DAVLIET

Main information

  • Trade name:
  • DAVLIET Capsules Hard 40 Milligram
  • Dosage:
  • 40 Milligram
  • Pharmaceutical form:
  • Capsules Hard
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug

Documents

Localization

  • Available in:
  • DAVLIET Capsules Hard 40 Milligram
    Ireland
  • Language:
  • English

Status

  • Source:
  • HPRA - Health Products Regulatory Authority - Ireland
  • Authorization number:
  • PA1499/001/003
  • Authorization date:
  • 30-05-2008
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

IRISHMEDICINESBOARDACTS1995AND2006

MEDICINALPRODUCTS(CONTROLOFPLACINGONTHEMARKET)REGULATIONS,2007

(S.I.No.540of2007)

PA1499/001/003

CaseNo:2071132

TheIrishMedicinesBoardinexerciseofthepowersconferredonitbytheabovementionedRegulationsherebygrantsto

VolkspharmaGmbH

August-Wessels-Str.5,Augsburg,D-86154,Germany

anauthorisation,subjecttotheprovisionsofthesaidRegulations,inrespectoftheproduct

Davliet,40Milligram

TheparticularsofwhicharesetoutinPartIandPartIIoftheattachedSchedule.Theauthorisationisalsosubjecttothegeneralconditionsas

maybespecifiedinthesaidRegulationsaslistedonthereverseofthisdocument.

Thisauthorisation,unlesspreviouslyrevoked,shallcontinueinforcefrom07/12/2009until31/05/2012.

SignedonbehalfoftheIrishMedicinesBoardthis

________________

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Date Printed 07/12/2009 CRN 2071132 page number: 1

PartII

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

Davliet40mgCapsules

2QUALITATIVEANDQUANTITATIVECOMPOSITION

Eachcapsulecontains40mgofOmeprazole

Alsocontainssucrose

Forafulllistofexcipients,seeSection6.1

3PHARMACEUTICALFORM

Capsules,hard,withgastro-resistantgranules.

Opaquebluecapandopaqueorangebody,containingwhitetobeigegranules.

Size0capsulemarkedwithO40

4CLINICALPARTICULARS

4.1TherapeuticIndications

Duodenalulcers

Benigngastriculcers

Refluxoesophagitis

Maintenancetreatmentofrefluxoesophagitistopreventrelapse

Zollinger-Ellisonsyndrome

TreatmentofNSAID(NonSteroidAntiInflammatoryDrug)relatedgastricandduodenalulcers

MaintenancetreatmentofNSAIDrelatedgastricandduodenalulcerstopreventrelapse

Symptomatictreatmentofgastrooesophagealrefluxdisease

IncombinationwithappropriateantibacterialtherapeuticregimensfortheeradicationofHelicobacterpyloriin

patientswithHelicobacterpyloriassociatedpepticulcers(see4.2Posologyandmethodofadministration)

4.2Posologyandmethodofadministration

Duodenalulcers

Theusualdoseis20mgoncedaily.Thedurationofthetreatmentis2-4weeks.

Maintenancetreatment:forpreventionofrecurrenceaoncedaily10mgcapsuleisadvised.

Benigngastriculcers:

Theusualdoseis20mgoncedaily.Thedurationofthetreatmentis4-(6)-8weeks.

Refluxoesophagitis:

Theusualdoseis20mgoncedaily.Thedurationoftreatmentis4-8weeks.

Notes:

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increasedto40mgomeprazoleoncedaily.

Onlyiferadicationtherapyisnotindicatedorhasbeenunsuccessful,duodenalandgastriculcersmaybetreatedwith

omeprazolemonotherapy.

Childrenabove2yearsandadolescentswithsevererefluxoesophagitis:

Theclinicalexperienceinchildrenislimited.Omeprazoleshouldonlybeusedinchildrenwithseverereflux

oesophagitisresistanttoothertherapeuticmeasures.

Treatmentshouldbeinitiatedbyahospitalbasedpaediatrician.

ContinuouspHmeasurementandgenotyping(concerningCYP2C19status)maybeperformedifappropriatefor

optimaltherapeuticresponse.

Thefollowingdosage(equivalenttoabout1mg/kg/day)shouldbeused:

Weight10kgto20kg:10mg/day

Weightover20kg:20mg/day

Treatmentdurationisusually4to8weeksandshouldnotexceed12weeksduetolackofdatawithlong-termusein

thisagegroup.

Maintenancetreatmentofrefluxoesophagitistopreventrelapse:

Theusualdoseis10to20mgdependingontheclinicalresponse.

Zollinger-Ellisonsyndrome:

Thedosageshouldbeadjustedindividuallyandcontinuedunderspecialistsupervisionaslongasclinicallyindicated.

Therecommendedinitialdosageis60mgoncedaily.Withdosesabove80mgdaily,thedoseshouldbedividedand

giventwicedaily.InpatientswithZollinger-Ellisonsyndromethetreatmentisnotsubjecttoatimelimit.

TreatmentofNSAIDrelatedgastricandduodenalulcers:

Theusualdoseis20mgdaily.Thetreatmentdurationis4to8weeks.

MaintenancetreatmentofNSAIDrelatedgastricandduodenalulcerstopreventrelapse:

Theusualdoseis20mgdaily.

Symptomatictreatmentofgastroesophagealrefluxdisease:

Theusualdoseis10to20mgdailydependingonclinicalresponse.Thetreatmentdurationis

2to4weeks.

Ifthepatientdoesnotexperienceanyimprovementinsymptomsaftera2weektreatmentfurtherexaminationsshould

beperformed.

Eradicationtherapy:

PatientswithpepticulcersduetoHelicobacterpyloriinfectionshouldbetreatedwitheradicationtherapywith

appropriatecombinationsofantibioticswithadequatedosingregimens.Theselectionofanappropriateregimenshould

bebasedonpatienttolerabilityandtherapeuticguidelines.Thefollowingcombinationshavebeentested:

Omeprazole20mg,Amoxicillin1000mg,Clarithromycin500mgall2timesdaily

Omeprazole20mg,Clarithromycin250mg,Metronidazole400-500mgall2timesdaily

Thetreatmentdurationfortheeradicationis1week.Toavoidthedevelopmentofresistancethetreatmentduration

shouldnotbereduced.

Inpatientswithactiveulcersanextensionofthetherapywithomeprazole-monotherapyaccordingtotheposologyand

treatmentdurationgivenabovemaybeperformed.

Combinationtherapyincludingmetronidazoleshouldnotbeconsideredasfirstchoicebecauseofthecarcinogenic

potentialofmetronidazole.Theapplicationofmetronidazoleshouldberestrictedtotreatmentperiodsoflessthan10

days.

Elderly:

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Children:

Omeprazoleshouldnotbeusedinchildrenunder2yearsofage.

Impairedrenalfunction:

Doseadjustmentisnotrequiredinpatientswithimpairedrenalfunction.

Impairedhepaticfunction:

Asbioavailabilityandhalf-lifecanincreaseinpatientswithimpairedhepaticfunction,thedoserequiresadjustment

withamaximumdailydoseof20mg.

Methodofadministration:

Thecapsulesshouldbeswallowedwholewithsufficientfluid(e.g.1glassofwater)beforeameal(e.g.before

breakfastordinner)oronanemptystomach.Thecapsulesshouldnotbechewedormilled.

Inpatientswithswallowingdifficulties,thecapsulesmaybeopenedandthecontentsswallowedaloneorsuspendedin

asmallamountoffruitjuiceoryogurtaftergentlemixing.Theresultingdispersionshouldbetaken

immediately

4.3Contraindications

Omeprazoleiscontraindicatedinpatientswithhypersensitivitytoomeprazoleortoanyoftheexcipients.

Combinationtherapywithclarithromycinshouldnotbeusedinpatientswithhepaticimpairment.

Omeprazoleshouldnotbeadministeredwithatazanavirduetoanimportantreductioninatazanavirexposure(see

section4.5)

4.4Specialwarningsandprecautionsforuse

InpatientswithpepticulcerdiseaseHelicobacterpylori-statusshouldbedeterminedifrelevant.Inpatientswhoare

showntobeHelicobacterpylori-positive,theeliminationofthebacteriumbyeradicationtherapyshouldbeaimed

whereverpossible.

Ifagastriculcerissuspected,thepossibilityofmalignancymustbeexcludedbeforetreatmentwithOmeprazole

capsulesisinstituted,astreatmentmayalleviatesymptomsanddelaydiagnosis.

Thediagnosisofrefluxoesophagitisshouldbeconfirmedendoscopically.

Decreasedgastricacidity,duetoanymeans-includingproton-pumpinhibitors–increasesgastriccountsofbacteria

normallypresentinthegastro-intestinaltract.Treatmentwithacid-reducingmedicinalproductsleadstoaslightly

increasedriskofgastrointestinalinfections,suchasSalmonellaandCampylobacter.

Inpatientswithsevereimpairedhepaticfunction,liverenzymevaluesshouldbecheckedperiodicallyduringtreatment

withOmeprazolecapsules.

Thismedicinalproductcontainssucrose.Patientswithrarehereditaryproblemsoffructoseintolerance,glucose-

galactosemalabsorptionorsucrase-isomaltaseinsufficiencyshouldnottakethismedicinalproduct.

ToensurebetterefficacyintreatmentofNSAID-relatedulcers,thepossibilityofstoppingtheintakeofthecausative

agentshouldbestronglyconsidered.

ThemaintenancetreatmentofulcersassociatedwiththeintakeofNSAIDsshouldberestrictedtopatientsatrisk.

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treatmentandthoroughrisk-benefitassessmentshouldbeperformedinlong-termuseexceeding1year.

Duringtherapywithomeprazolerequiringacombinedadministrationofmedicinalproducts(NSAIDrelatedulcersor

eradication)cautionshouldbeexercisedwhenadministeringadditionalmedicinalproductsasinteractionsmightaddup

orpotentiate(seesection4.5Interactionwithothermedicinalproductsandotherformsofinteraction).

Duringcombinationtreatmentcautionshouldalsobeexercisedinpatientswithrenalorhepaticdysfunction(fordose

restrictionsee4.2Posologyandmethodofadministration).

Omeprazoleshouldnotbeusedininfantsandchildrenundertheageof2years(seesection4.2).

Althoughnotknownfororallyadministeredomeprazole,blindnessanddeafnesshavebeenreportedintheuseofthe

injectionformofomeprazole;therefore,inseverelyillpatientsthemonitoringofvisualandauditorysensesis

recommended.

Thismedicinalproductcontains1.306mgsodiumperdose.Tobetakenintoconsiderationbypatientsonacontrolled

sodiumdiet.

4.5Interactionwithothermedicinalproductsandotherformsofinteraction

AsomeprazoleismetabolisedintheliverthroughcytochromeP450isoforms(mainlyCYP2C19,

S-mephenytoinhydroxylase)andinhibitsenzymesoftheCYP2Csubfamily(CYP2C19andCYP2C9)itcandelaythe

eliminationofotheractivesubstancesmetabolisedbytheseenzymes.Thishasbeenobservedfordiazepam(andalsoof

otherbenzodiazepinesastriazolamorflurazepam),phenytoinandwarfarin.Periodicmonitoringofpatientsreceiving

warfarinorphenytoinisrecommendedandareductionofwarfarinorphenytoindosemaybenecessary.

Otheractivesubstancesthatcouldbeaffectedarehexabarbital,citalopram,imipramine,clomipramineetc.

Omeprazolemayinhibitthehepaticmetabolismofdisulfiram.Somepossiblyrelatedcasesofmuscularrigidityhave

beenreported.

Therearecontradictorydataontheinteractionofomeprazolewithciclosporinandtacrolimus.Therefore,theplasma

levelsofciclosporinandtacrolimusshouldbemonitoredinthosepatientstreatedwithomeprazole,becauseanincrease

inciclosporinlevelsispossible.

Plasmaconcentrationsofomeprazoleandclarithromycinareincreasedduringconcomitantadministration.

Duetothedecreasedintragastricacidity,theabsorptionofketoconazoleoritraconazolemaybereducedduring

omeprazoletreatmentasitiswithotheracidsecretioninhibitors.

Simultaneoustreatmentwithomeprazoleanddigoxininhealthysubjectsleadtoa10%increaseinthebioavailabilityof

digoxinasaconsequenceoftheincreasedgastricpH.

OmeprazolemayreducetheoralabsorptionofvitaminB12.Thisshouldbetakenintoaccountinthosepatientswith

lowbasallevelswhoundergoalong-termtreatmentwithomeprazole.

BecauseofpotentialclinicallysignificantinteractionSt.John'swortshouldnotbeusedconcomitantlywith

omeprazole.

Co-administrationofomeprazole40mgO.D.withatazanavir300mg/ritonavir100mgO.D.resultedinasubstantial

reductioninatazanavirexposure(approximately75%decreaseinAUC,CmaxandCmin).Increasingtheatazanavir

doseto400mgdidnotcompensatefortheimpactofomeprazoleonatazanavirexposure.Thusprotonpumpinhibitors

shouldnotbeco-administeredwithatazanavir.

Althoughnotstudied,otherdailydosesofomeprazolemayproducesimilarresultsand,therefore,also

co-administrationofanyotherdosesofomeprazoleiscontraindicated(seesection4.3).

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increasedesomeprazoleAUCby280%.Adoseadjustmentofesomeprazoleisnotregularlyrequired.However,dose

adjustmentshouldbeconsideredinpatientswithseverehepaticimpairment,thosereceivingahighdose,andiflong-

termtreatmentisindicated.

Thereisnoevidenceofaninteractionofomeprazolewithcaffeine,propranolol,theophylline,metoprolol,lidocaine,

quinidine,erythromycin,phenacetin,estradiol,amoxicillin,budesonide,diclofenac,metronidazole,naproxen,

piroxicam,orantacids.Theabsorptionofomeprazoleisnotaffectedbyalcohol.

4.6Pregnancyandlactation

Limitedepidemiologicstudiesindicatenoadverseeffectsonpregnancyorincreasesingeneralmalformationrate.

However,thereisinsufficientinformationwithrespecttospecificabnormalities.

Inrats,omeprazoleanditsmetabolitesareexcretedintomilk.Thereisinsufficientdataonexposureofbabiesvia

breastmilk.Omeprazoleconcentrationinhumanbreastmilkreachesapproximately6%ofthemaximumplasma

concentrationinthemother.

Useofomeprazoleduringpregnancyandlactationrequiresacarefulbenefit-riskassessment.

4.7Effectsonabilitytodriveandusemachines

Nostudiesontheabilitytodriveandusemachineshavebeenperformed.However,apartfromsideeffectsaffecting

theCNSorvisualabilities(see4.8.),noeffectsontheabilitytodriveareexpectedfromtheintakeof

omeprazole.

4.8Undesirableeffects

Thefollowingdefinitionsapplytotheincidenceoftheundesirableeffects:

verycommon(>1/10)

common(>1/100,<1/10)

uncommon(>1/1,000,<1/100)

rare(>1/10,000,<1/1,000)

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

Bloodandthelymphaticsystemdisorders Rare:

Hypochrome,microcyticanaemiainchildren.

Veryrare:

changesinbloodcount,reversible

thrombocytopenia,

leucopeniaorpancytopeniaandagranulocytosis.

Immunosystemdisorders Veryrare:

urticaria,elevatedbodytemperature,angioedema,

bronchoconstriction,oranaphylaticshock,allergic

vasculitisandfever.

Nervoussystemdisorders Common:

somnolence,sleepdisturbances(insomnia),

dizziness,

headachesanddrowsiness.Thesecomplaintsusually

improveduringcontinuedtherapy.

Rare:

Paresthesiaandlightheadedness.Mentalconfusion

andhallucinationsinpredominantlyseverelyillor

elderlypatients.

Veryrare:

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4.9Overdose

Thereisnoinformationavailableontheeffectsofoverdosageofomeprazoleinhumans.

Largesingleoraldosesupto160mg/dayanddailydosesupto400mgaswellasintravenoussingledosesupto80mg

anddailyintravenousdosesupto200mgor520mgin3days,respectively,havebeentoleratedwithoutundesirable

severelyillorelderlypatients.

Eyedisorders Uncommon:

visualdisturbances(blurredvision,lossofvisual

acuityorreducedfieldofvision).Theseconditions

usuallyresolveoncessationoftherapy.

Earandlabyrinthdisorders Uncommon:

auditorydysfunction(e.g.tinnitus).Theseconditions

usuallyresolveoncessationoftherapy.

Gastrointestinaldisorders Common:

diarrhoea,constipation,flatulence(possiblywith

abdominalpain),nauseaandvomiting.Inthe

majorityofthesecasesthesymptomsimproveifthe

therapyiscontinued.

Uncommon:

tastedisturbances.Thisconditionusuallyresolves

oncessationoftherapy.

Rare:

brownish-blackdiscolorationofthetongueduring

concomitantadministrationofclarithromycinand

benignglandularcysts:bothwerereversibleafter

cessationoftreatment.

Veryrare:

drynessofthemouth,stomatitis,candidiasisor

pancreatitis.

Hepato-biliarydisorders Uncommon:

changesinliverenzymevalues(whichresolveafter

discontinuationoftherapy).

Veryrare:hepatitiswithorwithoutjaundice,hepatic

failureandencephalopathyinpatientswithpre-

existingsevereliverdisease.

Skinandsubcutaneoustissuedisorders Uncommon:

pruritus,skineruptions,alopecia,erythema

multiformeorphotosensitivityandincreased

tendencytosweat.

Veryrare:

Stevens-Johnson-syndromeortoxicepidermal

necrolysis

Musculoskeletal,connectivetissueandbone

disorders Rare:

muscleweakness,myalgiaandjointpain.

Renalandurinarydisorders Veryrare:

nephritis(interstitialnephritis)

Otheradverseeffects: Uncommon:

generalmalaise,peripheraloedema(whichresolved

oncessationof

therapy)

Veryrare:

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5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

Pharmacotherapeuticgroup:Drugsforpepticulcerandgastro-oesophagealrefluxdisease(GORD),protonpump

inhibitorsATC-code:A02BC01

Omeprazole,asubstitutedbenzimidazole,isagastricprotonpumpinhibitor,i.e.Omeprazoledirectlyanddose-

dependentlyinhibitstheenzymeH +

,K +

-ATPase,whichisresponsibleforthegastricacidsecretioninthegastric

parietalcells.Duetothisselectiveintracellularmodeofactionandthelowaffinityforothermembrane-bound

receptors(suchasthehistamineH

,muscarineM

orgastrinergicreceptors),omeprazolehasbeenassignedtoa

separateclassofacid-inhibitingagents,whichblockthefinalstepofacidproduction.

Asaconsequenceofitsmodeofaction,omeprazoleleadstoaninhibitionofbothbasalandstimulableacidsecretion,

irrespectiveofthestimulustype.

Thus,omeprazoleincreasesthepH-valueandreducesthevolumeofgastricacidsecretion.

Asaweakbasetheprodrugomeprazoleaccumulatesintheacidenvironmentoftheparietalcellsandwillonlybecome

effectiveasaninhibitoroftheH +

,K +

-ATPaseafterbeingprotonisedandrearranged.

InanacidenvironmentatapHoflessthan4theprotonisedomeprazoleisconvertedtoomeprazolesulphenamide,the

activesubstanceproper.

Comparedtotheplasmahalf-lifeoftheomeprazolebase,omeprazolesulphenamideremainsinthecellforalonger

periodoftime(see5.2Pharmacokineticproperties).AsufficientlylowpH-valueisonlyfoundinthegastricparietal

cells;thisexplainsthehighspecificityofomeprazole.Itistheomeprazolesulphenamidethatbindstotheenzymeand

inhibitsitsactivity.

Iftheenzyme-systemisinhibited,thepH-valueincreasesandlessomeprazoleaccumulatesorisconvertedinthe

gastricparietalcells.Consequently,theaccumulationofomeprazoleisregulatedbyakindoffeedback-mechanism.

Inlong-termtreatment,omeprazole,asaresultofacidinhibition,causesamoderategastrinincrease.Mildtomoderate

increaseinECL-cellsoccursduringlong-termuse.Carcinoidsasfoundinanimalexperiments(see5.3Preclinical

safetydata)werenotseeninhumansyet.

Mostavailableclinicalexperienceformcontrolledrandomisedclinicaltrialsindicatethatomeprazole20mgtwice

dailyincombinationwithtwoantibioticsfor1weekachieve>80%Helicobacterpylorieradicationrateinpatientswith

gastro-duodenalulcers.Asexpected,significantlylowereradicationrateswereobservedinpatientswithbaseline

metronidazole-resistantHelicobacterpyloriisolates.Hence,localinformationontheprevalenceofresistanceandlocal

therapeuticguidelinesshouldbetakenintoaccountinthechoiceofanappropriatecombinationregimenfor

Helicobacterpylorieradicationtherapy.Furthermore,inpatientswithpersistentinfection,potentialdevelopmentof

secondaryresistance(inpatientswithprimarysusceptiblestrains)toanantibacterialagentshouldbetakenintoaccount

intheconsiderationsforanewretreatmentregimen.

Clinicalevidenceadditionallyindicatesthat,followingsuccessfuleradicationtherapyinpatientswithpepticulcer

disease,relapserates,duodenalulcersandmostlikelyalsogastriculcersareexceptionallylowincomparisontothe

naturalcourseofthediseasewithongoinginfection.

5.2Pharmacokineticproperties

Omeprazoleisacidlabileandisadministeredorallyasgastro-resistantgranulesinhard-gelatincapsules.Absorption

takesplaceinthesmallintestine.

Peakplasmaconcentrationsofomeprazoleoccurwithin1to3hoursafteradministration.Theplasmahalf-lifeisabout

40minutes,andthetotalplasmaclearanceis0.3to0.6l/min.Inasmallpercentageofthepatients(CYP2C19poor

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Inthesecases,theterminaleliminationhalf-lifecanbeapproximately3timesaslongasthenormalvalue,andthearea

undertheplasmaconcentration-timecurve(AUC)canincreasebyupto10times.

Thedistributionvolumeofomeprazoleinthebodyisrelativelysmall(0.3l/kgofbodyweight)andcorrespondstothat

oftheextracellularfluid.Approximately95%isproteinbound.

Omeprazoleaccumulatesasaweakbaseintheacidenvironmentoftheintracellularchannelsystemoftheparietal

cells.Inthisacidenvironmentomeprazoleisprotonisedandconvertedintotheactivesubstance,omeprazole

sulphenamide.Theactivesubstancebindscovalentlytothegastricprotonpump(H +

,K +

-ATPase)onthesecretory

surfaceofthegastricparietalcellandinhibitsitsactivity.Thedurationoftheinhibitionofacidsecretionistherefore

substantiallylongerthantheperiodinwhichomeprazole-baseispresentinplasma.Thedegreeofinhibitionofacid

secretionisdirectlycorrelatedtotheareaundertheplasmaconcentration-timecurve(AUC)butnottotheplasma

concentrationatanygiventime.

Omeprazoleisentirelymetabolised,mainlyintheliverbyCYP2C19.Asmallpercentageofthepatientslacka

functionalCYP2C19enzymeandhavereducedeliminationrateofomeprazole.Thesulphone,sulphideandhydroxy-

omeprazolearefoundinplasma.Thesemetaboliteshavenosignificanteffectonacidsecretion.

About20%ofadministereddoseisexcretedinfaecesandtheremaining80%isexcretedinurineasmetabolites.The

twomajorurinarymetabolitesarehydroxy-omeprazoleandthecorrespondingcarboxylicacid.

Inpatientswithrenalimpairmentthekineticsofomeprazolewasverysimilartothatinhealthysubjects.But,because

therenaleliminationisthemostimportantexcretorypathwayformetabolisedomeprazole,theeliminationrateis

reducedtoadegreecorrespondingtothereductioninrenalfunction.Ifomeprazoleisgivenoncedaily,accumulation

canbeavoided.

Thebioavailabilityofomeprazoleisslightlyelevatedintheelderly,andtheeliminationrateisslightlydiminished.But

theindividualvaluesarenearlyequaltothatofyounghealthysubjects,andthereisnoindicationthatthetolerancein

elderlypatientstreatedwithnormaldosesofomeprazoleisreduced.

Afterintravenousadministrationof40mgomeprazolefor5days,theabsolutemeasuredbioavailabilityincreasedby

about50%;thiscanbeexplainedbydecreasedhepaticclearanceduetosaturationoftheCYP2C19enzyme.

Inpatientswithchronichepaticdiseasetheclearanceofomeprazoleisreduced,andtheplasmahalf-lifecanincreaseup

toapproximately3hours.Thebioavailabilitycanthenbegreaterthan90%.Omeprazolegiveninadosageregimeof20

mgoncedailyfor4weekswastoleratedwell,andnoaccumulationofomeprazoleoritsmetaboliteswasobserved.

Thebioavailabilityofasingleoraldoseofomeprazoleisapproximately35%.Withrepeatedadministrationthe

bioavailabilityincreasestoapproximately60%.Inpatientswithrestrictedhepaticfunctionitcanincreasetoover90%

duetoareducedfirstpasseffect.

Simultaneousintakewithfoodlowertheabsorptionrate.

5.3Preclinicalsafetydata

Non-clinicaldatarevealnospecialhazardforhumansbasedonconventionalstudiesofsafetypharmacology,repeated

dosetoxicity,genotoxicityandtoxicitytoreproduction

GastricECL-cellhyperplasiaandcarcinoidshavebeenobservedinlife-longstudiesinratstreatedwithomeprazoleor

subjectedtopartialfundectomy.Thesechangesaretheresultofsustainedhypergastrinaemiasecondarytoacid

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6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

Sugarspheres

SodiumstarchglycollateTypeA

Sodiumlaurilsulfate

PovidoneK30

Potassiumoleate

Hypromellose

Methacrylicacid-ethylacrylatecopolymer

Triethylcitrate

Titaniumdioxide(E171)

Talc

Erythrosine(E127)

Quinolineyellow(E104)

Indigocarmine(E132)

Gelatin

PrintingInk

Shellac

EthylAlcoholanhydrous

Isopropylalcohol

Propyleneglycol

N-ButylAlcohol

Polyvinylpyrrolidone

Sodiumhydroxide

Titaniumdioxide(E171)

6.2Incompatibilities

Notapplicable

6.3ShelfLife

3years.

6.4Specialprecautionsforstorage

Donotstoreabove30ºC.Keepthebottletightlyclosed.Storeintheoriginalpackage.

6.5Natureandcontentsofcontainer

HDPEbottleandpolypropylenecapwithintegralsilicageldessicant

Packsizes:5,7,14,15,20,21,28,30,42,50,56,60,84,98,100or500Capsules

Notallpacksizesmaybemarketed

6.6Specialprecautionsfordisposalofausedmedicinalproductorwastematerialsderivedfrom

suchmedicinalproductandotherhandlingoftheproduct

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7MARKETINGAUTHORISATIONHOLDER

VolkspharmaGmbH

August-Wessels-Str.5

Augsburg

Germany

D-86154

8MARKETINGAUTHORISATIONNUMBER

PA1499/1/3

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

1stJune2007.

10DATEOFREVISIONOFTHETEXT

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