ESOMEPRAZOLE

Main information

  • Trade name:
  • ESOMEPRAZOLE Tablets Gastro-Resistant 20 Milligram
  • Dosage:
  • 20 Milligram
  • Pharmaceutical form:
  • Tablets Gastro-Resistant
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug

Documents

Localization

  • Available in:
  • ESOMEPRAZOLE Tablets Gastro-Resistant 20 Milligram
    Ireland
  • Language:
  • English

Status

  • Source:
  • HPRA - Health Products Regulatory Authority - Ireland
  • Authorization number:
  • PA0408/081/001
  • Authorization date:
  • 04-02-2011
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

Esomeprazole20mggastro-resistanttablets

2QUALITATIVEANDQUANTITATIVECOMPOSITION

Eachtabletcontains:20mgesomeprazoleasesomeprazolemagnesium(amorphous).

Excipients:

Eachtabletalsocontainsnotmorethan27.45mgSucrose.

Forfulllistofexcipients,seesection6.1

3PHARMACEUTICALFORM

Gastro-resistanttablet

Lightbrickredtobrowncoloured,oval,biconvex,film-coatedtabletswith‘E5’debossedononesideandplainon

otherside

4CLINICALPARTICULARS

4.1TherapeuticIndications

EsomeprazoleGastro-resistanttabletsareindicatedfor:

GastroesophagealRefluxDisease(GERD)

treatmentoferosiverefluxesophagitis

long-termmanagementofpatientswithhealedesophagitistopreventrelapse

symptomatictreatmentofgastroesophagealrefluxdisease(GERD)

IncombinationwithappropriateantibacterialtherapeuticregimensfortheeradicationofHelicobacterpylori

and

healingofHelicobacterpyloriassociatedduodenalulcerand

preventionofrelapseofpepticulcersinpatientswithHelicobacterpyloriassociatedulcers

PatientsrequiringcontinuedNSAIDtherapy

HealingofgastriculcersassociatedwithNSAIDtherapy.Preventionofgastricandduodenalulcersassociatedwith

NSAIDtherapy,inpatientsatrisk.

TreatmentofZollingerEllisonSyndrome

4.2Posologyandmethodofadministration

Thetabletsshouldbeswallowedwholewithliquid.Thetabletsshouldnotbechewedorcrushed.

Forpatientswhohavedifficultyinswallowingthetabletscanalsobedispersedinhalfaglassofnon-carbonatedwater.

Nootherliquidsshouldbeusedastheentericcoatingmaybedissolved.Stiruntilthetabletsdisintegrateanddrinkthe

liquidwiththepelletsimmediatelyorwithin30minutes.Rinsetheglasswithhalfaglassofwateranddrink.The

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Forpatientswhocannotswallow,thetabletscanbedispersedinnon-carbonatedwaterandadministeredthrougha

gastrictube.Itisimportantthattheappropriatenessoftheselectedsyringeandtubeiscarefullytested.Forpreparation

andadministrationinstructionsseesection6.6.

Adultsandadolescentsfromtheageof12years

Gastro-esophagealRefluxDisease(GERD)

treatmentoferosiverefluxesophagitis

40mgoncedailyfor4weeks

Anadditional4weekstreatmentisrecommendedforpatientsinwhomesophagitishas

nothealedorwhohavepersistentsymptoms.

long-termmanagementofpatientswithhealedesophagitistopreventrelapse

20mgoncedaily

symptomatictreatmentofgastroesophagealrefluxdisease(GERD)

20mgoncedailyinpatientswithoutesophagitis.Ifsymptomcontrolhasnotbeen achievedafter4weeks,the

patientshouldbefurtherinvestigated.Oncesymptomshaveresolved,subsequentsymptomcontrolcanbeachieved

using20mgoncedaily.Inadults,anondemandregimentaking20mgoncedaily,whenneeded,canbeused.In

NSAIDtreatedpatientsatriskofdevelopinggastricandduodenalulcers,subsequentsymptomcontrolusinganon

demandregimenisnotrecommended.

Adults

IncombinationwithappropriateantibacterialtherapeuticregimensfortheeradicationofHelicobacterpylori

and

healingofHelicobacterpyloriassociatedduodenalulcerand

preventionofrelapseofpepticulcersinpatientswithHelicobacterpyloriassociatedulcers.

20mgEsomeprazoleTabletwith1gamoxicillinand500mgclarithromycin,alltwicedailyfor7days.

PatientsrequiringcontinuedNSAIDtherapy

HealingofgastriculcersassociatedwithNSAIDtherapy:Theusualdoseis20mgoncedaily.Thetreatmentdurationis

4-8weeks.

PreventionofgastricandduodenalulcersassociatedwithNSAIDtherapyinpatientsatrisk:20mgoncedaily.

TreatmentofZollingerEllisonSyndrome

TherecommendedinitialdosageisEsomeprazoleTablet40mgtwicedaily.Thedosageshouldthenbeindividually

adjustedandtreatmentcontinuedaslongasclinicallyindicated.Basedontheclinicaldataavailable,themajorityof

patientscanbecontrolledondosesbetween80to160mgesomeprazoledaily.Withdosesabove80mgdaily,thedose

shouldbedividedandgiventwicedaily.

Childrenbelowtheageof12years

EsomeprazoleTabletshouldnotbeusedinchildrenyoungerthan12yearssincenodataisavailable.

Impairedrenalfunction

Doseadjustmentisnotrequiredinpatientswithimpairedrenalfunction.Duetolimitedexperienceinpatientswith

severerenalinsufficiency,suchpatientsshouldbetreatedwithcaution.(Seesection5.2).

Impairedhepaticfunction

Doseadjustmentisnotrequiredinpatientswithmildtomoderateliverimpairment.Forpatientswithsevereliver

impairment,amaximumdoseof20mgEsomeprazoleTabletshouldnotbeexceeded.(Seesection5.2).

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4.3Contraindications

Knownhypersensitivitytoesomeprazole,substitutedbenzimidazolesoranyotherconstituentsoftheformulation

Hypersensitivitytoanyotherprotonpumpinhibitors

Esomeprazoleshouldnotbeusedconcomitantlywithnelfinavir(Seesection4.5)

4.4Specialwarningsandprecautionsforuse

Inthepresenceofanyalarmsymptom(e.g.significantunintentionalweightloss,recurrentvomiting,dysphagia,

haematemesisormelaena)andwhengastriculcerissuspectedorpresent,malignancyshouldbeexcluded,astreatment

withEsomeprazoleTabletmayalleviatesymptomsanddelaydiagnosis.

Patientsonlong-termtreatment(particularlythosetreatedformorethanayear)shouldbekeptunderregular

surveillance.

Patientsonon-demandtreatmentshouldbeinstructedtocontacttheirphysicianiftheirsymptomschangeincharacter.

Whenprescribingesomeprazoleforondemandtherapy,theimplicationsforinteractionswithotherpharmaceuticals,

duetofluctuatingplasmaconcentrationsofesomeprazoleshouldbeconsidered.Seesection4.5.

WhenprescribingesomeprazoleforeradicationofHelicobacterpyloripossibledruginterationsforallcomponentsin

thetripletherapyshouldbeconsidered.ClarithromycinisapotentinhibitorofCYP3A4andhencecontraindications

andinteractionsforclarithromycinshouldbeconsideredwhenthetripletherapyisusedinpatientsconcurrentlytaking

otherdrugsmetabolisedviaCYP3A4suchascisapride.

Thismedicinalproductcontainssucrose.Patientswithrarehereditaryproblemsoffructoseintolerance,glucose-

galactosemalabsorptionorsucrase-isomaltaseinsufficiencyshouldnottakethismedicine.

Treatmentwithprotonpumpinhibitorsmayleadtoslightlyincreasedriskofgastrointestinalinfectionssuchas

SalmonellaandCampylobacter(seesection5.1).

Co-administrationofesomeprazolewithatazanavirisnotrecommended(seesection4.5).Ifthecombinationof

atazanavirwithaprotonpumpinhibitorisjudgedunavoidable,closeclinicalmonitoringisrecommendedin

combinationwithanincreaseinthedoseofatazanavirto400mgwith100mgofritonavir;esomeprazole20mgshould

notbeexceeded.

4.5Interactionwithothermedicinalproductsandotherformsofinteraction

Effectsofesomeprazoleonthepharmacokineticsofotherdrugs

MedicinalproductswithpHdependentabsorption

Thedecreasedintragastricacidityduringtreatmentwithesomeprazole,mightincreaseordecreasetheabsorptionof

drugsifthemechanismofabsorptionisinfluencedbygastricacidity.Incommonwiththeuseofotherinhibitorsof

acidsecretionorantacids,theabsorptionofketoconazoleanditraconazolecandecreaseduringtreatmentwith

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Omeprazolehasbeenreportedtointeractwithsomeproteaseinhibitors.Theclinicalimportanceandthemechanisms

behindthesereportedinteractionsarenotalwaysknown.IncreasedgastricpHduringomeprazoletreatmentmay

changetheabsorptionoftheproteaseinhibitors.OtherpossibleinteractionmechanismsareviainhibitionofCYP

2C19.Foratazanavirandnelfinavir,decreasedserumlevelshavebeenreportedwhengiventogetherwithomeprazole

andconcomitantadministrationisnotrecommended.Co-administrationofomeprazole(40mgoncedaily)with

atazanavir300mg/ritonavir100mgtohealthyvolunteersresultedinasubstantialreductioninatazanavirexposure

(approximately75%decreaseinAUC,CmaxandCmin).Increasingtheatazanavirdoseto400mgdidnotcompensate

fortheimpactofomeprazoleonatazanavirexposure.Theco-administrationofomeprazole(20mgqd)withatazanavir

400mg/ritonavir100mgtohealthyvolunteersresultedinadecreaseofapproximately30%intheatazanavirexposure

ascomparedwiththeexposureobservedwithatazanavir300mg/ritonavir100mgqdwithoutomeprazole20mgqd.

Co-administrationofomeprazole(40mgqd)reducedmeannelfinavirAUC,CmaxandCminby36–39%andmean

AUC,CmaxandCminforthepharmacologicallyactivemetaboliteM8wasreducedby75-92%.Forsaquinavir(with

concomitantritonavir),increasedserumlevels(80-100%)havebeenreportedduringconcomitantomeprazoletreatment

(40mgqd).Treatmentwithomeprazole20mgqdhadnoeffectontheexposureofdarunavir(withconcomitant

ritonavir)andamprenavir(withconcomitantritonavir).Treatmentwithesomeprazole20mgqdhadnoeffectonthe

exposureofamprenavir(withandwithoutconcomitantritonavir).Treatmentwithomeprazole40mgqdhadnoeffect

ontheexposureoflopinavir(withconcomitantritonavir).Duetothesimilarpharmacodynamiceffectsand

pharmacokineticpropertiesofomeprazoleandesomeprazole,concomitantadministrationwithesomeprazoleand

atazanavirisnotrecommendedandconcomitantadministrationwithesomeprazoleandnelfinaviriscontraindicated.

MedicinalproductsmetabolisedbyCYP2C19

EsomeprazoleinhibitsCYP2C19,themajoresomeprazolemetabolisingenzyme.Thus,whenesomeprazoleis

combinedwithdrugsmetabolisedbyCYP2C19,suchasdiazepam,citalopram,imipramine,clomipramine,phenytoin

etc.,theplasmaconcentrationsofthesedrugsmaybeincreasedandadosereductioncouldbeneeded.Thisshouldbe

consideredespeciallywhenprescribingesomeprazoleforondemandtherapy.Concomitantadministrationof30mg

esomeprazoleresultedina45%decreaseinclearanceoftheCYP2C19substratediazepam.Concomitantadministration

of40mgesomeprazoleresultedina13%increaseintroughplasmalevelsofphenytoininepilepticpatients.Itis

recommendedtomonitortheplasmaconcentrationsofphenytoinwhentreatmentwithesomeprazoleisintroducedor

withdrawn.Omeprazole(40mgoncedaily)increasedvoriconazole(aCYP2C19substrate)CmaxandAUCby15%

and41%,respectively.

Concomitantadministrationof40mgesomeprazoletowarfarin-treatedpatientsinaclinicaltrialshowedthat

coagulationtimeswerewithintheacceptedrange.However,post-marketing,afewisolatedcasesofelevatedINRof

clinicalsignificancehavebeenreportedduringconcomitanttreatment.Monitoringisrecommendedwheninitiatingand

endingconcomitantesomeprazoletreatmentduringtreatmentwithwarfarinorothercoumarinederivatives.

Inhealthyvolunteers,concomitantadministrationof40mgesomeprazoleresultedina32%increaseinareaunderthe

plasmaconcentration-timecurve(AUC)anda31%prolongationofeliminationhalf-life(t1/2)butnosignificant

increaseinpeakplasmalevelsofcisapride.TheslightlyprolongedQTcintervalobservedafteradministrationof

cisapridealone,wasnotfurtherprolongedwhencisapridewasgivenincombinationwithesomeprazole(seealso

section4.4).

Esomeprazolehasbeenshowntohavenoclinicallyrelevanteffectsonthepharmacokineticsofamoxicillin,quinidine.

Studiesevaluatingconcomitantadministrationofesomeprazoleandeithernaproxenorrofecoxibdidnotidentifyany

clinicallyrelevantpharmacokineticinteractionsduringshort-termstudies.

Effectsofotherdrugsonthepharmacokineticsofesomeprazole

EsomeprazoleismetabolisedbyCYP2C19andCYP3A4.ConcomitantadministrationofesomeprazoleandaCYP3A4

inhibitor,clarithromycin(500mgb.i.d.),resultedinadoublingoftheexposure(AUC)toesomeprazole.Concomitant

administrationofesomeprazoleandacombinedinhibitorofCYP2C19andCYP3A4mayresultinmorethandoubling

oftheesomeprazoleexposure.TheCYP2C19andCYP3A4inhibitorvoriconazoleincreasedomeprazoleAUCby

280%.Adoseadjustmentofesomeprazoleisnotregularlyrequiredineitherofthesesituations.However,dose

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4.6Fertility,pregnancyandlactation

ForEsomeprazoleTablet,clinicaldataonexposedpregnanciesareinsufficient.Withtheracemicmixture,omeprazole,

dataonalargernumberofexposedpregnanciesfromepidemiologicalstudiesindicatenomalformativenorfoetotoxic

effect.Animalstudieswithesomeprazoledonotindicatedirectorindirectharmfuleffectswithrespectto

embryonal/fetaldevelopment.Animalstudieswiththeracemicmixturedonotindicatedirectorindirectharmfuleffects

withrespecttopregnancy,parturitionorpostnataldevelopment.Cautionshouldbeexercisedwhenprescribingto

pregnantwomen.

Itisnotknownwhetheresomeprazoleisexcretedinhumanbreastmilk.Nostudiesinlactatingwomenhavebeen

performed.ThereforeEsomeprazoleTabletshouldnotbeusedduringbreast-feeding.

4.7Effectsonabilitytodriveandusemachines

Noeffectshavebeenobserved.

4.8Undesirableeffects

Thefollowingadversedrugreactionshavebeenidentifiedorsuspectedintheclinicaltrialsprogrammefor

esomeprazoleandpost-marketing.Nonewasfoundtobedose-related.Thereactionsareclassifiedaccordingto

frequency(verycommon(1/10),common(1/100to<1/10),uncommon(1/1,000to<1/100),rare(1/10,000to

<1/1,000),veryrare(<1/10,000),notknown(cannotbeestimatedfromtheavailabledata)

Bloodandlymphaticsystemdisorders

Rare:Leukopenia,thrombocytopenia

Veryrare:Agranulocytosis,pancytopenia

Immunesystemdisorders

Rare:Hypersensitivityreactionse.g.fever,angioedemaandanaphylacticreaction/shock

Metabolismandnutritiondisorders

Uncommon:Peripheraloedema

Rare:Hyponatraemia

Psychiatricdisorders

Uncommon:Insomnia

Rare:Agitation,confusion,depression

Veryrare:Aggression,hallucinations

Nervoussystemdisorders

Common:Headache

Uncommon:Dizziness,paraesthesia,somnolence

Rare:Tastedisturbance

Eyedisorders

Rare:Blurredvision

Earandlabyrinthdisorders

Uncommon:Vertigo

Respiratory,thoracicandmediastinaldisorders

Rare:Bronchospasm

Gastrointestinaldisorders

Common:Abdominalpain,constipation,diarrhoea,flatulence,nausea/vomitingUncommon:Drymouth

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Hepatobiliarydisorders

Uncommon:Increasedliverenzymes

Rare:Hepatitiswithorwithoutjaundice

Veryrare:Hepaticfailure,encephalopathyinpatientswithpre-existingliverdisease

Skinandsubcutaneoustissuedisorders

Uncommon:Dermatitis,pruritus,rash,urticaria

Rare:Alopecia,photosensitivity

Veryrare:Erythemamultiforme,Stevens-Johnsonsyndrome,toxicepidermalnecrolysis(TEN)

Musculoskeletal,connectivetissueandbonedisorders

Rare:Arthralgia,myalgia

Veryrare:Muscularweakness

Renalandurinarydisorders

Veryrare:Interstitialnephritis

Reproductivesystemandbreastdisorders

Veryrare:Gynaecomastia

Generaldisordersandadministrationsiteconditions

Rare:Malaise,increasedsweating

4.9Overdose

Thereisverylimitedexperiencetodatewithdeliberateoverdose.Thesymptomsdescribedinconnectionwith280mg

weregastrointestinalsymptomsandweakness.Singledosesof80mgesomeprazolewereuneventful.Nospecific

antidoteisknown.Esomeprazoleisextensivelyplasmaproteinboundandisthereforenotreadilydialyzable.Asinany

caseofoverdose,treatmentshouldbesymptomaticandgeneralsupportivemeasuresshouldbeutilised.

5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

Pharmacotherapeuticgroup:protonpumpinhibitor

ATCCode:A02BC05

EsomeprazoleistheS-isomerofomeprazoleandreducesgastricacidsecretionthroughaspecifictargetedmechanism

ofaction.Itisaspecificinhibitoroftheacidpumpintheparietalcell.BoththeR-andS-isomerofomeprazolehave

similarpharmacodynamicactivity.

Siteandmechanismofaction

Esomeprazoleisaweakbaseandisconcentratedandconvertedtotheactiveforminthehighlyacidicenvironmentof

thesecretorycanaliculioftheparietalcell,whereitinhibitstheenzymeH+K+-ATPase–theacidpumpandinhibits

bothbasalandstimulatedacidsecretion.

Effectongastricacidsecretion

Afteroraldosingwithesomeprazole20mgand40mgtheonsetofeffectoccurswithinonehour.Afterrepeated

administrationwith20mgesomeprazoleoncedailyforfivedays,meanpeakacidoutputafterpentagastrinstimulation

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Afterfivedaysoforaldosingwith20mgand40mgofesomeprazole,intragastricpHabove4wasmaintainedfora

meantimeof13hoursand17hours,respectivelyover24hoursinsymptomaticGERDpatients.Theproportionof

patientsmaintaininganintragastricpHabove4foratleast8,12and16hoursrespectivelywereforesomeprazole20

mg76%,54%and24%.Correspondingproportionsforesomeprazole40mgwere97%,92%and56%.

UsingAUCasasurrogateparameterforplasmaconcentration,arelationshipbetweeninhibitionofacidsecretionand

exposurehasbeenshown.

Therapeuticeffectsofacidinhibition

Healingofrefluxesophagitiswithesomeprazole40mgoccursinapproximately78%ofpatientsafterfourweeks,and

in93%aftereightweeks.

Oneweektreatmentwithesomeprazole20mgb.i.d.andappropriateantibiotics,resultsinsuccessfuleradicationofH.

pyloriinapproximately90%ofpatients.

Aftereradicationtreatmentforoneweekthereisnoneedforsubsequentmonotherapywithantisecretorydrugsfor

effectiveulcerhealingandsymptomresolutioninuncomplicatedduodenalulcers.

Othereffectsrelatedtoacidinhibition

Duringtreatmentwithantisecretorydrugsserumgastrinincreasesinresponsetothedecreasedacidsecretion.

AnincreasednumberofECLcellspossiblyrelatedtotheincreasedserumgastrinlevels,havebeenobservedinsome

patientsduringlongtermtreatmentwithesomeprazole.

Duringlong-termtreatmentwithantisecretorydrugsgastricglandularcystshavebeenreportedtooccuratasomewhat

increasedfrequency.Thesechangesareaphysiologicalconsequenceofpronouncedinhibitionofacidsecretion,are

benignandappeartobereversible.

Decreasedgastricacidityduetoanymeansincludingprotonpumpinhibitors,increasesgastriccountsofbacteria

normallypresentinthegastrointestinaltract.Treatmentwithprotonpumpinhibitorsmayleadtoslightlyincreasedrisk

ofgastrointestinalinfectionssuchasSalmonellaandCampylobacter.

Intwostudieswithranitidineasanactivecomparator,EsomeprazoleTabletshowedbettereffectinhealingofgastric

ulcersinpatientsusingNSAIDs,includingCOX-2selectiveNSAIDs.

Intwostudieswithplaceboascomparator,EsomeprazoleTabletshowedbettereffectinthepreventionofgastricand

duodenalulcersinpatientsusingNSAIDs(aged>60and/orwithpreviousulcer),includingCOX-2selectiveNSAIDs.

5.2Pharmacokineticproperties

Absorptionanddistribution

Esomeprazoleisacidlabileandisadministeredorallyasenteric-coatedgranules.InvivoconversiontotheR-isomeris

negligible.Absorptionofesomeprazoleisrapid,withpeakplasmalevelsoccurringapproximately1-2hoursafterdose.

Theabsolutebioavailabilityis64%afterasingledoseof40mgandincreasesto89%afterrepeatedonce-daily

administration.For20mgesomeprazolethecorrespondingvaluesare50%and68%respectively.Theapparentvolume

ofdistributionatsteadystateinhealthysubjectsisapproximately0.22L/kgbodyweight.Esomeprazoleis97%plasma

proteinbound.

Foodintakebothdelaysanddecreasestheabsorptionofesomeprazolealthoughthishasnosignificantinfluenceonthe

effectofesomeprazoleonintragastricacidity.

Metabolismandexcretion

EsomeprazoleiscompletelymetabolisedbythecytochromeP450system(CYP).Themajorpartofthemetabolismof

esomeprazoleisdependentonthepolymorphicCYP2C19,responsiblefortheformationofthehydroxy-anddesmethyl

metabolitesofesomeprazole.Theremainingpartisdependentonanotherspecificisoform,CYP3A4,responsiblefor

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TheparametersbelowreflectmainlythepharmacokineticsinindividualswithafunctionalCYP2C19enzyme,

extensivemetabolisers.

Totalplasmaclearanceisabout17L/hafterasingledoseandabout9L/hafterrepeatedadministration.Theplasma

eliminationhalf-lifeisabout1.3hoursafterrepeatedonce-dailydosing.Thepharmacokineticsofesomeprazolehas

beenstudiedindosesupto40mgb.i.d.Theareaundertheplasmaconcentration-timecurveincreaseswithrepeated

administrationofesomeprazole.Thisincreaseisdose-dependentandresultsinamorethandoseproportionalincrease

inAUCafterrepeatedadministration.Thistime-anddose-dependencyisduetoadecreaseoffirstpassmetabolism

andsystemicclearanceprobablycausedbyaninhibitionoftheCYP2C19enzymebyesomeprazoleand/oritssulphone

metabolite.Esomeprazoleiscompletelyeliminatedfromplasmabetweendoseswithnotendencyforaccumulation

duringonce-dailyadministration.

Themajormetabolitesofesomeprazolehavenoeffectongastricacidsecretion.Almost80%ofanoraldoseof

esomeprazoleisexcretedasmetabolitesintheurine,theremainderinthefaeces.Lessthan1%oftheparentdrugis

foundinurine.

Specialpatientpopulations

Approximately2.91.5%ofthepopulationlackafunctionalCYP2C19enzymeandarecalledpoormetabolisers.In

theseindividualsthemetabolismofesomeprazoleisprobablymainlycatalysedbyCYP3A4.Afterrepeatedonce-daily

administrationof40mgesomeprazole,themeanareaundertheplasmaconcentration-timecurvewasapproximately

100%higherinpoormetabolisersthaninsubjectshavingafunctionalCYP2C19enzyme(extensivemetabolisers).

Meanpeakplasmaconcentrationswereincreasedbyabout60%.

Thesefindingshavenoimplicationsfortheposologyofesomeprazole.

Themetabolismofesomeprazoleisnotsignificantlychangedinelderlysubjects(71-80yearsofage).

Followingasingledoseof40mgesomeprazolethemeanareundertheplasmaconcentration-timecurveis

approximately30%higherinfemalesthaninmales.Nogenderdifferenceisseenafterrepeatedonce-daily

administration.Thesefindingshavenoimplicationsfortheposologyofesomeprazole.

Impairedorganfunction

Themetabolismofesomeprazoleinpatientswithmildtomoderateliverdysfunctionmaybeimpaired.Themetabolic

rateisdecreasedinpatientswithsevereliverdysfunctionresultinginadoublingoftheareaundertheplasma

concentration-timecurveofesomeprazole.Therefore,amaximumof20mgshouldnotbeexceededinpatientswith

severedysfunction.Esomeprazoleoritsmajormetabolitesdonotshowanytendencytoaccumulatewithonce-daily

dosing.Nostudieshavebeenperformedinpatientswithdecreasedrenalfunction.Sincethekidneyisresponsiblefor

theexcretionofthemetabolitesofesomeprazolebutnotfortheeliminationoftheparentcompound,themetabolismof

esomeprazoleisnotexpectedtobechangedinpatientswithimpairedrenalfunction.

Paediatric

Adolescents12-18years:

Followingrepeateddoseadministrationof20mgand40mgesomeprazole,thetotalexposure(AUC)andthetimeto

reachmaximumplasmadrugconcentration(tmax)in12to18year-oldswassimilartothatinadultsforboth

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5.3Preclinicalsafetydata

Preclinicalbridgingstudiesrevealnoparticularhazardforhumansbasedonconventionalstudiesofrepeateddose

toxicity,genotoxicity,andtoxicitytoreproduction.Carcinogenicitystudiesintheratwiththeracemicmixturehave

showngastricECL-cellhyperplasiaandcarcinoids.Thesegastriceffectsintherataretheresultofsustained,

pronouncedhypergastrinaemiasecondarytoreducedproductionofgastricacidandareobservedafterlong-term

treatmentintheratwithinhibitorsofgastricacidsecretion.

6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

Tabletscore

Hydroxypropylcellulose(E463)

Crospovidone(TypeA)

Coat

Povidone(K30)

Macrogol-400

Macrogol-4000

Macrogol6000

Hypromellosephthalate(HP-55S)

Hypromellosephthalate(HP-50)

Diethylphthalate

Hydroxypropylcellulose

Microcrystallinecellulose(PH101)

Microcrystallinecellulose(PH112)

Crosspovidone(TypeB)

Sodiumstearylfumarate

Opadry03B86651Brown

(HMPC2910/Hypromellose6cP

TitaniumDioxide,

Macrogol/PEG400

IronOxidered(E172))

Sugarspheres(sucroseandmaizestarch)

Talc(E553b)

6.2Incompatibilities

Notapplicable

6.3Shelflife

3years

6.4Specialprecautionsforstorage

Storebelow30°C

6.5Natureandcontentsofcontainer

OPA-AI-PE-dessicant-HDPE/AIblister7,14,15,28,30,50,56,60,90,98and100tablets

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6.6Specialprecautionsfordisposalandotherhandling

Anyunusedproductorwasteshouldbedisposedofinaccordancewithlocalrequirements

Administrationthroughgastrictube

1.Putthetabletintoanappropriatesyringeandfillthesyringewith

approximately25mlwaterandapproximately5mLair.Forsome

tubes,dispersionin50mlwaterisneededtopreventthepelletsfrom

cloggingthetube.

2.Immediatelyshakethesyringeforapproximately2minutesto

dispersethetablet.

3.Holdthesyringewiththetipupandcheckthatthetiphasnotclogged.

4.Attachthesyringetothetubewhilstmaintainingtheaboveposition.

5.Shakethesyringeandpositionitwiththetippointingdown.

Immediatelyinject5–10mlintothetube.Invertthesyringeafter

injectionandshake(thesyringemustbeheldwiththetippointingup

toavoidcloggingofthetip)

6.Turnthesyringewiththetipdownandimmediatelyinjectanother

5-10mlintothetube.Repeatthisprocedureuntilthesyringeis

empty.

7.Fillthesyringewith25mlofwaterand5mlofairandrepeatstep5

ifnecessarytowashdownanysedimentleftinthesyringe.Forsome

tubes,50mlwaterisneeded.

7MARKETINGAUTHORISATIONHOLDER

RanbaxyIrelandLimited,

Spafield,

CorkRoad,

Cashel,

Co.Tipperary.

8MARKETINGAUTHORISATIONNUMBER

PA408/81/1

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

Dateoffirstauthorisation:4thFebruary2011

10DATEOFREVISIONOFTHETEXT

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