DIADEON MR 60 MG MODIFIED RELEASE TABLETS

Main information

  • Trade name:
  • DIADEON MR 60 MG MODIFIED RELEASE TABLETS
  • Dosage:
  • 60 Milligram
  • Pharmaceutical form:
  • Modified-release Tablets
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug

Documents

Localization

  • Available in:
  • DIADEON MR 60 MG MODIFIED RELEASE TABLETS
    Ireland
  • Language:
  • English

Status

  • Source:
  • HPRA - Health Products Regulatory Authority - Ireland
  • Authorization number:
  • PA0568/007/003
  • Authorization date:
  • 18-12-2009
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

DiadeonMR60mgmodifiedreleasetablets.

2QUALITATIVEANDQUANTITATIVECOMPOSITION

Onemodifiedreleasetabletcontainsgliclazide60mg

Excipients:lactose

Forafulllistofexcipients,seesection6.1.

3PHARMACEUTICALFORM

Modifiedreleasetablet.

White,oblong,tablet,scoredandengraved,with‘DIA60’onbothfaces

Thetabletcanbedividedintoequalhalves.

4CLINICALPARTICULARS

4.1TherapeuticIndications

Noninsulin-dependentdiabetes(type2)inadultswhendietarymeasures,physicalexerciseandweightlossaloneare

notsufficienttocontrolbloodglucose.

4.2Posologyandmethodofadministration

Oraluse.

Foradultuseonly.

ThedailydoseofDiadeonMR60mgmayvaryfromonehalfto2tabletsperday,i.e.from30to120mgtakenorallyin

asingleintakeatbreakfasttime.

Itisrecommendedtoswallowthedosewithoutcrushingorchewing.

Ifadoseisforgotten,theremustbenoincreaseinthedosetakenthenextday.

Aswithanyhypoglycaemicagent,thedoseshouldbeadjustedaccordingtotheindividualpatient'smetabolicresponse

(bloodglucose,HbAlc).

Initialdose

Therecommendedstartingdoseis30mgdaily(halfatabletofDiadeonMR60mg).Ifbloodglucoseiseffectively

controlled,thisdosemaybeusedformaintenancetreatment.

Ifbloodglucoseisnotadequatelycontrolled,thedosemaybeincreasedto60,90or120mgdaily,insuccessivesteps.

Theintervalbetweeneachdoseincrementshouldbeatleast1monthexceptinpatientswhosebloodglucosehasnot

reducedaftertwoweeksoftreatment.Insuchcases,thedosemaybeincreasedattheendofthesecondweekof

treatment.

Themaximumrecommendeddailydoseis120mg.

OneDiadeonMR60mgmodifiedreleasetabletisequivalenttotwoDiadeonMR30mgmodifiedreleasetablets.The

breakabilityoftheDiadeonMR60mgmodifiedreleasetabletenablesflexibilityofdosingtobeachieved.

SwitchingfromDIAMICRON80mgtabletstoDiadeonMR60mgmodifiedreleasetablets:

OnetabletofDIAMICRON80mgiscomparableto30mgofthemodifiedreleaseformulation(i.e.halfatabletof

DiadeonMR60mg).Consequentlytheswitchcanbeperformedwithcarefulbloodmonitoring.

SwitchingfromanotheroralantidiabeticagenttoDiadeonMR60mg:

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Thedosageandthehalf-lifeofthepreviousantidiabeticagentshouldbetakenintoaccountwhenswitchingtoDiadeon

MR60mg.

Atransitionalperiodisnotgenerallynecessary.Astartingdoseof30mgshouldbeusedandthisshouldbeadjustedto

suitthepatient’sbloodglucoseresponse,asdescribedabove.

Whenswitchingfromahypoglycaemicsulphonylureawithaprolongedhalf-life,atreatmentfreeperiodofafewdays

maybenecessarytoavoidanadditiveeffectofthetwoproducts,whichmightcausehypoglycaemia.Theprocedure

describedforinitiatingtreatmentshouldalsobeusedwhenswitchingtotreatmentwithDiadeonMR60mg,i.e.a

startingdoseof30mg/day,followedbyastepwiseincreaseindose,dependingonthemetabolicresponse.

Combinationtreatmentwithotherantidiabeticagents:

DiadeonMR60mgcanbegivenincombinationwithbiguanides,alphaglucosidaseinhibitorsorinsulin.

InpatientsnotadequatelycontrolledwithDiadeonMR60mg,concomitantinsulintherapycanbeinitiatedunderclose

medicalsupervision.

Intheelderly(over65),DiadeonMR60mgshouldbeprescribedusingthesamedosingregimenrecommendedfor

patientsunder65yearsofage.

Inpatientswithmildtomoderaterenalinsufficiencythesamedosingregimencanbeusedasinpatientswithnormal

renalfunctionwithcarefulpatientmonitoring.Thesedatahavebeenconfirmedinclinicaltrials.

Inpatientsatriskofhypoglycaemia:

undernourishedormalnourished,

severeorpoorlycompensatedendocrinedisorders(hypopituitarism,hypothyroidism,adrenocorticotrophic

insufficiency),

withdrawalofprolongedand/orhighdosecorticosteroidtherapy,

severevasculardisease(severecoronaryheartdisease,severecarotidimpairment,diffusevasculardisease);

Itisrecommendedthattheminimumdailystartingdoseof30mgisused.

Therearenodataandclinicalstudiesavailableinchildren.

4.3Contraindications

-knownhypersensitivitytogliclazideortoanyoftheexcipients,othersulfonylurea,sulphonamides

-type1diabetes

-diabeticpre-comaandcoma,diabeticketo-acidosis

-severerenalorhepaticinsufficiency:inthesecasestheuseofinsulinisrecommended

-treatmentwithmiconazole(seesection4.5)

-lactation(seesection4.6)

4.4Specialwarningsandprecautionsforuse

HYPOGLYCAEMIA:

Thistreatmentshouldbeprescribedonlyifthepatientislikelytohavearegularfoodintake(includingbreakfast).Itis

importanttohavearegularcarbohydrateintakeduetotheincreasedriskofhypoglycaemiaifamealistakenlate,ifan

inadequateamountoffoodisconsumedorifthefoodislowincarbohydrate.Hypoglycaemiaismorelikelytooccur

duringlow-caloriediets,followingprolongedorstrenuousexercise,alcoholintakeorifacombinationof

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Hypoglycaemiamayoccurfollowingadministrationofsulfonylurea(seesection4.8.).Somecasesmaybesevereand

prolonged.Hospitalisationmaybenecessaryandglucoseadministrationmayneedtobecontinuedforseveraldays.

Carefulselectionofpatients,ofthedoseused,andclearpatientdirectionsarenecessarytoreducetheriskof

hypoglycaemicepisodes.

Factorswhichincreasetheriskofhypoglycaemia:

-patientrefusesor(particularlyinelderlysubjects)isunabletoco-operate

-malnutrition,irregularmealtimes,skippingmeals,periodsoffastingordietarychanges

-imbalancebetweenphysicalexerciseandcarbohydrateintake

-renalinsufficiency

-severehepaticinsufficiency

-overdoseofDiadeonMR60mg

-certainendocrinedisorders:thyroiddisorders,hypopituitarismandadrenalinsufficiency

-concomitantadministrationofcertainothermedicinalproducts(seesection4.5)

Renalandhepaticinsufficiency:thepharmacokineticsand/orpharmacodynamicsofgliclazidemaybealteredin

patientswithhepaticinsufficiencyorsevererenalfailure.Ahypoglycaemicepisodeoccurringinthesepatientsmaybe

prolonged,soappropriatemanagementshouldbeinitiated.

Patientinformation:

Therisksofhypoglycaemia,togetherwithitssymptoms,treatment,andconditionsthatpredisposetoitsdevelopment,

shouldbeexplainedtothepatientandtofamilymembers.

Thepatientshouldbeinformedoftheimportanceoffollowingdietaryadvice,oftakingregularexercise,andofregular

monitoringofbloodglucoselevels.

Poorbloodglucosecontrol:bloodglucosecontrolinapatientreceivingantidiabetictreatmentmaybeaffectedbyany

ofthefollowing:fever,trauma,infectionorsurgicalintervention.Insomecases,itmaybenecessarytoadminister

insulin.

Thehypoglycaemicefficacyofanyoralantidiabeticagent,includinggliclazide,isattenuatedovertimeinmany

patients:thismaybeduetoprogressionintheseverityofthediabetes,ortoareducedresponsetotreatment.This

phenomenonisknownassecondaryfailurewhichisdistinctfromprimaryfailure,whenanactivesubstanceis

ineffectiveasfirst-linetreatment.Adequatedoseadjustmentanddietarycomplianceshouldbeconsideredbefore

classifyingthepatientassecondaryfailure.

Laboratorytests:Measurementofglycatedhaemoglobinlevels(orfastingvenousplasmaglucose)isrecommendedin

assessingbloodglucosecontrol.Bloodglucoseself-monitoringmayalsobeuseful.

TreatmentofpatientswithG6PD-deficiencywithsulfonylureaagentscanleadtohaemolyticanaemia.Sincegliclazide

belongstothechemicalclassofsulfonylureadrugs,cautionshouldbeusedinpatientswithG6PD-deficiencyanda

non-sulfonylureaalternativeshouldbeconsidered.

Excipients:

DiadeonMR60mgshouldnotbeadministeredtopatientswithrarehereditaryproblemsofgalactoseintolerance,the

Lapplactasedeficiencyorglucose-galactosemalabsorption.

4.5Interactionwithothermedicinalproductsandotherformsofinteraction

Thefollowingproductsarelikelytoincreasetheriskofhypoglycaemia

Contra-indicatedcombination

Miconazole(systemicroute,oromucosalgel):increasesthehypoglycaemiceffectwithpossibleonsetof

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Combinationswhicharenotrecommended

Phenylbutazone(systemicroute):increasesthehypoglycaemiceffectofsulfonylurea(displacestheirbindingto

plasmaproteinsand/orreducestheirelimination).

Itispreferabletouseadifferentanti-inflammatoryagent,orelsetowarnthepatientandemphasisetheimportanceof

self-monitoring.Wherenecessary,adjustthedoseduringandaftertreatmentwiththeanti-inflammatoryagent.

Alcohol:increasesthehypoglycaemicreaction(byinhibitingcompensatoryreactions)thatcanleadtotheonsetof

hypoglycaemiccoma.

Alcoholormedicinalproductscontainingalcoholshouldbeavoided.

Combinationsrequiringprecautionsforuse

Potentiationofthebloodglucoseloweringeffectandthus,insomeinstances,hypoglycaemiamayoccurwhenoneof

thefollowingdrugsistaken,forexample:

otherantidiabeticagents(insulins,acarbose,biguanides),beta-blockers,fluconazole,angiotensinconvertingenzyme

inhibitors(captopril,enalapril),H2-receptorantagonists,MAOIs,sulfonamides,andnonsteroidalanti-inflammatory

agents.

Thefollowingproductsmaycauseanincreaseinbloodglucoselevels

Combinationwhichisnotrecommended

Danazol:diabetogeniceffectofdanazol.

Iftheuseofthisactivesubstancecannotbeavoided,warnthepatientandemphasisetheimportanceofurineandblood

glucosemonitoring.Itmaybenecessarytoadjustthedoseoftheantidiabeticagentduringandaftertreatmentwith

danazol.

Combinationsrequiringprecautionsduringuse

Chlorpromazine(neurolepticagent):highdoses(>100mgperdayofchlorpromazine)increasebloodglucoselevels

(reducedinsulinrelease).

Warnthepatientandemphasisetheimportanceofbloodglucosemonitoring.Itmaybenecessarytoadjustthedoseof

theantidiabeticactivesubstanceduringandaftertreatmentwiththeneurolepticagent.

Glucocorticoids(systemicandlocalroute:intra-articular,cutaneousandrectalpreparations)andtetracosactrin:

increaseinbloodglucoselevelswithpossibleketosis(reducedtolerancetocarbohydratesduetoglucocorticoids).

Warnthepatientandemphasisetheimportanceofbloodglucosemonitoring,particularlyatthestartoftreatment.It

maybenecessarytoadjustthedoseoftheantidiabeticactivesubstanceduringandaftertreatmentwithglucocorticoids.

Ritodrine,salbutamol,terbutaline:(I.V.)

Increasedbloodglucoselevelsduetobeta-2agonisteffects.

Emphasisetheimportanceofmonitoringbloodglucoselevels.Ifnecessary,switchtoinsulin.

Combinationwhichmustbetakenintoaccount

Anticoagulanttherapy(e.g.Warfarin...):

Sulfonylureasmayleadtopotentiationofanticoagulationduringconcurrenttreatment.

Adjustmentoftheanticoagulantmaybenecessary.

4.6Fertility,pregnancyandlactation

Pregnancy

Thereisnoexperiencewiththeuseofgliclazideduringpregnancyinhumans,eventhoughtherearefewdatawith

othersulfonylurea.

Inanimalstudies,gliclazideisnotteratogenic.

Controlofdiabetesshouldbeobtainedbeforethetimeofconceptiontoreducetheriskofcongenitalabnormalities

linkedtouncontrolleddiabetes.

Oralhypoglycaemicagentsarenotsuitable,insulinisthedrugoffirstchoicefortreatmentofdiabetesduring

pregnancy.Itisrecommendedthatoralhypoglycaemictherapyischangedtoinsulinbeforeapregnancyisattempted,

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Lactation

Itisnotknownwhethergliclazideoritsmetabolitesareexcretedinbreastmilk.Giventheriskofneonatal

hypoglycaemia,theproductiscontra-indicatedinbreast-feedingmother.

4.7Effectsonabilitytodriveandusemachines

Patientsshouldbemadeawareofthesymptomsofhypoglycaemiaandshouldbecarefulifdrivingoroperating

machinery,especiallyatthebeginningoftreatment.

4.8Undesirableeffects

Basedontheexperiencewithgliclazideandwithothersulfonylurea,thefollowingundesirableeffectshavetobe

mentioned.

Hypoglycaemia

Asforothersulfonylureas,treatmentwithDIADEONMRcancausehypoglycaemia,ifmealtimesareirregularand,in

particular,ifmealsareskipped.Possiblesymptomsofhypoglycaemiaare:headache,intensehunger,nausea,vomiting,

lassitude,sleepdisorders,agitation,aggression,poorconcentration,reducedawarenessandslowedreactions,

depression,confusion,visualandspeechdisorders,aphasia,tremor,paresis,sensorydisorders,dizziness,feelingof

powerlessness,lossofself-control,delirium,convulsions,shallowrespiration,bradycardia,drowsinessandlossof

consciousness,possiblyresultingincomaandlethaloutcome.

Inaddition,signsofadrenergiccounter-regulationmaybeobserved:sweating,clammyskin,anxiety,tachycardia,

hypertension,palpitations,anginapectorisandcardiacarrhythmia.

Usually,symptomsdisappearafterintakeofcarbohydrates(sugar).However,artificialsweetenershavenoeffect.

Experiencewithothersulfonylureashowsthathypoglycaemiacanrecurevenwhenmeasuresproveeffectiveinitially.

Ifahypoglycaemicepisodeissevereorprolonged,andevenifitistemporarilycontrolledbyintakeofsugar,

immediatemedicaltreatmentorevenhospitalisationisrequired.

Otherundesirableeffects:

Gastrointestinaldisturbances,includingabdominalpain,nausea,vomitingdyspepsia,diarrhoea,andconstipationhave

beenreported:iftheseshouldoccurtheycanbeavoidedorminimisedifgliclazideistakenwithbreakfast.

Thefollowingundesirableeffectshavebeenmorerarelyreported:

Skinandsubcutaneoustissuedisorders:rash,pruritus,urticaria,erythema,maculopapularrashes,bullousreactions.

Bloodandlymphaticsystemdisorders:Changesinhaematologyarerare.Theymayincludeanaemia,leucopenia,

thrombocytopenia,granulocytopenia.Theseareingeneralreversibleupondiscontinuationofmedication.

Hepato-biliarydisorders:raisedhepaticenzymelevels(AST,ALT,alkalinephosphatase),hepatitis(isolated

reports).Discontinuetreatmentifcholestaticjaundiceappears.

Thesesymptomsusuallydisappearafterdiscontinuationoftreatment.

Eyedisorders

Transientvisualdisturbancesmayoccurespeciallyoninitiationoftreatment,duetochangesinbloodglucoselevels.

Classattributioneffects:

Asforothersulphonylureas,thefollowingadverseeventshavebeenobserved:casesoferythrocytopenia,

agranulocytosis,haemolyticanaemia,pancytopenia,allergicvasculitis,hyponatraemia,elevatedliverenzymelevels

andevenimpairmentofliverfunction(e.g.withcholestasisandjaundice)andhepatitiswhichregressedafter

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4.9Overdose

Anoverdoseofsulfonylureamaycausehypoglycaemia.

Moderatesymptomsofhypoglycaemia,withoutanylossofconsciousnessorneurologicalsigns,mustbecorrectedby

carbohydrateintake,doseadjustmentand/orchangeofdiet.Strictmonitoringshouldbecontinueduntilthedoctoris

surethatthepatientisoutofdanger.

Severehypoglycaemicreactions,withcoma,convulsionsorotherneurologicaldisordersarepossibleandmustbe

treatedasamedicalemergency,requiringimmediatehospitalisation.

Ifhypoglycaemiccomaisdiagnosedorsuspected,thepatientshouldbegivenarapidI.V.injectionof50mLof

concentratedglucosesolution(20to30%).Thisshouldbefollowedbycontinuousinfusionofamorediluteglucose

solution(10%)ataratethatwillmaintainbloodglucoselevelsabove1g/L.Patientsshouldbemonitoredcloselyand,

dependingonthepatient'sconditionafterthistime,thedoctorwilldecideiffurthermonitoringisnecessary.

Dialysisisofnobenefittopatientsduetothestrongbindingofgliclazidetoproteins.

5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

SULFONAMIDES,UREADERIVATIVES

ATCcode:A10BB09

Gliclazideisahypoglycaemicsulphonylureaoralantidiabeticactivesubstancedifferingfromotherrelatedcompounds

byanN-containingheterocyclicringwithanendocyclicbond.

Gliclazidereducesbloodglucoselevelsbystimulatinginsulinsecretionfromthe-cellsoftheisletsofLangerhans.

IncreaseinpostprandialinsulinandC-peptidesecretionpersistsaftertwoyearsoftreatment.

Inadditiontothesemetabolicproperties,gliclazidehashaemovascularproperties.

Effectsoninsulinrelease

Intype2diabetics,gliclaziderestoresthefirstpeakofinsulinsecretioninresponsetoglucoseandincreasesthesecond

phaseofinsulinsecretion.Asignificantincreaseininsulinresponseisseeninresponsetostimulationinducedbya

mealorglucose.

Haemovascularproperties:

Gliclazidedecreasesmicrothrombosisbytwomechanismswhichmaybeinvolvedincomplicationsofdiabetes:

-apartialinhibitionofplateletaggregationandadhesion,withadecreaseinthemarkersofplateletactivation(beta

thromboglobulin,thromboxaneB

-anactiononthevascularendotheliumfibrinolyticactivitywithanincreaseintPAactivity.

5.2Pharmacokineticproperties

Plasmalevelsincreaseprogressivelyduringthefirst6hours,reachingaplateauwhichismaintainedfromthesixthto

thetwelfthhourafteradministration.

Intra-individualvariabilityislow.

Gliclazideiscompletelyabsorbed.Foodintakedoesnotaffecttherateordegreeofabsorption.

Therelationshipbetweenthedoseadministeredrangingupto120mgandtheareaundertheconcentrationtimecurve

islinear.

Plasmaproteinbindingisapproximately95%.

Gliclazideismainlymetabolisedintheliverandexcretedintheurine:lessthan1%oftheunchangedformisfoundin

theurine.Noactivemetaboliteshavebeendetectedinplasma.

Theeliminationhalf-lifeofgliclazidevariesbetween12and20hours.

Thevolumeofdistributionisaround30litres.

Noclinicallysignificantchangesinpharmacokineticparametershavebeenobservedinelderlypatients.

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5.3Preclinicalsafetydata

Preclinicaldatarevealnospecialhazardsforhumansbasedonconventionalstudiesofrepeateddosetoxicityand

genotoxicity.Longtermcarcinogenicitystudieshavenotbeendone.Noteratogenicchangeshavebeenshownin

animalstudies,butlowerfœtalbodyweightwasobservedinanimalsreceivingdoses25foldhigherthanthemaximum

recommendeddoseinhumans.

6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

Lactosemonohydrate

Maltodextrin

Hypromellose

Magnesiumstearate

Silica,colloidalanhydrous.

6.2Incompatibilities

Notapplicable.

6.3Shelflife

3years.

6.4Specialprecautionsforstorage

Thismedicinalproductdoesnotrequireanyspecialstorageconditions.

6.5Natureandcontentsofcontainer

TransparentPVC/Alblister,packedincardboardboxes.

Packsizes

7,10,14,15,20,28,30,56,60,84,90,100,112,120,180and500tablets.

Notallpacksizesmaybemarketed.

6.6Specialprecautionsfordisposalandotherhandling

Nospecialrequirements.

Anyunusedproductorwastematerialshouldbedisposedofinaccordancewithlocalrequirements.

7MARKETINGAUTHORISATIONHOLDER

LesLaboratoiresServier

22rueGarnier

92200Neuilly-sur-Seine

France

8MARKETINGAUTHORISATIONNUMBER

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9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

Dateoffirstauthorisation:18thofDecember2009.

10DATEOFREVISIONOFTHETEXT

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