DONA

Main information

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

Documents

Localization

  • Available in:
  • DONA Powder for Oral Solution 1500 Milligram
    Ireland
  • Language:
  • English

Status

  • Source:
  • HPRA - Health Products Regulatory Authority - Ireland
  • Authorization number:
  • PPA0465/191/001
  • Authorization date:
  • 05-01-2007
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

Dona1500mgPowderforOralSolution

2QUALITATIVEANDQUANTITATIVECOMPOSITION

Eachsachetcontains:

Excipients: Aspartame

sorbitol

Forafulllistofexcipients,seesection6.1

3PHARMACEUTICALFORM

Powderfororalsolution

ProductimportedfromGreece,ItalyandSpain.

Awhite,crystalline,odourlesspowder.

4CLINICALPARTICULARS

4.1TherapeuticIndications

Treatmentofthesymptomsofosteoarthritis,i.e.painandfunctionlimitation.

4.2Posologyandmethodofadministration

AdultsandtheElderly:

Thecontentsofonesachet(dissolvedinaglassofwater)shouldbetakenoncedaily,preferablyatmeals.

Pivotalproofofefficacyhasbeendemonstratedforperiodsofuptothreemonths,witharesidualeffectevidentfortwo

monthsafterdrugwithdrawal.Thesafetyandefficacyoftheproductwerealsoconfirmedinpivotalclinicaltrialsfor

treatmentuptothreeyears.Continuoustreatmentbeyond3yearscannotberecommendedasthesafetyhasnotbeen

establishedbeyondthisperiod.

Childrenandadolescents:

Glucosamineshouldnotbeusedinchildrenandadolescentsbelowtheageof18years(see4.4).

4.3Contraindications

Hypersensitivitytoglucosamine.Thepowderfororalsolutioncontainsaspartameandisthereforecontraindicatedin

Crystallineglucosaminesulfate 1884mg

equivalentto: glucosaminesulfate 1500mg

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4.4Specialwarningsandprecautionsforuse

Sinceglucosamineisobtainedfromshellfish,patientswhoareallergictoshellfishshouldexercisecautionintheuseof

theproduct.

Thismedicinalproductcontains151mgsodiumperdose.Tobetakenintoconsiderationbypatientsonacontrolled

sodiumdiet.

Cautionisadvisedintreatmentofpatientswithimpairedglucosetolerance.Closermonitoringofbloodsugarlevels

maybenecessaryindiabeticsatthebeginningoftreatment

Nospecialstudieswereperformedinpatientswithrenalorhepaticinsufficiency.Thetoxicologicaland

pharmacokineticprofileoftheproductdoesnotindicatelimitationsforthesepatients.However,administrationto

patientswithseverehepaticorrenalinsufficiencyshouldbeundermedicalsupervision.

Thepowderfororalsolutioncontainssorbitol.Patientswithrarehereditaryproblemsoffructoseintoleranceshouldnot

takethispharmaceuticalform.

Glucosamineshouldnotbeusedinchildrenandadolescentsundertheageof18yearssincesafetyandefficacyhave

notbeenestablished.

4.5Interactionwithothermedicinalproductsandotherformsofinteraction

Noformaldruginteractionstudieshavebeenperformed,however,thephysico-chemicalandpharmacokinetic

propertiesofglucosaminesulfatesuggestalowpotentialforinteractions.Thecompounddoesnotcompetefor

absorptionmechanismsand,afterabsorption,doesnotbindtoplasmaprotein,whileitsmetabolicfateasan

endogenoussubstanceincorporatedinproteoglycansordegradedindependentlyofthecytochromeenzymesystem,is

unlikelytogiverisetodruginteractions.However,anincreasedeffectofwarfarinduringconcomitanttreatmentwith

glucosaminehasbeenreportedinpost-marketingexperience.Therefore,morefrequentmeasurementofthewarfarin

effectmaybeconsidered.

Theoraladministrationofglucosaminesulfatecanenhancethegastrointestinalabsorptionoftetracyclines

4.6Fertility,pregnancyandlactation

Inanimalstudies,nounfavourableeffectsonreproductivefunctionoronlactationweredemonstrated.Intheabsence

ofsuchstudiesinhumans,theuseofglucosaminesulfateduringpregnancyandlactationshouldbelimitedtocases

wherethebenefitsoutweighthepotentialrisks.Administrationduringthefirstthreemonthsofpregnancymustbe

avoided.

4.7Effectsonabilitytodriveandusemachines

NoeffectsontheCNSormotorsystemareknownthatmightimpairtheabilitytodriveorusemachines.However,

cautionisrecommendedifheadache,somnolenceorvisualdisturbancesareexperienced.

4.8Undesirableeffects

Themorecommonlyobservedundesirableeffectsafteroraladministrationarestomachpain,flatulence,constipation

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Inthefollowingtable,adversereactionshavebeengroupedonthebasisof“InternationallyagreedOrderof

Importance”SystemOrganClass(SOC)MedDRAClassification.IneachSOC,undesirableeffectswereclassified

accordingtotheiroccurrencefrequency.Ineachfrequencyclasstheundesirableeffectsarereportedaccordingtoa

decreasingorderofseverity.

*Whichfrequencycannotbeestimatedbytheavailabledata

4.9Overdose

Nocasesofaccidentalorintentionaloverdoseareknown.Theanimalacuteandchronictoxicologicalstudiesindicate

thattoxiceffectsandsymptomsareunlikelytooccuratdosesupto200timesthetherapeuticdose.

5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

Productforthetreatmentofosteoarthritis.

(Productforthemusculoskeletalsystem-ATCcode:M01AX05).

Glucosaminesulfate,theactiveingredientofDONA,isachemicallywelldefinedandpurecompoundandisthesaltof

thenaturalamino-monosaccharideglucosaminewhichisphysiologicallypresentinthehumanbody.

Themechanismofactionofglucosaminesulfateinosteoarthritisisunknown.However,glucosamineisanormal

constituentofthepolysaccharidechainsofcartilagematrixandsynovialfluidglucosaminoglycans.Invitroandinvivo

studieshaveshownthatglucosaminesulfatestimulatesthesynthesisofphysiologicalglycosaminoglycansand

proteoglycansbychondrocytesandofhyaluronicacidbysynoviocytes.

Glucosaminesulfatehasalsobeenshowntoinhibittheactivityofcartilage-destroyingenzymessuchascollagenase

andphospholipaseA2,aswellasthegenerationofothertissue-damagingsubstancessuchassuperoxideradicals,orthe

activityoflysosomalenzymes.Theseactivitiesmaycontributetothemildanti-inflammatoryeffectsobservedinvivo

inexperimentalmodels,includingsometypesofexperimentalarthritis.UnlikeNSAIDs,glucosaminesulfatedoesnot

inhibitthesynthesisofprostaglandins.

Noeffectsonthecardiovascularandrespiratorysystems,ontheCNS,ortheautonomicnervoussystem,havebeen

showninsafetypharmacologystudies.

Pivotalproofofefficacyhasbeendemonstratedinkneeosteoarthritis,andhasbeenpartlyreplicatedinosteoarthritisof

SystemOrgan

Class Very

common

1/10 Common

from1/100

to1/10 Uncommon

from

1/1,000to

1/100 Rarefrom

1/10,000

to

1/1,000 Veryrare

1/10,000 Unknown*

Immunesystem

disorders Allergic

reaction

Nervoussystem

disorders Headache

Somnolence

Eyedisorders Visual

disturbance

Gastrointestinal

disorders Diarrhoea

Constipation

Nausea

Flatulence

Stomachpain

Dyspepsia

Skinand

subcutaneous

tissuedisorders Erythema

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osteoarthritisofthehand.

Evidenceofefficacyandsafetyhasbeenobtainedafterlong-term(threeyears)treatmentinkneeosteoarthritispatients.

AnalgesicsandNSAIDsmaybeusedconcomitantlywithglucosaminesulfate,eitherforrescueanalgesiaduring

possibleflaresofthedisease,orintheinitialperiodoftreatment,whenthesymptomaticeffectsofglucosaminesulfate

maybedelayedfor1-2weeks.Physicaltherapyprogramscanbeusedconcomitantlywithglucosaminesulfateinthe

overallmanagementofosteoarthritis.

5.2Pharmacokineticproperties

Thepharmacokineticpropertiesofglucosaminesulfatehavebeenstudiedintheratanddogusinguniformly 14

labelledglucosamine.

Followingintravenousadministration,radiolabelledglucosaminedisappearsrapidlyfrombloodandisincorporated

intovarioustissues,inparticulartheliver,kidneyandthearticularcartilage.Inthelatter,theradioactivityfromlabelled

glucosamineremainsforaprolongedperiodoftime,withabiologicalhalflifeofabout70hours.About50%ofthe

administeredradioactivityisexhaledasCO

duringthe6daysfollowingtheadministration,30-40%isfoundinthe

urine,whereastheexcretionviathefaecesisonlyabout2%.

Afteroraladministration,radiolabelledglucosamineisrapidlyandalmostcompletelyabsorbed.Thesubsequent

pharmacokineticandmetabolicpatternsareconsistentwiththoseafterintravenousadministration.

Apharmacokineticstudyinmanwithsingledosesofradiolabelledglucosaminebyi.v.,i.m.ororalrouteconfirmedthe

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/kggivenbytheoralroute;

subchronictoxicitystudiesof4weeksintherabbitbythei.v.routeupto80mg/kg,intheratbytheoralrouteto240

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

chronictoxicitystudiesof52weeksintheratwithoraldosesupto2700mg/kg,andof26weeksinthedogwithoral

dosesupto2149mg/kg;

embryotoxicitystudiesintheratandrabbitbytheoralrouteupto2500mg/kg,andfertilitystudiesintheratbythe

oralrouteupto2149mg/kg;

mutagenicpotentialstudiesinvitrouptoconcentrationof5000µg/mlandinvivouptotheoraldoseof1592mg/kg

intheratand7160mg/kginthemouse.

Thedosesusedrepresentaverylargemultipleofthedailydosecurrentlyusedinhumantherapy,whichisaround20-

25mg/kg.

6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

Aspartame(E951)

Macrogol4000

CitricAcid,Anhydrous(E330)

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6.2Incompatibilities

Notapplicable

6.3Shelflife

Theshelf-lifeexpirydateofthisproductisthedateshownonthecontainerandouterpackageoftheproductonthe

marketinthecountryororigin.

6.4Specialprecautionsforstorage

Donotstoreabove25°C.

6.5Natureandcontentsofcontainer

Cardboardboxcontaining30sachets.

6.6Specialprecautionsfordisposalandotherhandling

Nospecialrequirements.

7PARALLELPRODUCTAUTHORISATIONHOLDER

PCOManufacturing

Unit10,AshbourneBusinessPark

Rath

Ashbourne

Co.Meath

8PARALLELPRODUCTAUTHORISATIONNUMBER

PPA465/191/1

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

DateofFirstAuthorisation5 th

January2007

10DATEOFREVISIONOFTHETEXT

Irish Medicines Board

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