BENPROTAN

Main information

  • Trade name:
  • BENPROTAN Tablet Prolonged Release 5 Milligram
  • Dosage:
  • 5 Milligram
  • Pharmaceutical form:
  • Tablet Prolonged Release
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug

Documents

Localization

  • Available in:
  • BENPROTAN Tablet Prolonged Release 5 Milligram
    Ireland
  • Language:
  • English

Status

  • Source:
  • HPRA - Health Products Regulatory Authority - Ireland
  • Authorization number:
  • PA0126/160/001
  • Authorization date:
  • 15-12-2006
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

IRISHMEDICINESBOARDACT1995

MEDICINALPRODUCTS(LICENSINGANDSALE)REGULATIONS,1998

(S.I.No.142of1998)

PA0126/160/001

CaseNo:2014768

TheIrishMedicinesBoardinexerciseofthepowersconferredonitbytheabovementionedRegulationsherebygrantsto

ClonmelHealthcareLimited

WaterfordRoad,Clonmel,Co.Tipperary,Ireland

anauthorisation,subjecttotheprovisionsofthesaidRegulations,inrespectoftheproduct

Benprotan5mgProlongedReleaseTablets

TheparticularsofwhicharesetoutinPartIandPartIIoftheattachedSchedule.Theauthorisationisalsosubjecttothegeneralconditionsas

maybespecifiedinthesaidRegulationsaslistedonthereverseofthisdocument.

Thisauthorisation,unlesspreviouslyrevoked,shallcontinueinforcefrom15/12/2006until14/12/2011.

SignedonbehalfoftheIrishMedicinesBoardthis

________________

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PartII

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

Benprotan5mgProlongedReleaseTablets

2QUALITATIVEANDQUANTITATIVECOMPOSITION

Eachtabletcontains5mgalfuzosinhydrochloride

Excipients:

Eachtabletcontains55mgLactosemonohydrate.

Forafulllistofexcipients,seesection6.1.

3PHARMACEUTICALFORM

Prolonged-releasetablet.

White,round,bevelled-edge,uncoatedtablets.

4CLINICALPARTICULARS

4.1TherapeuticIndications

Treatmentofmoderatetoseverefunctionalsymptomsofbenignprostatichyperplasia(BPH).

4.2Posologyandmethodofadministration

Theprolonged-releasetabletshouldbeswallowedwholewithasufficientamountoffluid.

Thetabletcanbetakenwithorwithoutfood.

Adults

1prolonged-releasetablet5mgtwicedaily(morningandevening),notexceeding10mg/day.Thefirstdoseshouldbe

takenatbedtime.

Elderly(over65years)

1prolonged-releasetablet5mgdaily.Thefirstdoseshouldbetakenatbedtime.Thedosemaybeincreasedto10mg

dailyifitiswelltoleratedandifadditionalefficacyisrequired,givenas1prolonged-releasetablet5mgtwicedaily.

Pharmacokineticandclinicalsafety

datademonstratethatnodosereductionisnecessarytoelderlypatients.

Reducedrenalfunction

Mildtomoderaterenalinsufficiency:

1prolonged-releasetablet5mgdaily.Thefirstdoseshouldbetakenatbedtime.Thedoseistobeadjustedaccordingto

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Severerenalinsufficiency:

Alfuzosinshouldnotbegiventopatientswithseverelyimpairedrenalfunction

(creatinineclearance<30ml/min)astherearenoclinicalsafetydataavailableforthis

patientgroup.

Hepaticinsufficiency

Alfuzosinprolongedreleasetabletsarecontraindicatedinpatientswithhepatic

insufficiency.Aftercarefulmedicalconsideration,apreparationcontainingalowerdosage

ofalfuzosinhydrochloride(accordingtotherelevantdosageinstructions

forthisspecificpatientgroup)mightbeconsideredappropriate.

4.3Contraindications

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

Conditionswithorthostatichypotension.

Hepaticinsufficiency.

Combinationwithotheralpha-1receptorblockingagents.

4.4Specialwarningsandprecautionsforuse

Alfuzosinshouldnotbeadministeredtopatientswithseverelyimpairedrenal

function(creatinineclearance<30ml/min)astherearenoclinicalsafetydataavailable

forthispatientgroup.

Alfuzosinshouldbegivenwithcautiontopatientstreatedwithantihypertensivemedicinalproducts.Bloodpressure

shouldbemonitoredregularly,especiallyatthebeginning

oftreatment.

Insomepatientsposturalhypotensionmaydevelop,withorwithoutsymptoms(dizziness,fatigue,sweating)withina

fewhoursofadministration.Thiseffectistransient,occursatthebeginningoftreatment,anddoesnotusuallyprevent

thecontinuationoftreatment.The

patientshouldbewarnedofthepossibleoccurrenceofsuchevents.Insuchcases,thepatientshouldliedownuntilthe

symptomshavecompletelydisappeared.

Cautionshouldbeexercisedwhenalfuzosinisadministeredtopatientswhohaverespondedwithpronounced

hypotensiontoother1-receptorblockers.

Treatmentshouldbeinitiatedgraduallyinpatientswithhypersensitivitytoother1-receptorblockers.

Aswithall1-receptorblockers,alfuzosinshouldbeusedwithcautioninpatientswith

acutecardiacfailure.

Incardiacpatientsthetreatmentofcoronaryinsufficiencyshouldcontinuetakingintoaccountthattheconcomitant

administrationofnitratesandalfuzosinmayincreasetheriskof

occurrenceofhypotension.Ifanginapectorisrecursorworsens,treatmentwithalfuzosinshouldbediscontinued.

Patientsshouldbeinstructedtoswallowthetabletwhole.Othermethodsofadministration

suchascrushing,powderingorchewingthetablet,shouldbeavoided.Incorrect

administrationmayleadtoundesirablereleaseandabsorptionoftheactivesubstancewith

ariskofearlyundesirableeffects.

Thisproductcontainslactose.Patientswithrarehereditaryproblemsofgalactose

intolerance,theLapplactasedeficiencyorglucose-galactosemalabsorptionshouldnot

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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%oftreatedpatients.

Theadversereactionsconsideredatleastpossiblyrelatedtotreatmentarelistedbelowbybodysystemorganclassand

absolutefrequency.Frequenciesaredefinedasverycommon

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

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

Nervoussystemdisorders

Common:Headache,dizziness,vertigo,malaise.

Uncommon:Drowsiness.

Eyedisorders

Uncommon:Visualdisturbances.

Cardiacandvasculardisorders

Common:Posturalhypotension(initially,primarilywithtoohighadoseoriftreatmentisresumedafterashort

interruptionoftherapy).

Uncommon:Tachycardia,palpitations,syncope(inparticularatthebeginningof

treatment).

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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.Symptomatictreatment.

Gastriclavageand/oradministrationofmedicinalcharcoalshouldbeconsidered.Alfuzosinisnoteasilydialysable

becauseofitshighdegreeofproteinbinding.

5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

Pharmacotherapeuticgroup:Drugsusedinbenignprostatehypertrophy,alpha-adrenoreceptorantagonists.

ATCcode:G04CA01

Alfuzosin,whichisaracemate,isanorallyactingquinazolinederivative,whichselectivelyblockspost-synapticalpha-

1receptors.Invitrostudieshaveconfirmedtheselectivityofthesubstanceonalpha-1receptorsinthetrigoneofthe

urinebladder,theurethraandtheprostategland.TheclinicalsymptomsinBPHarenotonlyrelatedtothesizeofthe

prostate,butalsotosympathomimeticnerveimpulses,whichbystimulatingthepost-synapticalphareceptorsincrease

thetensionofthesmoothmuscleofthelowerurinarytract.Treatmentwithalfuzosinrelaxesthissmoothmuscle,thus

improvingtheurinaryflow.

Clinicalevidenceofuroselectivityhasbeendemonstratedbyclinicalefficacyandagoodsafetyprofileinmentreated

withalfuzosin,includingtheelderlyandpatientswithhypertension.Alfuzosinmaycausemoderateanti-hypertensive

effects.

Inman,alfuzosinimprovesthevoidingparametersbyreducingurethraltoneandbladderoutletresistance,andthus

facilitatesbladderemptying.

Alowerfrequencyofacuteurinaryretentionhasbeenobservedinpatientstreatedwithalfuzosinthaninuntreated

patients.

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-significantlyincreasedmaximumurinaryflow(Q

)inpatientswithQ

<15ml/sbyanaverageof30%.This

improvementwasobservedfromthefirstdose;

-significantlyreducedthedetrusorpressureandincreasedthevolumeproducingastrongdesiretovoid,

-significantlyreducedtheresidualurinevolume.

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

wellasvoiding(obstructive)symptoms,whichhasbeenclearlydemonstrated.

5.2Pharmacokineticproperties

Alfuzosinshowslinearpharmacokineticsinthetherapeuticdosagerange.Thekineticprofileischaracterisedbylarge

interindividualfluctuationsinplasmaconcentrations.

Absorption

Prolongedreleaseformulation:

Meanmaximumplasmaconcentrationfollowingsingledoseadministrationwas8.71

ng/ml,AUCinfwas93.5ngxh/ml(fasted)andtmaxwas5.46h(fasted).Themeanterminal

halflifewasfoundtobe5.23hours.

Understeadystateconditions(fasted)meanCmaxwas17.0ng/mlandCminwas7.90ng/ml.

Thepharmacokineticprofileisnotalteredwhenalfuzosinisadministeredwithfood.

Distribution

Plasmaproteinbindingisapproximately90%.Thevolumeofdistributionofalfuzosininhealthyvolunteersis2.5l/kg.

Ithasbeenshowntopreferentiallydistributeintheprostateincomparisontoplasma.

Elimination

Meanplasmahalf-lifeofalfuzosinisapproximately5hours.Alfuzosinisextensivelymetabolisedintheliver(several

routes),metabolitesareeliminatedviarenalexcretionandprobablyalsoviabiliaryexcretion.Ofanoraldose,75-91%

isexcretedinthefaeces;35%asunchangedsubstanceandtherestasmetabolites,indicatingsomedegreeofbiliary

excretion.About10%ofthedoseisexcretedinurineasunchangedsubstance.Noneofthemetaboliteshasany

pharmacologicalactivity.

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

3years.

6.4Specialprecautionsforstorage

Thismedicinalproductdoesnotrequireanyspecialstorageconditions.

6.5Natureandcontentsofcontainer

PVC/PVDC-aluminiumblister.

56,60and180tablets.

Notallpacksizesmaybemarketed.

6.6Specialprecautionsfordisposalofausedmedicinalproductorwastematerialsderivedfrom

suchmedicinalproductandotherhandlingoftheproduct

Nospecialrequirements.

7MARKETINGAUTHORISATIONHOLDER

ClonmelHealthcareLtd.

WaterfordRoad

Clonmel

CountyTipperary

Ireland

8MARKETINGAUTHORISATIONNUMBER

PA126/160/1

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

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