DYSPORT

Main information

  • Trade name:
  • DYSPORT Pdr for Soln for Injection 500 Units/ ml
  • Dosage:
  • 500 Units/ ml
  • Pharmaceutical form:
  • Pdr for Soln for Injection
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug

Documents

Localization

  • Available in:
  • DYSPORT Pdr for Soln for Injection 500 Units/ml
    Ireland
  • Language:
  • English

Status

  • Source:
  • HPRA - Health Products Regulatory Authority - Ireland
  • Authorization number:
  • PA0583/001/002
  • Authorization date:
  • 08-12-2008
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

IRISHMEDICINESBOARDACTS1995AND2006

MEDICINALPRODUCTS(CONTROLOFPLACINGONTHEMARKET)REGULATIONS,2007

(S.I.No.540of2007)

PA0583/001/002

CaseNo:2047433

TheIrishMedicinesBoardinexerciseofthepowersconferredonitbytheabovementionedRegulationsherebygrantsto

IpsenLimited

190BathRoad,Slough,BerkshireSL13XE,UnitedKingdom

anauthorisation,subjecttotheprovisionsofthesaidRegulations,inrespectoftheproduct

Dysport,powderforsolutionforinjection

TheparticularsofwhicharesetoutinPartIandPartIIoftheattachedSchedule.Theauthorisationisalsosubjecttothegeneralconditionsas

maybespecifiedinthesaidRegulationsaslistedonthereverseofthisdocument.

Thisauthorisation,unlesspreviouslyrevoked,shallcontinueinforcefrom19/12/2008until07/12/2013.

SignedonbehalfoftheIrishMedicinesBoardthis

________________

Irish Medicines Board

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Date Printed 19/12/2008 CRN 2047433 page number: 1

PartII

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

Dysport,powderforsolutionforinjection

2QUALITATIVEANDQUANTITATIVECOMPOSITION

ClostridiumbotulinumtypeAtoxin-haemagglutinin

complex 500U*

*U=UnitofActivity=1mouseLD50(MLD50)whichisthequantityofmaterialthatkills50%ofmicewhen

injectedintraperitoneally.

DuringthedevelopmentofbotulinumtypeAtoxinhaemagglutinincomplex,theactivitywascommonlyexpressedin

termsofanominalweight,baseduponastandardspecificactivityof4x10 7

units/mg.

Anyreferencetothisproductexpressedinnanograms,whetherintheliteratureorelsewhere,maythereforebereadily

convertedintounitsusingtheformula1ng=40U.

Forfulllistofexcipients,seesection6.1.

3PHARMACEUTICALFORM

PowderforSolutionforInjection

UncolouredTypeIglassvialcontainingasterilewhitelyophilisedpowder.

4CLINICALPARTICULARS

4.1TherapeuticIndications

Dysportisindicatedforthetreatmentof:

-Spasticityofthearminpatientsfollowingastroke.

-Dynamicequinusfootdeformityduetospasticityinambulantpaediatriccerebralpalsypatients,twoyearsofageor

older

-Spasmodictorticollis

-Blepharospasm

-Hemifacialspasm

-Persistentsevereprimaryhyperhidrosisoftheaxillae,whichinterfereswiththeactivitiesofdailylivingandis

resistanttotopicaltreatment.

4.2Posologyandmethodofadministration

Dysportshouldonlybeadministeredbyphysicianswhohaveexperienceinthediagnosisandtreatmentofthe

conditionsindicatedandwhohavereceivedappropriatetrainingintheadministrationofDysport.

TheunitsofDysportarespecifictothepreparationandarenotinterchangeablewithotherpreparationsofbotulinum

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Axillaryhyperhidrosis

Posology

Adultsandelderly:Therecommendedinitialdosageis100unitsperaxilla.Ifthedesiredeffectisnotattained,upto

200unitsperaxillacanbeadministeredforsubsequentinjections.

Themaximumeffectshouldbeseenbyweektwoafterinjection.Inthemajorityofcases,therecommendeddosewill

provideadequatesuppressionofsweatsecretionforapproximatelyoneyear.Thetimepointforfurtherapplications

shouldbedeterminedonanindividualbasis,whenthepatient'ssweatsecretionhasreturnedtonormal,butnotmore

oftenthanevery16weeks.Thereissomeevidenceforacumulativeeffectofrepeateddosessothetimeofeach

treatmentforagivenpatientshouldbeassessedindividually.

Children:ThesafetyandeffectivenessofDysportinthetreatmentofprimaryaxillaryhyperhidrosishasnotbeen

investigatedinchildrenandadolescentsunder18years.

Methodofadministration

Theexposedcentralportionoftherubberstoppershouldbecleanedwithalcoholimmediatelypriortopiercingthe

septum.Asterile23or25gaugeneedleshouldbeused.

Dysportisreconstitutedwith2.5mlofsodiumchloridesolution(0.9%)toyieldasolutioncontaining200unitsperml

ofDysport.Dysportisadministeredbyintradermalinjectionattensiteswhentreatingaxillaryhyperhidrosis.

Theareatobeinjectedshouldbedeterminedbeforehandusingtheiodine-starchtest.Bothaxillaeshouldbecleaned

anddisinfected.Intradermalinjectionsattensites,eachsitereceiving10units(0.05ml)i.e.100units(0.5ml)peraxilla,

arethenadministered.Theinjectionshouldbeadministeredinanevendistributionwithinthehyperhidroticarea

(delineatedwiththeiodine-starchtestandusingteninjectionpoints).

TheuseofDysportinspasmodictorticollisandadultpost-strokespasticityisrestrictedtohospital-basedspecialist

units.Forthetreatmentofspasmodictorticollis,paediatriccerebralpalsyspasticityandadultpost-strokespasticity,

Dysportshouldonlybeinjectedbyspecialistsexperiencedinthediagnosisandmanagementofthisconditionandwho

havereceivedtrainingontheadministrationofDysport.

Theexposedcentralportionoftherubberstoppershouldbecleanedwithalcoholimmediatelypriortopiercingthe

septum.Asterile23or25gaugeneedleshouldbeused.

Adultspasticityofthearmpost-stroke:

Posology

Therecommendeddoseis1000units,distributedamongstthefollowingfivemuscles:flexordigitorumprofundus

(FDP),flexordigitorumsuperficialis(FDS),flexorcarpiulnaris(FCU),flexorcarpiradialis(FCR)andbicepsbrachii

(BB).Thesitesofinjectionshouldbeguidedbystandardlocationsusedforelectromyography,althoughactual

locationoftheinjectionsitewillbedeterminedbypalpation.Itisrecommendedthattheadministrationoftheinjection

shouldalsobeunderelectromyographyguidance.Allmusclesexceptthebicepsbrachiiwillbeinjectedatonesite,

whilstthebicepswillbeinjectedattwosites.Therecommendeddistributionofdoseisgivenbelow:

Thestartingdoseshouldbeloweredifthereisevidencetosuggestthatthisdosemayresultinexcessiveweaknessof

thetargetmuscles,suchasforpatientswhosetargetmusclesaresmall,wheretheBBmuscleisnottobeinjectedor

patientswhoaretobeadministeredmulti-levelinjections.Clinicalimprovementmaybeexpectedwithintwoweeks

afterinjection.Injectionsmayberepeatedapproximatelyevery16weeks,orasrequiredtomaintainresponse,butnot

morefrequentlythaneverytwelveweeks.

Children:ThesafetyandeffectivenessofDysportinthetreatmentofarmspasticityinchildrenhasnotbeen

(units) FDP

(units) FDS

(units) FCU

(units) FCR

(units) TotalDose

(units)

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Methodofadministration

Dysportisreconstitutedwith1.0mlofsodiumchlorideinjectionB.P.(0.9%)toyieldasolutioncontaining500units

permlofDysport.Dysportisadministeredbyintramuscularinjectionintothefivemusclesdetailedabovewhen

treatingarmspasticity.

Paediatriccerebralpalsyspasticity:

Posology

Theinitialrecommendeddoseis20units/kgbodyweightgivenasadivideddosebetweenbothcalfmuscles.Ifonly

onecalfisaffected,adoseof10units/kgbodyweightshouldbeused.Considerationshouldbegiventoloweringthis

startingdoseifthereisevidencetosuggestthatthisdosemayresultinexcessiveweaknessofthetargetmuscles,such

asforpatientswhosetargetmusclesaresmallorpatientswhorequireconcomitantinjectionstoothermusclegroups.

Followingevaluationofresponsetothestartingdosesubsequenttreatmentmaybetitratedwithintherange10units/kg

and30units/kgdividedbetweenbothlegs.Themaximumdoseadministeredmustnotexceed1000units/patient.

Administrationshouldprimarilybetargetedtothegastrocnemius,althoughinjectionsofthesoleusandinjectionofthe

tibialisposteriorshouldalsobeconsidered.

Theuseofelectromyography(EMG)isnotroutineclinicalpracticebutmayassistinidentifyingthemostactive

muscles.

Clinicalimprovementmaybeexpectedwithintwoweeksafterinjection.Injectionsmayberepeatedapproximately

every16weeksorasrequiredtomaintainresponse,butnotmorefrequentlythaneverytwelveweeks.

Methodofadministration

Whentreatingpaediatriccerebralpalsyspasticity,Dysportisreconstitutedwith1.0mlofsodiumchlorideinjectionB.P.

(0.9%)toyieldasolutioncontaining500unitspermlofDysport.Dysportisadministeredbyintramuscularinjection

intothecalfmuscleswhentreatingspasticity.

Spasmodictorticollis:

Posology

Adultsandelderly:Thedosesrecommendedfortorticollisareapplicabletoadultsofallagesprovidingtheadultsare

ofnormalweightwithnoevidenceoflowneckmusclemass.Areduceddoseisappropriateifthepatientismarkedly

underweightandintheelderlywherereducedmusclemassmayexist.

Theinitialrecommendeddoseforthetreatmentofspasmodictorticollisis500units(1ml)perpatientgivenasa

divideddoseandadministeredtothetwoorthreemostactiveneckmuscles.

Forrotationaltorticollisdistributethe500unitsbyadministering350unitsintothespleniuscapitismuscle,ipsilateral

tothedirectionofthechin/headrotationand150unitsintothesternomastoidmuscle,contralateraltotherotation.

Forlaterocollis,distributethe500unitsbyadministering350unitsintotheipsilateralspleniuscapitismuscleand150

unitsintotheipsilateralsternomastoidmuscle.Incasesassociatedwithshoulderelevationtheipsilateraltrapezoidor

levatorscapulaemusclesmayalsorequiretreatment,accordingtovisiblehypertrophyofthemuscleor

electromyographic(EMG)findings.Whereinjectionsofthreemusclesarerequired,distributethe500unitsasfollows,

300unitsspleniuscapitis,100unitssternomastoidand100unitstothethirdmuscle.

Forretrocollisdistributethe500unitsbyadministering250unitsintoeachofthespleniuscapitismuscles.Thismaybe

followedbybilateraltrapeziusinjections(upto250unitspermuscle)after6weeks,ifthereisinsufficientresponse.

Bilateralspleniiinjectionsmayincreasetheriskofneckmuscleweakness.

AllotherformsoftorticollisarehighlydependentonspecialistknowledgeandEMGtoidentifyandtreatthemost

activemuscles.EMGshouldbeuseddiagnosticallyforallcomplexformsoftorticollis,forreassessmentafter

unsuccessfulinjectionsinnoncomplexcases,andforguidinginjectionsintodeepmusclesorinoverweightpatients

withpoorlypalpableneckmuscles.

Onsubsequentadministration,thedosesmaybeadjustedaccordingtotheclinicalresponseandsideeffectsobserved.

Doserangesfrom250-1000unitsarerecommended,althoughthehigherdosesmaybeaccompaniedbyincreaseinside

effects,particularlydysphagia.Dosesabove1000unitsarenotrecommended.

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Injectionsshouldberepeatedapproximatelyeverytwelveweeksorasrequiredtopreventrecurrenceofsymptoms.

Children:ThesafetyandeffectivenessofDysportinthetreatmentofspasmodictorticollisinchildrenhasnotbeen

demonstrated.

Methodofadministration

WhentreatingspasmodictorticollisDysportisreconstitutedwith1mlSodiumChlorideInjectionBP(0.9%w/v)to

yieldasolutioncontaining500unitspermlofDysport.Dysportisadministeredbyintramuscularinjectionasabove

whentreatingspasmodictorticollis.

Blepharospasmandhemifacialspasm:

Posology

Adultsandelderly:Inthetreatmentofbilateralblepharospasmtherecommendedinitialdoseis120unitspereye.

Aftertheskinaroundeacheyehasbeencleaned,injectionsof0.1ml(20units)shouldbemademediallyandof0.2ml

(40units)shouldbemadelaterallyintothejunctionbetweenthepreseptalandorbitalpartsofboththeupperandlower

orbicularisoculimusclesofeacheye.Forinjectionsintotheupperlid,theneedleshouldbedirectedawayfromits

centretoavoidthelevatormuscle.Adiagramtoaidplacementoftheseinjectionsisprovided . Thereliefofsymptoms

maybeexpectedtobeginwithintwotofourdayswithmaximaleffectwithintwoweeks.

Injectionsshouldberepeatedapproximatelyeverytwelveweeksorasrequiredtopreventrecurrenceofsymptoms.On

suchsubsequentadministrationthedosemayneedtobereducedto80unitspereye-viz-:0.1ml(20units)medially

and0.1ml(20units)laterallyaboveandbeloweacheyeinthemannerpreviouslydescribed.

Thedosemaybefurtherreducedto60unitspereyebyomittingthemediallowerlidinjection.

Incasesofunilateralblepharospasmtheinjectionsshouldbeconfinedtotheaffectedeye.Patientswithhemifacial

spasmshouldbetreatedasforunilateralblepharospasm.Thedosesrecommendedareapplicabletoadultsofallages

includingtheelderly.

Children:ThesafetyandeffectivenessofDysportinthetreatmentofblepharospasmandhemifacialspasminchildren

hasnotbeendemonstrated.

Methodofadministration

WhentreatingblepharospasmandhemifacialspasmDysportisreconstitutedwith2.5mlSodiumChlorideInjectionBP

(0.9%w/v)attoyieldasolutioncontaining200unitspermlofDysport.Dysportisadministeredbysubcutaneous

injectionmediallyandlaterallyintothejunctionbetweenthepreseptalandorbitalpartsofboththeupperandlower

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4.3Contraindications

Dysportiscontra-indicatedinindividualswithknownhypersensitivitytoanycomponentofDysport.Dysportis

contraindicatedinpregnancyandlactation.

4.4Specialwarningsandprecautionsforuse

Dysportshouldbeadministeredwithcautiontopatientswithexistingproblemsinswallowingorbreathingasthese

problemscanworsenfollowingthedistributionoftheeffectoftoxinintotherelevantmuscles.Aspirationhasoccurred

inrarecases,andisariskwhentreatingpatientswithspasmodictorticolliswhohaveachronicrespiratorydisorder.

Carefulconsiderationshouldbegivenbeforetheinjectionofpatientswhohaveexperiencedapreviousallergicreaction

toaproductcontainingbotulinumtoxintypeA.Theriskofafurtherallergicreactionmustbeconsideredinrelationto

thebenefitoftreatment.

Dysportshouldonlybeusedwithcautionunderclosesupervisioninpatientswithsubclinicalorclinicalevidenceof

markeddefectiveneuro-musculartransmission(e.g.myastheniagravis).Suchpatientsmayhaveanincreased

sensitivitytoagentssuchasDysportwhichmayresultinexcessivemuscleweakness.

TherearenoreportsofanyimmuneresponseafterthelocaladministrationofClostridiumbotulinumTypeAtoxin-

haemagglutinincomplexinaccordancewiththedosesrecommendedwhentreatinghemifacialspasm.Antibody

formationtobotulinumtoxinhasbeennotedrarelyinasmallnumberoftorticollispatientsreceivingDysport.

Clinically,neutralizingantibodieshavebeendetectedbysubstantialdeteriorationinresponsetotherapyoraneedfor

consistentlyincreasingdoses.

Forthetreatmentofcerebralpalsyinchildren,Dysportshouldonlybeusedinchildrenover2yearsofage.

Aswithanyintramuscularinjection,Dysportshouldbeusedonlywherestrictlynecessaryinpatientswithprolonged

bleedingtimes,infectionorinflammationattheproposedinjectionsite.

Thisproductcontainsasmallamountofhumanalbumin.Theriskoftransmissionofsomeviralinfectionscannotbe

excludedwithabsolutecertaintyfollowingtheuseofhumanbloodorbloodproduct.

Primaryaxillaryhyperhidrosis

Medicalhistoryandphysicalexamination,alongwithspecificadditionalinvestigationsasrequired,shouldbe

performedtoexcludepotentialcausesofsecondaryhyperhidrosis(e.g.hyperthyroidism,phaeochromocytoma).This

willavoidsymptomatictreatmentofhyperhidrosiswithoutthediagnosisand/ortreatmentofunderlyingdisease.

Adverseeffectsresultingfromthedistributionoftheeffectsofthetoxintositesremotefromthesiteofadministration

havebeenreported(seesection4.8).Patientstreatedwiththerapeuticdosesmaypresentexcessivemuscleweakness.

Theriskofoccurrenceofsuchundesirableeffectsmaybereducedbyusingthelowesteffectivedoseandbynot

exceedingtherecommendeddose.

Veryrarecasesofdeath,occasionallyinacontextofdysphagia,pneumopathyand/orinpatientswithsignificant

astheniahavebeenreportedaftertreatmentwithbotulinumtoxinAorB.

Patientswithdisordersresultingindefectiveneuro-musculartransmission,difficultyinswallowingorbreathingare

moreatriskofexperiencingtheseeffects.Inthesepatients,treatmentmustbeadministeredunderthecontrolofa

specialistandonlyifthebenefitoftreatmentoutweighstherisk.

Patientsandtheircare-giversmustbewarnedofthenecessityofimmediatemedicaltreatmentincaseofproblemswith

swallowing,speechorrespiratorydisorders.

4.5Interactionwithothermedicinalproductsandotherformsofinteraction

Theeffectofbotulinumtoxinmaybepotentiatedbyaminoglycosideantibioticsoranyotherdrugsthatinterferewith

neuromusculartransmission,eg.tubocurarine-typemusclerelaxants.Thesedrugsshouldbeusedwithcaution.

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Musclerelaxantsshouldalsobeusedwithcaution,perhapsreducingthestartingdoseofrelaxantorusingan

intermediate-actiondrug,suchasvecuroniumoratracurium,ratherthanthosewithlongerlastingeffects.

4.6Pregnancyandlactation

TeratologicalandotherreproductivestudieshavenotbeenperformedwithDysport.Thesafetyofitsuseinpregnantor

lactatingwomenhasnotbeendemonstrated.

4.7Effectsonabilitytodriveandusemachines

Noneknown.

4.8Undesirableeffects

Verycommon>1/10:Common>1/100,<1/10:Uncommon>1/1000,<1/100:

Rare>1/10000,<1/1000:Veryrare<1/10000

Adverseeffectsresultingfromdistributionoftheeffectsofthetoxintositesremotefromthesiteofinjectionhave

beenveryrarelyreported(excessivemuscleweakness,dysphagia,aspirationpneumoniathatmaybefatal)(seesection

4.4).

General

Atotalofapproximately7800patientsweretreatedwithDysportduringaseriesofclinicaltrialsinpatientssuffering

blepharospasm,hemifacialspasm,torticollisorspasticityassociatedwitheithercerebralpalsyorstrokeoraxillary

hyperhydrosis.

Approximately2200patientsincludedinthesetrialsexperiencedanadverseevent.

Nervoussystemdisorders

Rare:Neuralgicamyotrophy

Skinandsubcutaneoustissuedisorders

Uncommon:Itching

Rare:Skinrashes

Generaldisordersandadministrationsiteconditions

Common:Generalisedweakness,fatigue,flu-likesyndromeandpain/bruisingatinjectionsite

AxillaryHyperhidrosis

In4clinicaltrialsinvolvingapproximately217patientstreatedwithDysportthefollowingadversereactionswere

reported:

Skinandsubcutaneoustissuedisorders

Common:Compensatorysweating

Uncommon:Paraesthenia

Adultspasticityofthearmpost-stroke

In14clinicaltrialsinvolving141patientstreatedwithDysportthefollowingadversereactionswerereported:

Gastrointestinaldisorders

Common:Dysphagia

Musculoskeletalandconnectivetissuedisorders

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Injury,poisoningandproceduralcomplications

Common:Accidentalinjury/falls

Dysphagiawasreportedwhendosesinexcessof2700unitswereusedeitherasasingleordivideddose.

Paediatriccerebralpalsyspasticity

In14clinicaltrialsinvolvingapproximately900patientstreatedwithDysport,thefollowingadversereactionswere

reported:

Gastrointestinaldisorders

Common:Diarrhoea

Musculoskeletalandconnectivetissuedisorders

Common:Legmuscleweakness

Renalandurinarydisorders

Common:Urinaryincontinence

Generaldisordersandadministrationsiteconditions

Common:Abnormalgait

Injury,poisoningandproceduralcomplications

Common:Accidentalinjuryduetofalling

Accidentalinjuryduetofallingandabnormalgaitmayhavebeenduetotheover-weakeningofthetargetmuscleand/

orthelocalspreadofDysporttoothermusclesinvolvedinambulationandbalance.

Spasmodictorticollis

In21clinicaltrialsinvolvingapproximately4100patientsthefollowingadversereactionswerereported:

Nervoussystemdisorders

Common:Dysphonia

Uncommon:Headache

Eyedisorders

Uncommon:Diplopia,Blurredvision

Respiratory,thoracicandmediastinaldisorders

Rare:Respiratorydisorders

Gastrointestinaldisorders

Verycommon:Dysphagia

Uncommon:Drymouth

Musculoskeletalandconnectivetissuedisorders

Common:Neckmuscleweakness

Dysphagiaappearedtobedoserelatedandoccurredmostfrequentlyfollowinginjectionintothesternomastoidmuscle.

Asoftdietmayberequireduntilsymptomsresolve.

Blepharospasmandhemifacialspasm

In13clinicaltrialsinvolvingapproximately1400patientsthefollowingadversereactionswerereported:

Nervoussystemdisorders

Common:Facialmuscleweakness

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Eyedisorders

Verycommon:Ptosis

Common:Diplopia,Dryeyes,Tearing

Rare:Ophthalmoplegia

Skinandsubcutaneoustissuedisorders

Common:Eyelidoedema

Rare:Entropion

SideeffectsmayoccurduetodeepormisplacedinjectionsofDysporttemporarilyparalysingothernearbymuscle

groups.

Theprofileofadversereactionsreportedtothecompanyduringpost-marketingusereflectsthepharmacologyofthe

productandthoseseenduringclinicaltrials.

4.9Overdose

Excessivelocaldosesmayproducedistantandprofoundneuromuscularparalysis.Respiratorysupportmayberequired

whereexcessivedosescauseparalysisofrespiratorymuscles.Thereisnospecificantidote;antitoxinshouldnotbe

expectedtobebeneficial.Overdosecouldleadtoanincreasedriskoftheneurotoxinenteringthebloodstream,which

maycausecomplicationsassociatedwiththeeffectsoforalbotulinumpoisoning.(e.g.:deglutitionand

phonation).

5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

Pharmacotherapeuticgroup:

OtherDermatologicalPreparationATCcode:D11AX

ClostridiumbotulinumtypeAtoxin-haemagglutinincomplexblocksperipheralcholinergictransmissionatthe

neuromuscularjunctionbyapresynapticactionatasiteproximaltothereleaseofacetylcholine.Thetoxinactsonorin

thenerveendingtoantagonisethoseeventsthataretriggeredbycalciumandthatculminateintransmitterrelease.It

doesnotaffectcholinergictransmissionorpostganglionicsympathetictransmission.

Theactionoftoxininvolvesaninitialbindingstepwherebythetoxinattachesrapidlyandavidlytothepresynaptic

nervemembrane.Secondlythereisaninternalisationstepinwhichtoxincrossesthepresynapticmembrane,without

causingonsetofparalysis.FinallythetoxininhibitsthereleaseofacetylcholinebydisruptingtheCa2+mediated

acetylcholinereleasemechanism,therebydiminishingtheendplatepotentialandcausingparalysis.

Recoveryofimpulsetransmissionoccursgraduallyasnewnerveterminalssproutandcontactismadewiththepost

synapticmotorendplate,aprocesswhichtakes6-8weeksintheexperimentalanimal.

5.2Pharmacokineticproperties

Pharmacokineticstudieswithbotulinumtoxinposeproblemsinanimalsbecauseofthehighpotency,theminutedoses

involved,thelargemolecularweightofthecompoundandthedifficultyoflabellingtoproducesufficientlyhigh

specificactivity.StudiesusingI125labelledtoxinhaveshownthatthereceptorbindingisspecificandsaturable,and

thehighdensityoftoxinreceptorsisacontributoryfactorinthehighpotency.Doseandtimeresponsesinmonkeys

showedthatatlowdosestherewasadelayof2-3dayswithpeakeffectseen5-6daysafterinjection.Thedurationof

action,measuredbychangesofocularalignmentandmuscleparalysisvariedbetween2weeksand8months.This

patternisalsoseeninman,andisattributedtotheprocessofbinding,internalisationandchangesattheneuromuscular

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5.3Preclinicalsafetydata

6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

Humanalbuminsolution200g/l

Composedof:

Humanplasmaprotein(ofwhichatleast95%ishumanalbumin)

Sodiumcaprylate,

N-Acetyltryptophan/sodiumacetyltryptophanate

Sodiumchloride

Lactosemonohydrate

6.2Incompatibilities

Donotadmixwithothermedicinalproducts.

6.3ShelfLife

Unopenedproduct:24monthswhenstoredat2–8 o

Reconstitutedproduct:Chemicalandphysicalin–usestabilityhasbeendemonstratedfor8hoursat2-8°C.

Fromamicrobiologicalpointofview,unlessthemethodofopening/reconstitutionprecludestheriskof

microbiologicalcontamination,theproductshouldbeusedimmediately.

Ifnotusedimmediately,in–usestoragetimesandconditionspriortousearetheresponsibilityoftheuserandshould

notbelongerthan8hoursat2-8°C,theopening/reconstitutionoftheproducthavingtakenplaceincontrolledand

validatedasepticconditions.

6.4Specialprecautionsforstorage

Storeunopenedvialsinarefrigeratorat2°Cand8°C.Donotfreeze.

6.5Natureandcontentsofcontainer

Natureofcontainer/closure:

Dysportiscontainedin3mlwhiteneutralglassvials(Ph.Eur./BPTypeI),injectionsulphatetreatedtoreducethe

surfacealkalinity,with13mmneck.

Thevialissealedwitha13mmspecialbutylfreezedryingstopperand13mmTypeIaluminiumoverseal.

Contentsofcontainer:

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6.6Specialprecautionsfordisposalofausedmedicinalproductorwastematerialsderivedfrom

suchmedicinalproductandotherhandlingoftheproduct

Immediatelyaftertreatmentofthepatient,anyresidualDysportwhichmaybepresentineithervialorsyringeshould

beinactivatedwithdilutehypochloritesolution(1%availablechlorine).Thereafter,allitemsshouldbedisposedofin

accordancewithstandardhospitalpractice.

SpillagesofDysportshouldbewipedupwithanabsorbentclothsoakedindilutehypochloritesolution.

7MARKETINGAUTHORISATIONHOLDER

IpsenLimited,

190BathRoad,

Slough,

Berkshire,

SL13XE,

8MARKETINGAUTHORISATIONNUMBER

PA583/1/2

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

DateofFirstAuthorisation:8thDecember2008

10DATEOFREVISIONOFTHETEXT

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