AMIODARONE

Main information

  • Trade name:
  • AMIODARONE Tablets 100 Milligram
  • Dosage:
  • 100 Milligram
  • Pharmaceutical form:
  • Tablets
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug

Documents

Localization

  • Available in:
  • AMIODARONE Tablets 100 Milligram
    Ireland
  • Language:
  • English

Status

  • Source:
  • HPRA - Health Products Regulatory Authority - Ireland
  • Authorization number:
  • PA1046/003/001
  • Authorization date:
  • 17-10-2000
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

PartII

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

AmiodaroneHydrochloride100mgTablets

2QUALITATIVEANDQUANTITATIVECOMPOSITION

Eachtabletcontains100mgamiodaronehydrochloride.

Forexcipients,seesection6.1.

3PHARMACEUTICALFORM

Tablet

Whitetooffwhitecircular,biconvextabletengraved100withactionpotentialononesideandscoredonthereverse.

4CLINICALPARTICULARS

4.1TherapeuticIndications

Treatmentshouldbeinitiatedandnormallymonitoredonlyunderhospitalorspecialistsupervision.Amiodaroneis

indicatedforthetreatmentofsevererhythmdisordersonlywhennotrespondingtoothertherapiesorwhenother

treatmentscannotbeused.

TachyarrhythmiasassociatedwithWolff-Parkinson-Whitesyndrome.

Atrialflutterandfibrillationwhenotherdrugscannotbeused.

Alltypesoftachyarrhythmiasincludingsupraventricular,nodalandventriculartachycardias,ventricularfibrillation,

whenotherdrugscannotbeused.

Amiodaroneisindicatedforthepreventionofventriculararrhythmiasinhigh-riskpatientsfollowingmyocardial

infarctionorinpatientswithclinicalsignsofcongestivecardiacfailureand/orLeftVentricularEjectionFraction

(LVEF)lessthan40%whoarereceivingappropriatecardiacfailuretreatmentwhichincludesAngiotensinConverting

Enzyme(ACE)-inhibitors.Theminimumeffectivedosemustbeusedandtreatmentmustbeinitiatedandusedonly

underhospital/specialistsupervision.

4.2Posologyandmethodofadministration

AmiodaroneTabletsarefororaladministration.

Adults

Itisparticularlyimportantthattheminimumeffectivedosebeused.Inallcasesthepatient’smanagementmustbe

judgedontheindividualresponseandwellbeing.Thefollowingdosageregimenisgenerallyeffective.

InitialStabilisation

Treatmentshouldbestartedwith200mg,threetimesadayandmaybecontinuedfor1week.Thedosageshouldthen

bereducedto200mg,twicedailyforafurtherweek.

Maintenance

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requireahighermaintenancedose.Thescored100mgtabletshouldbeusedtotitratetheminimumdosagerequiredto

maintaincontrolofthearrhythmia.Themaintenancedoseshouldberegularlyreviewed,especiallywherethisexceeds

200mgdaily.

GeneralConsiderations

Initialdosing

Ahighdoseisneededinordertoachieveadequatetissuelevelsrapidly.

Maintenance

Toohighadoseduringmaintenancetherapycancausesideeffectswhicharebelievedtoberelatedtohightissuelevels

ofamiodaroneanditsmetabolites.

Amiodaroneisstronglyproteinboundandhasanaverageplasmahalf-lifeof50days(reportedrange20-100days).It

followsthatsufficienttimemustbeallowedforanewdistributionequilibriumtobeachievedbetweenadjustmentsof

dosage.Inpatientswithpotentiallylethalarrhythmiasthelonghalflifeisavaluablesafeguardasomissionof

occasionaldosesdoesnotsignificantlyinfluencetheoveralltherapeuticeffect.

Itisparticularlyimportantthattheminimumeffectivedosageisusedandthepatientismonitoredregularlytodetect

theclinicalfeaturesofexcessamiodaronedosage.Therapymaythenbeadjustedaccordingly.

Dosagereduction/withdrawal

Sideeffectsslowlydisappearasthetissuelevelsfall.Followingdrugwithdrawal,residualtissue-boundamiodarone

mayprotectthepatientforuptoamonth.However,thelikelihoodofrecurrenceofarrhythmiaduringthisperiod

shouldbeconsidered.

Elderly

Aswithallpatientsitisimportantthattheminimumeffectivedoseisused.Whilstthereisnoevidencethatdosage

requirementsaredifferentforthisgroupofpatientstheymaybemoresusceptibletobradycardiaandconduction

defectsiftoohighadoseisemployed.Particularattentionshouldbepaidtomonitoringthyroidfunction.(Seesections

4.3,4.4and4.8).

4.3Contraindications

Sinusbradycardiaandsino-atrialheartblock.Inpatientswithsevereconductiondisturbances(highgradeAVblock,

bifascicularortrifascicularblock)orsinusnodedisease,amiodaroneshouldbeusedonlyinconjunctionwitha

pacemaker.

Evidenceorhistoryofthyroiddysfunction.

Knownhypersensitivitytoiodineortoamiodarone,ortoanyoftheexcipients.(One100mgtabletscontain

approximately37.5mgiodine).

ConcomitantadministrationofamiodaronewithdrugswhichmayinduceTorsadesdePointes(seesection4.5).

Pregnancy,exceptinexceptionalcircumstances(seesection4.6).

Lactation(seesection4.6).

4.4Specialwarningsandprecautionsforuse

Patientswithrarehereditaryproblemsofgalactoseintolerance,theLapplactasedeficiencyofglucose-galactose

malabsorptionshouldnottakethismedicine.

Paediatricpatients:

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Cardiacdisorders(seesection4.8):

Toohighadosagemayleadtoseverebradycardiaandtoconductiondisturbanceswiththeappearanceofan

idioventricularrhythm,particularlyinelderlypatientsorduringdigitalistherapy.Inthesecircumstances,amiodarone

treatmentshouldbewithdrawn.Ifnecessarybeta-adrenostimulantsorglucagonmaybegiven.Becauseofthelonghalf-

lifeofamiodarone,ifbradycardiaissevereandsymptomatictheinsertionofapacemakershouldbeconsidered.

ThepharmacologicalactionofamiodaroneinducesECGchanges:QTprolongation(relatedtoprolonged

repolarisation)withthepossibledevelopmentofU-wavesanddeformedT-waves;thesechangesdonotreflecttoxicity.

Intheelderly,heartratemaydecreasemarkedly.

Treatmentshouldbediscontinuedincaseofonsetof2 nd

and3 rd

degreeA-Vblock,sino-atrialblockorbifascicular

block.

Amiodaronehasalowpro-arrhythmiceffect.Onsetsofnewarrhythmiasorworseningoftreatedarrhythmias,

sometimesfatal,havebeenreported.Itisimportant,butdifficult,todifferentiatealackofefficacyofthedrugfroma

proarrhythmiceffect,whetherornotthisisassociatedwithaworseningofthecardiaccondition.Proarrhythmiceffects

generallyoccurinthecontextofdruginteractionsand/orelectrolyticdisorders(seesections4.5and4.8).

Hyperthyroidism(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

normalisationofthyroidfunctiontests.

Coursesofanti-thyroiddrugshavebeenusedforthetreatmentofseverethyroidhyperactivity;largedosesmaybe

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

prednisolone)mayberequiredforseveralweeks.

Pulmonarydisorders(seesection4.8):

Onsetofdyspnoeaornon-productivecoughmayberelatedtopulmonarytoxicity(hypersensitivitypneumonitis,

alveolar/interstitialpneumonitisorfibrosis,pleuritis,bronchiolitisobliteransorganisingpneumonitis).Presenting

featurescanincludedyspnoea(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

amiodarone.

Liverdisorders(seesection4.8):

Amiodaronemaybeassociatedwithavarietyofhepaticeffects,includingcirrhosis,hepatitis,jaundiceandhepatic

failure.Somefatalitieshavebeenreported,mainlyfollowinglong-termtherapy,althoughrarelytheyhaveoccurred

soonafterstartingtreatmentparticularlyafterintravenousamiodarone.Itisadvisabletomonitorliverfunction

particularlytransaminasesbeforetreatmentandsixmonthlythereafter.

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occur.Thesemayreturntonormalwithdosereduction,orsometimesspontaneously.

Isolatedcasesofacuteliverdisorderswithelevatedserumtransaminasesand/orjaundicemayoccur;insuchcases

treatmentshouldbediscontinued.

Therehavebeenreportsofchronicliverdisease.Alterationoflaboratorytestswhichmaybeminimal(transaminases

elevated1.5to5timesnormal)orclinicalsigns(possiblehepatomegaly)duringtreatmentforlongerthan6months

shouldsuggestthisdiagnosis.Routinemonitoringofliverfunctiontestsisthereforeadvised.Abnormalclinicaland

laboratorytestresultsusuallyregressuponcessationoftreatment,butfatalcaseshavebeenreported.Histological

findingsmayresemblepseudo-alcoholichepatitis,buttheycanbevariableandincludecirrhosis.

Althoughtherehavebeennoliteraturereportsonthepotentiationofhepaticadverseeffectsofalcohol,patientsshould

beadvisedtomoderatetheiralcoholintakewhiletakingamiodarone.

Neuromusculardisorders(seesection4.8):

Amiodaronemayinduceperipheralsensorimotorneuropathyand/ormyopathy.Boththeseconditionsmaybesevere,

althoughrecoveryusuallyoccurswithinseveralmonthsafteramiodaronewithdrawal,butmaysometimesbe

incomplete.

Eyedisorders(seesection4.8):

Ifblurredordecreasedvisionoccurs,completeophthalmologicexaminationincludingfundoscopyshouldbepromptly

performed.Appearanceofopticneuropathyand/oropticneuritisrequiresamiodaronewithdrawalduetothepotential

progressiontoblindness.Unlessblurredordecreasedvisionoccurs,ophthalmologicalexaminationisrecommended

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,theminimumeffectivemaintenancedoseshould

begiven.

Patientsshouldbeinstructedtoavoidexposuretosunandtouseprotectivemeasuresduringtherapyaspatientstaking

amiodaronecanbecomeundulysensitivetosunlight,whichmaypersistafterseveralmonthsofdiscontinuationof

amiodarone.Inmostcasessymptomsarelimitedtotingling,burninganderythemaofsun-exposedskinbutsevere

phototoxicreactionswithblisteringmaybeseen.(seesection4.8).

Monitoring(seesections4.4and4.8):

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.

Thyroidabnormalities(seesection4.8):

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

free-T4,usTSH)remaininterpretable.Amiodaroneinhibitsperipheralconversionofthyroxine(T4)totriiodothyronine

(T3)andmaycauseisolatedbiochemicalchanges(increaseinserumfree-T4,free-T3beingslightlydecreasedoreven

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Hypothyroidismshouldbesuspectedifthefollowingclinicalsignsoccur:weightgain,coldintolerance,reduced

activity,excessivebradycardia.ThediagnosisissupportedbyanincreaseinserumusTSHandanexaggeratedTSH

responsetoTRH.T3andT4levelsmaybelow.Euthyroidismisusuallyobtainedwithin3monthsfollowingthe

discontinuationoftreatment.Inlife-threateningsituations,amiodaronetherapycanbecontinued,incombinationwith

L-Thyroxine.ThedoseofL-ThyroxineisadjustedaccordingtoTSHlevels.

Anaesthesia(seesections4.5and4.8):

Beforesurgery,theanaesthetistshouldbeinformedthatthepatientistakingamiodarone.

4.5Interactionwithothermedicinalproductsandotherformsofinteraction

Someofthemoreimportantdrugsthatinteractwithamiodaroneincludewarfarin,digoxin,phenytoinandanydrug

whichprolongstheQTinterval.

Amiodaroneraisestheplasmaconcentrationsoforalanticoagulants(warfarin)andphenytoinbyinhibitionofCYP

2C9.Thedoseofwarfarinshouldbereducedaccordingly.Morefrequentmonitoringofprothrombintimebothduring

andafteramiodaronetreatmentisrecommended.Phenytoindosageshouldbereducedifsignsofoverdosageappear,

andplasmalevelsmaybemeasured.

Administrationofamiodaronetoapatientalreadyreceivingdigoxinwillbringaboutanincreaseintheplasmadigoxin

concentrationandthusprecipitatesymptomsandsingsassociatedwithhighdigoxinlevels.Clinical,ECGand

biologicalmonitoringisrecommendedanddigoxindosageusuallyhastobereduced.Asynergisticeffectonheartrate

andatrioventricularconductionisalsopossible.

CombinedtherapywiththefollowingdrugswhichprolongtheQTintervalincontra-indicated(seesection4.3)dueto

theincreasedriskofTorsadedePointes;forexample:

ClassIaanti-arrhythmicdrugse.g.quinidine,procainamide,disopyramide.

ClassIIIanti-arrhythmicdrugse.g.sotalol,bretylium.

Intravenouserythromycin,co-trimoxazoleorpentamidineinjection.

Someanti-psychoticse.g.chlorpromazine,thioridazine,fluphenazine,pimozide,haloperidol,amisulprideand

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.

Cautionshouldbeexercisedovercombinedtherapywiththefollowingdrugswhichmaycausehypokalaemiaand/or

hypomagnesaemiae.g.diuretics,systemiccorticosteroids,tetracosactide,intravenousamphotericin.

Incasesofhypokalaemia,correctiveactionshouldbetakenandQTintervalmonitored.IncaseifTorsadedePointes,

antiarrhythmicagentsshouldnotbegiven;pacingmaybeinstitutedandIVmagnesiummaybeused.

Cautionisadvisedinpatientsundergoinggeneralanaesthesia,orreceivinghighdoseoxygentherapy.Potentially

severecomplicationshavebeenreportedinpatientstakingamiodaroneundergoinggeneralanaesthesia:bradycardia

unresponsivetoatropine,hypotension,disturbancesofconduction,decreasedcardiacoutput.Afewcasesofadult

respiratorydistresssyndromemostoftenintheperiodimmediatelyaftersurgeryhavebeenobserved.Apossible

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Flecainide

AmiodaroneraisesplasmaconcentrationsofflecainidebyinhibitionofCYP2D6;thedosageofflecainideshouldbe

adjusted.

DrugsmetabolisedbycytochromeP4503A4

Whensuchdrugsareco-administeredwithamiodarone,aninhibitorofCYP3A4,thismayresultinahigherlevelof

theirplasmaconcentrations,whichmayleadtoapossibleincreaseintheirtoxicity.

Ciclosporin:combinationwithamiodaronemayincreaseciclosporinplasmalevels.Dosageshouldbeadjusted.

Fentanyl:combinationwithamiodaronemayenhancethepharmacologiceffectsoffentanylandincreasetherisk

ofitstoxicity.

OtherdrugsmetabolisedbyCYP3A4:lidocaine,tacrolimus,sildenafil,midazolam,ergotamine;simvastatinand

otherstatinsmetabolisedbyCYP3A4(increasedriskofmusculartoxicity).

4.6Pregnancyandlactation

Pregnancy

Inviewofitseffectonthefoetalthyroidgland,amiodaroneiscontraindicatedduringpregnancy,exceptinexceptional

circumstances.

If,becauseofthelonghalflifeofamiodarone,discontinuationofthedrugisconsideredpriortoplannedconception,

therealriskofrecurrenceoflifethreateningarrhythmiasshouldbeweighedagainsttheunknownpossiblehazardfor

thefoetus.

Lactation

Amiodaroneisexcretedintothebreastmilkinsignificantquantitiesandbreast-feedingiscontraindicated.

4.7Effectsonabilitytodriveandusemachines

Accordingtothesafetydataforamiodarone,thereisnoevidencethatamiodaroneimpairstheabilitytodriveavehicle

oroperatemachinery.

4.8Undesirableeffects

Thefollowingadversereactionsareclassifiedbysystemorganclassandrankedunderheadingoffrequencyusingthe

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

(>=0.01%and<0.1%),veryrare(<0.01%).

Bloodandlymphaticsystemdisorders:

Veryrare

Haemolyticanemia.

Aplasticanaemia.

Thrombocytopenia.

Cardiacdisorders:

Common:bradycardia,generallymoderateanddose-related.

Uncommon:

Onsetorworseningofarrhythmia,sometimesfollowedbycardiacarrest(seesections4.4and4.5.).

Conductiondisturbances(sinoatrialblock,AVblockofvariousdegrees)(seesection4.4).

Veryrare:markedbradycardiaorsinusarrestinpatientswithsinusnodedysfunctionand/orinelderlypatients.

Endocrinedisorders(seesection4.4):

Common:

Hypothyroidism.

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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.

Hepato-biliarydisorders:(seesection4.4.).

Verycommon:isolatedincreaseinserumtransaminases,whichisusuallymoderate(1.5to3timesnormalrange),

occurringatthebeginningoftherapy.Itmayreturntonormalwithdosereductionorevenspontaneously.

Common:acuteliverdisorderswithhighserumtransaminasesand/orjaundice,includinghepaticfailure,which

aresometimesfatal

Veryrare:chronicliverdisease(pseudoalcoholichepatitis,cirrhosis),sometimesfatal.

Investigations:

Veryrare:increasedinbloodcreatinine.

Nervoussystemdisorders:

Common:

Extrapyramidaltremor,forwhichregressionusuallyoccursafterreductionofdoseorwithdrawal.

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,pleuritis,

bronchiolitisobliteransorganisingpneumonia(BOOP)],sometimesfatal(seesection4.4).

Veryrare:

Bronchospasminpatientswithsevererespiratoryfailureandespeciallyinasthmaticpatients.

Adultacuterespiratorydistresssyndrome,sometimesfatal,mostoftenimmediatelyaftersurgery(possible

interactionwithahighoxygenconcentration)(seesections4.4.and4.5).

Skinandsubcutaneoustissuedisorders:

Verycommon:photosensitivity(seesection4.4),

Common:slategreyorbluishpigmentationsoflight-exposedskin,particularlytheface,incaseofprolonged

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Veryrare:

Erythemaduringthecourseofradiotherapy.

Skinrashes,usuallynon-specific.

Exfoliativedermatitis.

Alopecia.

Vasculardisorders:

Veryrare:vasculitis.

4.9Overdose

Littleinformationisavailableregardingacuteoverdosagewithamiodarone.Fewcasesofsinusbradycardia,heart

block,attacksofventriculartachycardia,TorsadesdePointes,circulatoryfailureandhepaticinjuryhavebeenreported.

Intheeventofoverdosetreatmentshouldbesymptomatic,gastriclavagemaybeemployedtoreduceabsorptionin

additiontogeneralsupportivemeasures.Thepatientshouldbemonitoredandifbradycardiaensues,beta-

adrenostimulantsorglucagonmaybegiven.

Spontaneouslyresolvingattacksofventriculartachycardiamayalsooccur.Duetothepharmacokineticsofamiodarone,

adequateandprolongedsurveillanceofthepatient,particularlycardiacstatus,isrecommended.

Neitheramiodaroneoritsmetabolitesisdialysable.

5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

ATCcode:CO1BD01.

Pharmacotherapeuticgroup:Antiarrhythmics,ClassIII.

Amiodaroneslowssinoatrial,atrialandnodalconductionandincreasestherefractoryperiodattheatrial,nodaland

ventricularlevelsbutdoesnotalterintraventricularconduction.Thereisalsoslowinginconductionandprolongation

ofrefractoryperiodsinaccessoryatrioventricularpathways.

Amiodaronehasanti-adrenergic(non-competitivealphaandbetablocker)effects.Itinhibitsthemetabolicand

biochemicaleffectsofcatecholaminesontheheartandinhibitsNa +

andK +

activatedATP-ase.

Amiodaronehasanti-ischaemicandhaemodynamiceffects.Itcausesamoderatedropinperipheralresistanceand

decreaseinheartrateleadingtoareductioninoxygenintake.Itcausesanincreaseincoronaryoutputduetoadirect

effectonthesmoothmuscleofthemyocardialarteries.Cardiacoutputismaintainedduetoadecreaseinaortic

pressureandperipheralresistance.

Aunivariateanalysis(EMIAT)suggestedthatall-causemortalityisreducedonamiodaronetreatmentinpatientswith

anejectionfractionlessthan30%,witharrhythmiaontheinitialHolter,onbeta-blockertreatment,andwithan

increasedinitialheartrate.

5.2Pharmacokineticproperties

Followingoraladministrationabsorptionisslowandvariablewithanapproximatemeanof50%,andmaybe

prolongedduetoenterohepaticcycling.Followingsingleadministration,peakplasmaconcentrationsarereachedafter

3-7hours.Therapeuticeffectsareusuallyobservedafteroneweek(fromafewdaystotwoweeksdependingonthe

loadingdose).Duetotheabovecharacteristics,loadingdosesshouldbeusedinordertoobtainrapidlythetissuelevels

necessarytohaveatherapeuticeffect.

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

Themajormetaboliteisdesethylamiodarone.Amiodaronehasalonghalf-lifeandshowsconsiderableindividual

variability(from20to100days).Duringthefirstdaysoftherapy,thedrugaccumulatesinalmostalltissues,especially

theadiposetissue.Eliminationoccursafterafewdaysandsteady-stateplasmaconcentrationisreachedbetweenone

andseveralmonthsdependingupontheindividualpatient.

Renalexcretionisminimal;excretionismainlyviathebileandthefaeces.

Aftertreatmentdiscontinuation,theeliminationcontinuesoverseveralmonths;thepersistenceofapharmacodynamic

effectover10daystoonemonthshouldbetakenintoaccount.

5.3Preclinicalsafetydata

Therearenopreclinicaldataofrelevancetotheprescriberwhichareadditionaltothatalreadyincludedinother

sectionsoftheSPC.

6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

Lactosemonohydrate

Maizestarch

Povidone

Colloidalanhydroussilica

Magnesiumstearate

6.2Incompatibilities

Notapplicable.

6.3ShelfLife

5years.

6.4Specialprecautionsforstorage

Storeintheoriginalpackage.

6.5Natureandcontentsofcontainer

AmiodaroneHydrochlorideTablets100mgaresuppliedinPVC/aluminiumblisterpacksof28and30tabletspackedin

cardboardcartons.

6.6Specialprecautionsfordisposalofausedmedicinalproductorwastematerialsderivedfrom

suchmedicinalproductandotherhandlingoftheproduct

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7MARKETINGAUTHORISATIONHOLDER

WinthropPharmaceuticalsUKLimited

OneOnslowStreet

Guildford

SurreyGU14YS

T/A:

WinthropPharmaceuticalsUKLimited

POBox611

Guildford

SurreyGU14YS

UnitedKingdom

8MARKETINGAUTHORISATIONNUMBER

PA1046/3/1

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

Dateoffirstauthorisation:17October1995

Dateoflastrenewal:17October2005

10DATEOFREVISIONOFTHETEXT

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