APO-GO AMPOULES

Main information

  • Trade name:
  • APO-GO AMPOULES
  • Dosage:
  • 10 Mg/ Ml
  • Pharmaceutical form:
  • Solution for Inj/Inf
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug

Documents

Localization

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

Status

  • Source:
  • HPRA - Health Products Regulatory Authority - Ireland
  • Authorization number:
  • PA1496/002/001
  • Authorization date:
  • 08-10-2010
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

APO-goAMPOULES10mg/mlSolutionforInjectionorInfusion

2QUALITATIVEANDQUANTITATIVECOMPOSITION

1mlcontains10mgapomorphinehydrochloride

2mlcontains20mgapomorphinehydrochloride

5mlcontains50mgapomorphinehydrochloride

Excipient:Sodiummetabisulphite(E223)1mgperml

Forafulllistofexcipients,seesection6.1

3PHARMACEUTICALFORM

SolutionforInjectionorInfusion

Solutionisclearandcolourless

pH3.0-4.0

4CLINICALPARTICULARS

4.1TherapeuticIndications

Thetreatmentofdisablingmotorfluctuations(“on-off”phenomena)inpatientswithParkinson’sdiseasewhichpersist

despiteindividuallytitratedtreatmentwithlevodopa(withaperipheraldecarboxylaseinhibitor)and/orotherdopamine

agonists.

4.2Posologyandmethodofadministration

APO-goAmpoules10mg/mlSolutionforInjectionorInfusionisforsubcutaneoususebyintermittentbolusinjection.

APO-goAmpoules10mg/mlSolutionforInjectionorInfusionmayalsobeadministeredasacontinuoussubcutaneous

infusionbyminipumpand/orsyringe-driver(seesection6.6).

Apomorphinemustnotbeusedviatheintravenousroute.

Dosage

Adults

Administration

SelectionofPatientssuitableforAPO-goinjections:

PatientsselectedfortreatmentwithAPO-goshouldbeabletorecognisetheonsetoftheir‘off’symptomsandbe

capableofinjectingthemselvesorelsehavearesponsiblecarerabletoinjectforthemwhenrequired.

Itisessentialthatthepatientisestablishedondomperidone,usually20mgthreetimesdaily,foratleasttwodaysprior

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 13/03/2012 CRN 2105137 page number: 1

Apomorphineshouldbeinitiatedinthecontrolledenvironmentofaspecialistclinic.Thepatientshouldbesupervised

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

levodopa,withorwithoutdopamineagonists,shouldbeoptimisedbeforestartingAPO-gotreatment.

Determinationofthethresholddose.

Theappropriatedoseforeachpatientisestablishedbyincrementaldosingschedules.Thefollowingscheduleis

suggested:-

1mgofapomorphineHCl(0.1ml),thatisapproximately15-20micrograms/kg,maybeinjectedsubcutaneouslyduring

ahypokineticor‘off’periodandthepatientisobservedover30minutesforamotorresponse.

Ifnoresponse,oraninadequateresponse,isobtainedaseconddoseof2mgofapomorphineHCl(0.2ml)isinjected

subcutaneouslyandthepatientobservedforanadequateresponseforafurther30minutes.

Thedosagemaybeincreasedbyincrementalinjectionswithatleastafortyminuteintervalbetweensucceeding

injections,untilasatisfactorymotorresponseisobtained.

Establishmentoftreatment.

Oncetheappropriatedoseisdetermined,asinglesubcutaneousinjectionmaybegivenintothelowerabdomenorouter

thighatthefirstsignsofan‘off’episode.Itcannotbeexcludedthatabsorptionmaydifferwithdifferentinjectionsites

withinasingleindividual.Accordingly,thepatientshouldthenbeobservedforthenexthourtoassessthequalityof

theirresponsetotreatment.Alterationsindosagemaybemadeaccordingtothepatient’sresponse.

Theoptimaldosageofapomorphinehydrochloridevariesbetweenindividualsbut,onceestablished,remainsrelatively

constantforeachpatient.

Precautionsoncontinuingtreatment.

ThedailydoseofAPO-govarieswidelybetweenpatients,typicallywithintherangeof3-30mg,givenas1-10

injectionsandsometimesasmanyas12separateinjectionsperday.

ItisrecommendedthatthetotaldailydoseofapomorphineHClshouldnotexceed100mgandthatindividualbolus

injectionsshouldnotexceed10mg.

Inclinicalstudiesithasusuallybeenpossibletomakesomereductioninthedoseoflevodopa;thiseffectvaries

considerablybetweenpatientsandneedstobecarefullymanagedbyanexperiencedphysician.

Oncetreatmenthasbeenestablished,domperidonetherapymaybegraduallyreducedinsomepatientsbutsuccessfully

eliminatedonlyinafew,withoutanyvomitingorhypotension.

ContinuousInfusion

Patientswhohaveshownagood‘on’periodresponseduringtheinitiationstage,butwhoseoverallcontrolremains

unsatisfactoryusingintermittentinjections,orwhorequiremanyandfrequentinjections(morethan10perday),may

becommencedonortransferredtocontinuoussubcutaneousinfusionbyminipumpand/orsyringe-driver(seesection

6.6)asfollows:-

Continuousinfusionisstartedatarateof1mgapomorphineHCl(0.1ml)perhourthenincreasedaccordingtothe

individualresponse.Increasesintheinfusionrateshouldnotexceed0.5mgperhouratintervalsofnotlessthan4

hours.Hourlyinfusionratesmayrangebetween1mgand4mg(0.1mland0.4ml),equivalentto0.015-0.06

mg/kg/hour.Infusionsshouldrunforwakinghoursonly.Unlessthepatientisexperiencingseverenight-time

problems,24hourinfusionsarenotadvised.Tolerancetothetherapydoesnotseemtooccuraslongasthereisan

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 13/03/2012 CRN 2105137 page number: 2

Patientsmayneedtosupplementtheircontinuousinfusionwithintermittentbolusboostsviathepumpsystemas

necessary,andasdirectedbytheirphysician.

Areductionindosageofotherdopamineagonistsmaybeconsideredduringcontinuousinfusion.

Childrenandadolescents:

APO-goAmpoules10mg/mlSolutionforInjectionorInfusioniscontraindicatedforchildrenandadolescentsunder18

yearsofage(seesection4.3).

Elderly:

TheelderlyarewellrepresentedinthepopulationofpatientswithParkinson’sdiseaseandconstituteahighproportion

ofthosestudiedinclinicaltrialsofAPO-go.ThemanagementofelderlypatientstreatedwithAPO-gohasnotdiffered

fromthatofyoungerpatients.

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.

APO-goAmpoules10mg/mlSolutionforInjectionorInfusioncontainssodiummetabisulphitewhichmayrarelycause

severeallergicreactionsandbronchospasm.

Haemolyticanaemiaandthrombocytopeniahavebeenreportedinpatientstreatedwithapomorphine.Haematology

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 13/03/2012 CRN 2105137 page number: 3

Cautionisadvisedwhencombiningapomorphinewithothermedicinalproducts,especiallythosewithanarrow

therapeuticrange(seesection4.5).

Neuropsychiatricproblemsco-existinmanypatientswithadvancedParkinson’sdisease.Thereisevidencethatfor

somepatientsneuropsychiatricdisturbancesmaybeexacerbatedbyapomorphine.Specialcareshouldbeexercised

whenapomorphineisusedinthesepatients.

Apomorphinehasbeenassociatedwithsomnolence,andotherdopamineagonistscanbeassociatedwithsuddensleep

onsetepisodes,particularlyinpatientswithParkinson’sdisease.Patientsmustbeinformedofthisandadvisedto

exercisecautionwhiledrivingoroperatingmachinesduringtreatmentwithapomorphine.Patientswhohave

experiencedsomnolencemustrefrainfromdrivingoroperatingmachines.Furthermore,areductionofdosageor

terminationoftherapymaybeconsidered.

Pathologicalgambling,increasedlibidoandhypersexualityhavebeenreportedinpatientstreatedwithdopamine

agonistsforParkinson’sdisease,includingapomorphine.

4.5Interactionwithothermedicinalproductsandotherformsofinteraction

PatientsselectedfortreatmentwithapomorphineHClarealmostcertaintobetakingconcomitantmedicationsfortheir

Parkinson’sdisease.IntheinitialstagesofapomorphineHCltherapy,thepatientshouldbemonitoredforunusualside-

effectsorsignsofpotentiationofeffect.

Neurolepticmedicinalproductsmayhaveanantagonisticeffectifusedwithapomorphine.Thereisapotential

interactionbetweenclozapineandapomorphine,howeverclozapinemayalsobeusedtoreducethesymptomsof

neuropsychiatriccomplications.

IfneurolepticmedicinalproductshavetobeusedinpatientswithParkinson’sdiseasetreatedbydopamineagonists,a

gradualreductioninapomorphinedosemaybeconsideredwhenadministrationisbyminipumpand/orsyringe-driver

(symptomssuggestiveofneurolepticmalignantsyndromehavebeenreportedrarelywithabruptwithdrawalof

dopaminergictherapy).

ItisrecommendedtoavoidtheadministrationofapomorphinewithotherdrugsknowntoprolongtheQTinterval.

4.6Fertility,pregnancyandlactation

Thereisnoexperienceofapomorphineusageinpregnantwomen.

Animalreproductionstudiesdonotindicateanyteratogeniceffects,butdosesgiventoratswhicharetoxictothe

mothercanleadtofailuretobreatheinthenewborn.Thepotentialriskforhumansisunknown.SeeSection5.3.

APO-goshouldnotbeusedinpregnancyunlessclearlynecessary.

Itisnotknownwhetherapomorphineisexcretedinbreastmilk.Adecisiononwhethertocontinue/discontinue

breastfeedingortocontinue/discontinuetherapywithAPO-goshouldbemadetakingintoaccountthebenefitofbreast-

feedingtothechildandthebenefittoAPO-gotothewomen.

4.7Effectsonabilitytodriveandusemachines

Patientsbeingtreatedwithapomorphineandpresentingwithsomnolenceand/orsuddensleepepisodesmustbe

informedtorefrainfromdrivingorengaginginactivities(e.g.operatingmachines)whereimpairedalertnessmayput

themselvesorothersatriskofseriousinjuryordeathuntilsuchrecurrentepisodesandsomnolencehaveresolved(see

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 13/03/2012 CRN 2105137 page number: 4

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.

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 13/03/2012 CRN 2105137 page number: 5

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:

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 13/03/2012 CRN 2105137 page number: 6

4.9Overdose

Thereislittleclinicalexperienceofoverdosewithapomorphinebythisrouteofadministration.Symptomsofoverdose

maybetreatedempiricallyassuggestedbelow:-

Excessiveemesismaybetreatedwithdomperidone.

Respiratorydepressionmaybetreatedwithnaloxone.

Hypotension:appropriatemeasuresshouldbetaken,e.g.raisingthefootofthebed.

Bradycardiamaybetreatedwithatropine.

5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

Pharmacotherapeuticgroup:Dopamineagonists

ATCClassification: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),andthatthebriefdurationofclinicalactionoftheactivesubstance(about

1hour)isexplainedbyitsrapidclearance.Themetabolismofapomorphineisbyglucuronidationandsulphonationto

atleasttenpercentofthetotal;otherpathwayshavenotbeendescribed.

5.3Preclinicalsafetydata

Repeatdosesubcutaneoustoxicitystudiesrevealnospecialhazardforhumans,beyondtheinformationincludedin

othersectionsoftheSmPC.

Invitrogenotoxicitystudiesdemonstratedmutagenicandclastogeniceffects,mostlikelyduetoproductsformedby

oxidationofapomorphine.However,apomorphinewasnotgenotoxicintheinvivostudiesperformed.

Theeffectofapomorphineonreproductionhasbeeninvestigatedinrats.Apomorphinewasnotteratogenicinthis

species,butitwasnotedthatdoseswhicharetoxictothemothercancauselossofmaternalcareandfailuretobreathe

inthenewborn.

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 13/03/2012 CRN 2105137 page number: 7

6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

Sodiummetabisulphite(E223)

Hydrochloricacid,concentrated(forpHadjustment)

Sodiumhydroxide(forpHadjustment)

Waterforinjections

6.2Incompatibilities

Intheabsenceofcompatibilitystudies,thismedicinalproductmustnotbemixedwithothermedicinalproducts.

6.3Shelflife

3years

Onceopened,useimmediately.Discardanyunusedcontents.

6.4Specialprecautionsforstorage

Donotstoreabove25 o

Storeintheoriginalpackageinordertoprotectfromlight.

6.5Natureandcontentsofcontainer

TypeIglassampoulescontaining2mlSolutionforInjectionorInfusion,inpacksof5ampoules.

TypeIglassampoulescontaining5mlSolutionforInjectionorInfusion,inpacksof5ampoules.

Bundlepackof25and50ampoulesareavailableinsometerritories.

The25ampoulebundlespackconsistsof5packseachcontaining5ampoules.

The50ampoulebundlespackconsistsof10packseachcontaining5ampoules.

Notallpacksizesaremarketed.

6.6Specialprecautionsfordisposalandotherhandling

Donotuseifthesolutionhasturnedgreen.

Thesolutionshouldbeinspectedvisuallypriortouse.Onlyclearand colourlesssolutionsshouldbeused.

Forsingleuseonly.Anyunusedsolutionshouldbediscarded.

Continuousinfusionandtheuseofaminipumpand/orsyringe-driver.

Thechoiceofwhichminipumpand/orsyringe-drivertouse,andthedosagesettingsrequired,willbedeterminedbythe

physicianinaccordancewiththeparticularneedsofthepatient.

7MARKETINGAUTHORISATIONHOLDER

GenusPharmaceuticalsLimited

ParkViewHouse

65LondonRoad

Newbury

BerkshireRG141JN

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 13/03/2012 CRN 2105137 page number: 8

8MARKETINGAUTHORISATIONNUMBER

PA1496/002/001

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

Dateoffirstauthorisation:07March2003

Dateoflastrenewal: 25January2010

10DATEOFREVISIONOFTHETEXT

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 13/03/2012 CRN 2105137 page number: 9