DEPIXOL

Main information

  • Trade name:
  • DEPIXOL Solution for Injection 40/ 2 Mg/ Ml
  • Dosage:
  • 40/ 2 Mg/ Ml
  • Pharmaceutical form:
  • Solution for Injection
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug

Documents

Localization

  • Available in:
  • DEPIXOL Solution for Injection 40/2 Mg/Ml
    Ireland
  • Language:
  • English

Status

  • Source:
  • HPRA - Health Products Regulatory Authority - Ireland
  • Authorization number:
  • PA0115/001/002
  • Authorization date:
  • 21-06-1976
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

PartII

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

Depixol40mg/2mlSolutionforInjection

2QUALITATIVEANDQUANTITATIVECOMPOSITION

Each2mlampoulecontains40mg(2%w/v)cis(z)-flupentixoldecanoate(equivalentto20mg/ml).

Forafulllistofexcipients,seesection6.1.

3PHARMACEUTICALFORM

Solutionforinjection

Clear,yellowish,sterileoilysolution.

4CLINICALPARTICULARS

4.1TherapeuticIndications

Themanagementofschizophreniaandalliedparanoidpsychoses.

4.2Posologyandmethodofadministration

Routeofadministration:Deepintramuscularinjectionintotheupperouterbuttockorlateralthigh.Dosageanddosage

intervalshouldbeadjustedaccordingtothepatients’symptomsandresponsetotreatment.

Note:Aswithalloilbasedinjectionsitisimportanttoensure,byaspirationbeforeinjection,thatinadvertent

intravascularentrydoesnotoccur.

Adults:Theusualdoseisbetween20to40mgeverytwotofourweeks.Largerdosesmaybeusedifnecessary,

distributedbetweentwoinjectionsites.

Inpatientswhohavenotpreviouslyreceiveddepotneuroleptics,treatmentisusuallystartedwithasmalldose(e.g.20

mg)toassesstolerability.Anintervalofatleastone-weekshouldbeallowedbeforethesecondinjectionisgivenata

doseconsistentwiththepatients’condition.

Adequatecontrolofseverepsychoticsymptomsmaytakeupto4to6monthsathighenoughdosage.Oncestabilised

lowermaintenancedosesmaybeconsidered,butmustbesufficienttopreventrelapse.

TheappropriatepresentationofDepixolshouldbeselectedtoachieveaninjectionvolume,whichdoesnotexceed2

ml.Volumesgreaterthan2mlshouldbedistributedbetweentwoinjectionsites.

Whentransferringpatientsfromoraltodepotneuroleptictreatment,theoralmedicationshouldnotbediscontinued

immediately,butgraduallywithdrawnoveraperiodofseveraldaysafteradministeringthefirstinjection.

Elderly:Dosageshouldbeatthelowestlimitoftherange.

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 14/07/2006 CRN 2025473 page number: 1

4.3Contraindications

Useinpatientswhohaveprovedintolerantofthioxanthenes.

Useinchildren.

Useinsenileconfusionalstates.

Useinpatientswhoareexcitableoroveractive.

Useincomatosestates.

4.4Specialwarningsandprecautionsforuse

Cautionshouldbeexercisedinpatientshaving:liverdisease;cardiacdiseaseorarrhythmias;severerespiratorydisease;

renalfailure;epilepsy(andconditionspredisposingtoepilepsye.g.alcoholwithdrawalorbraindamage);Parkinson’s

disease;hypothyroidism;hyperthyroidism;myastheniagravis;phaeochromocytoma.

Theelderlyrequireclosesupervisionbecausetheyareespeciallypronetoexperiencesuchadverseeffectsassedation,

hypotension,confusionandtemperaturechanges.

Thefollowingwarningappliestotherapeuticclassofantipsychotics.Avoidconcomitantuseofotherantipsychotics.

FlupentixolshouldbeusedwithcautioninpatientswithcardiovasculardiseaseorfamilyhistoryofQTprolongation.

4.5Interactionwithothermedicinalproductsandotherformsofinteraction

Incommonwithotherneuroleptics,flupentixolenhancestheresponsetoalcohol,andtheeffectsofbarbituratesand

otherCNSdepressants,andmaypotentiatetheeffectsofgeneralanaesthetics.Neurolepticsmayantagonisetheeffects

ofadrenalineandothersympathomimeticagents,andreversetheantihypertensiveeffectsofguanethidineandsimilar

adrenergic-blockingagents.Neurolepticsmayimpairtheeffectoflevodopa,adrenergicdrugsandanticonvulsants.The

metabolismoftricyclicantidepressantsmaybeinhibitedandthecontrolofdiabetesmaybeimpaired.Theeffectof

anticoagulantsmaybeincreased.Concomitantuseofmetoclopramideandpiperazineincreasestheriskof

extrapyramidalsymptoms.Neurolepticsmayenhancethecardiacdepressanteffectsofquinidine;theabsorptionof

corticosteroidsanddigoxin;thehypotensiveeffectofvasodilatorantihypertensiveagentssuchashydralazineand

prolongtheactionofneuromuscularblockingagents.Thepossibilityofinteractionwithlithiumsaltsshouldbeborne

inmind.

Thefollowinginteractionsapplytothetherapeuticclassofantipsychotics.

ConcomitantuseofQTprolongingdrugs.

Concomitantuseofdrugscausingelectrolyteimbalance.

4.6Pregnancyandlactation

Asthesafetyofthisdrugduringpregnancyhasnotbeenestablished,useduringpregnancy,especiallythefirstandlast

trimesters,shouldbeavoided,unlesstheexpectedbenefittothepatientoutweighsthepotentialrisktothefoetus.

Flupentixolisexcretedintothebreastmilk.IftheuseofDepixolisconsideredessential,nursingmothersshouldbe

advisedtostopbreast-feeding.

Thenewbornofmotherstreatedwithneurolepticsinlatepregnancy,orlabour,mayshowsignsofintoxicationsuchas

lethargy,tremorandhyperexcitability,andhavealowAPGARscore.

4.7Effectsonabilitytodriveandusemachines

Alertnessmaybeimpaired,especiallyatthestartoftreatment,orfollowingtheconsumptionofalcohol;patientsshould

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 14/07/2006 CRN 2025473 page number: 2

4.8Undesirableeffects

Drowsinessandsedationareunusual.Sedation,ifitoccurs,ismoreoftenseenwithhighdosageandatthestartof

treatment,particularlyintheelderly.Otheradverseeffectsincludeblurringofvision,tachycardiaandhypotension.

Extrapyramidalreactionsintheformofacutedystonias(includingoculogyriccrisis),parkinsonianrigidity,tremor,

akinesiaandakathisiahavebeenreportedandmayoccurevenatlowerdosageinsusceptiblepatients.Sucheffects

wouldusuallybeencounteredearlyintreatment,butdelayedreactionsmayalsooccur.Antiparkinsonagentsshould

notbeprescribedroutinelybecauseofthepossibleriskofprecipitatingtoxic-confusionalstates,impairingtherapeutic

efficacyorcausinganticholinergicside-effects.Theyshouldonlybegivenifrequiredandtheirrequirementreassessed

atregularintervals.

Tardivedyskinesiacanoccurwithneuroleptictreatment.Itismorecommonathighdosesforprolongedperiodsbut

hasbeenreportedatlowerdosageforshortperiods.Theriskseemstobegreaterintheelderly,especiallyfemales.It

hasbeenreportedthatfinevermicularmovementsofthetongueareanearlysign.Ithasbeenobservedoccasionallyin

patientsreceivingDepixol.Theconcurrentuseofanticholinergicantiparkinsondrugsmayexacerbatethiseffect.The

potentialirreversibilityandseriousness,aswellastheunpredictabilityofthesyndrome,requiresespeciallycareful

assessmentoftheriskversusbenefit,andthelowestpossibledosageanddurationoftreatmentconsistentwith

therapeuticefficacy.Short-liveddyskinesiamayoccurafterabruptwithdrawalofthedrug.

Theneurolepticmalignantsyndromehasrarelybeenreportedinpatientsreceivingneuroleptics,includingflupentixol.

Thispotentiallyfatalsyndromeischaracterisedbyhyperthermia,afluctuatinglevelofconsciousness,muscularrigidity

andautonomicdysfunctionwithpallor,tachycardia,labilebloodpressure,sweatingandurinaryincontinence.

Neuroleptictherapyshouldbediscontinuedimmediatelyandvigoroussymptomatictreatmentimplemented.

Epilepticfitshaveoccasionallybeenreported.Confusionalstatescanoccur.

Thehormonaleffectsofantipsychoticneurolepticdrugsincludehyperprolactinaemia,whichmaybeassociatedwith

galactorrhoea,gynaecomastia,oligomenorrhoeaoramenorrhoea.Sexualfunction,includingerectionandejaculation

maybeimpaired;butincreasedlibidohasalsobeenreported.

Flupentixolmayimpairbodytemperaturecontrol,andcasesofhyperthermiahaveoccurredrarely.Thepossible

developmentofhypothermia,particularlyintheelderlyandhypothyroid,shouldbeborneinmind.

Blooddyscrasiashaveoccasionallybeenreported.Bloodcountsshouldbecarriedoutifapatientdevelopssignsof

persistentinfection.Jaundiceandotherliverabnormalitieshavebeenreportedrarely.

Weightgainandlesscommonlyweightlosshavebeenreported;oedemahasoccasionallybeenreportedandhasbeen

consideredtobeallergicinorigin.Rasheshaveoccurredrarely.Althoughlesslikelythanwithphenothiazines,

flupentixolcanrarelycauseincreasedsusceptibilitytosunburn.

Occasionallocalreactions,suchaserythema,swellingortenderfibrousnoduleshavebeenreported.

Flupentixol,eveninlowdoses,insusceptible(especiallynon-psychotic)individualsmayunusuallycausenausea,

dizzinessorheadache,excitement,agitation,insomnia,orunpleasantsubjectivefeelingsofbeingmentallydulledor

sloweddown.

Ifantipsychoticdrugsarewithdrawn,recurrenceofpsychoticsymptomsmaynotbecomeapparentforseveralweeksor

months.

Thefollowingadversereactionsapplytothetherapeuticclassofantipsychotics.

QTprolongation

Ventriculararrhythmias-ventricularfibrillation(VF),ventriculartachycardia(VT)(rare)

Suddenunexplaineddeath

Cardiacarrest

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 14/07/2006 CRN 2025473 page number: 3

4.9Overdose

Overdosagemaycausesomnolence,orevencoma,extrapyramidalsymptoms,convulsions,hypotension,shock,hyper-

orhypothermia.Treatmentissymptomaticandsupportive,withmeasuresaimedatsupportingtherespiratoryand

cardiovascularsystems.

Thefollowingspecificmeasuresmaybeemployedifrequired:

anticholinergicantiparkinsondrugsifextrapyramidalsymptomsoccur.

sedation(withbenzodiazepines)intheunlikelyeventofagitationorexcitementorconvulsions.

noradrenalineinsalineintravenousdripifthepatientisinshock.Adrenalinemustnotbegiven.

5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

cis(Z)-flupentixolisaneurolepticofthethioxantheneseries.

Theantipsychoticeffectofneurolepticsisrelatedtotheirdopaminereceptorblockingeffect.Thethioxantheneshave

highaffinityforboththeadenylatecyclasecoupleddopamineD

receptorsandforthedopamineD

receptors;inthe

phenothiazinegrouptheaffinityforD

receptorsismuchlowerthanthatforD

receptors,whereasbutyrophenones,

diphenylbutylpiperidinesandbenzamidesonlyhaveaffinityforD

receptors.

Inthetraditionaltestsforantipsychoticeffect,e.g.antagonismofstereotypicbehaviourinducedbydopamineagonists,

thechemicalgroupsofneurolepticsmentionedrevealequalbutdosage-dependentactivity.However,the

antistereotypiceffectsofphenothiazines,butyrophenones,diphenylbutylpiperidines,andbenzamidesisstrongly

counteractedbytheanticholinergicdrugscopolamine,whiletheantistereotypiceffectofthioxanthenes,e.g.cis(Z)-

flupentixolisnot,oronlyveryslightly,influencedbyconcomitanttreatmentwithanticholinergics.

5.2Pharmacokineticproperties

Byesterificationofcis(Z)-flupentixolwithdecanoicacidcis(Z)-flupentixolhasbeenconvertedtoahighlylipophilic

substance,cis(Z)-flupentixoldecanoate.Whendissolvedinoilandinjectedintramuscularlythissubstancediffuses

slowlyintothesurroundingbodywater,whereenzymaticbreakdownoccursreleasingtheactivecomponentcis(Z)-

flupentixol.Thedurationofactionis2-4weekswithmaximumserumlevelsbeingreachedbytheendofthefirstweek

afterinjection.

cis(Z)-flupentixolisdistributedinthebodyinasimilarwaytootherneuroleptics;withthehighestconcentrationsof

drugandmetabolitesinliver,lungs,intestinesandkidneysandlowerconcentrationsinheart,spleen,brainandblood.

Theapparentvolumeofdistributionisabout14L/kgandtheproteinbinding>95%.

cis(Z)-flupentixolcrossestheplacentalbarrierinsmallamounts;itisalsoexcretedinbreastmilkinverysmall

amounts.

Themetabolismofcis(Z)-flupentixolproceedsviathreemainroutes-sulphoxidation,sidechainN-dealkylationand

glucuronicacidconjugation.Themetabolitesaredevoidofpsychopharmacologicalactivity.Theexcretionproceeds

mainlywiththefaecesbutalsotosomedegreewiththeurinesystem;clearanceisabout0.4-0.5l/min.

5.3Preclinicalsafetydata

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 14/07/2006 CRN 2025473 page number: 4

6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

Triglycerides,mediumchain(Thinvegetableoil)

6.2Incompatibilities

ThisproductmaybemixedinthesamesyringewithotherproductsintheDepixolInjectionrange.Itshouldnotbe

mixedwithanyotherinjectionfluids.

6.3ShelfLife

4years.

Onceopened,useimmediately.Discardanyunusedsolution.

6.4Specialprecautionsforstorage

Donotstoreabove25 °

Keepintheoutercarton.

6.5Natureandcontentsofcontainer

Clearglass(typeI)ampoulesof2ml.

Packsize=10ampoulesperbox.

6.6Specialprecautionsfordisposalofausedmedicinalproductorwastematerialsderivedfrom

suchmedicinalproductandotherhandlingoftheproduct

Forsingleuseonly.Discardanyremainingcontentsafteruse.

7MARKETINGAUTHORISATIONHOLDER

LundbeckLtd.

SunningdaleHouse

CaldecotteLakeBusinessPark

Caldecotte

MiltonKeynesMK78LF

UnitedKingdom

8MARKETINGAUTHORISATIONNUMBER

PA115/1/2

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

Dateoffirstauthorisation:21June1976

Dateoflastrenewal:21June2006

10DATEOFREVISIONOFTHETEXT

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 14/07/2006 CRN 2025473 page number: 5