AMISULPRIDE ACTAVIS

Main information

  • Trade name:
  • AMISULPRIDE ACTAVIS
  • Dosage:
  • 400 Milligram
  • Pharmaceutical form:
  • Film Coated Tablet
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug

Documents

Localization

  • Available in:
  • AMISULPRIDE ACTAVIS
    Ireland
  • Language:
  • English

Status

  • Source:
  • HPRA - Health Products Regulatory Authority - Ireland
  • Authorization number:
  • PA1380/089/001
  • Authorization date:
  • 01-10-2010
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

AmisulprideActavis400mgfilm-coatedTablets

2QUALITATIVEANDQUANTITATIVECOMPOSITION

Eachtabletcontains400mgAmisulpride.

Excipients:Eachtabletcontains200mglactosemonohydrate.

Forafulllistofexcipients,seesection6.1

3PHARMACEUTICALFORM

Film-coatedtablet.

Whitetooff-white,ovoidal-shaped,biconvex,film-coatedtabletswithabreakline,18mmlongand8mmwide.

Thetabletcanbedividedintoequalhalves.

4CLINICALPARTICULARS

4.1TherapeuticIndications

Amisulprideisindicatedforthetreatmentofacuteandchronicschizophrenicdisorders,inwhichpositivesymptoms

(suchasdelusions,hallucinations,thoughtdisorders)and/ornegativesymptoms(suchasbluntedaffect,emotionaland

socialwithdrawal)areprominent,includingpatientscharacterisedbypredominantnegativesymptoms.

4.2Posologyandmethodofadministration

Foracutepsychoticepisodes,oraldosesbetween400mgperdayand800mgperdayarerecommended.Inindividual

cases,thedailydosemaybeincreasedupto1200mgperday.Dosesabove1200mgperdayhavenotbeenextensively

evaluatedforsafetyandthereforeshouldnotbeused.Nospecifictitrationisrequiredwheninitiatingthetreatmentwith

Amisulpride.Dosesshouldbeadjustedaccordingtoindividualresponse.

Forpatientswithmixedpositiveandnegativesymptoms,dosesshouldbeadjustedtoobtainoptimalcontrolofpositive

symptoms.

Maintenancetreatmentshouldbeestablishedindividuallywiththeminimallyeffectivedose.

Forpatientscharacterisedbypredominantnegativesymptoms,oraldosesbetween50mgperdayand300mgperday

arerecommended.Dosesshouldbeadjustedindividually.

Amisulpridecanbeadministeredoncedailyatoraldosesupto300mg,higherdosesshouldbeadministeredtwice

daily.

Elderly:Amisulprideshouldbeusedwithparticularcautionbecauseofapossibleriskofhypotensionorsedation.

Children:Amisulprideiscontra-indicatedinchildrenunder15yearsofageasitssafetyhasnotyetbeenestablished.

Renalinsufficiency:Amisulprideiseliminatedbytherenalroute.Inrenalinsufficiency,thedoseshouldbereducedto

halfinpatientswithcreatinineclearance(CR )between30-60ml/minandtoathirdinpatientswithCR between

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Asthereisnoexperienceinpatientswithsevererenalimpairment(CR <10ml/min)particularcareis

recommendedinthesepatients(seesection4.4)

Hepaticinsufficiency:sinceAmisulprideisweaklymetabolisedadosagereductionshouldnotbenecessary.

Fordosesnotachievable/feasiblewiththisstrength,otherstrengthsofthisactiveingredientareavailable.

Methodofadministration

Fororaluse.

Amisulpridemaybetakenwithoutregardtomeals.Thetabletsshouldbetakenunchewed,withasufficientamountof

fluid.

4.3Contraindications

Hypersensitivitytoamisulprideortoanyoftheexcipients.

Concomitantprolactin-dependenttumourse.g.pituitaryglandprolactinomasandbreastcancer

Phaeochromocytoma

Childrenunder15yearsofage

Lactation

Combinationwiththefollowingmedicineswhichcouldinducetorsadesdepointes:

ClassIaantiarrhythmicagentssuchasquinidine,disopyramide,procainamide.

ClassIIIantiarrhythmicagentssuchasamiodarone,sotalol.

Othermedicationssuchasbepridil,cisapride,sultopride,thioridazine,IVerythromycin,IVvincamine,

halofantrine,pentamidine,sparfloxacin.(Thislistisnotexhaustive.)

Combinationwithlevodopa(seesection4.5)

4.4Specialwarningsandprecautionsforuse

Aswithotherneuroleptics,NeurolepticMalignantSyndrome,characterisedbyhyperthermia,musclerigidity,

autonomicinstability,alteredconsciousnessandelevatedCPK,mayoccur.Intheeventofhyperthermia,particularly

withhighdailydoses,allantipsychoticmedicinesincludingAmisulprideshouldbediscontinued.

Amisulprideiseliminatedbytherenalroute.Incasesofsevererenalinsufficiency,thedoseshouldbedecreasedand

intermittenttreatmentshouldbeconsidered(seesection4.2).

Amisulpridemaylowertheseizurethreshold.Thereforepatientswithahistoryofepilepsyshouldbecloselymonitored

duringtherapywithAmisulpride.

Concomitantneurolepticsshouldbeavoided(seesection4.5).

Hyperglycaemiahasbeenreportedduringtreatmentwithsomeatypicalantipsychoticsincludingamisulpride.Patients

onamisulpridewithoratriskofdiabetesshouldmonitortheirglucoselevelsregularly.

Inelderlypatients(over65yearsofage),Amisulpride,likeotherneuroleptics,shouldbeusedwithparticularcaution

becauseofapossibleriskofhypotensionorsedation.

Aswithotherantidopaminergicagents,cautionshouldbealsoexercisedwhenprescribingAmisulpridetopatientswith

Parkinson’sdiseasesinceitmaycauseworseningofthedisease.Amisulprideshouldbeusedonlyifneuroleptic

treatmentcannotbeavoided.

ProlongationoftheQTinterval

Amisulprideinducesadose-dependentprolongationoftheQTinterval.Thiseffect,knowntopotentiatetheriskof

seriousventriculararrhythmiassuchastorsadesdepointes,isenhancedbythepre-existenceofbradycardia,

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Hypokalaemiashouldbecorrected.

Beforeanyadministration,andifpossibleaccordingtothepatient’sclinicalstatus,itisrecommendedtomonitor

factorswhichcouldfavourtheoccurrenceofthisrhythmdisorder:

bradycardialessthan55bpm,

-hypokalaemia,

-congenitalprolongationoftheQTinterval.

-on-goingtreatmentwithamedicationlikelytoproducepronouncedbradycardia(<55bpm),hypokalaemia,decreased

intracardiacconduction,orprolongationoftheQTcinterval(seesection4.5).

CautionshouldbeusedinpatientswithcardiovasculardiseaseorafamilyhistoryofQTprolongation.

BaselineECGisrecommendedpriortotreatmentinallpatientsespeciallyintheelderlyandpatientswithapositive

personalorfamilyhistoryofcardiacdiseaseorabnormalfindingsoncardiacclinicalexamination.

Duringtherapy,theneedforECGmonitoring(e.g.atdoseescalation)shouldbeassessedonanindividualpatientbasis.

ThedoseofamisulprideshouldbereducedifQTisprolongedanddiscontinuedifQTcis>500ms.

Periodicelectrolytemonitoringisrecommendedparticularlyifthepatientistakingdiureticsorduringinter-current

illness.

Patientswithrarehereditaryproblemsofgalactoseintolerance,theLapplactasedeficiencyorglucose-galactose

malabsorptionshouldnottakethismedicine.

Stroke

Inrandomizedclinicaltrialsversusplaceboperformedinapopulationofelderlypatientswithdementiaandtreatedwith

certainatypicalantipsychoticmedicines,a3-foldincreaseoftheriskofcerebrovasculareventshasbeenobserved.The

mechanismofsuchriskincreaseisnotknown.Anincreaseintheriskwithotherantipsychoticmedicines,orother

populationsofpatientscannotbeexcluded.Amisulprideshouldbeusedwithcautioninpatientswithstrokeriskfactors.

Acutewithdrawalsymptomsincludingnausea,vomitingandinsomniahavebeenrarelydescribedafterabruptcessation

ofhighdosesofantipsychoticagents.Recurrenceofpsychoticsymptomsmayalsooccur,andtheemergenceof

involuntarymovementdisorders(suchasakathisia,dystoniaanddyskinesia)hasbeenreported.Therefore,gradual

withdrawalisadvisable.

Casesofvenousthrombolembolism(VTE)havebeenreportedwithantipsychoticdrugs.Sincepatientstreatedwith

antipsychoticsoftenpresentwithacquiredriskfactorsforVTE,allpossibleriskfactorsforVTEshouldbeidentified

beforeandduringtreatmentwithrisperidoneandpreventativemeasuresundertaken.

4.5Interactionwithothermedicinalproductsandotherformsofinteraction

Combinationscontra-indicated

MedicineswhichcouldinduceQTprolongationandtorsadesdepointes:

ClassIaantiarrhythmicagentssuchasquinidine,disopyramide,procainamide.

ClassIIIantiarrhythmicagentssuchasamiodarone,sotalol.

Othersmedicationssuchasbepridil,cisapride,sultopride,thioridazine,IVerythromycin,methadone,IVvincamine,

halofantrine,pentamidine,sparfloxacin.

(Thislistisnotexhaustive.)

Levodopa:reciprocalantagonismofeffectsbetweenlevodopaandneuroleptics.

Combinationsnotrecommended

Amisulpridemayenhancethecentraleffectsofalcohol.

Combinationstobeusedwithcaution

Medicineswhichenhancetheriskoftorsadesdepointes:

Bradycardia-inducingmedicationssuchasbeta-blockers,bradycardia-inducingcalciumchannelblockerssuchas

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Medicineswhichcauseelectrolyteimbalancesuchashypokalaemia:hypokalemicdiuretics,stimulantlaxatives,IV

amphotericinB,glucocorticoids,tetracosactides.

Neurolepticssuchaspimozide,haloperidol;imipramineantidepressants;lithiumconcomitantuseshouldbeavoided.

Combinationstobeconsidered

depressants including narcotics, anaesthetics, analgesics, sedative H1 antihistamines, barbiturates,

benzodiazepinesandotheranxiolyticdrugs,clonidineandderivatives

Antihypertensivedrugsandotherhypotensivemedicines.

Dopamineagonists(eg:levodopa)sinceitmayattenuatetheiraction.

4.6Pregnancyandlactation

Pregnancy

Amisulpridedidnotshowreproductivetoxicityinanimals.Adecreaseinfertilitylinkedtothepharmacologicaleffects

ofthemedicine(prolactinmediatedeffect)wasobserved.Noteratogeniceffectswerenoted.

Verylimitedclinicaldataonexposedpregnanciesareavailable.Therefore,thesafetyofSolianduringhuman

pregnancyhasnotbeenestablished.

Useofthedrugisnotrecommendedduringpregnancyunlessthebenefitsjustifythepotentialrisks.Ifamisulprideis

usedduringpregnancy,neonatesmayshowadverseeffectsofamisulprideandthusappropriatemonitoringshouldbe

considered.

Forwomenofchildbearingpotential,effectivecontraceptionshouldbefullydiscussedwiththephysicianpriorto

treatment.

Lactation

ItisnotknownwhetherAmisulprideisexcretedinbreastmilk,breast-feedingisthereforecontra-indicated.

4.7Effectsonabilitytodriveandusemachines

Evenusedasrecommended,Amisulpridemayaffectreactiontimesothattheabilitytodrivevehiclesoroperate

machinerycanbeimpaired.

4.8Undesirableeffects

Adverseeffectshavebeenrankedunderheadingsoffrequencyusingthefollowingconvention:verycommon( ≥1/10);

common( ≥1/100;<1/10);uncommon(≥1/1,000;<1/100);rare(≥1/10,000;<1/1,000);veryrare(<1/10,000);frequency

notknown(cannotbeestimatedfromtheavailabledata).

Immunesystemdisorders

Uncommon:Allergicreaction

Platelet,bleedingandclottingdisorders

Frequencyunknown:Casesofvenousthromboembolism,includingcasesofpulmonaryembolismandcasesofdeep

veinthrombosishavebeenreportedwithantipsychoticdrugs.

Endocrinedisorders:

Common:Amisulpridecausesanincreaseinplasmaprolactinlevelswhichisreversibleafterdrugdiscontinuation.This

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Psychiatricdisorders:

Common:Insomnia,anxiety,agitation,orgasmicdysfunction

NervousSystemDisorders:

Verycommon:Extrapyramidalsymptomsmayoccur:tremor,rigidity,hypokinesia,hypersalivation,akathisia.These

symptomsaregenerallymildatoptimaldosagesandpartiallyreversiblewithoutdiscontinuationofAmisulprideupon

administrationofantiparkinsonianmedication.Theincidenceofextrapyramidalsymptoms,whichisdoserelated,

remainsverylowinthetreatmentofpatientswithpredominantlynegativesymptomswithdosesof50-300mg/day.

Common:Acutedystonia(spasmtorticolis,oculogyriccrisis,trismus)mayappear.Thisisreversiblewithout

discontinuationofAmisulprideupontreatmentwithanantiparkinsonianagent.Somnolence.

Uncommon:Tardivedyskinesiacharacterisedbyrhythmic,involuntarymovementsprimarilyofthetongueand/orface

havebeenreported,usuallyafterlongtermadministration.Antiparkinsonianmedicationisineffectiveormayinduce

aggravationofthesymptoms.Seizures.

Frequencynotknown:NeurolepticMalignantSyndromehasbeenreported(seesection4.4).

Cardiovasculardisorders

Common:Hypotension

Uncommon:Bradycardia

Frequencynotknown:QTprolongation,ventriculararrhythmias–VF,VT(rare),suddenunexplaineddeath,cardiac

arrest,Torsadesdepointes.

Gastrointestinaldisorders

Common:Constipation,nausea,vomiting,drymouth,weightgain

Investigations:

Uncommon:Elevationsofhepaticenzymes,mainlytransaminases

4.9Overdose

ExperiencewithAmisulprideinoverdosageislimited.Exaggerationoftheknownpharmacologicaleffectsofthedrug

havebeenreported.Theseincludedrowsinessandsedation,coma,hypotensionandextrapyramidalsymptoms.

Incasesofacuteoverdosage,thepossibilityofmultipledrugintakeshouldbeconsidered.

SinceAmisulprideisweaklydialysed,hemodialysisisofnousetoeliminatethedrug.

ThereisnospecificantidotetoAmisulpride.

Appropriatesupportivemeasuresshouldthereforebeinstitutedwithclosesupervisionofvitalfunctionsincluding

continuouscardiacmonitoringduetotheriskofprolongationoftheQTinterval.

Ifsevereextrapyramidalsymptomsoccur,anticholinergicagentsshouldbeadministered.

5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

Pharmacotheraputicgroup:Antipsychotic,benzamides

ATCcode:N05AL05

AmisulpridebindsselectivelywithahighaffinitytohumandopaminergicD/Dreceptorsubtypeswhereasitis

devoidofaffinityforD,DandDreceptorsubtypes.

Unlikeclassicalandatypicalneuroleptics,amisulpridehasnoaffinityforserotonin,-adrenergic,histamineHand

cholinergicreceptors.Inaddition,amisulpridedoesnotbindtosigmasites. 2 3

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Inanimalstudies,athighdoses,amisulprideblocksdopaminereceptorslocatedinthelimbicstructuresinpreference

tothoseinthestriatum.

Atlowdosesitpreferentiallyblockspre-synapticD/Dreceptors,producingdopaminereleaseresponsibleforits

disinhibitoryeffects.

ThispharmacologicalprofileexplainstheclinicalefficacyofAmisulprideagainstbothnegativeandpositivesymptoms

ofschizophrenia.

5.2Pharmacokineticproperties

Inman,Amisulprideshowstwoabsorptionpeaks:onewhichisattainedrapidly,onehourpost-doseandasecond

between3and4hoursafteradministration.Correspondingplasmaconcentrationsare39±3and54±4ng/mlaftera

50mgdose.

Thevolumeofdistributionis5.8l/kg,plasmaproteinbindingislow(16%)andnodruginteractionsaresuspected.

Absolutebioavailabilityis48%.Amisulprideisweaklymetabolised:twoinactivemetabolites,accountingfor

approximately4%ofthedose,havebeenidentified.Thereisnoaccumulationofamisulprideanditspharmacokinetics

remainunchangedaftertheadministrationofrepeateddoses.Theeliminationhalf-lifeofamisulprideisapproximately

12hoursafteranoraldose.

Amisulprideiseliminatedunchangedintheurine.Fiftypercentofanintravenousdoseisexcretedviatheurine,of

which90%iseliminatedinthefirst24hours.Renalclearanceisintheorderof20l/hor330ml/min.

Acarbohydraterichmeal(containing68%fluids)significantlydecreasestheAUCs,T

andC

ofamisulpridebut

nochangeswereseenafterahighfatmeal.However,thesignificanceofthesefindingsinroutineclinicaluseisnot

known.

Hepaticinsufficiency:sincethedrugisweaklymetabolisedadosagereductionshouldnotbenecessaryinpatients

withhepaticinsufficiency.

Renalinsufficiency:Theeliminationhalf-lifeisunchangedinpatientswithrenalinsufficiencywhilesystemic

clearanceisreducedbyafactorof2.5to3.TheAUCofAmisulprideinmildrenalfailureincreasedtwofoldand

almosttenfoldinmoderaterenalfailure(seesection4.2).Experienceishoweverlimitedandthereisnodatawithdoses

greaterthan50mg.

Amisulprideisveryweaklydialysed.

Limitedpharmacokineticdatainelderlysubjects(>65years)showthata10-30%riseoccursinC

,T

andAUC

afterasingleoraldoseof50mg.Nodataareavailableafterrepeatdosing.

5.3Preclinicalsafetydata

Thesafetyprofileofamisulprideuseislargelyrelatedtothepharmacologiceffectsoftheactivesubstance.

Anoverallreviewofthecompletedsafetystudiesindicatesthatamisulprideisdevoidofanygeneral,organ-specific,

teratogenic,orgenotoxicrisk.

Carcinogenicitystudiesinmiceandratsrevealedthattreatmentwithamisulprideresultedinanincreasedincidenceof

hormone-dependenttumourswithnoclinicalrelevanceinman.

Amisulpridetreatmentmightbeassociatedwithdecreasedfertilitypresumablyduetothepharmacologicaleffectsof

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6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

Tabletcore

lactosemonohydrate

methylcellulose

sodiumstarchglycolatetypeA

magnesiumstearate

microcrystallinecellulose

Coating

methacrylatepolymers

titaniumdioxide(E171)

talc

magnesiumstearate

macrogol6000

6.2Incompatibilities

Noneknown

6.3ShelfLife

3years

6.4Specialprecautionsforstorage

Thismedicinalproductdoesnotrequireanyspecialstorageconditions.

6.5Natureandcontentsofcontainer

Blisterscomprisingof25µmAlfoiland250µmPVCcontainedwithinaprintedcartonbox.

Packsizes:10,20,28,30,50,56,60,84,90,100or150.

Notallpacksizesmaybemarketed.

6.6Specialprecautionsfordisposal

Nospecialrequirements.

7MARKETINGAUTHORISATIONHOLDER

ActavisGroupPTCehf

Reykjavikurvegi76-78

220Hafnarfjordur

Iceland

8MARKETINGAUTHORISATIONNUMBER

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9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

Dateoffirstauthorisation:1stOctober2010

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