ALZMERAN XL

Main information

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

Documents

Localization

  • Available in:
  • ALZMERAN XL
    Ireland
  • Language:
  • English

Status

  • Source:
  • HPRA - Health Products Regulatory Authority - Ireland
  • Authorization number:
  • PA0408/070/001
  • Authorization date:
  • 03-10-2008
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

AlzmeranXL10mgprolonged-releasetablets

2QUALITATIVEANDQUANTITATIVECOMPOSITION

Eachtabletcontains10mgalfuzosinhydrochloride.

Excipients:lactose

Forafulllistofexcipients,seesection6.1.

3PHARMACEUTICALFORM

Prolonged-releasetablet.

Whitetooff-white,round,uncoated,biconvextabletswithflattenededges,debossedwith‘RY10’ononeside.

4CLINICALPARTICULARS

4.1TherapeuticIndications

Treatmentofmoderatetoseverefunctionalsymptomsofbenignprostatehyperplasia(BPH).

4.2Posologyandmethodofadministration

Oraluse.

Theprolonged-releasetabletshouldbetakenwholewithsufficientamountoffluid(e.g.aglassofwater).The

prolonged-releasetabletsmustnotbecrushed,chewedordivided(seesection4.4).

Thefirstdoseshouldbetakenatbedtime.Theprolonged-releasetablet10mgshouldbetakenimmediatelyafterthe

samemealeachday.

Adults:

Therecommendeddoseisone10mgprolonged-releasetabletdaily.

Elderlypatients(overtheageof65years)

Therecommendeddoseisthesameasthatforadults.Pharmacokineticandclinicalsafetystudieshaveshownthatdose

adjustmentisnotnecessaryinthecaseofelderlypatients.

Impairedrenalfunction

Mildtomoderaterenalinsufficiency(creatinineclearance>30ml/min):

Dosereductionisusuallynotnecessary(seesection5.2).

Severerenalinsufficiency

AlzmeranXL10mgshouldnotbegiventopatientswithseverelyimpairedrenalfunction(creatinineclearance<30

ml/min)astherearenoclinicalsafetydataavailableforthispatientgroup(seesection4.4).

Hepaticinsufficiency:

Alfuzosin,givenas10mgprolonged-releasetabletsarecontraindicatedinpatientswithhepaticinsufficiency.

Preparationscontainingalowdoseofalfuzosinhydrochloridemightbeusedinpatientswithmildtomoderatehepatic

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Paediatricpopulation:

EfficacyofAlfuzosinhasnotbeendemonstratedinchildrenaged2to16years(seesection5.1).Therefore,Alfuzosinis

notindicatedforuseinpaediatricpopulation.

4.3Contraindications

Hypersensitivitytoalfuzosin,otherquinazolines(e.g.terazosine,doxazosine)oranyoneoftheexcipients

Previoushistoryoforthostatichypotension

Hepaticinsufficiency

Combinationwithotheralpha1receptorblockers

4.4Specialwarningsandprecautionsforuse

Thepatientshouldbeexaminedbeforecommencementoftherapywithalfuzosintoexcludethepresenceofother

conditionsthatcanproducesimilarsymptomstothoseofBPH.

CaremustbetakenifAlmerzanXL10mgProlonged-releasetabletsareadministeredtopatientswhoarebeing

treatedwithantihypertensivesornitrates.Bloodpressuremustberegularlymonitored,particularlyatthestart

ofthetreatment.

Insomepatientsorthostatichypotensionmaydevelopwithinafewhoursfollowingadministrationwithor

withoutsymptoms(dizziness,tiredness,sweating).

Theseeffectsaretransient,occuratthestartofthetreatmentandusuallydonotrequirethetreatmenttobe

stopped.Thepatientshouldbewarnedthatthesesymptomsmaypossiblyoccur.Insuchcasesthepatient

shouldrestlyingdownuntilthesymptomshavecompletelydisappeared.

The’InteroperativeFloppyIrisSyndrome’(IFIS,avariantofsmallpupilsyndrome)hasbeenobservedduring

cataractsurgeryinsomepatientsonorpreviouslytreatedwithtamsulosin.Isolatedreportshavealsobeen

receivedwithotheralpha-1blockersandthepossibilityofaclasseffectcannotbeexcluded.AsIFISmaylead

toincreasedproceduralcomplicationsduringthecataractoperation,currentorpastuseofalpha-1blockers

shouldbemadeknowntotheopthalmicsurgeoninadvanceofsurgery,althoughtheriskofthiseventwith

alfuzosinappearsverylow.

Alfuzosinisnotrecommendedforpatientstreatedwithotheralpha-1receptorblockersduetoincreased

hypotensiveeffectandriskofsevereorthostatichypotension.

Cautionisurgedifalfuzosinisadministeredtopatientswhohavereactedtootheralpha-1-receptorblockerswith

severehypotension.

Thetreatmentshouldbestartedgraduallyinpatientswhoaresensitivetootheralpha-l-receptorblockers.

Likeallalpha-1-receptorblockersalfuzosinshouldbeusedwithcautioninpatientswithacutecardiacfailure.

Inthecaseofcardiacpatientsthetreatmentofcoronaryinsufficiencyshouldbecontinued,takingintoaccount

thefactthatconcomitantadministrationofnitratesandalfuzosincanincreasetheriskofhypotensionoccurring.

Ifanginapectorisrecursthetreatmentwithalfuzosinshouldbestopped.

Astherearenoclinicalsafetydataavailableinpatientswithsevererenalimpairment(creatinineclearance<

30ml/min),AlmerzanXL10mgprolonged-releasetabletsshouldnotbeadministeredtothispatientgroup.

Patientsshouldbeinstructedtotakethetabletwhole.Othermethodsofadministrationsuchascrushing,

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andabsorptionoftheactivesubstancewiththeriskofearlysideeffects.

Thisproductcontainslactose.Patientswithrarehereditaryconditionssuchasgalactoseintolerance,Lapplactase

deficiencyorglucose-galactosemalabsorptionshouldnotusethismedicinalproduct.

PatientswithcongenitalQTcprolongation,withaknownhistoryofacquiredQTcprolongationorwhoaretaking

drugsknowntoincreasetheQTcintervalshouldbeevaluatedbeforeandduringtheadministrationofalfuzosin.

4.5Interactionwithothermedicinalproductsandotherformsofinteraction

Combinationsnotrecommended

-Alpha-1receptorblockingagentsIncreasedhypotensiveeffect.Riskofsevereorthostatichypotension.

-PotentCYP3A4inhibitors(ketoconazole,itraconazole,ritonavir,clarithromycin,erythromycin)

Increasetheplasmaconcentrationofalfuzosinandincreasetheriskofundesirableeffects.

Combinationstobetakenintoaccount(seesection4.4)

-Antihypertensivedrugsantihypertensiveeffectandriskofincreasedhypotension(cumulativeeffect).

-Nitratepreparations.

Administrationofgeneralanaestheticstoapatientbeingtreatedwithalfuzosinmayleadtoprofoundhypotension.Itis

recommendedthatthetabletsbewithdrawn24hoursbeforesurgery.

4.6Fertility,pregnancyandlactation

Inviewoftheareaofindicationthissectionisnotapplicable.

4.7Effectsonabilitytodriveandusemachines

Therearenodataavailableontheeffectondrivingvehicles.

Undesirableeffectssuchasvertigo,dizzinessandastheniacanoccurparticularlyatthestartofthetreatment.This

shouldbetakenintoaccountwhendrivingvehiclesorusingmachines.

4.8Undesirableeffects

Theadversereactionsconsideredatleastpossiblyrelatedtotreatmentarelistedbelowbybodysystemorganclassand

absolutefrequency.Frequenciesaredefinedasverycommon(1/10);common(>1/100to<1/10);uncommon

(>1/1000to<1/100);rare(>1/10000to<1/1000);veryrare(<1/10000),notknown(cannotbeestimatedfromthe

availabledata)

Frequency

Common Uncommon Veryrare NotKnown

Bloodand

lymphatic

system

disorders Neutropenia

Nervoussystem

disorders Dizziness/tiredness,

headache Vertigo,

Drowsiness

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*Althoughonlyreportedinisolatedcaseswithalfuzosin,occurrenceofpriapismcannotbeexcludedasitisgenerally

acceptedasbeingattributabletoallotheralphaadrenoreceptorblockers.

4.9Overdose

Incaseofoverdose,thepatientshouldbeadmittedtohospital,keptinsupineposition,andgivennormalsupport

therapyforhypotension.Theappropriateantidoteisavasoconstrictorthatactsdirectlyonthesmoothmuscleinthe

bloodvesselssuchasnoradrenaline.

Gastricflushingand/ortheadministrationofmedicinalcharcoalshouldbeconsidered.Alfuzosinisnoteasilydialysed

Eyedisorders Visualdisturbances floppyiris

syndrome

Cardiacdisorders Tachycardia,

palpitations,

syncope(in

particularatthe

beginningofthe

treatment),

Flushing NewOnset,

Aggravationor

recurrenceof

anginapectorisin

patientwithpre-

coronaryartery

disorders(see

section4.4) Atrialfibrillation

Vascular

disorders Postural

hypotension

(initially,primarily

withtoohighadose

oriftreatmentis

resumedaftera

shortinterruptionof

therapy)

Respiratory,

thoracicand

mediastinal

disorders Rhinitis

Gastrointestinal

disorders Nausea,abdominal

pain, Diarrhoea,dry

mouth Vomiting

Hepatobiliary

disorders Hepatotoxicity Hepatocellular

injury,cholestatic

liverdisease.

Skinand

subcutaneous

tissuedisorders Skinrashes,

pruritus, Urticaria,

Angioneurotic

oedema

Renalandurinary

disorders Urineincontinence

Generaldisorders

administration

siteconditions Asthenia, Oedema,chest

pains(seesection

4.4),malaise

Reproductive

systemandbreast

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5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

Pharmacotherapeuticcategory:alpha-adrenoreceptorantagonists.ATCcode:G04CA01Alfuzosin

Alfuzosin,aracemiccompound,isanorallyactivequinazolinederivativethatselectivelyblockspost-synapticalpha-l-

receptors.Invitrostudieshaveshownthatthesubstanceactsselectivelyonalpha-1-receptorsinthetrigoneoftheurine

bladder,theurethraandtheprostategland.Theclinicalsymptomsofbenignprostatehyperplasiaarenotonlyrelatedto

thesizeoftheprostatebutalsotothesympathicomimeticnerveimpulseswhichthroughstimulationofthepostsynaptic

alpha-receptorsincreasethetensionofthesmoothmusclesofthelowerurinarytract.Throughtreatmentwithalfuzosin

thesmoothmusclesrelaxasaresultofwhichtheurineflowimproves.

Theclinicalevidenceoftheselectiveeffectontheurinarytractisshownbytheclinicalefficacyandthegoodsafety

profileinmentreatedwithalfuzosin,includingelderlypatientsandpatientswithhypertension.Alfuzosincanresultin

moderateantihypertensiveeffects.

Inmen,alfuzosinimprovesthevoidingofwaterbyreducingurethralmuscletoneandbladderoutletresistance,thereby

facilitatingbladderemptying.

Inpatientstreatedwithalfuzosinalowerfrequencyofacuteurineretentionwasobservedthaninuntreatedpatients.

Inplacebo-controlledstudiesinpatientswithbenignprostatehyperplasiaalfuzosin:

significantlyincreasedmaximumurineflow(Qmax)inpatientswithQmax<15ml/secbyanaverageof30%.

Thisimprovementwasobservedfromthefirstdose;

asignificantlyreduceddetrusorpressureandanincreasedvolume,producingastrongdesiretovoid,

asignificantlyreducedtheresidualurinevolume.

Theseurodynamiceffectsresultinanimprovementinlowerurinarytractsymptoms(LUTS),i.e.symptomsrelatingto

retention(irritating)andurinedischarge(obstructive)whichisclearlydemonstrated.

Paediatricpopulation

Alfuzosinisnotindicatedforuseinthepaediatricpopulation(seesection4.2).

Efficacyofalfuzosinhydrochloridewasnotdemonstratedinthetwostudiesconductedin197patients2to16yearsof

agewithelevateddetrusorleakpointpressure(LPP40cmH2O)ofneurologicorigin.Patientsweretreatedwith

alfuzosinhydrochloride0.1mg/kg/dayor0.2mg/kg/dayusingadaptedpaediatricformulations.

5.2Pharmacokineticproperties

Alfuzosinhaslinearpharmacokineticsinthetherapeuticdosagerange.Thekineticprofileischaracterisedbylarge

inter-individualfluctuationsintheplasmaconcentration.Thekineticprofileischaracterisedbylargeinter-individual

fluctuationsinplasmaconcentrations.Absorptionisincreasedwhenthemedicationisadministeredafterameal.

Absorption

Afterthefirstdose(followingameal)themeanmaximumplasmaconcentrationwas7.72ng/mlandtheAUCinf127

ngxh/ml(afterameal)andthetmaxwas6.69hours(afterameal).Insteadystateconditions(afterameal)themean

AUCoverthedosageinterval(AUC)was145ngxh/ml,themeanCmax10.6ng/mlandCminwas3.23ng/ml.

Distribution

Plasmaproteinbindingisapprox.90%.Thedistributionvolumeofalfuzosininhealthytestsubjectsis2.5l/kg.Ithas

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Elimination

Theapparenteliminationhalf-lifeisapproximately8hours.Alfuzosinislargelymetabolisedintheliver(various

routes),themetabolitesareeliminatedbythekidneysandprobablyalsoviathebile,75-91%ofanoraldoseis

eliminatedinthefaeces,35%inunmodifiedformandtherestasmetabolites,whichindicatesthatsomeexcretionvia

thebiletakesplace.Around10%ofthedoseiseliminatedinunmodifiedformintheurine.Noneofthemetabolitesare

pharmacologicallyactive.

Renalorhepaticimpairment

Thevolumeofdistributionandclearanceincreaseswithreducedrenalfunction,possiblyowingtoadecreaseddegree

ofproteinbinding.Thehalf-life,however,isunchanged.Thischangeinthepharmacokineticprofileisnotconsidered

clinicallyrelevant.Therefore,thisdoesnotnecessitateadosingadjustmentinpatientswithmildtomoderaterenal

insufficiency(seesections4.2and4.4).

Thehalf-lifeisprolongedinpatientswithseverehepaticinsufficiency.Thepeakplasmaconcentrationisdoubledand

thebioavailabilityincreasesinrelationtothatinyoung,healthyvolunteers.Alzmeran10mgprolongedreleasetablets

arecontraindicatedinhepaticinsufficiency(seesection4.3).

Elderlypatients

Comparedtohealthymiddle-agedvolunteers,thepeakplasmaconcentration(Cmax)andbioavailability(AUC)arenot

increasedinelderlypatients.Theeliminationhalf-life(t½)remainsunchanged.

5.3Preclinicalsafetydata

Pre-clinicaldatarevealnospecialhazardforhumansbasedonconventionalstudiesofgenotoxicity,carcinogenic

potentialorreproductivetoxicityformales.Invitro,alfuzosinprolongedtheactionpotentialdurationandQTinterval

durationataclinicallyrelevantconcentration.

6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

Lactoseanhydrous

Colloidalanhydroussilica

Povidone

Talc

Magnesiumstearate

Hypromellose

Hydroxypropylcellulose

6.2Incompatibilities

Notapplicable.

6.3Shelflife

2years

6.4Specialprecautionsforstorage

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6.5Natureandcontentsofcontainer

PVC-aluminiumblister.

Packsizes:10,30and90tablets.

Notallpacksizesmaybemarketed.

6.6Specialprecautionsfordisposal

Nospecialrequirements.

7MARKETINGAUTHORISATIONHOLDER

RanbaxyIrelandLimited

Spafield

CorkRoad

Cashel

Co.Tipperary

8MARKETINGAUTHORISATIONNUMBER

PA0408/070/001

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

Datoffirstauthorisation:3rdOctober2008

10DATEOFREVISIONOFTHETEXT

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