AMLIST

Main information

  • Trade name:
  • AMLIST Tablets 5 Milligram
  • Dosage:
  • 5 Milligram
  • Pharmaceutical form:
  • Tablets
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug

Documents

Localization

  • Available in:
  • AMLIST Tablets 5 Milligram
    Ireland
  • Language:
  • English

Status

  • Source:
  • HPRA - Health Products Regulatory Authority - Ireland
  • Authorization number:
  • PA0577/062/001
  • Authorization date:
  • 19-11-2004
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

Amlist5mgTablets

2QUALITATIVEANDQUANTITATIVECOMPOSITION

Eachtabletcontains5mgofamlodipine(asamlodipinemaleate).

Excipient(s):151.60mgLactosemonohydrate

Forafulllistofexcipients,seeSection6.1.

3PHARMACEUTICALFORM

Tablet.

Whiteroundtablets.

4CLINICALPARTICULARS

4.1TherapeuticIndications

Essentialhypertension.

Chronicstableandvasospasticanginapectoris.

4.2Posologyandmethodofadministration

Inadults

Fortreatmentofbothhypertensionandanginapectoristheusualinitialdoseis5mgoncedaily.Ifthedesired

therapeuticeffectcannotbeachievedwithin2-4weeks,thisdosemaybeincreasedtoamaximumdoseof10mgdaily

(assingledose)dependingontheindividualpatient’sresponse.

Amlodipinemaybeusedeitherasmonotherapyorincombinationwithotherantianginaldrugsinpatientswithangina.

Childrenwithhypertensionfrom6yearsto17yearsofage

Therecommendedantihypertensiveoraldoseinpaediatricpatientsages6-17yearsis2.5mgoncedailyasastarting

dose,up-titratedto5mgoncedailyifbloodpressuregoalisnotachievedafter4weeks.Dosesinexcessof5mgdaily

havenotbeenstudiedinpaediatricpatients(seesection5.1PharmacodynamicPropertiesandsection5.2

PharmacokineticProperties).Theeffectofamlodipineonbloodpressureinpatientslessthan6yearsofageisnot

knownThe2.5mgdosecannotbeobtainedwithAmlodipinetablets5mgasthesetabletsarenotmanufacturedto

breakintotwoequalhalves

Intheelderly

Normaldosageregimensarerecommendedintheelderly,butcautionshouldbeexercisedwhenincreasingthedosage

(seesection5.2“Pharmacokineticproperties”).

Inpatientswithrenalimpairment

Inthesepatientsamlodipinecanbeusedinthenormaldosage(seesection5.2“Pharmacokineticproperties”).

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Inpatientswithhepaticimpairment

Adosageregimenforpatientswithhepaticimpairmenthasnotbeenestablished,thereforeamlodipineshouldbe

administeredwithcaution(seesection4.4“Specialwarningsandprecautionsforuse”).

Thetabletsshouldbetakenwithaglassofwaterindependentlyfrommeals.

4.3Contraindications

Amlodipineiscontra-indicatedinpatientswith:

hypersensitivitytodihydropyridinederivates,amlodipineoranyoftheexcipients

severehypotension

shock(includingcardiogenicshock)

haemodynamicallyunstableheartfailureafteracutemycocardialinfarction

obstructionoftheoutflowtractoftheleftventricle(e.g.highgradeaorticstenosis)

4.4Specialwarningsandprecautionsforuse

Thesafetyandefficacyofamlodipineinhypertensivecrisishasnotbeenestablished.

Patientswithcardiacfailure

Patientswithheartfailureshouldbetreatedwithcaution.Inalong-term,placebocontrolledstudyinpatientswith

severeheartfailure(NYHAgradeIIIandIV)thereportedincidenceofpulmonaryoedemawashigherinthe

amlodipinetreatedgroupthanintheplacebogroup,butthiswasnotassociatedwiththeworseningoftheheartfailure

(seeSection5.1).

Useinpatientswithimpairedhepaticfunction

Thehalf-lifeofamlodipineisprolongedinpatientswithimpairedliverfunction;dosagerecommendationshavenot

beenestablished.Amlodipineshouldthereforebeadministeredwithcautioninthesepatients.

Useinelderlypatients

Intheelderlyincreaseofthedosageshouldtakeplacewithcare(seeSection5.2).

Useinrenalfailure

Amlodipinemaybeusedinsuchpatientsatnormaldoses.Changesinamlodipineplasmaconcentrationsarenot

correlatedwithdegreeofrenalimpairment.Amlodipineisnotdialysable.

Patientswithlactoseintolerance

Thisproductcontainslactose.Patientswithrarehereditaryproblemsofgalactoseintolerance,theLapplactase

deficiencyorglucose-galactosemalabsorptionshouldnottakethisproduct.

4.5Interactionwithothermedicinalproductsandotherformsofinteraction

Effectsofothermedicinalproductsonamlodipine

CYP3A4inhibitors:WithconcomitantusewiththeCYP3A4inhibitorerythromycininyoungpatients

anddiltiazeminelderlypatientsrespectivelytheplasmaconcentrationofamlodipineincreasedby22%and50%

respectively.However,theclinicalrelevanceofthisfindingisuncertain.Itcannotberuledoutthatstronginhibitorsof

CYP3A4(i.e.ketoconazole,itraconazole,ritonavir)mayincreasetheplasmaconcentrationsofamlodipinetoagreater

extentthandiltiazem.AmlodipineshouldbeusedwithcautiontogetherwithCYP3A4inhibitors.However,noadverse

eventsattributabletosuchinteractionhavebeenreported.

CYP3A4inducers:ThereisnodataavailableregardingtheeffectofCYP3A4inducersonamlodipine.The

concomitantuseofCYP3A4inducers(i.e.rifampicin,hypericumperforatum)maygivealowerplasmaconcentration

ofamlodipine.AmlodipineshouldbeusedwithcautiontogetherwithCYP3A4inducers.

Inclinicalinteractionstudiesgrapefruitjuice,cimetidine,aluminium/magnesium(antacid)andsildenafildidnotaffect

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Effectsofamlodipineonothermedicinalproducts

Thebloodpressureloweringeffectsofamlodipineaddstothebloodpressure-loweringeffectsofotherantihypertensive

agents.

Inclinicalinteractionstudies,amlodipinedidnotaffectthepharmacokineticsofatorvastatin,digoxin,ethanol

(alcohol),warfarinorciclosporin.

Thereisnoeffectofamlodipineonlaboratoryparameters.

4.6Fertility,pregnancyandlactation

Pregnancy

Thesafetyofamlodipineinhumanpregnancyhasnotbeenestablished.

Reproductivestudiesinratshaveshownnotoxicityexceptfordelayeddateofdeliveryandprolongeddurationof

labouratdosages50timesgreaterthanthemaximumrecommendeddosageforhumans.

Useinpregnancyisonlyrecommendedwhenthereisnosaferalternativeandwhenthediseaseitselfcarriesgreaterrisk

forthemotherandfoetus.

Lactation

Itisnotknownwhetheramlodipineisexcretedinbreastmilk.Adecisiononwhethertocontinue/discontinuebreast-

feedingortocontinue/discontinuetherapywithamlodipineshouldbemadetakingintoaccountthebenefitofbreast-

feedingtothechildandthebenefitofamlodipinetherapytothemother.

4.7Effectsonabilitytodriveandusemachines

Amlodipinecanhaveminorormoderateinfluenceontheabilitytodriveandusemachines.Ifpatientstaking

amlodipinesufferfromdizziness,headache,fatigueornauseatheabilitytoreactmaybeimpaired.

4.8Undesirableeffects

Thefollowingundesirableeffectshavebeenobservedandreportedduringtreatmentwithamlodipine

withthefollowingfrequencies:Verycommon(1/10);common(1/100to<1/10);uncommon

(1/1,000to1/100);rare(1/10,000to1/1,000);veryrare(1/10,000).

SystemOrganClass Frequency Undesirableeffects

Bloodandlymphaticsystem

disorders VeryRare Leukocytopenia,thrombocytopenia

Immunesystemdisorders VeryRare Allergicreactions

Metabolismandnutrition

disorders VeryRare Hyperglycaemia

Psychiatricdisorders Uncommon Insomnia,moodchanges(includinganxiety),depression

Rare Confusion

Nervoussystemdisorders Common Somnolence,dizziness,headache(especiallyatthebeginningof

thetreatment)

Uncommon Tremor,dysgeusia,syncope,hypoesthesia,paresthesia

VeryRare Hypertonia,peripheralneuropathy

Eyedisorders Uncommon Visualdisturbance(includingdiplopia)

Earandlabyrinthdisorders Uncommon Tinnitus

Cardiacdisorders Uncommon Palpitations

VeryRare Myocardialinfarction,arrhythmia(includingbradycardia,

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*mostlyconsistentwithcholestatis

4.9Overdose

Inhumans,experiencewithintentionaloverdoseislimited.

Symptoms:

Availabledatasuggestthatgrossoverdosagecouldresultinexcessiveperipheralvasodilatationandpossiblyreflex

tachycardia.Markedandprobablyprolongedsystemichypotensionuptoandincludingshockwithfataloutcomehave

beenreported.

Treatment

Clinicallysignificanthypotensionduetoamlodipineoverdosecallsforactivecardiovascularsupportincludingfrequent

monitoringofcardiacandrespiratoryfunction,elevationofextremities,andattentiontocirculatingfluidvolumeand

urineoutput.

Avasoconstrictormaybehelpfulinrestoringvasculartoneandbloodpressure,providedthatthereisno

contraindicationtoitsuse.Intravenouscalciumgluconatemaybebeneficialinreversingtheeffectsofcalciumchannel

blockade.Gastriclavagemaybeworthwhileinsomecases.Inhealthyvolunteerstheuseofcharcoalupto2hoursafter

administrationofamlodipine10mghasbeenshowntoreducetheabsorptionrateofamlodipine.

Vasculardisorders Common Flushing

Uncommon Hypotension

VeryRare Vasulitis

Respiratory,thoracicand

mediastinaldisorders Uncommon Dyspnoea,rhinitis

VeryRare Cough

Gastrointestinaldisorders Common Abdominalpain,nausea

Uncommon Vomiting,dyspepsia,alteredbowelhabits(includingdiaarhoea

andconstipation),drymouth

VeryRare Pancreatitis,gastritis,gingivalhyperplasia

Hepato-biliarydisorders VeryRare Hepatitis,jaundice,hepaticenzymesincreased*

Skinandsubcutaneoustissue

disorders Uncommon Alopecia,purpura,skindiscolouration,hyperhydrosis,pruritus,

rash,exanthema

VeryRare Angioedema,erythemamultiforme,urticaria,exfoliative

dermatitis,Stevens-Johnsonsyndrome,Quinckeoedema,

photosensitivity

Musculoskeletal,connective

tissueandbonedisorders Common Ankleswelling

Uncommon Arthralgia,myalagia,musclecramps,backpain

Renalandurinarydisorders Uncommon Micturitiondisorder,nocturia,increasedurinaryfrequency

Reproductivesystemandbreast

disorders Uncommon Impotence,gynecomastia

Generaldisordersand

administrationsiteconditions Common Oedema,fatigue

Uncommon Chestpain,asthenia,pain,malaise

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5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

Pharmacotherapeuticgroup:Dihydropyridinederivates

ATCcode:C08CA01

Amlodipineisacalciumantagonistandinhibitstheinfluxofcalciumionsintocardiacandsmoothmusclecells.The

mechanismoftheantihypertensiveactionisduetothedirectspasmolyticeffectonvascularsmoothmusclecells.The

precisemechanismbywhichamlodipinerelievesanginapectorishasnotbeenfullydetermined,butthefollowingtwo

actionsplayarole:

1.Amlodipinedilatesperipheralarteriolesandthusreducestheperipheralresistance(afterload)againstwhichtheheart

pumps.Thisunloadingoftheheartreducesmyocardialenergyconsumptionandoxygenrequirements.

2.Dilatationofthemaincoronaryarteriesandthecoronaryarteriolesalsoprobablyplaysaroleinitsaction.This

dilationincreasesthesupplyinoxygentomyocardiacmuscleinpatientswithPrinzmetalanginalattack.

Useinchildren

Inastudyinvolving268childrenaged6-17yearswithpredominantlysecondaryhypertension,comparisonofa2.5mg

dose,and5.0mgdoseofamlodipinewithplacebo,showedthatbothdosesreducedSystolicBloodPressure

significantlymorethanplacebo.Thedifferencebetweenthetwodoseswasnotstatisticallysignificant.

Thelong-termeffectsofamlodipineongrowth,pubertyandgeneraldevelopmenthavenotbeenstudied.Thelong-term

efficacyofamlodipineontherapyinchildhoodtoreducecardiovascularmorbidityandmortalityinadulthoodhavealso

notbeenestablished.

Useinpatientswithhypertension,oncedailydosingprovidesclinicallysignificantreductionsofbloodpressure(in

bothsupineandstandingpositions)thatpersistfor24hours.

Useinpatientswithanginapectoris,oncedailyadministrationofamlodipineincreasestotalexercisetime,thedelayof

occurrenceofanginalattackandthedelayoftheoccurrenceofa1-mmSTinterval.Amlodipinedecreasesbothattack

frequencyandglyceryltrinitratetabletconsumption.

UseinPatientswithHeartFailure

HaemodynamicstudiesandexercisebasedcontrolledclinicaltrialsinNYHAClassII-IVheartfailurepatientshave

shownthatamlodipinedidnotleadtoclinicaldeteriorationasmeasuredbyexercisetolerance,leftventricularejection

fractionandclinicalsymptomatology.

Aplacebocontrolledstudy(PRAISE)designedtoevaluatepatientsinNYHAClassIII-IVheartfailurereceiving

digoxin,diureticsandangiotensin-convertingenzyme(ACE)inhibitorshasshownthatamlodipinedidnotleadtoan

increaseinriskofmortalityorcombinedmortalityandmorbidityinpatientswithheartfailure.

Inafollow-up,long-term,placebocontrolledstudy(PRAISE-2)ofamlodipineinpatientswithNYHAIIIandIVheart

failurewithoutclinicalsymptomsorobjectivefindingssuggestiveofunderlyingischaemicdisease,onstabledosesof

ACEinhibitors,digitalis,anddiuretics,amlodipinehadnoeffectontotalorcardiovascularmortality.Inthissame

populationamlodipinewasassociatedwithincreasedreportsofpulmonaryoedemadespitenosignificantdifferencein

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5.2Pharmacokineticproperties

Absorption/Distribution

Afteroraladministrationoftherapeuticdosesamlodipineisslowlyabsorbedfromthegastrointestinaltract.The

absorptionofamlodipineisunaffectedbytheconcomitantintakeoffood.Theabsolutebioavailabilityofthe

unchangedcompoundisestimatedas64-80%.Peakplasmalevelsarereached6to12hourspost-dose.Thevolumeof

distributionisabout20l/kg.ThepKaofamlodipineis8.6.Plasmaproteinbindinginvitroisapproximately98%.

Metabolism/Elimination

Theplasmaeliminationhalf-lifeisabout35to50hours.

Steadystateplasmalevelsarereachedafter7-8consecutivedays.

Amlodipineispredominantlymetabolisedtoinactivemetabolites.About60%oftheadministereddoseisexcretedin

theurine,about10%ofwhichintheformofunchangedamlodipine.

UseinElderly

Thetimetoreachpeakplasmaconcentrationsofamlodipineissimilarinelderlyandyoungersubjects.Amlodipine

clearancetendstobedecreasedwithresultingincreasesinAUCandeliminationhalflifeinelderlypatients.Increases

inAUCandeliminationhalflifeinpatientswithcongestiveheartfailurewereasexpectedforthepatientagegroupin

thisstudy(SeeSection4.4).

Inpatientswithimpairedrenalfunction

Amlodipineisextensivelybiotransformedtoinactivemetabolites.Tenpercentofthesubstanceisexcretedunchanged

intheurine.Changesinamlodipineplasmaconcentrationarenotcorrelatedwiththedegreeofrenalimpairment.In

thesepatientsamlodipinemaybeadministeredatthenormaldosage.Amlodipineisnotdialysable.

Patientswithhepaticimpairment

Thehalf-lifeofamlodipineisprolongedinpatientswithimpairedhepaticfunction.

Useinchildren

ApopulationPKstudyhasbeenconductedin74hypertensivechildrenagedfrom1monthto17years(with34patients

aged6to12yearsand28patientsaged13to17years)receivingamlodipinebetween1.25and20mggiveneitheronce

ortwicedaily.Inchildren6to12yearsandinadolescents13-17yearsofagethetypicaloralclearance(CL/F)was

22.5and27.4L/hrrespectivelyinmalesand16.4and21.3L/hrrespectivelyinfemales.Largevariabilityinexposure

betweenindividualswasobserved.Datareportedinchildrenbelow6yearsislimited.

5.3Preclinicalsafetydata

Preclinicaldatarevealnospecialhazardforhumansbasedonconventionalstudiesofsafetypharmacology,repeated

dosetoxicity,genotoxicityandcarcinogenicpotential.Inanimalstudieswithrespecttothereproductioninratsathigh

dosesdelayedparturition,difficultlabourandimpairedfoetalandpupsurvivalwereseen(seeSection4.6“Pregnancy

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6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

Lactosemonohydrate

Povidonek30

Povidonek90

Microcrystallinecellulose

Crospovidone

Sodiumstearylfumarate.

6.2Incompatibilities

Notapplicable.

6.3Shelflife

2years

6.4Specialprecautionsforstorage

Donotstoreabove25°C.Storeintheoriginalpackageinordertoprotectfrommoisture.

6.5Natureandcontentsofcontainer

Amlist5mgTabletsaresuppliedinAlu/Alublisterstripsof10,20,28,30,50,98,100,300(10x30)tablets.

Notallpacksizesmaybemarketed.

6.6Specialprecautionsfordisposalofausedmedicinalproductorwastematerialsderivedfrom

suchmedicinalproductandotherhandlingoftheproduct

Nospecialrequirements.

7MARKETINGAUTHORISATIONHOLDER

McDermottLaboratoriesLimited

TradingasGerardLaboratories

35/36BaldoyleIndustrialEstate

GrangeRoad

Dublin13

Ireland

8MARKETINGAUTHORISATIONNUMBER

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9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

Dateoffirstauthorisation:19 th

November2004

Dateoflastrenewal:21 st

February2008

10DATEOFREVISIONOFTHETEXT

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