ALFUZOSIN WINTHROP 10MG PROLONGED RELEASE TABLETS

Main information

  • Trade name:
  • ALFUZOSIN WINTHROP 10MG PROLONGED RELEASE TABLETS
  • Dosage:
  • 10 Milligram
  • Pharmaceutical form:
  • Tablet Prolonged Release
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug

Documents

Localization

  • Available in:
  • ALFUZOSIN WINTHROP 10MG PROLONGED RELEASE TABLETS
    Ireland
  • Language:
  • English

Status

  • Source:
  • HPRA - Health Products Regulatory Authority - Ireland
  • Authorization number:
  • PA0540/163/001
  • Authorization date:
  • 10-08-2007
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

IRISHMEDICINESBOARDACTS1995AND2006

MEDICINALPRODUCTS(CONTROLOFPLACINGONTHEMARKET)REGULATIONS,2007

(S.I.No.540of2007)

PA0540/163/001

CaseNo:2067390

TheIrishMedicinesBoardinexerciseofthepowersconferredonitbytheabovementionedRegulationsherebygrantsto

sanofi-aventisIrelandLimited

CitywestBusinessCampus,Dublin24,Ireland

anauthorisation,subjecttotheprovisionsofthesaidRegulations,inrespectoftheproduct

AlfuzosinWinthrop10mgProlongedReleaseTablets

TheparticularsofwhicharesetoutinPartIandPartIIoftheattachedSchedule.Theauthorisationisalsosubjecttothegeneralconditionsas

maybespecifiedinthesaidRegulationsaslistedonthereverseofthisdocument.

Thisauthorisation,unlesspreviouslyrevoked,shallcontinueinforcefrom16/09/2009until09/08/2012.

SignedonbehalfoftheIrishMedicinesBoardthis

________________

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PartII

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

AlfuzosinWinthrop10mgProlongedReleaseTablets

2QUALITATIVEANDQUANTITATIVECOMPOSITION

Eachtabletcontains10mgalfuzosinhydrochloride.

Forexcipients,see6.1.

3PHARMACEUTICALFORM

Tablet,prolongedrelease.

Roundbiconvexthreelayertablet:onewhitelayerbetweentwoyellowlayers.

4CLINICALPARTICULARS

4.1TherapeuticIndications

Treatmentofthefunctionalsymptomsofbenignprostatichypertrophy.

AdjunctivetherapywithurethralcatheterisationforAcuteUrinaryRetentionrelatedtoBPH.

4.2Posologyandmethodofadministration

AlfuzosinWinthrop10mgprolongedreleasetabletsarefororaladministration.

AlfuzosinWinthrop10mgProlongedReleaseTabletsshouldbeswallowedwhole.

BPH:Therecommendeddoseisone10mgtabletoncedailytobetakenafterameal.

AUR:One10mgtabletdailyafteramealtobetakenfromthefirstdayofcatheterisation.

4.3Contraindications

Hypersensitivitytoalfuzosinoranycomponent.

Historyoforthostatichypotension.

Combinationwithotheralpha-1blockers.

Hepaticinsufficiency.

4.4Specialwarningsandprecautionsforuse

Warnings

Aswithallalpha

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hypotensionwithorwithoutsymptoms(dizziness,fatigue,sweating)maydevelopwithinafewhoursfollowing

administration.Insuchcases,thepatientshouldliedownuntilthesymptomshavecompletelydisappeared.

Theseeffectsareusuallytransient,occuratthebeginningoftreatmentanddonotusuallypreventthecontinuationof

treatment.Thepatientshouldbewarnedofthepossibleoccurrenceofsuchevents.

The‘IntraoperativeFloppyIrisSyndrome’(IFIS,avariantofsmallpupilsyndrome)hasbeenobservedduringcataract

surgeryinsomepatientsonorpreviouslytreatedwithtamsulosin.Isolatedreportshavealsobeenreceivedwithother

alpha-1blockersandthepossibilityofaclasseffectcannotbeexcluded.AsIFISmayleadtoincreasedprocedural

complicationsduringthecataractoperationcurrentorpastuseofalpha-1blockersshouldbemadeknowntothe

ophthalmicsurgeoninadvanceofsurgery.

Precautions

Treatmentshouldbeinitiatedgraduallyinpatientswithhypersensitivitytoanotheralpha-1-blocker.Alfuzosin

Winthrop10mgProlongedReleaseTabletsshouldbeadministeredcarefullytopatientsbeingtreatedwith

antihypertensives.Bloodpressureshouldbemonitoredregularly,especiallyatthebeginningoftreatment.

Inpatientswithcoronaryinsufficiencyspecifictherapyforcoronaryinsufficiencyshouldbecontinued.Iftheangina

pectorisreappearsorworsensAlfuzosinWinthrop10mgProlongedReleaseTabletsshouldbediscontinued.

Patientsshouldbewarnedthatthetabletshouldbeswallowedwhole.Anyothermodeofadministration,suchas

crunching,crushing,chewing,grindingorpoundingtopowdershouldbeprohibited.Theseactionsmayleadto

inappropriatereleaseandabsorptionofthedrugandthereforepossibleearlyadversereactions.

4.5Interactionwithothermedicinalproductsandotherformsofinteraction

Combinationscontra-indicated:

Alpha1-receptorblockers(seesection4.3)

Combinationstobetakenintoaccount:

Antihypertensivedrugs(seesection4.4).

Nitrates

PotentCYP3A4inhibitors,suchasketoconazole,itraconazoleandritonavirsincealfuzosinbloodlevelsare

increased(seesection5.2)

Concomitantusewithotheralpha-1-receptorblockersshouldbeavoidedandantihypertensiveagentsshouldbeused

withcautionbecauseoftheriskofahypotensiveeffect.

TheadministrationofgeneralanaestheticstopatientsreceivingAlfuzosinWinthrop10mgProlongedReleaseTablets

couldcauseprofoundhypotension.Itisrecommendedthatthetabletsbewithdrawn24hoursbeforesurgery.

4.6Pregnancyandlactation

Duetothetypeofindicationthissectionisnotapplicable.

4.7Effectsonabilitytodriveandusemachines

Therearenodataavailableontheeffectondrivingvehicles.Adversereactionssuchasvertigo,dizzinessandasthenia

mayoccur.Somesubjectsparticularlythoseonantihypertensivemedicationmayexperienceposturalhypotension,

whichmayormaynotresultinsymptomssuchasdizzinessandfatigue.Thishastobetakenintoaccountwhendriving

vehiclesandoperatingmachinery.

4.8Undesirableeffects

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CNSandPsychiatricdisorders

Common:faintness/dizziness,headache

Uncommon:vertigo

Cardiovasculardisorders

Uncommon:tachycardia,hypotension(postural),syncope,

Veryrare:Anginapectorisinpatientswithpre-existingcoronaryarterydisease(seesection4.4SpecialWarningsand

PrecautionsforUse)

Respiratorysystemdisorders

Uncommon:rhinitis

Gastro-intestinaldisorders

Common:nausea,abdominalpain

Uncommon:diarrhoea

Skinandappendages

Uncommon:rash,pruritus

Veryrare:urticaria,angioedema

Bodyasawhole

Common:asthenia

Uncommon:flushes,oedema,chestpain

Eyedisorders

Unknown:intraoperativefloppyirissyndrome(seesection4.4SpecialWarningsandPrecautionsforUse)

Hepato-biliarydisorders

Unknown:hepatocellularinjury,cholestaticliverdisease

Reproductivesystemandbreastdisorders

Unknown:priapism

4.9Overdose

Incaseofoverdosage,thepatientshouldbehospitalised,keptinthesupineposition,andconventionaltreatmentof

hypotensionshouldtakeplace.

Alfuzosinisnotdialysablebecauseofitshighdegreeofproteinbinding.

5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

Alfuzosinisanorallyactivequinazolinederivative.Itisaselective,peripherallyactingantagonistofpostsynaptic

alpha

-adrenoceptors.

Invitropharmacologicalstudieshavedocumentedtheselectivityofalfuzosinforthealpha

-adrenoreceptorslocatedin

theprostate,bladderbaseandprostaticurethra.

ClinicalmanifestationsofBenignProstaticHypertrophyareassociatedwithinfravesicalobstructionwhichistriggered

bybothanatomical(static)andfunctional(dynamic)factors.Thefunctionalcomponentofobstructionarisesfromthe

tensionofprostaticsmoothmusclewhichismediatedbyalpha

-adrenoceptors.Activationofalpha

-adrenoceptors

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andbladderbase,and,consequently,increasingtheresistancetobladderoutflow.Thisinturnleadstooutflow

obstructionandpossiblesecondarybladderinstability.

Alpha-blockadedecreasesinfravesicalobstructionviaadirectactiononprostaticsmoothmuscle.

Invivo,animalstudieshaveshownthatalfuzosindecreasesurethralpressureandtherefore,resistancetourineflow

duringmicturition.Moreover,alfuzosininhibitsthehypertonicresponseoftheurethramorereadilythanthatof

vascularmuscleandshowsfunctionaluroselectivityinconsciousnormotensiveratsbydecreasingurethralpressureat

dosesthatdonotaffectbloodpressure.

Inman,alfuzosinimprovesvoidingparametersbyreducingurethraltoneandbladderoutletresistance,andfacilitates

bladderemptying.

InplacebocontrolledstudiesinBPHpatients,alfuzosin:

significantlyincreasespeakflowrate(Qmax)inpatientswithQmax 15ml/sbyameanof30%.

Thisimprovementisobservedfromthefirstdose,

significantlyreducesthedetrusorpressureandincreasesthevolumeproducingastrongdesiretovoid,

significantlyreducestheresidualurinevolume.

Inaddition,theefficacyonpeakflowismaintainedupto24hoursafterintake.

Thesefavourableurodynamiceffectsleadtoanimprovementoflowerurinarytractsymptomsi.e.filling(irritative)as

wellasvoiding(obstructive)symptoms.

Alfuzosinmaycausemoderateantihypertensiveeffects.

Alowerfrequencyofacuteurinaryretentionisobservedinthealfuzosintreatedpatientthanintheuntreatedpatient.In

addition,alfuzosinsignificantlyincreasesthesuccessrateofspontaneousvoidingaftercatheterremovalinmenwithan

episodeofAURrelatedtoBPH.

5.2Pharmacokineticproperties

Prolonged-releaseformulation:

Themeanvalueoftherelativebioavailabilityis104.4%versustheimmediatereleaseformulation(2.5mgtid)in

middle-agedhealthyvolunteersandthemaximumplasmaconcentrationisbeingachieved9hoursafteradministration

comparedto1hourfortheimmediatereleaseformulation.

Theapparenteliminationhalf-lifeis9.1hours.

Studieshaveshownthatconsistentpharmacokineticprofilesareobtainedwhentheproductisadministeredaftera

meal.

Underfedconditions,meanCmaxandCtroughvaluesare13.6(SD=5.6)and3.2(SD=1.6)ng/mlrespectively.Mean

0-24 is194(SD=75)ng.h/ml.Aplateauofconcentrationsisobservedfrom3to14hourswithconcentrations

above8.1ng/ml(Cav)for11hours.

Comparedtohealthymiddleagedvolunteers,thepharmacokineticparameters(CmaxandAUC)arenotincreasedin

elderlypatients.

Comparedtosubjectswithnormalrenalfunction,meanCmaxandAUCvaluesaremoderatelyincreasedinpatients

withrenalimpairment,withoutmodificationoftheapparenteliminationhalf-life.Thischangeinthepharmacokinetic

profileisnotconsideredclinicallyrelevant.Therefore,thisdoesnotnecessitateadosingadjustment.

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only11%oftheparentcompoundbeingexcretedunchangedintheurine.Themajorityofthemetabolites(whichare

inactive)areexcretedinthefaeces(75to91%).

Thepharmacokineticprofileofalfuzosinisnotaffectedbychroniccardiacinsufficiency.

Metabolicinteractions:CYP3A4istheprincipalhepaticenzymeisoforminvolvedinthemetabolismofalfuzosin.

Ketoconazoleisastrong-potencyinhibitorofCYP3A4.Repeated200mgdailydosingofketoconazole,forsevendays

resultedinanincreaseoftheCmax(2.11-fold)andAUClast(2.46-fold)ofalfuzosin10mgODunderfedconditions.

Otherparameterssuchastmaxandt1/2Zwerenotmodified.The8-dayrepeatedadministrationofketoconazole400

mgdailyincreasedCmaxofalfuzosinby2.3-fold,AUClastandAUCby3.2and3.0,respectively(seesection4.5).

5.3Preclinicalsafetydata

Nodataoftherapeuticrelevance.

6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

Ethylcellulose

Hydrogenatedcastoroil

Hypromellose

Yellowferricoxide

Magnesiumstearate

Microcrystallinecellulose

Povidone

Silicacolloidalhydrated

Mannitol

6.2Incompatibilities

Notapplicable.

6.3ShelfLife

Blisterstrips:3years

Polyethylenecontainers:2years

6.4Specialprecautionsforstorage

Donotstoreabove25 ˚C.

Keepinoriginalpackage.

6.5Natureandcontentsofcontainer

Boxeswith10or30tabletsinPVC/foilblisterstripsorpolyethylenecontainers.

6.6Specialprecautionsfordisposalofausedmedicinalproductorwastematerialsderivedfrom

suchmedicinalproductandotherhandlingoftheproduct

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7MARKETINGAUTHORISATIONHOLDER

sanofi-aventisIrelandLimited

CitywestBusinessCampus

Dublin24

8MARKETINGAUTHORISATIONNUMBER

PA540/163/1

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

Dateoffirstauthorisation:10thAugust2007

10DATEOFREVISIONOFTHETEXT

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