BYLANS

Main information

  • Trade name:
  • BYLANS Capsules Gastro-Resistant 15 Milligram
  • Dosage:
  • 15 Milligram
  • Pharmaceutical form:
  • Capsules Gastro-Resistant
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug

Documents

Localization

  • Available in:
  • BYLANS Capsules Gastro-Resistant 15 Milligram
    Ireland
  • Language:
  • English

Status

  • Source:
  • HPRA - Health Products Regulatory Authority - Ireland
  • Authorization number:
  • PA0749/131/001
  • Authorization date:
  • 02-07-2010
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

ByLans15mgGastro-resistantCapsules

2QUALITATIVEANDQUANTITATIVECOMPOSITION

Eachcapsulecontainslansoprazole,15mg

Excipients:

Eachcapsulecontains64.8mgsucrose(insugarspheres)

Forafulllistofexcipients,seesection6.1

3PHARMACEUTICALFORM

Gastro-resistantcapsule,hard.

Size3,whitecapmarkedwith‘L’andwhitebodymarkedwith‘15’,containingwhitetobeigegastro-resistant

micropellets.

4CLINICALPARTICULARS

4.1TherapeuticIndications

HealingandlongtermmanagementofGastroOesophagealRefluxDisease(GORD).

Healingforpatientswithduodenaland/orbenigngastriculcer.

TreatmentandprophylaxisofNSAID-associatedbenigngastriculcers,duodenalulcersandreliefofsymptomsin

patientsrequiringcontinuedNSAIDtreatment.

TreatmentofZollinger-Ellisonsyndrome.

Lansoprazoleisalsoeffectiveinpatientswithbenignpepticlesions,includingrefluxoesophagitis,unresponsivetoH2

receptorantagonists.

EradicationofHelicobacterpyloriconcurrentlygivenwiththeappropriateantibiotictherapyandpreventionofrelapse

ofpepticulcersinpatientswithH.pyloriassociatedulcers.

4.2Posologyandmethodofadministration

Dosage:

GastroOesophagealRefluxDisease:Lansoprazole30mgoncedailyfor4weeks.Themajorityofpatientswillbe

healedafterthefirstcourse.Forthosepatientsnotfullyhealedatthistime,afurther4weekstreatmentatthesame

dosageshouldbegiven.

Forlongtermmanagement,amaintenancedoseofLansoprazole15mgor30mgoncedailycanbeuseddependent

uponpatientresponse.

Duodenalulcer:Lansoprazole30mgoncedailyfor4weeks.

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TreatmentofNSAID-associatedbenigngastricandduodenalulcersandreliefofsymptoms:Lansoprazole15mgor

30mgoncedailyfor4or8weeks.Mostpatientswillbehealedafter4weeks;forthosepatientsnotfullyhealed,a

further4weekstreatmentcanbegiven.

Forpatientsatparticularriskorwithulcersthatmaybedifficulttoheal,thehigherdoseand/orthelongertreatment

durationshouldbeused.

ProphylaxisofNSAID-associatedbenigngastriculcers,duodenalulcersandsymptoms:Lansoprazole15mgor30mg

oncedaily.

Zollinger-EllisonSyndrome:Theinitialdoseshouldbelansoprazole60mgoncedaily.Thedosageshouldthenbe

adjustedindividually.Treatmentshouldbecontinuedforaslongasclinicallyindicated.

Forpatientswhorequire120mgormoreperday,thedoseshouldbedividedandadministeredtwicedaily.

Helicobacterpylorieradication:

Therecommendeddoseis30mglansoprazole2timesdailyforoneweekincombinationwithoneofthefollowing

threecombinations:

Amoxicillin1gtwicedaily+clarithromycin500mgtwicedaily,

Clarithromycin250mgtwicedaily+metronidazole400-500mgtwicedaily,

C)Amoxicillin1gtwicedaily+metronidazole400-500mgtwicedaily.

Considerationshouldbegiventoofficiallocalguidance(e.g.nationalrecommendations)regardingbacterialresistance

andtheappropriateuseandprescriptionofantibacterialagents.

Toachievetheoptimalacidinhibitoryeffect,andhencemostrapidhealingandsymptomrelief,lansoprazole'once

daily'shouldbeadministeredinthemorningbeforefood.Lansoprazole'twicedaily'shouldbeadministeredonceinthe

morningbeforefood,andonceintheevening.

Thecapsulesshouldbeswallowedwhole.Donotcrushorchew.

Elderly:Duetodelayedeliminationoflansoprazoleintheelderlyitmaybenecessarytoadministerthetreatmentin

dosesof15-30mgadjustedtoindividualrequirements.However,thedailydoseintheelderlyshouldnotexceed30

Children:Theuseoflansoprazoleisnotrecommendedinchildrenasclinicaldataarelimited.Treatmentofsmall

childrenbelowoneyearofageshouldbeavoidedasavailabledatahavenotshownbenificialeffectsinthetreatmentof

gastro-oesophegealreflux.

ImpairedHepaticandRenalFunction:

Lansoprazoleismetabolisedsubstantiallybytheliver.Clinicaltrialsinpatientswithliverdiseaseindicatethat

metabolismoflansoprazoleisprolongedwhendailydosesof30mgareadministeredtopatientswithseverehepatic

impairment.Itisthereforerecommendedthatthedailydoseforpatientswithsevereliverdiseaseisindividually

adjustedto15mgor30mg.Thesepatientsshouldbekeptunderregularsupervisionandadailydosageof30mg

shouldnotbeexceeded.

Thereisnoneedtoalterthedosageinpatientswithmildtomoderateimpairmentofhepaticfunctionorimpairedrenal

function.

4.3Contraindications

Theuseoflansoprazoleiscontra-indicatedinpatientswithahistoryofhypersensitivitytoanyoftheingredientsof

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4.4Specialwarningsandprecautionsforuse

Incommonwithotheranti-ulcertherapies,thepossibilityofmalignancyshouldbeexcludedwhengastriculceris

suspected,assymptomsmaybealleviatedanddiagnosisdelayed.

Lansoprazoleshouldbeusedwithcautioninpatientswithseverehepaticdysfunction.Thesepatientsshouldbekept

underregularsupervisionandadailydosageof30mgshouldnotbeexceeded(SeeSection4.2).

Decreasedgastricacidityduetoanymeans,includingprotonpumpinhibitors,increasesgastriccountsofbacteria

normallypresentinthegastrointestinaltract.Treatmentwithacid-reducingdrugsmayleadtoaslightlyincreasedrisk

ofgastrointestinalinfectionssuchasSalmonellaandCampylobacter.

Forpatientssufferingfromgastro-duodenalulcers,thepossibilityofH.pyloriinfectionasanetiologicalfactorshould

beconsidered.Iflansoprazole,incombinationwithantibiotics,isusedforeradicationtherapyofH.pylori,then

instructionsfortheuseoftheseantibioticsshouldalsobefollowed.

Maintenancetreatmentshouldnotcontinueformorethanoneyearunlessconsideredessentialbytheprescribing

physician.

Ifvisualdisturbancesoccurduringlong-termuse(>1year),anophthalmologistshouldbeconsulted.

Thisproductcontainssucroseandthereforepatientswithrarehereditaryproblemsoffructoseintolerance,glucose-

galactosemalabsorptionorsucrase-isomaltaseinsufficiencyshouldnottakethismedicine.

4.5Interactionwithothermedicinalproductsandotherformsofinteraction

LansoprazoleishepaticallymetabolisedandstudiesindicatethatitisaweakinducerofCytochromeP450.Thereisthe

possibilityofinteractionwithdrugswhicharemetabolisedbytheliver.Cautionshouldbeexercisedwhenoral

contraceptivesandpreparationssuchasphenytoin,carbamazepine,theophylline,orwarfarinaretakenconcomitantly

withtheadministrationoflansoprazole.

DrugswhichinhibitCYP2C19DrugswhichinhibitCYP2C19mayincreasetheplasmaconcentrationoflansoprazole.

Fluvoxamine,aninhibitorofCYP2C19,increasedtheplasmaconcentrationsoflansoprazoleupto4-fold.

DrugswhichinhibitCYP3A4DrugswhichinhibitCYP3A4suchasketoconazole,itraconazole,proteaseinhibitors,

macrolidesetcmaymarkedlyincreasetheplasmaconcentrationsoflansoprazole.

KetoconazoleanditraconazoleTheabsorptionofketoconazoleanditraconazolefromthegastrointestinaltractis

enhancedbythepresenceofgastricacid.Administrationoflansoprazolemayresultinsubtherapeuticconcentrationsof

ketoconazoleanditraconazoleandthecombinationshouldbeavoided.Theeffectmayalsobepresentiflansoprazoleis

combinedwithotherdrugswithpH-dependentabsorption.

TacrolimusCoadministrationoflansoprazoleincreasestheplasmaconcentrationsoftacrolimus(aCYP3AandP-gp

substrate).Lansoprazoleexposureincreasedthemeanexposureoftacrolimusbyupto81%.Monitoringoftacrolimus

plasmaconcentrationsisadvisedwhenconcomitanttreatmentwithlanzoprazoleisinitiatedorended.

NoclinicallysignificanteffectsonNSAIDsordiazepamhavebeenfound.

Antacidsandsucralfatemayreducethebioavailabilityoflansoprazoleandshould,therefore,notbetakenwithinan

houroflansoprazole.

Cautionshouldbeexercisedwhencombininglansoprazolewithdrugswhichhaveanarrowtherapeuticindex,asthe

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TherapyofHelicobacterpyloriinfectionisintendedtobecombinedwithconcurrentadministrationoflansoprazole

withtwoantibiotics.Theinfluenceofthiscombinedadministrationhasnotyetbeeninvestigatedsystemically.

Forreasonsoftheoreticalconsiderations,enhancedinteractionswithothermedicinalproductsmustbeexpectedasa

precaution.Monitoringoftheserumlevelsofothermedicinalproductstakenduringthefirstweekoferadication

therapyisthereforerecommended.Thisconcernsparticularlysuchmedicinalproductsalsometabolisedviathe

cytochromeP450system.

Thefollowinginteractionsbetweenlansoprazoleandone/twoantibioticsusedineradicationtherapyhavebeenfound

sofar:

4.6Fertility,pregnancyandlactation

Forlansoprazolenoclinicaldataonexposedpregnanciesareavailable.Animalstudiesdonotindicatedirectorindirect

harmfuleffectswithrespecttopregnancy,embryonal/fetaldevelopment,parturitionorpostnataldevelopment.

Theuseoflansoprazoleduringpregnancyisnotrecommended.

Itisnotknownwhetherlansoprazoleisexcretedinhumanbreastmilk.Animalstudieshaveshownexcretionof

lansoprazoleinmilk.Adecisiononwhethertocontinue/discontinuebreast-feedingortocontinue/discontinuetherapy

withlansoprazoleshouldbemadetakingintoaccountthebenefitofbreast-feedingtothechildandthebenefitof

lansoprazoletherapytothewoman.

TheuseofLansoprazoleduringbreastfeedingshouldbeavoidedunlessconsideredessential.

4.7Effectsonabilitytodriveandusemachines

Adversedrugreactionssuchasdizzinessandfatiguemayoccur(seesection4.8).Undertheseconditionstheability

toreactmaybedecreased.Thisshouldbetakenintoaccountwhendrivingorusingmachines.

4.8Undesirableeffects

Lansoprazoleiswell-tolerated,withadverseeventsgenerallybeingmildandtransient.

Thefollowingundesirableeffectshavebeenobservedduringtreatmentwithlansoprazolewiththefollowing

frequencies:

Common(>1/100,<1/10),uncommon(>1/100,<1/100),rare(>1/10,000,<1/1000),veryrare(<1/10,000)including

Co-administered

medicinalproducts Dosageanddurationof

combinedadministration Effect*

lansoprazole+

clarithromycin 30mg+500mg3

times/dayfor5days Increasedplasmalevelsofaclarithromycin

metaboliteby16%;increasedbioavailability

oflansoprazoleby19%upto32%

lansoprazole+

amoxicillin 30mg+1000mg3

times/dayfor5days Deceleratesuptakeofamoxicillin

lansoprazole+

metronidazole Notyetinvestigated

lansoprazole+

clarithromycin+

amoxicillin 30mg+500mg+1000mg

twicedailyfor5days Increasebioavailabilityandhalf-lifeof

lansoprazoleby30%each;increasedplasma

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Common

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

(>1/1000,

<1/100) Rare

(>1/10,000,<1/1000) VeryRare

(<1/10,000)

Includingisolated

reports NotKnown

Gastrointestinal

disorders Vomiting,

nausea,

diarrhoea,

stomachache,

constipation,

flatulenceand

dyspepsia. Drymouthor

throat,and

anorexia Pancreatitis,candidiasisof

oesophagusandglossitis Colitis,stomatitisand

blacktongue

Skinandsubcutaneous

tissuedisorders Eczema,urticaria

anditching. Erythemamultiforme,

petechia,hairloss,

hyperhidrosis,bruisingand

purpura, Stevens-Johnson

syndromeandtoxic

epidermalnecrolysis. Subacute

Cutaneous

lupus

erythematosus

Nervoussystem

disorders Headache,

dizzines Depression,hallucination,

confusion,insomnia,

somnolence,drowsiness,

vertigo,tremor,paresthesia,

andrestlessness.

Hepatobiliary

disorders Increasein

liverenzyme

levels. Hepatitisandicterus

Renalandurinary

disorders Interstitialnephritis.

Bloodandlymphatic

systemdisorders Thrombocytopenia,

eosinophilia,pancytopenia,

anemia,leucopenia. Agranulocytosis

Cardiacdisorders Palpitationandchestpain.

Vasculardisorders Peripheraledema,

Musculoskeletaland

connectivetissue

disorders Muscleandjointpain

Eyeandtastedisorders Taste

disturbances Visualdisturbances,

photosensitivity

Endocrinedisorders Gynecomastia,

galactorrhoea.

Generaldisordersand

administrationsite

conditions Fatigue,malaise. Angiodema,bronchial

constriction,fever Anaphylacticshock,

impotence

Investigations Increasein

cholesteroland

triglyceridelevels. Hypomagnes

aemia(after

prolonged

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4.9Overdose

Thereisnoinformationontheeffectofoverdosage.However,Lansoprazolehasbeengivenatdosesupto120mg/day

withoutsignificantadverseeffects.Symptomaticandsupportivetherapyshouldbegivenasappropriate.

Lansoprazoleisnotsignificantlyeliminatedbyhaemodialysis.Ifnecessary,gastricemptying,administrationof

charcoalandsymptomatictherapyarerecommended.

5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

Pharmacotherapeuticgroup:Protonpumpinhibitors,ATCcode:A02BC03.

Uses

Lansoprazoleiseffectiveinthetreatmentofacid-relateddisordersoftheuppergastro-intestinaltract,withthebenefit

ofrapidsymptomrelief.

Lansoprazoleisamemberofaclassofdrugscalledprotonpumpinhibitors.Itsmodeofactionistoinhibitspecifically

theH+/K+ATPase(protonpump)oftheparietalcellinthestomach,theterminalstepinacidproduction,thus

reducinggastricacidity,akeyrequirementforhealingofacid-relateddisorderssuchasgastriculcer,duodenalulcer

andrefluxoesophagitis.Itisbelievedthattheparentdrugisbiotransformedintoitsactiveform(s)intheacidic

environmentoftheparietalcell,whereuponitreactswiththesulphydrylgroupoftheH+/K+ATPasecausing

inhibition.Thisinhibitionisreversibleinvitrobyintrinsicandextrinsicreducingagents.Lansoprazole'smodeofaction

differssignificantlyfromtheH2antagonistswhichinhibitoneofthethreepathwaysinvolvedinstimulationofacid

production.Asingledoseof30mginhibitspentagastrin-stimulatedacidsecretionbyapproximately80%,indicating

effectiveacidinhibitionfromthefirstdayofdosing.

Lansoprazolehasaprolongedpharmacologicalactionprovidingeffectiveacidsuppressionover24hours,thereby

promotingrapidhealingandsymptomrelief.

5.2Pharmacokineticproperties

Absorption

Lansoprazoleisrapidlyinactivatedbygastricacid.Thereforeitisformulatedasenteric-coatedgranulesincellulose

capsules.Lansoprazoleisrapidlyabsorbedfromtheduodenum;peakplasmaconcentrationsareachievedwithin1.5–

2.0hours.Intakeoffoodslowstheabsorptionrateandreducesitsbioavailability(AUC)byapproximately25%.

Distribution

Thebioavailabilityafterasinglelansoprazole30mgdoseandafterrepeateddailyadministrationis80–90%.The

bioavailabilityoflansoprazolemaybereducedifantacidsandsucralfateareco-administered.Plasmaproteinbindingis

approximately95%.Thishasnosignificanteffectonotherproteinboundactivesubstances.

Metabolism

Lansoprazoleismainlymetabolisedintheliver.

LansoprazoleismainlycatalysedbytheenzymeCYP2C19.CYP3A4alsocontributestothemetabolismof

lansoprazole.CYP2C19issubjecttogeneticpolymorphismandapproximately2–65ofthegeneralpopulationare

termedpoormetabolisers(PMs)whoarehomozygoteforamutantCYP2C19allele.PMslackafunctionalCYP2C19

enzyme.InthesePMs,exposureoflansoprazoleisseveral-foldhigherthaninextensivemetabolisers.

Threemetaboliteshavebeenidentifiedintheplasma:thesulfone,5-hydroxylansoprazoleandthesulfide.These

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Excretion

Theeliminationhalf-lifeoflansoprazoleis1.0–2.0hours.Halflifeisnotchangedduringrepeateddosingof

lansoprazole.Asingledoseoflansoprazolehasaninhibitoryeffectongastricacidsecretion,whichlastsformorethan

24hours.Sincelansoprazoleisactivatedintheparietalcells,itsplasmaconcentrationisnotrelatedtogastricacid

secretion.

Approximately,15–50%ofthemetabolitesareexcretedintheurineandtheremainderinthefaeces.Three

metaboliteshavebeenidentifiedintheurinenamely:5-hydroxysulfone,5-hydroxysulphideand5-hydroxy

lansoprazole.

Inpatientswithcirrhosis,theAUCoflansoprazoleissignificantlyincreasedandtheeliminationhalflifeisprolonged;

however,nosignsofaccumulationhavebeendetected.

Thebioavailabilityoflansoprazoleisnotsignificantlychangedinpatientswithrenalinsufficiency.

Intheelderly,eliminationoflansoprazoleisslightlydelayed.

5.3Preclinicalsafetydata

Non-clinicaldatarevealnospecialhazardforhumansbasedonconventionalstudiesofsafetypharmacology,repeated

dosetoxicity,toxicitytoreproductionorgenotoxicity.

Intworatcarcinogenicitystudies,lansoprazoleproduceddose-relatedgastricECLcellhyperplasiaandECLcell

carcinoidsassociatedwithhypergastrinaemiaduetoinhibitionofacidsecretion.Intestinalmetaplasiawasalso

observed,aswereLeydigcellhyperplasiaandbenignLeydigcelltumours.After18monthsoftreatmentretinal

atrophywasobserved.Thiswasnotseeninmonkeys,dogsormice.

Inmousecarcinogenicitystudiesdose-relatedgastricECLcellhyperplasiadevelopedaswellaslivertumoursand

adenomaofretetestis.

6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

CapsuleContent:

Sugarspheres(sucroseandmaizestarch)

SodiumstarchglycolateTypeA

Sodiumlaurilsulfate

PovidoneK30

Potassiumoleate

Oleicacid

Hypromellose

Methacrylicacid-ethylacrylatecopolymer1:1

Triethylcitrate

Titaniumdioxide(E171)

Talc

CapsuleShell:

Titaniumdioxide(E171)

Hypromellose

Carrageenan

Potassiumchloride

Carnaubawax

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PrintingInk:

Shellac

Propyleneglycol

Ammoniumhydroxide

Potassiumhydroxide

Blackironoxide(E172)

6.2Incompatibilities

NotApplicable.

6.3Shelflife

2years.

6.4Specialprecautionsforstorage

Donotstoreabove30ºC.Storeintheoriginalpackage.

6.5Natureandcontentsofcontainer

Al//PA/Al/PVCBlisterswithinacartonbox.

Packsof7,14,28or56capsules(2x28capsules)

Notallpacksizesaremarketed.

6.6Specialprecautionsfordisposalofausedmedicinalproductorwastematerialsderivedfrom

suchmedicinalproductandotherhandlingoftheproduct

Nospecialrequirements.

7MARKETINGAUTHORISATIONHOLDER

TevaPharmaB.V.

Computerweg10

3542DRUtrecht

TheNetherlands

8MARKETINGAUTHORISATIONNUMBER

PA0749/131/001

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

Dateoffirstrenewal:12thJanuary2007

Dateoflastrenewal:8thDecember2010

10DATEOFREVISIONOFTHETEXT

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