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:
  • PPA1473/031/001
  • Authorization date:
  • 09-10-2009
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

IRISHMEDICINESBOARDACTS1995AND2006

MEDICINALPRODUCTS(CONTROLOFPLACINGONTHEMARKET)REGULATIONS,2007

(S.I.No.540of2007)

PPA1473/031/001

CaseNo:2061420

TheIrishMedicinesBoardinexerciseofthepowersconferredonitbytheabovementionedRegulationsherebygrantsto

McDowellPharmaceuticals

4AltonaRoad,Lisburn,N.Ireland,BT275QB

anauthorisation,subjecttotheprovisionsofthesaidRegulations,inrespectoftheproduct

DiamicronMR30mgModifiedReleaseTablets

TheparticularsofwhicharesetoutinPartIandPartIIoftheattachedSchedule.Theauthorisationisalsosubjecttothegeneralconditionsas

maybespecifiedinthesaidRegulationsaslistedonthereverseofthisdocument.

Thisauthorisation,unlesspreviouslyrevoked,shallcontinueinforcefrom09/10/2009.

SignedonbehalfoftheIrishMedicinesBoardthis

________________

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PartII

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

DiamicronMR30mgModifiedReleaseTablets

2QUALITATIVEANDQUANTITATIVECOMPOSITION

Onetabletcontainsgliclazide30mg

Forafulllistofexcipients,seesection6.1.

3PHARMACEUTICALFORM

ModifiedReleaseTablet

ProductimportedfromtheUK:

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,insuccessive

steps.Theintervalbetweeneachdoseincrementshouldbeatleast1monthexceptinpatientswhoseblood

glucosehasnotreducedaftertwoweeksoftreatment.Insuchcases,thedosemaybeincreasedattheendofthe

secondweekoftreatment.

Themaximumrecommendeddailydoseis120mg.

SwitchingfromDiamicron80mgtabletstoDiamicron30mgmodifiedreleasetablets

1tabletofDiamicron80mgiscomparableto1tabletofDiamicron30mg.Consequentlytheswitchcanbe

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SwitchingfromanotheroralantidiabeticagenttoDiamicron30mg:

Diamicron30mgcanbeusedtoreplaceotheroralantidiabeticagents.

Thedosageandthehalf-lifeofthepreviousantidiabeticagentshouldbetakenintoaccountwhenswitchingto

Diamicron30mg.

Atransitionalperiodisnotgenerallynecessary.Astartingdoseof30mgshouldbeusedandthisshouldbe

adjustedtosuitthepatient’sbloodglucoseresponse,asdescribedabove.

Whenswitchingfromahypoglycaemicsulphonylureawithaprolongedhalf-life,atreatmentfreeperiodofafew

daysmaybenecessarytoavoidanadditiveeffectofthetwoproducts,whichmightcausehypoglycaemia.The

proceduredescribedforinitiatingtreatmentshouldalsobeusedwhenswitchingtotreatmentwithDiamicron30

mg,i.e.astartingdoseof30mg/day,followedbyastepwiseincreaseindose,dependingonthemetabolic

response.

Combinationtreatmentwithotherantidiabeticagents:

Diamicron30mgcanbegivenincombinationwithbiguanides,alphaglucosidaseinhibitorsorinsulin.

InpatientsnotadequatelycontrolledwithDiamicron30mg,concomitantinsulintherapycanbeinitiatedunder

closemedicalsupervision.

Intheelderly(over65),Diamicron30mgshouldbeprescribedusingthesamedosingregimenrecommendedfor

patientsunder65yearsofage.Inpatientswithmildtomoderaterenalinsufficiencythesamedosingregimencan

beusedasinpatientswithnormalrenalfunctionwithcarefulpatientmonitoring.Thesedatahavebeenconfirmed

inclinicaltrials.

Inpatientsatriskofhypoglycaemia:

undernourishedormalnourished,

severeorpoorlycompensatedendocrinedisorders(hypopituitarism,hypothyroidism,

adrenocorticotrophicinsufficiency),

withdrawalofprolongedand/orhighdosecorticosteroidtherapy,

severevasculardisease(severecoronaryheartdisease,severecarotidimpairment,diffusevascular

disease).

Itisrecommendedthattheminimumdailystartingdoseof30mgisused.

Therearenodataandclinicalstudiesavailableinchildren.

4.3Contraindications

knownhypersensitivitytogliclazideortoanyoftheexcipients,othersulphonylureas,sulphonamides,

type1diabetes,

diabeticpre-comaandcoma,diabeticketo-acidosis,

severerenalorhepaticinsufficiency:inthesecasestheuseofinsulinisrecommended,

treatmentwithmiconazole(seeSection4.5,Interactionswithothermedicinalproductsandotherformsof

interaction),

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4.4Specialwarningsandprecautionsforuse

HYPOGLYCAEMIA:

Thistreatmentshouldbeprescribedonlyifthepatientislikelytohavearegularfoodintake(includingbreakfast).Itis

importanttohavearegularcarbohydrateintakeduetotheincreasedriskofhypoglycaemiaifamealistakenlate,ifan

inadequateamountoffoodisconsumedorifthefoodislowincarbohydrate.Hypoglycaemiaismorelikelytooccur

duringlow-caloriediets,followingprolongedorstrenuousexercise,alcoholintakeorifacombinationof

hypoglycaemicagentsisbeingused.

Hypoglycaemiamayoccurfollowingadministrationofsulphonylureas(seesection4.8,Undesirableeffects).Some

casesmaybesevereandprolonged.Hospitalisationmaybenecessaryandglucoseadministrationmayneedtobe

continuedforseveraldays.

Carefulselectionofpatients,ofthedoseused,andclearpatientdirectionsarenecessarytoreducetheriskof

hypoglycaemicepisodes.

Factorswhichincreasetheriskofhypoglycaemia:

patientrefusesor(particularlyinelderlysubjects)isunabletoco-operate,

malnutrition,irregularmealtimes,skippingmeals,periodsoffastingordietarychanges,

imbalancebetweenphysicalexerciseandcarbohydrateintake,

renalinsufficiency,

severehepaticinsufficiency,

overdoseofDiamicron30mg,

certainendocrinedisorders:thyroiddisorders,hypopituitarismandadrenalinsufficiency,

concomitantadministrationofcertainothermedicines(seesection4.5,Interactionwithothermedicinalproducts

andotherformsofinteraction).

Renalandhepaticinsufficiency:Thepharmacokineticsand/orpharmacodynamicsofgliclazidemaybealteredin

patientswithhepaticinsufficiencyorsevererenalfailure.Ahypoglycaemicepisodeoccurringinthesepatientsmaybe

prolonged,soappropriatemanagementshouldbeinitiated.

Patientinformation:Therisksofhypoglycaemia,togetherwithitssymptoms,treatment,andconditionsthatpredispose

toitsdevelopment,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

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4.5Interactionwithothermedicinalproductsandotherformsofinteraction

1)Thefollowingproductsarelikelytoincreasetheriskofhypoglycaemia

Contra-indicatedcombination

Miconazole(systemicroute,oromucosalgel):increasesthehypoglycaemiceffectwithpossibleonsetof

hypoglycaemicsymptoms,orevencoma.

Combinationswhicharenotrecommended

Phenylbutazone(systemicroute):increasesthehypoglycaemiceffectofsulphonylureas(displacestheirbinding

toplasmaproteinsand/orreducestheirelimination).

Itispreferabletouseadifferentanti-inflammatoryagent,orelsetowarnthepatientandemphasisethe

importanceofself-monitoring.Wherenecessary,adjustthedoseduringandaftertreatmentwiththeanti-

inflammatoryagent.

Alcohol:increasesthehypoglycaemicreaction(byinhibitingcompensatoryreactions)thatcanleadtotheonset

ofhypoglycaemiccoma.

Avoidalcoholormedicinescontainingalcohol.

Combinationsrequiringprecautionsforuse

Potentiationofthebloodglucoseloweringeffectandthus,insomeinstances,hypoglycaemiamayoccurwhenoneof

thefollowingdrugsistaken,forexample:

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

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

agents.

2)Thefollowingproductsmaycauseanincreaseinbloodglucoselevels

Combinationwhichisnotrecommended

Danazol:diabetogeniceffectofdanazol.

Iftheuseofthisactivesubstancecannotbeavoided,warnthepatientandemphasisetheimportanceofurineand

bloodglucosemonitoring.Itmaybenecessarytoadjustthedoseoftheantidiabeticagentduringandafter

treatmentwithdanazol.

Combinationsrequiringprecautionsduringuse

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

levels(reducedinsulinrelease).

Warnthepatientandemphasisetheimportanceofbloodglucosemonitoring.Itmaybenecessarytoadjustthe

doseoftheantidiabeticactivesubstanceduringandaftertreatmentwiththeneurolepticagent.

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

increaseinbloodglucoselevelswithpossibleketosis(reducedtolerancetocarbohydratesduetoglucocorticoids).

Warnthepatientandemphasisetheimportanceofbloodglucosemonitoring,particularlyatthestartof

treatment.Itmaybenecessarytoadjustthedoseoftheantidiabeticactivesubstanceduringandaftertreatment

withglucocorticoids.

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

Increasedbloodglucoselevelsduetobeta-2agonisteffects.

Emphasisetheimportanceofmonitoringbloodglucoselevels.Ifnecessary,switchtoinsulin.

3)Combinationwhichmustbetakenintoaccount

Anticoagulanttherapy(Warfarin.):

Sulfonylureasmayleadtopotentiationofanticoagulationduringconcurrenttreatment.

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4.6Pregnancyandlactation

Pregnancy

Thereisnoexperiencewiththeuseofgliclazideduringpregnancyinhumans,eventhoughtherearefewdatawith

othersulfonylurea.

Inanimalstudies,gliclazideisnotteratogenic.

Controlofdiabetesshouldbeobtainedbeforethetimeofconceptiontoreducetheriskofcongenitalabnormalities

linkedtouncontrolleddiabetes.

Oralhypoglycaemicagentsarenotsuitable,insulinisthedrugoffirstchoicefortreatmentofdiabetesduring

pregnancy.Itisrecommendedthatoralhypoglycaemictherapyischangedtoinsulinbeforeapregnancyisattempted,

orassoonaspregnancyisdiscovered.

Lactation

Itisnotknownwhethergliclazideoritsmetabolitesareexcretedinbreastmilk.Giventheriskofneonatal

hypoglycaemia,theproductiscontra-indicatedinbreast-feedingmother.

4.7Effectsonabilitytodriveandusemachines

Patientsshouldbemadeawareofthesymptomsofhypoglycaemiaandshouldbecarefulifdrivingoroperating

machinery,especiallyatthebeginningoftreatment.

4.8Undesirableeffects

Basedontheexperiencewithgliclazideandwithothersulphonylureas,thefollowingundesirableeffectshavetobe

mentioned.

Hypoglycaemia

Asforothersulfonylureas,treatmentwithDiamicron30mgcancausehypoglycaemia,ifmealtimesareirregularand,

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,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(isolatedreports).

Discontinuetreatmentifcholestaticjaundiceappears.

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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

SULFONAMIDES,UREADERIVATIVES

ATCcode:A10BB09

Gliclazideisahypoglycaemicsulphonylureaoralantidiabeticactivesubstancedifferingfromotherrelatedcompounds

byanN-containingheterocyclicringwithanendocyclicbond.

Gliclazidereducesbloodglucoselevelsbystimulatinginsulinsecretionfromthe -cellsoftheisletsofLangerhans.

IncreaseinpostprandialinsulinandC-peptidesecretionpersistsaftertwoyearsoftreatment.

Inadditiontothesemetabolicproperties,gliclazidehashaemovascularproperties.

Effectsoninsulinrelease

Intype2diabetics,gliclaziderestoresthefirstpeakofinsulinsecretioninresponsetoglucoseandincreasesthesecond

phaseofinsulinsecretion.Asignificantincreaseininsulinresponseisseeninresponsetostimulationinducedbya

mealorglucose.

Haemovascularproperties:

Gliclazidedecreasesmicrothrombosisbytwomechanismswhichmaybeinvolvedincomplicationsofdiabetes:

Apartialinhibitionofplateletaggregationandadhesion,withadecreaseinthemarkersofplateletactivation

(betathromboglobulin,thromboxaneB

AnactiononthevascularendotheliumfibrinolyticactivitywithanincreaseintPAactivity.

5.2Pharmacokineticproperties

Plasmalevelsincreaseprogressivelyduringthefirst6hours,reachingaplateauwhichismaintainedfromthesixthto

thetwelfthhourafteradministration.

Intra-individualvariabilityislow.

Gliclazideiscompletelyabsorbed.Foodintakedoesnotaffecttherateordegreeofabsorption.

Therelationshipbetweenthedoseadministeredrangingupto120mgandtheareaundertheconcentrationtimecurve

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Plasmaproteinbindingisapproximately95%.

Gliclazideismainlymetabolisedintheliverandexcretedintheurine:lessthan1%oftheunchangedformisfoundin

theurine.Noactivemetaboliteshavebeendetectedinplasma.

Theeliminationhalf-lifeofgliclazidevariesbetween12and20hours.

Thevolumeofdistributionisaround30litres.

Noclinicallysignificantchangesinpharmacokineticparametershavebeenobservedinelderlypatients.

AsingledailydoseofDiamicron30mgmaintainseffectivegliclazideplasmaconcentrationsover24hours.

5.3Preclinicalsafetydata

Preclinicaldatarevealnospecialhazardsforhumansbasedonconventionalstudiesofrepeateddosetoxicityand

genotoxicity.Longtermcarcinogenicitystudieshavenotbeendone.Noteratogenicchangeshavebeenshownin

animalstudies,butlowerfœtalbodyweightwasobservedinanimalsreceivingdoses25foldhigherthanthemaximum

recommendeddoseinhumans.

6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

Calciumhydrogenphosphatedihydrate,

Maltodextrin,

Hypromellose,

Magnesiumstearate,

Silica,colloidalanhydrous

6.2Incompatibilities

Notapplicable.

6.3ShelfLife

Theshelf-lifeexpirydateofthisproductshallbethedateshownontheoverlabelledblisterandouterpackageofthe

productonthemarketinthecountryoforigin.

6.4Specialprecautionsforstorage

Storeintheoriginalpackage.

6.5Natureandcontentsofcontainer

Aluminium/Poly(vinylchloride)blister,packedincardboardboxes.

Packsize:28and56tablets

6.6Specialprecautionsfordisposalofausedmedicinalproductorwastematerialsderivedfrom

suchmedicinalproductandotherhandlingoftheproduct

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7ParallelProductAuthorisationHolder

McDowellPharmaceuticals

4AltonaRoad

Lisburn

BT275QB

NorthernIreland

8ParallelProductAuthorisationNumber

PPA1473/31/1

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

Dateoffirstauthorisation:9thOctober2009

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