DILZEM SR

Main information

  • Trade name:
  • DILZEM SR
  • Dosage:
  • 60 Milligram
  • Pharmaceutical form:
  • Capsules Hard
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug

Documents

Localization

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

Status

  • Source:
  • HPRA - Health Products Regulatory Authority - Ireland
  • Authorization number:
  • PPA0465/164/001
  • Authorization date:
  • 26-08-2005
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

IRISHMEDICINESBOARDACT1995,asamended

MedicinalProducts(ControlofPlacingontheMarket)Regulations,2007,asamended

PPA0465/164/001

CaseNo:2081982

TheIrishMedicinesBoardinexerciseofthepowersconferredonitbytheabovementionedRegulationsherebygrantsto

PCOManufacturingLimited

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

anauthorisation,subjecttotheprovisionsofthesaidRegulations,inrespectoftheproduct

DilzemSR60mgProlonged-releasehardcapsules

theparticularsofwhicharesetoutintheattachedSchedule.Theauthorisationisalsosubjecttothegeneralconditionsasmaybespecifiedin

thesaidRegulationsaslistedonthereverseofthisdocument.

Thisauthorisation,unlesspreviouslyrevoked,shallcontinueinforcefrom26/07/2010until25/08/2010.

SignedonbehalfoftheIrishMedicinesBoardthis

________________

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Date Printed 26/07/2010 CRN 2081982 page number: 1

PartII

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

DilzemSR60mgProlonged-releasehardcapsules

2QUALITATIVEANDQUANTITATIVECOMPOSITION

Eachprolongedreleasecapsulecontains60mgdiltiazemhydrochloride.

Forexcipients,see6.1

3PHARMACEUTICALFORM

Prolongedrelease,hardcapsule.

ProductimportedfromtheUK:

Buffcolouredgelatincapsules,printedwith‘60mg’.

4CLINICALPARTICULARS

4.1TherapeuticIndications

TreatmentofanginapectorisincludingPrinzmentalsangina.

Treatmentofmildtomoderatehypertension.

4.2Posologyandmethodofadministration

Oraluseonly.

Adults

Hypertension:Theusualinitialdoseis90mgtwicedaily(correspondingto180mgofDiltiazemhydrochloride).

Dependinguponclinicalresponsethepatient'sdosagemaybeincreasedto180mgtwicedailyifrequired.

AnginaPectoris:Theusualinitialdoseis90mgtwicedaily(correspondingto180mgofDiltiazemhydrochloride).

Dependinguponclinicalresponsethepatient'sdosagemaybeincreasedto180mgtwicedailyifrequired.

Elderlypatientsandthosewithrenalorhepaticimpairment

Dosageshouldcommenceatthelowerlevelof60mgtwicedailyandbeincreasedslowly.Donotincreasethedoseif

theheartratefallsbelow50beatsperminute.

Children

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4.3Contraindications

Useinwomenofchild-bearingpotential.

Concomitantadministrationofdantroleneinfusionduetotheriskofventricularfibrillation.

Shock.

Acutecardiacinfarctwithcomplications(bradycardia,severehypotension,leftheartinsufficiency).

Bradycardia(pulserate,atrest,oflessthan50perminute),hypotension(lessthan90mmHgsystole),secondor

thirddegreeheartblockorsicksinussyndrome,exceptinthepresenceofafunctioningventricularpacemaker.

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

riskoftriggeringaventriculartachycardia).

Manifestmyocardialinsufficiency.

Leftventricularfailurewithstasis.

Hypersensitivitytodiltiazemoranyoftheexcipients.

4.4Specialwarningsandprecautionsforuse

Capsulesshouldnotbesuckedorchewed.

Theuseofdiltiazemhydrochlorideindiabeticpatientsmayrequireadjustmentoftheircontrol.

Theproductshouldbeusedwithcautioninpatientswithhepaticdysfunction.Abnormalitiesofliverfunction

mayoccurduringtherapy.Veryoccasionalreportsofabnormalliverfunctionhavebeenreceived;thesereactions

havebeenreversibleupondiscontinuationoftherapy.

FirstdegreeAVblockorprolongedPRinterval.DilzemprolongsAVnoderefractoryperiodswithout

significantlyprolongingsinusnoderecoverytime,exceptinpatientswithsicksinussyndrome.Thiseffectmay

rarelyresultinabnormallyslowheartrates(particularlyinpatientswithsicksinussyndrome)orsecond-orthird-

degreeAVblock(seeinteractionssectionforinformationconcerningbeta-blockersanddigitalis).

Mildbradycardia

Patientswithreducedleftventricularfunction.

Renallyimpairedpatients.

Owingtothepresenceofsucrose,patientswithrarehereditaryproblemsoffructoseintolerance,glucose-

galactosemalabsorptionorsucrase-isomaltaseinsufficiencyshouldnottakethismedicine.

Aswithanydruggivenoverprolongedperiods,laboratoryparametersshouldbemonitoredatregularintervals.

4.5Interactionwithothermedicinalproductsandotherformsofinteraction

DiltiazemundergoesbiotransformationbycytochromeP-450mixedfunctionoxidase.Coadministrationwithother

agents,whichfollowthesamerouteofbiotransformation,mayresultincompetitiveinhibitionofmetabolism.

Diltiazemhydrochlorideshouldbeadministeredwithgreatcaretopatientsreceivingconcurrenttreatmentwith

antihypertensivesorotherhypotensiveagentsincludinghalogenatedanaestheticsordrugswithmoderateprotein

binding.

Diltiazemhydrochloridewillnotprotectagainsteffectsofwithdrawalofß-adrenoceptorblockingagents,northe

reboundeffectsseenwithvariousantihypertensives.Combinationwithß-adrenoceptorblockershavingasignificant

"firstpass"losse.g.propranololmayrequireadecreaseintheirdoseandmayleadtobradycardia.Theremaybean

additiveeffectwhenusedwithdrugs,whichmayinducebradycardia,orwithotherantihypertensives.ConcomitantH

antagonisttherapymayincreasediltiazembloodlevels.

Diltiazemmayaffectthebloodlevelsofconcomitantcarbamazepine,theophylline,cyclosporinanddigoxin.Careful

attentionshouldthereforebegiventosignsofoverdosage,ifnecessarythelevelsshouldbedeterminedandthedoseof

carbamazepine,theophylline,cyclosporinA,ordigoxinreducedifnecessary.Patientsreceivingß-blockers,diuretics,

ACEinhibitorsorotherantihypertensiveagentsshouldberegularlymonitored.Usewithalphablockersshouldbe

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Thesimultaneousadministrationofdiltiazemwithdrugssuchasß-blockers,antiarrythmicsorheartglycosidesmay

causeagreaterdegreeofAVblocking,reducetheheartrateorinduceahypotensiveeffect.Intravenousadministration

ofß-blockersshouldbediscontinuedduringtherapywithdiltiazem.

Anaesthetistsshouldbewarnedthatapatientisonacalciumantagonist.Thedepressionofcardiaccontractility,

conductivity,andautomaticityaswellasthevasculardilationassociatedwithanaestheticsmaybepotentiatedby

calciumchannelblockers.Whenusedconcomitantly,anaestheticsandcalciumchannelblockersshouldbetitrated

carefully.

Therehavebeenreportsintheliteratureofdiltiazeminteractionswithwarfarin,rifampacinandlithium.

4.6Pregnancyandlactation

Diltiazemmustnotbetakenduringpregnancyasexperimentalstudieshaveshownindicationsofteratogenicity.There

isnoexperienceofitseffectsinhumans.Asdiltiazemisknowntoenterthebreastmilkandthereisnoexperienceof

possibleeffectsininfants,infantsshouldbeweanediftreatmentofthemotherwithdiltiazemisnecessary.

4.7Effectsonabilitytodriveandusemachines

Notapplicable.

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%)observedinclinicalstudiesofover2100anginaandhypertensivepatients

receivingdiltiazemwere: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.Dermatologicaleventsmaybe

transientandmaydisappeardespitecontinueduseofdiltiazem.Shouldadermatologicreactionpersist,thedrugshould

bediscontinued.

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

osteoarticularpain,polyuria,sexualdifficulties.

4.9Overdose

Experienceofoverdosageinmanislimitedbutcasesofspontaneousrecoveryhavebeenreported.However,itis

recommendedthatpatientswithsuspectedoverdose,shouldbeplacedunderobservationinacoronarycareunitwith

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Mostpatientssufferingfromoverdosageofdiltiazembecomehypotensivewithin8hoursofingestion.With

bradycardiaandfirsttothirddegreeatrioventricularblockalsodevelopingcardiacarrestmayensue.Hyperglycaemiais

alsoarecognisedcomplication.Theeliminationhalf-lifeofdiltiazemafteroverdosageisestimatedtobeabout5.5-

10.2hours.Ifapatientpresentsearlyafteroverdose,gastriclavageshouldbeperformedandactivatedcharcoal

administeredtoreducediltiazemabsorption.

Hypotensionshouldbecorrectedwithplasmaexpanders,intravenouscalciumgluconateandionotropicagents

(dopamine,dobutamine,isoprenaline),symptomaticbradycardiaandhighgradeAVblockmayrespondtoatropine,

isoprenalineoroccasionallycardiacpacingwhichmaybeusefulifcardiacstandstilloccurs.

5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

Diltiazemisacalciumchannelblockingagent.Theprecisemechanismofaction,whichisdosedependent,isunknown,

butcalciumchannelblockersactpredominantlyatspecificvoltage-sensitiveion-selectivechannels,"slowcalcium

channels"ofcardiacandsmoothmusclecellswhoseexcitation-contractioncouplingrequiresaninwarddisplacement

ofcalcium.

Calciumchannelblockersarevasodilatorswhoseantihypertensiveeffectsareassociatedwithdecreasesinperipheral

resistanceleadingtoadropinbloodpressure.Theantianginaleffectsofdiltiazemhydrochlorideareprobablyrelatedto

itscoronaryarteryvasodilatingeffectandtoitshaemodynamiceffects.

Theformulationispresentedasasustainedreleasepreparationfortwicedailyadministration.

5.2Pharmacokineticproperties

a) GeneralCharacteristics

Absorption:Capsulesseemtohaveasimilarbioavailabilitytotablets(30-40%),withpeakconcentrationsforthe

sustainedreleaseproductafter8-11hourscomparedwith1-2hoursaftertheconventionalreleaseproduct.The

relativelylowbioavailabilityisduetofirstpassmetabolisminthelivertoanactivemetabolite.

Distribution:Diltiazemhydrochlorideislipophilicandhasahighvolumeofdistribution.Typicalstudyresultsarein

therangeof3-8litres/kg.Proteinbindingisabout80%andisnotconcentrationdependentatlevelslikelytobefound

clinically.Proteinbindingdoesnotappeartobeinfluencedbyphenylbutazone,warfarin,propanolol,salicylicacidor

digoxin.

Metabolism:Diltiazemhydrochlorideisextensivelymetabolisedintheliver.N-monodesmethyldiltiazemisthe

predominantmetabolitefollowedquantitativelybythedesacetylmetabolite,whichhassomepharmacologicalactivity.

Theefficacyofthemetabolites,desacetyldiltiazemandN-monodesmethyldiltiazemis25-50%andabout20%

respectivelyofthatofdiltiazem.Inliverfunctiondisordersdelayedmetabolismintheliverislikely.Thesemetabolites

areconvertedtoconjugates,generallytheglucuronideorthesulphate.

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

2-4%)viathekidneyswhileabout60%isexcretedviathefaeces.Theaverageeliminationhalflifeperiodfordiltiazem

is6-8hoursbutmayvarybetween2and11hours.Althoughtheeliminationhalflifeperiodisnotchangedafter

repeatedoraladministration,diltiazemandalsothedesacetylmetaboliteshowaslightaccumulationintheplasma.

b) CharacteristicsinPatients

Decreasedfirst-passmetabolismintheelderlytendstoresultinincreasedplasmaconcentrationsofcalciumantagonists

butnomajorchangeshavebeenfoundwithdiltiazem.Renalimpairmentdidnotcausesignificantchangesindiltiazem

pharmacokinetics.Plasmaconcentrationsofdiltiazemalsotendtobehigherinhepaticcirrhosisduetoimpaired

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5.3Preclinicalsafetydata

Chronictoxicitystudiesinratsrevealednoremarkablechangesatoraldosesupto125mg/kg/dayalthoughtherewasa

60%mortalityatthisdose.Indogschronicallytreatedwithoraldosesof20mg/kg/day,transientrisesinSGPTwere

observed.Embryotoxicityhasbeenreportedinmice,ratsandrabbitsfollowingi.p.administrationofdiltiazem.Main

typesofmalformationsincludedlimbandtaildefectswithasmallnumberofvertebralandribdeformitiesalsonoted.

6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

Fumaricacid

Talc

Povidone

Nonpareilseeds

Poly(ethylacrylate,methylmethacrylate,trimethylammonio-ethylmethacrylatechloride)

(1:2:0.1)(EudragitRS12.5%)

Poly(ethylacrylate,methylmethacrylate,trimethylammonio-ethylmethacrylatechloride)

(1:2:0.2)(EudragitRL12.5%)

Thecapsuleshellcontains

Yellowironoxide(E172)

Erythrosine(E127)

Titaniumdioxide(E171)

Gelatin

Shellac

Soyalecithin

Dimeticone

Blackironoxide(E172)

6.2Incompatibilities

Notapplicable.

6.3ShelfLife

Theshelflifeexpirydateofthisproductisthedateshownonthecontainerandouterpackageoftheproductonthe

marketinthecountryoforigin.

6.4Specialprecautionsforstorage

Donotstoreabove25°C.

Storeinoriginalpackage.

6.5Natureandcontentsofcontainer

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6.6Specialprecautionsfordisposalofausedmedicinalproductorwastematerialsderivedfrom

suchmedicinalproductandotherhandlingoftheproduct

Nospecialrequirements.

7PARALLELPRODUCTAUTHORISATIONHOLDER

PCOManufacturingLimited

Unit10,AshbourneBusinessPark

Rath

Ashbourne

Co.Meath

8PARALLELPRODUCTAUTHORISATIONNUMBER

PPA0465/164/001

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

Dateoffirstauthorisation: 26August2005

10DATEOFREVISIONOFTHETEXT

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