DOLFLASH

Main information

  • Trade name:
  • DOLFLASH Orodispersible Tablet 500 Milligram
  • Dosage:
  • 500 Milligram
  • Pharmaceutical form:
  • Orodispersible Tablet
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug

Documents

Localization

  • Available in:
  • DOLFLASH Orodispersible Tablet 500 Milligram
    Ireland
  • Language:
  • English

Status

  • Source:
  • HPRA - Health Products Regulatory Authority - Ireland
  • Authorization number:
  • PA0549/011/001
  • Authorization date:
  • 07-03-2003
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

Dolflash500mgorodispersibletablets.

2QUALITATIVEANDQUANTITATIVECOMPOSITION

Eachorodispersibletabletcotains500mgparacetamol(ascoatedparacetamolcystals)

Excipients:eachtabletalsoincludes40mgaspartame(E951).

Forafulllistofexcipients,seesection6.1.

3PHARMACEUTICALFORM

Orodispersibletablet.

White,round,bi-convextabletwithcentralconcavedepressionwithacharacteristicodourofblackcurrant.

4CLINICALPARTICULARS

4.1TherapeuticIndications

Symptomatictreatmentformildtomoderatepainand/orfever.

4.2Posologyandmethodofadministration

Posology

ThismedicinalproductisforADULTUSEONLY.

Themaximumrecommendedposologyis3000mgofparacetamolperday,correspondingto6tabletsdaily.Theusual

posologyis1tabletof500mg,toberepeatedifnecessaryafteraminimumof4hours.Intheeventofintensepainor

intensefever,2tabletsof500mg,toberepeatedifnecessaryafteraminimumintervalof4hours.

Donotexceed6tabletsof500mgoveraperiodof24hours.

Maximumrecommendedposology:Thetotaldoseofparacetamolshouldnotexceed3gdailyforadults(SeeSection

4.9,Overdose).

Frequencyofadministration

Inadults,administrationshouldtakeplaceatintervalsofaminimumoffourhours.

Renalinsufficiency

Inthecaseofsevererenalinsufficiencytheminimumintervalbetween2administrationsshouldbe8hours.

MethodofAdministration

Oralroute.

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4.3Contraindications

Hypersensitivitytoparacetamolortoanyoftheexcipients.

Phenylketonuria(duetothepresenceofaspartame).

Severehepatocellularinsufficiency.

4.4Specialwarningsandprecautionsforuse

Warnings

Donotexceedthestateddose.

Prolongeduseofthisproduct,exceptundermedicalsupervision,maybeharmful.

Thisproductshouldonlybeusedwhenclearlynecessary.

Doseshigherthanrecommendedentailriskforveryseriousliverdamage.Treatmentwithantidoteshouldbegivenas

soonaspossible.Seesection4.9.

Toavoidtheriskofoverdose,patientsshouldbeadvisednottotakeotherparacetamol-containingproduct

concurrently.

Thismedicinalproductcontainsaspartame,asourceofphenylalaninequivalentto0.2mgpertablet,andistherefore

contraindicatedforpeoplewithphenylketonuria(seesection4.3,Contraindications).

PrecautionsforUse

Paracetamolshouldbeusedwithcautionincasesof:

Adultsweighinglessthan50kg

Mildtomoderatehepatocellularinsufficiency(comment:acetaminopheniscontraindicatedincasesofsevere

hepatocellularinsufficiency)

Chronicalcoholism

Chronicmalnutrition(lowreservesofhepaticgluthatione)

Dehydration

Severerenalinsufficiency(creatinineclearance 10mL/min(seesection4.2,PosologyandAdministration)

Inthecaseofhighfever,orsignsofsecondaryinfectionorpersistanceofsymptomsbeyond3days,areevaluationof

treatmentshouldbemade.

Duringlong-term,highdoseofflabeltreatmentwithanalgesicdrugs,headachescanoccurwhichmustnotbetreated

withhigherdosesofthemedicinalproduct.Ingeneralthehabitualuseofanalgesics,especiallythecombinationof

differentanalgesicdrugsubstances,canleadtolastingrenallesionswiththeriskofrenalfailure(analgesic

nephropathy).Ifthissituationisexperiencedorsuspected,medicaladviceshouldbeobtainedandtreatmentshouldbe

discontinued.Thediagnosisof‘MedicationOveruseHeadacheshouldbesuspectedinpatientswhohavefrequentor

dailyheadachesdespite(orbecauseof)theregularuseofheadachemedications.

4.5Interactionwithothermedicinalproductsandotherformsofinteraction

Probenecidcausesanalmost2-foldreductioninclearanceofparacetamolbyinhibitingitsconjugationwith

glucuronidacid.Areductionoftheparacetamoldoseshouldbeconsideredforconcomitanttreatmentwith

probenecid.

Salicylamidemayprolongtheeliminationt1/2ofparacetamol.

Cautionshouldbepaidtotheconcomitantintakeofenzyme-inducingsubstances(suchascarbamazepine,

phenobarbitone,phenytoin,primidone,rifampicin,StJohn'sWort,etc.)orpotentiallyhepatotoxicsubstances(see

section4.9,Overdose).

Metoclopramideanddomperidone:accelerateabsorptionofparacetamol.

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Concomitantuseofparacetamol(4gperdayforatleast4days),withoralanticoagulantsmayleadtoslight

variationsofINRvalues.Inthiscase,increasedmonitoringofINRvaluesshouldbedoneduringthedurationof

thecombinationandafteritsdiscontinuation.

ParaclinicalTestInteraction

Theadministrationofparacetamolcanaffecttheassayofuricacidfortestscarriedoutbythephosphotungsticacid

method,andalsotheassayofglycemiacarriedoutbytheglucoseoxydase-peroxydasemethod.

4.6Fertility,pregnancyandlactation

Pregnancy

Epidemiologicaldatafromtheuseoforaltherapeuticdosesofparacetamolindicatenoundesirableeffectsonthe

pregnancyoronthehealthofthefetus/newborninfant.Prospectivedataonpregnanciesexposedtooverdosesdidnot

showanincreaseinmalformationrisk.Reproductivestudieswiththeoralroutedidnotshowanymalformationor

foetotoxiceffects.

Consequentlyundernormalconditionsofuse,paracetamolcanbeusethroughoutthedurationofpregnancy,aftera

benefit-riskassessment.

Duringpregnancy,paracetamolshouldnotbetakenforlongsperiods,athighdosesorincombinationwithother

medicinalproducts,assafetyofuseinsuchcasesisnotestablished.

Lactation

Afteroraladministration,paracetamolisexcretedintobreastmilkinsmallquantities.Noundesirableeffectsonnursing

infantshavebeenreported.Therapeuticdosesofthismedicinalproductmaybeusedduringbreast-feeding.

4.7Effectsonabilitytodriveandusemachines

Notrelevant.

4.8Undesirableeffects

4.9Overdose

Thereisariskofliverinjury(includingfulminanthepatitis,hepatiticfailure,cholestatichepatitis,cytolytichepatitis),

particularlyinelderlysubjects,inyoungchildren,inpatientswithliverdisease,incasesofchronicalcoholism,in

patientswithchronicmalnutritionandinpatientsreceivingenzymeinducers.Overdosingmaybefatalinthesecases.

Symptomsgenerallyappearwithinthefirst24hoursandcomprise:nausea,vomiting,anorexia,pallor,andabdominal

pain.

Overdose,7.5gormoreofparacetamolinasingleadministrationinadultsor140mg/kgofbodyweightinasingle

administrationinchildren,causeslivercellnecrosislikelytoinducecompleteandirreversiblenecrosis,resultingin

OrganSystem Rare(1/10,000to

<1/1,000) Veryrare(<1/10,000),not

known(cannotbeestimated

fromtheavailabledata)

Hepatobiliary

disorders -increasedlevelsofhepatic

transaminases

Immunesystem

disorders -hypersensitivityreaction(from

simpleskinrashorurticariato

anaphylacticshockrequiring

discontinuationofthetreatment)

Bloodand

lymphaticsystem

disorders -thrombopenia,leucopenia,

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Simultaneously,increasedlevelsofhepatictransaminases(AST,ALT),lactatedehydrogenaseandbilirubineare

observedtogetherwithincreasedprothrombintimethatmayappear12to48hoursafteradministration.Clinical

symptomsofliverdamageareusuallyevidentinitiallyafter2days,andreachamaximumafter4to6days.

Acuterenalfailurewithacutetubularnecrosismaydevelop,evenintheabsenceofsevereliverdamage.Othernon-

hepaticsymptomsthathavebeenreportedfollowingparacetamoloverdosageincludemyocardialabnormalitiesand

pancreatitis.

EmergencyProcedure

immediatetransfertohospital,eveniftherearenosignificantearlysymptoms

bloodsamplingtodetermineinitialparacetamolplasmaconcentration

gastriclavage

IV(ororalifpossible)administrationoftheantidoteN-acetylcysteineifpossiblebeforethe10thhourpost-

ingestion.N-acetylcysteinecan,however,givesomedegreeofprotectionevenafter10hours,andupto48hours,

butinthesecasesprolongedtreatmentisgiven.

symptomatictreatmentshouldbeimplemented.

methioninebyoralroutecouldbeusedasanalternativetoN-acetylcysteineprovidedthat,itisadministeredas

soonaspossibleafteroverdoseandinallcaseswithin10hoursoftheoverdose.

5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

Pharmacotherapeuticgroup:analgesicsandantipyretics,anilides

ATC-code:N02BE01

Theprecisemechanismoftheanalgesicandantipyreticpropertiesofparacetamolhasyettobeestablished;itmay

involvecentralandperipheralactions.

5.2Pharmacokineticproperties

Absorption

Theabsorptionofparacetamolbytheoralrouteiscompleteandrapid.Maximalplasmaconcentrationsarereached30

to60minutesafteringestion.

Distribution

Paracetamolisdistributedrapidlythroughoutalltissues.Concentrationsarecomparableintheblood,thesalivaandthe

plasma;proteinbindingislow.

Metabolism

Paracetamolismetabolizedmainlyintheliverfollowing2majorpathways:glucuronicacidandsulphuricacid

conjugates.Thislatterrouteisrapidlysaturatedatdoseshigherthanthetherapeuticdosages.Aminorroute,catalyzed

byCytochromeP450(CYP2E1),resultsintheformationofanintermediaryreagent,N-acetyl-p-benzoquinoneimine,

which,undernormalconditionsofuse,israpidlydetoxifiedbyglutathioneandeliminatedintheurineafterconjugation

withcysteineandmercapturicacid.Conversely,whenmassiveintoxicationoccurs,thequantityofthistoxicmetabolite

isincreased.

Elimination

Eliminationisessentiallythroughtheurine.90%oftheingesteddoseiseliminatedbythekidneysin24hours,

principallyasglucuronide(60to80%)andsulphateconjugates(20to30%).Lessthan5%iseliminatedinunchanged

form.

Theeliminationhalf-lifeisabout2hours.

Renalinsufficiency

Incaseofsevererenalinsufficiency(creatinineclearancelessthan10ml/min),theeliminationofparacetamolandits

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Elderlysubject:Conjugationcapacityisnotmodified.

5.3Preclinicalsafetydata

Inanimalexperimentsregardingacute,subchronicandchronictoxicityofparacetamolinratsandmice,gastro-

intestinallesions,bloodcountchanges,degenerationofliverandrenalparenchyma,evennecroseswereobserved.The

causesforthesechangesareattributedtothemechanismofactionontheonehandandontheothertothemetabolism

ofparacetamol.Themetabolitespresumedtoyieldthetoxiceffectsandthecorrespondingchangesinorganshavealso

beenfoundinhumans.Moreover,duringlongtermuse(i.e.1year)veryrarecasesofreversiblechronicaggressive

hepatitishavebeendescribedintherangeofmaximumtherapeuticdoses.Incaseofsubtoxicdoses,signsof

intoxicationcanoccuraftera3-weekintake.Therefore,paracetamolshouldnotbetakenoveralongperiodoftimeand

notathigherdoses.

Extensiveinvestigationsshowednoevidenceofarelevantgenotoxicriskofparacetamolattherapeutic,i.e.non-toxic

doses.

Long-termstudiesinratsandmiceyieldednoevidenceonrelevanttumorigeniceffectsatnon-hepatotoxicdosagesof

paracetamol.

Paracetamolpassesthroughtheplacenta.

Animalstudiesandexperienceinhumanstodateyieldnoevidenceonreproductivetoxicity.

6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

Coatedparacetamolcrystals:

Basisbutylatedmethacrylatecopolymer

Polyacrylatedispersion30percent

Hydrophobiccolloidalsilica

Tabletmatrix

Mannitol(granulatedpowder)

Crospovidone

Aspartame(E951)

Blackcurrantflavouring

Magnesiumstearate

6.2Incompatibilities

Notapplicable.

6.3Shelflife

Thermoformedblister(Polyamide/PVC/Aluminium):4years.

Thermo-setstrips(Aluminium/Polyethylene):3years.

6.4Specialprecautionsforstorage

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6.5Natureandcontentsofcontainer

Thermoformedblister(Polyamide/PVC/Aluminium):Packsizesof2,4,6,12,16or20tablets

thermo-setstrips(Aluminium/Polyethylene):Packsizesof2,4,6,12or16tablets.

Notallpacksizesmaybemarketed.

6.6Specialprecautionsfordisposalofausedmedicinalproductorwastematerialsderivedfrom

suchmedicinalproductandotherhandlingoftheproduct

Nospecialrequirements.

7MARKETINGAUTHORISATIONHOLDER

Ethypharm

194BureauxdelaColline,BâtimentD

92213Saint-Cloudcedex

France

8MARKETINGAUTHORISATIONNUMBER

PA0549/011/001

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

Dateoffirstauthorisation: 07March2003

Dateoflastrenewal: 22May2008

10DATEOFREVISIONOFTHETEXT

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