CORDARONE X 200 MG TABLETS

Main information

  • Trade name:
  • CORDARONE X 200 MG TABLETS
  • Dosage:
  • 200 Milligram
  • Pharmaceutical form:
  • Tablets
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug

Documents

Localization

  • Available in:
  • CORDARONE X 200 MG TABLETS
    Ireland
  • Language:
  • English

Status

  • Source:
  • HPRA - Health Products Regulatory Authority - Ireland
  • Authorization number:
  • PPA0465/119/001A
  • Authorization date:
  • 05-03-2004
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

CordaroneX200mgTablets.

2QUALITATIVEANDQUANTITATIVECOMPOSITION

Eachtabletcontains200mgamiodaronehydrochloride.

Excipient:LactoseMonohydrate

Forafulllistofexcipients,seesection6.1.

3PHARMACEUTICALFORM

Tablet

ProductimportedfromtheNetherlandsandHungary:

Round,whitetabletwithabreakline,‘200’andalogoononeside,plainontheotherside.

Thebreaklineisonlytofacilitatebreakingforeaseofswallowingandnottobedividedintoequaldoses.

4CLINICALPARTICULARS

4.1TherapeuticIndications

Treatmentshouldbeinitiatedandnormallymonitoredonlyunderhospitalorspecialistsupervision.OralCordaroneX

isindicatedonlyforthetreatmentofsevererhythmdisordersnotrespondingtoothertherapiesorwhenother

treatmentscannotbeused.

TachyarrhythmiasassociatedwithWolff-Parkinson-Whitesyndrome.

Atrialflutterandfibrillationwhenotherdrugscannotbeused.

Alltypesoftachyarrhythmiasofparoxysmalnatureincluding;supraventricular,nodalandventriculartachycardias,

ventricularfibrillation:whenotherdrugscannotbeused.

Cordaroneisindicatedforthepreventionofventriculararrhythmiasinhigh-riskpatientsfollowingmyocardial

infarctionorinpatientswithclinicalsignsofcongestivecardiacfailureand/orLVEFlessthan40%whoarereceiving

appropriatecardiacfailuretreatmentwhichincludesACE-inhibitors.Theminimumeffectivedosemustbeusedand

treatmentmustbeinitiatedandusedonlyunderhospital/specialistsupervision.

4.2Posologyandmethodofadministration

CordaroneX200Tabletsarefororaladministration.

Adults

Itisparticularlyimportantthattheminimumeffectivedosebeused.Inallcasesthepatient'smanagementmustbe

judgedontheindividualresponseandwellbeing.Thefollowingdosageregimenisgenerallyeffective.

InitialStabilisation

Treatmentshouldbestartedwith200mg,threetimesadayandmaybecontinuedfor1week.Thedosageshouldthen

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Maintenance

Aftertheinitialperiodthedosageshouldbereducedto200mgdaily,orlessifappropriate.Rarely,thepatientmay

requireahighermaintenancedose.Thescored100mgtabletshouldbeusedtotitratetheminimumdosagerequiredto

maintaincontrolofthearrhythmia.Themaintenancedoseshouldberegularlyreviewed,especiallywherethisexceeds

200mgdaily.

GeneralConsiderations

Initialdosing

Ahighdoseisneededinordertoachieveadequatetissuelevelsrapidly.

Maintenance

Toohighadoseduringmaintenancetherapycancausesideeffectswhicharebelievedtoberelatedtohightissuelevels

ofamiodaroneanditsmetabolites.

Amiodaroneisstronglyproteinboundandhasanaverageplasmahalflifeof50days(reportedrange20-100days).It

followsthatsufficienttimemustbeallowedforanewdistributionequilibriumtobeachievedbetweenadjustmentsof

dosage.Inpatientswithpotentiallylethalarrhythmiasthelonghalflifeisavaluablesafeguard,asomissionof

occasionaldosesdoesnotsignificantlyinfluencetheoveralltherapeuticeffect.

Itisparticularlyimportantthattheminimumeffectivedosageisusedandthepatientismonitoredregularlytodetect

theclinicalfeaturesofexcessamiodaronedosage.Therapymaythenbeadjustedaccordingly.

Dosagereduction/withdrawal

Sideeffectsslowlydisappearastissuelevelsfall.

Followingdrugwithdrawal,residualtissueboundamiodaronemayprotectthepatientforuptoamonth.However,the

likelihoodofrecurrenceofarrhythmiaduringthisperiodshouldbeconsidered.

Elderly

Aswithallpatientsitisimportantthattheminimumeffectivedoseisused.Whilstthereisnoevidencethatdosage

requirementsaredifferentforthisgroupofpatientstheymaybemoresusceptibletobradycardiaandconduction

defectsiftoohighadoseisemployed.Particularattentionshouldbepaidtomonitoringthyroidfunction.See4.3

Contra-indications,4.4SpecialWarnings,4.8Undesirableeffects).

4.3Contraindications

Sinusbradycardiaandsino-atrialheartblock.Inpatientswithsevereconductiondisturbances(highgradeAVblock,

bifascicularortrifascicularblock)orsinusnodedisease,CordaroneXshouldbeusedonlyinconjunctionwitha

pacemaker.

Evidenceorhistoryofthyroiddysfunction.

Knownhypersensitivitytoiodineortoamiodaroneortoanyoftheexcipients.(One200mgtabletcontains

approximately75mgiodine)

ConcomitantadministrationofCordaroneXwithdrugswhichmayinduceTorsadesdePointes(see4.5Interactions).

Preganacy,exceptinexceptionalcircumstances(seesection4.6)

Lactation(seesection4.6).

4.4Specialwarningsandprecautionsforuse

Patientswithrarehereditaryproblemsofgalactoseintolerance,theLapplactasedeficiencyofglucose-galactose

malabsorptionshouldnottakethismedicine.

Paediatricpatients

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patientsisnotrecommended.

Cardiacdisorders(seesection4.8)

Toohighadosagemayleadtoseverebradycardiaandtoconductiondisturbanceswiththeappearanceofan

idioventricularrhythm,particularlyinelderlypatientsorduringdigitalistherapy.Inthesecircumstances,CordaroneX

treatmentshouldbewithdrawn.Ifnecessarybeta-adrenostimulantsorglucagonmaybegiven.Becauseofthelonghalf-

lifeofamiodarone,ifbradycardiaissevereandsymptomatictheinsertionofapacemakershouldbeconsidered.

ThepharmacologicalactionofamiodaroneinducesECGchanges:QTprolongation(relatedtoprolonged

repolarisation)withthepossibledevelopmentofU-wavesanddeformedT-waves;thesechangesdonotreflecttoxicity.

Intheelderly,heartratemaydecreasemarkedly.

Treatmentshouldbediscontinuedincaseofonsetof2 nd

or3 rd

degreeA-Vblock,sino-atrialblock,orbifascicular

block.

Amiodaronehasalowpro-arrhythmiceffect.Onsetsofnewarrhythmiasorworseningoftreatedarrhythmias,

sometimesfatal,havebeenreported.Itisimportant,butdifficult,todifferentiatealackofefficacyofthedrugfroma

proarrhythmiceffect,whetherornotthisisassociatedwithaworseningofthecardiaccondition.

Proarrhythmiceffectsgenerallyoccurinthecontextofdruginteractionsand/orelectrolyticdisorders(seesections4.5

and4.8).

Hyperthyrodism(seesections4.4and4.8)

Hyperthyroidismmayoccurduringamiodaronetreatment,or,uptoseveralmonthsafterdiscontinuation.Clinical

features,suchasweightloss,asthenia,restlessness,increaseinheartrate,onsetofarrhythmia,angina,congestiveheart

failureshouldalertthephysician.ThediagnosisissupportedbyadecreaseinserumultrasensitiveTSH(usTSH)level,

elevatedT

andareducedTSHresponsetothyrotropinreleasinghormone(TRH).ElevationofreverseT

)may

alsobefound.

Inthecaseofhyperthyroidism,therapyshouldbewithdrawn.Clinicalrecoveryusuallyoccurswithinafewmonths,

althoughseverecases,sometimesresultinginfatalities,havebeenreported. Clinicalrecoveryprecedesthe

normalizationofthyroidfunctiontests.

Coursesofanti-thyroiddrugshavebeenusedforthetreatmentofseverethyroidhyperactivity;largedosesmaybe

requiredinitially.Thesemaynotalwaysbeeffectiveandconcomitanthighdosecorticosteroidtherapy(e.g.1mg/kg/

prednisolone)mayberequiredforseveralweeks.

Pulmonarydisorders(Seesection4.8)

Onsetdyspnoeaornon-productivecoughmayberelatedtopulmonarytoxicity(hypersensitivitypneumonitis,

alveolar/interstitalpneumonitisorfibrosis,pleuritis,bronchiolitisobliteransorganizingpneumonitis).Presenting

freaturescanincludedyspnoea(whichmaybesevereandunexplainedbythecurrentcardiacstatus),non-productive

coughanddeteriorationingeneralhealth(fatigue,weightlossandfever).Theonsetisusuallyslowbutmayberapidly

progressive.Whilstthemajorityofcaseshavebeenreportedwithlongtermtherapy,afewhaveoccurredsoonafter

startingtreatment.

PatientsshouldbecarefullyevaluatedclinicallyandconsiderationgiventochestX-raybeforestartingtherapy.During

treatment,ifpulmonarytoxicityissuspected,thisshouldberepeatedandassociatedwithlungfunctiontesting

includingwherepossiblemeasurementoftransferfactor.Initialradiologicalchangesmaybedifficulttodistinguish

frompulmonaryvenouscongestion.Pulmonarytoxicityhasusuallybeenreversiblefollowingearlywithdrawalof

amiodaronetherapy,withorwithoutcorticosteroidtherapy.Clinicalsymptomsoftenresolvewithinafewweeks

followedbyslowerradiologicalandlungfunctionimprovement.Somepatientscandeterioratedespitediscontinuing

CordaroneX.

Liverdisorders(Seesection4.8)

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duringtreatment.Acuteliverdisorders(includingseverehepatocellularinsufficiencyorhepaticfailure,sometimes

fatal)andchronicliverdisordersmayoccurwithoralandintravenousformswithinthefirst24hoursofIVamiodarone.

Thereforetheamiodaronedoseshouldbereducedorthetreatmentdiscontinuedifthetransaminasesincreaseexceeds

threetimesthenormalrange.Clinicalandbiologicalsignsofchronicliverdisordersduetooralamiodaronemaybe

minimal(hepatomegaly,transaminasesincreasedupto5timesthenormalrange)andreversibleafterwithdrawal,

howeverfatalcaseshavebeenreported.

Histologicalfindingsmayresemblepseudo-alcoholichepatitis,buttheycanbevariableandincludecirrhosis.

Althoughtherehavebeennoliteraturereportsonthepotentiationofhepaticadverseeffectsofalcohol,patientsshould

beadvisedtomoderatetheiralcoholintakewhiletakingCordaroneX.

Neuromusculardisorders(seesection4.8)

Amiodaronemayinduceperipheralsensorimotorneuropathyand/ormyopathy.Boththeseconditionsmaybesevere,

althoughrecoveryusuallyoccurswithinseveralmonthsafteramiodaronewithdrawal,butmaysometimesbe

incomplete.

Eyedisorders(seesection4.8)

Ifblurredordecreasedvisionoccurs,completeophthalmologicexaminationincludingfundoscopyshouldbepromptly

performed.Appearanceofopticneuopathyand/oropticneuritisrequiresamiodaronewithdrawalduetothepotential

progressiontoblindness.Unlessblurredordecreasedvisionoccurs,opthamologicalexaminationisrecommended

annually.

Druginteractions(seesection4.5)

Concomitantuseofamiodaroneisnotrecommendedwiththefollowingdrugs:beta-blockers,heartratelowering

calciumchannelinhibitors(verapamil,diltiazem),stimulantlaxativeagentswhichmaycausehypokalaemia.

Amiodaronecancauseseriousadversereactionsaffectingtheeyes,heart,lung,liver,thyroidgland,skinandperipheral

nervoussystem(seesection4.8).Becausethesereactionscanbedelayed,patientsonlong-termtherapyshouldbe

carefullysupervised.

Asundesirableeffectsareusuallydose-related,theminimumeffectivemaintenancedoseshouldbegiven.

Patientsshouldbeinstructedtoavoidexposuretosunandtouseprotectivemeasuresduringtherapyaspatientstaking

CordaroneXcanbecomeundulysensitivetosunlight,whichmaypersistafterseveralmonthsofdiscontinuationof

CordaroneX.Inmostcasessymptomsarelimitedtotingling,burninganderythemaofsun-exposedskinbutsevere

phototoxicreactionswithblisteringmaybeseen.(seesection4.8)

Monitoring(Seesection4.4and4.8)

Beforestartingamiodarone,itisrecommendedtoperformanECGandserumpotassiummeasurement.Monitoringof

transaminases(seesection4.4)andECGisrecommendedduringtreatment.

Asamiodaronemayinducehypothyroidismorhyperthyroidism,particularlyinpatientswithapersonalhistoryof

thyroiddisorders,clinicalandbiological(usTSH)monitoringshouldbeperformedbeforestartingamiodarone.This

monitoringshouldbecarriedoutduringtreatment,atsix-monthlyintervals,andforseveralmonthsfollowingits

discontinuation.Thisisparticularlyimportantintheelderly.Inpatientswhosehistoryindicatesanincreasedriskof

thyroiddysfunction,regularassessmentisrecommended.SerumusTSHlevelshouldbemeasuredwhenthyroid

dysfunctionissuspected.

Inparticularinthecontextofchronicadministrationofantiarrhythmicdrugs,casesofincreaseintheventricular

fibrillationand/orpacingthresholdofthepacemakerorimplantablecardioverterdefibrillatordevicehavebeen

reported,potentiallyaffectingitsefficacy.Therefore,arepeatedverificationofthefunctioningofthedevicebeforeand

duringamiodaronetreatmentisrecommended.

Thyroidabnormalities(seesection4.8)

Amiodaronecontainsiodineandthusmayinterferewithradio-iodineuptake.However,thyroidfunctiontests(T3,T4,

ultrasensitiveTSH(usTSH)remaininterpretable.Amiodaroneinhibitsperipheralconversionofthyroxine(T

)to

triiodothyronine(T

)andmaycauseisolatedbiochemicalchanges(increaseinserumfree-T

,freeT

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decreasedorevennormal)inclinicallyeuthyroidpatients.Thereisnoreasoninsuchcasestodiscontinueamiodarone

teatment.

Hypothyroidismshouldbesuspectedifthefollowingclinicalsignsoccur:weightgain,coldintolerance,reduced

activity,excessivebradycardia.ThediagnosisissupportedbyanincreaseinserumusTSHandanexaggeratedTSH

responsetoTRH.T

andT

levelsmaybelow.Euthyroidismisusuallyobtainedwithin3monthsfollowingthe

discontinuationoftreatment.Inlife-threateningsituations,amiodaronetherapycanbecontinued,incombinationwith

L-Thyroxine.ThedoseofL-ThyroxineisadjustedtoTSHlevels.

Anaesthesia(seeSection4.5and4.8)

Beforesurgery,theanaesthetistshouldbeinformedthatthepatientistakingamiodarone.

4.5Interactionwithothermedicinalproductsandotherformsofinteraction

Someofthemoreimportantdrugsthatinteractwithamiodaroneincludewarfarin,digoxin,phenytoinandanydrug

whichprolongstheQTinterval.

Amiodaroneraisestheplasmaconcentrationsoforalanticoagulants(warfarin)andphenytoinbyinhibitionofCYP

2C9.

Thedoseofwarfarinshouldbereducedaccordingly.Morefrequentmonitoringofprothrombintimebothduringand

afteramiodaronetreatmentisrecommended.Phenytoindosageshouldbereducedifsignsofoverdosageappear,and

plasmalevelsmaybemeasured.

AdministrationofCordaroneXtoapatientalreadyreceivingdigoxinwillbringaboutanincreaseintheplasma

digoxinconcentrationandthusprecipitatesymptomsandsignsassociatedwithhighdigoxinlevels.Clinical,ECGand

biologicalmonitoringisrecommendedanddigoxindosageusuallyhastobereduced.Asynergisticeffectonheartrate

andatrioventricularconductionisalsopossible.

CombinedtherapywiththefollowingdrugswhichprolongtheQTintervaliscontra-indicated(see4.3Contra-

indications)duetotheincreasedriskoftorsadesdepointes;forexample:

ClassIaanti-arrhythmicdrugse.g.quinidine,procainamide,disopyramide

ClassIIIanti-arrhythmicdrugse.g.sotalol,bretylium

intravenouserythromycin,co-trimoxazoleorpentamidineinjectionwhenparenterallyadministered),asthereisan

increasedriskofpotentiallylethal“torsadesdepointes”,vincamine,someneurolepticagents,cisapride

someanti-psychoticse.g.chlorpromazine,thioridazine,fluphenazine,pimozide,haloperidol,amisulpirideand

sertindole.

lithiumandtricyclicanti-depressantse.g.doxepin,maprotiline,amitriptyline

certainantihistaminese.g.terfenadine,astemizole,mizolastine

anti-malarialse.g.quinine,mefloquine,chloroquine,halofantrine.

Combinedtherapywiththefollowingdrugsisnotrecommended:

Betablockersandcertaincalciumchannelinhibitors(diltiazem,verapamil);potentiationofnegativechronotropic

propertiesandconductionslowingeffectsmayoccur.

Stimulantlaxatives,whichmaycausehypokalaemiathusincreasingtheriskoftorsadesdepointes;othertypesof

laxativesshouldbeused.

Flouroquinolonesshouldbeavoidedinpatientsreceivingamiodarone.

Cautionshouldbeexercisedovercombinedtherapywiththefollowingdrugswhichmayalsocausehypokalaemia

and/orhypomagnesaemiae.gdiuretics,systemiccorticosteroids,tetracosactrideintravenousamphotericin.

GrapefruitjuiceinhibitscytochromeP4503A4andmayincreasetheplasmaconcentrationofamiodarone.Grapefruit

juiceshouldbeavoidedduringtreatmentwithoralamiodarone.

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antiarrhythmicagentsshouldnotbegiven;pacingmaybeinstitutedandIVmagnesiummaybeused.

Cautionisadvisedinpatientsundergoinggeneralanaesthesia,orreceivinghighdoseoxygentherapy.Potentially

severecomplicationshavebeenreportedinpatientstakingamiodaroneundergoinggeneralanaesthesia:bradycardia

unresponsivetoatropine,hypotension,disturbancesofconduction,decreasedcardiacoutput.Afewcasesofadult

respiratorydistresssyndrome,mostoftenintheperiodimmediatelyaftersurgery,havebeenobserved.Apossible

interactionwithahighoxygenconcentrationmaybeimplicated.

Flecainide

AmiodaroneraisesplasmaconcentrationsofflecainidebyinhibitonofCYP2D6;thedosageofflecainideshouldbe

adjusted.

DrugsmetabolisedbycytochromeP4503A4

Whensuchdrugsareco-administeredwithamiodarone,aninhibitorofCYP3A4,thismayresultinahigherlevelof

theirplasmaconcentrations,whichmayleadtoapossibleincreaseintheirtoxicity.

Cyclosporin:combinationwithamiodaronemayincreasecyclosporinplasmalevels.Dosageshouldbeadjusted.

Fentanyl:combinationwithamiodaronemayenhancethepharmacologiceffectsoffentanylandincreasetheriskof

itstoxicity.

Statins:Theriskofmusculartoxicityisincreasedbyconcomitantadministrationofamiodaronewithstatins

metabolizedbyCYP3A4suchassimvastatin,atorvastatinandlovastatin.Itisrecommendedtouseastatinnot

metabolizedbyCYP3A4whengivenwithamiodarone.

OtherdrugsmetabolisedbyCYP3A4:lidocaine,tacrolimus,sildenafil,midazolam,triazolam,dihydroergotamine,

ergotamine.

4.6Fertility,pregnancyandlactation

Pregnancy

Inviewofitseffectonthefoetalthyroidgland,amiodaroneiscontraindicatedduringpregnancy,exceptinexceptional

circumstances.

If,becauseofthelonghalflifeofamiodarone,discontinuationofthedrugisconsideredpriortoplannedconception,

therealriskofreoccurrenceoflifethreateningarrhythmiasshouldbeweighedagainsttheunknownpossiblehazardfor

thefoetus.

Lactation

Amiodaroneisexcretedintothebreastmilkinsignificantquantitiesandbreast-feedingiscontra-indicated.

4.7Effectsonabilitytodriveandusemachines

Accordingtothesafetydataforamiodarone,thereisnoevidencethatamiodaroneimpairstheabilitytodriveavehicle

oroperatemachinery.

4.8Undesirableeffects

Thefollowingadversereactionsareclassifiedbysystemorganclassandrankedunderheadingoffrequencyusingthe

followingconvention:verycommon>=10%),common>=1%and<10%),uncommon>=0.1%and<1%),rare

>=0.01%and<0.0%),veryrare(<0.01%).

Bloodandlymphaticsystemsdisorders:

Veryrare

-haemolyticanemia

-aplasticanaemia

-thrombocytopenia

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Common:bradycardia,generallymoderateanddose-related.

Uncommon:

-onsetorworseningofarrhythmia,sometimesfollowedbycardiacarrest(seesections4.4and4.5)

-conductiondisturbances(sinoatrialblock,AVblockofvariousdegrees)(seesection4.4)

Veryrare:markedbradycardiaorsinusarrestinpatientswithsinusnodedysfunctionand/orinelderlypatients.

Endocrinedisorders(seesection4.4)

Common:

-hypothyroidism

-hyperthyroidism,sometimesfatal.

Veryrare:

-syndromeofinappropriateantidiuretichormonesecretion(SIADH).

Eyedisorders

Verycommon:cornealmicrodepositsusuallylimitedtotheareaunderthepupil,whichareusuallyonly

discernablebyslit-lampexaminations.Theymaybeassociatedwithcolouredhalosindazzlinglightorblurred

vision.Cornealmicro-depositsconsistofcomplexlipiddepositsandarereversiblefollowingdiscontinuationof

treatment.Thedepositsareconsideredessentiallybenignanddonotrequirediscontinuationofamiodarone.

Veryrare:opticneuropathy/neuritisthatmayprogresstoblindness(seesection4.4)

Gastrointestinaldisorders

Verycommon:benigngastrointestinaldisorders(nausea,vomiting,dysgeusia)usuallyoccurringwithloading

dosageandresolvingwithdosereduction.

Hepatobiliarydisorders:(seesection4.4)

Verycommon:isolatedincreaseinserumtransaminases,whichisusuallymoderate(1.5to3timesnormal

range),occurringatthebeginningoftherapy.Itmayreturntonormalwithdosereductionorevenspontaneously.

Common:acuteliverdisorderswithhighserumtransaminasesand/orjaundice,includinghepaticfailure,which

aresometimesfatal.

Veryrare:chronicliverdisease(pseudoalcoholichepatitis,cirrhosis),sometimesfatal.

Investigations:

Veryrare:increasedinbloodcreatinine.

Nervoussystemdisorders:

Common:

-Extrapyramidaltremor,forwhichregressionusuallyoccursafterreductionofdosewithdrawal

-nightmares

-sleepdisorders

Uncommon:peripheralsensorimotorneuropathyand/ormyopathy,usuallyreversibleonwithdrawalofthedrug

(seesection4.4)

Veryrare:

-cerebellarataxia,forwhichregressionusuallyoccursafterreductionofdoseorwithdrawal

-benignintracranialhypertension(pseudo-tumorcerebri)

-headache

-vertigo

Reproductivesystemandbreastdisorders

Veryrare:

-epididymo-orchitis

-impotence

Respiratory,thoracicandmediastinaldisorders:

Common:pulmonarytoxicity[hypersensitivitypneumonitis,alveolar/interstitialpneumonitisorfibrosis,

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Veryrare:

-bronchospasminpatientswithsevererespiratoryfailureandespeciallyinasthmaticpatients.

-adultacuterespiratorydistresssyndrome,sometimesfatal,mostoftenimmediatelyaftersurgery(possibleinteraction

withahighoxygenconcentration)(seesections4.4and4.5)

Pulmonaryhaemorrhage

Frequency:Notknown

Skinandsubcutaneoustissuedisorders:

Verycommon:photosensitivity(seesection4.4.2)

Common:slategreyorbluishpigmentationsoflight-exposedskin,particularlytheface,incaseofprolonged

treatmentwithhighdailydosages;suchpigmentationsslowlydisappearfollowingtreatmentdiscontinuation.

Veryrare:

-erythemaduringthecourseofradiotherapy

-skinrashes,usuallynon-specific

-exfoliativedermatitis

-alopecia

Frequencynotknown:

-urticaria.

Vasculardisorders:

Veryrare:vasculitis.

Immunesystemdisorders

Angioneuroticedema(Quincke'soedema)

(Frequency:Notknown)

4.9Overdose

Littleinformationisavailableregardingacuteoverdosagewithamiodarone.Fewcasesofsinusbradycardia,heart

block,attacksofventriculartachycardia,torsadesdepointes,circulatoryfailureandhepaticinjuryhavebeenreported.

Intheeventofoverdosetreatmentshouldbesymptomatic,gastriclavagemaybeemployedtoreduceabsorptionin

additiontogeneralsupportivemeasures.Thepatientshouldbemonitoredandifbradycardiaoccursbeta-

adrenostimulantsorglucagonmaybegiven.

Spontaneouslyresolvingattacksofventriculartachycardiamayalsooccur.Duetothepharmacokineticsofamiodarone,

adequateandprolongedsurveillanceofthepatient,particularlycardiacstatus,isrecommended.

Neitheramiodaronenoritsmetabolitesaredialysable.

5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

ATCcode:CO1BD01

Pharmacotherapeuticgroup:Antiarrhythmics,ClassIII

Amiodaroneshowssinoatrial,atrialandnodalconductionandincreasestherefractoryperiodattheatrial,nodaland

ventricularlevelsbutdoesnotalterintraventricularconduction.Thereisalsoslowinginconductionandprolongation

ofrefractoryperiodsinaccessoryatrioventricularpathways.Amiodaronehasanti-adrenergic(non-competitivealpha

andbetablocker)effects.Itinhibitsthemetabolicandbiochemicaleffectsofcatecholaminesontheheartandinhibits

andK +

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Amiodaronehasanti-ischaemicandhaemodynamiceffects.Itcausesamoderatedropinperipheralresistanceand

decreaseinheartrateleadingtoareductioninoxygenintake.Itcausesanincreaseincoronaryoutputduetoadirect

effectonthesmoothmuscleofthemyocardialarteries.Cardiacouputismaintainedduetoadecreaseinaorticpressure

andperipheralresistance.

Aunivariateanalysis(EMIAT)suggestedthatall-causemortalityisreducedonamiodaronetreatmentinpatientswith

ejectionfractionlessthan30%,witharrhythmiaontheinitialHolter,onbeta-blockertreatment,andwithanincreased

initialheartrate.

5.2Pharmacokineticproperties

Followingoraladministrationabsorptionisslowandvariablewithanapproximatemeanof50%,andmaybe

prolongedduetoenterohepaticcycling.Followingsingleadministration,peakplasmaconcentrationsarereachedafter

3-7hours.

Therapeuticeffectsareusuallyobservedafteroneweek(fromafewdaystotwoweeksdependingontheloading

dose).Duetotheabovecharacteristics,loadingdosesshouldbeusedinordertoobtainrapidlythetissuelevels

necessarytohaveatherapeuticeffect.

Amiodaronehasalargebutvariablevolumeofdistributionbecauseofextensiveaccumulationinvarioussites(adipose

tissue,highlyperfusedorganssuchastheliver,lungandspleen).Amiodaroneishighlyproteinbound(>95%).

Themajormetaboliteisdesethylamiodarone.Amiodaronehasalonghalf-lifeandshowconsiderableindividual

variability(from20to100days).Duringthefirstdaysoftherapy,thedrugaccumulatesinalmostalltissues,

especiallytheadiposetissue.Eliminationoccursafterafewdaysandsteady-stateplasmaconcentrationisreached

betweenoneandseveralmonthsdependingupontheindividualpatient.

Renalexcretionisminimal;excretionismainlyviathebileandthefaeces.

Aftertreatmentdiscontinuation,theeliminationcontinuesoverseveralmonths;thepersistenceofapharmacodynamic

effectover10daystoonemonthshouldbetakenintoaccount.

5.3Preclinicalsafetydata

Therearenopreclinicaldataofrelevancetotheprescriberwhichareadditionaltothatalreadyincludedinother

sectionsoftheSPC.

6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

Lactosemonohydrate

Maizestarch

Povidone

Colloidalanhydroussilica

Magnesiumstearate

6.2Incompatibilities

Notapplicable.

6.3ShelfLife

Theshelf-lifeexpirydateofthisproductshallbethedateshownonthecontainerandouterpackageoftheproducton

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6.4Specialprecautionsforstorage

Donotstoreabove25°C.

Storeintheoriginalpackage.

6.5Natureandcontentsofcontainer

Blisterpacksof30and60tabletsinanoverlabelledoutercarton.

Notallpacksizesmaybemarketed.

6.6Specialprecautionsfordisposalofausedmedicinalproductorwastematerialsderivedfrom

suchmedicinalproductandotherhandlingoftheproduct

Nospecialrequirements.

7PARALLELPRODUCTAUTHORISATIONHOLDER

PCOManufacturing

Unit10,AshbourneBusinessPark

Rath

Ashbourne

Co.Meath

Ireland

8PARALLELPRODUCTAUTHORISATIONNUMBER

PPA0465/119/001

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

Dateoffirstauthorizations:05March2004

Dateoflastrenewal:05March2009

10DATEOFREVISIONOFTHETEXT

Irish Medicines Board

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Date Printed 14/04/2011 CRN 2091269 page number: 10