DOXATAN

Main information

  • Trade name:
  • DOXATAN Tablets 1mg Milligram
  • Dosage:
  • 1mg Milligram
  • Pharmaceutical form:
  • Tablets
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug

Documents

Localization

  • Available in:
  • DOXATAN Tablets 1mg Milligram
    Ireland
  • Language:
  • English

Status

  • Source:
  • HPRA - Health Products Regulatory Authority - Ireland
  • Authorization number:
  • PA0593/020/001
  • Authorization date:
  • 21-01-2000
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

Doxatan1mgTablets

2QUALITATIVEANDQUANTITATIVECOMPOSITION

Eachtabletcontains1mgdoxazosin(asmesilate).

Excipients:Eachtabletcontains:40mglactose.

Forafulllistofexcipients,seesection6.1

3PHARMACEUTICALFORM

Tablets.

White,roundconvextablet,embossed‘D1’ononeside

4CLINICALPARTICULARS

4.1TherapeuticIndications

Doxatan1mgTabletsareindicatedforthetreatmentofessentialhypertension.

4.2Posologyandmethodofadministration

Unlessprescribedotherwise,thefollowingdosageregimenisrecommended:

Starttherapywith1mgofdoxazosinoncedaily.Dependingontheindividualpatient'sbloodpressureresponse,dosage

may,after12weeks,beincreasedto2mgofdoxazosinoncedaily,ifnecessary,thento4mgofdoxazosinoncedaily,

andeventuallyto8mgofdoxazosinoncedaily.

Averagedailydoseformaintenancetherapy:24mgofdoxazosinoncedaily.

Maximumdailydose:16mgofdoxazosin.

Useinelderlypeopleandpatientswithrenalinsufficiency:

Asthepharmacokineticpropertiesofdoxazosinareunchangedinelderlypatientsandthosewithrenalinsufficiency,

thesepatientscanbetreatedwiththeusualdose.

However,dosageshouldbekeptaslowaspossibleandincrementsmadeunderclosesupervision.

Asdoxazosinishighlyproteinbound,itisnotremovedbydialysis.

Useinpatientswithhepaticinsufficiency:

Thedoxazosindoseshouldbetitratedparticularlycarefullyinpatientswithimpairedliverfunction.Noclinicalpractice

experienceisavailableinpatientswithserioushepaticdysfunction(seesection4.4).

Doxazosintabletscanbeusedasmonotherapyorincombinationwithathiazidediuretic,beta-blockingagentswhen

treatmentwiththesealonehasnotgiventhedesiredeffectorisunsuitable.

Thetabletsshouldbetakenwithasufficientamountofwaterinthemorning.Thedurationoftherapywillbedecided

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4.3Contraindications

Doxatan1mgTabletsarecontra-indicated

inpatientswithknownhypersensitivitytoitsactiveingredient,doxazosin,andotherquinazolines(egprazosin,

terazosin)ortoanyoftheexcipients.

duringlactation(pleaseseesection4.6).

inpatientswithahistoryoforthostatichypotension

inpatientswithbenignprostatichyperplasiaandconcomitantcongestionoftheupperurinarytract,chronic

urinarytractinfectionorbladderstones.

asmonotherapyinpatientswitheitheroverflowbladderoranuriawithorwithoutprogressiverenal

insufficiency.

4.4Specialwarningsandprecautionsforuse

InitiationofTherapy:

Intheinitialphaseoftherapy,patientsmayexperiencecirculatorydisturbanceswithatendencyforbloodpressurefall

onposturalchange(orthostatichypotension)evidencedbydizzinessandweakness,orrarelylossofconsciousness

(syncope).Tominimisetheriskofbloodpressurefallonposturalchange,patientsshouldbemonitoredatthestartof

therapy.Asthelikelihoodofsuchresponsesisgreaterwithahigherthanrecommendedstartingdose,the

recommendeddosageregimenshouldbefollowedcarefully.Thepatientshouldbecautionedtoavoidsituationswhere

injurycouldresultshoulddizzinessorweaknessoccurduringtheinitiationofdoxazosintherapy.

Patientsonsodium-lowdietortreatedwithdiureticsseemmoresensitiveforthepotentialforposturaleffects.

Useinpatientsundergoingcataractsurgery:

The‘IntraoperativeFloppyIrisSyndrome‘(IFIS,avariantofsmallpupilsyndrome)hasbeenobservedduringcataract

surgeryinsomepatientsonorpreviouslytreatedwithtamsulosin.Isolatedreportshavealsobeenreceivedwithother

alpha-1blockersandthepossibilityofaclasseffectcannotbeexcluded.AsIFISmayleadtoincreasedprocedural

complicationsduringthecataractoperationcurrentorpastuseofalpha-1blockersshouldbemadeknowntothe

ophthalmicsurgeoninadvanceofsurgery.

UseinpatientswithAcuteCardiacConditions:

Becauseofitsvasodilatoraction,doxazosinshouldbeusedwithcautioninpatientswithanyofthefollowingcardiac

emergencies:

pulmonaryoedemaduetoaorticormitralstenosis

highoutputcardiacinsufficiency

rightventricularheartfailureduetopulmonaryembolismorpericardialeffusion

leftventricularheartfailurewithlowfillingpressure.

Cautionisalsorecommended,whendoxazosinisadministeredconcomitantlywithdrugs,whichmayinfluencehepatic

metabolism(eg.cimetidine).

UsewithPDE-5inhibitors:Concomitantuseofphosphodiesterase-5inhibitors(e.g.sildenafil,tadalafil,vardenafil)and

doxazosinmayleadtosymptomatichypotensioninsomepatients.Inordertominimisetheriskfordevelopingpostural

hypotensionthepatientshouldbestableonthealpha-blockertherapybeforeinitiatinguseofphosphodiesterase-5-

inhibitors.

Useinpatientswithhepaticinsufficiency:

Doxazosinshouldbeusedwithparticularcautioninpatientswithliverfunctionimpairment.Asthereisnoclinical

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Useinchildren:

Asthereisinadequateclinicalpracticeexperienceinchildren,useofDoxatan1mgTabletsinchildrenisnot

recommended.

Doxatan1mgTabletscontainlactose.Patientswithrarehereditaryproblemsofgalactoseintolerance,theLapplactase

deficiencyorglucose-galactosemalabsorptionshouldnottakethismedicinalproduct.

4.5Interactionwithothermedicinalproductsandotherformsofinteraction

Concomitantuseofphosphodiesterase-5inhibitors(e.g.sildenafil,tadalafil,vardenafil)anddoxazosinmayleadto

symptomatichypotensioninsomepatients(seesection4.4).

Doxatan1mgTabletsincreasethebloodpressureloweringeffectofotherantihypertensivedrugs.

Theantihypertensiveeffectmaybeincreased,whendoxazosinisadministeredconcomitantlywithvasodilatorsand

nitrates.

Most(98%)ofplasmadoxazosinisproteinbound.Invitrodatainhumanplasmaindicatethatdoxazosinhasnoeffect

onproteinbindingofdigoxin,warfarin,phenytoinorindometacin.

Asforotherantihypertensiveagents,non-steroidalantirheumaticsorestrogensmayreducetheantihypertensiveeffect

ofdoxazosin.

Sympathomimeticsmayreducetheantihypertensiveeffectofdoxazosin;doxazosinmayreducebloodpressureand

vascularreactionstodopamine,ephedrine,epinephrine,metaramizol,methoxamineandphenylephrine.

Conventionaldoxazosinhasbeenadministeredwithoutanyadversedruginteractioninclinicalexperiencewiththiazide

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

uricosuricagents,andanticoagulants.However,datafromformaldrug/druginteractionstudiesarenotpresent.

Inanopen-label,randomized,placebo-controlledtrialin22healthymalevolunteers,theadministrationofasingle1

mgdoseofdoxazosinonday1ofafour-dayregimenoforalcimetidine(400mgtwicedaily)resultedina10%

increaseinmeanAUCofdoxazosin,andnostatisticallysignificantchangesinmeanCmaxandmeanhalf-lifeof

doxazosin.The10%increaseinthemeanAUCfordoxazosinwithcimetidineiswithinintersubjectvariation(27%)of

themeanAUCfordoxazosinwithplacebo.

Doxazosinmayincreaseplasmareninactivityandurinaryexcretionofvanillylmandelicacid.Thisshouldbe

consideredwheninterpretinglaboratorydata.

4.6Fertility,pregnancyandlactation

Astherearenoadequateandwell-controlledstudiesinpregnantwomenandnursingmothers,safeuseofDoxatan1mg

Tabletsduringpregnancyandlactationhasnotbeenestablished.Doxatan1mgTablets,therefore,shouldbeusedin

pregnantwomenonlyafterthedoctorhascarefullyweighedexpectedbenefitsagainstpotentialrisks.Althoughno

teratogeniceffectswereseeninanimaltesting,reducedfoetalsurvivalwasobservedinanimalsathighdoses.

Itisnotknown,whetherdoxazosinisexcretedintohumanbreastmilk.Studiesinlactatingratsgivenasingleoraldose

ofradioactivedoxazosingaveanaccumulationinthebreastmilkwithamaximumconcentrationofabout20times

greaterthanthematernalplasmaconcentration.Therefore,doxazosinmustnotbeusedduringlactation.

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4.7Effectsonabilitytodriveandusemachines

RegularmedicalmonitoringisnecessaryduringtreatmentofhighbloodpressurewithDoxatan1mgTablets.

Individuallydifferentreactionsmayreducementalalertnesstosuchanextentthattheabilitytoactivelyparticipatein

roadtraffic,operatemachinesorworkwithoutafirmsupportisimpaired,especiallyatthestartoftherapy,when

increasingthedose,switchingmedicationsorusingalcoholatthesametime.

4.8Undesirableeffects

Side-effectsarisemainlyfromthepharmacologicalpropertiesofthepreparation.Mostoftheside-effectshavebeen

transientorhavebeentoleratedoncontinuedtreatment.

Inthissectionfrequenciesofundesirableeffectsaredefinedasfollows:Verycommon(1/10);common(1/100to

<1/10);uncommon(1/1,000to<1/100);rare(1/10,000to<1/1,000);veryrare(<1/10,000),notknown(cannotbe

estimatedfromtheavailabledata).

Investigations

Notknown:Weightincrease.

Cardiacdisorders

Common:Palpitations,tachycardia

Uncommon:Cardiacarrhythmia,anginapectoris,myocardialinfarction.

Veryrare:Bradycardia

Bloodandlymphaticsystemdisorders

Veryrare:decreaseoferythrocytes,leukocytesandthrombocytes.

Nervoussystemdisorders

Verycommon:Dizziness,headache

Common:Paresthesia,tiredness,somnolence,apathy,posturaldizziness.

Uncommon:Tremor,musclestiffness

Notknown:Syncope,hypoaesthesia,dysgeusia.

Eyedisorders

Common:Accomodationdisturbances.

Uncommon:Abnormaltearflow,photophobia.

Rare:Blurredvision.

Notknown:IFIS(intra-operativefloppyirissyndrome,seesection4.4)

Earandlabyrinthdisorders

Uncommon:Tinnitus.

Notknown:Vertigo.

Respiratory,thoracicandmediastinaldisorders

Common:Bronchitis,nasalcongestion,rhinitis,cough

Uncommon:Epistaxis,bronchospasm,pharyngitis.

Rare:Laryngealoedema.

Notknown:Dyspnoea.

Gastrointestinaldisorders

Common:Diarrhoea,abdominalpain,nausea,constipation,dyspepsia,drymouth.

Uncommon:Vomiting,gastroenteritis.

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Renalandurinarydisorders

Common:Incontinence,cystitis,increasedurination/polyuria,frequentneedtourinate

Uncommon:Urinarydisturbances,dysuria,hematuria.

Rare:Priapism.

Veryrare:IncreaseinplasmaofBUNandcreatinine.

Notknown:Nocturia,

Skinandsubcutaneoustissuedisorders

Common:Pruritus

Uncommon:Alopecia,skinrash,purpura.

Rare:Itching

Veryrare:urticaria

Musculoskeletalandconnectivetissuedisorders

Common:Musclecramps,myalgia.

Uncommon:Arthralgia,muscleweakness,jointswelling.

Notknown:Backpain.

Metabolismandnutritiondisorders

Common:Anorexia

Uncommon:Thirst,hypokalaemia,gout,increasedappetite.

Rare:Hypoglycaemia.

Infectionsandinfestations

Common:Respiratorytractinfection,urinarytractinfection

Vasculardisorders

Common:Giddiness,oedema,posturalhypotension.

Uncommon:Syncope,hotflushes,peripheralischemia

Rare:Cerebrovasculardisturbances.

Notknown:Hypotension.

Posturalhypotensionandsyncopecanoccurinitiallyduringtreatment,especiallyattoohighdoses,butcanalsoariseif

therapyisrestartedafterashortbreak.

Generaldisordersandadministrationsiteconditions

Common:Asthenia,chestpain

Uncommon:Facial/generaloedema,facialredness,fever/shivering,paleness.

Rare:Decreasedbodytemperatureinelderly.

Notknown:Fatigue,malaise,generalpain.

Immunesystemdisorders

Notknown:Allergicreaction.

Hepatobiliarydisorders

Uncommon:abnormalliverfunctiontest

Rare:Jaundice,increasedliverenzymes.

Veryrare:Cholestasis,hepatitis.

Reproductivesystemandbreastdisorders

Common:Ejaculationdisorders.

Uncommon:Impotence

Notknown:Gynaecomastia,retrogradeejaculation.

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Common:Nervousness.

Uncommon:Nightmares,agitation,depression,memoryloss,emotionallability.

Notknown:Anxiety,insomnia.

4.9Overdose

Overdosagewithdoxazosinusuallyproduceshypotension,whichmaygiverisetosyncope.

Ifadoxazosinoverdoseproduceshypotension,cardiovascularsupportwillbemostimportant.Movethepatienttothe

horizontalpositionforbloodpressureandheartratenormalisation.Incaseofseverehypotension,administerplasma

expandersandvasopressors.Kidneyfunctionshouldbemonitoredand,ifnecessary,supported.Asdoxazosinishighly

proteinbound,dialysiswouldnotbeindicated.

5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

Pharmacotherapeuticgroup:Antihypertensives,

ATCcode:C02CA04

Doxazosinselectivelyandcompetitivelyblockspostsynapticalpha-adrenergicreceptors,thusproducingperipheral

vasodilatation.

Inhypertensivepatientsdoxazosinproducesbloodpressurereductionbyreducingperipheralvascularresistance.

Withsingledailydosing,bloodpressureresponsecontinuestobedemonstrableaslateas24hpost-dose.Gradualblood

pressurereductionisobservedafterthestartoftherapy,andpatientsmayexperienceorthostaticresponses.Maximum

reductionsinbloodpressureusuallyoccur26hafterdosing.Inhypertensivepatientssupineandstandingblood

pressuresaresimilarduringdoxazosintherapy.

Notolerancedevelopmentrelativetoantihypertensiveeffecthasbeenobservedduringlong-termdoxazosintherapy.

Withcontinuedusetherehavebeenoccasionalreportsofincreasesinplasmareninactivityandoftachycardia.

AfteraninterimanalysisofALLHAT(Antihypertensiveandlipid-loweringtreatmenttopreventheartattacktrial)the

doxazosintreatmentarmbasedoncomparisonswithchlorthalidonewasdiscontinued.Therewasasignificantlyhigher

(25%)incidenceofcombinedcardiovasculardiseaseeventsandinparticularcongestiveheartfailure(CHF)compared

withthechlorthalidonegroup.TheriskofCHFwasalmostdoubled.Therewerealsonegativetrendsforstrokeandfor

combinedcoronaryheartdisease(CHD),thatisfatalCHD,nonfatalmyocoardialinfarction,coronaryrevascularization

proceduresandhospitalizedangina.Thetotalmortalitydidnotdifferbetweenthedoxazosinandchlorthalidonearms.

5.2Pharmacokineticproperties

Oraldoxazosinisabsorbedreadily,andpeakplasmaconcentrationsoccurat2h.Plasmaeliminationisbiphasic,witha

terminaleliminationhalf-lifeof22h,allowingonce-dailydosing.

Bioavailability

Absolutebioavailabilityisalmost63%.

98.3%ofcirculatingdoxazosinisboundtoplasmaproteins.Doxazosinisextensivelymetabolised(O-demethylation

andhydroxylation),withthefaecesbeingthepredominantrouteofelimination(only5%oftheadministereddoseis

eliminatedasunchangeddoxazosininfaeces).6´-hydroxy-doxazosinisapotentandselective -blockerandinman

accountsfor5%ofanoraldose.Therefore6´-hydroxy-doxazosincontributeslittletotheantihypertensiveactivityof

doxazosin.

Studiesinelderlypatientsandpatientswithrenalimpairmenthaveshownnosignificantdifferencesin

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Thereareonlylimiteddataontheuseofdoxazosininpatientswithliverimpairmentandontheeffectsofdrugsknown

toinfluencehepaticmetabolism(egcimetidine).Inaclinicalstudyin12patientswithmildhepaticinsufficiency,the

areaundertheplasmaconcentration-timecurve(AUC)wasincreasedby43%,andclearanceaftersingleoraldosing

wasreducedby30%.

Asdoxazosinismetabolisedalmostentirelyintheliver,Doxatan1mgTabletsshouldbetitratedcarefullyinpatients

withhepaticimpairment(cf4.4,'Warningsandprecautionsforuse').

5.3Preclinicalsafetydata

Preclinicaldatarevealnospecialhazardforhumansbasedonconventionalstudiesofgenotoxicityandcarcinogenicity.

Formoreinformationseesection4.6.

Althoughanimalstudieshaveproducednoevidenceofateratogeniceffect,dosesapproximately300timesthe

maximumrecommendedhumantherapeuticdosewereassociatedwithreducedfoetalsurvivalinanimals.

6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

Microcrystallinecellulose

Lactoseanhydrous

Magnesiumstearate

Sodiumlaurilsulfate

Sodiumstarchglycolate(typeA)

Colloidalanhydroussilica

6.2Incompatibilities

Notapplicable

6.3Shelflife

5years

6.4Specialprecautionsforstorage

Donotstoreabove30°C.

6.5Natureandcontentsofcontainer

BlistersmadeofPVC/PVDCandaluminium.

Packsizes:10,20,28,30,40,50,56,98,100,150,200,250,300,400,500or1000tablets.

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6.6Specialprecautionsfordisposal

Nospecialrequirements

7MARKETINGAUTHORISATIONHOLDER

STADAArzneimittelAG

Stadastrasse2-18

D-61118BadVilbel

Germany

8MARKETINGAUTHORISATIONNUMBER

PA593/20/1

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

Dateoffirstauthorisation:21 st

January2000

Dateoflastrenewal:9 th

August2010

10DATEOFREVISIONOFTHETEXT

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