ASACOLON

Main information

  • Trade name:
  • ASACOLON Tablets Gastro-Resistant 400 Milligram
  • Dosage:
  • 400 Milligram
  • Pharmaceutical form:
  • Tablets Gastro-Resistant
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug

Documents

Localization

  • Available in:
  • ASACOLON Tablets Gastro-Resistant 400 Milligram
    Ireland
  • Language:
  • English

Status

  • Source:
  • HPRA - Health Products Regulatory Authority - Ireland
  • Authorization number:
  • PA1204/001/002
  • Authorization date:
  • 07-01-2005
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

Asacolon400mgGastro-ResistantTablets

2QUALITATIVEANDQUANTITATIVECOMPOSITION

Eachgastro-resistanttabletcontains:Mesalazine400mg.

Excipients:alsocontains76.4mgoflactosemonohydrate,seesection4.4.forfurtherdetails.

Forafulllistofexcipients,seesection6.1.

3PHARMACEUTICALFORM

Gastro-resistantTablet.

Thetabletsarereddishtobrownishandoblong-shaped.

4CLINICALPARTICULARS

4.1TherapeuticIndications

Forthetreatmentofmildacuteulcerativecolitis.Forthemaintenanceofremissionofulcerativecolitis.

Forthemaintenanceofsurgically-inducedremissionofCrohn’sDisease.

4.2Posologyandmethodofadministration

Oraladministration.

Thetabletsshouldbeswallowedwholewithaglassofwateronehourbeforefoodintake.

Theymustnotbechewed,crushedorbrokenbeforeswallowing.Ifoneormoredoseshavebeenmissed,thenextdose

istobetakenasusual.

Adults:

Ulcerativecolitis:

Inductionofremission:

2.4g(6tablets)perdayindivideddoses.Ifrequiredthedosemaybeincreasedto4g(10tablets)daily.

Thedosagecanbeadjustedinaccordancewiththeresponsetothetreatment.

Maintenanceofremission:

1.2to2.4g(3to6tablets)perdayindivideddoses.

Crohn’sdisease:

Maintenanceofremission:

2.4g(6tablets)perdayindivideddoses.

Theelderly

Asforadultsaboveunlessrenalfunctionisimpaired(see4.3and4.4).Nostudieshavebeencarriedoutintheelderly.

Children

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4.3Contraindications

Asacoloniscontraindicatedincasesof:

-Historyofhypersensitivitytosalicylates.

-Hypersensitivitytomesalazineoranyoftheexcipients(seesection6.1).

-Severerenalimpairment(GFRlessthan30mLperminute).

-Severeliverimpairment.

-Gastricandduodenalulcers

-Childrenunder2yearsofage.

4.4Specialwarningsandprecautionsforuse

Renalimpairment

Urinarystatus(dipsticks)shouldbedeterminedpriortoandduringtreatment,atthediscretionofthetreating

physician.Notrecommendedforuseinpatientswithrenalimpairment.Cautionshouldbeexercisedinpatientswith

raisedbloodureaorproteinuria.

Thepossibilityofmesalazine-inducednephrotoxicityshouldbesuspectedinpatientsdevelopingimpairmentofrenal

functionduringtreatment.

ItisrecommendedthatallpatientshaveanevaluationoftheirrenalfunctionpriortoinitiationofAsacolontherapyand

periodicallywhileonAsacolontherapy.Asaguideline,follow-uptestsarerecommended14daysofinitiationof

therapyandthenevery4weeksforthefollowing12weeks.ShortmonitoringintervalsearlyafterthestartofAsacolon

therapywilldiscoverrareacuteallergicimpairmentofrenalfunction.Intheabsenceofanacuteallergicrenalresponse

monitoringintervalscanbeextendedtoevery3monthsandthenannuallyafter5years.Ifadditionalsignsofillness

appear,thesetestsshouldbeperformedimmediately.TreatmentwithAsacolonshouldbestoppedimmediatelyifthere

isevidenceofrenalimpairmentandpatientsshouldseekimmediatemedicaladvice.

Liverimpairment

Therehavebeenreportsofincreasedliverenzymelevelsinpatientstakingpreparationscontainingmesalazine.Caution

isrecommendedifAsacolonisadministeredtopatientswithliverimpairment.Bloodtests(liverfunctionparameters

suchasALTorAST)shouldbedeterminedpriortoandduringtreatment,atthediscretionofthetreatingphysician.As

aguideline,follow-uptestsarerecommended14daysaftercommencementoftreatment,thenafurthertwotothree

testsatintervalsof4weeks.Ifthefindingsarenormal,follow-uptestsshouldbecarriedoutevery3months.If

additionalsymptomsoccur,thesetestsshouldbeperformedimmediately.

Cardiachypersensitivityreactions

Mesalazine-inducedcardiachypersensitivityreactions(myo-andpericarditis)havebeenreportedrarelywithAsacolon.

Incaseofpreviousmesalazine-inducedcardiacAT400-IEhypersensitivityAsacolonmustnotbereintroduced.Caution

shouldbeusedinpatientswithpreviousmyo-andpericarditisofallergicbackgroundregardlessofitsorigin.

Pulmonarydisease

Patientswithpulmonarydisease,inparticularasthma,shouldbeverycarefullymonitoredduringacourseoftreatment

withAsacolon.

HypersensitivitytoSulphasalazine

Inpatientswithahistoryofhypersensitivitytosulphasalazine,therapyshouldbeinitiatedonlyunderclosemedical

supervision.Treatmentmustbestoppedimmediatelyifacutesymptomsofintoleranceoccursuchasabdominal

cramps,acuteabdominalpain,fever,severeheadacheandrash.

Blooddyscrasia

Veryrarelyseriousblooddyscrasiahasbeenreportedwiththismedicinalproduct.TreatmentwithAsacolonshouldbe

stoppedimmediatelyifthereisasuspicionorevidenceofblooddyscrasia,suchasunexplainedbleeding,haematoma,

purpura,anaemia,persistentfeverorsorethroat,andpatientsshouldseekimmediatemedicaladvice.Haematological

investigationsincludingacompletebloodcountshouldbeperformedpriortoinitiationandwhileontherapyatthe

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oftherapyandthenevery4weeksforthefollowing12weeks.Iftheresultsarenormal,follow-uptestsshouldbe

carriedoutevery3months.Ifadditionalsymptomsoccur,thesetestsshouldbeperformedimmediately.

Tabletsinstool

Alimitednumberofreportsofintacttabletsinstoolhavebeenreceived.Whatappeartobeintacttabletsmayinsome

casesrepresentlargelyemptyshellsofthetabletcoating.Asacolon400mgGastro-resistantTabletsreleasetheir

contentinthelowergutevenifthecoatingdoesnotdissolveentirely.OncepH7.0isreached,cracksinthecoatingare

sufficientforthereleaseofmesalazinefromthetablets.Thisprocessisirreversiblefromhereonandmesalazinewill

thereforebereleasedcontinuously,independentofintestinalpH.Iftabletsareobservedinthestoolrepeatedly,the

patientshouldconsulthis/herphysician.

Intolerancetocarbohydrates

Patientswithrarehereditaryproblemsofgalactoseintolerance,theLapplactasedeficiencyorglucose-galactose

malabsorptionshouldnottakethismedicine.

Theelderly

Useintheelderlyshouldbehandledwithcautionandtheproductshouldonlybeprescribedtopatientshavinganormal

renalfunction.

Children

SafetyandeffectivenessofAsacolontabletsinchildrenhavenotbeenestablished.

4.5Interactionwithothermedicinalproductsandotherformsofinteraction

Specificinteractionstudieshavenotbeenperformed.

Sulphasalazinedecreasestheabsorptionofdigoxin.Therearenodataoninteractionofdigoxinwithmesalazine.

Mesalazinecanincreasethemyelosuppressiveeffectsofazathioprine,or6-mercaptopurine,orthioguanine.Life-

threateninginfectioncanoccur.Patientsshouldbecloselyobservedforsignsofinfectionandmyelosuppression.

Haematologicalparameters,suchasleukocyteandlymphocytecellcountsshouldbemonitoredregularly(weekly),

especiallyatinitiationofsuchcombinationtherapy(seesection4.4).Ifwhitebloodcellsarestableafter1month,

testingevery4weeksforthefollowing12weeksfollowedby3monthlymonitoringintervalsappearstobejustified.

Theconcurrentuseofknownnephrotoxicagents,suchasNSAIDs,azathioprine,ormethotrexate,mayincreasetherisk

ofrenalreactions.However,noadverseeventsprovingsuchinteractionshavebeenreported(seesection4.4).

Thereisweakevidencethatmesalazinemightdecreasetheanticoagulanteffectofwarfarin.

Apartfrompurineantimetabolitesinteractionstudiesinadultsandchildren,nootherinteractionstudiesinadultsor

paediatricpatientshavebeenperformed.

4.6Fertility,pregnancyandlactation

TherearenoadequatedataontheuseofAsacoloninpregnantwomen.However,datafromalimitednumber(627)of

exposedpregnanciesindicatenoadverseeffectofmesalazineonthepregnancyoronthehealthofthefetus/newborn

child,butmorefrequentpre-termbirthscannotbeexcluded.Todatenootherrelevantepidemiologicdataareavailable.

Inonesinglecaseafterlong-termuseofahighdoseofmesalazine(2-4g,orally)duringpregnancy,renalfailureina

neonatewasreported.

Animalstudiesonoralmesalazinedonotindicatedirectorindirectharmfuleffectswithrespecttopregnancy,

embryonic/fetaldevelopment,parturitionorpostnataldevelopment.

Mesalazinecrossestheplacentalbarrier.Asacolonshouldonlybeusedduringpregnancyif

thepotentialbenefitoutweighsthepossiblerisk.Cautionshouldbeexercisedwhenusinghighdosesofmesalazine.

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ofthishasnotbeendetermined.Onlylimitedexperienceduringlactationinwomenisavailabletodate.

Hypersensitivityreactionssuchasdiarrhoeaintheinfantcannotbeexcluded.Therefore,Asacolonshouldonlybeused

duringbreast-feeding,ifthepotentialbenefitoutweighsthepossiblerisk.Iftheinfantdevelopsdiarrhoea,breastfeeding

shouldbediscontinued.

4.7Effectsonabilitytodriveandusemachines

Noeffectsontheabilitytodriveandusemachineshavebeenobserved.

4.8Undesirableeffects

TheAsacolonclinicaltrialdatabaseincludes651patientstreatedwithAsacolon400mgGRTablets.Themesalazine

doseswereintherangeof0.8to4.8g/day,theaveragetreatmentdurationvariedbetweenfourweeksandfouryears.

Undesirableeffectsrelevantforthelabellingreportedfromninedouble-blindandsixopenclinicalstudiesand

informationfromspontaneousreportingortheliteratureislistedbelow.

Thelatterwasreportedfromapopulationofunknownsize.Theirfrequencyisnotknown.

Bloodandlymphaticsystemdisorders

Uncommon:anaemia.

Veryrare:alteredbloodcounts(aplasticanaemia,agranulocytosis,pancytopenia,neutropenia,leucopenia,

thrombocytopenia),bonemarrowdepression,eosinophilia,blooddisorder.

Immunesystemdisorders

Veryrare:hypersensitivityreactionssuchasallergicexanthema,drugfever,lupus

erythematosussyndrome,pancolitis.

Nervoussystemdisorders

Uncommon:tinnitus,paresthesia.

Rare:headache,dizziness.

Veryrare:peripheralneuropathy.

Cardiacdisorders

Rare:myocarditis,pericarditis.

Respiratory,thoracicandmediastinaldisorders

Veryrare:allergicandfibroticlungreactions(includingdyspnoea,cough,

bronchospasm,alveolitis,pulmonaryeosinophilia,lunginfiltration,

pneumonitis),pneumonia,interstitialpneumonia,eosinophilicpneumonia,

lungdisorder.

Gastrointestinaldisorders

Rare:abdominalpain,diarrhoea,flatulence,nausea,vomiting,dyspepsia.

Veryrare:acutepancreatitis.

Notknown:exacerbationofthesymptomsofcolitis.

Hepato-biliarydisorders

Veryrare:changesinliverfunctionparameters(increaseintransaminasesand

cholestasisparameters),hepatitis,cholestatichepatitis.

Skinandsubcutaneoustissuedisorders

Common:rash.

Uncommon:pruritus,urticaria.

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Musculoskeletalandconnectivetissuedisorders

Veryrare:myalgia,arthralgia.

Notknown:lupus-likesyndromewithpericarditisandpleuropericarditisasprominentsymptomsaswellas

rashandarthralgia.

Renalandurinarydisorders

VeryRare:impairmentofrenalfunctionincludingacuteandchronicinterstitialnephritisandrenal

insufficiency,nephroticsyndrome,renalfailurewhichmaybereversibleonwithdrawal.

Reproductivesystemandbreastdisorders

Veryrare:oligospermia(reversible).

Generaldisordersandadministrationsiteconditions

Common:drugfever.

Uncommon:drugineffective.

Veryrare:chestpain.

Verycommon: 1/10,common: 1/100and<1/10,uncommon: 1/1,000and

<1/100,rare: 1/10,000and<1/1,000,veryrare:<1/10,000,notknown(cannotbeestimatedfromthe

availabledata)

AnunknownnumberoftheaboveundesirableeffectsareprobablyassociatedtotheunderlyingIBDratherthan

Asacolon/mesalazinemedication.Thisholdstrueespeciallyforgastrointestinalundesirableeffectsandarthralgia.

Mesalazine-inducednephrotoxicity,whichmaybereversibleonwithdrawal,shouldbesuspectedinpatients

developingrenaldysfunctionduringtreatment(seesection4.4).

Toavoidblooddyscrasiaresultingfromdevelopingbonemarrowdepressionpatientsshouldbemonitoredwithcare

(seesection4.4).

Co-administrationofmyelosuppressivedrugssuchasazathioprine,or6-MP,orthioguaninecanprecipitateleucopenia

(seesection4.5).

ConcurrentuseofNSAIDs,azathioprine,ormethotrexatemayincreasetheriskofrenalreactions(seesection4.5).

4.9Overdose

Thereareraredataonoverdose(e.g.intendedsuicidewithhighoraldosesofmesalazine),whichdonotindicaterenal

orhepatictoxicity.Thereisnospecificantidoteandtreatmentissymptomaticandsupportive.

5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

Asacolon400mgGastro-resistantTabletscontainmesalazine[ATCA07EC02],or5-aminosalicylicacid,whichhasan

anti-inflammatoryeffectthroughamechanismthathasnotyetbeenfullyclarified.Mesalazineinhibitsmigrationof

polymorphnuclearleukocytesandlipooxygenaseofcellsatconcentrationsreachedinthelargeintestineduring

treatment.Theproductionofpro-inflammatoryleukotrienes(LTB4and5-HETE)inmacrophagesoftheintestinalwall

istheninhibited.Intrialconditionsmesalazinehasalsoinhibitedcyclooxygenaseandthus,thereleaseofthromboxane

B2andprostaglandinE2,buttheclinicalmeaningofthiseffectisstillunclear.Mesalazineinhibitsformationofplatelet

activatingfactor(PAF).Mesalazineisalsoanantioxidant;ithasbeenshowntodecreaseformationofreactiveoxygen

productsandtocapturefreeradicals.Furthermore,mesalazineinhibitssecretionofwaterandchlorideandincreasesthe

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5.2Pharmacokineticproperties

Asacolon400mgGastro-resistantTabletsarecoatedwithapolymer[EudragitTMS]whichallowstheactiveprinciple

tobereleasedwhentheintraluminalpHisabove7,thatiswithintheterminalileumandcolon,whicharethemainsites

ofinflammation.Asacolontabletshavebeendesignedtominimiseabsorptionofmesalazineinthedigestivetract.

Absorptionbytheoralrouteisapproximately26%.Consequently,74%oftheadministereddoseremainwithinthe

terminalileum,colon,andrectum,beingavailabletoexertatopicalanti-inflammatoryeffect.Mesalazineis

metabolisedbothbytheliverandtheintestinalmucosatoaninactivederivative,N-acetyl-5-aminosalicylicacid.

Mesalazinehasaneliminationhalf-lifebetween9hours(singledose)and11hours(steadystate).Theeliminationof

mesalazineisessentiallyfaecalandurinary,intheformofmesalazineanditsN-acetylmetabolite.

5.3Preclinicalsafetydata

Toxicityofmesalazineafteroraladministrationhasbeeninvestigatedinseveralstudieswithbothsingleandrepeated

doses.Whenadoseof1g/kgbodyweight/daywasadministeredrepeatedlytorats,itcauseddamageinkidneysandthe

gastro-intestinaltract.

6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

Lactosemonohydrate

Sodiumstarchglycolate(TypeA)

Magnesiumstearate

Talc(E553b)

Povidone(E1201)

FilmCoating

Methacrylicacid-methylmethacrylatecopolymer(1:2)

Talc(E553b)

TriethylCitrate

Yellowpigment(ferricoxide)(E172)

Macrogol6000

Redpigment(ferricoxide)(E172)

6.2Incompatibilities

Notapplicable.

6.3Shelflife

3years

6.4Specialprecautionsforstorage

Donotstoreabove25ºC.Storeintheoriginalpackageinordertoprotectfrommoisture.

6.5Natureandcontentsofcontainer

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6.6Specialprecautionsfordisposalofausedmedicinalproductorwastematerialsderivedfrom

suchmedicinalproductandotherhandlingoftheproduct

Nospecialrequirements.

7MARKETINGAUTHORISATIONHOLDER

TillottsPharmaLimited

UnitedDrugHouse

MagnaDrive

MagnaBusinessPark

CitywestRoad

Dublin24

Tradingas:

TillottsPharmaLimited

8MARKETINGAUTHORISATIONNUMBER

PA1204/001/002

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

Dateoffirstauthorisation: 11December1990

Dateoflastrenewal: 11December2010

10DATEOFREVISIONOFTHETEXT

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