraindications

Doxazosiniscontra-indicatedforpatientswithaknownhypersensitivitytodoxazosin,otherquinazolines(e.g.

prazosin,terazosin)ortoanyoftheexcipientsused.

Doxazosinisnotrecommendedforchildrenundertheageof12,sincesafeconditionsforuseinchildrenhavenot

beendetermined.

Useduringlactation:Safetyduringlactationhasnotbeenfullyestablishedandthereforeiscontra-indicatedin

nursingmothers.

4.4Specialwarningsandprecautionsforuse

Patientsonastrictlow-saltdietorthosetreatedwithdiureticsappeartobemoresensitivetothesideeffectsofan

orthostaticnature.Thepatientsshouldbewarnedtoavoidsituationsinwhichtheycouldbeinjuredifdizzinessor

weaknessshouldoccurduringtheinitialphaseofthedoxazosintreatment.Tominimisetheriskofbloodpressurefall

orsyncopeonposturalchange,thebloodpressureofthepatientsshouldbemonitoredattheinitialperiodoftherapy.

Becauseofitsvasodilatoraction,doxazosinshouldbeusedwithcautioninpatientswithanyofthefollowingcardiac

emergencies:

pulmonaryoedemaduetoaorticormitralstenosis

highoutputcardiacinsufficiency

rightventricularheartfailureduetopulmonaryembolismorpericardialeffusion

leftventricularheartfailurewithlowfillingpressure

Inpatientswithseriouscoronarysufferingatooquickortoodistinctloweringofthebloodpressurecanresultin

worseningofanginalcomplaints.

Useinpatientswithhepaticinsufficiency:

Doxazosinshouldbeusedwithparticularcautioninpatientswithliverfunctionimpairment.Asthereisnoclinical

experienceinpatientswithseverehepaticdysfunction,useinsuchpatientsisnotrecommended.

Cautionisalsorecommendedwhendoxazosinisadministeredconcomitantlywithdrugs,whichmayinfluencehepatic

metabolism(e.g.cimetidine).

Patientswithrarehereditaryproblemsofgalactoseintolerance,theLapplactasedeficiencyorglucose-galactose

malabsorptionshouldnottakethismedicine.

CautionisalsorecommendedwhenDoxazosinisadministeredduringpregnancy.

The'IntraoperativeFloppyIrisSyndrome'(IFIS,avariantofsmallpupilsyndrome)hasbeenobservedduringcataract

surgeryinsomepatientsonorpreviouslytreatedwithtamulosin.Isolatedreportshavealsobeenreceivedwithother

alpha-1blockersandthepossibilityofaclasseffectcannotbeexcluded.AsIFISmayleadtoincreasedprocedural

complicationsduringcataractoperation,currentorpastuseofalpha-1blockersshouldbemadeknowntothe

ophthalmicsurgeoninadvanceofsurgery.

4.5Interactionwithothermedicinalproductsandotherformsofinteraction

Doxazosinincreasesthebloodpressureloweringeffectofotherantihypertensivedrugs.Theantihypertensiveeffect

maybeincreased,whendoxazosinisadministeredconcomitantlywithvasodilatorsandnitrates.

Asforotherantihypertensiveagents,non-steroidalanti-inflammatorydrugsmayreducetheantihypertensiveeffectof

doxazosin.

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 27/06/2007 CRN 2021543 page number: 3

vascularreactionstodopamine,ephedrine,epinephrine,metaraminolandphenylephrine.

Doxazosinmayincreaseplasmareninactivityandurinaryexcretionofvanillylmandelicacid.Thisshouldbe

consideredwheninterpretinglaboratorydata.

4.6Pregnancyandlactation

Useduringpregnancy:

Doxazosincrossestheplacenta.Noteratogeniceffectswereseeninanimaltesting.Astherearenoadequateorwell

controlledstudiesinpregnantwomen,thesafetyofdoxazosinduringpregnancyhasnotbeenestablished.Accordingly,

theproductshouldonlybeusedwhen,intheopinionofthephysician,potentialbenefitoutweighspotentialrisk.

Useduringlactation:

Safetyduringlactationhasnotbeenfullyestablishedandthereforeiscontra-indicatedinnursingmothers.

4.7Effectsonabilitytodriveandusemachines

Theabilitytodriveandtohandlemachinescanbeadverselyinfluenced,especiallyatthestartofthetherapy.Patients

affectedshouldnotdriveoroperatemachinery.

4.8Undesirableeffects

Undesirableeffectsarisemainlyfromthepharmacologicalpropertiesofthepreparation.Mostoftheundesirable

effectshavebeentransientorhavebeentoleratedoncontinuedtreatment.

Common(>1%)

General:Tiredness/nausea,asthenia,headache,chestpain,somnolence,musclecramps.

Cardiovascular:Oedema,palpitations.

CNS:Dizziness,vertigo.

GI:Constipation,dyspepsia.

Respiratory:Shortnessofbreath,nasalcongestion.

Psych:Delayedejaculation,apathy.

Urogenital:Frequentneedtourinate,increasedurination.

Eyes:Accommodationdisturbances.

Lesscommon

General:Facial/generaloedema,syncope,facialredness,fever/shivering,paleness.

Cardiovascular:Posturalhypotension,arrhythmia,peripheralischemia,anginapectoris,tachycardia,myocardial

infarction.

CNS:Tremor,musclestiffness.

GI:Anorexia,increasedappetite.

Skin:Alopecia.

Respiratory:Epistaxis,bronchospasm,cough,pharyngitis.

Metabolism:Thirst,hypokalaemia,gout.

Musculoskeletal:Musclepains,jointswelling/aches,muscleweakness.

Psych:Nightmares,memoryloss,emotionalliability.

Urogenital:Incontinence,urinarydisturbances,dysuria.

Eyes:Abnormaltearflow,photophobia.

Ears:Tinnitus.

Miscellaneous:Disturbedsenseoftaste.

Rare(<0.1%)

Cardiovascular:Cerebrovasculardisturbances.

CNS:Depression,agitation,paresthesia.

Haematological:Decreaseofleukocytesandthrombocytes.

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 27/06/2007 CRN 2021543 page number: 4

Skin:Rash,itching,purpura.

GI:Stomachpains,diarrhoea,vomiting.

Liver:Icterus,increasedliverenzymes,hepatitis.

Metabolism:Hypoglycaemia.

Eyes:Blurredvision.

Miscellaneous:Impotence,priapism,dysgeusia,decreasedbodytemperatureinelderly.

Singlecases

IncreaseofBUNandcreatinine,decreaseoferythrocytes.Posturalhypotensionand,inrarecasessyncopecanoccur

initiallyduringtreatment,especiallyattoohighdoses,butcanalsoariseiftherapyisrestartedafterashortbreak.

4.9Overdose

Ifanoverdosageresultsinhypotension,thepatientshouldbeplacedinalyingpositionimmediately,withhishead

downward.Othersupportingmeasuresshouldbetakenifnecessary(e.g.administrationofplasmaexpandersand

vasopressoragentsincaseofseverehypotension).Renalfunctionshouldbemonitoredand,ifnecessary,supported.

Dialysisisnotcalledforasdoxazosinisprotein-bound.

5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

ATCcode:C02CA04

Doxazosinisaselectiveandcompetitiveantagonistofpostsynapticalpha-1-adrenergicreceptors.

Administrationofdoxazosinwillcauseasignificantreductioninbloodpressureduetodecreasedperipheralvascular

resistance.Followingonce-dailyadministrationaclinicallysignificantreductioninthebloodpressureismaintainedfor

upto24hours.Afteradministrationagradualreductioninbloodpressurewillcomeabout;orthostaticeffectsatthe

startofthetreatmentmayoccur.Maximumreductioninbloodpressurewillbeachievedabout2-6hoursafter

administration.

Inhypertensivepatientsthebloodpressureduringthedoxazosintherapyissimilarinalyingandinastandingposition.

Unlikethenon-selectivealphaadrenergicreceptorblockingagents,notolerancehasbeenobservedafteraprolonged

doxazosintherapy.Anincreaseintheplasmareninactivityandtachycardiahaveonlyinfrequentlybeenobservedafter

acontinuedtherapy.

Inclinicalstudiesdoxazosincausedaslightreductionintheplasmaconcentrationsoftriglycerides,totalcholesterol

andtheLDLfraction.AslightincreaseinHDL/totalcholesterolratio(approximately4%to13%ofbaseline)hasbeen

observed.Theclinicalsignificanceofthesefindingsremainstobeestablished.

Studieswhichinvestigateaneffectoncardiovascularmorbidityormortalityareongoing.

AdministrationofdoxazosintopatientswithsymptomaticBPHresultsinanimprovementofurodynamicsymptoms.

Theeffectisreportedtobeduetoselectiveblockadeofthealpha-adrenoreceptorsinthesmoothmuscleofbladder

neck,prostatecapsuleandurethra.

5.2Pharmacokineticproperties

Followingoraladministration,doxazosinisabsorbedwell.Maximumplasmalevelsarereachedafter2hoursandthe

absolutebioavailabilityisapproximately63%.Doxazosinistolargeextentboundtoplasmaprotein(about98%).The

plasmaeliminationisbiphasic;theterminalhalf-lifeis16-30hourssothatonce-dailyadministrationispossible.

Doxazosinismetabolisedinthelivertoalargeextentandmainlyexcretedinthefaeces,withlessthan5%ofthedose

excretedasunchangeddoxazosin.

Pharmacokinetictestsintheelderlyandinpatientswithrenalinsufficiencyhavenotshownanyimportant

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 27/06/2007 CRN 2021543 page number: 5

patientswithliverfunctiondisorders,andneitherhavetheeffectsbeentestedofmedicinesthatareknowntoinfluence

thelivermetabolism(suchascimetidine).

5.3Preclinicalsafetydata

Noteratogeniceffectswereseeninanimaltesting.

6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

Cellulose,Microcrystalline

Lactose,Anhydrous

SodiumStarchGlycolate,TypeA

MagnesiumStearate

Silica,ColloidalAnhydrous

SodiumLaurilsulfate

6.2Incompatibilities

Notapplicable.

6.3ShelfLife

5years.

6.4Specialprecautionsforstorage

Donotstoreabove30°C.

6.5Natureandcontentsofcontainer

PVC/PVDC-Aluminiumblisterstrips,2,3,5,10,20or50x10tabletsor1,2or7x14tablets.

Notallpacksizesmaybemarketed.

6.6Specialprecautionsfordisposalofausedmedicinalproductorwastematerialsderivedfrom

suchmedicinalproductandotherhandlingoftheproduct

Nospecialrequirements.

7MARKETINGAUTHORISATIONHOLDER

HelsinnBirexTherapeuticsLtd

Damastown

Mulhiddart

Dublin15

Ireland

8MARKETINGAUTHORISATIONNUMBER

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 27/06/2007 CRN 2021543 page number: 6

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

Dateoffirstauthorisation:22 nd

April2005

10DATEOFREVISIONOFTHETEXT

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 27/06/2007 CRN 2021543 page number: 7