ARYTHMOL 300 Milligram Film Coated Tablet

Ireland - English - HPRA (Health Products Regulatory Authority)

Buy It Now

Active ingredient:
PROPAFENONE HYDROCHLORIDE
Available from:
Abbott Laboratories Ireland Ltd
INN (International Name):
PROPAFENONE HYDROCHLORIDE
Dosage:
300 Milligram
Pharmaceutical form:
Film Coated Tablet
Prescription type:
Product subject to prescription which may be renewed (B)
Authorization status:
Authorised
Authorization number:
PA0038/079/003
Authorization date:
0000-00-00

Arythmol®150 mg Film-Coated Tablets

Arythmol®300 mg Film-Coated Tablets

Propafenonehydrochloride

IMPORTANT INFORMATION

Read all of this leaflet carefully before you start taking this medicine.

Keep this leaflet as you may need to read it again

Thisleaflet provides a summary of the information currently available for Arythmol

For further information or advice ask your doctor or pharmacist

This medicine is for you only and should never be given to anyone else, even if they appear to

have the same symptoms as you

Tell your doctor or pharmacist if you experience any side effects

In this leaflet:

1. What Arythmolis& what itisused for

2. Beforeyou takeArythmol

3. Howtotake Arythmol

4. Possible side effects

5. Howtostore Arythmol

6. Further information

1. WHAT ARYTHMOLIS& WHAT ITISUSED FOR

Arythmol belongs to a group of medicines called antiarrhythmic agents. Arythmol slows down

the heart rate and helps to regulate the heartbeat. Arythmol tablets are used to treat arrhythmias

(abnormal heart rhythms).

2. BEFOREYOU TAKEARYTHMOL

Do not take this medicine

If you:

are allergic (hypersensitive) to propafenone hydrochloride or any of the other ingredients of

this medicine (see section 6).

suffer from a heart rhythm disorder called Brugada syndrome.

have had a heart attackwithin the last 3 months.

suffer from heart failure or any other heart problemsother than abnormal heart rate/heart

rhythm.

have an unusually slow heart rate or low blood pressure (hypotension).

suffer from breathing problems, such as chronic bronchitis or emphysema (sometimes known

as COPD).

have been told you that you have an imbalance of potassium or sodium in your blood.

suffer from myasthenia gravis which causes muscle weakness

are taking ritonavir.

Take special care with Arythmol

Tell your doctor BEFORE you take this medicine ifyou

are pregnant or thinking of becoming pregnant

are breast feeding

Propafenone

SOLID 1000553547 1.0

suffer from liver or kidney disease

have a heart pacemaker, it may need to be altered.

If surgery is planned, tell your surgeon or dentist that you are taking this medicine. It may affect

the anaesthetic used.

Arythmol is NOT suitable for children.

Your doctor may perform ECGs and blood pressure monitoring prior to and during treatment to

monitor your individual dose.

Taking other medicines

Please tell your doctor or pharmacist if you are taking or have recently taken any other medicines,

including medicines obtained without a prescription and herbal medicines.

Tell your doctor if you are using or have recently used:

Any other medicines used to treat heart conditions, angina and high blood pressure, or

medicines that may impact the heart rate including:

obeta blockers (propanolol, metoprolol)

odigoxin

oquinidine

oamiodarone

Medicines used to treat depression (e.g. amitriptyline, dothiepin, desipramine, venlafaxine,

fluoxetine, paroxetine).

Antibiotic and antifungal medicines (e.g. erythromycin, rifampicin, ketoconazole)

Medicines used to prevent organ transplant rejection (cyclosporine)

Local anaesthetic medicines for dental surgery, or other minor surgical procedures (e.g.

lidocaine).

Medicine used for thinning blood (anticoagulant medicines e.g. warfarin)

Other medicines used to treat stomach ulcers (cimetidine),

Medicines for asthma (e.g. theophylline)

Medicines for epilepsy or seizures (e.g. phenobarbital).

TakingArythmolwith food and drink

This medicine can be taken after food with some water.

You should not however, drink grapefruit juice whilst taking this medicine as it increases the

amount of medicine your body absorbs.

Pregnancy and breast-feeding

If you are pregnant or thinking of becoming pregnant, tell your doctor before taking this

medicine.

The active ingredient, propafenonehydrochloride, may pass into human breast milk. Before

taking this medicine, you should tell your doctor if you are breast-feeding or plan to breast-feed.

Ask your doctor or pharmacist for advice before taking any medicines.

Driving and using machines

Arythmol can cause blurred vision, dizziness, tiredness and low blood pressure in some people.

This may affect your speed of reaction. Do not drive, operate machinery or do anything that

requires you to be alert until you know how thetablets affect you.

3. HOWTOTAKE ARYTHMOL

Follow your doctor’s directions about when and how to take your tablets and look at the label on

the carton. Your pharmacist will also help if you are not sure. The number of tablets that you will

Propafenone

SOLID 1000553547 1.0

This may be one Arythmol150 mg tablet three times a day or one Arythmol 300 mg tablet twice

a day. Depending on your condition your doctor may give you one Arythmol 300 mg tablet three

times a day.

You may need a lower dose of Arythmol if you have problems with your kidneys or liver, or if

you have a low bodyweight.

Swallow your tablets without chewing them.

Itis best to take them after food with some water. Do not take them with grapefruit juice as it

reacts with this medicine.

IF YOU OR SOMEONE YOU KNOW TAKES MORE ARYTHMOL THAN PRESCRIBED

(AN OVERDOSE) you should contact a doctor or go to the nearest hospital casualty department

IMMEDIATELY, taking your tablets with you.

IF YOU FORGET TO TAKE YOUR ARYTHMOLTABLET take it as soon as you remember,

unless it isalmost time for your next dose. If it is, do not take themissed dose at all.

Never double up on a dose to make up for the one youhave missed.

IF YOU STOP TAKING ARYTHMOL, without yourdoctor’s advice, your condition may get

worse. It isimportant that you keep taking thesetablets until yourdoctor tells you to stop. Do

NOT stop just because you feelbetter.

4. POSSIBLE SIDE EFFECTS

Like all medicines Arythmol can cause side effects, although not everybody gets them.

Tell your doctor immediately if you develop any of the following conditions:

oa rash, itching or skin reddening or other signs of an allergic reaction such as difficulty

breathing. Although these are rare, they can be serious.

oyellowing of the skin and/or eyes, as these may be a sign of liver problems

oyou start tobruise easily or if you develop a very sore throat with a high fever, as in very

rare cases, treatment may affect the amount of white blood cells and platelets in the

blood.

Other side effects with Arythmol may include:

Very Common

dizziness

heart rhythm disorders, palpitations

Common

anxiety, sleep disorders

headache, change to sense of taste

blurred vision

heart rhythm disorders such as fast or slow heartbeat

shortness of breath

abdominal pain, vomiting, feeling sick, diarrhoea, constipation, dry mouth

abnormal liver function

chest pain, fatigue, muscle weakness, fever

Uncommon

low platelet levels in the blood

loss of appetite

nightmares

fainting,problems with coordination (ataxia), numbness or tingling sensation

Propafenone

SOLID 1000553547 1.0

heart rhythm disorders such as irregular heartbeat

low blood pressure

bloating, wind

hives, itchy skin, rash, redness of the skin

difficulty getting or maintaining an erection

Frequency not known

decrease in number of white blood cells

allergic reactions

confusion

seizures, movement disorders, restlessness

abnormal heart rhythm, heart failure, reduced heart rate

low blood pressure on standing up

retching, stomach problems

liver cell damage, blockage of the flow of bile from the liver (cholestasis), inflammation of

the liver (hepatitis), yellowing of the skin or whites of the eyes (jaundice)

a disorder of the immune system calledlupus-like syndrome

decreased sperm count

If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet,

please tell your doctor or pharmacist.

Reporting of side effects

If you get any side effects, talk to your doctor, pharmacist or nurse.This includes any possible

side effects not listed in this leaflet. You can also report side effects directly viaIMB

Pharmacovigilance, Earlsfort Terrace,IRL-Dublin 2;

Tel: +353 1 6764971;Fax: +353 1 6762517.

Website: www.imb.ie;

e-mail:imbpharmacovigilance@imb.ie

By reporting side effects you can help provide more information on the safety of this medicine.

5. HOWTOSTORE ARYTHMOL

Your tablets should be stored in a safe place out of thereach and sight of children. Do not store

them above30 °C.

Do NOT use Arythmol after the expiry date (Use by) printedon the packaging. The expiry date

refers to the last day ofthat month.

If your doctor decides to stop the treatment, return any leftover tablets to your pharmacist. Only

keep the tablets ifyour doctor tells you to. Do not dispose of the leftovertablets carelessly (e.g.

down the toilet or in with yourgeneral rubbish). These measures will help to protect the

environment.

6. FURTHER INFORMATION

The active ingredient in Arythmol is propafenonehydrochloride.

The film coated tablets are white and are available in twostrengths, containing either 150 mg or

300 mg ofpropafenone hydrochloride. Other ingredients include:microcrystalline cellulose,

maize starch, hypromellose,croscarmellose sodium, macrogol 400 and macrogol6000, titanium

Propafenone

SOLID 1000553547 1.0

The 150 mg tablets are embossed with ‘150’ and the300 mg tablets are embossed with ‘300’.

Each pack of Arythmol 150 mg film coated tablets contains90 tablets.

Each pack of Arythmol 300 mg film coated tablets contains60 tablets.

Marketing Authorisation Holder:

Abbott Laboratories IrelandLtd., 4051 Kingswood Drive,Citywest Business Campus, Dublin 24,

Ireland.

Manufactured by:

AbbVie DeutschlandGmbH & Co. KG,Knollstrasse, 67061 Ludwigshafen, Germany.

Famar Lyon, 29 avenue Charles de Gaulle, 69230 Saint-Genis-Laval, France

Propafenone

SOLID 1000553547 1.0

Document Outline

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

Arythmol300mgFilm-coatedTablets.

2QUALITATIVEANDQUANTITATIVECOMPOSITION

Eachtabletcontains300mgpropafenonehydrochloride.

Forafulllistofexcipientsseesection6.1.

3PHARMACEUTICALFORM

Film-coatedtablets.

Whitetooff-whitefilm-coatedtablet,biconvex,embossed“300”ononeface.

4CLINICALPARTICULARS

4.1TherapeuticIndications

Symptomaticsupraventriculartachyarrhythmiasrequiringtreatment,suchasAVjunctionaltachycardias,

supraventriculartachycardiasinpatientswithWolff-Parkinson-White(WPW)syndromeorparoxysmalatrial

fibrillation.

Severesymptomaticventriculartachyarrhythmias,ifthephysicianconsidersthesetobelife-threatening.

4.2Posologyandmethodofadministration

Thedosageistobeadjustedtotheindividualpatient’srequirements.

InthosepatientsinwhomsignificantwideningoftheQRScomplexorsecondorthirddegreeAVblockoccurs,adose

reductionshouldbeconsidered.

Adults:

Adailydoseof450to600mgofpropafenonehydrochloride,dividedintwoorthreedosesperday,isrecommendedin

thetitrationperiodandformaintenancetherapyinpatientsweighingaround70kilograms.Occasionally,itmaybe

necessarytoincreasethedailydoseto900mgofpropafenonehydrochloride.Thedailydoseshouldbereduced

accordinglyforpatientswithalowerbodyweight.Doseincreasesshouldnotbeattempteduntilthepatientisreceiving

treatmentforthreetofourdays.

Elderlypopulation:

Nooveralldifferencesinsafetyoreffectivenesswereobservedinthispatientpopulation,butgreatersensitivityof

someolderindividualscannotberuledout,thesepatientsshouldbecarefullymonitored.Treatmentshouldbeinitiated

graduallyandwithparticularcautioninsmallincrementaldoses.Thesameappliestomaintenancetherapy.Anydose

increasesthatmayberequiredshouldnotbeundertakenuntilafterfivetoeightdaysoftherapy.

Liver/RenalImpairment:

Inpatientswhoseliverand/orkidneyfunctionisimpaired,theremaybedrugaccumulationafterthestandard

therapeuticdoses.Nonetheless,patientswiththeseconditionscanstillbetitratedonpropafenonehydrochlorideunder

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Children

Arythmoltabletsarenotrecommendedforuseinchildren.

Methodofadministration:

Owingtothebittertasteandsurfaceanestheticactionofpropfaenone,thefilm-coatedtabletsshouldbeswallowed

whole(withoutchewing)withliquid.

4.3Contraindications

HypersensitivitytotheactiveingredientpropafenonehydrochlorideandexcipientslistedinSection6.1

KnownBrugadasyndrome(SeeSection4.4)

Incidentofmyocardialinfarctionwithinthelast3months

Significantstructuralheartdiseasesuchas:

Uncontrolledcongestiveheartfailurewhereleftventricularoutputis lessthan35%.

Cardiogenicshock,unlessthisiscausedbyarrhythmia

Severesymptomaticbradycardia

Thepresenceofsinusnodedysfunction,atrialconductiondefects,seconddegreeorgreater

atrioventricularblockorbundlebranchblockordistalblockintheabsenceofanartificialpacemaker.

Severehypotension

Manifestelectrolyteimbalance(e.g.potassiummetabolismdisorders)

Severeobstructivepulmonarydisease

Myastheniagravis

Concomitanttreatmentwithritonavir

4.4Specialwarningsandprecautionsforuse

Itisessentialthateachpatientgivenpropafenonehydrochloridebeevaluatedelectrocardiographicallyandclinically

priortoandduringtherapytodeterminewhethertheresponsetopropafenonehydrochloridesupportscontinued

treatment.

ABrugadasyndromemaybeunmaskedorBrugada-likeelectrocardiogram(ECG)changesmaybeprovokedafter

exposuretopropafenoneinpreviouslyasymptomaticcarriersofthesyndrome.Afterinitiatingtherapywith

propafenone,anECGshouldbeperformedtoruleoutchangessuggestiveofBrugadasyndrome.

Propafenonehydrochloridetreatmentmayaffectboththepacingandsensingthresholdsofartificialpacemakers.

Pacemakersfunctionshouldthereforebecheckedand,ifnecessary,re-programmed.

Thereisthepotentialforconversionofparoxysmalatrialfibrillationtoatrialflutterwithaccompanying2:1conduction

blockor1:1conduction(seesection4.8).

AswithotherclassIcantiarrhythmicagents,patientswithsignificantstructuralheartdiseasemaybepredisposedto

seriousadverseevents,therefore,propafenonehydrochlorideiscontraindicatedinthesepatients(seesection4.3).

Propafenonehydrochlorideshouldbeusedwithcautioninpatientswithobstructionoftheairways,e.g.,asthma.

4.5Interactionwithothermedicinalproductsandotherformsofinteraction

MedicinalproductsthatinhibitCYP2D6,CYP1A2andCYP3A4e.g.ketoconazole,cimetidine,quinidine,

erythromycinandgrapefruitjuicemightleadtoincreasedlevelsofpropafenonehydrochloride.Whenpropafenone

hydrochlorideisadministeredwithinhibitorsoftheseenzymes,thepatientsshouldbecloselymonitoredandthedose

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Nosignificanteffectsonthepharmacokineticsofpropafenoneorlidocainehavebeenseenfollowingtheirconcomitant

useinpatients.However,concomitantuseofpropafenonehydrochlorideandlidocainehasbeenreportedtoincrease

therisksofcentralnervousadversereactionsoflidocaine.

Combinationtherapyofamiodaroneandpropafenonehydrochloridecanaffectconductionandrepolarisationandlead

toabnormalitiesthathavethepotentialtobeproarrhythmic.Doseadjustmentsofbothcompoundsbasedontherapeutic

responsemayberequired.

ElevatedlevelsofplasmapropafenonemayoccurwhenpropafenonehydrochlorideisusedconcomitantlywithSSRIs,

suchasfluoxetineandparoxetine.Concomitantadministrationofpropafenonehydrochlorideandfluoxetinein

extensivemetabolisersincreasedtheS-propafenoneC

andAUCby39and50%andtheR-propafenoneC

AUCby71and50%.Lowerdosesofpropafenonemaybesufficienttoachievethedesiredtherapeuticresponse.

Apossiblepotentiationofdrugsideeffectsmayoccurwhenpropafenonehydrochlorideistakeninconjunctionwith

localanaesthetics(e.g.pacemakerimplantation,surgeryordentalwork)andothermedicinalproductswhichhavean

inhibitoryeffectontheheartrateand/ormyocardialcontractility(e.g.,beta-blockers,tricyclicantidepressants).

Co-administrationofpropafenonehydrochloridewithdrugsmetabolisedbyCYP2D6(suchasvenlafaxine)mightlead

toincreasedlevelsofthesedrugs.

Increasesinpropranolol,metoprolol,desipramine,cyclosporine,theophyllineanddigoxinplasmalevelsorbloodlevels

havebeenreportedduringpropafenonehydrochloridetherapy.Dosesofthesemedicinalproductsshouldbereduced,as

appropriate,ifsignsofoverdoseareobserved.

Duetothepotentialforincreasedplasmaconcentrations,co-administrationofritonavirandpropafenonehydrochloride

iscontraindicated(seesection4.3).

PhenobarbitalisknowninducerofCYP3A4.Responsetopropafenonehydrochloridetherapyshouldbemonitored

duringconcomitantchronicphenobarbitaluse.

Concomitantuseofpropafenonehydrochlorideandrifampicinmayreducetheantiarrhythmicefficacyofpropafenone

hydrochlorideastheresultofareductioninthepropafenoneplasmalevels.

Closemonitoringoftheclottingstatusinpatientsreceivingconcomitantoralanti-coagulants(e.g.phenoprocoumon,

warfarin)isrecommendedaspropafenonehydrochloridemayenhancetheefficacyofthesemedicinalproducts

resultinginanincreasedprothrombintime.Dosesofthesemedicinalproductsshouldbeadjustedifnecessary.

Cautionshouldbetakenwithregardstodigitalistoxicity.

SpecialPopulations:

Paediatricpopulation

Interactionstudieshaveonlybeenperformedinadults.Itisnotknowswhethertheextentofinteractionsissimilarin

thepaediatricagedgrouptothatinadults.

4.6Fertility,pregnancyandlactation

Pregnancy

Therearenoadequateandwell-controlledstudiesinpregnantwomen.Propafenonehydrochlorideshouldbeused

duringpregnancyonlyifthepotentialbenefitjustifiesthepotentialrisktothefetus.Propafenonehydrochlorideis

knowntopasstheplacentalbarrierinhumans.Theconcentrationofpropafenoneintheumbilicalcordhasbeen

reportedtobeabout30%ofthatofthematernalblood.

Lactation

Excretionofpropafenoneinhumanbreastmilkhasnotbeenstudied.Limiteddatasuggeststhatpropafenonemaybe

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4.7Effectsonabilitytodriveandusemachines

Blurredvision,dizziness,fatigueandposturalhypotensionmayaffectthepatient’sspeedofreactionandimpairthe

individual’sabilitytooperatemachineryormotorvehicles.

4.8Undesirableeffects

a.Summaryofthesafetyprofile

Themostfrequentandverycommonadversereactionsrelatedtopropafenonetherapyaredizziness,cardiacconduction

disordersandpalpitations.

b.Tabulatedsummaryofadversereactions

Thefollowingtabledisplaysadversereactionsreportedinclinicaltrialsandfrompost-marketingexperiencewith

propafenone.

Thereactionsconsideredatleastpossiblyrelatedtopropafenonearedisplayedbysystemorganclassandfrequency

usingthefollowingconvention:verycommon(1/10),common(1/100to<1/10),uncommon(1/1000to<1/100)

andnotknown(adversereactionsfrompost-marketingexperience;cannotbeestimatedfromtheavailabledata).

Withineachfrequencygrouping,adversereactionsarepresentedinorderofdecreasingseriousnesswhenthe

seriousnesscouldbeassessed.

SystemOrgan

Class Verycommon

1/10 Common1/100

to<1/10 Uncommon

1/1000to<1/100 NotKnown

(cannotbe

estimatedfrom

theavailable

data)

Bloodand

lymphaticsystem

disorders Thrombocytopenia Agranulocytosis

Leukopenia

Granulocytopenia

Immunesystem

disorders Hypersensitivity 1

Metabolismand

nutritiondisorders Decreasedappetite

Psychiatric

disorders Anxiety

Sleepdisorders Nightmare Confusionalstate

Nervoussystem

disorders Dizziness 2 Headache

Dysgeusia Syncope

Ataxia

Paraesthesia Convulsion

Extrapyramidal

symptoms

Restlessness

Eyedisorders Visionblurred

Earandlabyrinth

disorders Vertigo

Cardiacdisorders Cardiac

conduction

disorders 3

Palpitations Sinusbradycardia

Bradycardia

Tachycardia

Atrialflutter Ventricular

tachycardia

Arrhythmia 4 Ventricular

fibrillation

Cardiacfailure 5

Heartratereduced

Vasculardisorders Hypotension Orthostatic

hypotension

Respiratory,

thoracicand

mediastinal

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1.Maybemanifestedbycholestasis,blooddyscrasiasandrash

2.Excludingvertigo

3.Includingsinoatrialblock,atrioventricularblockandintraventricularblock

4.Propafenonemaybeassociatedwithproarrhythmiceffectswhichmanifestasanincreaseinheartrate

(tachycardia)orventricularfibrillation.Someofthesearrhythmiascanbelife-threateningandmayrequire

resuscitationtopreventapotentiallyfataloutcome

5.Anaggravationofpreexistingcardiacinsufficiencymayoccur

6.Thistermcoversabnormalliverfunctiontests,suchasaspartateaminotransferaseincreased,alanine

aminotransferaseincreased,gamma-glutamyltransferaseincreasedandbloodalkalinephosphataseincreased

7.Decreasedspermcountisreversibleupondiscontinuationofpropafenone

ReportingofsuspectedAdverseReactions

Reportingsuspectedadversereactionsafterauthorisationofthemedicinalproductisimportant.Itallowscontinued

monitoringofthebenefit/riskbalanceofthemedicinalproduct.Healthcareprofessionalsareaskedtoreportany

suspectedadversereactionsviaHPRAPharmacovigilance,EarlsfortTerrace,IRL-Dublin2;Tel:+35316764971;

Fax:+35316762517.Website: http://www.hpra.ie/ ;e-mail: medsafety@hpra.ie

4.9Overdose

Symptomsofoverdosage:

Myocardialsymptoms

Theeffectsofpropafenonehydrochlorideoverdoseinthemyocardiummanifestasimpulsegenerationandconduction

disorderssuchasPQprolongation,QRSwidening,suppressionofsinusnodeautomaticity,AVblock,ventricular

tachycardia,ventricularflutterandventricularfibrillation.Reductionofcontractility(negativeinotropiceffect)can

Gastrointestinal

disorders Abdominalpain

Vomiting

Nausea

Diarrhoea

Constipation

Drymouth Abdominal

distension

Flatulence Retching

Gastrointestinal

disturbance

Hepatobiliary

disorders Hepaticfunction

abnormal 6 Hepatocellular

injury

Cholestasis

Hepatitis

Jaundice

Skinand

subcutaneous

tissuedisorders Urticaria

Pruritus

Rash

Erythema

Musculoskeletal

andconnective

tissuedisorders Lupus-like

syndrome

Reproductive

systemandbreast

disorders Erectile

dysfunction Spermcount

decreased 7

Generaldisorders

andadministration

siteconditions Chestpain

Asthenia

Fatigue

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Non-cardiacsymptoms

Headache,dizziness,blurredvision,paraesthesia,tremor,nausea,constipationanddrymouthmayoccurfrequently.

Inseverecasesofoverdosage,tonic-clonicconvulsions,paraesthesia,somnolence,comaandrespiratoryarrestmay

occur.

Inextremelyrarecases,convulsionshavebeenreportedonoverdose.Somnolenceanddeathhasalsobeenreported.

Treatment

Inadditiontogeneralemergencymeasures,thepatient’svitalparametersshouldbemonitoredinanintensivecare

setting,andrectified,asappropriate.

Defibrillationaswellasinfusionofdopamineandisoprenalinehavebeeneffectiveincontrollingrhythmandblood

pressure.Convulsionshavebeenalleviatedwithintravenousdiazepam.Generalsupportivemeasuressuchas

mechanicalrespiratoryassistanceandexternalcardiacmassagemaybenecessary.

Attemptstoachieveeliminationviahaemoperfusionareoflimitedefficacy.

Owingtohighproteinbinding(>95%)andthelargevolumeofdistribution,haemodialysisisineffective.

5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

Pharmacotherapeuticgroup:Antiarrhythmics,classIC

ATC-Code:C01BC03

Mechanicsofactionandpharmacodynamiceffects

Propafenonehydrochlorideisanantiarrhythmicagentwithamembranestabilising,sodiumchannelblockingproperties

(VaughanWilliams,classIc).Italsopossessesweakbeta-blockingefficacy(classIIaccordingtoVaughanWilliams).

Propafenonehydrochloridereducestherateoftheriseoftheactionpotentialtherebyslowingdowntheimpulse

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

ventriclesareprolonged.Propafenonehydrochlorideprolongstherefractoryperiodsintheaccessorypathwaysin

patientswithWPWsyndrome.

5.2Pharmacokineticproperties

Absorbtion:

Maximalplasmaconcentrationsarereachedbetweentwotothreehoursfollowingtheadministrationofpropafenone

hydrochloride.Propafenoneisknowntoundergoextensiveandsaturablepresystemicbiotransformation(CYP2D6

hepaticfirstpasseffect)whichresultsinadose-anddosageform-dependantabsolutebioavailability.

Althoughfoodincreasedthemaximumplasmaconcentrationandbioavailabilityinasingledosestudy,duringmultiple

doseadministrationofprepafenonetohealthysubjectsfooddidnotchangebioavailabilitysignificantly.

Distribution:

Propafenonedistributesrapidly.Thesteady-statevolumeofdistributionis1.9to3.0L/kg.Thedegreeofplasma

proteinbindingofpropafenoneisconcentrationdependentanddecreasedfrom97.3%at0.25ng/mLto91.3%at100

ng/mL.

Biotransformationandelimination:

Therearetwogeneticallydeterminedpatternsofpropafenonehydrochloridemetabolism.Inover90%ofpatients,the

drugisrapidlyandextensivelymetabolisedwithaneliminationhalf-lifefromtwototenhours(i.e.,extensive

metabolisers).Thesepatientsmetabolisepropafenoneintotwoactivemetabolites:5-hydroxypropafenonewhichis

formedbyCYP2D6andN-depropylpropafenone(norpropafenone)whichisformedbybothCYP3A4andCYP1A2.In

lessthan10%ofpatients,metabolismofpropafenoneisslowerbecausethe5-hydroxymetaboliteisnotformedoris

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Theestimatedpropafenoneeliminationhalf-liferangesfromtwototenhoursforextensivemetabolisersandfromten

to32hoursforpoormetabolisers.Clearanceofpropafenoneis0.67to.081L/h/kg.

Linearity/non-linearity

Inextensivemetabolisers,thesaturablehydroxylationpathway(CYP2D6)resultsinnon-linearpharmacokinetics.In

slowmetabolisers,propafenonepharmacokineticsarelinear.

Becausethesteadystateisreachedafterthreetofourdaysofdosing,therecommendeddosingregimenofpropafenone

hydrochlorideisthesameforregardlessofthemetabolicstatusforallpatients(poorversusextensivemetabolisers).

Inter/intrasubjectvariability

Withpropafenonehydrochloride,thereisaconsiderabledegreeofindividualvariabilityinpharmacokineticswhichis

dueinlargeparttothefirstpasshepaticeffectandnon-linearpharmacokineticsinextensivemetabolisers.Thelarge

variabilityinbloodlevelsrequiresthatthedosebetitratedcarefullyinpatients,payingcloseattentiontoclinicaland

electrocardiographicevidenceoftoxicity.

Elderlypopulation

Proafenoneexposureinelderlysubjectswithnormalrenalfunctionwashighlyvariable,andnotsignificantlydifferent

fromhealthyyoungsubjects.Exposureto5-hydroxypropafenonewassimilar,butexposuretopropafenone

glucuronideswasdoubled.

Paediatricpopulation

Arythmolisnotrecommendedfortheuseinchildren.

Renalimpairment

Inpatientswithrenalimpairment,exposuretoprepafenoneand5-hydroxypropafenonewassimilartothainhealthy

controls,whileaccumulationofglucuronidemetaboliteswasobserved.Propafenonehydrochlorideshouldbe

administeredcautiouslyinpatientswithrenaldisease.

Hepaticimpairment

Propafenoneshowsanincreasedoralbioavailabilityandhalf-lifeinpatientswithliverimpairment.Thedosagemust

beadjustedinpatientswithliverdisease.

5.3Preclinicalsafetydata

Preclinicaldatarevealnospecialhazardforhumansbasedonconventionalstudiesofsafetypharmacology,repeated

dosetoxicity,gentotoxicity,carcinogenicpotentialortoxicitytoreproduction.

6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

Tabletcore:

Microcrystallinecellulose,

Maizestarch,

Croscarmellosesodium,

Hypromellose,

Magnesiumstearate.

Tabletcoating:

Hypromellose,

Macrogol400,

Macrogol6000,

Health Products Regulatory Authority

______________________________________________________________________________________________________________________

Date Printed 22/08/2014 CRN 2147852 page number: 7

6.2Incompatibilities

Notapplicable.

6.3Shelflife

36months.

6.4Specialprecautionsforstorage

Thismedicinalproductdoesnotrequireanyspecialstorageconditions.

6.5Natureandcontentsofcontainer

PVC/aluminiumblisterstripspackedincartons.

Packsize:60.

6.6Specialprecautionsfordisposalofausedmedicinalproductorwastematerialsderivedfrom

suchmedicinalproductandotherhandlingoftheproduct

Nospecialrequirements.

Anyunusedproductorwastematerialshouldbedisposedofinaccordancewithlocalrequirements.

7MARKETINGAUTHORISATIONHOLDER

AbbottLaboratoriesIrelandLimited

4051KingswoodDrive

CitywestBusinessCampus

Dublin24

8MARKETINGAUTHORISATIONNUMBER

PA38/79/3

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

Dateoffirstauthorisation: 20July1983

Dateoflastrenewal: 20July2008

10DATEOFREVISIONOFTHETEXT

Health Products Regulatory Authority

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Date Printed 22/08/2014 CRN 2147852 page number: 8

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