DIACARDYNE SR

Main information

  • Trade name:
  • DIACARDYNE SR
  • Dosage:
  • 300 Milligram
  • Pharmaceutical form:
  • Prolonged Release Capsules
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug

Documents

Localization

  • Available in:
  • DIACARDYNE SR
    Ireland
  • Language:
  • English

Status

  • Source:
  • HPRA - Health Products Regulatory Authority - Ireland
  • Authorization number:
  • PA0549/001/004
  • Authorization date:
  • 18-01-1991
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

IRISHMEDICINESBOARDACT1995

MEDICINALPRODUCTS(LICENSINGANDSALE)REGULATIONS,1998

(S.I.No.142of1998)

PA0549/001/004

CaseNo:2015522

TheIrishMedicinesBoardinexerciseofthepowersconferredonitbytheabovementionedRegulationsherebygrantsto

EthypharmSA

17-21rueSt.Mattieu,78550Houdan,France

anauthorisation,subjecttotheprovisionsofthesaidRegulations,inrespectoftheproduct

DiacardyneSR300mgprolonged-releasecapsules,hard

TheparticularsofwhicharesetoutinPartIandPartIIoftheattachedSchedule.Theauthorisationisalsosubjecttothegeneralconditionsas

maybespecifiedinthesaidRegulationsaslistedonthereverseofthisdocument.

Thisauthorisation,unlesspreviouslyrevoked,shallcontinueinforcefrom18/01/2006.

SignedonbehalfoftheIrishMedicinesBoardthis

________________

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PartII

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

DiacardyneSR300mgprolonged-releasecapsules,hard

2QUALITATIVEANDQUANTITATIVECOMPOSITION

Eachcapsulecontainsdiltiazemhydrochloride300mg.

Excipients:Sucrose 60.87mg

Forfulllistofexcipients,seesection6.1.

3PHARMACEUTICALFORM

Prolonged-releasecapsule,hard.

Hardgelatincapsuleswithanopaquewhitebodyandopaqueyellowcap,markedwith‘300mg’inblackinkonthe

bodyandcontainingoff-whitesphericalmicrogranules.

4CLINICALPARTICULARS

4.1TherapeuticIndications

Treatmentofanginapectoris.

Treatmentofmildtomoderatehypertension.

4.2Posologyandmethodofadministration

Oraluseonly

Adults:

Hypertension:Theusualinitialdoseis90mgtwicedaily(correspondingto180mgofdiltiazemhydrochloride).

Dependinguponclinicalresponsethepatient’sdosagemaybeincreasedgraduallyto180mgdaily,120mgtwice

daily,240mgdaily,300mgdaily,or180mgtwicedailyifrequired.

AnginaPectoris:Theusualinitialdoseis90mgtwicedaily(correspondingto180mgofdiltiazemhydrochloride).

Dependinguponclinicalresponsethepatient’sdosagemaybeincreasedto180mgdaily,120mgtwicedaily,240mg

daily,300mgdaily,or180mgtwicedailyifrequired.

Elderlypatientsandthosewithimpairedrenalorhepaticdysfunction:

Dosageshouldcommenceatthelowerlevelof60mgtwicedailyandbeincreasedslowly.Donotincreasethedoseif

theheartratefallsbelow50beatsperminute.

Children:

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4.3Contraindications

Useinwomenofchild-bearingpotentialandlactation

Concomitantadministrationofdantroleneinfusionduetotheriskofventricularfibrillation

Shock

Acutecardiacinfarctwithcomplications(bradycardia,severehypotension,leftheartinsufficiency)

Bradycardia(pulserate,atrest,oflessthan50bpm),hypotension(lessthan90mmHgsystole),secondorthirddegreeheartblock

orsicksinussyndrome,exceptinthepresenceofafunctioningventricularpacemaker

Atrialfibrillation/flutterandsimultaneouspresenceofaWPW(Wolff-Parkinson-White)syndrome(increasedriskoftriggeringa

ventriculartachycardia)

Manifestmyocardialinsufficiency

Leftventricularfailurewithstasis

Hypersensitivitytodiltiazemoranyoftheexcipients

4.4Specialwarningsandprecautionsforuse

Capsulesshouldnotbesuckedorchewed.

Theuseofdiltiazemhydrochlorideindiabeticpatientsmayrequireadjustmentoftheircontrol.

Theproductshouldbeusedwithcautioninpatientswithhepaticdysfunction.Abnormalitiesofliverfunctionmay

occurduringtherapy.Veryoccasionalreportsofabnormalliverfunctionhavebeenreceived;thesereactionshavebeen

reversibleupondiscontinuationoftherapy.

FirstdegreeAVblockorprolongedPRinterval.DiltiazemprolongsAVnoderefractoryperiodswithoutsignificantly

prolongingsinusnoderecoverytime,exceptinpatientswithsicksinussyndrome.Thiseffectmayrarelyresultin

abnormallyslowheartrates(particularlyinpatientswithsicksinussyndrome)orsecondorthirddegreeAVblock

(referSection4.5).

Mildbradycardia.

Patientswithreducedleftventricularfunction.

Renallyimpairedpatients.

Owingtothepresenceofsucrose,patientswithrarehereditaryproblemsoffructoseintolerance,glucose-galactose

malabsorptionorsucrase-isomaltaseinsufficiencyshouldnottakethismedicine.

Aswithanydruggivenoverprolongedperiods,laboratoryparametersshouldbemonitoredatregularintervals.

4.5Interactionwithothermedicinalproductsandotherformsofinteraction

DiltiazemundergoesbiotransformationbycytochromeP-450mixedfunctionoxidase.Coadministrationwithother

agentswhichfollowthesamerouteofbiotransformationmayresultincompetitiveinhibitionofmetabolism.

Diltiazemhydrochlorideshouldonlybeadministeredwithgreatcaretopatientsreceivingconcurrenttreatmentwith

antihypertensivesorotherhypotensiveagentsincludinghalogenatedanaestheticsordrugswithmoderateprotein

binding.

Diltiazemhydrochloridewillnotprotectagainsteffectsofwithdrawalof -adrenoceptorblockingagents,northe

reboundeffectsseenwithvariousantihypertensives.Combinationwith -adrenoceptorblockershavingasignificant

“firstpass”loss,e.g.propranololmayrequireadecreaseintheirdoseandmayleadtobradycardia.Theremaybean

additiveeffectwhenusedwithdrugswhichmayinducebradycardiaorwithotherantihypertensives.

ConcomitantH

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Diltiazemmayaffectthebloodlevelsofconcomitantcarbamazepine,theophylline,ciclosporinanddigoxin.Careful

attentionshouldthereforebegiventosignsofoverdosage.Thelevelsshouldbedeterminedandthedoseof

carbamazepine,theophylline,ciclosporin,ordigoxinreducedifnecessary.Patientsreceiving -b1ockers,diuretics,

ACEinhibitorsorotherantihypertensiveagentsshouldberegularlymonitored.Usewithalphablockersshouldbe

strictlymonitored.

Thesimultaneousadministrationofdiltiazemwithdrugssuchas-blockers,antiarrhythmicsorheartglycosidesmay

causeagreaterdegreeofAVblocking,reducetheheartrateorinduceahypotensiveeffect.Intravenousadministration

of-blockersshouldbediscontinuedduringtherapywithdiltiazem.

Anaesthetistsshouldbewarnedthatapatientisonacalciumantagonist.Calciumchannelblockersmaypotentiatethe

depressionofcardiaccontractility,conductivity,andautomaticity,aswellasthevasculardilationassociatedwith

anaesthetics.Whenusedconcomitantly,anaestheticsandcalciumchannelblockersshouldbetitratedcarefully.

Therehavebeenreportsintheliteratureofdiltiazeminteractionswithwarfarin,rifampicin,andlithium.

4.6Pregnancyandlactation

Diltiazemhydrochlorideiscontra-indicatedinpregnantwomenorwomenofchild-bearingpotential,andisnot

recommendedinnursingmothers.

4.7Effectsonabilitytodriveandusemachines

Noneknown.

4.8Undesirableeffects

Instudiescarriedouttodate,seriousadversereactionswithdiltiazemhavebeenrare;however,itshouldberecognised

thatpatientswithimpairedventricularfunctionandcardiacconductionabnormalitieshaveusuallybeenexcludedfrom

thesestudies.

In900patientswithhypertension,themostcommonadverseeventswereoedema(9%),headache(8%),dizziness

(6%),asthenia(5%),sinusbradycardia(3%),flushing(3%),andfirstdegreeAVblock(3%).Onlyoedemaandperhaps

bradycardiaweredoserelated.Themostcommonadverseevents(>1%)observedinclinicalstudiesofover2100

anginaandhypertensivepatientsreceivingdiltiazemwere:oedema(5.4%),headache(4.5%),dizziness(3.4%),

asthenia(2.8%),first-degreeAVblock(1.8%),flushing(1.7%),nausea(1.6%),bradycardia(1.5%)andrash(1.5%).

Lesscommonadverseeventshaveincludedthefollowing:

Cardiovascular:angina,arrhythmia,AVblock(secondorthirddegree),congestiveheartfailure,hypotension,

palpitations,syncope.

Nervoussystem:amnesia,depression,gaitabnormality,hallucinations,insomnia,nervousness,paraesthesia,

personalitychange,somnolence,tinnitus,tremor.

Gastrointestinal:anorexia,constipation,diarrhoea,dyspepsia,mildelevationsofalkalinephosphatase,SGOT,SGPT

andLDH(seeSpecialWarningsandPrecautions),vomiting,weightincrease,gingivitis.

Dermatologic:petechiae,pruritus,photosensitivity,urticaria.Allergicskinreactionsincludingerythemamultiforme,

vasculitis,lymphadenopathyandeosinophiliahavebeenobservedinisolatedcases.Dermatologicaleventsmaybetransientandmay

disappeardespitecontinueduseofdiltiazem.Shouldadermatologicreactionpersist,thedrugshouldbediscontinued.

Other:amblyopia,CKelevation,dyspnoea,epistaxis,eyeirritation,hyperglycaemia,nasalcongestion,nocturia,

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4.9Overdose

Experienceofoverdosageinmanislimitedbutcasesofspontaneousrecoveryhavebeenreported.However,itis

recommendedthatpatientswithsuspectedoverdoseshouldbeplacedunderobservationinacoronarycareunitwith

facilitiesavailablefortreatmentofanypossiblehypotensionandconductiondisturbancesthatmayoccur.Mostpatients

sufferingfromoverdosageofdiltiazembecomehypotensivewithin8hoursofingestion.Withbradycardiaandfirstto

thirddegreeatrioventricularblockalsodevelopingcardiacarrestmayensue.Hyperglycaemiaisalsoarecognised

complication.Theeliminationhalf-lifeofdiltiazemafteroverdosageisestimatedtobeabout5.5-10.2hours.Ifa

patientpresentsearlyafteroverdose,gastriclavageshouldbeperformedandactivatedcharcoaladministeredtoreduce

diltiazemabsorption.

Hypotensionshouldbecorrectedwithplasmaexpanders,intravenouscalciumgluconateandinotropicagents

(dopamine,dobutamineorisoprenaline).SymptomaticbradycardiaandhighgradeAVblockmayrespondtoatropine,

isoprenalineoroccasionallycardiacpacingwhichmaybeusefulifcardiacstandstilloccurs.

5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

Pharmacotherapeuticgroup:Selectivecalciumchannelblockerwithdirectcardiaceffects.

ATCCode:C08DB01

Diltiazemhaspharmacologicactionssimilartothoseofothercalciumchannelblockingagentssuchasnifedipineor

verapamil.Theprincipalphysiologicactionofdiltiazemistoinhibitthetransmembraneinfluxofextracellularcalcium

ionsacrossthemembranesofmyocardialcellsandvascularsmoothmusclecells.

Calciumplaysimportantrolesintheexcitation-contractioncouplingprocessesoftheheartandvascularsmoothmuscle

cellsandintheelectricaldischargeofthespecialisedconductioncellsoftheheart.Themembranesofthesecells

containnumerouschannelsthatcarryaslowinwardcurrentandthatareselectiveforcalcium.

Byinhibitingcalciuminflux,diltiazeminhibitsthecontractileprocessesofcardiacandvascularsmoothmuscle,

therebydilatingthemaincoronaryandsystemicarteries.Dilationofsystemicarteriesbydiltiazemresultsinadecrease

intotalperipheralresistance,adecreaseinsystemicbloodpressureandadecreaseintheafterloadoftheheart.The

reductioninafterload,seenatrestandwithexercise,anditsresultantdecreaseinmyocardialoxygenconsumptionare

thoughttoberesponsibleforthebeneficialeffectsofdiltiazeminpatientswithchronicstableanginapectoris.In

patientswithprinzmetalvariantangina,inhibitionofspontaneousandergonovine-inducedcoronaryarteryspasmby

diltiazemresultsinincreasedmyocardialoxygendelivery.

5.2Pharmacokineticproperties

GeneralCharacteristics

Absorption:Capsulesseemtohaveasimilarbioavailabilitytotablets(30-40%),withpeakconcentrationsforthe

prolongedreleaseproductafter5.5hourscomparedwith1-2hoursaftertheconventionalreleaseproduct.The

relativelylowbioavailabilityisduetofirstpassmetabolisminthelivertoanactivemetabolite.

Distribution:Diltiazemhydrochlorideislipophilicandhasahighvolumeofdistribution.Typicalstudyresultsarein

therangeof3-8litres/kg.Proteinbindingisabout80%andisnotconcentration-dependentatlevelslikelytobefound

clinically.Proteinbindingdoesnotappeartobeinfluencedbyphenylbutazone,warfarin,propranolol,salicylicacidor

digoxin.

Metabolism:Diltiazemhydrochlorideisextensivelymetabolisedintheliver.N-monodesmethyldiltiazemisthe

predominantmetabolitefollowedquantitativelybythedesacetylmetabolite,whichhassomepharmacologicalactivity.

Theefficacyofthemetabolites,desacetyldiltiazemandN-monodesmethyldiltiazemis25-50%andabout20%

respectivelyofthatofdiltiazem.Inliverfunctiondisordersdelayedmetabolismintheliverislikely.Thesemetabolites

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Elimination:Diltiazemisexcretedintheformofitsmetabolites(about35%)andinthenon-metabolisedform(about2-

4%)viathekidneyswhileabout60%isexcretedviathefaeces.Theaverageeliminationhalflifeperiodfordiltiazemis

6-8hoursbutmayvarybetween2and11hours.Althoughtheeliminationhalflifeisnotchangedafterrepeatedoral

administration,diltiazemandalsothedesacetylmetaboliteshowaslightaccumulationintheplasma.

CharacteristicsinPatients

Decreasedfirst-passmetabolismintheelderlytendstoresultinincreasedplasmaconcentrationsofcalciumantagonists

butnomajorchangeshavebeenfoundwithdiltiazem.Renalimpairmentdidnotcausesignificantchangesindiltiazem

pharmacokinetics.Plasmaconcentrationsofdiltiazemalsotendtobehigherinhepaticcirrhosisduetoimpaired

oxidativemetabolism.

5.3Preclinicalsafetydata

Chronictoxicitystudiesinratsrevealednoremarkablechangesatoraldosesupto125mg/kg/dayalthoughtherewas

60%mortalityatthisdose.Indogschronicallytreatedwithoraldosesof20mg/kg/day,transientrisesinSGPTwere

observed.Embryotoxicityhasbeenreportedinmice,ratsandrabbitsfollowingi.p.administrationofdiltiazem.Main

typesofmalformationsincludedlimbandtaildefectswithasmallnumberofvertebralandribdeformitiesalsonoted.

6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

Sugarspheresconsistingof

Sucroseandmaizestarch

PovidoneK30

Sucrose

Ethylcellulose4mPa.s

Talc

Dispersionofethylcellulose(AquacoatECD30)containing:

Ethylcellulose

Sodiumlaurilsulfate

Cetylalcohol

Dibutylsebacate

Compositionofcapsuleshell:

Titaniumdioxide(E171)

Gelatin

Blackironoxide(E172)

Yellowironoxide(E172)

6.2Incompatibilities

Notapplicable.

6.3ShelfLife

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6.4Specialprecautionsforstorage

Donotstoreabove30°C.Storeintheoriginalpackage.

6.5Natureandcontentsofcontainer

Aluminium/PVCblisterspackedincardboardcartonscontaining28,30,56or60capsules.

Sampleblisterpackof14capsules.

Notallpacksizesmaybemarketed.

6.6Specialprecautionsfordisposalofausedmedicinalproductorwastematerialsderivedfrom

suchmedicinalproductandotherhandlingoftheproduct

Nospecialrequirements.

7MARKETINGAUTHORISATIONHOLDER

EthypharmS.A.

17-21RueSaintMatthieu

78550Houdan

FRANCE

8MARKETINGAUTHORISATIONNUMBER

PA549/1/4

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

Dateoffirstauthorisation:18 th

January1991

Dateoflastrenewal:18 th

January2006

10DATEOFREVISIONOFTHETEXT

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