ADIZEM-XL

Main information

  • Trade name:
  • ADIZEM-XL Prolonged Release Capsules 200 Milligram
  • Dosage:
  • 200 Milligram
  • Pharmaceutical form:
  • Prolonged Release Capsules
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug

Documents

Localization

  • Available in:
  • ADIZEM-XL Prolonged Release Capsules 200 Milligram
    Ireland
  • Language:
  • English

Status

  • Source:
  • HPRA - Health Products Regulatory Authority - Ireland
  • Authorization number:
  • PA0913/014/008
  • Authorization date:
  • 19-04-2002
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

Adizem-XL200mgProlongedReleaseCapsules.

2QUALITATIVEANDQUANTITATIVECOMPOSITION

Eachcapsulecontains200mgdiltiazemhydrochloride.

Excipients:alsocontainssoyalecithin,tracequantitiespercapsule.

Forafulllistofexcipients,seesection6.1.

3PHARMACEUTICALFORM

Prolongedreleasecapsules,hard.

Size1,hardgelatincapsuleswithbrownbodyandbrowncapmarked‘DCR200’.

4CLINICALPARTICULARS

4.1TherapeuticIndications

Managementofanginapectoris.

Treatmentofmildtomoderatehypertension.

4.2Posologyandmethodofadministration

Oral.

Thecapsulesshouldbeswallowedwholeandnotchewed.

Adults:

Theusualstartingdoseisone240mgcapsuledaily.Howeverpatients'responsesmayvaryanddosage

requirementscandiffersignificantlybetweenindividualpatients.Thereisnoevidenceofanydecreaseinefficacy

athigherdoses.Ifnecessarythedosemaybegraduallyincreasedto300mgor360mgperday.Dosesof480

mg/dayhavebeenusedwithbenefitinsomeanginapatients.

Elderly:

Theusualstartingdoseisone120mgcapsuledaily.Ifnecessarythedosemaybegraduallyincreasedbutcareful

monitoringofthisgroupofpatientsisadvised.

Children:

Notrecommendedforuseinchildren.

AdizemXLshouldnotbetakenatthesametimeasanalcoholicbeverage(refertoSection4.5,Interactionswithother

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4.3Contraindications

Sicksinussyndromenotrequiringpacemaker,secondorthirddegreeAV-block,bradycardia(lessthan40beatsper

minute).Congestiveheartfailureandinpatientswithleftventriculardysfunctionfollowingmyocardialinfarction.

Pregnantwomenorthoseofchildbearingpotential.Concurrentusewithdantroleneinfusioniscontraindicated

becauseoftheriskofventricularfibrillation.Peanutorsoyaallergies.

4.4Specialwarningsandprecautionsforuse

PatientswithmildbradycardiaoraprolongedPRintervalshouldbeobservedclosely.

Diltiazemshouldbeusedwithcautioninpatientswithreducedleftventricularfunction.

Diltiazemshouldbeusedwithcautioninpatientswithhepaticdysfunction.

Diltiazemisconsideredunsafeinpatientswithacuteporphyria.

Isolatedcasesofmoderateandtransientincreasedlivertransaminaseshavebeenobservedatthestartoftreatment.

Isolatedcasesofclinicalhepatitishavebeenreported,whichresolvedwhendiltiazemwaswithdrawn.

Theuseofdiltiazemindiabeticpatientsmayrequireadjustmentoftheircontrol.

4.5Interactionwithothermedicinalproductsandotherformsofinteraction

DiltiazemhydrochlorideisextensivelymetabolisedbyCYP3A4,andasaresultserumlevelsofdiltiazemmaybe:

IncreasedbyconcomitantusageofCYP3A4inhibitorssuchasH

antagonists(e.g.cimetidine,ranitidine)and

proteaseinhibitors(e.g.atazanavir,ritonavir)

DecreasedbyconcomitantusageofCYP3A4inducerssuchasbarbituates(phenobarbital,primidone),phenytoin

andrifampicin

DiltiazemhydrochlorideisalsoaninhibitorofCYP3A4,andmaythereforeincreaseserumlevelsofCYP3A4

substratessuchasbenzodiazepines(especiallymidazolamandtriazolam),carbamazepine,ciclosporin,cilostazol,

ivabradine,statins(simvastatin,atorvastatin,lovastatin),sirolimus,tacrolimusandtheophylline.Careshouldbe

exercisedinpatientstakingthesedrugs.Concomitantuseofdiltiazemhydrochloridewithcilostazolandivabradine

shouldbeavoided.

Theremaybeanadditiveeffect(increaseddepressionofcardiacconductionwithriskofbradycardiaandAVblock)

whendiltiazemhydrochlorideisprescribedwithdrugswhichmayinducebradycardiaorotheranti-arrhythmicdrugs

(e.g.amiodaroneandbeta-blockers).Patientswithpre-existingconductiondefectsshouldnotreceivethecombination

ofdiltiazemandbeta-blockers.

Enhancedantihypertensiveeffectmayoccurwithconcomitantuseofotherhypertensivedrugs(e.g.beta-blockers,

diuretics,ACE-inhibitors)ordrugsthatcausehypotensionsuchasaldesleukinandantipsychotics.Concomitantuse

withalph-blockers(e.g.prazosin)shouldbestrictlymonitoredbecauseofthepossiblesynergistichypotensiveeffectof

thiscombination.

Diltiazemhydrochloridemaycausesmallincreasesinplasmalevelsofdigoxin,requiringcarefulmonitoringofAV

conduction.

Diltiazemhydrochloridemayincreaseserumlevelsofphenytoin.

Diltiazemhydrochloridemayincreasebioavailabilityoftricyclicantidepressants.

Treatmentwithdiltiazemhydrochloridehasbeencontinuedwithoutproblemduringanaesthesia,buttheanaesthesist

shouldbemadeawareofthetreatmentregimen.

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prolongedreleasepreparation.Inadditionthecombinationofalcoholanddiltiazemmayhaveanadditivevasodilatory

effect.

4.6Fertility,pregnancyandlactation

Notrecommended.

4.7Effectsonabilitytodriveandusemachines

Noneknown.

4.8Undesirableeffects

Theadverseeventslistedbelowareclassifiedbybodysystem.

4.9Overdose

Theclinicalsymptomsofacuteintoxicationmayincludepronouncedhypotensionorevencollapseandsinus

bradycardiawithorwithoutatrioventricularconductiondefects.

Thepatientshouldbecloselymonitoredinhospitaltoexcludearrhythmiasoratrioventricularconductiondefects.

Gastriclavageandosmoticdiuresisshouldbeundertakenwhenconsideredappropriate.Symptomaticbradycardiaand

highgradeatrioventricularblockmayrespondtoatropine,isoprenalineoroccasionallytemporarycardiacpacing.

Hypotensionmayrequirecorrectionwithplasmavolumeexpanders,intravenouscalciumgluconateandpositive

inotropicagents.Theformulationemploysaprolongedreleasesystemwhichwillcontinuetoreleasediltiazemfor

BloodandLymphaticsystemdisorders Thrombocytopenia

Metabolismandnutritiondisorders Anorexia

Nervoussystemdisorders Dizziness

Extrapyramidaldisorder

Headache

Cardiacdisorders Atrioventricularblock

Bradycardia

Palpitations

Sinoatrialblock

Vasculardisorders Facialflushing

Hypotension

Vasculitis

Gastrointestinaldisorders Gastrointestinaldisorder

Gingivalhyperplasia

Nausea

Hepato-biliarydisorders Increasedhepaticenzyme

Hepatitis

Skinandsubcutaneousdisorders Allergicdermatitis

Erythemamultiforme

Exfoliativedermatitis

Photosensitivityreaction

Rash

Angioneuroticoedema

Reproductivesystemandbreastdisorders Gynaecomastia

Generaldisorders Fatigue

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5PHARMACOLOGICALPROPERTIES

Pharmacotherapeuticgroup:Selectivecalciumchannelblockerwithdirectcardiaceffects.

ATCCode:C08DB01.

5.1Pharmacodynamicproperties

Diltiazemisacalciumantagonist.Itrestrictstheslowchannelentryofcalciumionsintothecellandsoreducesthe

liberationofcalciumfromstoresinthesarcoplasmicreticulum.

Thisresultsinareductionintheamountofavailableintra-cellularcalciumandconsequentlya(1)reductionof

myocardialoxygenconsumption,(2)dilationofsmallandlargecoronaryarteries,(3)mildperipheralvasodilation,(4)

negativedromotropiceffects,(5)reflexpositivechronotropicandinotropiceffectsduetoreflexsympatheticactivity

arepartiallyinhibitedandresultinaslightreductionornochangeinheartrate.

Theantihypertensiveeffectisduetothereductioninperipheralvascularresistance.

Theantianginaleffectisduetoareductionintheperipheralresistance,therebydecreasingtheafter-load,whilsta

reductioninthevasomotortoneofthecoronarycirculationmaintainsthecoronarybloodflow.Cardiaccontractility

andventricularejectionfractionareunchanged.Diltiazemincreasesexercisecapacityandimprovesindicesof

myocardialischaemiaintheanginapatient.Diltiazemrelievesthespasmofvasospastic(Prinzmetal)angina.

5.2Pharmacokineticproperties

Anoraldoseofdiltiazemisalmostcompletelyabsorbed.Despitethis,diltiazemhasalowbioavailabilityowingto

hepaticfirst-passmetabolism.Diltiazemismetabolisedextensivelyandonly1.0-3.0%ofthedoseisexcretedinurine

asunmetaboliseddiltiazem.

Thereleaseofthedrughasbeenprolongedinthecapsulesbyspecialpharmaceuticaltechnology.Thehighpeak

concentrationsoftheabsorptionphasehavebeeneliminated.Thisallowsthecapsulestobeadministeredoncedaily.

5.3Preclinicalsafetydata

Therearenopre-clinicaldataofrelevancetotheprescriberwhichareadditionaltothatalreadyincludedinother

sectionsoftheSPC.

6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

Microcrystallinecellulose

EthylcelluloseN10

Colloidalanhydroussilica

Polysorbate80

Dibutylsebacate

Magnesiumstearate

Capsuleshell

IronoxideRed(E172)

IronoxideYellow(E172)

IronoxideBlack(E172)

Titaniumdioxide(E171)

Gelatin

Sodiumlaurilsulfate

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Shellac

Soyalecithin

2-ethoxyethanol

Dimeticone

Titaniumdioxide(E171)

6.2Incompatibilities

Notapplicable.

6.3ShelfLife

2years.

6.4Specialprecautionsforstorage

Donotstoreabove25°C.

6.5Natureandcontentsofcontainer

PVdCcoatedPVCblisterpackswithaluminiumfoilbacking(4,28and30capsules).

Notallpacksizesmaybemarketed

6.6Specialprecautionsfordisposalofausedmedicinalproductorwastematerialsderivedfrom

suchmedicinalproductandotherhandlingoftheproduct

Nospecialrequirements.

7MARKETINGAUTHORISATIONHOLDER

NappPharmaceuticalsLimited,

CambridgeSciencePark,

MiltonRoad,

Cambridge,

CB40GW,

UnitedKingdom.

8MARKETINGAUTHORISATIONNUMBER

PA913/14/8

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

Dateoffirstauthorisation:19/04/02

Dateoflastrenewal:16/12/2009

10DATEOFREVISIONOFTHETEXT

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