ASACOLON

Main information

  • Trade name:
  • ASACOLON Tablets Gastro-Resistant 800 Milligram
  • Dosage:
  • 800 Milligram
  • Pharmaceutical form:
  • Tablets Gastro-Resistant
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug

Documents

Localization

  • Available in:
  • ASACOLON Tablets Gastro-Resistant 800 Milligram
    Ireland
  • Language:
  • English

Status

  • Source:
  • HPRA - Health Products Regulatory Authority - Ireland
  • Authorization number:
  • PA1204/001/003
  • Authorization date:
  • 07-01-2005
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

Asacolon800mgGastro-resistantTablets.

2QUALITATIVEANDQUANTITATIVECOMPOSITION

Eachtabletcontains:mesalazine800mg

Excipients:contains152.8mgoflactosemonohydrate.

Forafulllistofexcipients,seesection6.1.

3PHARMACEUTICALFORM

Gastro-resistanttablet.

Thetabletsarereddishtobrownishandoblong-shaped.

4CLINICALPARTICULARS

4.1TherapeuticIndications

Forthetreatmentofmildacuteulcerativecolitis.Forthemaintenanceofremissionofulcerativecolitis.

Forthemaintenanceofsurgically-inducedremissionofCrohn’sDisease.

4.2Posologyandmethodofadministration

Oraladministration.

Thetabletsshouldbeswallowedwholewithaglassofwateronehourbeforefoodintake.Theymustnotbechewed,

crushedorbrokenbeforeswallowing.Ifoneormoredoseshavebeenmissed,thenextdoseistobetakenasusual.

Adults:

Ulcerativecolitis:

Inductionofremission:

2.4g(3tablets)perdayindivideddoses.Ifrequiredthedosemaybeincreasedto4g(5tablets)daily.

Thedosagecanbeadjustedinaccordancewiththeresponsetothetreatment.

Maintenanceofremission:

1.2to2.4gperdayindivideddoses.

Crohn’sdisease:

Maintenanceofremission:

2.4g(3tablets)perdayindivideddoses.

Paediatricpatients

Thereisnodoserecommendationforchildren(seesection4.3and4.4).

Geriatricpatients

Asforadultsaboveunlessrenalfunctionisimpaired(seesection4.3and4.4).Nostudieshavebeencarriedoutinthe

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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-inducednephrotoxicityshouldbesuspectedinpatients

developingimpairmentofrenalfunctionduringtreatment.

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-inducedcardiachypersensitivityAsacolonmustnotbereintroduced.Cautionshouldbe

usedinpatientswithpreviousmyo-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

investigationsincludingacompletebloodcountshouldbeperformedpriortoinitiationandwhileontherapy,atthe

discretionofthetreatingphysician.Asaguideline,follow-uptestsaregenerallyrecommended14daysafterinitiation

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carriedoutevery3months.Ifadditionalsymptomsoccur,thesetestsshouldbeperformedimmediately.

Tabletsinstool

Alimitednumberofreportsofintacttabletsinstoolhavebeenreceived.Whatappeartobeintacttabletsmayinsome

casesrepresentlargelyemptyshellsofthetabletcoating.Asacolon800mgGastro-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.

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N-acetyl-5-aminosalicylicacidandtoalesserdegreemesalazineareexcretedinbreastmilk.

Theclinicalsignificanceofthishasnotbeendetermined.Onlylimitedexperienceduringlactationinwomenis

availabletodate.Hypersensitivityreactionssuchasdiarrhoeaintheinfantcannotbeexcluded.Therefore,Asacolon

shouldonlybeusedduringbreast-feeding,ifthepotentialbenefitoutweighsthepossiblerisk.Iftheinfantdevelops

diarrhoea,breastfeedingshouldbediscontinued.

4.7Effectsonabilitytodriveandusemachines

Noeffectsontheabilitytodriveandusemachines.

4.8Undesirableeffects

TheAsacolonclinicaltrialdatabaseincludes651patientstreatedwithAsacolon400mgGRTablets.Themesalazine

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

Undesirableeffectsrelevantforthelabellingreportedfromninedouble-blindandsixopenclinicalstudiesand

informationfromspontaneousreportingortheliteratureislistedbelow.Thelatterwasreportedfromapopulationof

unknownsize.Theirfrequencyisnotknown.

Bloodandlymphaticsystemdisorders

Uncommon: anaemia.

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

thrombocytopenia),bonemarrowdepression,eosinophilia,blooddisorder.

Immunesystemdisorders

Veryrare: hypersensitivityreactionssuchasallergicexanthema,drugfever,lupuserythematosussyndrome,

pancolitis.

Nervoussystemdisorders

Uncommon: tinnitus,paresthesia.

Rare: headache,dizziness.

Veryrare: peripheralneuropathy.

Cardiacdisorders

Rare: myocarditis,pericarditis.

Respiratory,thoracicandmediastinaldisorders

Veryrare: allergicandfibroticlungreactions(includingdyspnoea,cough,bronchospasm,alveolitis,pulmonary

eosinophilia,lunginfiltration,pneumonitis),pneumonia,interstitialpneumonia,eosinophilicpneumonia,

lungdisorder.

Gastrointestinaldisorders

Rare: abdominalpain,diarrhoeaflatulence,nausea,,vomiting,dyspepsia.

Veryrare: acutepancreatitis.

Notknown: exacerbationofthesymptomsofcolitis.

Hepato-biliarydisorders

Veryrare: changesinliverfunctionparameters(increaseintransaminasesandcholestasisparameters),hepatitis,

cholestatichepatitis.

Skinandsubcutaneoustissuedisorders

Common: Rash.

Uncommon: pruritus,urticaria.

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Musculoskeletalandconnectivetissuedisorders

Veryrare: myalgia,arthralgia.

Notknown: lupus-likesyndromewithpericarditisandpleuropericarditisasprominentsymptomsaswellasrashand

arthralgia.

Renalandurinarydisorders

Veryrare: impairmentofrenalfunctionincludingacuteandchronicinterstitialnephritisandrenalinsufficiency,

nephroticsyndrome,renalfailurewhichmaybereversibleonwithdrawal.

Reproductivesystemandbreastdisorders

Veryrare: oligospermia(reversible).

Generaldisordersandadministrationsiteconditions

Common: drugfever.

Uncommon: drugineffective.

Veryrare: chestpain.

Investigations

Notknown: bloodbilirubinincreased,liverfunctiontestabnormal.

Verycommon: 1/10,common: 1/100and<1/10,uncommon: 0.1/1,000and<1/100,rare: 1/10,000and<

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

AnunknownnumberoftheaboveundesirableeffectsareprobablyassociatedtotheunderlyingIBDratherthan

Asacolon/mesalazinemedication.Thisholdstrueespeciallyforgastrointestinalundesirableeffectsandarthralgia.

Mesalazine-inducednephrotoxicity,whichmaybereversibleonwithdrawal,shouldbesuspectedinpatients

developingrenaldysfunctionduringtreatment(seesection4.4).

Toavoidblooddyscrasiaresultingfromdevelopingbonemarrowdepressionpatientsshouldbemonitoredwithcare

(seesection4.4).

Co-administrationofmyelosuppressivedrugssuchasazathioprine,or6-MP,orthioguaninecanprecipitateleucopenia

(seesection4.5).

ConcurrentuseofNSAIDsandazathioprinemayincreasetheriskofrenalreactions(seesection4.5).

4.9Overdose

Thereareraredataonoverdose(e.g.intendedsuicidewithhighoraldosesofmesalazine),whichdonotindicaterenal

orhepatictoxicity.Thereisnospecificantidoteandtreatmentissymptomaticandsupportive.

5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

Asacolon800mgGastro-resistantTabletscontainmesalazine[ATCA07EC02],or5-aminosalicylicacid,whichhas

ananti-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

Asacolon800mgGastro-resistantTabletsarecoatedwithapolymer[Eudragit™S]whichallowstheactiveprinciple

tobereleasedwhentheintraluminalpHisabove7,thatiswithintheterminalileumandcolon,whicharethemainsites

ofinflammation.Asacolontabletshavebeendesignedtominimiseabsorptionofmesalazineinthedigestivetract.

Absorptionbytheoralrouteisapproximately26%.Consequently,74%oftheadministereddoseremainwithinthe

terminalileum,colon,andrectum,beingavailabletoexertatopicalanti-inflammatoryeffect.Mesalazineis

metabolisedbothbytheliverandtheintestinalmucosato

aninactivederivative,N-acetyl-5-aminosalicylicacid.Mesalazinehasaneliminationhalf-life

between9hours(singledose)and11hours(steadystate).Theeliminationofmesalazineis

essentiallyfaecalandurinary,intheformofmesalazineanditsN-acetylmetabolite.

5.3Preclinicalsafetydata

Toxicityofmesalazineafteroraladministrationhasbeeninvestigatedinseveralstudieswithbothsingleandrepeated

doses.Whenadoseof1g/kgperdaywasadministeredrepeatedlytorats,itcauseddamageinkidneysandgastro-

intestinaltract.

6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

Lactosemonohydrate

Sodiumstarchglycolate

Magnesiumstearate(E572)

Talc(E553b)

Povidone

FilmCoating

Methacrylicacid-methylmethacrylatecopolymer(1:2)

Talc

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

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7MARKETINGAUTHORISATIONHOLDER

TillottsPharmaLimited

UnitedDrugHouse

MagnaDrive

CitywestRoad

Dublin24

Tradingas:

TillottsPharmaLimited

8MARKETINGAUTHORISATIONNUMBER

PA1204/001/003

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

Dateoffirstauthorisation:07February2003

Dateoflastrenewal:07February2008

10DATEOFREVISIONOFTHETEXT

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