DIAMICRON MR

Main information

  • Trade name:
  • DIAMICRON MR
  • Dosage:
  • 30 Milligram
  • Pharmaceutical form:
  • Modified-release Tablets
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug

Documents

Localization

  • Available in:
  • DIAMICRON MR
    Ireland
  • Language:
  • English

Status

  • Source:
  • HPRA - Health Products Regulatory Authority - Ireland
  • Authorization number:
  • PPA1328/010/002
  • Authorization date:
  • 22-09-2006
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

IRISHMEDICINESBOARDACTS1995AND2006

MEDICINALPRODUCTS(CONTROLOFPLACINGONTHEMARKET)REGULATIONS,2007

(S.I.No.540of2007)

PPA1328/010/002

CaseNo:2052901

TheIrishMedicinesBoardinexerciseofthepowersconferredonitbytheabovementionedRegulationsherebygrantsto

B&SHealthcare

Unit4,BradfieldRoad,Ruislip,Middlesex,HA40NU,UnitedKingdom

anauthorisation,subjecttotheprovisionsofthesaidRegulations,inrespectoftheproduct

DiamicronMR30mg,Modified-releaseTablets

TheparticularsofwhicharesetoutinPartIandPartIIoftheattachedSchedule.Theauthorisationisalsosubjecttothegeneralconditionsas

maybespecifiedinthesaidRegulationsaslistedonthereverseofthisdocument.

Thisauthorisation,unlesspreviouslyrevoked,shallcontinueinforcefrom31/03/2009until21/09/2011.

SignedonbehalfoftheIrishMedicinesBoardthis

________________

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PartII

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

DiamicronMR30mg,Modified-releaseTablets.

2QUALITATIVEANDQUANTITATIVECOMPOSITION

Eachmodifiedreleasetabletcontains30mggliclazide.

Forafulllistofexcipients,seesection6.1.

3PHARMACEUTICALFORM

Modifiedreleasetablet.

ProductimportedfromtheNetherlands:

White,oblongtabletengravedonbothfaces,‘DIA30’ononefaceandtheServierlogoontheother.

4CLINICALPARTICULARS

4.1TherapeuticIndications

Noninsulin-dependentdiabetes(type2)inadultswhendietarymeasures,physicalexerciseandweightlossaloneare

notsufficienttocontrolbloodglucose.

4.2Posologyandmethodofadministration

Oraluse.

Foradultuseonly.

Thedailydosemayvaryfrom1to4tabletsperday,i.e.from30to120mgtakenorallyinasingleintakeatbreakfast

time.

Itisrecommendedthatthetablet(s)beswallowedwhole.

Ifadoseisforgotten,theremustbenoincreaseinthedosetakenthenextday.

Aswithanyhypoglycaemicagent,thedoseshouldbeadjustedaccordingtotheindividualpatient'smetabolicresponse

(bloodglucose,HbAlc).

Initialdose

Therecommendedstartingdoseis30mgdaily.

Ifbloodglucoseiseffectivelycontrolled,thisdosemaybeusedformaintenancetreatment.

Ifbloodglucoseisnotadequatelycontrolled,thedosemaybeincreasedto60,90or120mgdaily,insuccessivesteps.

Theintervalbetweeneachdoseincrementshouldbeatleast1monthexceptinpatientswhosebloodglucosehasnot

reducedaftertwoweeksoftreatment.Insuchcases,thedosemaybeincreasedattheendofthesecondweekof

treatment.

Themaximumrecommendeddailydoseis120mg.

SwitchingfromDiamicron80mgtabletstoDiamicronMR30mgmodifiedreleasetablets:

1tabletofDiamicron80mgiscomparableto1tabletofDiamicronMR30mg.Consequentlytheswitchcanbe

performedprovidedacarefulbloodmonitoring.

SwitchingfromanotheroralantidiabeticagenttoDiamicronMR30mg:

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Thedosageandthehalf-lifeofthepreviousantidiabeticagentshouldbetakenintoaccountwhenswitchingto

DiamicronMR30mg.

Atransitionalperiodisnotgenerallynecessary.Astartingdoseof30mgshouldbeusedandthisshouldbeadjustedto

suitthepatient'sbloodglucoseresponse,asdescribedabove.

Whenswitchingfromahypoglycaemicsulphonylureawithaprolongedhalf-life,atreatmentfreeperiodofafewdays

maybenecessarytoavoidanadditiveeffectofthetwoproducts,whichmightcausehypoglycaemia.Theprocedure

describedforinitiatingtreatmentshouldalsobeusedwhenswitchingtotreatmentwithDiamicronMR30mg,i.e.a

startingdoseof30mg/day,followedbyastepwiseincreaseindose,dependingonthemetabolicresponse.

Combinationtreatmentwithotherantidiabeticagents:

DiamicronMR30mgcanbegivenincombinationwithbiguanides,alphaglucosidaseinhibitorsorinsulin.

InpatientsnotadequatelycontrolledwithDiamicronMR30mg,concomitantinsulintherapycanbeinitiatedunder

closemedicalsupervision.

Intheelderly(over65),DiamicronMR30mgshouldbeprescribedusingthesamedosingregimenrecommendedfor

patientsunder65yearsofage.Inpatientswithmildtomoderaterenalinsufficiencythesamedosingregimencanbe

usedasinpatientswithnormalrenalfunctionwithcarefulpatientmonitoring.Thesedatahavebeenconfirmedin

clinicaltrials.

Inpatientsatriskofhypoglycaemia:

undernourishedormalnourished,

severeorpoorlycompensatedendocrinedisorders(hypopituitarism,hypothyroidism,adrenocorticotrophic

insufficiency),

withdrawalofprolongedand/orhighdosecorticosteroidtherapy,

severevasculardisease(severecoronaryheartdisease,severecarotidimpairment,diffusevasculardisease);

Itisrecommendedthattheminimumdailystartingdoseof30mgisused.

Therearenodataandclinicalstudiesavailableinchildren.

4.3Contraindications

knownhypersensitivitytogliclazideortoanyoftheexcipients,othersulphonylureas,sulphonamides,

type1diabetes,

diabeticpre-comaandcoma,diabeticketo-acidosis,

severerenalorhepaticinsufficiency:inthesecasestheuseofinsulinisrecommended,

treatmentwithmiconazole(seeSection"Interactionswithothermedicinalproductsandotherformsofinteraction"),

lactation(seeSection"PregnancyandLactation").

4.4Specialwarningsandprecautionsforuse

HYPOCLYCAEMIA:

Thistreatmentshouldbeprescribedonlyifthepatientislikelytohavearegularfoodintake(includingbreakfast).Itis

importanttohavearegularcarbohydrateintakeduetotheincreasedriskofhypoglycaemiaifamealistakenlate,ifan

inadequateamountoffoodisconsumedorifthefoodislowincarbohydrate.Hypoglycaemiaismorelikelytooccur

duringlow-caloriediets,followingprolongedorstrenuousexercise,alcoholintakeorifacombinationof

hypoglycaemicagentsisbeingused.

Hypoglycaemiamayoccurfollowingadministrationofsulphonylureas(see4.8.Undesirableeffects).Somecasesmay

besevereandprolonged.Hospitalisationmaybenecessaryandglucoseadministrationmayneedtobecontinuedfor

severaldays.

Carefulselectionofpatients,ofthedoseused,andclearpatientdirectionsarenecessarytoreducetheriskof

hypoglycaemicepisodes.

Factorswhichincreasetheriskofhypoglycaemia:

patientrefusesor(particularlyinelderlysubjects)isunabletoco-operate,

malnutrition,irregularmealtimes,skippingmeals,periodsoffastingordietarychanges,

imbalancebetweenphysicalexerciseandcarbohydrateintake,

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severehepaticinsufficiency,

overdoseofDiamicronMR30mg,

certainendocrinedisorders:thyroiddisorders,hypopituitarismandadrenalinsufficiency,

concomitantadministrationofcertainothermedicines(seeInteractions).

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

belongtotheclassofsulfonylureaagents,cautionshouldbeusedinpatientswithG6PD-definciencyandanon-

sulfonylureaalternativeshouldbeconsidered.

4.5Interactionwithothermedicinalproductsandotherformsofinteraction

1.Thefollowingproductsarelikelytoincreasetheriskofhypoglycaemia

Contra-indicatedcombination

Miconazole(systemicroute,oromucosalgel):increasesthehypoglycaemiceffectwithpossibleonsetof

hypoglycaemicsymptoms,orevencoma.

Combinationswhicharenotrecommended

Phenylbutazone(systemicroute):increasesthehypoglycaemiceffectofsulphonylureas(displacestheirbindingto

plasmaproteinsand/orreducestheirelimination).

Itispreferabletouseadifferentanti-inflammatoryagent,orelsetowarnthepatientandemphasisetheimportanceof

self-monitoring.Wherenecessary,adjustthedoseduringandaftertreatmentwiththeanti-inflammatoryagent.

Alcohol:increasesthehypoglycaemicreaction(byinhibitingcompensatoryreactions)thatcanleadtotheonsetof

hypoglycaemiccoma.Avoidalcoholormedicinescontainingalcohol.

Combinationsrequiringprecautionsforuse

Potentiationofthebloodglucoseloweringeffectandthus,insomeinstances,hypoglycaemiamayoccurwhenoneof

thefollowingdrugsistaken,forexample:otherantidiabeticagents(insulins,acarbose,biguanides),beta-blockers,

fluconazole,angiotensinconvertingenzymeinhibitors(captopril,enalapril),H2-receptorantagonists,MAOIs,

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2.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.

3.Combinationwhichmustbetakenintoaccount

Anticoagulanttherapy(Warfarin.):

Sulfonylureasmayleadtopotentiationofanticoagulationduringconcurrenttreatment.

Adjustmentoftheanticoagulantmaybenecessary.

4.6Pregnancyandlactation

Pregnancy

Thereisnoexperiencewiththeuseofgliclazideduringpregnancyinhumans,eventhoughtherearefewdatawith

othersulfonylureas.

Inanimalstudies,gliclazideisnotteratogenic.

Controlofdiabetesshouldbeobtainedbeforethetimeofconceptiontoreducetheriskofcongenitalabnormalities

linkedtouncontrolleddiabetes.

Oralhypoglycaemicagentsarenotsuitable,insulinisthedrugoffirstchoicefortreatmentofdiabetesduring

pregnancy.Itisrecommendedthatoralhypoglycaemictherapyischangedtoinsulinbeforeapregnancyisattempted,

orassoonaspregnancyisdiscovered.

Lactation

Itisnotknownwhethergliclazideoritsmetabolitesareexcretedinbreastmilk.Giventheriskofneonatal

hypoglycaemia,theproductiscontra-indicatedinbreast-feedingmothers.

4.7Effectsonabilitytodriveandusemachines

Patientsshouldbemadeawareofthesymptomsofhypoglycaemiaandshouldbecarefulifdrivingoroperating

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4.8Undesirableeffects

Basedontheexperiencewithgliclazideandwithothersulphonylureas,thefollowingundesirableeffectshavetobe

mentioned.

Hypoglycaemia

Asforothersulfonylureas,treatmentwithDiamicronMR30mgcancausehypoglycaemia,ifmealtimesareirregular

and,inparticular,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.

Experiencewithothersulphonylureasshowsthathypoglycaemiacanrecurevenwhenmeasuresproveeffective

initially.

Ifahypoglycaemicepisodeissevereorprolonged,andevenifitistemporarilycontrolledbyintakeofsugar,

immediatemedicaltreatmentorevenhospitalisationarerequired.

Gastrointestinaldisturbances,includingabdominalpain,nausea,vomiting,dyspepsia,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(isolatedreports).

Discontinuetreatmentifcholestaticjaundiceappears.

Thesesymptomsusuallydisappearafterdiscontinuationoftreatment.

Eyedisorders

Transientvisualdisturbancesmayoccurespeciallyoninitiationoftreatment,duetochangesinbloodglucoselevels.

Classattributioneffects:

Casesoferythrocytopenia,agranulocytosis,haemolyticanaemia,pancytopeniaandallergicvasculitis,havebeen

describedforothersulphonylureas.

Withothersulfonylureascaseswerealsoobservedofelevatedliverenzymelevelsandevenimpairmentofliver

function(e.g.withcholestasisandjaundice)andhepatitiswhichregressedafterwithdrawalofthesulfonylureaorledto

life-threateningliverfailureinisolatedcases.

4.9Overdose

Anoverdoseofsulphonylureasmaycausehypoglycaemia.

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.

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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.

AsingledailydoseofDiamicronMR30mgmaintainseffectivegliclazideplasmaconcentrationsover24hours.

5.3Preclinicalsafetydata

Preclinicaldatarevealnospecialhazardsforhumansbasedonconventionalstudiesofrepeateddosetoxicityand

genotoxicity.Longtermcarcinogenicitystudieshavenotbeendone.Noteratogenicchangeshavebeenshownin

animalstudies,butlowerfœtalbodyweightwasobservedinanimalsreceivingdoses25foldhigherthanthemaximum

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6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

Calciumhydrogenphosphatedihydrate

Maltodextrin

Hypromellose

Magnesiumstearate

Colloidalanhydroussilica.

6.2Incompatibilities

Notapplicable

6.3ShelfLife

Theshelf-lifeexpirydateofthisproductshallbethedateshownonthecontainerandouterpackageoftheproducton

themarketinthecountryoforigin.

6.4Specialprecautionsforstorage

Storeintheoriginalpackage.

6.5Natureandcontentsofcontainer

Aluminium/Poly(vinylchloride)blister,packedincardboardboxes.Eachpackcontaining60tablets.

6.6Specialprecautionsfordisposalofausedmedicinalproductorwastematerialsderivedfrom

suchmedicinalproductandotherhandlingoftheproduct

Nospecialrequirements.

7ParallelProductAuthorisationHolder

B&SHealthcare

Unit4

BradfieldRoad

Ruislip

Middlesex

HA40NU

UnitedKingdom.

8ParallelProductAuthorisationNumber

PPA1328/010/002

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

DateofFirstAuthorisation:22ndSeptember2006

10DATEOFREVISIONOFTHETEXT

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