DONA

Main information

  • Trade name:
  • DONA Capsules Hard 500 Milligram
  • Dosage:
  • 500 Milligram
  • Pharmaceutical form:
  • Capsules Hard
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug

Documents

Localization

  • Available in:
  • DONA Capsules Hard 500 Milligram
    Ireland
  • Language:
  • English

Status

  • Source:
  • HPRA - Health Products Regulatory Authority - Ireland
  • Authorization number:
  • PA0868/001/002
  • Authorization date:
  • 14-07-2006
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

Dona500mgCapsules

2QUALITATIVEANDQUANTITATIVECOMPOSITION

Eachcapsulecontains:

Crystallineglucosaminesulfate 628mg

Equivalentto glucosaminesulfate 500mg

Sodiumchloride 128mg

Thecontentofsodiumineachcapsuleis2.2mmol.

Forafulllistofexcipients,seesection6.1.

3PHARMACEUTICALFORM

Capsule,hard(Capsule)

Hardgelatine,snap-fit,red-redcapsule(size0),reportingthelogoROTTAprintedinblackinkonthebodyandthe

head.

4CLINICALPARTICULARS

4.1TherapeuticIndications

Treatmentofthesymptomsofosteoarthritis,i.e.painandfunctionlimitation.

4.2Posologyandmethodofadministration

AdultsandtheElderly

Onecapsuleshouldbetakenthreetimesdaily,preferablyatmeals.

Pivotalproofofefficacyhasbeendemonstratedforperiodsofuptothreemonths,witharesidualeffect

evidentfortwomonthsafterdrugwithdrawal.Thesafetyandtheefficacyoftheproductwerealsoconfirmed

inpivotalclinicaltrialsfortreatmentuptothreeyears.Continuoustreatmentbeyond3yearscannotbe

recommendedasthesafetyhasnotbeenestablishedbeyondthisperiod.

Childrenandadolescents:

Glucosamineshouldnotbeusedinchildrenandadolescentsbelowtheageof18years(see4.4).

4.3Contraindications

Hypersensitivitytoglucosamine.

4.4Specialwarningsandprecautionsforuse

Sinceglucosamineisobtainedfromshellfish,patientswhoareallergictoshellfishshouldexercisecautionin

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Thismedicinalproductcontains50mgsodiumperdose.Thedailysodiumintakeis150mg(equivalentto6.6

mmol).Tobetakenintoconsiderationbypatientsonacontrolledsodiumdiet.

Cautionisadvisedintreatmentofpatientswithimpairedglucosetolerance.Closermonitoringofbloodsugarlevels

maybenecessaryindiabeticsatthebeginningoftreatment.

Nospecialstudieswereperformedinpatientswithrenalorhepaticinsufficiency.Thetoxicologicaland

pharmacokineticprofileoftheproductdoesnotindicatelimitationsforthesepatients.However,

administrationtopatientswithseverehepaticorrenalinsufficiencyshouldbeundermedicalsupervision.

Glucosamineshouldnotbeusedinchildrenandadolescentsundertheageof18yearssincesafetyand

efficacyhavenotbeenestablished.

4.5Interactionwithothermedicinalproductsandotherformsofinteraction

Noformaldruginteractionstudieshavebeenperformed,however,thephysico-chemicalandpharmacokinetic

propertiesofglucosaminesulfatesuggestalowpotentialforinteractions.Thecompounddoesnotcompetefor

absorptionmechanismsand,afterabsorption,doesnotbindtoplasmaprotein,whileitsmetabolicfateasan

endogenoussubstanceincorporatedinproteoglycansordegradedindependentlyofthecytochromeenzyme

system,isunlikelytogiverisetodruginteractions.

However,anincreasedeffectofwarfarinduringconcomitanttreatmentwithglucosaminehasbeenreportedinpost-

marketingexperience.Therefore,morefrequentmeasurementofthewarfarineffectmaybeconsidered.

Theoraladministrationofglucosaminesulphatecanenhancethegastrointestinalabsorptionoftetracyclines.

4.6Fertility,pregnancyandlactation

Inanimalstudies,nounfavourableeffectsonreproductivefunctionoronlactationweredemonstrated.Inthe

absenceofsuchstudiesinhumans,theuseofglucosaminesulfateduringpregnancyandlactationshouldbe

limitedtocaseswherethebenefitsoutweighthepotentialrisks.Administrationduringthefirstthreemonthsof

pregnancymustbeavoided.

4.7Effectsonabilitytodriveandusemachines

NoimportanteffectsontheCNSormotorsystemareknownthatmightimpairtheabilitytodriveoruse

machines.However,cautionisrecommendedifheadache,somnolenceorvisualdisturbancesareexperienced.

4.8Undesirableeffects

Themorecommonlyobservedundesirableeffectsafteroraladministrationarestomachpain,flatulence,constipation

anddiarrhoea.

Inthefollowingtable,adversereactionshavebeengroupedonthebasisof“InternationallyagreedOrderof

Importance”SystemOrganClass(SOC)MedDRAClassification.IneachSOC,undesirableeffectswereclassified

accordingtotheiroccurrencefrequency.Ineachfrequencyclasstheundesirableeffectsarereportedaccordingtoan

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*whichfrequencycannotbeestimatedbytheavailabledata

4.9Overdose

Nocasesofaccidentalorintentionaloverdoseareknown.Theanimalacuteandchronictoxicologicalstudies

indicatethattoxiceffectsandsymptomsareunlikelytooccuratdosesupto200timesthetherapeuticdose.

5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

Productforthetreatmentofosteoarthritis.

(Productforthemusculoskeletalsystem-ATCcode:M01AX05).

Glucosaminesulfate,theactiveingredientofDONA,isachemicallywelldefinedandpurecompoundandisthesaltof

thenaturalamino-monosaccharideglucosaminewhichisphysiologicallypresentinthehumanbody.

Themechanismofactionofglucosaminesulfateinosteoarthritisisunknown.However,glucosamineisanormal

constituentofthepolysaccharidechainsofcartilagematrixandsynovialfluidglucosaminoglycans.

Invitroandinvivostudieshaveshownthatglucosaminesulfatestimulatesthesynthesisofphysiological

glycosaminoglycansandproteoglycansbychondrocytesandofhyaluronicacidbysynoviocytes.

Glucosaminesulfatehasalsobeenshowntoinhibittheactivityofcartilage-destroyingenzymessuchascollagenase

andphospholipaseA2,aswellasthegenerationofothertissue-damagingsubstancessuchassuperoxideradicals,orthe

activityoflysosomalenzymes.Theseactivitiesmaycontributetothemildanti-inflammatoryeffectsobservedinvivo

inexperimentalmodels,includingsometypesofexperimentalarthritis.UnlikeNSAIDs,glucosaminesulfatedoesnot

inhibitthesynthesisofprostaglandins.

Noeffectsonthecardiovascularandrespiratorysystems,ontheCNS,ortheautonomicnervoussystem,havebeen

showninsafetypharmacologystudies.

Pivotalproofofefficacyhasbeendemonstratedinkneeosteoarthritis,andhasbeenpartlyreplicatedinosteoarthritisof

thespineandofotherjoints,includingthehip.Theefficacyofglucosaminesulfatehasnotbeenestablished

forosteoarthritisofthehand.

SystemOrgan

Class Very

common

1/10 Common

from 1/100

1/10 Uncommonfrom

1/1,000

1/100 Rarefrom

1/10,000

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

subcutaneoustissue

disorders Erythema

Pruritus

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AnalgesicsandNSAIDsmaybeusedconcomitantlywithglucosaminesulfate,eitherforrescueanalgesiaduring

possibleflaresofthedisease,orintheinitialperiodoftreatment,whenthesymptomaticeffectsofglucosaminesulfate

maybedelayedfor1-2weeks.Physicaltherapyprogramscanbeusedconcomitantlywithglucosaminesulfateinthe

overallmanagementofosteoarthritis.

5.2Pharmacokineticproperties

Thepharmacokineticpropertiesofglucosaminesulfatehavebeenstudiedintheratanddogusinguniformly

C-labelledglucosamine.

Followingintravenousadministration,radiolabelledglucosaminedisappearsrapidlyfrombloodandis

incorporatedintovarioustissues,inparticulartheliver,kidneyandthearticularcartilage.Inthelatter,the

radioactivityfromlabelledglucosamineremainsforaprolongedperiodoftime,withabiologicalhalflifeof

about70hours.About50%oftheadministeredradioactivityisexhaledasCO

duringthe6daysfollowing

theadministration,30-40%isfoundintheurine,whereastheexcretionviathefaecesisonlyabout2%.

Afteroraladministration,radiolabelledglucosamineisrapidlyandalmostcompletelyabsorbed.The

subsequentpharmacokineticandmetabolicpatternsareconsistentwiththoseafterintravenousadministration.

Apharmacokineticstudyinmanwithsingledosesofradiolabelledglucosaminebyi.v.,i.m.ororalroute

confirmedtheanalogyofthepharmacokineticpatternofglucosaminewiththatfoundinanimals.

Theabsolutebioavailabilityinmanafterasingleoraldoseofradiolabelledglucosaminewas25%,duetothe

first-passeffectintheliverinwhichmorethan70%ofglucosamineismetabolised.Thegastrointestinal

absorptioniscloseto90%,sinceonly11%oftheadministeredradioactivityisexcretedinfaeces.

Studiesinmanwerealsoperformedafteri.v.ororaladministrationofunlabelledglucosamineand

glucosaminewasassayedbyionexchangechromatographyinbloodandurine.Thisassaymethodhasa

quantitationlimitinsufficientforsoundpharmacokineticstudies.Nevertheless,theresultswereconsistentwith

thoseobtainedwithradiolabelledglucosamine.

5.3Preclinicalsafetydata

Thetoxicologicalstudiesperformedwithglucosaminesulfateindicatethelargesafetymarginofthedrug.

Thefollowingpreclinicalstudieswerecarriedout.Themaximumtesteddosesreportedherearethoseshowing

noorminimaleffects,thesewerereversibleandtherewasnodetectabletargetorgantoxicity:

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

subchronictoxicitystudiesof4weeksintherabbitbythei.v.routeupto80mg/kg,intheratbytheoral

routeto240mg/kg,andinthedogbythei.v.routefor13weeksupto300mg/kg;

chronictoxicitystudiesof52weeksintheratwithoraldosesupto2700mg/kg,andof26weeksinthe

dogwithoraldosesupto2149mg/kg;

embryotoxicitystudiesintheratandrabbitbytheoralrouteupto2500mg/kg,andfertilitystudiesin

theratbytheoralrouteupto2149mg/kg;

mutagenicpotentialstudiesinvitrouptoconcentrationof5000µg/mlandinvivouptotheoraldoseof

1592mg/kgintheratand7160

Thedosesusedrepresentaverylargemultipleofthedailydosecurrentlyusedinhumantherapy,whichisaround20-

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6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

Talc

Magnesiumstearate

Thecapsuleshellcontains:

Erythrosine(E127)

Redironoxide(E172)

Titaniumdioxide(E171)

Yellowironoxide(E172)

Gelatine

TheblackinkusedforprintingthelogoROTTAcontains:

Shellacglaze

Blackironoxide(E172)

Propyleneglycol

6.2Incompatibilities

Notapplicable.

6.3Shelflife

3years

6.4Specialprecautionsforstorage

Themedicinalproductdoesnotrequireanyspecialstorageconditions

6.5Natureandcontentsofcontainer

PEbottlewithasnap-on-neckprovidedwiththecapandaremovablesecurityclosuresystem,containing6,60or90

capsules

Thecapisprovidedwithasilicagelbaseddesiccantfittedinthetop.

Cardboardboxcontainingonebottleof6,60or90capsules

Notallpacksizesmaybemarketed

6.6Specialprecautionsfordisposalofausedmedicinalproductorwastematerialsderivedfrom

suchmedicinalproductandotherhandlingoftheproduct

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7MARKETINGAUTHORISATIONHOLDER

RottapharmLtd

DamastownIndustrialPark

Mulhuddart

Dublin15

Ireland

8MARKETINGAUTHORISATIONNUMBER

PA868/1/2

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

DateofFirstAuthorisation:14thJuly2006

DateofLastRenewal:14thJuly2011

10DATEOFREVISIONOFTHETEXT

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