ARYTHMOL 300MG FILM-COATED TABLETS.

Main information

  • Trade name:
  • ARYTHMOL 300MG FILM-COATED TABLETS.
  • Dosage:
  • 300 Milligram
  • Pharmaceutical form:
  • Film Coated Tablet
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug

Documents

Localization

  • Available in:
  • ARYTHMOL 300MG FILM-COATED TABLETS.
    Ireland
  • Language:
  • English

Status

  • Source:
  • HPRA - Health Products Regulatory Authority - Ireland
  • Authorization number:
  • PA0038/079/003
  • Authorization date:
  • 20-07-1998
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

IRISHMEDICINESBOARDACT1995,asamended

MedicinalProducts(ControlofPlacingontheMarket)Regulations,2007,asamended

PA0038/079/003

CaseNo:2076590

TheIrishMedicinesBoardinexerciseofthepowersconferredonitbytheabovementionedRegulationsherebygrantsto

AbbottLaboratoriesIrelandLtd

4051KingswoodDrive,CitywestBusinessCampus,Dublin24,Ireland

anauthorisation,subjecttotheprovisionsofthesaidRegulations,inrespectoftheproduct

Arythmol300mgFilm-coatedTablets.

theparticularsofwhicharesetoutintheattachedSchedule.Theauthorisationisalsosubjecttothegeneralconditionsasmaybespecifiedin

thesaidRegulationsaslistedonthereverseofthisdocument.

Thisauthorisation,unlesspreviouslyrevoked,shallcontinueinforcefrom24/02/2010.

SignedonbehalfoftheIrishMedicinesBoardthis

________________

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Date Printed 25/06/2010 CRN 2076590 page number: 1

PartII

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

Arythmol300mgFilm-coatedTablets.

2QUALITATIVEANDQUANTITATIVECOMPOSITION

Eachtabletcontains300mgpropafenonehydrochloride.

Forafulllistofexcipientsseesection6.1.

3PHARMACEUTICALFORM

Film-coatedtablets.

White,biconvex,film-coatedtabletsandembossed“300”ononeface.

4CLINICALPARTICULARS

4.1TherapeuticIndications

Symptomaticsupraventriculartachyarrhythmiaswarrantingtreatment,suchasAVjunctionaltachycardias,

supraventriculartachycardiasinpatientswithWPWsyndromeorparoxysmalatrialfibrillation.

Serioussymptomaticventriculartachyarrhythmiasiflife-threateningornecessitatingtreatmentinthejudgementofthe

physician.

4.2Posologyandmethodofadministration

Thetabletsshouldbeswallowedwholeandtakenwithadrinkafterfood.Thedosageshouldbeadjustedtothe

individualpatient’srequirements.InthosepatientsinwhomsignificantwideningoftheQRScomplexorsecondor

thirdAVblockoccurs,adosereductionshouldbeconsidered.

Adults:Adailydoseof450to600mgofpropafenonehydrochloride,dividedintwoorthreedosesperday,is

recommendedinthetitratedperiodandformaintenancetherapyinpatientsweighingaround70kilograms.

Occasionally,itmaybenecessarytoincreasethedailydoseto900mgofpropafenonehydrochloride.Thedailydose

shouldbereducedaccordinglyforpatientswithalowerbodyweight.Doseincreasesshouldnotbeattempteduntilthe

patientisreceivingtreatmentforthreetofourdays.

TheindividualmaintenancedoseshouldbedeterminedundercardiologicalsurveillanceincludingECGmonitoringand

repeatedbloodpressurecontrol(titrationphase).

Elderly:Inelderlypatientsorpatientswithrelevantimpairmentofventricularfunction(leftventricularejection

fractionlessthan35%)orstructuralmyocardialdisease,treatmentshouldbeinitiatedgraduallyandwithparticular

cautioninsmallincrementaldoses.Thesameappliestomaintenancetherapy.Anydoseincreasesthatmaybe

requiredshouldnotbeundertakenuntilafterfivetoeightdaysoftherapy.

Inpatientswhoseliverand/orkidneyfunctionisimpaired,theremaybedrugaccumulationafterthestandard

therapeuticdoses.Nonetheless,patientswiththeseconditionscanstillbetitratedonpropafenonehydrochlorideunder

ECGandplasmalevelmonitoring.

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4.3Contraindications

Knownhypersensitivitytopropafenoneortoanyoftheotheringredients.

Significantstructuralheartdiseasesuchas:

Uncontrolledcongestiveheartfailurewhereleftventricularoutputislessthan35%.

Cardiogenicshock,unlessthisiscausedbyarrhythmia.

Severesymptomaticbradycardia.

Thepresenceofsinusnodedysfunction,atrialconductiondefects,seconddegreeorgreateratrioventricularblockor

bundlebranchblockordistalblockintheabsenceofanartificialpacemaker.

Severehypotension.

Manifestelectrolyteimbalance(e.g.potassiummetabolismdisorders).

Severeobstructivepulmonarydisease.

4.4Specialwarningsandprecautionsforuse

IfisessentialthateachpatientgivenpropafenonehydrochlorideIRbeevaluatedelectrocardiographicallyandclinically

priortoandduringtherapytodeterminewhethertheresponsetopropafenonehydrochlorideIRsupportscontinued

treatment.

PropafenonehydrochlorideIRmayworsenmyastheniagravis.

Propafenonehydrochloridetreatmentmayaffectboththepacingandsensingthresholdsofartificialpacemakers.

Pacemakerfunctionshouldthereforebecheckedand,ifnecessary,reprogrammed.

Thereispotentialforconversionofparoxysmalatrialfibrillationtoatrialflutterwithaccompany2:1or1:1conduction

block.Aswithotherclass1Canti-arrhythmicagents,patientswithsignificantstructuralheartdiseasemaybe

predisposedtoseriousadverseeffects.

Becauseofthebeta-blockereffect,careshouldbetakeninthetreatmentofpatientswithasthma.

4.5Interactionwithothermedicinalproductsandotherformsofinteraction

ApossiblepotentiationofdrugsideeffectsmayoccurwhenpropafenonehydrochlorideIRistakeninconjunctionwith

localanaesthetics(e.g.pacemakerimplantation,surgeryordentalwork)andotherdrugswhichmayhaveaninhibitory

effectontheheartrateand/ormyocardialcontractility(e.g.betablockers,tricyclicantidepressants).

Co-administrationofpropafenonehydrochloridewithdrugsmetabolisedbyCYP2D6(suchasvenlafaxine)mightlead

toincreasedlevelsofthesedrugs.Increaseinpropranolol,metoprolol,desipramine,cyclosporin,theophyllineand

digoxinplasmalevelsorbloodlevelshavebeenreportedduringpropafenonehydrochloridetherapy.

DrugsthatinhibitCYP2D6,CYP1A2andCYP3A4e.g.ketoconazole,cimetidine,quinidine,erythromycinand

grapefruitjuicemightleadtoincreasedlevelsofpropafenonehydrochloride.Whenpropafenonehydrochlorideis

administeredwithinhibitorsoftheseenzymes,thepatientsshouldbecloselymonitoredandthedoseadjusted

accordingly.

Duetothepotentialforincreasedplasmaconcentrations,co-administrationof800-1200mg/daydosesofritonavirand

propafenonehydrochlorideiscontraindicated.

Combinationtherapyofamiodaroneandpropafenonehydrochloridecanaffectconductionandrepolarisationandlead

toabnormalitiesthathavethepotentialtobeproarrhythmic.Doseadjustmentsofbothcompoundsbasedon

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Nosignificanteffectsonthepharmacokineticsofpropafenoneorlidocainehavebeenseenfollowingtheirconcomitant

useinpatients.However,concomitantuseofpropafenonehydrochlorideandintravenouslidocainehavebeenreported

toincreasetheriskofcentralnervoussideeffectsoflidocaine.

PhenobarbitalisaknowninducerofCYP3A4.Responsetopropafenonehydrochloridetherapyshouldbemonitored

duringconcomitantchronicphenobarbitaluse.

Concomitantuseofpropafenonehydrochlorideandrifampicinmayreducetheanti-arrhythmicefficacyofpropafenone

hydrochlorideastheresultofareductioninthepropafenoneplasmalevels.

Closemonitoringoftheclottingstatusinpatientsreceivingoralanti-coagulants(e.g.Phenoprocoumon,warfarin)is

recommendedaspropafenonehydrochloridemayenhancetheefficacyofthedrugsresultinginanincreased

prothrombintime.

ConcomitantadministrationofpropafenonehydrochlorideandfluoxetineinextensivemetabolisersincreaseintheS

propafenoneC

andAUCby39and50%andtheRpropafenoneC

andAUCby71and50%.Elevatedlevelsof

plasmapropafenonemayoccurwhenpropafenonehydrochlorideisusedconcomitantlywithparoxetine.Lowerdoses

ofpropafenonemaybesufficienttoachievethedesiredtherapeuticresponse.

Cautionshouldbetakenwithregardstodigitalistoxicity.

4.6Pregnancyandlactation

Pregnancy

PropafenonehydrochlorideIRshouldbeusedduringpregnancyonlyifthepotentialbenefitjustifiesthepotentialrisk

tothefetus.Propafenonehydrochlorideisknowntopasstheplacentalbarrierinhumans.Theconcentrationof

propafenoneintheumbilicalcordhasbeenreportedtobeabout30%ofthatofthematernalblood.

Animalstudieshavenotshownanyteratogeniceffects,butthereisnotexperienceoftheuseofthedruginhuman

pregnancy.

Lactation

Excretionofpropafenoneinbreastmilkhasnotbeenstudied.Limiteddatasuggeststhatpropafenonemaybeexcreted

inbreastmilk.Propafenonehydrochlorideshouldbeusedwithcautioninnursingmothers.

4.7Effectsonabilitytodriveandusemachines

Blurredvision,dizziness,fatigueandposturalhypotensionmayaffectthepatient’sspeedofreactionandimpairthe

individual’sabilitytooperatemachineryormotorvehicles.

4.8Undesirableeffects

Thefollowingadverseeventshavebeenreportedwiththisorotherformulationsofpropafenonehydrochloride.A

causeandeffectrelationshipmaynothavebeenestablished.

BodySystem PreferredTerm

Bloodandlymphaticsystem

disorders Isolatedcaseofleukocytopeniaand/orgranulocytopeniaor

thrombocytopenia;agranulocytosishavebeenreported.

Immunesystemdisorders Allergicreactions.

Metabolismandnutritional

disorders Anorexia.

Psychiatricdisorders Anxiety,confusioncanoccurrarely.

Nervoussystemdisorders Dizziness,headache,syncope,ataxiaandparesthesia.

Veryrarely,restlessness,nightmares,sleepdisordersand

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4.9Overdose

Symptoms

Myocardialsymptoms

Experiencewithoverdosageislimited.Nospecificantidoteisknown.Procedurestoenhancedrugeliminationfromthe

bodybyhaemodialysisorhaemoperfusionareunlikelytosucceedbecauseofthelargevolumeofdrugdistribution.

Theeffectsofpropafenonehydrochlorideoverdoseinthemyocardiummanifestasimpulsegenerationandconduction

disorderssuchasPQprolongation,QRSwidening,suppressionofsinusnodeautomaticity,AVblock,ventricular

tachycardia,ventricularflutterandventricularfibrillation.Hypotensionmayalsooccur.Convulsions,somnolenceand

deathmayoccur.Theusualemergencymeasuresforacutecardiovascularcollapseshouldbeapplied.Insevere

conductiondisturbanceassociatedwithcompromisedcardiacfunction,atropine,isoprenalineorpacemakertherapy

mayberequired.Ifelectricalstimulationisnotpossible,anattemptshouldbemadetoshortentheQRSdurationand

increasetheheartratewithhighdosesofisoprenaline.Bundlebranchblockbyitselfisnotanindicationfor

isoprenaline.Hypotensionmayrequireinotropicsupport.Convulsionsshouldbetreatedwithi.v.diazepam.

Non–cardiacsymptoms

Convulsions,somnolenceanddeathmayoccur.

occasionally.

Eyedisorders Blurredvisionmayoccuroccasionallyafterahighinitial

dose.

Cardiacdisorders Amarkedreductioninheartrate(bradycardia)orconduction

disorders(i.e.atrioventricularorinterventricularblock)may

occurveryrarely.

Occasionallyproarrhythmiceffectswhichmanifestasan

increaseinheartrate(tachycardia),orventricularfibrillation

mayalsooccur.

Vasculardisorders Hypotension,includingposturalhypotensionandorthostatic

hypotensioncanbeseenoccasionally.

Gastrointestinaldisorders Occasionally,especiallywithhighinitialdoses,nausea,

vomiting,constipation,drymouth,bittertaste,abdominal

paincanoccur.

Hepatobiliarydisorders Rarely,liverabnormalities,includinghepatocellularinjury,

cholestasis,jaundiceandhepatitismayoccurduetothe

individualshypersensitivityofthehyperergic-allergictype.

Skinandsubcutaneoustissue

disorders Rarely,allergicreactionsuchasreddeningoftheskin,rash,

itching,urticariamayoccur.

Musculoskeletalandconnective

tissuedisorders Isolatedcaseoflupussyndromehavebeenreported,these

arereversibleondiscontinuationofthemedicine.

Reproductivesystemandbreast

disorders Impotence,insomecases,adiminutionofpotencyanda

dropinspermcounthavebeenobservedafterhighdosesof

Arythmol.Thisphenomenonisreversiblewhentreatmentis

discontinued.However,sincetreatmentwithArythmolis

vital,thedrugmustnotbediscontinuedwithoutconsulting

yourdoctor.

Generaldisordersand

administrationsiteconditions Rarelyfatiguecanoccur.

Chestpain.

Convulsionsfollowinganoverdosehasbeenreportedvery,

veryrarely.

Bronchialspasmsmayrarelyoccuronpredisposedpatients.

Investigations Elevatedliverenzymes(serumtransaminasesandalkaline

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5.1Pharmacodynamicproperties

Propafenonehydrochlorideisanantiarrhythmicagentwithamembranestabilising,sodiumchannelblockingproperties

(VaughanWilliams,class1C).Italsopossessesweakbetablockingefficacy(classIIaccordingtoVaughanWilliams).

Propafenonehydrochloridereducestherateoftheriseoftheactionpotentialtherebyslowingdowntheimpulse

conduction(negativedromotropiceffect):Therefractoryperiodsintheatrium,atrioventricular(AV)nodeand

ventriclesareprolonged.Propafenonehydrochlorideprolongstherefractoryperiodsintheaccessorypathwayson

patientswithWPWsyndrome.

5.2Pharmacokineticproperties

Maximalplasmaconcentrationsarereachedbetweentwoandthreehoursfollowingtheadministrationofpropafenone

hydrochlorideIR.Propafenoneisknowntoundergoextensiveandsaturablepre-systemicbiotransformation(CYP2D6

hepaticfirstpasseffect)whichresultsinadose-anddosage-form-dependantabsolutebioavailability.

Therearetwogeneticallydeterminedpatternsofpropafenonehydrochloridemetabolism.Inover90%ofpatients,the

drugisrapidlyandextensivelymetabolisedwithaneliminationhalf-lifefromtwototenhours.Thesepatients

metabolisepropafenoneintotwometabolites:5-hydroxypropafenonewhichisformedbyCYP2D6andN-

depropylpropafenone(norpropafenone)whichisformedbybothCYP3A4andCYP1A2.Inlessthan10%ofpatients,

metabolismofpropafenoneisslowerbecausethe5-hydroxymetaboliteisnotformedorisminimallyformed.The

estimatedpropafenoneIReliminationhalf-liferangesfrom2.8to11hoursforextensivemetabolisersandisaround17

hoursforpoormetabolisers.

Inextensivemetabolisers,thesaturablehydroxylationpathway(CYP2D6)resultsinnonlinearpharmacokinetics.In

slowmetabolisers,propafenonepharmacokineticsarelinear.

Becausethesteadystateisreachedafterthreetofourdaysofdosinginallpatients,therecommendeddosingregimen

ofpropafenonehydrochlorideIRisthesameforallpatients.

WithArythmol,thereisaconsiderabledegreeofindividualvariabilityinpharmacokineticswhichisdueinlargepartto

thefirstpasshepaticeffectandnon-linearpharmacokineticsinextensivemetabolisers.Thelargevariabilityinblood

levelsrequiresthatthedosebetitratedcarefullyinpatients,payingcloseattentiontoclinicalandelectrocardiographic

evidenceoftoxicity.

Renalimpairment

Propafenonehydrochlorideshouldbeadministeredcautiouslyinpatientswithrenaldisease.

Hepaticimpairment

Thedosagemustbeadjustedinpatientswithliverdisease.

5.3Preclinicalsafetydata

Intravenousadministrationofpropafenoneatdoseswithinthetoxicrangehascausedreversibledisordersof

spermatogenesisatirregularintervalsinmonkeys,dogsandrabbits.

6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

Tabletcore:

Microcrystallinecellulose,

Maizestarch,

Croscarmellosesodium,

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Magnesiumstearate.

Tabletcoating:

Hypromellose,

Macrogol400,

Macrogol6000,

Titaniumdioxide(E171).

6.2Incompatibilities

Notapplicable.

6.3ShelfLife

5years.

6.4Specialprecautionsforstorage

Donotstoreabove30 °

6.5Natureandcontentsofcontainer

PVC/aluminiumblisterstripspackedincartons.

Packsize:60.

6.6Specialprecautionsfordisposalofausedmedicinalproductorwastematerialsderivedfrom

suchmedicinalproductandotherhandlingoftheproduct

Nospecialrequirements.

Anyunusedproductorwastematerialshouldbedisposedofinaccordancewithlocalrequirements.

7MARKETINGAUTHORISATIONHOLDER

AbbottLaboratories(Ireland)Limited

4051KingswoodDrive

CitywestBusinessCampus

Dublin24

8MARKETINGAUTHORISATIONNUMBER

PA0038/079/003

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

Dateoffirstauthorisation: 20July1983

Dateoflastrenewal: 20July2008

10DATEOFREVISIONOFTHETEXT

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