ARYTHMOL

Main information

  • Trade name:
  • ARYTHMOL Film Coated Tablet 150 Milligram
  • Dosage:
  • 150 Milligram
  • Pharmaceutical form:
  • Film Coated Tablet
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug

Documents

Localization

  • Available in:
  • ARYTHMOL Film Coated Tablet 150 Milligram
    Ireland
  • Language:
  • English

Status

  • Source:
  • HPRA - Health Products Regulatory Authority - Ireland
  • Authorization number:
  • PPA1328/049/001
  • Authorization date:
  • 09-01-2009
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

IRISHMEDICINESBOARDACTS1995AND2006

MEDICINALPRODUCTS(CONTROLOFPLACINGONTHEMARKET)REGULATIONS,2007

(S.I.No.540of2007)

PPA1328/049/001

CaseNo:2026019

TheIrishMedicinesBoardinexerciseofthepowersconferredonitbytheabovementionedRegulationsherebygrantsto

B&SHealthcare

Unit4,BradfieldRoad,Ruislip,Middlesex,HA40NU,UnitedKingdom

anauthorisation,subjecttotheprovisionsofthesaidRegulations,inrespectoftheproduct

Arythmol150mgFilm-CoatedTablets

TheparticularsofwhicharesetoutinPartIandPartIIoftheattachedSchedule.Theauthorisationisalsosubjecttothegeneralconditionsas

maybespecifiedinthesaidRegulationsaslistedonthereverseofthisdocument.

Thisauthorisation,unlesspreviouslyrevoked,shallcontinueinforcefrom09/01/2009.

SignedonbehalfoftheIrishMedicinesBoardthis

________________

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Date Printed 09/01/2009 CRN 2026019 page number: 1

PartII

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

Arythmol150mgFilm-CoatedTablets

2QUALITATIVEANDQUANTITATIVECOMPOSITION

Eachtabletcontains150mgpropafenonehydrochloride.

Forafulllistofexcipients,seesection6.1.

3PHARMACEUTICALFORM

Film-coatedtablet

ProductimportedfromtheUK:

White,round,biconvextabletmarked“150”ononesideandplainontheother.

4CLINICALPARTICULARS

4.1TherapeuticIndications

Symptomaticsupraventriculartachyarrhythmiaswarrantingtreatment,suchasAVjunctionaltachycardias,

supraventriculartachycardiasinpatientswithWPWsyndromeorparoxysmalatrialfibrillation.

Serioussymptomaticventriculartachyarrhythmiasiflife-threateningornecessitating

treatmentinthejudgementofthephysician.

4.2Posologyandmethodofadministration

Thetabletsshouldbeswallowedwholeandtakenwithadrinkafterfood.

Thedosageshouldbeadjustedtotheindividualpatient'srequirements.

InthosepatientsinwhomsignificantwideningoftheQRScomplexorsecondorthirdAVblockoccurs,adose

reductionshouldbeconsidered.

Adults:Adailydoseof450to600mgofpropafenonehydrochloride,dividedintwoorthreedosesperday,is

recommendedinthetitratedperiodandformaintenancetherapyinpatientsweighingaround70kilograms.

Occasionally,itmaybenecessarytoincreasethedailydoseto900mgofpropafenonehydrochloride.Thedailydose

shouldbereducedaccordinglyforpatientswithalowerbodyweight.Doseincreasesshouldnotbeattempteduntilthe

patientisreceivingtreatmentforthreetofourdays.

TheindividualmaintenancedoseshouldbedeterminedundercardiologicalsurveillanceincludingECGmonitoringand

repeatedbloodpressurecontrol(titrationphase).

Elderly:Inelderlypatientsorpatientswithrelevantimpairmentofventricularfunction(leftventricularejection

fractionlessthan35%)orstructuralmyocardialdisease,treatmentshouldbeinitiatedgraduallyandwithparticular

cautioninsmallincrementaldoses.Thesameappliestomaintenancetherapy.Anydoseincreasesthatmayberequired

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Inpatientswhoseliverand/orkidneyfunctionisimpaired,theremaybedrugaccumulationafterthestandard

therapeuticdoses.Nonetheless,patientswiththeseconditionscanstillbetitratedonpropafenonehydrochlorideunder

ECGandplasmalevelmonitoring.

Arythmoltabletsarenotrecommendedforuseinchildren.

4.3Contraindications

Knownhypersensitivitytopropafenoneortoanyoftheotheringredients.

Significantstructuralheartdiseasesuchas:

Uncontrolledcongestiveheartfailurewhereleftventricularoutputislessthan35%

Cardiogenicshock,unlessthisiscausedbyarrhythmia.

Severesymptomaticbradycardia.

Thepresenceofsinusnodedysfunction,atrialconductiondefects,seconddegreeorgreateratrioventricular

blockorbundlebranchblockordistalblockintheabsenceofanartificialpacemaker.

Severehypotension.

Manifestelectrolyteimbalance(e.g.potassiummetabolismdisorders).

Severeobstructivepulmonarydisease.

4.4Specialwarningsandprecautionsforuse

ItisessentialthateachpatientgivenpropafenonehydrochlorideIRbeevaluatedelectrocardiographicallyandclinically

priortoandduringtherapytodeterminewhethertheresponsetopropafenonehydrochlorideIRsupportscontinued

treatment.

PropafenonehydrochlorideIRmayworsenmyastheniagravis.

Propafenonehydrochloridetreatmentmayaffectboththepacingandsensingthresholdsofartificialpacemakers.

Pacemakerfunctionshouldthereforebecheckedand,ifnecessary,reprogrammed.

Thereisthepotentialforconversionofparoxysmalatrialfibrillationtoatrialflutterwithaccompanying2:1or1:1

conductionblock.

Aswithotherclass1Canti-arrhythmicagents,patientswithsignificantstructuralheartdiseasemaybepredisposedto

seriousadverseeffects.

Becauseofthebeta-blockereffect,careshouldbetakeninthetreatmentofpatientswithasthma.

4.5Interactionwithothermedicinalproductsandotherformsofinteraction

ApossiblepotentiationofdrugsideeffectsmayoccurwhenpropafenonehydrochlorideIRistakeninconjunctionwith

localanaesthetics(e.g.pacemakerimplantation,surgeryordentalwork)andotherdrugswhichmayhaveaninhibitory

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

Co-administrationofpropafenonehydrochloridewithdrugsmetabolizedbyCYP2D6(suchasvenlafaxine)mightlead

toincreasedlevelsofthesedrugs.

Increasesinpropranolol,metoprolol,desipramine,cyclosporin,theophyllineanddigoxinplasmalevelsorbloodlevels

havebeenreportedduringpropafenonehydrochloridetherapy.

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

grapefruitjuicemightleadtoincreasedlevelsofpropafenonehydrochloride.Whenpropafenonehydrochlorideis

administeredwithinhibitorsoftheseenzymes,thepatientsshouldbecloselymonitoredandthedoseadjusted

accordingly.

Duetothepotentialforincreaseplasmaconcentrations,co-administrationof800-1200mg/daydosesofritonavirand

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Combinationtherapyofamiodaroneandpropafenonehydrochloridecanaffectconductionandrepolarisationandlead

toabnormalitiesthathavethepotentialtobeproarrhythmic.Doseadjustmentsofbothcompoundsbasedontherapeutic

responsemayberequired.

Nosignificanteffectsonthepharmacokineticsofpropafenoneorlidocainehavebeenseenfollowingtheirconcomitant

useinpatients.However,concomitantuseofpropafenonehydrochlorideandintravenouslidocainehavebeenreported

toincreasetherisksofcentralnervoussideeffectsoflidocaine.

PhenobarbitalisaknowninducerofCYP3A4.Responsetopropafenonehydrochloridetherapyshouldbemonitored

duringconcomitantchronicphenobarbitaluse.

Concomitantuseofpropafenonehydrochlorideandrifampinmayreducetheanti-arrhythmicefficacyofpropafenone

hydrochlorideastheresultofareductioninthepropafenoneplasmalevels.

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

recommendedaspropafenonehydrochloridemayenhancetheefficacyofthedrugsresultinginanincreased

prothrombintime.

ConcomitantadministrationofpropafenonehydrochlorideandfluoxetineinextensivemetabolisersincreasedtheS

propafenoneC

andAUCby71and50%.Elevatedlevelsofplasmapropafenonemayoccurwhenpropafenone

hydrochlorideisusedconcomitantlywithparoxetine.Lowerdosesofpropafenonemaybesufficienttoachievethe

desiredtherapeuticresponse.

Cautionshouldbetakenwithregardstodigitalistoxicity.

4.6Pregnancyandlactation

Pregnancy

PropafenonehydrochlorideIRshouldbeusedduringpregnancyonlyifthepotentialbenefitjustifiesthepotentialrisk

tothefetus.Propafenonehydrochlorideisknowntopasstheplacentalbarrierinhumans.Theconcentrationof

propafenoneintheumbilicalcordhasbeenreportedtobeabout30%ofthatofthematernalblood.

Animalstudieshavenotshownanyteratogeniceffects,butthereisnoexperienceoftheuseofthedruginhuman

pregnancy.

Lactation

Excretionofpropafenoneinbreastmilkhasnotbeenstudied.Limiteddatasuggeststhatpropafenonemaybeexcreted

inbreastmilk.Propafenonehydrochlorideshouldbeusedwithcautioninnursingmothers.

4.7Effectsonabilitytodriveandusemachines

Blurredvision,dizziness,fatigueandposturalhypotensionmayaffectthepatient'sspeedofreactionandimpairthe

individual'sabilitytooperatemachineryormotorvehicles.

4.8Undesirableeffects

Thefollowingadverseeventshavebeenreportedwiththisorotherformulationsofpropafenonehydrochloride.A

causeandeffectrelationshipmaynothavebeenestablished.

BodySystem PreferredTerm

Bloodandlymphaticsystem

disorders Isolatedcaseofleukocytopeniaand/or

granulocytopeniaorthrombocytopenia;

agranulocytosishavebeenreported.

Immunesystemdisorders Allergicreactions

Metabolismandnutritional

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Psychiatricdisorders Anxiety,confusioncanoccurrarely.

Nervoussystemdisorders Dizziness,headache,syncope,ataxia.

Veryrarely,restlessness,nightmares,sleep

disordersandextrapyramidalsymptomsmayoccur.

Eyedisorders Blurredvisionandvertigomayoccuroccasionally

afterahighinitialdose.

Cardiacdisorders Amarkedreductioninheartrate(bradycardia)or

conductiondisorders(i.e.atrioventricularor

interventricularblock)mayoccurveryrarely.

Occasionallyproarrhythmiceffectswhichmanifest

asanincreaseinheartrate(tachycardia),or

ventricularfibrillationmayalsooccur.

Vasculardisorders Hypotension,includingposturalhypotensionand

orthostatichypotensioncanbeseenoccasionally.

Gastrointestinaldisorders Occasionally,especiallywithhighinitialdoses,

nausea,vomitingconstipation,drymouth,bitter

taste,abdominalpaincanoccur.

Hepatobiliarydisorders Rarely,liverabnormalities,includinghepatocellular

injury,cholestasis,jaundiceandhepatitismayoccur

duetotheindividualshypersensitivityofthe

hyperergic-allergictype.

Skinandsubcutaneoustissue

disorders Rarely,allergicreactionsuchasreddeningofthe

skin,rash,itching,urticariamayoccur.

Musculoskeletaland

connectivetissuedisorders Isolatedcaseoflupussyndromehavebeenreported,

thesearereversibleondiscontinuationofthe

medicine.

Reproductivesystemand

breastdisorders Impotence,insomecases,adiminutionofpotency

andadropinspermcounthavebeenobservedafter

highdosesofArythmol.Thisphenomenonis

reversiblewhentreatmentisdiscontinued.

However,sincetreatmentwithArythmolisvital,

thedrugmustnotbediscontinuedwithout

consultingyourdoctor.

Generaldisordersand

administrationsiteconditions Rarelyfatiguecanoccur.

Chestpain.

Convulsionsfollowinganoverdosehasbeen

reportedvery,veryrarely.

Bronchialspasmsmayrarelyoccuronpredisposed

patients.

Investigations Elevatedliverenzymes(serumtransaminasesand

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4.9Overdose

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.

5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

Propafenonehydrochlorideisanantiarrhythmicdrugwithmembrane-stabilising,sodium-channel-blockingproperties

(VaughanWilliamsClassIc).Itisalsopossessesweakbeta-blockingproperties(ClassIIaccordingtoVaughan

Williams).Propafenonereducestherateofriseoftheactionpotential,therebyslowingdownimpulseconduction

(negativedromotropism).Therefractoryperiodsintheatrium,atrioventricularAVnodeandventriclesareprolonged.

PropafenonehydrochlorideprolongstherefractoryperiodsintheaccessorypathwaysonpatientswithWPW

syndrome.

5.2Pharmacokineticproperties

Maximalplasmaconcentrationsarereachedbetweentwoandthreehoursfollowingtheadministrationofpropafenone

hydrochlorideIR.propafenoneisknowntoundergoextensiveandsaturablepre-systemicbiotransformation(CYP2D6

hepaticfirstpasseffect)whichresultsinadose-anddosage-form-dependantabsolutebioavailability.

Therearetwogeneticallydeterminedpatternsofpropafenonehydrochloridemetabolism.Inover90%ofpatients,the

drugisrapidlyandextensivelymetabolisedwithaneliminationhalf-lifeformtwototenhours.Thesepatients

metabolisepropafenoneintotwometabolites:5-hydroxypropfenonewhichisformedbyCYP2D6andN-

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

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5.3Preclinicalsafetydata

Intravenousadministrationofpropafenoneatdoseswithinthetoxicrangehascausedreversibledisordersof

spermatogenesisatirregularintervalsinmonkeys,dogsandrabbits.

6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

Microcrystallinecellulose,

Maizestarch,

Croscarmellosesodium,

Hypromellose,

Magnesiumstearate,

Macrogol6000,

Titaniumdioxide(E171),

Macrogol400.

6.2Incompatibilities

Notapplicable.

6.3ShelfLife

Theshelf-lifeexpirydateofthisproductshallbethedateshownonthecontainerandouterpackageoftheproducton

themarketinthecountryoforigin .

6.4Specialprecautionsforstorage

Donotstoreabove30 º

6.5Natureandcontentsofcontainer

PVC/aluminiumblisterstripspackedincartonpacksof90tablets.

6.6Specialprecautionsfordisposalofausedmedicinalproductorwastematerialsderivedfrom

suchmedicinalproductandotherhandlingoftheproduct

Nospecialrequirements.

7ParallelProductAuthorisationHolder

B&SHealthcare

Unit4BradfieldRoad

Ruislip

MiddlesexHA40NU

8ParallelProductAuthorisationNumber

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9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

DateofFirstAuthorisation:9thJanuary2009

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