BENPH

Main information

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

Documents

Localization

  • Available in:
  • BENPH Tablets 1 Milligram
    Ireland
  • Language:
  • English

Status

  • Source:
  • HPRA - Health Products Regulatory Authority - Ireland
  • Authorization number:
  • PA0577/049/001
  • Authorization date:
  • 05-09-2003
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

IRISHMEDICINESBOARDACTS1995AND2006

MEDICINALPRODUCTS(CONTROLOFPLACINGONTHEMARKET)REGULATIONS,2007

(S.I.No.540of2007)

PA0577/049/001

CaseNo:2068759

TheIrishMedicinesBoardinexerciseofthepowersconferredonitbytheabovementionedRegulationsherebygrantsto

McDermottLaboratoriesLtdt/aGerardLaboratories

35-36BaldoyleIndustrialEstate,GrangeRoad,Dublin13,Ireland

anauthorisation,subjecttotheprovisionsofthesaidRegulations,inrespectoftheproduct

Benph1mgTablet

TheparticularsofwhicharesetoutinPartIandPartIIoftheattachedSchedule.Theauthorisationisalsosubjecttothegeneralconditionsas

maybespecifiedinthesaidRegulationsaslistedonthereverseofthisdocument.

Thisauthorisation,unlesspreviouslyrevoked,shallcontinueinforcefrom27/11/2009.

SignedonbehalfoftheIrishMedicinesBoardthis

________________

Irish Medicines Board

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Date Printed 20/02/2010 CRN 2068759 page number: 1

PartII

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

Benph1mgTablet

2QUALITATIVEANDQUANTITATIVECOMPOSITION

Eachtabletcontains1mgofterazosin(intheformofterazosinhydrochloridedihydrate).

Excipient(s):55mglactoseMonohydrate

Forafulllistofexcipients,seesection6.1.

3PHARMACEUTICALFORM

Tablets

White,round,flat,beveledged,tabletimprinted“E”and“451”ononeside.

4CLINICALPARTICULARS

4.1TherapeuticIndications

Benph®tabletsareindicatedfor:

-symptomatictreatmentofbenignprostatichyperplasia(BPH).

4.2Posologyandmethodofadministration

Thedoseofterazosinshouldbemanagedaccordingtoeachpatient’sresponse.

Aninitialdoseof1.0mgdailyshouldbegivenintheevening.Thisdosemaybeincreasedbyapproximatelydoubling

thedoseatweeklyintervalstoachievethedesiredreductioninsymptoms.Themaintenancedoseisusually5to10mg

oncedaily.Atpresentthereareinsufficientdatatosuggestsymptomaticreliefwithdosesabove10mg.

Usewiththiazidediureticsandotherantihypertensiveagents

Thedoseofterazosinshouldbere-titratedifathiazidediureticorantihypertensiveagentisaddedtoapatients

medication.Oninitiationofthenewmedicationhypotensionmaybeobserved.

Elderly:

Intheelderly,dosageshouldbekeptaslowaspossibleandincrementsmadeunderclosesupervision.

Renaldysfunction:

Pharmacokineticstudiesindicatethatpatientswithimpairedrenalfunctionneednoalterationintherecommended

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Paediatricpatients:

Therearenoreportsregardingtheefficacyandsafetyofthedruginchildren,theuseofterazosinisthereforenot

recommendedforthisgroup.

Methodofadministration:

Benph®tabletsshouldbeswallowedwholeandnotchewedandcanbetakenwithorwithoutfood.

4.3Contraindications

Benph®tabletsshouldnotbegiven:

toindividualswithknownhypersensitivitytoterazosin,ortoastructurallysimilara-adrenergicantagonist,or

topatientsthatarehypersensitivetoquinazolines,or

inthepresenceofcongestiveheartfailureduetomechanicalobstruction(e.g.aorticvalveormitralvalve

stenosis,pulmonaryembolism,restrictivepericarditis).

4.4Specialwarningsandprecautionsforuse

Aswithotheralphaadrenoceptorblockingagents,terazosinshouldnotbeadministeredtopatientssufferingfrom(or

withahistoryof)micturitionsyncope.

‘Firstdose’effectmightoccurafterthefirstterazosindoseorduringtheinitialperiodoftreatment.Thisconsistsof:

markedreductionofbloodpressuremainlyasorthostatichypotension(vertigo,unsteadiness,syncope).Volume

depletion,restrictedsalt-intakeandadvancedage(i.e.65yearsorover)increasetheriskofposturalhypotension.It

shouldbeborninmindthatthisisalsolikelytohappenwhenterazosintreatmentisre-startedafterafewdaysbreak.In

suchcase,the1mginitialdoseshouldbeprescribed.

Syncopehasbeenseeninonepercentofpatientsinhypertensiontrials.Rapiddoseincreaseaswellascombining

terazosinwithadiureticand/oranotherantihypertensivemightresultinsyncope.Syncopeisrelatedtomarkedpostural

hypotension,andinsomecasesitisprecededbytachycardia(120-160/min).Posturalhypotensionismostpronounced

withinashorttimeofdrugintake,whiletheriskofsyncopeisthegreatest30-90minutesfollowingdrug

administration.Dizziness,unsteadinessandsyncopearemostlikelytobeprovokedbyanyofthefollowing:standing

upfromasittingorasupineposition,longperiodsofstanding,increasedphysicalload,warmweatherandconcomitant

drinkingofalcoholicbeverages(pleasealsoseeSection4.7EffectsonAbilitytoDriveandUseMachines).

Managementofsyncope:thepatientshouldbekeptinasupinepositionwithelevatedlowerextremities.Supportive

and/orsymptomatictreatmentmightbenecessary.

Specialcareshouldbetakenwhengivingterazosintoindividualswithknownsusceptibilitytodevelopingorthostatic

hypotensionortothosesufferingfrom:ischaemicoranyotherheartdiseases,cerebrovasculardisorders,IIIand/orIV

degreehypertensiveretinopathy,insulindependentdiabetes,hepaticand/orrenalfailure.

Incertainpatientswithleftventricularfailure,thedecreaseinleftventricularfillingconsequenttovigoroustherapy

mayresultinasignificantfallincardiacoutputandsystemicbloodpressureafteradministrationofterazosin.These

effectsshouldbekeptinmindwhenintroducingtherapyandcontinuoustitrationofdoseused.

Theusualhalf-lifeofterazosinis10-12hours.Thismaybesignificantlyprolongedinpatientswithcongestivecardiac

failure(byupto7-8hours),usuallywithreductiononclinicalimprovement.

BeforestartingterazosintherapyforBPH,carcinomaoftheprostateshouldbeexcluded.Thebloodpressureofpatients

withBPHshouldbemeasuredatbaselineandmonitoredthereafterparticularlyattimesofdoseadjustment.Possible

antihypertensivetreatmentshouldalsobetakenintoconsideration.EffectivenessofTerazosininthemanagementof

BPHshouldbeevaluatedafterallowingaperiodof4-6weeksoftreatmentwiththemaintenancedose.

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Priapism:rarely,terazosinhasbeenassociatedwithpriapism(painfulpenileerection,sustainedforhoursand

unrelievedbysexualintercourseormasturbation).Becausethisconditioncanleadtopermanentimpotenceifnot

promptlytreated,patientsmustbeadvisedabouttheseriousnessofthatcondition.

Concomitantuseofphosphodiesterase-5-inhibitors(sildenafil,tadalafil,vardenafil)andalpha1adrenoceptor

antagonists(terazosin,prazosin,doxazosin)mayleadtosymptomatichypotensioninsomepatients.Inorderto

minimisetheriskfordevelopingposturalhypotensionthepatientshouldbestableonthealpha-blockertherapybefore

initiatinguseofphospodiesterase-5-inhibitors.Inaddition,phosphodiesterase-5-inhibitorsshouldbestartedonthe

lowestdoseandwithatimeinterval(e.g.6hours)followingterazosinadministration.

‘IntraoperativeFloppyIrisSyndrome’(IFIS,avariantofsmallpupilsyndrome)hasbeenobservedduringcataract

surgeryinsomepatientsonorpreviouslytreatedwithtamsulosin.Isolatedreportshavealsobeenreceivedwithother

alpha-1adrenergicblockersandthepossibilityofaclasseffectcannotbeexcluded.AsIFISmayleadtoincreased

proceduralcomplicationsduringthecataractoperation,currentorpastuseofalpha-1blockersshouldbemadeknown

totheophthalmicsurgeonandtheophthalmologistinadvanceofsurgery.

Patientswithrarehereditaryproblemsofgalactoseintolerance,theLapplactasedeficiencyorglucosegalactose

malabsorptionshouldnottakethismedicine.

4.5Interactionwithothermedicinalproductsandotherformsofinteraction

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

symptomatichypotensioninsomepatients(seesection4.4).

Thedrugishighlyproteinbound.Thereisatheoreticalpotentialforinteractionwithsuchdrugsasanticoagulantsand

nonsteroidalanti-inflammatorydrugsleadingtohigherplasmalevelsofdrug.

Exceptforangiotensinconvertingenzyme(ACE)inhibitorsanddiuretics,noclinicallysignificantinteractionshave

beenobservedwithterazosininBPH.InBPHpatientstheadverseeventsprofileofpatientstreatedconcurrentlywith

non-steroidalanti-inflammatorydrugs(NSAIDs),theophylline,antianginalagents,oralhypoglycaemiaagents,ACE

inhibitorsordiureticswascomparativetotheprofileinthegeneraltreatedpopulation.

InthesmallsubsetpatientswhoweretreatedwithterazosinandACEinhibitorsordiuretics,thepercentreporting

dizzinessorotherdizziness-relatedadverseeventsappearstobegreaterthaninthetotalpopulationofterazosin

patientsfromdouble-blindplacebo-controlledstudies.

Cautionshouldbeobservedwhenterazosinisadministeredconcomitantlywithotherantihypertensiveagents(e.g.

calciumantagonists)toavoidthepossibilityofsignificanthypotension.Whenaddingterazosintoadiureticorother

antihypertensiveagent,dosingreductionandretitrationoftheseagentsmaybenecessary.

Laboratorytests:Laboratoryfindingssuggestiveofhaemodilution(e.g.decreaseinhaematocrit,haemoglobin,white

bloodcells,totalproteinandalbumin)havebeenobservedincontrolledclinicaltrials.Nosignificanteffectonprostate

specificantigen(PSA)levelswasreportedafterterazosintreatmentforupto24months.

4.6Pregnancyandlactation

Therearenosufficientdataontheuseofthedruginpregnantandlactatingwomen.Terazosinisnotrecommendedin

thetreatmentofpregnantwomenand/orbreastfeedingmothersunlessthepotentialbenefitisconsideredtooutweigh

therisk.

4.7Effectsonabilitytodriveandusemachines

Thedrugmayinducedrowsiness,dizzinessorlight-headedness.Patientsshouldbeadvisednotdriveavehicle,operate

machineryorperformactivitieswithincreasedriskofaccidentsfor12hoursafterstartingterazosinand12hoursafter

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Thereafter,patientsshouldnotdrive,operatemachineryorperformactivitieswithincreasedriskofaccidentsunless

terazosinhasbeenshownnottoaffecttheirphysicalormentalcapacity.

4.8Undesirableeffects

Aswithotheralphaadrenoceptorblockingantagonists,terazosinmaycausesyncope.

Syncopalepisodesmayoccurwithin30-90minutesoftheinitialdoseofthemedicinalproduct.Occasionallythe

syncopalepisodemaybeprecededbytachycardiawithheartratesof120to160beatsperminute.First-dose

hypotensionmightoccurwhichcouldleadtovertigoandinseverecasessyncope.Toavoidhypotension,terazosin

treatmentshouldbestartedwitha1mgdoseatbed-time.(Seesection4.4SpecialWarningsandPrecautionsforUse).

Thefollowingadverseeventshavebeenreported:

Additionaladversereactionsreportedinclinicaltrialsorreportedduringmarketingexperiencebutnotclearly

associatedwiththeuseofterazosinhavebeenlistedunderthefrequencyheading‘NotKnown’.

Common

(1/100to

<

1/10) Uncommon

≥1/1,000to≤

1/100) Rare

≥1/10,000

≤1/1,000) VeryRare

≤1/10,000) NotKnown

(cannotbe

estimatedfrom

availabledata)

Bloodandthe

lymphaticsystem

disorders thrombocytopenia

Immunesystem

disorders anaphylactic

reactions

Psychiatric

disorders anxiety,insomnia

Nervoussystem

disorders nervousness,

somnolence,

paraesthesia depression

Eyedisorders blurredvision abnormalvision,

conjunctivitis,IFIS

(intraoperative

floppyiris

syndrome)see

section4.4.

Earandlabyrinth

disorders tinnitus

Cardiacdisorders palpitations,

tachycardia,

chestpain atrialfibrillation arrhythmia

Vascular

disorders peripheral

oedema vasodilation

Respiratory,

thoracicand

mediastinal

disorders dyspnoea,

nasal

congestion,

sinusitis,

epistaxis bronchitis,flu

symptoms,

pharyngitis,

rhinitis,cold

symptoms,

increasedcough

Gastrointestinal

disorders nausea,

constipation,

diarrhoea,

vomiting drymouth,

dyspepsia,

flatulence

Skinand

subcutaneous

tissuedisorders pruritus,rash facialoedema,

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4.9Overdose

Ifacutehypotensionoccursasaresultofterazosintreatment,cardiovascularsupportshouldbeofprimaryimportance.

Thepatientshouldbekeptinasupinepositioninordertorestorebloodpressureandheartratetonormal.Ifthis

measureisunsuccessfulthenshockshouldbetreatedwithvolumeexpansionfollowedbyadministrationof

vasopressors.Plasmaandelectrolytebalanceshouldberestored.Renalfunctionshouldbemonitoredandgeneral

supportivemeasuresappliedasrequired.Terazosinishighlyproteinbound;therefore,dialysismaynotbeofbenefit.

5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

Terazosin,theactiveingredientofBenph®tablets,isaselectiveperipherala1-adrenergicblockingagent.Its

antihypertensiveeffectsmayresultfrompostsynaptica1-adrenergicblockade,leadingtovasodilatation,decreasedtotal

peripheralresistanceandvenousreturn.Terazosinisalong-actingoralagentthatisusefulwhengivenoncedailyto

hypertensives.Long-termtreatmentwithterazosindoesnotusuallycausereflextachycardia;whilecardiacoutput,

Musculoskeletal,

connectivetissue

andbone

disorders backpain abdominal,neck

andshoulder

pain,gout,

arthralgia,

arthritis,joint

disorders,

myalgia

Renalandurinary

disorders urinarytract

infectionand

urinary

incontinence,

(primarily

reportedin

post-

menopausal

urinaryfrequency

Reproductive

systemandbreast

disorders impotence decreased

libido priapism

Generaldisorders

administration

siteconditions Dizziness,

light-

headedness,

fainting

(especially

whenstanding

upquickly

fromalying

orasitting

position-

postural

hypotension),

asthenia,

oedema,

headache,pain

inthe

weightgain,

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AlthoughithasnoeffectontheunderlyingpathophysiolgicmechanisminvolvedinBPH,terazosinhasbeenshownto

significantlyincreaseurinaryflowratesanddecreaseoutflowobstruction.ItisalsoeffectiveineasingBPH-related

symptomsbypreventingstimulationofa1-adrenergicreceptorsandconsequentsmoothmusclecontractionsinthe

bladderandprostaticurethra.Urodynamicimprovementmayhelpreduceurinarytractinfection.Thedrug,however,

doesnotaffectthesizeoftheprostate.

Asignificantantihypertensiveeffecthasbeenobserved3hoursfollowingoraladministrationofterazosin.Thedrug’s

antihypertensiveeffecthasbeenreportedtopersistfor24hoursafteroraladministration.

5.2Pharmacokineticproperties

ABSORPTION

Terazosinisrapidlyandalmostcompletelyabsorbedfromthegastrointestinaltract,withoutbeingaffectedbyfood

intake.Ithasa90%bioavailability.

ONSETandDURATION

Followingadministrationofthesmallestdose,meanpeakserumlevelswereachievedwithinonehour.Terazosinhasa

half-lifeofapproximately12hours.36hoursfollowingdrugintake,terazosincouldstillbetracedinplasma.

DISTRIBUTION,METABOLISMandEXCRETION

Terazosinis90-94%plasmaprotein-bound.Itisextensivelymetabolisedintheliverviahydrolysis,demethylationand

dealkylationwithfivedifferentmetabolitesidentified.Meaneliminationhalf-lifeofparentcompoundis12hours.10%

oftheorallyadministereddrugisexcretedintheformofunchangeddrugintheurineand30%asinactivemetabolites.

Faecaleliminationaccountsfor55-60%oftheoraldose.Therearenoreportsonpossibledrugexcretioninbreastmilk.

5.3Preclinicalsafetydata

Terazosinhasbeenshowntoproducetumoursinmaleratswhenadministeredinhighdosesoveralongperiod.No

suchoccuranceswereobservedinfemaleratsorinasimilarstudywithmice.Therelevanceofthesefindingswith

respecttotheclinicaluseofthedruginmanisunknown.

6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

Magnesiumstearate

Talc

Povidone

Pregelatinisedstarch

Lactosemonohydrate

6.2Incompatibilities

Notapplicable

6.3ShelfLife

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6.4Specialprecautionsforstorage

Donotstoreabove30°C,storeintheoriginalpackage.

6.5Natureandcontentsofcontainer

Benph1mgtabletsareprovidedinAluminium/foil/PVC/PVDCblisterstrippacks.

Packsize:

Benph1mgtabletsarepresentedincartonsof7,10,14,20,28,50and100.

Notallpacksizesmaybemarketed.

6.6Specialprecautionsfordisposalofausedmedicinalproductorwastematerialsderivedfrom

suchmedicinalproductandotherhandlingoftheproduct

Nospecialrequirements.

7MARKETINGAUTHORISATIONHOLDER

McDermottLaboratoriesLimited

T/AGerardLaboratories.

35/36BaldoyleIndustrialEstate

GrangeRoad

Dublin13

8MARKETINGAUTHORISATIONNUMBER

PA0577/049/001

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

Dateoffirstauthorisation:05September2004

Dateoflastrenewal:31October2006

10DATEOFREVISIONOFTHETEXT

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