GALOXIWAY

Main information

  • Trade name:
  • GALOXIWAY Tablets 15 Milligram
  • Dosage:
  • 15 Milligram
  • Pharmaceutical form:
  • Tablets
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug

Documents

Localization

  • Available in:
  • GALOXIWAY Tablets 15 Milligram
    Ireland
  • Language:
  • English

Status

  • Source:
  • HPRA - Health Products Regulatory Authority - Ireland
  • Authorization number:
  • PA0043/043/002
  • Authorization date:
  • 24-07-2006
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

IRISHMEDICINESBOARDACTS1995AND2006

MEDICINALPRODUCTS(CONTROLOFPLACINGONTHEMARKET)REGULATIONS,2007

(S.I.No.540of2007)

PA0043/043/002

CaseNo:2019779

TheIrishMedicinesBoardinexerciseofthepowersconferredonitbytheabovementionedRegulationsherebygrantsto

CrookesHealthcareLtd

1ThaneRoadWest,Nottingham,NG23AA,UnitedKingdom

anauthorisation,subjecttotheprovisionsofthesaidRegulations,inrespectoftheproduct

Galoxiway15mgTablets

TheparticularsofwhicharesetoutinPartIandPartIIoftheattachedSchedule.Theauthorisationisalsosubjecttothegeneralconditionsas

maybespecifiedinthesaidRegulationsaslistedonthereverseofthisdocument.

Thisauthorisation,unlesspreviouslyrevoked,shallcontinueinforcefrom20/02/2008until23/07/2011.

SignedonbehalfoftheIrishMedicinesBoardthis

________________

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PartII

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

Galoxiway15mgTablets.

2QUALITATIVEANDQUANTITATIVECOMPOSITION

Eachtabletcontainsmeloxicam15mg.

Excipient:thisproductcontains86mglactosepertablet

Forafulllistofexcipientsseesection6.1

3PHARMACEUTICALFORM

Tablet

Paleyellowcolouredroundtabletwithascorelineononeside.Thetabletcanbedividedintoequalhalves.

4CLINICALPARTICULARS

4.1TherapeuticIndications

Short-termsymptomatictreatmentofexacerbationsofosteoarthrosis.

Long-termsymptomatictreatmentofrheumatoidarthritisorankylosingspondylitis

4.2Posologyandmethodofadministration

Oraluse

Exacerbationsofosteoarthrosis:7.5mg/day.(halfa15mgtablet)

Ifnecessary,intheabsenceofimprovement,thedosemaybeincreasedto15mg/day(one15mgtablet).

Rheumatoidarthritis,ankylosingspondylitis:15mg/day.(one15mgtablet)

Accordingtothetherapeuticresponse,thedosemaybereducedto7.5mg/day.(halfa15mgtablet)

DONOTEXCEEDTHEDOSEOF15mg/day.

Thetotaldailyamountshouldbetakenasasingledose,withwateroranotherliquid,duringameal.

Undesirableeffectsmaybeminimizedbyusingthelowesteffectivedosefortheshortestdurationnecessarytocontrol

symptoms(seesection4.4).Thepatient'sneedforsymptomaticreliefandresponsetotherapyshouldbere-evaluated

periodically,especiallyinpatientswithosteoarthritis.

Specialpopulations

Elderlypatientsandpatientswithincreasedrisksforadversereaction(seesection5.2):Therecommendeddosefor

longtermtreatmentofrheumatoidarthritisandankylosingspondylitisinelderlypatientsis7.5mgperday.Patients

withincreasedrisksforadversereactionsshouldstarttreatmentwith7.5mgperday(seesection4.4).

Renalimpairment(seesection5.2):

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Nodosereductionisrequiredinpatientswithmildtomoderaterenalimpairment(i.e.patientswithacreatinine

clearanceofgreaterthan25ml/min).(Forpatientswithnon-dialysedsevererenalfailure,seesection4.3).

Hepaticimpairment(seesection5.2):

Nodosereductionisrequiredinpatientswithmildtomoderatehepaticimpairment(Forpatientswithseverely

impairedliverfunction,seesection4.3).

ChildrenandAdolescents(<15years):

Meloxicamshouldnotbeusedinchildrenandadolescentsagedunder15years.

Meloxicamexistsinotherstrengthswhichmaybemoreappropriate.

4.3Contraindications

Themedicinalproductiscontra-indicatedinthefollowingsituations:

hypersensitivitytomeloxicamortoanyoftheexcipientsorhypersensitivitytosubstanceswithasimilaraction

e.g.NSAID’s,acetylsalicylicacid.Meloxicamtabletsshouldnotbegiventopatientswhohavedevelopedsigns

ofasthma,nasalpolyps,angioneuroticoedemaorurticariafollowingtheadministrationofacetylsalicylicacidor

otherNSAID’s;

thirdtrimesterofpregnancyandlactation

Activeorhistoryofrecurrentpepticulcer/haemorrhage(twoormoredistinctepisodesofprovenulcerationor

bleeding),severelyimpairedliverfunction

non-dialysedsevererenalfailure;

HistoryofgastrointestinalbleedingorperforationrelatedtopreviousNSAIDstherapy,cerebrovascularbleeding

orotherbleedingdisorders.

severecongestiveheartfailure

4.4Specialwarningsandprecautionsforuse

Undesirableeffectsmaybeminimisedbyusingthelowesteffectivedosefortheshortestdurationnecessarytocontrol

symptoms(seesection4.2andGIandcardiovascularrisksbelow)

Anyhistoryofoesophagitis,gastritisand/orpepticulcermustbesoughtinordertoensuretheirtotalcurebefore

startingtreatmentwithmeloxicam.Attentionshouldroutinelybepaidtothepossibleonsetofarecurrenceinpatients

treatedwithmeloxicamandwithapasthistoryofthistype.

NSAIDsshouldbegivenwithcaretopatientswithgastrointestinalsymptomsorahistoryofgastrointestinaldisease

(i.e.ulcerativecolitis,Crohn’sdisease)astheirconditionmaybeexacerbated(Seesection4.8).Patientsshouldbe

monitoredfordigestivedisturbances,especiallyforgastrointestinalbleeding.

Gastrointestinalbleeding,ulcerationorperforationwhichcanbefatal,havebeenreportedwithallNSAIDsatanytime

duringtreatment,withorwithoutwarningssymptomsorprevioushistoryofseriousgastrointestinalevents.

TheelderlyhaveanincreasedfrequencyofadversereactionstoNSAIDsespeciallygastrointestinalbleedingand

perforation,whichmaybefatal(seesection4.2)

Inpatientswithahistoryofulcer,thereisahigherriskofgastrointestinalbleeding,ulcerationorperforationwith

increasedNSAIDdoses,particularlyifthepatientiselderlyorcomplicatedwithhaemorrhageorperforation(see

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Combinationtherapywithprotectiveagents(e.gmisoprostolorprotonpumpinhibitors)shouldbeconsideredforthese

patients,andalsoforpatientsrequiringconcomitantlowdoseaspirin,orotherdrugslikelytoincreasegastrointestinal

risk(seesection4.5).

Ifgastrointestinalbleedingorulcerationoccursinpatientsreceivingmeloxicam,thedrugshouldbewithdrawn.

Thepossibleoccurrenceofsevereskinreactionsandseriouslifethreateninghypersensitivityreactions(i.e.

anaphylacticreaction)isknowntooccurwithNSAIDsincludingoxicams.Inthosecases,Meloxicamshouldbe

withdrawnimmediatelyandcarefulobservationisnecessary.

seriousskinreactions,someofthemfatal,includingexfoliativedermatitis,Stevens-Johnsonsyndrome,andtoxic

epidermalnecrolysis,havebeenreportedveryrarelyinassociationwiththeuseofNSAIDs(see4.8).Patientsappearto

beathighestriskofthesereactionsearlyinthecourseoftherapy,theonsetofthereactionoccurringinthemajorityof

caseswithinthefirstmonthoftreatment.Galoxiwayshouldbediscontinuedatthefirstappearanceofskinrash,

mucosallesions,oranyothersignofhypersensitivity.

Inrareinstances,NSAIDsmaybethecauseofinterstitialnephritis,glomerulonephritis,renalmedullarynecrosisor

nephroticsyndrome.

AswithmostNSAIDsoccasionalincreasesinserumtransaminaselevels,increasesinserumbilirubinorotherliver

functionparametersaswellasincreasesinserumcreatinineandbloodureanitrogenaswellasotherlaboratory

disturbanceshavebeenreported.Themajorityoftheseinstancesinvolvedtransitoryandslightabnormalities.Should

anysuchabnormalityprovesignificantorpersistent,theadministrationofmeloxicamshouldbestoppedand

appropriateinvestigationsundertaken.

Functionalrenalfailure:NSAIDsbyinhibitingthevasodilatingeffectofrenalprostaglandinsmayinduceafunctional

renalfailurebyreductionofglomerularfiltration.Thisadverseeventisdose-dependent.Atthebeginningofthe

treatment,orafterdoseincrease,carefulmonitoringofthediuresisandtherenalfunctionisrecommendedinpatients

withthefollowingriskfactors:

Elderly

ConcomitanttreatmentssuchasACEinhibitors,angiotensinIIantagonists,sartans,diuretics,(seesection4.5)

Congestiveheartfailure

Renalfailure

Nephroticsyndrome

Lupusnephropathy

Severehepaticdysfunction(serumalbumin<25g/lorchild-pughscore ≥10)

Sodiumandwaterretention:Sodiumandwaterretentionwithpossibilityofoedema,hypertensionaggravation,cardiac

failureaggravation.Clinicalmonitoringisnecessary,assoonasstartingtherapyincaseofhypertensionorcardiac

failure.Adecreaseoftheantihypertensiveeffectcanoccur(seesection4.5).

Hyperkalaemia:Hyperkalaemiacanbefavouredby diabetesorconcomitanttreatmentknowntoincreasekalaemia

(seesection4.5).Regularmonitoringofpotassiumvaluesshouldbeperformedinsuchcases.

Adversereactionsareoftenlesswelltoleratedinelderly,fragileorweakenedindividuals,whothereforerequirecareful

monitoring.AswithotherNSAIDsparticularcautionisrequiredintheelderly,inwhomrenal,hepaticandcardiac

functionsarefrequentlyimpaired.

UsewithconcomitantNSAIDsincludingcyclooxygenase-2selectiveinhibitorsshouldbeavoided.

Cautionshouldbeadvisedinpatientsreceivingconcomitantmedicationswhichcouldincreasetheriskofulcerationor

bleeding,suchascorticosteroids,anticoagulantssuchaswarfarin,selectiveserotoninreuptakeinhibitorsoranti-platelet

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Therecommendedmaximumdailydoseshouldnotbeexceededincaseofinsufficienttherapeuticeffectnorshouldan

additionalNSAIDbeaddedtothetherapybecausethismayincreasethetoxicitywhiletherapeuticadvantagehasnot

beenproven.Intheabsenceofimprovementafterseveraldays,theclinicalbenefitofthetreatmentshouldbe

reassessed.

Meloxicam,aswithotherNSAIDs,maymasksymptomsofanunderlyinginfectiousdisease

Theuseofmeloxicam,aswithanydrugknowntoinhibit

cyclooxygenase/prostaglandinsynthesis,mayimpairfertilityandisnotrecommendedinwomenattemptingto

conceive.Inwomenwhohavedifficultiesconceiving,orwhoareundergoinginvestigationofinfertility,withdrawalof

meloxicamshouldbeconsidered”

Cautionisrequiredifmeloxicamisadministeredtopatientssufferingfrom,orwithaprevioushistoryof,bronchial

asthmasincethereisapossibilitythatNSAIDscouldcausebronchospasminsuchpatients.

Thismedicinalproductcontainslactose.Patientswithrarehereditaryproblemsofgalactoseintolerance,theLapp

lactasedeficiencyorglucose-galactosemalabsorptionshouldnottakethismedicine.

Cardiovascularandcerebrovasculareffects:Appropriatemonitoringandadvicearerequiredforpatientswithahistory

ofhypertensionand/ormildtomoderatecongestiveheartfailureasfluidretentionandoedemahavebeenreportedin

associationwithNSAIDtherapy.

ClinicaltrialandepidemiologicaldatasuggestthatuseofsomeNSAIDs(particularlyathighdosesandinlongterm

treatment)maybeassociatedwithasmallincreasedriskofarterialthromboticevents(forexamplemyocardial

infarctionorstroke).Thereisinsufficientdatatoexcludesuchariskformeloxicam.

Patientswithuncontrolledhypertension,congestiveheartfailure,establishedischaemicheartdisease,peripheral

arterialdisease,and/orcerebrovasculardiseaseshouldonlybetreatedwithmeloxicamaftercarefulconsideration.

Similarconsiderationshouldbemadebeforeinitiatinglonger-termtreatmentofpatientswithriskfactorsfor

cardiovasculardisease(e.g.hypertension,hyperlipidaemia,diabetesmellitus,smoking).

4.5Interactionwithothermedicinalproductsandotherformsofinteraction

PharmacodynamicInteractions:

OtherNSAIDs,includingsalicylates(acetylsalicylicforplatelet

inhibitionexclude)d:

AdministrationofseveralNSAIDstogethermayincreasetheriskofgastrointestinalulcersandbleeding,viaa

synergisticeffect.TheconcomitantuseofmeloxicamwithotherNSAIDsisnotrecommended(seesection4.4).

Oralanticoagulants:

Increasedriskofbleeding,viainhibitionofplateletfunctionanddamagetothegastroduodenalmucosa.The

concomitantuseofNSAIDsandoralanticoagulantsisnotrecommended(seesection4.4).

CarefulmonitoringoftheINRisrequiredifitprovesimpossibletoavoidsuchacombination.

Thrombolyticsandantiplateletdrugs:

Increasedriskofbleeding,viainhibitionofplateletfunctionanddamagetothegastroduodenalmucosa(seesection

4.4).

Selectiveserotonin-reuptakeinhibitors(SSRIs)

Increasedriskofgastrointestinalbleeding(seesection4.4)

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NSAIDs(includingacetylsalicylicacidatdoses 3g/d)andangiotensin-IIreceptorantagonistsexertasynergistic

effectonthedecreaseofglomerularfiltration,whichmaybeexacerbatedwhenrenalfunctionisaltered.Whengiven

totheelderlyand/ordehydratedpatients,thiscombinationcanleadtoacuterenalfailurebyactingdirectlyon

glomerularfiltration.Monitoringofrenalfunctionatthebeginningofthetreatmentisrecommendedaswellasregular

hydrationofthepatient.Additionally,concomitanttreatmentcanreduceantihypertensiveeffectofACEinhibitorsand

angiotensinIIreceptorantagonists,leadingtopartiallossofefficacy(duetoinhibitionofprostaglandinswith

vasodilatoryeffect).

Otherantihypertensivedrugs(e.g.Beta-blockers):

Asforthelatter,adecreaseoftheantihypertensiveeffectofbeta-blockers(duetoinhibitionofprostaglandinswith

vasodilatoryeffect)canoccur.

Cyclosporin:

NephrotoxicityofcyclosporinmaybeenhancedbyNSAIDsviarenalprostaglandinmediatedeffects.During

combinedtreatmentrenalfunctionistobemeasured.Acarefulmonitoringoftherenalfunctionisrecommended,

especiallyintheelderly.

Corticosteroids:

Increasedriskofgastrointestinalulcerationorbleeding.

Intrauterinedevices.

AdecreaseoftheefficacyofintrauterinedevicesbyNSAIDshasbeenpreviouslyreportedbutneedsfurther

confirmation.

PharmacokineticInteractions(Effectofmeloxicamonthepharmacokineticsofotherdrugs).

Lithium:

NSAIDshavebeenreportedtoincreasebloodlithiumlevels(viadecreasedrenalexcretionoflithium),whichmay

reachtoxicvalues.TheconcomitantuseoflithiumandNSAIDsisnotrecommended(seesection4.4).Ifthis

combinationappearsnecessary,lithiumplasmaconcentrationsshouldbemonitoredcarefullyduringtheinitiation,

adjustmentandwithdrawalofmeloxicamtreatment.

Methotrexate:

NSAIDscanreducethetubularsecretionofmethotrexatetherebyincreasingtheplasmaconcentrationsof

methotrexate.Forthisreason,forpatientsonhighdosagesofmethotrexate(morethan15mg/week)theconcomitant

useofNSAIDsisnotrecommended(seesection4.4).

TheriskofaninteractionbetweenNSAIDpreparationsandmethotrexateshouldbeconsideredalsoinpatientsonlow

dosageofmethotrexate,especiallyinpatientswithimpairedrenalfunction.Incasecombinationtreatmentisnecessary

bloodcellcountandtherenalfunctionshouldbemonitored.CautionshouldbetakenincasebothNSAIDand

methotrexatearegivenwithin3days,inwhichcasetheplasmalevelofmethotrexatemayincreaseandcauseincreased

toxicity.

Althoughthepharmacokineticsofmethotrexate(15mg/week)werenotrelevantlyaffectedbyconcomitantmeloxicam

treatment,itshouldbeconsideredthatthehaematologicaltoxicityofmethotrexatecanbeamplifiedbytreatmentwith

NSAIDdrugs(seeabove).(Seesection4.8).

PharmacokineticInteractions(Effectofotherdrugsonthepharmacokineticsofmeloxicam)

Cholestyramine:

Cholestyramineacceleratestheeliminationofmeloxicambyinterruptingtheenterohepaticcirculationsothatclearance

formeloxicamincreasesby50%andthehalf-lifedecreasesto13 ±

3hrs.Thisinteractionisofclinicalsignificance.

Noclinicallyrelevantpharmacokineticdrug-druginteractionsweredetectedwithrespecttotheconcomitant

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4.6Pregnancyandlactation

Pregnancy:

Inhibitionofprostaglandinsynthesismayadverselyaffectthepregnancyand/ortheembryo/foetaldevelopment.Data

fromepidemiologicalstudiessuggestanincreasedriskofmiscarriageandofcardiacmalformationandgastroschisis

afteruseofaprostaglandinsynthesisinhibitorinearlypregnancy.Theabsoluteriskforcardiovascularmalformation

wasincreasedfromlessthan1%,uptoapproximately1.5%.theriskisbelievedtoincreasewithdoseanddurationof

therapy.Inanimals,administrationofaprostaglandinsynthesisinhibitorhasbeenshowntoresultinincreasedpre-and

post-implantationlossandembryo-foetallethality.Inaddition,increasedincidencesofvariousmalformations,

includingcardiovascular,havebeenreportedinanimalsgivenaprostaglandinsynthesisinhibitorduringthe

organogeneticperiod.

Duringthefirstandsecondtrimesterofpregnancy,meloxicamshouldnotbegivenunlessclearlynecessary.If

meloxicamisusedbyawomanattemptingtoconceive,orduringthefirstandsecondtrimesterofpregnancy,thedose

shouldbekeptaslowanddurationoftreatmentasshortaspossible.

Duringthethirdtrimesterofpregnancy,allprostaglandinsynthesisinhibitorsmayexposethefoetusto:

Cardiopulmonarytoxicity(withprematureclosureoftheductusarteriosusandpulmonaryhypertension);

Renaldysfunction,whichmayprogresstorenalfailurewitholigo-hydroamniosis;

themotherandtheneonate,attheendofpregnancy,to:

Possibleprolongationofbleedingtime,ananti-aggregatingeffectwhichmayoccurevenatverylowdoses;

Inhibitionofuterinecontractionsresultingindelayedorprolongedlabour.

Consequently,meloxicamiscontraindicatedduringthethirdtrimesterofpregnancy.

Lactation:

Whilenospecificexperienceexistsformeloxicam,NSAIDsareknowntopassintomother’smilk.Administrationof

meloxicamiscontraindicatedinwomenwhoarebreastfeeding.

4.7Effectsonabilitytodriveandusemachines

Therearenospecificstudiesaboutsucheffects.

However,onthebasisofthepharmacodynamicprofileandreportedadversedrugreactions,meloxicamislikelyto

havenoornegligibleinfluenceontheseabilities.However,whenvisualdisturbancesordrowsiness,vertigoorother

centralnervoussystemdisturbancesoccur,itisadvisabletorefrainfromdrivingandoperatingmachinery.

4.8Undesirableeffects

a) GeneralDescription

Thefrequenciesofadversedrugreactionsgivenbelowarebasedoncorrespondingoccurrencesofreportedadverse

eventsinclinicaltrials.Theinformationisbasedonclinicaltrialsinvolving3750patientswhohavebeentreatedwith

dailyoraldosesof7.5or15mgmeloxicamtabletsorcapsulesoveraperiodofupto18months(meandurationof

treatment127days).

Adversedrugreactionsthathavecometolightasaresultofreportsreceivedinrelationtoadministrationofthe

marketedproductareincluded.

Gastrointestinal:themostcommonlyobservedadverseeventsaregastrointestinalinnature.Pepticulcers,perforation

orGIbleeding,sometimesfatal,particularlyintheelderly,mayoccur(seesection4.4).Nausea,vomiting,diarrhoea,

flatulence,constipation,dyspepsia,abdominalpain,melaena,haematemesis,ulcerativestomatitis,exacerbationof

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administration.Lessfrequently,gastritishasbeenobserved.

ClinicaltrialandepidemiologicaldatasuggestthatuseofsomeNSAIDs(particularlyathighdosesandinlongterm

treatment)maybeassociatedwithanincreasedriskofarterialthromoboticevents(forexamplemyocardialinfarction

orstroke)(seesection4.4).

Oedema,hypertensionandcardiacfailurehavebeenreportedinassociationwithNSAIDtreatment.

Adversereactionshavebeenrankedunderheadingsoffrequencyusingthefollowingconvention:

Verycommon( ≥1/10),common(≥1/100,<1/10),uncommon(≥1/1000,<1/100),rare(≥1/10000,<1/1000),very

rare(<1/10000).

Tableofadversereactions

Bloodandthelymphaticsystemdisorders

Common: Anaemia

Uncommon:Disturbancesofbloodcount:leucocytopenia;thrombocytopenia; agranulocytosis(seesectionc)

Immunesystemdisorders

Rare: Anaphylactic/anaphylactoidreactions

Psychiatricdisorders

Rare: Mooddisorders,insomniaandnightmares

Nervoussystemdisorders

Common: Lightheadedness,headache

Uncommon:Vertigo,tinnitus,drowsiness

Rare: Confusion

Eyedisorders

Rare: Visualdisturbancesincludingblurredvision

Cardiacdisorders

Uncommon: Palpitations

Vasculardisorders

Uncommon: Increaseinbloodpressure(seesection4.4),flushes

Respiratory,thoracicandmediastinaldisorders

Rare: OnsetofasthmaattacksincertainindividualsallergictoaspirinorotherNSAIDs

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Common:Dyspepsia,nauseaandvomitingsymptoms,abdominalpain,constipation,flatulence,diarrhoea

Uncommon:Gastrointestinalbleeding,gastroduodenalulcers,oesophagitis,stomatitis

Rare:Gastrointestinalperforation,melaena,haemetemesis,ulcerativestomatis,exacerbationofcolitisandCrohn’s

disease(seesection4.4)

Lessfrequentlygastritishasbeenobserved

Thepepticulcers,perforationorgastrointestinalbleeding,thatmayoccurcanbefatalparticularlyintheelderly(see

section4.4).

Hepato-biliarydisorders

Rare: Hepatitis

Skinandsubcutaneoustissuedisorders

Common: Pruritus,rash

Uncommon: Urticaria

Rare: Stevens-JohnsonSyndromeandtoxicepidermalnecrolysis,angioedema,bullousreactionssuch

aserythemamultiforme,photosensitivityreactions

Renalandurinarydisorders

Uncommon: Sodiumandwaterretention,hyperkaleamia(seesection4.4andsection4.5)

Rare: Acuterenalfailureinpatientswithriskfactors(seesection4.4)

Generaldisordersandadministrationsiteconditions

Common: Oedemaincludingoedemaofthelowerlimbs

Investigations

Uncommon: transitorydisturbanceofliverfunctiontest(e.g.raisedtransaminasesorbilirubin)

Uncommon: disturbanceoflaboratorytestsinvestigatingrenalfunction(e.g.raisedcreatinineorurea)

c) InformationCharacterisingIndividualSeriousand/orFrequentlyOccurringAdverseReactions

Isolatedcasesofagranulocytosishavebeenreportedinpatientstreatedwithmeloxicamandotherpotentially

myelotoxicdrugs(seesection4.5).

d) Adversereactionswhichhavenotbeenobservedyetinrelationtotheproduct,butwhicharegenerally

acceptedasbeingattributabletoothercompoundsintheclass

Organicrenalinjuryprobablyresultinginacuterenalfailure;isolatedcasesofinterstitialnephritis,acutetubular

necrosis,nephriticsyndrome,andpapillarynecrosishavebeenreported(seesection4.4).

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SymptomsfollowingacuteNSAIDoverdoseareusuallylimitedtolethargy,drowsiness,nausea,vomitingand

epigastricpain,whicharegenerallyreversiblewithsupportivecare.Gastrointestinalbleedingcanoccur.Severe

poisoningmayresultinhypertension,acuterenalfailure,hepaticdysfunction,respiratorydepression,coma,

convulsions,cardiovascularcollapseandcardiacarrest.Anaphylactoidreactionshavebeenreportedwiththerapeutic

ingestionofNSAIDsandmayoccurfollowinganoverdose.

PatientsshouldbemanagedwithsymptomaticandsupportivecarefollowinganNSAIDoverdose.Acceleratedremoval

ofmeloxicamby4goraldosesofcholestyraminegiventhreetimesadaywasdemonstratedinaclinicaltrial.

5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

Pharmacotherapeuticgroup:Anti-inflammatoryandantirheumaticproducts,non-steroids;Oxicams

ATCCode:M01AC06

Meloxicamisanon-steroidalanti-inflammatorydrug(NSAID)oftheoxicamfamily,withanti-inflammatory,analgesic

andantipyreticproperties.

Theanti-inflammatoryactivityofmeloxicamhasbeenproveninclassicalmodelsofinflammation.Aswithother

NSAIDsitsprecisemechanismofactionremainsunknown.However,thereisatleastonecommonmodeofaction

sharedbyallNSAIDs(includingmeloxicam):inhibitionofthebiosynthesisofprostaglandins,knowninflammation

mediators.

5.2Pharmacokineticproperties

Absorption

Meloxicamiswellabsorbedfromthegastrointestinaltract,whichisreflectedbyahighabsolutebioavailabilityof89%

followingoraladministration(capsule).Tablets,oralsuspensionandcapsuleswereshowntobebioequivalent.

Followingsingledoseadministrationofmeloxicam,meanmaximumplasmaconcentrationsareachievedwithin2

hoursforthesuspensionandwithin5-6hourswithsolidoraldosageforms(capsulesandtablets).

Withmultipledosing,steadystateconditionswerereachedwithin3to5days.Oncedailydosingleadstodrugplasma

concentrationswitharelativelysmallpeak-troughfluctuationintherangeof0.4-1.0 µ

g/mlfor7.5mgdosesand0.8–

g/mlfor15mgdoses,respectively(C

andC

atsteadystate,respectively).Maximumplasma

concentrationsofmeloxicamatsteadystateareachievedwithinfivetosixhoursforthetablet,capsuleandtheoral

suspension,respectively.Continuoustreatmentforperiodsofmorethanoneyearresultsinsimilardrugconcentrations

tothoseseenoncesteadystateisfirstachieved.Extentofabsorptionformeloxicamfollowingoraladministrationis

notalteredbyconcomitantfoodintake.

Distribution

Meloxicamisverystronglyboundtoplasmaproteins,essentiallyalbumin(99%).Meloxicampenetratesintosynovial

fluidtogiveconcentrationsapproximatelyhalfofthoseinplasma.Volumeofdistributionislow,onaverage11l.

Interindividualvariationistheorderof30-40%.

Biotransformation

Meloxicamundergoesextensivehepaticbiotransformation.Fourdifferentmetabolitesofmeloxicamwereidentified

inurine,whichareallpharmacodynamicallyinactive.Themajormetabolite,5’-carboxymeloxicam(60%ofdose),is

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extent(9%ofdose).InvitrostudiessuggestthatCYP2C9playsanimportantroleinthismetabolicpathway,witha

minorcontributionfromtheCYP3A4isoenzyme.Thepatient’speroxidaseactivityisprobablyresponsibleforthe

othertwometabolites,whichaccountfor16%and4%oftheadministereddoserespectively.

Elimination

Meloxicamisexcretedpredominantlyintheformofmetabolitesandoccurstoequalextentsinurineandfaeces.Less

than5%ofthedailydoseisexcretedunchangedinfaeces,whileonlytracesoftheparentcompoundareexcretedin

urine.

Themeaneliminationhalf-lifeisabout20hours.Totalplasmaclearanceamountsonaverage8ml/min.

Linearity/non-linearity

Meloxicamdemonstrateslinearpharmacokineticsinthetherapeuticdoserangeof7.5mgand15mgfollowingperoral

orintramuscularadministration.

Specialpopulations

Hepatic/renalInsufficiency:

Neitherhepatic,mildnormoderaterenalinsufficiencyhasasubstantialeffectonmeloxicampharmacokinetics.In

terminalrenalfailure,theincreaseinthevolumeofdistributionmayresultinhigherfreemeloxicamconcentrations,

andadailydoseof7.5mgmustnotbeexceeded(seesection4.2).

Elderly:

Meanplasmaclearanceatsteadystateinelderlysubjectswasslightlylowerthanthatreportedforyoungersubjects.

5.3Preclinicalsafetydata

ThetoxicologicalprofileofmeloxicamhasbeenfoundinpreclinicalstudiestobeidenticaltothatofNSAIDs:

gastrointestinalulcersanderosions,renalpapillarynecrosisathighdosesduringchronicadministrationintwoanimal

species.

Oralreproductivestudiesintherathaveshownadecreaseofovulationsandinhibitionofimplantationsand

embryotoxiceffects(increaseofresorptions)atmaternotoxicdoselevelsat1mg/kgandhigher.Studiesoftoxicityon

reproductioninratsandrabbitsdidnotrevealteratogenicityuptooraldosesof4mg/kginratsand80mg/kginrabbits.

Theaffecteddoselevelsexceededtheclinicaldose(7.5–15mg)byafactorof10to5-foldonamg/kgdosebasis(75

kgperson).Fetotoxiceffectsattheendofgestation,sharedbyallprostaglandinsynthesisinhibitors,havebeen

described.Noevidencehasbeenfoundofanymutageniceffect,eitherinvitroorinvivo.Nocarcinogenicriskhas

beenfoundintheratandmouseatdosesfarhigherthanthoseusedclinically.

6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

MicrocrystallineCellulose

PregelatinisedMaizeStarch

LactoseMonohydrate

MaizeStarch

SodiumCitrate

ColloidalAnhydrousSilica

MagnesiumStearate

Irish Medicines Board

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Date Printed 06/03/2008 CRN 2019779 page number: 11

Notapplicable.

6.3ShelfLife

3years.

6.4Specialprecautionsforstorage

Thismedicinalproductdoesnotrequireanyspecialstorageconditions.

6.5Natureandcontentsofcontainer

BlistersofPVC/PVdCandhardtemperedAluminiumfoil.Cartonsof7,10,14,15,20,28,30,50,60,100,140,280,

300,500,or1000tablets,(notallpacksizesmaybemarketed).

6.6Specialprecautionsfordisposal

Nospecialrequirements.

7MARKETINGAUTHORISATIONHOLDER

CrookesHealthcareLtd.,

1ThaneRoadWest,

Nottingham,NG23AA,

UnitedKingdom.

8MARKETINGAUTHORISATIONNUMBER

PA43/43/2

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

DateofFirstAuthorisation:24thJuly2006

10DATEOFREVISIONOFTHETEXT

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Date Printed 06/03/2008 CRN 2019779 page number: 12