ASACOLON

Main information

  • Trade name:
  • ASACOLON Suppositories 500 Milligram
  • Dosage:
  • 500 Milligram
  • Pharmaceutical form:
  • Suppositories
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug

Documents

Localization

  • Available in:
  • ASACOLON Suppositories 500 Milligram
    Ireland
  • Language:
  • English

Status

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

Summary of Product characteristics: dosage, interactions, side effects

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

Asacolon500mgSuppositories

2QUALITATIVEANDQUANTITATIVECOMPOSITION

Eachsuppositorycontains:Mesalazine500mg.

Forafulllistofexcipients,seesection6.1.

3PHARMACEUTICALFORM

Suppository.

Torpedo-shapedsuppositorieswithalightgrey-browncolour.

4CLINICALPARTICULARS

4.1TherapeuticIndications

Forthetreatmentofmildtomoderateproctitisandproctosigmoiditis.

Asanadjuncttooraltherapyinseveregeneralisedulcerativecolitisaffectingtherectumorrectosigmoidcolon.

4.2Posologyandmethodofadministration

Rectaladministration.

Adults:

Onesuppositorytobeinserteduptothreetimesdaily,afterdefaecation.Thedosageisdependentupontheseverityof

thediseaseanditmaybepossibletoreducethedosageastheconditionimproves.Inseveregeneralisedulcerative

colitisaffectingtherectumorrectosigmoid,andincasesslowtorespondtooraltherapy,onesuppositorymaybeused

morningandevening,asanadjuncttooraltherapy.

Renalimpairment/hepaticimpairment:

Nodatafromcontrolledclinicalstudiesareavailablewarrantingaspecificdoseadjustmentinpatientswithmildto

moderaterenalorhepaticimpairment.Themaximumdailyadultdoseof1.5gmesalazineforrectaladministration

appearstocarrylittleadditionalriskinthesepatientsconsidering4.0gmesalazinebeingapprovedasmaximumdaily

dosefororaladministration(Asacolontablets)totreatmildacuteulcerativecolitis,seesection4.4.Forsevererenalor

hepaticimpairment,seesection4.3.

Theelderly:

Asforadultsaboveunlessrenalfunctionisseverelyimpaired(seesection4.3and4.4).Nostudieshavebeencarried

outintheelderly.

Children:

Thereisnodoserecommendationforchildren(seesection4.3and4.4).

4.3Contraindications

Asacoloniscontraindicatedincasesof:

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 07/11/2011 CRN 2103419 page number: 1

-Hypersensitivitytomesalazineoranyoftheexcipients(seesection6.1).

-Severerenalimpairment(GFRlessthan30mLperminute).

-Severeliverimpairment.

-Gastricandduodenalulcers

-Childrenunder2yearsofage.

4.4Specialwarningsandprecautionsforuse

Renalimpairment

Urinarystatus(dipsticks)shouldbedeterminedpriortoandduringtreatment,atthediscretionofthetreating

physician.Cautionshouldbeexercisedinpatientswithraisedbloodureaorproteinuria.Thepossibilityofmesalazine-

inducednephrotoxicityshouldbesuspectedinpatientsdevelopingimpairmentofrenalfunctionduringtreatment.Itis

recommendedthatallpatientshaveanevaluationoftheirrenalfunctionpriortoinitiationofAsacolontherapyand

periodicallywhileonAsacolontherapy.Asaguideline,follow-uptestsarerecommended14daysafterinitiationof

therapyandthenevery4weeksforthefollowing12weeks.ShortmonitoringintervalsearlyafterthestartofAsacolon

therapywilldiscoverrareacuteallergicimpairmentofrenalfunction.Intheabsenceofanacuteallergicrenalresponse

monitoringintervalscanbeextendedtoevery3monthsandthenannuallyafter5years.Ifadditionalsymptomsoccur,

thesetestsshouldbeperformedimmediately.TreatmentwithAsacolonshouldbestoppedimmediatelyifthereis

evidenceofrenalimpairmentandpatientsshouldseekimmediatemedicaladvice.

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.

Haematologicalinvestigationsincludingacompletebloodcountshouldbeperformedpriortoinitiationandwhileon

therapyatthediscretionofthetreatingphysician.Asaguideline,follow-uptestsarerecommended14daysafter

initiationoftherapyandthenevery4weeksforthefollowing12weeks.Iftheresultsarenormal,follow-uptestsare

recommendedshouldbecarriedoutevery3months.Ifadditionalsymptomsoccur,thesetestsshouldbeperformed

immediately.Thisprocedureistobefollowedespecially,ifapatientdevelopssignsandsymptomssuggestiveofblood

dyscrasiaduringtreatment,suchasunexplainedbleeding,haematoma,purpura,anaemia,persistentfeverorsorethroat.

TreatmentwithAsacolonshouldbestoppedimmediatelyifthereisasuspicionorevidenceofblooddyscrasiaand

patientsshouldseekimmediatemedicaladvice.

Theelderly

Useintheelderlyshouldbehandledwithcautionandtheproductshouldonlybeprescribedtopatientshavinganormal

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 07/11/2011 CRN 2103419 page number: 2

Children

SafetyandeffectivenessofAsacolonsuppositoriesinchildrenhavenotbeenestablished.

4.5Interactionwithothermedicinalproductsandotherformsofinteraction

Specificinteractionstudieshavenotbeenperformed.

Mesalazinecanincreasethemyelosuppressiveeffectsofazathioprineand6-mercapto-purine,orthioguanine.Life-

threateninginfectioncanoccur.Patientsshouldbecloselyobservedforsignsofinfectionandmyelosuppression.

Haematologicalparameters,suchasleukocyteandlymphocytecellcountsshouldbemonitoredregularly(weekly),

especiallyatinitiationofsuchcombinationtherapy(seesection4.4).Ifwhitebloodcellsarestableafter1month,

testingevery4weeksforthefollowing12weeksfollowedby3monthlymonitoringintervalsappearstobejustified.

Concurrentuseofknownnephrotoxicagents,suchasNSAIDs,azathioprine,ormethotrexate,mayincreasetheriskof

renalreactions.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/feetaldevelopment,parturitionorpostnataldevelopment.

Mesalazinecrossestheplacentalbarrier.Asacolonshouldonlybeusedduringpregnancyifthepotentialbenefit

outweighsthepossiblerisk.Cautionshouldbeexercisedwhenusinghighdosesofmesalazine.

N-acetyl-5-aminosalicylicacidandtoalesserdegreemesalazineareexcretedinbreastmilk.Theclinicalsignificance

ofthishasnotbeendetermined.Onlylimitedexperienceduringlactationinwomenisavailabletodate.

Hypersensitivityreactionssuchasdiarrhoeaintheinfantcannotbeexcluded.Therefore,Asacolonshouldonlybeused

duringbreast-feeding,ifthepotentialbenefitoutweighsthepossiblerisk.Iftheinfantdevelopsdiarrhoea,breastfeeding

shouldbediscontinued.

4.7Effectsonabilitytodriveandusemachines

Noeffectsontheabilitytodriveandusemachineshavebeenobserved.

4.8Undesirableeffects

TheAsacolonclinicaltrialdatabaseincludes246patientstreatedwithAsacolon500mgSuppositories.Themesalazine

doseswereintherangeof1.0g/dayto1.5g/day,thetreatmentdurationvariedbetweenfourweeksandtwelvemonths.

Undesirableeffectsrelevantforthelabellingreportedfromfourdouble-blindandoneopenclinicalstudyand

informationfromspontaneousreportingandtheliteratureislistedbelow.

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 07/11/2011 CRN 2103419 page number: 3

Bloodandlymphaticsystemdisorders

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

thrombocytopenia),bonemarrowdepression,eosinophilia,blooddisorder.

Immunesystemdisorders

Veryrare: hypersensitivityreactionssuchasallergicexanthema,drugfever,lupuserythematosussyndrome,

pancolitis.

Nervoussystemdisorders

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.

Veryrare: acutepancreatitis.

Notknown: exacerbationofthesymptomsofcolitis.

Hepato-biliarydisorders

Veryrare: changesinliverfunctionparameters(increaseintransaminasesandcholestasisparameters),hepatitis,

cholestatichepatitis,bloodbilirubinincreased.

Skinandsubcutaneoustissuedisorders

Veryrare: alopecia.

Musculoskeletal,connectivetissueandbonedisorders

Veryrare: myalgia,arthralgia.

Notknown: lupus-likesyndromewithpericarditisandpleuropericarditisasprominentsymptomsaswellasrashand

arthralgia.

Renalandurinarydisorders

Veryrare: impairmentofrenalfunctionincludingacuteandchronicinterstitialnephritisandrenalinsufficiency,

nephroticsyndrome,renalfailurewhichmayreversibleonwithdrawal.

Reproductivesystemandbreastdisorders

Veryrare: oligospermia(reversible).

Generaldisordersandadministrationsiteconditions

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(cannotbeestimatedfromtheavailabledata)

AnunknownnumberoftheaboveundesirableeffectsareprobablyassociatedtotheunderlyingIBDratherthan

Asacolon/mesalazinemedication.Thisholdstrueespeciallyforgastrointestinalundesirableeffects.

Mesalazine-inducednephrotoxicity,whichmaybereversibleonwithdrawal,shouldbesuspectedinpatients

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 07/11/2011 CRN 2103419 page number: 4

Toavoidblooddyscrasiaresultingfromdevelopingbonemarrowdepressionpatientsshouldbemonitoredwithcare

(seesection4.4).

Co-administrationofmyelosuppressivedrugssuchasazathioprine,or6-MPorthioguaninecanprecipitateleucopenia

(seesection4.5).

ConcurrentuseofNSAIDs,azathioprine,ormethotrexate,mayincreasetheriskofrenalreactions(seesection4.5).

4.9Overdose

Thereareraredataonoverdose(e.g.intendedsuicidewithhighoraldosesofmesalazine),whichdonotindicaterenal

orhepatictoxicity.Thereisnospecificantidoteandtreatmentissymptomaticandsupportive.

5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

Asacolon500mgSuppositoriescontainmesalazine[ATCA07EC02],alsoknownas5-aminosalicylicacid,whichhas

ananti-inflammatoryeffectthroughamechanismthathasnotyetbeenfullyclarified.Mesalazineinhibitsmigrationof

polymorphnuclearleucocytesandlipoxygenaseofcellsatconcentrationsreachedinthelargeintestineduring

treatment.Theproductionofpro-inflammatoryleukotrienes(LTB4and5-HETE)inmacrophagesoftheintestinalwall

istheninhibited.Undertrialconditionsmesalazinehasalsoinhibitedthecyclooxygenaseandthus,thereleaseof

thromboxaneB2andprostaglandinE2,buttheclinicalmeaningofthiseffectisstillunclear.Mesalazineinhibitsthe

formationofplateletactivatingfactor(PAF).RecentlymesalazinehasbeenshowntoactivatePPAR-receptorswhich

counteractnuclearactivationofintestinalinflammatoryresponses.Mesalazineisalsoanantioxidant;ithasbeenshown

todecreaseformationofreactiveoxygenproductsandtocapturefreeradicals.

5.2Pharmacokineticproperties

Aswiththetablets,onlyaproportionofmesalazinecontainedinthesuppositoriesisabsorbedandavailabletothe

systemiccirculation.Themodeofactionofmesalazineislocalratherthansystemic.AcetylationofmesalazinetoN-

acetylmesalazineoccursinthegastrointestinalwallandintheliver.N-acetylmesalazineispredominantlyexcretedin

theurine.AfterasingledoseofAsacolon500mgSuppositoriesinhealthyvolunteersthemeanCmaxandTmaxwere

211ng/mLand2.0hoursformesalazineand443ng/mLand3.0hoursforNacetylmesalazine,respectively.

MesalazineandthemainmetaboliteN-acetylmesalazinewerereportedtohavebiologicalhalf-livesof4.97hoursand

8.32hours,respectively.About43%ofmesalazineandabout78%ofN-acetylmesalazineareboundtoplasma

proteins.LowconcentrationsofmesalazineanditsN-acetylmetabolitehavebeendetectedinhumanbreastmilk.The

clinicalsignificanceofthishasnotbeendetermined.

5.3Preclinicalsafetydata

Toxicityofmesalazineafteroraladministrationhasbeeninvestigatedinseveralstudieswithbothsingleandrepeated

doses.Whenadoseof1g/kgbodyweight/daywasadministeredrepeatedlytorats,itcauseddamageinkidneysandthe

gastro-intestinaltract.

6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

HardFat.

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 07/11/2011 CRN 2103419 page number: 5

6.2Incompatibilities

Notapplicable.

6.3Shelflife

3years.

6.4Specialprecautionsforstorage

Donotstoreabove25°C.Storeinadryplaceprotectedfromdirectheat.Storeintheoriginalpackageinorderto

protectfromlight.

6.5Natureandcontentsofcontainer

PVC/polyethylenelaminatefoilstripsof5suppositoriespackedinanoutercardboardcartoncontaining20

suppositories.

6.6Specialprecautionsfordisposalofausedmedicinalproductorwastematerialsderivedfrom

suchmedicinalproductandotherhandlingoftheproduct

Nospecialrequirements.

7MARKETINGAUTHORISATIONHOLDER

TillottsPharmaLimited

UnitedDrugHouse

MagnaDrive

MagnaBusinessPark

CitywestRoad

Dublin24

8MARKETINGAUTHORISATIONNUMBER

PA1204/1/1

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

Dateoffirstauthorisation:26June1995

Dateoflastrenewal:26June2010

10DATEOFREVISIONOFTHETEXT

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 07/11/2011 CRN 2103419 page number: 6