BENPROTAN

Main information

  • Trade name:
  • BENPROTAN Tablet Prolonged Release 10 Milligram
  • Dosage:
  • 10 Milligram
  • Pharmaceutical form:
  • Tablet Prolonged Release
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug

Documents

Localization

  • Available in:
  • BENPROTAN Tablet Prolonged Release 10 Milligram
    Ireland
  • Language:
  • English

Status

  • Source:
  • HPRA - Health Products Regulatory Authority - Ireland
  • Authorization number:
  • PA0126/160/002
  • Authorization date:
  • 15-12-2006
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

IRISHMEDICINESBOARDACTS1995AND2006

MEDICINALPRODUCTS(CONTROLOFPLACINGONTHEMARKET)REGULATIONS,2007

(S.I.No.540of2007)

PA0126/160/002

CaseNo:2052342

TheIrishMedicinesBoardinexerciseofthepowersconferredonitbytheabovementionedRegulationsherebygrantsto

ClonmelHealthcareLimited

WaterfordRoad,Clonmel,Co.Tipperary,Ireland

anauthorisation,subjecttotheprovisionsofthesaidRegulations,inrespectoftheproduct

Benprotan10mgProlongedReleaseTablets

TheparticularsofwhicharesetoutinPartIandPartIIoftheattachedSchedule.Theauthorisationisalsosubjecttothegeneralconditionsas

maybespecifiedinthesaidRegulationsaslistedonthereverseofthisdocument.

Thisauthorisation,unlesspreviouslyrevoked,shallcontinueinforcefrom26/08/2008until14/12/2011.

SignedonbehalfoftheIrishMedicinesBoardthis

________________

Irish Medicines Board

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Date Printed 21/10/2008 CRN 2052342 page number: 1

PartII

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

Benprotan10mgProlongedReleaseTablets

2QUALITATIVEANDQUANTITATIVECOMPOSITION

Eachtabletcontains10mgalfuzosinhydrochloride.

Excipients:

Eachtabletconains8mglactosemonohydrate.

Forafulllistofexcipients,seesection6.1.

3PHARMACEUTICALFORM

Prolonged-releasetablet.

White,round,bevelled-edge,uncoatedtablets.

4CLINICALPARTICULARS

4.1TherapeuticIndications

Treatmentofmoderatetoseverefunctionalsymptomsofbenignprostatichyperplasia(BPH).

4.2Posologyandmethodofadministration

Theprolonged-releasetabletshouldbeswallowedwholewithasufficientamountoffluid.

Thetabletshouldbetakenimmediatelyafterthesamemealeachday.

Adults

1prolonged-releasetablet10mgoncedaily.Thefirstdoseshouldbetakenatbedtime.

Elderly(over65years)

1prolonged-releasetablet10mgoncedailyiftherecommendedinitiallowerdoseofalfuzosinhydrochlorideiswell

toleratedandadditionalefficacyisrequired.Thefirstdoseshouldbetakenatbedtime.

Pharmacokineticandclinicalsafetydatademonstratethatnodosereductionisnecessarytoelderlypatients.

Reducedrenalfunction

Mildtomoderaterenalinsufficiency:

Ifalowerdoseisnotsufficient,therapycanbeadjustedto1prolonged-releasetablet10mgdailyaccordingtoclinical

response.Thefirstdoseshouldbetakenatbedtime.

Severerenalinsufficiency:

Alfuzosin10mgshouldnotbegiventopatientswithseverelyimpairedrenalfunction(creatinineclearance<30

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Hepaticinsufficiency

Alfuzosingivenas10mgprolongedreleasetabletsarecontraindicatedinpatientswithhepaticinsufficiency.After

carefulmedicalconsideration,apreparationcontainingalowdoseofalfuzosinhydrochloride(accordingtotherelevant

dosageinstructionsforthisspecificpatientgroup)mightbeconsideredappropriate.Refertocorrespondingproduct

informationfordosinginstructions.

4.3Contraindications

Hypersensitivitytoalfuzosin,otherquinazolines(e.g.terazosin,doxazosin)ortoanyoftheexcipients.

Conditionswithorthostatichypotension.

Hepaticinsufficiency.

Combinationwithotheralpha-1receptorblockingagents.

4.4Specialwarningsandprecautionsforuse

Alfuzosin10mgshouldnotbeadministeredtopatientswithseverelyimpairedrenalfunction(creatinineclearance<

30ml/min)astherearenoclinicalsafetydataavailableforthispatientgroup.AlfuzosinStadashouldbegivenwith

cautiontopatientstreatedwithantihypertensivemedicinalproducts.Bloodpressureshouldbemonitoredregularly,

especiallyatthebeginningoftreatment.

Insomepatientsposturalhypotensionmaydevelop,withorwithoutsymptoms(dizziness,asthenia,sweating)withina

fewhoursofadministration.Insuchcases,thepatientshouldliedownuntilthesymptomshavecompletely

disappeared.Thiseffectsareusuallytemporary.Theyoccuratthestartofthetreatmentandnormallydonotprevent

continuationthetreatment.Patientsshouldbewarnedaboutthepossibilityofsideeffects.

Cautionshouldbeexercisedwithalfuzosinisadministeredtopatientswhohaverespondedwithpronounced

hypotensiontootheralpha-1blockers.

Treatmentshouldbeinitiatedgraduallyinpatientswithhypersensitivitytootheralpha-1receptorblockers.

Aswithallalpha-1receptorblockers,alfuzosinshouldbeusedwithcautioninpatientswithacutecardiacfailure.

The"IntraoperativeFloppyIrisSyndrome"(IFIS,avariantofsmallpupilsyndrome)hasbeenobservedduringcataract

surgeryinsomepatientsonorpreviouslytreatedwithtamsulosin.Isolatedreportshavealsobeenreceivedwithother

alpha-blockersandthepossibilityofaclasseffectcannotbeexcluded.AsIFISmayleadtoincreasedprocedural

complicationsduringthecataractoperationcurrentorpastuseofalpha-1blockersshouldbemadeknowntothe

opthalmicsurgeoninadvanceofsurgery.

Incardiacpatientsthetreatmentofcoronaryinsufficiencyshouldcontinuetakingintoaccountthattheconcomitant

administrationofnitratesandalfuzosinmayincreasetheriskofoccurrenceofhypotension.Alfuzosinshouldbe

discontinuedifanginapectorisrecursorworsens.

Patientsshouldbeinstructedtoswallowthetabletwhole.Othermethodsofadministrationsuchascrushing,powdering

orchewingthetablet,shouldbeavoided.Incorrectadministrationmayleadtoundesirablereleaseandabsorptionofthe

activesubstancewithariskofearlyundesirableeffects.

Thisproductcontainslactose.Patientswithrarehereditaryproblemsofgalactoseintolerance,theLapplactase

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4.5Interactionwithothermedicinalproductsandotherformsofinteraction

Contra-indicatedcombinations:

Alpha-1receptorblockingagents(seesection4.3).

Combinationsrequiringcaution:

-AlfuzosinbloodlevelsareincreasedbypotentCYP3A4inhibitorslikeketoconazole,

itraconazoleandritonavir.

-Antihypertensiveagents(seesection4.4).

-Nitrates.

Concomitantusewithantihypertensiveagentsornitratesincreasestheriskofhypotension.

Seealsosection4.4.

Administrationofananaesthetictoapatientbeingtreatedwithalfuzosinmayleadtoprofoundhypotension.Itis

recommendedthatthetabletsbewithdrawn24hoursbeforesurgery.

Nopharmacodynamicorpharmacokineticinteractionshavebeenobservedinstudieswithhealthyvolunteersbetween

alfuzosinandthefollowingactivesubstances:warfarin,digoxinandhydrochlorothiazide.

4.6Pregnancyandlactation

Duetothetypeofindicationthissectionisnotapplicable.

4.7Effectsonabilitytodriveandusemachines

Nostudiesontheeffectsontheabilitytodriveandusemachineshavebeenperformed.

Adversereactionssuchasvertigo,dizzinessandastheniamayoccur,especiallyatthebeginningoftreatment.Thishas

tobetakenintoconsiderationwhendrivingvehiclesandoperatingmachines.

4.8Undesirableeffects

Themostcommonlyreportedeventisdizziness,whichoccursinapproximately5%oftreated

patients.

Theadversereactionsconsideredatleastpossiblyrelatedtotreatmentarelistedbelowby

bodysystemorganclassandabsolutefrequency.Frequenciesaredefinedasverycommon

(>1/10);common(>1/100to<1/10);uncommon(>1/1000to<1/100);rare(>1/10000to

<1/1000);veryrare(<1/10000).

Nervoussystemdisorders

Common:tiredness,dizziness,headache,vertigo.

Uncommon:Drowsiness.

Eyedisorders

Uncommon:Visualdisturbances.

Cardiacandvasculardisorders

Common:Posturalhypotension(initially,primarilywithtoohighadoseoriftreatmentis

resumedafterashortinterruptionoftherapy).

Uncommon:Tachycardia,palpitations,syncope(inparticularatthebeginningof

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Veryrare:Aggravationorrecurrenceofanginapectoris(seesection4.4).

Respiratory,thoracicandmediastinaldisorders

Uncommon:Rhinitis.

Gastrointestinaldisorders

Common:Nausea,dyspepsia,drymouth,diarrhoea,abdominalpain.

Uncommon:vomiting.

Hepato-biliarydisorders

Veryrare:Hepatotoxicity.

Skinandsubcutaneoustissuedisorders

Uncommon:Rash(urticaria,exanthema),pruritus.

Veryrare:Angioedema.

Renalandurinarydisorders

Uncommon:Urinaryincontinence.

Veryrare:Isolatedcasesofpriapismwerereported.

Generaldisordersandadministrationsiteconditions

Common:Asthenia.

Uncommon:Hotflushes,oedema,chestpain.

4.9Overdose

Incaseofoverdose,conventionaltreatmentinahospitalisrecommended,e.g.i.v.fluidsandvasopressors.The

appropriateantidoteisavasoconstrictorthatactsdirectlyonthesmoothmuscleinthebloodvesselssuchas

noradrenaline.

Gastriclavageand/oradministrationofmedicinalcharcoalshouldbeconsidered.Alfuzosinisnoteasilydialysable

becauseofitshighdegreeofproteinbinding.

5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

Pharmacotherapeuticgroup:Drugsusedinbenignprostatehypertrophy,alpha-adrenoreceptorantagonists.

ATCcode:G04CA01

Alfuzosin,whichisaracemate,isanorallyactingquinazolinederivative,whichselectivelyblockspost-synapticalpha-

1receptors.Invitrostudieshaveconfirmedtheselectivityofalfuzosinforalpha-1receptorsinthetrigoneoftheurine

bladder,theurethraandtheprostategland.TheclinicalsymptomsinBPHarenotonlyrelatedtothesizeofthe

prostate,butalsotosympathomimeticnerveimpulses,whichbystimulatingthepost-synapticalphareceptorsincrease

thetensionofthesmoothmuscleofthelowerurinarytract.Treatmentwithalfuzosinrelaxesthissmoothmuscle,thus

improvingtheurinaryflow.

Clinicalevidenceofuroselectivityhasbeendemonstratedbyclinicalefficacyandagoodsafetyprofileinmentreated

withalfuzosin,includingtheelderlyandpatientswithhypertension.Alfuzosinmaycausemoderateanti-hypertensive

effects.

Inman,alfuzosinimprovesthevoidingparametersbyreducingurethraltoneandbladderoutletresistance,andthus

facilitatesbladderemptying.

Alowerfrequencyofacuteurinaryretentionhasbeenobservedinpatientstreatedwithalfuzosinthaninuntreated

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Inplacebo-controlledstudiesofBPHpatients,alfuzosinhas:

-significantlyincreasedmaximumurinaryflow(Q

)inpatientswithQ

<15ml/sbyanaverageof30%.This

improvementwasobservedfromthefirstdose;

-significantlyreducedthedetrusorpressureandincreasedthevolumeproducingastrongdesiretovoid,

-significantlyreducedtheresidualurinevolume.

TheseurodynamiceffectsleadtoanimprovementofLowerUrinaryTractSymptoms(LUTS),i.e.filling(irritative)as

wellasvoiding(obstructive)symptoms,whichhasbeenclearlydemonstrated.

5.2Pharmacokineticproperties

Alfuzosinshowslinearpharmacokineticsinthetherapeuticdoserange.Thepeakplasmaconcentrationisreached

approx.5hoursafteradministration.Thekineticprofileischaracterisedbylargeinterindividualfluctuationsinplasma

concentrations.Absorptionisincreasedwhenthemedicationisadministeredafterameal.

Absorption

Prolongedreleaseformulation:

Afterthefirstdose(fed)themeanmaximumplasmaconcentrationwas7.72ng/mland

AUCinfwas127ngxh/ml(fed),andtmaxwas6.69h(fed).Understeadystateconditions

(fed)themeanAUCoverthedosinginterval(AUC)was145ngxh/ml,meanCmaxwas

10.6ng/mlandCminwas3.23ng/ml.

Distribution

Plasmaproteinbindingisapproximately90%.Alfuzosin'sdistributionis2.5l/kginhealthyvolunteers.Ithasbeen

showntopreferentiallydistributeintheprostateincomparisontoplasma.

Elimination

Theapparenteliminationhalf-lifeisapprox.8hours.Alfuzosinisextensivelymetabolisedintheliver(severalroutes),

metabolitesareeliminatedviarenalexcretionandprobablyalsoviabiliaryexcretion.Ofanoraldose,75-91%is

excretedinthefaeces;35%asunchangedsubstanceandtherestasmetabolites,indicatingsomedegreeofbiliary

excretion.About10%ofthedoseisexcretedinurineasunchangedsubstance.Noneofthemetabolitesare

pharmacologicallyactive.

Renalorhepaticimpairment

Volumeofdistributionandclearanceincreasewithreducedrenalfunction,possiblyowingtoadecreaseddegreeof

proteinbinding.Thehalf-life,however,isunchanged.Inpatientswithseverehepaticinsufficiencythehalf-lifeis

prolonged.Thepeakplasmaconcentrationisdoubled,andthebioavailabilityincreasesinrelationtothatinyoung,

healthyvolunteers.

Elderlypatients

Oralabsorptionismorerapid,andAUCvaluesaregreaterinelderly(>75years)thaninyoungersubjects.The

increaseinplasmaconcentrationmaybeexplainedbyareductioninthemetaboliccapacityoftheelderly.Oral

bioavailabilityissomewhathigherthaninyoungersubjects.Theeliminationhalf-liferemainsunchanged.

5.3Preclinicalsafetydata

Preclinicaldatarevealnospecialhazardforhumansbasedonconventionalstudiesofsafetypharmacology,repeated

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6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

Lactosemonohydrate

Hypromellose(E464)

PovidoneK25

Magnesiumstearate(E470b)

6.2Incompatibilities

Notapplicable.

6.3ShelfLife

4years.

6.4Specialprecautionsforstorage

Donotstoreabove30 o

6.5Natureandcontentsofcontainer

PVC/PVDC-aluminiumblister.

10,28,30and90tablets.

Notallpacksizesmaybemarketed.

6.6Specialprecautionsfordisposalofausedmedicinalproductorwastematerialsderivedfrom

suchmedicinalproductandotherhandlingoftheproduct

Nospecialrequirements.

7MARKETINGAUTHORISATIONHOLDER

ClonmelHealthcareLtd.

WaterfordRoad

Clonmel

CountyTipperary

Ireland

8MARKETINGAUTHORISATIONNUMBER

PA126/160/2

Irish Medicines Board

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10DATEOFREVISIONOFTHETEXT

Irish Medicines Board

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