DONA 1500MG POWDER FOR ORAL SOLUTION

Main information

  • Trade name:
  • DONA 1500MG POWDER FOR ORAL SOLUTION
  • Dosage:
  • 1500 Milligram
  • Pharmaceutical form:
  • Powder for Oral Solution
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug

Documents

Localization

  • Available in:
  • DONA 1500MG POWDER FOR ORAL SOLUTION
    Ireland
  • Language:
  • English

Status

  • Source:
  • HPRA - Health Products Regulatory Authority - Ireland
  • Authorization number:
  • PA0868/001/001
  • Authorization date:
  • 03-04-1998
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

Dona1500mgPowderForOralSolution.

2QUALITATIVEANDQUANTITATIVECOMPOSITION

Eachsachetcontains:

Crystallineglucosaminesulfate 1884mg

equivalentto:glucosaminesulfate 1500mg

sodiumchloride 384mg

Excipients:Contains2.5mgAspartameand2028.5mgSorbitol.

Forafulllistofexcipients,seesection6.1

3PHARMACEUTICALFORM

Powderfororalsolution.

Awhite,crystalline,odourlesspowder.

4CLINICALPARTICULARS

4.1TherapeuticIndications

Treatmentofthesymptomsofosteoarthritis,i.e.painandfunctionlimitation.

4.2Posologyandmethodofadministration

Thecontentsofonesachet(dissolvedinaglassofwater)shouldbetakenoncedaily,preferablyatmeals.

Pivotalproofofefficacyhasbeendemonstratedforperiodsofuptothreemonths,witharesidualeffectevidentfortwo

monthsafterdrugwithdrawal.Thesafetyandefficacyoftheproductwerealsoconfirmedinpivotalclinicaltrialsfor

treatmentuptothreeyears.Continuoustreatmentbeyond3yearscannotberecommendedasthesafetyhasnotbeen

establishedbeyondthisperiod.

Glucosamineisnotindicatedforthetreatmentofacutepainfulsymptoms.Reliefofsymptoms(especiallypainrelief)

maynotbeexperienceduntilaftersomeweeksoftreatmentandinsomecasesevenlonger.Ifnoreliefofsymptomsis

experiencedafter2-3months,continuedtreatmentwithglucosamineshouldbere-evaluated.

Elderly:

Nospecificstudieshavebeenperformedinelderly,butaccordingtoclinicalexperiencedosageadjustmentisnot

requiredwhentreatingotherwisehealthy,elderlypatients.

Patientwithimpairedrenaland/orliverfunction:

Inpatientswithimpairedrenaland/orliverfunctionnodoserecommendationscanbegiven,sincenostudieshavebeen

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Childrenandadolescents:

Glucosamineshouldnotbeusedinchildrenandadolescentsbelowtheageof18years(see4.4).

4.3Contraindications

Hypersensitivitytoglucosamineortoanyoftheexcipients.Thepowderfororalsolutioncontainsaspartameandis

thereforecontraindicatedinpatientswithphenylketonuria.

Theproductshouldnotbegiventopatientswhoareallergictoshellfishastheactiveingredientisobtainedfrom

shellfish.

4.4Specialwarningsandprecautionsforuse

Exacerbationofasthmasymptomsafterinitiationofglucosaminehavebeendescribed.Therefore,asthmaticpatients

startingonglucosamineshouldbeawareofpotentialworseningofsymptoms.

Thismedicinalproductcontains151mgsodiumperdose.Tobetakenintoconsiderationbypatientsonacontrolled

sodiumdiet.

Cautionisadvisedintreatmentofpatientswithimpairedglucosetolerance.Closermonitoringofbloodsugarlevels

maybenecessaryindiabeticsatthebeginningoftreatment.

Nospecialstudieswereperformedinpatientswithrenalorhepaticinsufficiency.Thetoxicologicaland

pharmacokineticprofileoftheproductdoesnotindicatelimitationsforthesepatients.However,administrationto

patientswithseverehepaticorrenalinsufficiencyshouldbeundermedicalsupervision.

Thepowderfororalsolutioncontainssorbitol.Patientswithrarehereditaryproblemsoffructoseintoleranceshouldnot

takethispharmaceuticalform.

Glucosamineshouldnotbeusedinchildrenandadolescentsundertheageof18yearssincesafetyandefficacyhave

notbeenestablished.

4.5Interactionwithothermedicinalproductsandotherformsofinteraction

Nospecificdruginteractionstudieshavebeenperformed,however,thephysico-chemicalandpharmacokinetic

propertiesofglucosaminesulfatesuggestalowpotentialforinteractions.InonestudyGlucosaminewasfoundnotto

beaninhibitoroftheactivitiesofthefollowinghumancytochromeP450enzymes:CYP1A2,CYP2E1,CYP2C19,

CYP2C9,CYP2D6,CYP3A4,astestedbymetaboliteformationfromselectedsubstratesforeachoftheCYPenzymes

tested.

Thecompounddoesnotcompeteforabsorptionmechanismsand,afterabsorption,doesnotbindtoplasmaprotein,

whileitsmetabolicfateasanendogenoussubstanceincorporatedinproteoglycansordegradedindependentlyofthe

cytochromeenzymesystem,isunlikelytogiverisetodruginteractions.

However,anincreasedeffectofcoumarinicanticoagulantsduringconcomitanttreatmentwithglucosaminesulfatehas

beenreported.Therefore,aclosermonitoringofthecoagulationparametersmaybeconsideredinthesepatientswhen

initiatingorendingglucosaminetherapy.

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4.6Fertility,pregnancyandlactation

Pregnancy

Thereisnoadequatedatafromtheuseofglucosamineinpregnantwomen.Fromanimalstudiesonlyinsufficientdata

areavailable.Glucosamineshouldnotbeusedduringpregnancy.

BreastFeeding

Thereisnodataavailableontheexcretionofglucosamineinhumanmilk.Theuseofglucosamineduringbreastfeeding

isthereforenotrecommendedasthereisnodataonthesafetyofthenewborn.

4.7Effectsonabilitytodriveandusemachines

Nostudiesoftheeffectsontheabilitytodriveandusemachineshavebeenperformed.Ifheadache,somnolence,

tiredness,dizzinessorvisualdisturbancesareexperienced,drivingacaroroperatingmachineryisnotrecommended

(seesection4.8).

4.8Undesirableeffects

Themostcommonadversereactionsassociatedwithoraladministrationarenauseaabdominalpain,dyspepsia,

flatulence,constipationanddiarrhoea.Thereportedadversereactionsareusuallymildandtransitory.

Inthefollowingtable,adversereactionshavebeengroupedonthebasisof“InternationallyagreedOrderof

Importance”SystemOrganClass(SOC)MedDRAClassification.IneachSOC,undesirableeffectswereclassified

accordingtotheiroccurrencefrequency.Ineachfrequencyclasstheundesirableeffectsarereportedaccordingtoan

decreasingorderofseverity.

System

Organ

Class Very

common

≥1/10 Common

from ≥1/100

≤1/10 Uncommon

from ≥

1/1,000to ≤

1/100 Rare

from ≥

1/10,000

1/1,000 Veryrare

1/10,000 Unknown*

Immune

system

disorders Allergic

reaction

Nervous

system

disorders Headache

Somnolence

Tiredness Dizziness

disorders Visual

disturbances

Gastrointestinal

disorders Diarrhoea

Constipation

Nausea

Flatulence

Abdominal

pain

Dyspepsia

Skinand

subcutaneous

tissue

disorders Erythema

Pruritus

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4.9Overdose

Nocasesofaccidentalorintentionaloverdoseareknown.Theanimalacuteandchronictoxicologicalstudiesindicate

thattoxiceffectsandsymptomsareunlikelytooccuratdosesupto200timesthetherapeuticdose.However,if

overdoseoccurstreatmentshouldbesymptomaticandstandardsupportivemeasuresshouldbeadoptedasrequired.

5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

Productforthetreatmentofosteoarthritis.

(Productforthemusculoskeletalsystem-ATCcode:M01AX05).

Glucosaminesulfate,theactiveingredientofDONA,isachemicallywelldefinedandpurecompoundandisthesaltof

thenaturalamino-monosaccharideglucosaminewhichisphysiologicallypresentinthehumanbody.

Themechanismofactionofglucosaminesulfateinosteoarthritisisunknown.However,glucosamineisanormal

constituentofthepolysaccharidechainsofcartilagematrixandsynovialfluidglucosaminoglycans.Invitroandinvivo

studieshaveshownthatglucosaminesulfatestimulatesthesynthesisofphysiologicalglycosaminoglycansand

proteoglycansbychondrocytesandofhyaluronicacidbysynoviocytes.

Glucosaminesulfatehasalsobeenshowntoinhibittheactivityofcartilage-destroyingenzymessuchascollagenaseand

phospholipaseA2,aswellasthegenerationofothertissue-damagingsubstancessuchassuperoxideradicals,orthe

activityoflysosomalenzymes.Theseactivitiesmaycontributetothemildanti-inflammatoryeffectsobservedinvivoin

experimentalmodels,includingsometypesofexperimentalarthritis.UnlikeNSAIDs,glucosaminesulfatedoesnot

inhibitthesynthesisofprostaglandins.

Noeffectsonthecardiovascularandrespiratorysystems,ontheCNS,ortheautonomicnervoussystem,havebeen

showninsafetypharmacologystudiesPivotalproofofefficacyhasbeendemonstratedinkneeosteoarthritis,andhas

beenpartlyreplicatedinosteoarthritisofthespineandofotherjoints,includingthehip.Theefficacyofglucosamine

sulfatehasnotbeenestablishedforosteoarthritisofthehand.

Evidenceofefficacyandsafetyhasbeenobtainedafterlong-term(threeyears)treatmentinkneeosteoarthritispatients.

AnalgesicsandNSAIDsmaybeusedconcomitantlywithglucosaminesulfate,eitherforrescueanalgesiaduring

possibleflaresofthedisease,orintheinitialperiodoftreatment,whenthesymptomaticeffectsofglucosaminesulfate

maybedelayedfor1-2weeks.Physicaltherapyprogramscanbeusedconcomitantlywithglucosaminesulfateinthe

overallmanagementofosteoarthritis.

5.2Pharmacokineticproperties

Thepharmacokineticpropertiesofglucosaminesulfatehavebeenstudiedintheratanddogusinguniformly 14

labelledglucosamine.

Followingintravenousadministration,radiolabelledglucosaminedisappearsrapidlyfrombloodandisincorporatedinto

varioustissues,inparticulartheliver,kidneyandthearticularcartilage.Inthelatter,theradioactivityfromlabelled

glucosamineremainsforaprolongedperiodoftime,withabiologicalhalflifeofabout70hours.About50%ofthe

administeredradioactivityisexhaledasCO

duringthe6daysfollowingtheadministration,30-40%isfoundinthe

urine,whereastheexcretionviathefaecesisonlyabout2%.

Afteroraladministration,radiolabelledglucosamineisrapidlyandalmostcompletelyabsorbed.Thesubsequent

pharmacokineticandmetabolicpatternsareconsistentwiththoseafterintravenousadministration.

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analogyofthepharmacokineticpatternofglucosaminewiththatfoundinanimals.

Theabsolutebioavailabilityinmanafterasingleoraldoseofradiolabelledglucosaminewas25%,duetothefirst-pass

effectintheliverinwhichmorethan70%ofglucosamineismetabolised.Thegastrointestinalabsorptioniscloseto

90%,sinceonly11%oftheadministeredradioactivityisexcretedinfaeces.

Studiesinmanwerealsoperformedafteri.v.ororaladministrationofunlabelledglucosamineandglucosaminewas

assayedbyionexchangechromatographyinbloodandurine.Thisassaymethodhasaquantitationlimitinsufficientfor

soundpharmacokineticstudies.Nevertheless,theresultswereconsistentwiththoseobtainedwithradiolabelled

glucosamine.

5.3Preclinicalsafetydata

Thetoxicologicalstudiesperformedwithglucosaminesulfateindicatethelargesafetymarginofthedrug.

Thefollowingpreclinicalstudieswerecarriedout.Themaximumtesteddosesreportedherearethoseshowingnoor

minimaleffects,thesewerereversibleandtherewasnodetectabletargetorgantoxicity:

acutetoxicitystudiesinmiceandratsbyi.v.,i.m.andoralroute,withupto5000mg/kggivenbythe

oralroute;

subchronictoxicitystudiesof4weeksintherabbitbythei.v.routeupto80mg/kg,intheratbythe

oralrouteto240mg/kg,andinthedogbythei.v.routefor13weeksupto300mg/kg;

chronictoxicitystudiesof52weeksintheratwithoraldosesupto2700mg/kg,andof26weeksin

thedogwithoraldosesupto2149mg/kg;

embryotoxicitystudiesintheratandrabbitbytheoralrouteupto2500mg/kg,andfertilitystudiesin

theratbytheoralrouteupto2149mg/kg;

mutagenicpotentialstudiesinvitrouptoconcentrationof5000µg/mlandinvivouptotheoraldose

of1592mg/kgintheratand7160mg/kginthemouse.

Thedosesusedrepresentaverylargemultipleofthedailydosecurrentlyusedinhumantherapy,whichisaround20-

25mg/kg.

6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

Aspartame(E951)

Macrogol4000

CitricAcid,Anhydrous(E330)

Sorbitol(E420)

6.2Incompatibilities

Notapplicable.

6.3Shelflife

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6.4Specialprecautionsforstorage

Donotstoreabove25°C.

6.5Natureandcontentsofcontainer

Thesingle-dosesachetconsistsofthreelayeredmaterialmadeofpaper,aluminiumandpolyethylene.

Cardboardboxcontaining4,20or30sachets.

Notallpacksizesmaybemarketed.

6.6Specialprecautionsfordisposalofausedmedicinalproductorwastematerialsderivedfrom

suchmedicinalproductandotherhandlingoftheproduct

Nospecialrequirements

7MARKETINGAUTHORISATIONHOLDER

RottapharmLimited

DamastownIndustrialPark,

Mulhuddart,

Dublin15

Ireland

8MARKETINGAUTHORISATIONNUMBER

PA868/1/1

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

Dateoffirstauthorisation:3 rd

April1998

Dateoflastrenewal: 3 rd

April2008

10DATEOFREVISIONOFTHETEXT

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