BYSEC

Main information

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

Documents

Localization

  • Available in:
  • BYSEC Capsules Gastro-Resistant 20 Milligram
    Ireland
  • Language:
  • English

Status

  • Source:
  • HPRA - Health Products Regulatory Authority - Ireland
  • Authorization number:
  • PA0966/015/002
  • Authorization date:
  • 13-05-2005
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

BySec20mggastro-resistantcapsules,hard

2QUALITATIVEANDQUANTITATIVECOMPOSITION

Eachgastro-resistantcapsulecontains20mgofomeprazole.

Excipient:eachcapsulecontains52.40mgofsucrose,methyl-p-hydroxybenzoate(E218)andpropyl-p-

hydroxybenzoate(E216).

Forafulllistofexcipients,seesection6.1.

3PHARMACEUTICALFORM

Gastro-resistantcapsule,hard

Opaquewhitecapsulewithimprint‘20mg’.

4CLINICALPARTICULARS

4.1TherapeuticIndications

BySeccapsulesareindicatedfor:

Adults

Treatmentofduodenalulcers

Preventionofrelapseofduodenalulcers

Treatmentofgastriculcers

Preventionofrelapseofgastriculcers

Incombinationwithappropriateantibiotics,Helicobacterpylori(H.pylori)eradicationinpeptic

ulcerdisease

TreatmentofNSAID-associatedgastricandduodenalulcers

PreventionofNSAID-associatedgastricandduodenalulcersinpatientsatrisk

Treatmentofrefluxesophagitis

Long-termmanagementofpatientswithhealedrefluxesophagitis

Treatmentofsymptomaticgastro-esophagealrefluxdisease

TreatmentofZollinger-Ellisonsyndrome

Paediatricuse

Childrenover1yearofageand10kg

Treatmentofrefluxesophagitis

Symptomatictreatmentofheartburnandacidregurgitationingastro-esophagealrefluxdisease

Childrenandadolescentsover4yearsofage

IncombinationwithantibioticsintreatmentofduodenalulcercausedbyH.pylori

4.2Posologyandmethodofadministration

Posologyinadults

Treatmentofduodenalulcers

TherecommendeddoseinpatientswithanactiveduodenalulcerisBySec20mgoncedaily.Inmostpatientshealing

occurswithintwoweeks.Forthosepatientswhomaynotbefullyhealedaftertheinitialcourse,healingusuallyoccurs

duringafurthertwoweekstreatmentperiod.InpatientswithpoorlyresponsiveduodenalulcerBySec40mgoncedaily

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Preventionofrelapseofduodenalulcers

ForthepreventionofrelapseofduodenalulcerinH.pylorinegativepatientsorwhenH.pylorieradicationisnot

possibletherecommendeddoseisBySec20mgoncedaily.Insomepatientsadailydoseof10mgmaybesufficient.

Incaseoftherapyfailure,thedosecanbeincreasedto40mg.

Treatmentofgastriculcers

TherecommendeddoseisBySec20mgoncedaily.Inmostpatientshealingoccurswithinfourweeks.Forthose

patientswhomaynotbefullyhealedaftertheinitialcourse,healingusuallyoccursduringafurtherfourweeks

treatmentperiod.InpatientswithpoorlyresponsivegastriculcerBySec40mgoncedailyisrecommendedandhealing

isusuallyachievedwithineightweeks.

Preventionofrelapseofgastriculcers

ForthepreventionofrelapseinpatientswithpoorlyresponsivegastriculcertherecommendeddoseisBySec20mg

oncedaily.IfneededthedosecanbeincreasedtoBySec40mgoncedaily.

H.pylorieradicationinpepticulcerdisease

FortheeradicationofH.pyloritheselectionofantibioticsshouldconsidertheindividualpatient’sdrugtolerance,and

shouldbeundertakeninaccordancewithnational,regionalandlocalresistancepatternsandtreatmentguidelines.

BySec20mg+clarithromycin500mg+amoxicillin1,000mg,eachtwicedailyforone

week,or

BySec20mg+clarithromycin250mg(alternatively500mg)+metronidazole400mg(or500mgortinidazole500

mg),eachtwicedailyforoneweekor

BySec40mgoncedailywithamoxicillin500mgandmetronidazole400mg(or500mgortinidazole500mg),both

threetimesadayforoneweek.

Ineachregimen,ifthepatientisstillH.pyloripositive,therapymayberepeated.

TreatmentofNSAID-associatedgastricandduodenalulcers

ForthetreatmentofNSAID-associatedgastricandduodenalulcers,therecommendeddoseisBySec20mgoncedaily.

Inmostpatientshealingoccurswithinfourweeks.Forthosepatientswhomaynotbefullyhealedaftertheinitial

course,healingusuallyoccursduringafurtherfourweekstreatmentperiod.

PreventionofNSAID-associatedgastricandduodenalulcersinpatientsatrisk

ForthepreventionofNSAID-associatedgastriculcersorduodenalulcersinpatientsatrisk(age>60,previoushistory

ofgastricandduodenalulcers,previoushistoryofupperGIbleeding)therecommendeddoseisBySec20mgonce

daily.

Treatmentofrefluxesophagitis

TherecommendeddoseisBySec20mgoncedaily.Inmostpatientshealingoccurswithinfourweeks.Forthose

patientswhomaynotbefullyhealedaftertheinitialcourse,healingusuallyoccursduringafurtherfourweeks

treatmentperiod.InpatientswithsevereesophagitisBySec40mgoncedailyisrecommendedandhealingisusually

achievedwithineightweeks.

Long-termmanagementofpatientswithhealedrefluxesophagitis

Forthelong-termmanagementofpatientswithhealedrefluxesophagitistherecommendeddoseisBySec10mgonce

daily.Ifneeded,thedosecanbeincreasedtoBySec20-40mgoncedaily.

Treatmentofsymptomaticgastro-esophagealrefluxdisease

TherecommendeddoseisBySec20mgdaily.Patientsmayrespondadequatelyto10mgdaily,andtherefore

individualdoseadjustmentshouldbeconsidered.Ifsymptomcontrolhasnotbeenachievedafterfourweekstreatment

withBySec20mgdaily,furtherinvestigationisrecommended.

TreatmentofZollinger-Ellisonsyndrome

InpatientswithZollinger-Ellisonsyndromethedoseshouldbeindividuallyadjustedandtreatmentcontinuedaslong

asclinicallyindicated.TherecommendedinitialdoseisBySec60mgdaily.Allpatientswithseverediseaseand

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controlledandmorethan90%ofthepatientsmaintainedondosesofBySec20-120mgdaily.Whendoseexceed

BySec80mgdaily,thedoseshouldbedividedandgiventwicedaily.

Posologyinchildren

Childrenover1yearofageand10kg

Treatmentofrefluxesophagitis

Symptomatictreatmentofheartburnandacidregurgitationingastro-esophagealrefluxdisease

Theposologyrecommendationsareasfollows:

Refluxesophagitis:Thetreatmenttimeis4-8weeks.

Symptomatictreatmentofheartburnandacidregurgitationingastro-esophagealrefluxdisease:Thetreatmenttimeis

2–4weeks.Ifsymptomcontrolhasnotbeenachievedafter2–4weeksthepatientshouldbeinvestigatedfurther.

Childrenandadolescentsover4yearsofage

TreatmentofduodenalulcercausedbyH.pylori

Whenselectingappropriatecombinationtherapy,considerationshouldbegiventoofficialnational,regionalandlocal

guidanceregardingbacterialresistance,durationoftreatment(mostcommonly7daysbutsometimesupto14days),

andappropriateuseofantibacterialagents.

Thetreatmentshouldbesupervisedbyaspecialist.

Theposologyrecommendationsareasfollows:

Specialpopulations

Impairedrenalfunction

Doseadjustmentisnotneededinpatientswithimpairedrenalfunction(seesection5.2).

Impairedhepaticfunction

Inpatientswithimpairedhepaticfunctionadailydoseof10–20mgmaybesufficient(seesection5.2).

Elderly(>65yearsold)

Weight Posology

≥1yearofage

10-20g 10mgoncedaily.Thedosecan

beincreasedto20mgonce

dailyifneeded

≥2yearsofage >20kg 20mgoncedaily.Thedosecan

beincreasedto40mgonce

dailyifneeded

Weight Posology

15-30kg Combinationwithtwoantibiotics:BySec10

mg,amoxicillin25mg/kgbodyweightand

clarithromycin7.5mg/kgbodyweightareall

administratedtogethertwotimesdailyforone

week.

31-40kg Combinationwithtwoantibiotics:BySec20

mg,amoxicillin750mgandclarithromycin7.5

mg/kgbodyweightarealladministratedtwo

timesdailyforoneweek.

>40kg Combinationwithtwoantibiotics:BySec20

mg,amoxicillin1gandclarithromycin500mg

arealladministratedtwotimesdailyforone

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Methodofadministration:

ItisrecommendedtotakeBySeccapsulesinthemorning,preferablywithoutfood,swallowedwholewithhalfaglass

ofwater.Thecapsulesmustnotbechewedorcrushed.

Forpatientswithswallowingdifficultiesandforchildrenwhocandrinkorswallowsemi-solidfood

Patientscanopenthecapsuleandswallowthecontentswithhalfaglassofwateroraftermixingthecontentsina

slightlyacidicfluide.g.,fruitjuiceorapplesauce,orinnon-carbonatedwater.Patientsshouldbeadvisedthatthe

dispersionshouldbetakenimmediately(orwithin30minutes)andalways

bestirredjustbeforedrinkingandrinseddownwithhalfaglassofwater.

Alternativelypatientscansuckthecapsuleandswallowthepelletswithhalfaglassofwater.Theentericcoatedpellets

mustnotbechewed.

4.3Contraindications

Omeprazoleiscontraindicatedinpatientswithhypersensitivitytoomeprazoleortoanyoftheexcipients.

Childrenunder2yearsofage.

ConcomitantusewithSt.John’swortoratazanavirsulphate(Seesection4.5).

4.4Specialwarningsandprecautionsforuse

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

haematemesisormelena)andwhengastriculcerissuspectedorpresent,malignancyshouldbeexcluded,astreatment

mayalleviatesymptomsanddelaydiagnosis.

Co-administrationofatazanavirwithprotonpumpinhibitorsisnotrecommended(seesection4.5).Ifthecombination

ofatazanavirwithaprotonpumpinhibitorisjudgedunavoidable,closeclinicalmonitoring(e.gvirusload)is

recommendedincombinationwithanincreaseinthedoseofatazanavir

to400mgwith100mgofritonavir;omeprazole20mgshouldnotbeexceeded.

Omeprazole,asallacid-blockingmedicines,mayreducetheabsorptionofvitaminB12(cyanocobalamin)duetohypo-

orachlorhydria.ThisshouldbeconsideredinpatientswithreducedbodystoresorriskfactorsforreducedvitaminB12

absorptiononlong-termtherapy.

OmeprazoleisaCYP2C19inhibitor.Whenstartingorendingtreatmentwithomeprazole,thepotentialforinteractions

withdrugsmetabolisedthroughCYP2C19shouldbeconsidered.Aninteractionisobservedbetweenclopidogreland

omeprazole(seesection4.5).Theclinicalrelevanceofthis

interactionisuncertain.Asaprecaution,concomitantuseofomeprazoleandclopidogrelshouldbediscouraged.

Somechildrenwithchronicillnessesmayrequirelong-termtreatmentalthoughitisnotrecommended.

Thisproductcontainssucroseandpatientswithrarehereditaryproblemsoffructoseintolerance,glucose-galactose

malabsorptionorsucrase-isomaltaseinsufficiencyshouldnottakethisproduct.

Thisproductcontainsparahydroxybenzoatesandmaycauseallergicreactions(possiblydelayed).

Treatmentwithprotonpumpinhibitorsmayleadtoslightlyincreasedriskofgastrointestinalinfectionssuchas

SalmonellaandCampylobacter(seesection5.1).

Asinalllong-termtreatments,especiallywhenexceedingatreatmentperiodof1year,patientsshouldbekeptunder

regularsurveillance.

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Effectsofomeprazoleonthepharmacokineticsofotheractivesubstances

ActivesubstanceswithpHdependentabsorption

Thedecreasedintragastricacidityduringtreatmentwithomeprazolemightincreaseordecreasetheabsorptionofactive

substanceswithagastricpHdependentabsorption.

Nelfinavir,atazanavir

Theplasmalevelsofnelfinavirandatazanaviraredecreasedincaseofco-administrationwithomeprazole.

Concomitantadministrationofomeprazolewithnelfinaviriscontraindicated(seesection4.3).Coadministrationof

omeprazole(40mgoncedaily)reducedmeannelvinavirexposurebyca.40%andthemeanexposureofthe

pharmacologicallyactivemetaboliteM8wasreducedbyca.75–90%.TheinteractionmayalsoinvolveCYP2C19

inhibition.

Concomitantadministrationofomeprazolewithatazanavirisnotrecommended(seesection4.4).

Concomitantadministrationofomeprazole(40mgoncedaily)andatazanavir300mg/ritonavir100mgtohealthy

volunteersresultedina75%decreaseoftheatazanavirexposure.Increasingtheatazanavirdoseto400mgdidnot

compensatefortheimpactofomeprazoleonatazanavirexposure.

Theco-administrationofomeprazole(20mgoncedaily)withatazanavir400mg/ritonavir100mgtohealthyvolunteers

resultedinadecreaseofapproximately30%intheatazanavirexposureascomparedtoatazanavir300mg/ritonavir100

mgoncedaily.

Digoxin

Concomitanttreatmentwithomeprazole(20mgdaily)anddigoxininhealthysubjectsincreasedthebioavailabilityof

digoxinby10%.Digoxintoxicityhasbeenrarelyreported.Howevercautionshouldbeexercisedwhenomeprazoleis

givenathighdosesinelderlypatients.Therapeuticdrugmonitoringofdigoxinshouldbethenbereinforced.

Clopidogrel

Inacrossoverclinicalstudy,clopidogrel(300mgloadingdosefollowedby75mg/day)aloneandwithomeprazole(80

mgatthesametimeasclopidogrel)wereadministeredfor5days.Theexposuretotheactivemetaboliteofclopidogrel

wasdecreasedby46%(Day1)and42%(Day5)whenclopidogrelandomeprazolewereadministeredtogether.Mean

inhibitionofplateletaggregation(IPA)wasdiminishedby47%(24hours)and30%(Day5)whenclopidogreland

omeprazolewereadministeredtogether.Inanotherstudyitwasshownthatadministeringclopidogrelandomeprazole

atdifferenttimesdidnotpreventtheirinteractionthatislikelytobedrivenbytheinhibitoryeffectofomeprazoleon

CYP2C19.InconsistentdataontheclinicalimplicationsofthisPK/PDinteractionintermsofmajorcardiovascular

eventshavebeenreportedfromobservationalandclinicalstudies.

Otheractivesubstances

Theabsorptionofposaconazole,erlotinib,ketoconazoleanditraconazoleissignificantlyreducedandthusclinical

efficacymaybeimpaired.Forposaconazoleanderlotinibconcomitantuseshouldbeavoided.

ActivesubstancesmetabolisedbyCYP2C19

OmeprazoleisamoderateinhibitorofCYP2C19,themajoromeprazolemetabolisingenzyme.Thus,themetabolismof

concomitantactivesubstancesalsometabolisedbyCYP2C19,maybedecreasedandthesystemicexposuretothese

substancesincreased.ExamplesofsuchdrugsareR-warfarinandothervitaminKantagonists,cilostazol,diazepamand

phenytoin.

Cilostazol

Omeprazole,givenindosesof40mgtohealthysubjectsinacross-overstudy,increasedCmaxandAUCforcilostazol

by18%and26%respectively,andoneofitsactivemetabolitesby29%and69%respectively.

Phenytoin

Monitoringphenytoinplasmaconcentrationisrecommendedduringthefirsttwoweeksafterinitiatingomeprazole

treatmentand,ifaphenytoindoseadjustmentismade,monitoringandafurtherdoseadjustmentshouldoccurupon

endingomeprazoletreatment.

Unknownmechanism

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Concomitantadministrationofomeprazolewithsaquinavir/ritonavirresultedinincreasedplasmalevelsupto

approximately70%forsaquinavirassociatedwithgoodtolerabilityinHIV-infectedpatients.

Tacrolimus

Concomitantadministrationofomeprazolehasbeenreportedtoincreasetheserumlevelsoftacrolimus.Areinforced

monitoringoftacrolimusconcentrationsaswellasrenalfunction(creatinineclearance)shouldbeperformed,and

dosageoftacrolimusadjustedifneeded.

Effectsofotheractivesubstancesonthepharmacokineticsofomeprazole

InhibitorsCYP2C19and/orCYP3A4

SinceomeprazoleismetabolisedbyCYP2C19andCYP3A4,activesubstancesknowntoinhibitCYP2C19or

CYP3A4(suchasclarithromycinandvoriconazole)mayleadtoincreasedomeprazoleserumlevelsbydecreasing

omeprazole’srateofmetabolism.Concomitantvoriconazoletreatment

resultedinmorethandoublingoftheomeprazoleexposure.Ashighdosesofomeprazolehavebeenwell-tolerated

adjustmentoftheomeprazoledoseisnotgenerallyrequired.However,doseadjustmentshouldbeconsideredin

patientswithseverehepaticimpairmentandiflong-termtreatmentis

indicated.

InducersofCYP2C19and/orCYP3A4

ActivesubstancesknowntoinduceCYP2C19orCYP3A4orboth(suchasrifampicinandStJohn’swort)mayleadto

decreasedomeprazoleserumlevelsbyincreasingomeprazole’srateofmetabolism.

4.6Fertility,pregnancyandlactation

Resultsfromthreeprospectiveepidemiologicalstudies(morethan1000exposedoutcomes)indicatenoadverseeffects

ofomeprazoleonpregnancyoronthehealthofthefoetus/newbornchild.

Omeprazolecanbeusedduringpregnancy.

Omeprazoleisexcretedinbreastmilkbutisnotlikelytoinfluencethechildwhentherapeuticdosesareused.

4.7Effectsonabilitytodriveandusemachines

Omeprazoleisnotlikelytoaffecttheabilitytodriveorusemachines.Adversedrugreactionssuchasdizzinessand

visualdisturbancesmayoccur(seesection4.8).Ifaffected,patientsshouldnotdriveoroperatemachinery.

4.8Undesirableeffects

Themostcommonsideeffects(1-10%ofpatients)areheadache,abdominalpain,constipation,diarrhoea,flatulence

andnausea/vomiting.

Thefollowingadversedrugreactionshavebeenidentifiedorsuspectedintheclinicaltrialsprogrammeforomeprazole

andpost-marketing.Nonewasfoundtobedose-related.Adversereactionslistedbelowareclassifiedaccordingto

frequencyandSystemOrganClass(SOC).Frequencycategoriesaredefinedaccordingtothefollowingconvention:

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).

SOC/frequency Adversereaction

Bloodandlymphaticsystemdisorders

Rare: Leukopenia,thrombocytopenia

Veryrare: Agranulocytosis,pancytopenia

Immunesystemdisorders

Rare: Hypersensitivityreactionse.g.fever,

angioedemaandanaphylacticreaction/shock

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Paediatricpopulation

Thesafetyofomeprazolehasbeenassessedinatotalof310childrenaged0to16yearswithacidrelateddisease.There

arelimitedlongtermsafetydatafrom46childrenwhoreceivedmaintenancetherapyofomeprazoleduringaclinical

studyforsevereerosiveesophagitisforupto749days.Theadverseeventprofilewasgenerallythesameasforadults

inshort-aswellasinlong-termtreatment.Therearenolongtermdataregardingtheeffectsofomeprazoletreatment

onpubertyandgrowth.

4.9Overdose

Rare: Hyponatraemia

Veryrare: Hypomagnesaemia

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/vomiting

Rare: Drymouth,stomatitis,gastrointestinal

candidiasis

Hepatobiliarydisorders

Uncommon: Increasedliverenzymes

Rare: Hepatitiswithorwithoutjaundice

Veryrare: Hepaticfailure,encephalopathyinpatientswith

pre-existingliverdisease

Skinandsubcutaneoustissuedisorders

Uncommon: Dermatitis,pruritus,rash,urticaria

Rare: Alopecia,photosensitivity

Veryrare: Erythemamultiforme,Stevens-Johnson

syndrome,toxicepidermalnecrolysis

(TEN)

Musculoskeletalandconnectivetissuedisorders

Rare: Arthralgia,myalgia

Veryrare: Muscularweakness

Renalandurinarydisorders

Rare: Interstitialnephritis

Reproductivesystemandbreastdisorders

Veryrare: Gynaecomastia

Generaldisordersandadministrationsiteconditions

Uncommon: Malaise,peripheraloedema

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upto560mghavebeendescribed,andoccasionalreportshavebeenreceivedwhensingleoraldoseshavereachedup

to2,400mgomeprazole(120timestheusualrecommendedclinicaldose).Nausea,vomiting,dizziness,abdominal

pain,diarrhoeaandheadachehavebeenreported.Alsoapathy,depressionandconfusionhavebeendescribedinsingle

cases.

Thesymptomsdescribedhavebeentransient,andnoseriousoutcomehasbeenreported.Therateofeliminationwas

unchanged(firstorderkinetics)withincreaseddoses.Treatment,ifneeded,issymptomatic.

5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

Pharmacotherapeuticgroup:Protonpumpinhibitors

ATCcode:A02BC01

Mechanismofaction

Omeprazole,aracemicmixtureoftwoenantiomersreducesgastricacidsecretionthroughahighlytargetedmechanism

ofaction.Itisaspecificinhibitoroftheacidpumpintheparietalcell.Itisrapidlyactingandprovidescontrolthrough

reversibleinhibitionofgastricacidsecretionwithoncedailydosing.

Omeprazoleisaweakbaseandisconcentratedandconvertedtotheactiveforminthehighlyacidicenvironmentofthe

intracellularcanaliculiwithintheparietalcell,whereitinhibitstheenzymeH+K+-ATPase-theacidpump.Thiseffect

onthefinalstepofthegastricacidformationprocessisdose-dependentandprovidesforhighlyeffectiveinhibitionof

bothbasalacidsecretionandstimulatedacidsecretion,irrespectiveofstimulus.

Pharmacodynamiceffects

Allpharmacodynamiceffectsobservedcanbeexplainedbytheeffectofomeprazoleonacidsecretion.

Effectongastricacidsecretion

Oraldosingwithomeprazoleoncedailyprovidesforrapidandeffectiveinhibitionofdaytimeandnighttimegastric

acidsecretionwithmaximumeffectbeingachievedwithin4daysoftreatment.Withomeprazole20mg,amean

decreaseofatleast80%in24-hourintragastricacidityisthenmaintainedinduodenalulcerpatients,withthemean

decreaseinpeakacidoutputafterpentagastrinstimulationbeingabout70%24hoursafterdosing.

Oraldosingwithomeprazole20mgmaintainsanintragastricpHof ≥3forameantimeof17hoursofthe24-hour

periodinduodenalulcerpatients.

Asaconsequenceofreducedacidsecretionandintragastricacidity,omeprazoledose-dependentlyreduces/normalizes

acidexposureoftheesophagusinpatientswithgastro-esophagealrefluxdisease.

Theinhibitionofacidsecretionisrelatedtotheareaundertheplasmaconcentration-timecurve(AUC)ofomeprazole

andnottotheactualplasmaconcentrationatagiventime.

Notachyphylaxishasbeenobservedduringtreatmentwithomeprazole.

EffectonH.pylori

H.pyloriisassociatedwithpepticulcerdisease,includingduodenalandgastriculcerdisease.H.pyloriisamajor

factorinthedevelopmentofgastritis.H.pyloritogetherwithgastricacidaremajorfactorsinthedevelopmentofpeptic

ulcerdisease.H.pyloriisamajorfactorinthedevelopmentofatrophicgastritiswhichisassociatedwithanincreased

riskofdevelopinggastriccancer.

EradicationofH.pyloriwithomeprazoleandantimicrobialsisassociatedwith,highratesofhealingandlong-term

remissionofpepticulcers.

Dualtherapieshavebeentestedandfoundtobelesseffectivethantripletherapies.Theycould,however,beconsidered

incaseswhereknownhypersensitivityprecludesuseofanytriplecombination.

Othereffectsrelatedtoacidinhibition

Duringlong-termtreatmentgastricglandularcystshavebeenreportedinasomewhatincreasedfrequency.These

changesareaphysiologicalconsequenceofpronouncedinhibitionofacidsecretion,arebenignandappeartobe

reversible.

Decreasedgastricacidityduetoanymeansincludingprotonpumpinhibitors,increasesgastriccountsofbacteria

normallypresentinthegastrointestinaltract.Treatmentwithacid-reducingdrugsmayleadtoslightlyincreasedriskof

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Paediatricuse

Inanon-controlledstudyinchildren(1to16yearsofage)withsevererefluxesophagitis,omeprazoleatdosesof0.7to

1.4mg/kgimprovedesophagitislevelin90%ofthecasesandsignificantlyreducedrefluxsymptoms.Inasingle-blind

study,childrenaged0–24monthswithclinicallydiagnosedgastroesophagealrefluxdiseaseweretreatedwith0.5,1.0

or1.5mgomeprazole/kg.Thefrequencyofvomiting/regurgitationepisodesdecreasedby50%after8weeksof

treatmentirrespectiveofthedose.

EradicationofH.pyloriinchildren

Arandomised,doubleblindclinicalstudy(Héliotstudy)concludedthatomeprazoleincombinationwithtwo

antibiotics(amoxicillinandclarithromycin),wassafeandeffectiveinthetreatmentofH.pyloriinfectioninchildren

age4yearsoldandabovewithgastritis:H.pylorieradicationrate:74.2%

(23/31patients)withomeprazole+amoxicillin+clarithromycinversus9.4%(3/32patients)withamoxicillin+

clarithromycin.However,therewasnoevidenceofanyclinicalbenefitwithrespecttodyspepticsymptoms.Thisstudy

doesnotsupportanyinformationforchildrenagedlessthan4years.

5.2Pharmacokineticproperties

Absorption

Omeprazoleandomeprazolemagnesiumareacidlabileandarethereforeadministeredorallyasenteric-coatedgranules

incapsulesortablets.Absorptionofomeprazoleisrapid,withpeakplasmalevelsoccurringapproximately1-2hours

afterdose.Absorptionofomeprazoletakesplaceinthe

smallintestineandisusuallycompletedwithin3-6hours.Concomitantintakeoffoodhasnoinfluenceonthe

bioavailability.Thesystemicavailability(bioavailability)fromasingleoraldoseofomeprazoleisapproximately40%.

Afterrepeatedonce-dailyadministration,thebioavailabilityincreasestoabout60%.

Distribution

Theapparentvolumeofdistributioninhealthysubjectsisapproximately0.3l/kgbodyweight.Omeprazoleis97%

plasmaproteinbound.

Metabolism

OmeprazoleiscompletelymetabolisedbythecytochromeP450system(CYP).Themajorpartofitsmetabolismis

dependentonthepolymorphicallyexpressedCYP2C19,responsiblefortheformationofhydroxyomeprazole,the

majormetaboliteinplasma.Theremainingpartisdependentonanotherspecificisoform,CYP3A4,responsibleforthe

formationofomeprazolesulphone.AsaconsequenceofhighaffinityofomeprazoletoCYP2C19,thereisapotential

forcompetitiveinhibitionandmetabolicdrugdruginteractionswithothersubstratesforCYP2C19.However,dueto

lowaffinitytoCYP3A4,omeprazolehasnopotentialtoinhibitthemetabolismofotherCYP3A4substrates.In

addition,omeprazolelacksaninhibitoryeffectonthemainCYPenzymes.

Approximately3%oftheCaucasianpopulationand15-20%ofAsianpopulationslackafunctionalCYP2C19enzyme

andarecalledpoormetabolisers.Insuchindividualsthemetabolismofomeprazoleisprobablymainlycatalysedby

CYP3A4.Afterrepeatedonce-dailyadministrationof20mgomeprazole,themeanAUCwas5to10timeshigherin

poormetabolisersthaninsubjectshavingafunctionalCYP2C19enzyme(extensivemetabolisers).Meanpeakplasma

concentrationswerealsohigher,by3to5times.Thesefindingshavenoimplicationsfortheposologyofomeprazole.

Excretion

Theplasmaeliminationhalf-lifeofomeprazoleisusuallyshorterthanonehourbothaftersingleandrepeatedoral

once-dailydosing.Omeprazoleiscompletelyeliminatedfromplasmabetweendoseswithnotendencyfor

accumulationduringonce-dailyadministration.Almost80%ofanoraldoseof

omeprazoleisexcretedasmetabolitesintheurine,theremainderinthefaeces,primarilyoriginatingfrombile

secretion.

TheAUCofomeprazoleincreaseswithrepeatedadministration.Thisincreaseisdose-dependentandresultsinanon-

lineardose-AUCrelationshipafterrepeatedadministration.Thistime-anddosedependencyisduetoadecreaseoffirst

passmetabolismandsystemicclearanceprobablycaused

byaninhibitionoftheCYP2C19enzymebyomeprazoleand/oritsmetabolites(e.g.thesulphone).Nometabolitehas

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Specialpopulations

Impairedhepaticfunction

Themetabolismofomeprazoleinpatientswithliverdysfunctionisimpaired,resultinginanincreasedAUC.

Omeprazolehasnotshownanytendencytoaccumulatewithoncedailydosing.

Impairedrenalfunction

Thepharmacokineticsofomeprazole,includingsystemicbioavailabilityandeliminationrate,areunchangedinpatients

withreducedrenalfunction.

Elderly

Themetabolismrateofomeprazoleissomewhatreducedinelderlysubjects(75-79yearsofage).

Paediatricpatients

Duringtreatmentwiththerecommendeddosestochildrenfromtheageof1year,similarplasmaconcentrationswere

obtainedascomparedtoadults.Inchildrenyoungerthan6months,clearanceofomeprazoleislowduetolowcapacity

tometaboliseomeprazole.

5.3Preclinicalsafetydata

GastricECL-cellhyperplasiaandcarcinoids,havebeenobservedinlife-longstudiesinratstreatedwithomeprazole.

Thesechangesaretheresultofsustainedhypergastrinaemiasecondarytoacidinhibition.Similarfindingshavebeen

madeaftertreatmentwithH2-receptorantagonists,protonpump

inhibitorsandafterpartialfundectomy.Thus,thesechangesarenotfromadirecteffectofanyindividualactive

substance.

6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

Capsulecontents:

-Sugarspheres(containingsucroseandmaizestarch)

-Hypromellose

-Dimeticoneemulsion(containingpropyl-p-hydroxybenzoate(E216),methyl-p-hydroxybenzoate(E218),sorbicacid,

sodiumbenzoate,polyethyleneglycolsorbitanmonolaureate,octylphenoxypolyethoxyethanolandpropyleneglycol)

-Polysorbate80

-Mannitol

-Diacetylatedmonoglycerides

-Talc

-Methacrylicacid–ethylacrylatecopolymer(1:1)

-Triethylcitrate

-Stearoylmacrogolglycerides

Capsulesshell:

Gelatin

Titaniumdioxide(E171)

Blackink:

Shellac

Blackironoxide(E172)

6.2Incompatibilities

Notapplicable.

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HDPEbottles:

2years

Afterfirstopening:3months

Aluminiumblisters:

2years

6.4Specialprecautionsforstorage

HDPEbottles:

Donotstoreabove30°C.Storeintheoriginalpackageandkeepthebottletightlyclosed,inordertoprotectfromlight

andmoisture.

Aluminiumblisters:

Donotstoreabove30°C.Storeintheoriginalpackage,inordertoprotectfromlightandmoisture.

6.5Natureandcontentsofcontainer

Bottles(HDPE)containing1gsilicageldessicant,sealedwithanaluminiumsheet,withchildresistantclosure,packed

incardboardboxes.Packsizes:7,14,or28capsules.

PA-Aluminium-PVC/Aluminiumfoilblister,packedincardboardboxes.

Peel-to-open,perforatedunitdoseblister:

PA-Aluminium-PVC/Aluminiumfoilblister,packedincardboardboxes

PA-Aluminium-PVC/Aluminium-PETfoilblister,packedincardboardboxes

Packsizes:7,14,15,28,30,50,60,90or100capsules.

Notallpacksizesmaybemarketed.

6.6Specialprecautionsfordisposalofausedmedicinalproductorwastematerialsderivedfrom

suchmedicinalproductandotherhandlingoftheproduct

Nospecialrequirements.

7MARKETINGAUTHORISATIONHOLDER

ErghaHealthcareLtd.

Damastown

Mulhuddart

Dublin15

8MARKETINGAUTHORISATIONNUMBER

PA0966/015/002

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

Dateoffirstauthorisation:13May2005

Dateoflastrenewal:05October2010

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May2011 Irish Medicines Board

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Date Printed 24/05/2011 CRN 2095350 page number: 12