ARTHRIMEL

Main information

  • Trade name:
  • ARTHRIMEL Film Coated Tablet 750 Milligram
  • Dosage:
  • 750 Milligram
  • Pharmaceutical form:
  • Film Coated Tablet
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug

Documents

Localization

  • Available in:
  • ARTHRIMEL Film Coated Tablet 750 Milligram
    Ireland
  • Language:
  • English

Status

  • Source:
  • HPRA - Health Products Regulatory Authority - Ireland
  • Authorization number:
  • PA0126/149/002
  • Authorization date:
  • 15-07-2011
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

Arthrimel750mgFilmCoatedTablets

2QUALITATIVEANDQUANTITATIVECOMPOSITION

Eachfilm-coatedtabletcontains942mgglucosaminesulfatesodiumchlorideequivalentto750mgglucosamine

sulfate.

Excipients:

Eachtabletcontains75.9mg(3.3mmol)ofsodium.

Lactosemonohydrate3.0mg

Forafulllistofexcipients,seesection6.1.

3PHARMACEUTICALFORM

Film-coatedtablets

Off-white,oblongshapedfilm-coatedtablet

4CLINICALPARTICULARS

4.1TherapeuticIndications

Arthrimeltabletsareindicatedforthetreatmentofosteoarthritisoflowtomoderatedegree.

4.2Posologyandmethodofadministration

Administration:

Arthrimeltabletsshouldbeswallowedwhole.

Adultsandtheelderly:

OneArthrimeltabletshouldbetakentwicedaily.

TwoArthrimeltabletstobetakenoncedaily.

Efficacyofglucosaminehasbeendemonstratedforperiodsofuptothreemonths,witharesidualeffectevidentfortwo

monthsafterdrugwithdrawal.Thesafetyandefficacyoftheproductwerealsoconfirmedinpivotalclinicaltrialsfor

treatmentuptothreeyears.Continuoustreatmentbeyond3yearscannotberecommendedasthesafetyhasnotbeen

establishedbeyondthisperiod.

Children:

Safetyandefficacyhasnotbeenestablishedinchildren,therefore,Arthrimeltabletsshouldnotbeusedinpersons

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4.3Contraindications

Knownsensitivitytoglucosamine(oranyofitsderivatives),sulfatesoranyoftheotheringredientsinArthrimeltablets

(listedinsection6.1).

4.4Specialwarningsandprecautionsforuse

Warnings

Arthrimeltabletscontainlactosemonohydrate,patientswithrarehereditaryproblemsofgalactoseintolerance,the

Lapplactasedeficiencyorglucose-galactosemalabsorptionshouldnottakethismedicine.

Thismedicinalproductcontains75.9mgsodiumperdose.Thedailysodiumintakeis151.7mg(equivalentto6.6

mmol).Tobetakenintoconsiderationbypatientsonacontrolledsodiumdiet.

Precautions

Sinceglucosamineisextractedfromshellfish,personswhoareallergictoshellfishshouldexercisecautionintheuseof

theproduct,althoughtherehavebeennoreportedcasesoftheseallergiestoglucosamine.

Cautionisadvisedintreatmentofpatientswithimpairedglucosetolerance.Closermonitoringofbloodsugarlevels

maybenecessaryindiabeticsatthebeginningoftreatment.

Inpatientswithaknownriskfactorforcardiovasculardisease,monitoringofthebloodlipidlevelsisrecommended

sincehypercholesterolemiahasbeenobservedinafewpatientstreatedwithglucosamine.

Nospecialstudieshavebeenperformedinpatientswithrenalorhepaticinsufficiency;however,thetoxicologicaland

pharmacokineticprofileoftheproductdoesnotindicatelimitationsforthesepatients.Administrationtopatientswith

severerenalorhepaticinsufficiencyshouldbeunderclosemedicalsupervision.

4.5Interactionwithothermedicinalproductsandotherformsofinteraction

Noformaldruginteractionstudieshavebeenperformed,however,thephysico-chemicalandpharmacokinetic

propertiesofglucosaminesulfatesuggestalowpotentialforinteractions.Thecompounddoesnotcompetefor

absorptionmechanismsand,afterabsorption,doesnotbindtoplasmaprotein,whileitsmetabolicfateasan

endogenoussubstanceincorporatedinproteoglycansordegradedindependentlyofthecytochromeenzymesystem,is

unlikelytogiverisetodruginteractions.

However,anincreasedeffectofwarfarinduringconcomitanttreatmentwithglucosaminehasbeenreportedinpost-

marketingexperience.Therefore,morefrequentmeasurementofthewarfarineffectmaybeconsidered.

Closemonitoringofbloodsugarlevelsisrecommendedfordiabeticsonhypoglycaemicagents.

Theoraladministrationofglucosaminesulfate,canenhancethegastrointestinalabsorptionoftetracyclines.

4.6Fertility,pregnancyandlactation

Inanimalstudies,nounfavourableeffectsonreproductivefunctionoronlactationhavebeendemonstrated.Inthe

absenceofsuchstudiesinhumans,theuseofglucosaminesulfateduringpregnancyandlactationshouldbelimitedto

caseswherethebenefitsoutweighthepotentialrisks.Administrationduringthefirst3monthsofpregnancyshouldbe

avoided.

4.7Effectsonabilitytodriveandusemachines

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4.8Undesirableeffects

Themostcommonadversereactionsassociatedwithtreatmentwithglucosaminearenausea,abdominalpain,

indigestion,constipationanddiarrhoea.Inaddition,headache,tiredness,rash,itching,andflushinghavebeen

reported.Thereportedadversereactionsareusuallymildandtransitory.

Sporadic,spontaneouscasesofhypercholesterolaemiahavebeenreported,butcausalityhasnotbeenestablished.

Patientswithdiabetesmellitus

Bloodglucosecontrolworsenedinpatientswithdiabetesmellitus.Frequencynotknown.

4.9Overdose

Nocasesofaccidentalordeliberateoverdoseareknown.Theanimalacuteandchronictoxicologicalstudiesindicate

SystemOrgan

Class Common(

1/100to<1/10) Uncommon(

1/1,000to

<1/100) Rare(

1/10,000to

<1/1000) Notknown

(cannotbe

estimatedfromthe

availabledata)

Immunesystem

disorders Allergicreaction

Eyedisorders Visualdisturbance

Nervoussystem

disorders Headache

Somnolence Dizziness

Gastrointestinal

disorders Nausea

Abdominal

pain

Dyspepsia

Diarrhoea

Constipation

Vomiting

Skinand

subcutaneous

tissuedisorders Erythema

Pruritus

Rash Angiodema

Urticaria

Hairloss

General

disordersand

administration

siteconditions Oedema/peripheral

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5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

Arthrimeltabletsareindicatedforthetreatmentofosteoarthritis.

Pharmacotherapeuticgroup:Otheranti-inflammatoryandanti-rheumaticagents,nonsteroids

ATCcode: M01AX05.

TheactiveingredientofArthrimeltablets,glucosaminesulfate,isanamino-monosaccharide.Itisanaturallyoccurring

compoundinallanimalsandhumanbeings.Glucosamineisaprecursorofthesynthesisofglucosaminoglycans

(GAGs)andhyaluronicacid,bothincludedinthecartilageaggrecan,andinothermacromoleculesincluding

gangliosides,glycolipidsandglycoproteins.

Anumberofin-vitroandanimalexperimentsillustratetheeffectsofglucosaminesulfate,butthemechanismofaction

relevanttohumanosteoarthritishasnotbeenfullyestablished.However,glucosamineisanormalconstituentofthe

polysaccharidechainsofcartilagematrixandsynovialfluidglucosaminoglycans.In-vitroandin-vivostudieshave

shownthatglucosaminesulfatestimulatesthesynthesisofphysiologicalglycosaminoglycansandproteoglycansby

chondrocytesandofhyaluronicacidbysynoviocytes.

Glucosaminesulfatehasalsobeenshowntoinhibittheactivityofcartilage-destroyingenzymessuchascollagenase

andphospholipaseA2,aswellasthegenerationofothertissue-damagingsubstancessuchassuperoxideradicals,orthe

activityoflysosomalenzymes.Theseactivitiesmaycontributetothemildanti-inflammatoryeffectsobservedin-vivo

inexperimentalmodels,includingsometypesofexperimentalarthritis.UnlikeNSAIDs,glucosaminesulfatedoesnot

inhibitthesynthesisofprostaglandins.

Noeffectsonthecardiovascularandrespiratorysystems,ontheCNS,ortheautonomicnervoussystem,havebeen

showninsafetypharmacologystudies.

Efficacyofglucosaminehasbeendemonstratedinkneeosteoarthritis,andhasbeenpartlyreplicatedinosteoarthritisof

thespineandofotherjoints,includingthehip.Theefficacyofglucosaminesulfatehasnotbeenestablishedfor

osteoarthritisofthehand.

Evidenceofefficacyandsafetyhasbeenobtainedafterlong-term(threeyears)treatmentinkneeosteoarthritispatients.

AnalgesicsandNSAIDsmaybeusedconcomitantlywithglucosaminesulfate,eitherforrescueanalgesiaduring

possibleflaresofthedisease,orintheinitialperiodoftreatment,whenthesymptomaticeffectsofglucosaminesulfate

maybedelayedfor1-2weeks.Physicaltherapyprogramscanbeusedconcomitantlywithglucosaminesulfateinthe

overallmanagementofosteoarthritis.

5.2Pharmacokineticproperties

Thepharmacokineticpropertiesofglucosaminesulfatehavebeenstudiedintheratanddogusinguniformly 14

labelledglucosamine.

Followingintravenousadministration,radiolabelledglucosaminedisappearsrapidlyfrombloodandisincorporated

intovarioustissues,inparticulartheliver,kidneyandarticularcartilage.Inthelatter,theradioactivityfromlabelled

glucosamineremainsforaprolongedperiodoftime,withabiologicalhalflifeofabout70hours.About50%ofthe

administeredradioactivityisexhaledasCO

duringthe6daysfollowingtheadministration,30–40%isfoundinthe

urine,whereastheexcretionviathefaecesisonlyabout2%.

Afteroraladministration,radiolabelledglucosamineisrapidlyandalmostcompletelyabsorbed.Thesubsequent

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Apharmacokineticstudyinmanwithsingledosesofradiolabelledglucosaminebyi.v.,i.m.ororalrouteconfirmedthe

analogyofthepharmacokineticpatternofglucosaminewiththatfoundinanimals.

Theabsolutebioavailabilityinmanafterasingleoraldoseofradiolabelledglucosaminewas25%,duetothefirst-pass

effectintheliverinwhichmorethan70%ofglucosamineismetabolised.Thegastrointestinalabsorptioniscloseto

90%,sinceonly11%oftheadministeredradioactivityisexcretedinfaeces.

Studiesinmanwerealsoperformedafteri.v.ororaladministrationofunlabelledglucosamineandglucosaminewas

assayedbyionexchangechromatographyinbloodandurine.Thisassaymethodhasaquantitationlimitsufficientfor

soundpharmacokineticstudies.Nevertheless,theresultswereconsistentwiththoseobtainedwithradiolabelled

glucosamine.

5.3Preclinicalsafetydata

Thetoxicologicalstudiesperformedwithglucosaminesulfateindicatethelargesafetymarginofthedrug.

Thefollowingpreclinicalstudieswerecarriedout.Themaximumtesteddosesreportedherearethoseshowingnoor

minimaleffects,thesewerereversibleandtherewasnodetectabletargetorgantoxicity.

acutetoxicitystudiesinmiceandratsbyi.v.,i.m.andoralroute,withupto5000mg/kggivenbytheoralroute;

subchronictoxicitystudiesof4weeksintherabbitbythei.v.routeupto80mg/kg,intheratbytheoralrouteof

240mg/kg,andinthedogbythei.v.routefor13weeksupto300mg/kg;

chronictoxicitystudiesof52weeksintheratwithoraldosesupto2700mg/kg,andof26weeksinthedogwith

oraldosesofupto2149mg/kg;

embryotoxicitystudiesintheratandrabbitbytheoralrouteupto2500mg/kg,andfertilitystudiesintheratby

theoralrouteupto2149mg/kg;

mutagenicpotentialstudiesinvitrouptoconcentrationof5000µg/mlandinvivouptothedoseof1592mg/kg

intheratand7160mg/kginthemouse.

Thedosesusedrepresentaverylargemultipleofthedailydosecurrentlyusedinhumantherapy,whichisaround20-

25mg/kg.

6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

Microcrystallinecellulose

Lactosemonohydrate

Pregelatinisedmaizestarch

Crospovidone

Stearicacid

Polyvinyl-alcoholparthydrolyzed

Titaniumdioxide(E171)

TalcE553b

LecithinsoyaE322

Macrogol3350

6.2Incompatibilities

Notapplicable.

6.3Shelflife

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6.4Specialprecautionsforstorage

Storeintheoriginalpackageinordertoprotectfrommoisture.

6.5Natureandcontentsofcontainer

CartonscontainingPVdCcoatedPVC/Alblisterstrips,orHDPEcontainersfittedwithatamper-evidentHDPEscrew

cap.

PackSize:8,10,12,14,20,28,30,56,60,112,120,168,180,336,360film-coatedtablets.

Notallpacksizesmaybemarketed.

6.6Specialprecautionsfordisposalofausedmedicinalproductorwastematerialsderivedfrom

suchmedicinalproductandotherhandlingoftheproduct

Nospecialrequirements.

7MARKETINGAUTHORISATIONHOLDER

ClonmelHealthcareLimited

WaterfordRoad

Clonmel

Co.Tipperary

Ireland

8MARKETINGAUTHORISATIONNUMBER

PA126/149/2

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

Dateoffirstauthorisation:15 th

July2011

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