APO-GO PFS

Main information

  • Trade name:
  • APO-GO PFS
  • Dosage:
  • 5 Mg/ Ml
  • Pharmaceutical form:
  • Solution for Infusion
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug

Documents

Localization

  • Available in:
  • APO-GO PFS
    Ireland
  • Language:
  • English

Status

  • Source:
  • HPRA - Health Products Regulatory Authority - Ireland
  • Authorization number:
  • PA1496/002/003
  • Authorization date:
  • 04-12-2009
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

APO-goPFS5mg/mlSolutionforInfusioninPre-filledSyringe

2QUALITATIVEANDQUANTITATIVECOMPOSITION

1mlcontains5mgapomorphinehydrochloride.

Each10mlpre-filledsyringecontains50mgapomorphinehydrochloride.

Excipient:

Sodiummetabisulphite(E223)0.5mgperml

Forafulllistofexcipients,seeSection6.1

3PHARMACEUTICALFORM

SolutionforInfusion,pre-filledsyringe

Solutionisclearandcolourless

pH3.0-4.0

4CLINICALPARTICULARS

4.1TherapeuticIndications

Treatmentofmotorfluctuations('on-off'phenomena)inpatientswithParkinson’sdiseasewhicharenotsufficiently

controlledbyoralanti-Parkinsonmedication.

4.2Posologyandmethodofadministration

SelectionofPatientsSuitableforAPO-g

PatientsselectedfortreatmentwithAPO-goshouldbeabletorecognisetheonsetoftheir‘off’symptomsandbe

capableofinjectingthemselvesorelsehavearesponsiblecarerabletoinjectforthemwhenrequired.

Itisessentialthatthepatientisestablishedondomperidone,usually20mgthreetimesdailyforatleasttwodaysprior

toinitiationoftherapy.

Apomorphineshouldbeinitiatedinthecontrolledenvironmentofaspecialistclinic.Thepatientshouldbesupervised

byaphysicianexperiencedinthetreatmentofParkinson’sdisease(e.g.neurologist).Thepatient’streatmentwith

levodopa,withorwithoutdopamineagonists,shouldbeoptimisedbeforestartingAPO-gotreatment.

Administration

APO-goPFS5mg/mlSolutionforInfusioninPre-filledSyringeisapre-dilutedpre-filledsyringeintendedforuse

withoutdilutionasacontinuoussubcutaneousinfusionbyminipumpand/orsyringe-driver.Itisnotintendedtobe

usedforintermittentinjection.

Apomorphinemustnotbeusedviatheintravenousroute.

Donotuseifthesolutionhasturnedgreen.Thesolutionshouldbeinspectedvisuallypriortouse.Onlyclear,

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ContinuousInfusion

Patientswhohaveshownagood‘on’periodresponseduringtheinitiationstageofapomorphinetherapy,butwhose

overallcontrolremainsunsatisfactoryusingintermittentinjections,orwhorequiremanyandfrequentinjections(more

than10perday),maybecommencedonortransferredtocontinuoussubcutaneousinfusionbyminipumpand/or

syringedriverasfollows:-

Thechoice,ofwhichminipumpand/orsyringe-drivertouse,andthedosagesettingsrequired,willbedeterminedby

thephysicianinaccordancewiththeparticularneedsofthepatient.

Thethresholddoseforcontinuousinfusionshouldbedeterminedasfollows:Continuousinfusionisstartedatarateof

1mgapomorphineHCl(0.2ml)perhourthenincreasedaccordingtotheindividualresponseeachday.Increasesin

theinfusionrateshouldnotexceed0.5mgatintervalsofnotlessthan4hours.Hourlyinfusionratesmayrange

between1mgand4mg(0.2mland0.8ml),equivalentto0.014–0.06mg/kg/hour.Infusionsshouldrunforwaking

hoursonly.Unlessthepatientisexperiencingseverenight-timeproblems,24hourinfusionsarenotadvised.

Tolerancetothetherapydoesnotseemtooccuraslongasthereisanovernightperiodwithouttreatmentofatleast4

hours.Inanyevent,theinfusionsiteshouldbechangedevery12hours.

Patientsmayneedtosupplementtheircontinuousinfusionwithintermittentbolusboosts,asnecessary,andasdirected

bytheirphysician.

Areductionindosageofotherdopamineagonistsmaybeconsideredduringcontinuousinfusion.

Establishmentoftreatment.

Alterationsindosagemaybemadeaccordingtothepatient’sresponse.

Theoptimaldosageofapomorphinehydrochloridevariesbetweenindividualsbut,onceestablished,remainsrelatively

constantforeachpatient.

Precautionsoncontinuingtreatment

ThedailydoseofAPO-govarieswidelybetweenpatients,typicallywithintherangeof3-30mg.

ItisrecommendedthatthetotaldailydoseofapomorphineHClshouldnotexceed100mg.

Inclinicalstudiesithasusuallybeenpossibletomakesomereductioninthedoseoflevodopa;thiseffectvaries

considerablybetweenpatientsandneedsto becarefullymanagedbyanexperiencedphysician.

Oncetreatmenthasbeenestablisheddomperidonetherapymaybegraduallyreducedinsomepatientsbutsuccessfully

eliminatedonlyinafew,withoutanyvomitingorhypotension.

Childrenandadolescents

APO-goPFS5mg/mlSolutionforInfusioninPre-filledSyringeiscontra-indicatedforchildrenandadolescentsunder

18yearsofage(seeSection4.3).

Elderly

TheelderlyarewellrepresentedinthepopulationofpatientswithParkinson’sdiseaseandconstituteahighproportion

ofthosestudiedinclinicaltrialsofAPO-go.ThemanagementofelderlypatientstreatedwithAPO-gohasnotdiffered

fromthatofyoungerpatients.However,extracautionisrecommendedduringinitiationoftherapyinelderlypatients

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Renalimpairment

Adoseschedulesimilartothatrecommendedforadults,andtheelderly,canbefollowedforpatientswithrenal

impairment(seeSection4.4).

4.3Contraindications

Inpatientswithrespiratorydepression,dementia,psychoticdiseasesorhepaticinsufficiency.

IntermittentapomorphineHCltreatmentisnotsuitableforpatientswhohavean'on'responsetolevodopawhichis

marredbyseveredyskinesiaordystonia.

APO-goshouldnotbeadministeredtopatientswhohaveaknownhypersensitivitytoapomorphineoranyexcipientsof

themedicinalproduct.

APO-goiscontraindicatedforchildrenandadolescentsunder18yearsofage.

4.4Specialwarningsandprecautionsforuse

ApomorphineHClshouldbegivenwithcautiontopatientswithrenal,pulmonaryorcardiovasculardiseaseand

personspronetonauseaandvomiting.

Extracautionisrecommendedduringinitiationoftherapyinelderlyand/ordebilitatedpatients.

Sinceapomorphinemayproducehypotension,evenwhengivenwithdomperidonepretreatment,careshouldbe

exercisedinpatientswithpre-existingcardiacdiseaseorinpatientstakingvasoactivemedicinalproductssuchas

antihypertensives,andespeciallyinpatientswithpre-existingposturalhypotension.

Sinceapomorphine,especiallyathighdose,mayhavethepotentialforQTprolongation,cautionshouldbeexercised

whentreatingpatientsatriskfortorsadesdepointesarrhythmia.

Apomorphineisassociatedwithlocalsubcutaneouseffects.Thesecansometimesbereducedbytherotationof

injectionsitesorpossiblybytheuseofultrasound(ifavailable)toareasofnodularityandinduration.

Haemolyticanaemiaandthrombocytopeniahavebeenreportedinpatientstreatedwithapomorphine.Haematology

testsshouldbeundertakenatregularintervalsaswithlevodopa,whengivenconcomitantlywithapomorphine.

Cautionisadvisedwhencombiningapomorphinewithothermedicinalproducts,especiallythosewithanarrow

therapeuticrange(seeSection4.5)

Neuropsychiatricproblemsco-existinmanypatientswithadvancedParkinson’sdisease.Thereisevidencethatfor

somepatientsneuropsychiatricdisturbancesmaybeexacerbatedbyapomorphine.Specialcareshouldbeexercised

whenapomorphineisusedinthesepatients.

Apomorphinehasbeenassociatedwithsomnolence,andotherdopamineagonistscanbeassociatedwithsuddensleep

onsetepisodes,particularlyinpatientswithParkinson’sdisease.Patientsmustbeinformedofthisandadvisedto

exercisecautionwhiledrivingoroperatingmachinesduringtreatmentwithapomorphine.Patientswhohave

experiencedsomnolencemustrefrainfromdrivingoroperatingmachines.Furthermoreareductionofdosageor

terminationoftherapymaybeconsidered.

Pathologicalgambling,increasedlibidoandhypersexualityhavebeenreportedinpatientstreatedwithdopamine

agonistsforParkinson'sdisease,includingapomorphine.

APO-goPFS5mg/mlSolutionforInfusioninPre-filledSyringecontainssodiummetabisulphitewhichmayrarely

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Thismedicinalproductcontainslessthan1mmolsodium(23mg)per10ml,i.e.essentially“sodium-free”.

4.5Interactionwithothermedicinalproductsandotherformsofinteraction

PatientsselectedfortreatmentwithapomorphineHClarealmostcertaintobetakingconcomitantmedicinalproducts

fortheirParkinson’sdisease.IntheinitialstagesofapomorphineHCltherapy,thepatientshouldbemonitoredfor

unusualundesirableeffectsorsignsofpotentiationofeffect.

Neurolepticmedicinalproductsmayhaveanantagonisticeffectifusedwithapomorphine.Thereisapotential

interactionbetweenclozapineandapomorphine,howeverclozapinemayalsobeusedtoreducethesymptomsof

neuropsychiatriccomplications.

IfneurolepticmedicinalproductshavetobeusedinpatientswithParkinson’sdiseasetreatedbydopamineagonists,a

gradualreductioninapomorphinedosemaybeconsideredwhenadministrationisbyminipumpand/orsyringe-driver

(symptomssuggestiveofneurolepticmalignantsyndromehavebeenreportedrarelywithabruptwithdrawalof

dopaminergictherapy).

Thepossibleeffectsofapomorphineontheplasmaconcentrationsofothermedicinalproductshavenotbeenstudied.

Thereforecautionisadvisedwhencombiningapomorphinewithothermedicinalproducts,especiallythosewitha

narrowtherapeuticrange.

AntihypertensiveandCardiacActiveMedicinalProducts

Evenwhenco-administeredwithdomperidone,apomorphinemaypotentiatetheantihypertensiveeffectsofthese

medicinalproducts(seeSection4.4).

ItisrecommendedtoavoidtheadministrationofapomorphinewithotherdrugsknowntoprolongtheQTinterval.

4.6Fertility,pregnancyandlactation

Thereisnoexperienceofapomorphineusageinpregnantwomen.

Animalreproductionstudiesdonotindicateanyteratogeniceffects,butdosesgiventoratswhicharetoxictothe

mothercanleadtofailuretobreatheinthenewborn.Thepotentialrisktohumansisunknown.SeeSection5.3.

APO-goshouldnotbeusedinpregnancyunlessclearlynecessary.

Itisnotknownwhetherapomorphineisexcretedinbreastmilk.Adecisiononwhethertocontinue/discontinue

breastfeedingortocontinue/discontinuetherapywithAPO-goshouldbemadetakingintoaccountthebenefitofbreast-

feedingtothechildandthebenefitofAPO-gotothewoman.

4.7Effectsonabilitytodriveandusemachines

ApomorphineHClhasminorormoderateinfluenceontheabilitytodriveandusemachines.

Patientsbeingtreatedwithapomorphineandpresentingwithsomnolenceand/orsuddensleepepisodesmustbe

informedtorefrainfromdrivingorengaginginactivities(e.g.operatingmachines)whereimpairedalertnessmayput

themselvesorothersatriskofseriousinjuryordeathuntilsuchrecurrentepisodesandsomnolencehaveresolved(see

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4.8Undesirableeffects

Verycommon(1/10)

Common(1/100to<1/10)

Uncommon(1/1,000to<1/100)

Rare(1/10,000to<1/1,000)

Veryrare(<1/10,000)

Notknown(cannotbeestimatedfromtheavailabledata)

Bloodandlymphaticsystemdisorders

Uncommon:

Haemolyticanaemiaandthrombocytopeniahasbeenreportedinpatientstreatedwithapomorphine.

Rare:

EosinophiliahasrarelyoccurredduringtreatmentwithapomorphineHCl.

Immunesystemdisorders

Rare:

Duetothepresenceofsodiummetabisulphite,allergicreactions(includinganaphylaxisandbronchospasm)mayoccur.

Psychiatricdisorders

Common:

Neuropsychiatricdisturbancesarecommoninparkinsonianpatients.APO-goshouldbeusedwithspecialcautionin

thesepatients.Neuropsychiatricdisturbances(includingtransientmildconfusionandvisualhallucinations)have

occurredduringapomorphineHCltherapy.

Notknown:

PatientstreatedwithdopamineagonistsfortreatmentofParkinson'sdisease,includingapomorphine,especiallyathigh

doses,havebeenreportedasexhibitingsignsofpathologicalgambling,increasedlibidoandhypersexuality;generally

reversibleuponreductionofthedoseortreatmentdiscontinuation.

Nervoussystemdisorders

Common:

TransientsedationwitheachdoseofapomorphineHClatthestartoftherapymayoccur;thisusuallyresolvesoverthe

firstfewweeks.

Apomorphineisassociatedwithsomnolence.

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Uncommon:

Apomorphinemayinducedyskinesiasduring‘on’periods,whichcanbesevereinsomecases,andinafewpatients

mayresultincessationoftherapy.

Vasculardisorders

Uncommon:

Posturalhypotensionisseeninfrequentlyandisusuallytransient(SeeSection4.4).

Respiratory,thoracicandmediastinaldisorders

Common:

Yawninghasbeenreportedduringapomorphinetherapy.

Uncommon:

Breathingdifficultieshavebeenreported.

Gastrointestinaldisorders

Common:

Nauseaandvomiting,particularlywhenapomorphinetreatmentisfirstinitiated,usuallyasaresultoftheomissionof

domperidone(SeeSection4.2).

Skinandsubcutaneoustissuedisorders

Uncommon:

Localandgeneralisedrasheshavebeenreported.

Generaldisordersandadministrationsiteconditions

Verycommon:

Mostpatientsexperienceinjectionsitereactions,particularlywithcontinuoususe.Thesemayincludesubcutaneous

nodules,induration,erythema,tendernessandpanniculitis.Variousotherlocalreactions(suchasirritation,itching,

bruisingandpain)mayalsooccur.

Uncommon:

Injectionsitenecrosisandulcerationhavebeenreported.

Notknown:

Peripheraloedemahasbeenreported.

Investigations

Uncommon:

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4.9Overdose

Thereislittleclinicalexperienceofoverdosewithapomorphinebythisrouteofadministration.Symptomsofoverdose

maybetreatedempiricallyassuggestedbelow:-

Excessiveemesismaybetreatedwithdomperidone.

Respiratorydepressionmaybetreatedwithnaloxone.

Hypotension:appropriatemeasuresshouldbetaken,e.g.raisingthefootofthebed.

Bradycardiamaybetreatedwithatropine.

5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

Pharmatherapeuticgroup:Dopamineagonists

ATCCode:N04BC07

Apomorphineisadirectstimulantofdopaminereceptorsand,whilepossessingbothD1andD2receptoragonist

properties,doesnotsharetransportormetabolicpathwayswithlevodopa.

Althoughinintactexperimentalanimals,administrationofapomorphinesuppressestherateoffiringofnigro-striatal

cellsandinlowdosehasbeenfoundtoproduceareductioninlocomotoractivity(thoughttorepresentpre-synaptic

inhibitionofendogenousdopaminerelease)itsactionsonparkinsonianmotordisabilityarelikelytobemediatedat

post-synapticreceptorsites.Thisbiphasiceffectisalsoseeninhumans.

5.2Pharmacokineticproperties

Aftersubcutaneousinjectionofapomorphineitsfatecanbedescribedbyatwo-compartmentmodel,withadistribution

half-lifeof5(±1.1)minutesandaneliminationhalf-lifeof33(±3.9)minutes.Clinicalresponsecorrelateswellwith

levelsofapomorphineinthecerebrospinalfluid;theactivesubstancedistributionbeingbestdescribedbyatwo-

compartmentmodel.Apomorphineisrapidlyandcompletelyabsorbedfromsubcutaneoustissue,correlatingwiththe

rapidonsetofclinicaleffects(4-12minutes),andthebriefdurationofclinicalactionoftheactivesubstance(about1

hour)isexplainedbyitsrapidclearance.Themetabolismofapomorphineisbyglucuronidationandsulphonationtoat

leasttenpercentofthetotal;otherpathwayshavenotbeendescribed.

5.3Preclinicalsafetydata

Repeatdosesubcutaneoustoxicitystudiesrevealnospecialhazardforhumans,beyondtheinformationincludedin

othersectionsoftheSmPC.

Invitrogenotoxicitystudiesdemonstratedmutagenicandclastogeniceffects,mostlikelyduetoproductsformedby

oxidationofapomorphine.However,apomorphinewasnotgenotoxicintheinvivostudiesperformed.

Theeffectofapomorphineonreproductionhasbeeninvestigatedinrats.Apomorphinewasnotteratogenicinthis

species,butitwasnotedthatdoseswhicharetoxictothemothercancauselossofmaternalcareandfailuretobreathe

inthenewborn.

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6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

Sodiummetabisulphite(E223)

Hydrochloricacid,concentrated(forpHadjustment)

WaterforInjections

6.2Incompatibilities

Intheabsenceofcompatibilitystudies,thismedicinalproductmustnotbemixedwithothermedicinalproducts.

6.3Shelflife

2years

Onceopenedthepre-filledsyringeshouldbeusedimmediately.

Fromamicrobiologicalpointofview,unlessthemethodofopeningprecludestheriskofmicrobialcontamination,the

productshouldbeusedimmediately.

Ifnotusedimmediatelyin-usestoragetimesandconditionsaretheresponsibilityoftheuser.

6.4Specialprecautionsforstorage

Keepthepre-filledsyringeintheoutercartoninordertoprotectfromlight.

ForstorageoftheproductafteropeningseeSection6.3.

Donotstoreabove25 o

6.5Natureandcontentsofcontainer

Clearglass(TypeI)pre-filledsyringe,10mlwithachlorobutylrubberstopperandtip.

Packscontain5Pre-filledSyringesinacardboardtrayinanoutercardboardcarton.

Bundlepacksof25and50Pre-filledSyringesareavailableinsometerritories:

The25pre-filledsyringesbundlepacksconsistsof5packseachcontaining5pre-filledsyringes.

The50pre-filledsyringesbundlepacksconsistsof10packseachcontaining5pre-filledsyringes.

Notallpacksizesaremarketed.

6.6Specialprecautionsfordisposalandotherhandling

APO-goPFS5mg/mlSolutionforInfusioninPre-filledSyringeisforsingleuseonly.Anyunusedsolutionshouldbe

discarded.

Donotuseifthesolutionhasturnedgreen.Thesolutionshouldbeinspectedvisuallypriortouse.Onlyclear,

colourlessandparticlefreesolutionshouldbeused.

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7MARKETINGAUTHORISATIONHOLDER

GenusPharmaceuticalsLimited

ParkViewHouse

65LondonRoad

Newbury

BerkshireRG141JN

UnitedKingdom

8MARKETINGAUTHORISATIONNUMBER

PA1496/2/3

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

Dateoffirstauthorisation:29February2008

Dateoflastrenewal:15September2009

10DATEOFREVISIONOFTHETEXT

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