APO-GO PEN

Main information

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

Documents

Localization

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

Status

  • Source:
  • HPRA - Health Products Regulatory Authority - Ireland
  • Authorization number:
  • PA1496/002/002
  • Authorization date:
  • 25-01-2010
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

APO-goPEN10mg/mlSolutionforInjection

2QUALITATIVEANDQUANTITATIVECOMPOSITION

1mlcontains10mgapomorphinehydrochloride

Excipients:Alsocontainssodiumbisulphite0.93mgperml.

Forafulllistofexcipientsseesection6.1

3PHARMACEUTICALFORM

Solutionforinjection.

Solutionisclearandcolourless.

4CLINICALPARTICULARS

4.1TherapeuticIndications

Thetreatmentofdisablingmotorfluctuations(‘on-off’phenomena)inpatientswithParkinson’sdiseasewhichpersist

despiteindividuallytitratedtreatmentwithlevodopa(withaperipheraldecarboxylaseinhibitor)and/orotherdopamine

agonists.

4.2Posologyandmethodofadministration

APO-goPen10mg/mlSolutionforInjectionisforsubcutaneoususebyintermittentbolusinjection.Seesection4.4

Dosage

Adults

Administration

SelectionofpatientssuitableforAPO-goinjections:

PatientsselectedfortreatmentwithAPO-goshouldbeabletorecognisetheonsetoftheir‘off’symptomsandbe

capableofinjectingthemselvesorelsehavearesponsiblecarerabletoinjectforthemwhenrequired.

Itisessentialthatthepatientisestablishedondomperidone,usually20mgthreetimesdailyforatleasttwodays

priortoinitiationoftherapy.

Apomorphineshouldbeinitiatedinthecontrolledenvironmentofaspecialistclinic.Thetreatmentshouldbe

supervisedbyaphysicianexperiencedinthetreatmentofParkinson’sdisease(e.g.Neurologist).Thepatient’s

Irish Medicines Board

______________________________________________________________________________________________________________________

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

Determinationofthethresholddose.

Theappropriatedoseforeachpatientisestablishedbyincrementaldosingschedules.Thefollowingscheduleis

suggested:-

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

ahypokinetic,or‘off’periodandthepatientisobservedover30minutesforamotorresponse.

Ifnoresponse,oraninadequateresponse,isobtainedaseconddoseof2mgofapomorphineHCl(0.2ml)isinjected

subcutaneouslyandthepatientobservedforanadequateresponseforafurther30minutes.

Thedosagemaybeincreasedbyincrementalinjectionswithatleastafortyminuteintervalbetweensucceeding

injections,untilasatisfactorymotorresponseisobtained.

Establishmentoftreatment.

Oncetheappropriatedoseisdeterminedasinglesubcutaneousinjectionmaybegivenintothelowerabdomenorouter

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.

Oncetreatmenthasbeenestablisheddomperidonetherapymaybegraduallyreducedinsomepatientsbutsuccessfully

eliminatedonlyinafew,withoutanyvomitingorhypotension.

Childrenandadolescents:

APO-goPen10mg/mlSolutionforInjectioniscontra-indicatedforchildrenandadolescentsunder18yearsofage(see

section4.3Contraindications).

Elderly:

TheelderlyarewellrepresentedinthepopulationofpatientswithParkinson’sdiseaseandconstituteahighproportion

ofthosestudiedinclinicaltrialsofAPO-go.ThemanagementofelderlypatientstreatedwithAPO-gohasnotdiffered

fromthatofyoungerpatients.

Renalimpairment:

Adoseschedulesimilartothatrecommendedforadults,andtheelderly,canbefollowedforpatientswithrenal

impairment(seesection4.4Specialwarningsandprecautionsforuse).

4.3Contraindications

Inpatientswithrespiratorydepression,dementia,psychoticdiseasesorhepaticinsufficiency.

IntermittentapomorphineHCltreatmentisnotsuitableforpatientswhohavean‘on’responsetolevodopawhichis

marredbyseveredyskinesiaordystonia.

APO-goshouldnotbeadministeredtopatientswhohaveaknownhypersensitivitytoapomorphineoranyexcipientsof

Irish Medicines Board

______________________________________________________________________________________________________________________

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

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-goPen10mg/mlSolutionforInjectioncontainssodiumbisulphitewhichmayrarelycausesevereallergic

reactionsandbronchospasm.

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.Furthermore,areductionofdosageor

terminationoftherapymaybeconsidered.

Pathologicalgambling,increasedlibidoandhypersexualityhavebeenreportedinpatientstreatedwithdopamine

agonistsforParkinson’sdisease,includingapomorphine.

Thismedicinalproductcontainslessthan1mmolsodium(23mg)per3ml,i.e.essentially“sodium-free”.

4.5Interactionwithothermedicinalproductsandotherformsofinteraction

PatientsselectedfortreatmentwithapomorphineHClarealmostcertaintobetakingconcomitantmedicationsfortheir

Parkinson’sdisease.IntheinitialstagesofapomorphineHCltherapythepatientshouldbemonitoredforunusualside-

effectsorsignsofpotentiationofeffect.

Neurolepticmedicinalproductsmayhaveanantagonisticeffectifusedwithapomorphine.Thereisapotential

interactionbetweenclozapineandapomorphine,howeverclozapinemayalsobeusedtoreducethesymptomsof

neuropsychiatriccomplications.

Thepossibleeffectsofapomorphineontheplasmaconcentrationsofotherdrugshavenotbeenstudied.Therefore

Irish Medicines Board

______________________________________________________________________________________________________________________

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

AntihypertensiveandCardiacActiveMedicinalDrugs

Evenwhenco-administeredwithdomperidone,apomorphinemaypotentiatetheantihypertensiveeffectsofthese

drugs.(Seesection4.4Specialwarningsandprecautionsforuse).

ItisrecommendedtoavoidtheadministrationofapomorphinewithotherdrugsknowntoprolongtheQTinterval.

4.6Fertility,pregnancyandlactation

Thereisnoexperienceofapomorphineusageinpregnantwomen.

Animalreproductionstudiesdonotindicateanyteratogeniceffects,butdosesgiventoratswhicharetoxictothe

mothercanleadtofailuretobreatheinthenewborn.Thepotentialriskforhumansisunknown.SeeSection5.3.

APO-goshouldnotbeusedduringpregnancyunlessclearlynecessary.

Itisnotknownwhetherapomorphineisexcretedinbreastmilk.Adecisiononwhethertocontinue/discontinue

breastfeedingortocontinue/discontinuetherapywithAPO-goshouldbemadetakingintoaccountthebenefitofbreast-

feedingtothechildandthebenefitofAPO-gotothewoman.

4.7Effectsonabilitytodriveandusemachines

Apomorphinemayhaveasedativeeffectandpatientsaffectedshouldnotdriveoroperatemachinery.

Patientsbeingtreatedwithapomorphineandpresentingwithsomnolencemustbeinformedtorefrainfromdrivingor

engaginginactivities(e.g.operatingmachines)whereimpairedalertnessmayputthemselvesorothersatriskof

seriousinjuryordeathunlesspatientshaveovercomesuchexperiencesofsomnolence(seealsoSection4.4Special

warningsandprecautionsforuse).

4.8Undesirableeffects

Bloodandlymphaticsystemdisorders

Uncommon:

Haemolyticanaemiaandthrombocytopeniahavebeenreportedinpatientstreatedwithapomorphine.

Rare:

EosinophiliahasrarelyoccurredduringtreatmentwithapomorphineHCl.

Immunesystemdisorders

Rare:

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)

Irish Medicines Board

______________________________________________________________________________________________________________________

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

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.

Dizziness/light-headednesshavealsobeenreported.

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:

Irish Medicines Board

______________________________________________________________________________________________________________________

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

Investigations

Uncommon:

PositiveCoombs'testshavebeenreportedforpatientsreceivingapomorphine.

4.9Overdose

Thereislittleclinicalexperienceofoverdosewithapomorphinebythisrouteofadministration.Symptomsofoverdose

maybetreatedempiricallyassuggestedbelow:-

Excessiveemesismaybetreatedwithdomperidone.

Respiratorydepressionmaybetreatedwithnaloxone.

Hypotension:appropriatemeasuresshouldbetaken,e.g.raisingthefootofthebed.

Bradycardiamaybetreatedwithatropine.

5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

Pharmatherapeuticgroup:Dopamineagonists

ATCClassification:N04BC07

ApomorphineisadirectstimulantofdopaminereceptorsandwhilepossessingbothD1andD2receptoragonist

propertiesdoesnotsharetransportormetabolicpathwayswithlevodopa.

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;thedrugdistributionbeingbestdescribedbyatwo-compartment

model.Apomorphineisrapidlyandcompletelyabsorbedfromsubcutaneoustissue,correlatingwiththerapidonsetof

clinicaleffects(4-12minutes),andthatthebriefdurationofclinicalactionofthedrug(about1hour)isexplainedbyits

rapidclearance.Themetabolismofapomorphineisbyglucuronidationandsulphonationtoatleasttenpercentofthe

total;otherpathwayshavenotbeendescribed.

5.3Preclinicalsafetydata

Repeatdosesubcutaneoustoxicitystudiesrevealnospecialhazardforhumans,beyondtheinformationincludedin

othersectionsoftheSmPC.

Invitrogenotoxicitystudiesdemonstratedmutagenicandclastogeniceffects,mostlikelyduetoproductsformedby

oxidationofapomorphine.However,apomorphinewasnotgenotoxicintheinvivostudiesperformed.

Theeffectofapomorphineonreproductionhasbeeninvestigatedinrats.Apomorphinewasnotteratogenicinthis

species,butitwasnotedthatdoseswhicharetoxictothemothercancauselossofmaternalcareandfailuretobreathe

Irish Medicines Board

______________________________________________________________________________________________________________________

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

Nocarcinogenicitystudieshavebeenperformed.

6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

6.2Incompatibilities

Intheabsenceofcompatibilitystudies,thismedicinalproductmustnotbemixedwithothermedicinalproducts.

6.3Shelflife

Unopened:2years

Afteropening:48hours

6.4Specialprecautionsforstorage

Donotstoreabove25°C.

Storeintheoriginalcontainer.

6.5Natureandcontentsofcontainer

Cartridge.

APO-goPen10mg/mlisadisposablemultipledosepeninjectorsystemincorporatingaclearglass(typeI)cartridge

containingaclearsolutionforinjection.Theglasscartridgeissealedatoneendwithabromobutylrubberpiston,and

attheotherendwithabromobutylrubber/aluminiummembrane.

Eachpencontains3mlofsolutionforinjection.

Packscontaining1,5,or10x3mlpensinamouldedplastictrayinanoutercardboardcarton.

Notallpacksizesmaybemarketed

6.6Specialprecautionsfordisposalandotherhandling

APO-goPEN

Donotuseifsolutionhasturnedgreen.

Discardeachpennolaterthan48hoursfromfirstuse.

Sodiumbisulphite(E222)

HydrochloricAcid(37%),concentrated

(toadjustpHto3.0–4.0)

Irish Medicines Board

______________________________________________________________________________________________________________________

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

HOWTOUSEYOURAPO-goPEN

Readtheseinstructionscarefully

DONOTPULLTHEREDDIALBEFOREYOUHAVESETTHEDOSAGE(Seef)

(seeattacheddiagram)

ATTACHINGTHENEEDLE

(a)Beforeusingyourpensystemyouwillneedasurgicalwipeandoneneedleinitsprotectivecone(see9).Takethe

penoutofitsboxandremovetheoutersleeve(see8).

Irish Medicines Board

______________________________________________________________________________________________________________________

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

(c)Peeloffthepaperfromtheneedlecone(see10),andscrewtheconeclockwiseontothemembrane.Thiswillattach

needlesecurely.

PLEASENOTE

ItisimportanttobringtheneedletothePeninastraightline,asshown.Iftheneedleispresentedatanangleit

maycausethePentoleak.Thiswillattachtheneedlesecurely.

(d)Removetheprotectivecone,butdonotthrowitaway.Donotremovetheneedleprotectoratthisstage(see7).

(e)Replacethepen’soutersleeve.

HOWTOSELECTYOURCORRECTDOSAGE

(seeattacheddiagram)

(f)Pressthereddosagedial(see1)andturnthedialclockwiseuntilthearrowpointstoyourprescribeddosage(see

2,3).Thenreleasedownwardpressureonthereddial.Thedoseisnowset,andyoudonotneedtoredialfor

Irish Medicines Board

______________________________________________________________________________________________________________________

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

Important;Ifyoupassyourprescribeddosewhileturningthedial,justcontinuepressingandturninginthesame

directionuntilyouarriveatitagain.Neverpullandturnthereddosagedialatthesametime.

Ifyourprescribeddoseis2mgorless,itisnecessaryto“prime”thepenbeforeinjectingthefirstdose.Dothisby

emptyingthefirst2mgdoseontoapapertissueanddiscard.Then,setthedoseyourequireforinjectionandinjectin

theusualway(seebelowunder“INJECTING”).Ifthefirstdoserequiredismorethan2mg,thenitisnotnecessaryto

“prime”thepen.

INJECTING

(seeattacheddiagram)

(g)Pulloutthereddosagedialasfarasitwillgo.Checkthewhitescaleontheplungerandinjectonlyifthehighest

numbervisiblecorrespondstotheintendeddose.

(h)Usingasurgicalwipe,cleantheareaofskinaroundtheproposedsiteofinjection.

Removethepen’soutersleeve.

(i)Removetheneedleprotector(see7).

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 13/03/2012 CRN 2105137 page number: 10

Toinject,pressthereddosagedialdownasfarasitwillgo,usingyourthumbifpossible.Oncethereddosagedialis

fullydepressed,counttothreebeforewithdrawingtheneedle.

(k)Removeanddiscardtheneedle,usingtheprotectivecone(see9).Thisisdonebyreplacingtheprotectivecone

ontotheusedneedle,andpushingitgentlyintoplace.Oncesecure,youcanunscrewtheneedleanti-clockwise.

Discardtheneedleinasafeplace.

Important:Eachneedlecanonlybeusedonce.

PREPARINGFORTHENEXTINJECTION:

Checkthatthereisenoughapomorphineleftinthecartridgeforthenextinjection(see4).Ifthereis,putanewneedle

inplace,followingthesameprocedureasbefore.(Remembernottothrowawaytheprotectivecone).

Ifthereisnotenoughapomorphineleftforanotherinjection,prepareanotherpen.

Finally,replacetheoutersleeveofthepen.

7MARKETINGAUTHORISATIONHOLDER

GenusPharmaceuticalsLimited

ParkViewHouse

65LondonRoad

Newbury

BerkshireRG141JN

8MARKETINGAUTHORISATIONNUMBER

PA1496/2/2

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

Dateoffirstauthorisation:6 th

April2001

Dateoflastrenewal:31 st

March2009

10DATEOFREVISIONOFTHETEXT

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 13/03/2012 CRN 2105137 page number: 11