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:
  • PPA0465/045/002A
  • Authorization date:
  • 01-08-2002
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

IRISHMEDICINESBOARDACT1995,asamended

MedicinalProducts(ControlofPlacingontheMarket)Regulations,2007,asamended

PPA0465/045/002A

CaseNo:2083314

TheIrishMedicinesBoardinexerciseofthepowersconferredonitbytheabovementionedRegulationsherebygrantsto

PCOManufacturingLimited

Unit10,AshbourneBusinessPark,Rath,Ashbourne,Co.Meath,Ireland

anauthorisation,subjecttotheprovisionsofthesaidRegulations,inrespectoftheproduct

DiamicronMR30mgModifiedReleaseTablets

theparticularsofwhicharesetoutintheattachedSchedule.Theauthorisationisalsosubjecttothegeneralconditionsasmaybespecifiedin

thesaidRegulationsaslistedonthereverseofthisdocument.

Thisauthorisation,unlesspreviouslyrevoked,shallcontinueinforcefrom02/07/2010.

SignedonbehalfoftheIrishMedicinesBoardthis

________________

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 02/07/2010 CRN 2083314 page number: 1

PartII

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

DiamicronMR30mgModifiedReleaseTablets

2QUALITATIVEANDQUANTITATIVECOMPOSITION

Eachtabletcontainsgliclazide30mg

Forafulllistofexcipients,seesection6.1

3PHARMACEUTICALFORM

Modifiedreleasetablet.

ProductimportedfromtheUK,GreeceandBelgium:

Whiteoblongtabletengravedonbothfaces,‘DIA30’ononefaceand ontheother.

4CLINICALPARTICULARS

4.1TherapeuticIndications

Noninsulin-dependentdiabetes(type2)inadultswhendietarymeasures,physicalexerciseandweightlossaloneare

notsufficienttocontrolbloodglucose.

4.2Posologyandmethodofadministration

Oraluse.

Foradultuseonly.

Thedailydosemayvarybetween1and4tabletsperday,i.e.from30to120mgtakenorally,oncedaily.

Itisrecommendedthatthetablet(s)betakenatbreakfasttime.

Itisrecommendedthatthetablet(s)beswallowedwhole.

Ifadoseisforgotten,theremustbenoincreaseinthedosetakenthenextday.Aswithanyhypoglycaemicagent,the

doseshouldbeadjustedaccordingtotheindividualpatient'smetabolicresponse(bloodglucose,HbAlc).

Initialdose

Therecommendedstartingdoseis30mgdaily.

Ifbloodglucoseiseffectivelycontrolled,thisdosemaybeusedformaintenancetreatment.

Ifbloodglucoseisnotadequatelycontrolled,thedosemaybeincreasedto60,90or120mgdaily,insuccessivesteps.

Theintervalbetweeneachdoseincrementshouldbeatleast1monthexceptinpatientswhosebloodglucosehasnot

reducedaftertwoweeksoftreatment.Insuchcases,thedosemaybeincreasedattheendofthesecondweekof

treatment.

Themaximumrecommendeddailydoseis120mg.

SwitchingfromDiamicron80mgtabletstoDiamicronMR30mg:

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 02/07/2010 CRN 2083314 page number: 2

performedprovidedthereiscarefulbloodmonitoring.

SwitchingfromanotheroralantidiabeticagenttoDiamicronMR30mg:

DiamicronMR30mgcanbeusedtoreplaceotheroralantidiabeticagents.

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)

DiamicronMR30mgshouldbeprescribedusingthesamedosingregimenrecommendedforpatientsunder65yearsof

age.Inpatientswithmildtomoderaterenalinsufficiencythesamedosingregimencanbeusedasinpatientswith

normalrenalfunctionwithcarefulpatientmonitoring.Thesedatahavebeenconfirmedinclinicaltrials.

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"Interactionswithothermedicinalproductsandotherformsof

interaction")

Lactation(seeSection"Pregnancyandlactation”).

4.4Specialwarningsandprecautionsforuse

HYPOGLYCAEMIA

Thistreatmentshouldbeprescribedonlyifthepatientislikelytohavearegularfoodintake(includingbreakfast).Itis

importanttohavearegularcarbohydrateintakeduetotheincreasedriskofhypoglycaemiaifamealistakenlate,ifan

inadequateamountoffoodisconsumedorifthefoodislowincarbohydrate.Hypoglycaemiaismorelikelytooccur

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 02/07/2010 CRN 2083314 page number: 3

hypoglycaemicagentsisbeingused.

Hypoglycaemiamayoccurfollowingadministrationofsulphonylureas(see4.8.Undesirableeffects).Somecasesmay

besevereandprolonged.Hospitalisationmaybenecessaryandglucoseadministrationmayneedtobecontinuedfor

severaldays.

Carefulselectionofpatients,ofthedoseused,andclearpatientdirectionsarenecessarytoreducetheriskof

hypoglycaemicepisodes.

Factorswhichincreasetheriskofhypoglycaemia:

Patientrefusesor(particularlyinelderlysubjects)isunabletocooperate

Malnutrition,irregularmealtimes,skippingmeals,periodsoffastingordietarychanges

Imbalancebetweenphysicalexerciseandcarbohydrateintake

Renalinsufficiency

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:

Bloodglucosecontrolinapatientreceivingantidiabetictreatmentmaybeaffectedbvanyofthefollowing:fever,

trauma,infectionorsurgicalintervention.Insomecases,itmaybenecessarytoadministerinsulin.

Thehypoglycaemicefficacyofanyoralantidiabeticagent,includinggliciazide,isattenuatedovertimeinmany

patients:thismaybeduetoprogressionintheseverityofthediabetes,ortoareducedresponsetotreatment.This

phenomenonisknownassecondaryfailurewhichisdistinctfromprimaryfailure,whenanactivesubstanceis

ineffectiveasfirst-linetreatment.Adequatedoseadjustmentanddietarycomplianceshouldbeconsideredbefore

classifyingthepatientassecondaryfailure.

Laboratorytests:

Measurementofglycatedhaemoglobinlevels(orfastingvenousplasmaglucose)isrecommendedinassessingblood

glucosecontrol.Bloodglucoseself-monitoringmayalsobeuseful.

TreatmentofpatientswithG6PD-deficiencywithsulfonylureacanleadtohaemolyticanaemia.Sincegliclazide

belongstotheclassofsulfonylureaagents,cautionshouldbeusedinpatientswithG6PD-deficiencyandanon-

sulfonylureaalternativeshouldbeconsidered.

4.5Interactionwithothermedicinalproductsandotherformsofinteraction

1.Thefollowingproductsarelikelytoincreasetheriskofhypoglycaemia:

Contra-indicatedcombination

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 02/07/2010 CRN 2083314 page number: 4

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,angiotensinconvertingenzyme

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

agents.

2.Thefollowingproductsmaycauseanincreaseinbloodglucoselevels:

Combinationwhichisnotrecommended

Danazol:diabetogeniceffectofdanazol.

Iftheuseofthisactivesubstancecannotbeavoided,warnthepatientandemphasisetheimportanceofurineandblood

glucosemonitoring.Itmaybenecessarytoadjustthedoseoftheantidiabeticagentduringandaftertreatmentwith

danazol.

Combinationsrequiringprecautionsduringuse

Chlorpromazine(neurolepticagent):highdoses>100mgperdayofchlorpromazine)increasebloodglucose

levels(reducedinsulinrelease).

Warnthepatientandemphasisetheimportanceofbloodglucosemonitoring.Itmaybenecessarytoadjustthedoseof

theantidiabeticactivesubstanceduringandaftertreatmentwiththeneurolepticagent.

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

increaseinbloodglucoselevelswithpossibleketosis(reducedtolerancetocarbohydratesduetoglucocorticoids).

Warnthepatientandemphasisetheimportanceofbloodglucosemonitoring,particularlyatthestartoftreatment.It

maybenecessarytoadjustthedoseoftheantidiabeticactivesubstanceduringandaftertreatmentwithglucocorticoids.

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

Increasedbloodglucoselevelsduetobeta-2agonisteffects.Emphasisetheimportanceofmonitoringbloodglucose

levels.Ifnecessary,switchtoinsulin.

3.Combinationwhichmustbetakenintoaccount

Anticoagulanttherapy(Warfarin):

Sulphonylureasmayleadtopotentiationofanticoagulationduringconcurrenttreatment.Adjustmentofthe

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 02/07/2010 CRN 2083314 page number: 5

4.6Pregnancyandlactation

Pregnancy

Thereisnoexperiencewiththeuseofgliclazideduringpregnancyinhumans,eventhoughtherearefewdatawith

othersulphonylureas.

Inanimalstudies,gliclazideisnotteratogenic.

Controlofdiabetesshouldbeobtainedbeforethetimeofconceptiontoreducetheriskofcongenitalabnormalities

linkedtouncontrolleddiabetes.

Oralhypoglycaemicagentsarenotsuitable,insulinisthedrugoffirstchoicefortreatmentofdiabetesduring

pregnancy.Itisrecommendedthatoralhypoglycaemictherapyischangedtoinsulinbeforeapregnancyisattempted,

orassoonaspregnancyisdiscovered.

Lactation

Itisnotknownwhethergliclazideoritsmetabolitesareexcretedinbreastmilk.Giventheriskofneonatal

hypoglycaemia,theproductiscontra-indicatedinbreastfeedingmothers.

4.7Effectsonabilitytodriveandusemachines

Patientsshouldbemadeawareofthesymptomsofhypoglycaemiaandshouldbecarefulifdrivingoroperating

machinery,especiallyatthebeginningoftreatment.

4.8Undesirableeffects

Basedontheexperiencewithgliclazideandwithothersulphonylureas,thefollowingundesirableeffectshavetobe

mentioned.

Hypoglycaemia

Asforothersulphonylureas,treatmentwithDiamicronMR30mgcancausehypoglycaemia,ifmealtimesareirregular

and,inparticular,ifmealsareskipped.Possiblesymptomsofhypoglycaemiaare:headache,intensehunger,nausea,

vomiting,lassitude,drowsiness,sleepdisorders,agitation,aggression,poorconcentration,reducedawarenessand

slowedreactions,depression,confusion,visualandspeechdisorders,aphasia,tremor,paresis,sensorydisorders,

dizziness,feelingofpowerlessness,lossofself-control,delirium,convulsions,shallowrespiration,bradycardia,

drowsinessandlossofconsciousness,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:iftheseshouldoccuritisrecommendedtotakethetabletsafterbreakfast.

Thefollowingundesirableeffectshavebeenmorerarelyreported:

Skinandsubcutaneoustissuedisorders:rash,pruritus,urticaria,erythema,maculopapularrashes,bullous

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 02/07/2010 CRN 2083314 page number: 6

Bloodandlymphaticsystemdisorders:Changesinhaematologyarerare.Theymayincludeanaemia,leucopenia,

thrombocytopenia,granulocytopenia.Theseareingeneralreversibleupondiscontinuationofmedication.

Rarecasesoferythrocytopenia,agranulocytosis,haemolyticanaemiaandpancytopeniahavebeendescribedforother

sulphonylureas.

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

reports).Discontinuetreatmentifcholestaticjaundiceappears.

Withothersulphonylureasrarecaseswereobservedofelevatedliverenzymelevelsandevenimpairmentofliver

function(e.g.withcholestasisandjaundice)andhepatitiswhichregressedafterwithdrawalofthesulphonylureaorled

tolife-threateningliverfailureinisolatedcases.

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.

Dialysisisofnobenefittopatientsduetothestrongbindingofgliclazidetoproteins.

5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

HYPOGLYCAEMICSULPHONYLUREA-ORALBLOODGLUCOSELOWERINGDRUG

(A10BB09:Alimentarytractandmetabolism)

Gliclazideisahypoglycaemicsulphonylureaoralantidiabeticactivesubstancedifferingfromotherrelatedcompounds

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 02/07/2010 CRN 2083314 page number: 7

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.Therelationship

betweenthedoseadministeredrangingupto120mgandtheareaundertheconcentrationtimecurveislinear.

Plasmaproteinbindingisapproximately95%.

Gliclazideismainlymetabolisedintheliverandexcretedintheurine:lessthan1%oftheunchangedformisfoundin

theurine.Noactivemetaboliteshavebeendetectedinplasma.

Theeliminationhalf-lifeofgliclazidevariesbetween12and20hours.

Thevolumeofdistributionisaround30litres.

Noclinicallysignificantchangesinpharmacokineticparametershavebeenobservedinelderlypatients.

AsingledailydoseofDiamicronMR30mgmaintainseffectivegliclazideplasmaconcentrationsover24hours.

5.3Preclinicalsafetydata

Preclinicaldatarevealnospecialhazardsforhumansbasedonconventionalstudiesofrepeateddosetoxicityand

genotoxicity.Longtermcarcinogenicitystudieshavenotbeendone.Noteratogenicchangeshavebeenshownin

animalstudies,butlowerfoetalbodyweightwasobservedinanimalsreceivingdoses25foldhigherthanthemaximum

recommendeddoseinhumans.

6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

Calciumhydrogenphosphatedihydrate

Maltodextrin

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 02/07/2010 CRN 2083314 page number: 8

Magnesiumstearate

Anhydrouscolloidalsilica.

6.2Incompatibilities

Notapplicable.

6.3ShelfLife

Theshelf-lifeexpriydateofthisproductisthedateshownonthecontainerandouterpackageoftheproductonthe

marketinthecountryoforigin.

6.4Specialprecautionsforstorage

Storeintheoriginalpackage.

6.5Natureandcontentsofcontainer

Blisterpackscontaining56tablets.

6.6Specialprecautionsfordisposalofausedmedicinalproductorwastematerialsderivedfrom

suchmedicinalproductandotherhandlingoftheproduct

Nospecialrequirements.

7PARALLELPRODUCTAUTHORISATIONHOLDER

PCOManufacturingLtd.,

Unit10,AshbourneBusinessPark

Rath

Ashbourne

Co.Meath

8PARALLELPRODUCTAUTHORISATIONNUMBER

PPA0465/045/002

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

Dateoffirstauthorisation:01August2002

Dateoflastrenewal: 01August2007

10DATEOFREVISIONOFTHETEXT

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 02/07/2010 CRN 2083314 page number: 9