DOXANE

Main information

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

Documents

Localization

  • Available in:
  • DOXANE Tablets 2mg Milligram
    Ireland
  • Language:
  • English

Status

  • Source:
  • HPRA - Health Products Regulatory Authority - Ireland
  • Authorization number:
  • PA0711/098/002
  • Authorization date:
  • 09-01-2006
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

PartII

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

Doxane2mgTablets.

2QUALITATIVEANDQUANTITATIVECOMPOSITION

Eachtabletcontains2mgDoxazosin(asMesilate).

Forexcipientssee6.1.

3PHARMACEUTICALFORM

Tablet.

White,oblong,biconvextabletswithabreaklineononeside.Thetabletcanbedividedintoequalhalves.

4CLINICALPARTICULARS

4.1TherapeuticIndications

Hypertension:DOXANEisindicatedforthetreatmentofhypertensionandcanbeusedasasoleagenttocontrol

bloodpressureinhypertensivepatients.

Inpatientsinadequatelycontrolledonsingleantihypertensivetherapy,DOXANEmaybeusedincombinationwitha

thiazidediuretic,beta-adrenoceptorblockingagent,calciumantagonistoranangiotensin-convertingenzymeinhibitor.

Benignprostatichyperplasia:Doxazocinisindicatedasanadjunctinthetreatmentofurinaryoutflowobstructionand

symptomsassociatedwithbenignprostatichyperplasia(BPH).Itmaythereforebeofvalueinpatientsawaiting

prostaticsurgeryorforwhomsurgeryisnotpossible.

DoxazocinmaybeusedinBPHpatientswhoareeitherhypertensiveornormotensive.

4.2Posologyandmethodofadministration

RouteofAdministration: Oral

RecommendedDosageSchedule:

Hypertension:

Adults:DOXANEisusedinaoncedailyregimenandmaybeadministeredinthemorningorevening.

Itisrecommendedthattherapybeinitiatedat1mggivenoncedailyforoneortwoweekstominimizethepotentialfor

posturalhypotensionand/orsyncope(seesection4.4SpecialWarningsandSpecialPrecautionsforuse).Thedosage

maythenbeincreasedto2mgoncedailyforanadditionaloneortwoweeks.Ifnecessarythedailydosageshouldthen

beincreasedgraduallyatsimilarintervalsto4mg,8mg,and16mgasdeterminedbypatientresponsetoachievethe

desiredreductioninbloodpressure.Theusualdoseis2-4mgoncedaily.Themaximumdailydoseshouldnotexceed

16mg.

Diuretictherapymaybeintroduced,ifrequired.

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Therecommendedinitialdosageofdoxazocinis1mggivenoncedailytominimizethepotentialforpostural

hypotensionand/orsyncope(seesection4.4SpecialWarningsandSpecialPrecautionsforuse).Dependingonthe

individualpatientsurodynamicsandBPHsymptomatology,dosagemaythenbeincreasedto2mgandthereafterto

4mganduptothemaximumrecommendeddoseof8mg.Therecommendedtitrationintervalis1-2weeks.Theusual

recommendeddoseis2-4mgoncedaily.

Children:ThereisinsufficientexperiencetorecommendtheuseofDOXANEinchildrenunder12yearsofage.

Elderly:Normaladultdosage.Incommonwithotherdrugsofthisclass,dosageshouldbekeptaslowaspossibleand

incrementsmadeunderclosesupervision.

Patientswithrenalimpairment:Sincethereisnochangeinpharmacokineticsinpatientswithimpairedrenalfunction

theusualadultdoseofDOXANEisrecommended.DOXANEisnotdialyzable.

Patientswithhepaticimpairment:DOXANEshouldbeusedwithcareinpatientswithsignificantexistinghepatic

dysfunction.(SeealsoSpecialWarningsandPrecautionsforUseandsection5.2PharmacokineticProperties.)

4.3Contraindications

DOXANEiscontra-indicatedinpatientswithaknownhypersensitivitytoquinazolines,doxazocinortoanyofthe

excipientsusedBPHpatientswithhypotensionorahistoryoforthostatichypotensionshouldnotusedoxazocin.

Patientswithbenignprostatichyperplasiaandconcomitantcongestionoftheupperurinarytract,chronicurinary

tractinfectionsorbladderstonesshouldnotbetreatedwithdoxazocin.

Inaccordancewithprudentmedicalpractice,thisdrugclassshouldnotbeusedinpatientswith:

Overflowbladder,anuriaorprogressiverenalinsufficiency

Historyofesophagealorgastrointestinalobstructionordecreasedlumendiameterofthegastrointestinaltractor

judgedtobeatincreasedriskforsuchobstruction.

Useduringlactation:Animalstudieshaveshownthatdoxazosinaccumulatesinbreastmilk.Theclinicalsafetyof

DOXANEduringlactationhasnotbeenestablished,consequentlyDOXANEiscontra-indicatedinnursingmothers.

4.4Specialwarningsandprecautionsforuse

Patientswithrenalimpairment:ThereisnoevidencethatDOXANEaggravatesrenaldysfunction.However,

DOXANEdosageintroductionandadjustmentshouldbecarriedoutwithgreatcare.

Patientswithhepaticimpairment:Thereareonlylimiteddatainpatientswithliverimpairment,thereforeDOXANE

shouldbeusedwithcareinpatientswithsignificantexistinghepaticdysfunction.Therehavebeennostudiesonthe

effectsofdrugsknowntoinfluencehepaticmetabolism(e.g.cimetidine)onthepharmacokineticsofDOXANE.

Aswithallalpha-blockers,averysmallpercentageofpatientshaveexperiencedposturalhypotensionevidencedby

dizzinessandweakness,orrarelylossofconsciousness(syncope),particularlywiththecommencementoftherapy.

Wheninstitutingtherapywithanyeffectivealpha-blocker,thepatientshouldbeadvisedhowtoavoidsymptoms

resultingfromposturalhypotensionandwhatmeasurestotakeshouldtheydevelop.

Itisrecommendedthattheinitialdosageshouldbegivenwhenthepatientisnotrequiredtoundertakeanyactivity

suchasdrivingoroperatingmachinery.

Themeanterminalhalf-lifeofdoxazosinis22hours.Thismaybeprolongedinpatientswithcongestiveheartfailure.

Therateofdoseadjustmentmayneedtobeslowed.

Insomepatientswithleftventricularfailure,thedecreaseinleftventricularfillingassociatedwithvigoroustherapy

mayresultinasignificantfallincardiacoutputandsystemicbloodpressureafteradministrationofdoxazosin.These

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Patientswithrarehereditaryproblemsofgalactoseintolerance,theLapp-lactasedeficiencyorglucose-galactose

malabsorptionshouldnottakethismedicine.

DoxazosinshouldbeusedwithcareinpatientswithDiabeticAutonomicNeuropathy.

ConcomitantadministrationofPDE-5-inhibitors(suchassildenafil,tadalafilandvardenafil)anddoxazocinshouldbe

exercisedwithcaution,asthismayleadtosymptomatichypotensioninsomepatients(seesection4.5Interactionwith

othermedicinalproductsandotherformsofinteraction).

The‘intraopeativefloppyIrisSyndrome’(IFIS,avariantofsmallpupilsyndrome)hasbeenobservedduringcataract

surgeryinsomepatientsonorpreviouslytreatedwithtamsulosin,Isolatedreportshavealsobeenreceivedwithother

alpha-1blockersandthepossibilityofaclasseffectcannotbeexcluded.AsIFISmayleadtoincreasedprocedural

complicationsduringthecataractoperation,currentorpastuseofalpha-1blockersshouldbemadeknowntothe

ophthalmicsurgeoninadvanceorsurgery.

Doxazosinmayinfluenceplasmareninactivityandurinaryexcretionofvanillylmandelicacid.Thisshouldbe

consideredwheninterpretinglaboratorydata.

4.5Interactionwithothermedicinalproductsandotherformsofinteraction

Doxazosinishighlyboundtoplasmaproteins(98%).Invitrodatainhumanplasmaindicatesthatdoxazosinhasno

effectonproteinbindingofthedrugstested(digoxin,phenytoin,warfarinorindomethacin),howeverthetheoretical

potentialforinteractionwithotherproteinbounddrugsshouldbeborneinmind.

Noadversedruginteractionshavebeenobservedwiththiazidediuretics,frusemide,beta-blockingagents,non-steroidal

anti-inflammatorydrugs,antibiotics,oralhypoglycaemicdrugs,uricosuricagents,oranticoagulants.

Doxazosinincreasesthebloodpressureloweringeffectofotherantihypertensivedrugs.Theantihypertensiveeffect

maybeincreasedwhendoxazosinisadministeredconcomitantlywithvasodilatorsandnitrates.

ConcomitantadministrationofPDE-5-inhibitors(suchassildenafil,tadaladilandvardenafil)anddoxazocinshouldbe

exercisedwithcaution,asthismayleadtosymptomatichypotensioninsomepatients.

4.6Pregnancyandlactation

Useduringpregnancy:Doxazosincrossestheplacenta.Althoughnoteratogeniceffectswereseeninanimaltesting,

reducedfoetalsurvivalwasobservedinanimalsatextremelyhighdoses.Thesedoseswereapproximately300times

themaximumrecommendedhumandose.

Astherearenoadequateandwellcontrolledstudiesinpregnantwomen,thesafetyofDOXANE’suseduring

pregnancyhasnotyetbeenestablished.Accordingly,DOXANEshouldbeusedonlywhen,intheopinionofthe

physician,potentialbenefitoutweighspotentialrisk.

Useduringlactation:Contraindicated.Seeabove

4.7Effectsonabilitytodriveandusemachines

Theabilitytodriveorusemachinerymaybeimpaired,especiallywheninitiatingtherapy.Thedrugmayalsoinduce

drowsiness.Patientsshouldnotdriveoroperatemachineryunlessithasbeenshownnottoaffecttheiralertnessor

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4.8Undesirableeffects

Thefollowingadversereactionshavebeenreported:

Verycommon(>1/10);common(>1/100,<1/10);uncommon(>1/1,000,<1/100);rare(>1/10,000);veryrare

(<1/10,000),notknown(cannotbeestimatedfromtheavailabledata)

Bloodandthelymphaticsystemdisorders:

Veryrare:Reductionoferythrocytes,leucocytopeniaandthrombocytopenia.

Metabolismandnutritiondisorders:

Uncommon:thirst,hypokalaemia,gout

Rare:hypoglycaemia

Psychiatricdisorders:

Common:apathia

Uncommon:nighmares,amnesia,emotionalinstability

Rare:depression,agitation

Nervoussystemdisorders:

Common:fatigue,malaise,headache,somnolence

Uncommon:tremor,muscularstiffness

Rare:paraesthesia

Eyedisorders;

Common:accommodationdisturbances

Uncommon:lacrimation,photophobia

Rare:blurredvision

Earandlabyrinthdisorders:

Uncommon:tinnitus,vertigo

Cardiacdisorders:

Common:palpitations,chestpain

Uncommon:arrhythmia,anginapectoris,bradycardia,tachycardia,myocardialinfarction

Vasculardisorders:

Common:giddiness,dizziness,oedema,orthostaticdysregulation

Uncommon:posturalhypotension,peripheralischaemia,syncope

Rare:cerebrovasculardisturbances

Respiratory,thoracicandmediastinaldisorders:

Common:dyspnoea,rhinitis

Uncommon:epistaxis,bronchospasms,cough,pharyngitis

Rare:oedemaoflarynx

Gastrointestinaldisorders:

Common:constipation,dyspepsia,nausea

Uncommon:anorexia,increasedappetite,tastedisturbances

Rare:abdominalpain,diarrhoea,vomiting

Hepato-biliarydisorders:

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Skinandsubcutaneoustissuedisorders:

Uncommon:alopecia,oedemaoftheface/generaloedema

Rare:rash,pruritus,purpura.

Musculoskeletal,connectivetissueandbonedisorders:

Common:musclecramps

Uncommon:muscularpain,swellingofjoints/arthralgia,muscleweakness

Renalandurinarydisorders:

Common:frequentdesiretomicturate,increasedmicturation

Uncommon:incontinence,micturationdisturbances,dysuria

Veryrare:increaseofserumcreatinineandserumurea.

ReproductiveSystemandbreastdisorders:

Common:delayedejaculation,gynaecomastia

Rare:impotence,priapism

Generaldisordersandadministrationsiteconditions:

Common:asthenia

Uncommon:flushing,fever/shiver,paleness

Rare:lowbodytemperatureinelderly

Particularcaution:

Posturalhypotensionandinrarecasessyncopemayoccuratthebeginningoftherapy,especiallyatveryhighdosesbut

alsowhentreatmentisrecommendedafterabreak.

4.9Overdose

Shouldoverdosageleadtohypotension,thepatientshouldbeimmediatelyplacedinasupine,headdownposition.

Othersupportivemeasuresmaybeappropriateinindividualcases.Sincedoxazosinishighlyproteinbound,dialysisis

notindicated.

5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

ATCcode: CO2CAO4,GO4CA

Pharmacotherapeuticclassification:Alpha-adrenoceptorantagonistsUrologicals.

AdministrationofDOXANEreducesbloodpressureduetoadecreaseinsystemicvascularresistance.Withoncedaily

dosing,clinicallysignificantreductionsinbloodpressurearemaintainedthroughoutthedayand24hourspost-dose.

Duringtheonsetoftherapy,agradualreductioninbloodpressureoccurs,andorthostaticeffectsarecomparablewith

thoseofotherantihypertensives.

DOXANEhasbeenshowntobefreeofadversemetaboliceffectsandissuitableforuseinpatientswithco-existent

diabetesmellitus,insulinresistanceandgout.

DOXANEissuitabletouseinpatientswithco-existentasthma,leftventricularhypertrophyandinelderlypatients.

TreatmentwithDOXANEhasbeenshowntoresultinregressionofleftventricularhypertrophy,inhibitionofplatelet

aggregationandenhancedactivityoftissueplasminogenactivator.Additionally,DOXANEimprovesinsulin

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DOXANEproducesfavourableeffectsonbloodlipids,withasignificantincreaseintheHDL/totalcholesterolratio

andtrendstoafavourablereductionintotaltriglycerides.

5.2Pharmacokineticproperties

Followingoraladministrationinhumans(youngmaleadultsortheelderlyoreithersex),doxazosiniswellabsorbed

andapproximatelytwothirdsofthedoseisbioavailable.Themeanplasmaeliminationhalflifeis22hoursthus

makingthedrugsuitableforoncedailyadministration.

Doxazosinisextensivelymetabolizedinmanandintheanimalspeciestested,withthefaecesbeingthepredominant

routeofexcretion.

Afteroraladministrationofdoxazosintheplasmaconcentrationsofthemetabolitesarelow.Themostactive(6’

hydroxy)metaboliteispresentinmanatonefortiethoftheplasmaconcentrationoftheparentcompoundwhich

suggeststhattheantihypertensiveactivityisinthemainduetodoxazosin.

Pharmacokineticstudiesintheelderlyandpatientswithrenalinsufficiencyhaveshownnosignificantalterations

comparedtoyoungerpatientswithnormalrenalfunction.Thereareonlylimiteddatainpatientswithliverimpairment

andontheeffectsofdrugsknowntoinfluencehepaticmetabolism(e.g.cimetidine).Aswithanydrugwholly

metabolizedbytheliver,useofdoxazosininpatientswithalteredliverfunctionshouldbeundertakenwithcaution(see

Specialwarningsandspecialprecautionsforuse).

5.3Preclinicalsafetydata

Preclinicaldatarevealnospecialhazardforhumansbasedonconventionalstudiesofsafetypharmacology,repeated

dosetoxicity,genotoxicity,carcinogenicpotentialandtoxicitytoreproduction.

6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

LactoseMonohydrate

MagnesiumStearate

MicrocrystallineCellulose

SodiumLaurilsulfate

SodiumStarchGlycolate(TypeA).

6.2Incompatibilities

Notapplicable.

6.3ShelfLife

2years.

6.4Specialprecautionsforstorage

Donotstoreabove30ºC.

6.5Natureandcontentsofcontainer

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6.6Specialprecautionsfordisposalofausedmedicinalproductorwastematerialsderivedfrom

suchmedicinalproductandotherhandlingoftheproduct

Nospecialrequirements.

7MARKETINGAUTHORISATIONHOLDER

RowexLimited

Bantry

Co.Cork

8MARKETINGAUTHORISATIONNUMBER

PA0711/098/002

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

Dateoffirstauthorisation:04November2005

10DATEOFREVISIONOFTHETEXT

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