AMISULPRIDE TEVA

Main information

  • Trade name:
  • AMISULPRIDE TEVA
  • Dosage:
  • 100 Milligram
  • Pharmaceutical form:
  • Tablets
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug

Documents

Localization

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

Status

  • Source:
  • HPRA - Health Products Regulatory Authority - Ireland
  • Authorization number:
  • PA0749/075/002
  • Authorization date:
  • 17-04-2009
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

AmisulprideTeva100mgTablets

2QUALITATIVEANDQUANTITATIVECOMPOSITION

Eachtabletcontains100mgamisulpride.

Excipients

Eachtabletcontains60.2mglactose.

Forafulllistofexcipients,seesection6.1.

3PHARMACEUTICALFORM

Tablet

Whitetoalmostwhite,flat,roundtablet,debossed“MS100”ononesidewithascorelineontheother.

Thetabletcanbedividedintoequalhalves.

4CLINICALPARTICULARS

4.1TherapeuticIndications

Amisulprideisindicatedforthetreatmentofacuteandchronicschizophrenicdisorderswith:

positivesymptomssuchasdelusions,hallucinations,thoughtdisorders,hosility,suspiciousness

primarynegativesymptoms(deficitsyndrome)suchasbluntedaffect,emotionalandsocialwithdrawal.

4.2Posologyandmethodofadministration

Positivesymptoms

Therecommendeddoseis400-800mgamisulpridedaily.

Inindividualcases,thedailydosemaybeincreasedto1,200mgamisulpride.Dosesabove1,200mg/dayhavenotbeen

sufficientlyevaluatedforsafetyandthereforeshouldnotbeused.

Amisulpridecanbeadministeredoncedailyatoraldosesupto300mg,higherdosesshouldbeadministeredindivided

doses.

Nospecifictitrationisrequiredwheninitiatingtreatmentwithamisulpride.

Forpatientswithmixedpositiveandnegativesymptoms,dosesshouldbeadjustedtoobtainoptimalcontrolofpositive

symptoms.

Maintenancetreatmentshouldbeestablishedindividuallywiththeminimallyeffectivedose.

Ashigherdosesaregenerallyrequiredforthetreatmentofpositivesymptoms,higherstrengthtabletsshouldbeused.

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Therecommendeddoseis50-300mgamisulpridedaily.

Dosesshouldbeadjustedindividually.

Amisulpridemaybeadministeredasasingledoseupto300mg.

Specialpopulations

Renalinsufficiency

Thedailydoseshouldbereducedtohalfinpatientswithcreatinineclearancebetween30and60ml/minandtoathird

inpatientswithcreatinineclearancebetween10and30ml/min.Asthereisnoexperienceinpatientswithsevererenal

insufficiency(creatinineclearancelessthan10ml/min),amisulprideiscontraindicatedinthesepatients(seesection

4.3).

Hepaticinsufficiency

Sinceamisulprideisweaklymetaboliseddosereductionshouldnotbenecessaryinpatientswithhepaticinsufficiency.

Elderly

Treatmentofelderlypatients(>65years)isnotrecommendedasthereisinsufficientclinicalexperience.Treatment

withamisulpridebearsapossibleriskofhypotensionorsedation(seealsosection5.2).

Paediatricpatients

Amisulprideiscontraindicatedinchildrenandadolescentsunder18yearsofage(seesection4.3).

Methodofadministration

Amisulpridemaybetakenwithoutregardtomeals.Thetabletsshouldbetakenunchewed,withasufficientamountof

fluid.

Durationoftreatment

Datafromcontrolledclinicaltrialscoveringaperiodof1yearisavailable.Thedurationoftreatmentshouldbe

determinedbythetreatingphysician.

Fordosesnotrealisable/practicablewiththisstrength,otherstrengthsofthismedicinalproductareavailable.

4.3Contraindications

Hypersensitivitytotheactivesubstanceortoanyoftheexcipients

Concomitantprolactin-dependenttumourse.g.pituitaryglandprolactinomasandbreastcancer

Phaeochromocytoma

Combinationwithlevodopa(seesection4.5)

Childrentillpuberty

Lactation.

4.4Specialwarningsandprecautionsforuse

Neurolepticmalignantsyndrome,characterizedbyhyperthermia,musclerigidity,autonomicinstability,altered

consciousnessandelevatedcreatinephosphokinase(CPK),mayoccur.Intheeventofhyperthermia,particularlywith

highdailydoses,allantipsychoticsincludingamisulprideshouldbediscontinued.

CautionshouldbealsoexercisedwhenprescribingamisulpridetopatientswithParkinson'sdiseasesinceitmaycause

worseningofthedisease.Amisulprideshouldbeusedonlyifneuroleptictreatmentcannotbeavoided.

ProlongationoftheQTinterval

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potentiatetheriskofseriousventriculararrhythmiassuchastorsadesdepointes.Beforeanyadministration,andif

possibleaccordingtothepatient'sclinicalstatus,itisrecommendedtoexcludethefollowingfactorswhichcould

favourtheoccurrenceofthisrhythmdisorder:

priorcardiacdisorders,

bradycardialessthan55beatsperminute(bpm),

electrolytedisorders,especiallyhypokalaemia,hypomagnesaemia,hypocalcaemia,

congenitalprolongationoftheQTinterval,

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

intracardiacconduction,orprolongationoftheQTinterval(seesection4.5).

Cerebrovascularaccident(CVA)

Inrandomised,placebo-controlledclinicaltrialsinelderlypatientswithdementiatreatedwithatypicalantipsychotics,a

three-foldincreasewasobservedintheriskofcerebrovascularadverseevents.Themechanismleadingtothisincrease

inriskisunknown.Itcannotbeexcludedthatthiseffectmightoccurwithotherantipsychoticsorinotherpatient

populations.AmisulprideshouldthereforebeusedwithcautioninpatientsatriskforCVA.

Venousthromboembolism(VTE)

Casesofvenousthromboembolism(VTE)havebeenreportedwithantipsychoticagents.Sincepatientstreatedwith

antipsychoticsoftenpresentwithacquiredriskfactorsforVTE,allpossibleriskfactorsforVTEshouldbeidentified

beforeandduringtreatmentwithamisulprideandpreventivemeasuresundertaken.

Hyperglycaemiahasbeenreportedduringtreatmentwithsomeatypicalantipsychoticsincludingamisulpride.Patients

onamisulpridewithoratriskofdiabetesshouldmonitortheirglucoselevelsregularly.

Amisulpridemaylowertheseizurethreshold.Thereforepatientswithahistoryofepilepsyshouldbecloselymonitored

duringtherapywithamisulpride.

Amisulprideiseliminatedbytherenalroute.Incasesofmild-to-moderaterenalinsufficiency(creatinineclearance

greaterthan10ml/min),thedailydoseshouldbedecreased(seesection4.2).

Amisulprideisnotrecommendedforuseinpatientsover65yearsofage,owingtoalackofexperience.Itmayleadto

sedationandhypotensioninthispatientpopulation(seesection5.2).

Acutewithdrawalsymptomsincludingnausea,vomitingandinsomniahavebeenrarelydescribedafterabruptcessation

ofhighdosesofantipsychoticagents.Recurrenceofpsychoticsymptomsmayalsooccur,andtheemergenceof

involuntarymovementdisorders(suchasakathisia,dystoniaanddyskinesia)hasbeenreported.Therefore,gradual

withdrawalisadvisable.

Thismedicinalproductcontainslactosemonohydrate.Patientswithrarehereditaryproblemsofgalactoseintolerance,

theLapplactasedeficiencyorglucose-galactosemalabsorptionshouldnottakethismedicinalproduct.

4.5Interactionwithothermedicinalproductsandotherformsofinteraction

Combinationswhicharecontraindicated

Amisulprideshouldnotbeadministeredconcomitantlywithagentswhichcouldinduceseriouscardiacarrhythmias

(torsadedepointes):

ClassIandIIIantiarrhythmics(quinidine,disopyramide,procainamide,mexiletine,flecainide,propafenone,

amiodarone,sotalol),

Thioridazine,sultopride(neuroleptics),

Someantibiotics(pentamidine),antimalarials(halofantrine),gyraseinhibitors(sparfloxacin),imidazole

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Cisapride(gastro-intestinalagent)

Bepridil

Methadone

IVvincamine(vasodilator)

Amisulprideshouldnotbeadministeredconcomitantlywithdopamineagonists(e.g.levodopaforParkinson's

disease)duetoreciprocalantagonism(seesection4.3).

Combinationswhicharenotrecommended

Amisulprideisnotrecommendedincombinationwiththefollowingagentswhichincreasetheriskofseriouscardiac

arrhythmias(torsadedepointes)orwhichmayaffectcardiacconduction(QTprolongation):

Bradycardia-inducingagentssuchasbeta-blockers,somecalciumchannelblockerssuchasdiltiazemor

verapamil,clonidine,guanfacine,digitalisglycosides

Hypokalaemicagentssuchasdiuretics,stimulantlaxatives,IVamphotericinB,glucorticoids, tetracosactide.

Hypokalaemiamustbetreated.

Neurolepticssuchaspimozide,haloperidol

Tricyclicantidepressants

Lithium

Someantihistamines(astemizole,terfenadine).

Amisulpridemaypotentiatethecentraleffectsofalcohol,whichshouldthereforenotbeconsumedduringtreatment.

Combinationsrequiringprecautionsforuse

Cautionisrequiredwhenusingthefollowingagentsconcomitantly(duetopotentiationofeffect):

Centrally-actingagentssuchasnarcotics,anaesthetics,sedativeH

antihistamines,barbiturates,

benzodiazepinesandotheranxiolytics,clonidineanditsderivatives

Antihypertensivesandotherblood-pressure-loweringagents.

ThereisnodataoninteractionswithH

antagonistssuchascimetidine.

4.6Fertility,pregnancyandlactation

Pregnancy

Thereisonlyverylimitedclinicaldataontheuseofamisulprideduringpregnancy.Animalstudiesindicatethat

amisulprideexertsaninfluenceonembryofetaldevelopmentandgrowthwithouthavingteratogenicpotential.

Thesafetyofamisulprideduringhumanpregnancyhasnotbeenestablished.Therefore,useisnotrecommendedduring

pregnancyunlessthebenefitsjustifythepotentialrisks.

Neonatesexposedtoamisulprideduringpregnancymayexhibitadverseeventsandshouldthereforebemonitored.

Adecreaseinfemalefertilitylinkedtothepharmacologicaleffectsofthesubstance(prolactin-mediatedeffect)was

observed.

Lactation

Itisnotknownwhetheramisulprideisexcretedinbreastmilk,breast-feedingisthereforecontra-indicatedandmustbe

discontinuedbeforeinitiationoftherapy(seesection4.3).

4.7Effectsonabilitytodriveandusemachines

Amisulpridehasmoderateinfluenceontheabilitytodriveandusemachines.Evenusedasrecommended,itmayaffect

reactiontime(e.g.throughsomnolence)sothattheabilitytodrivevehiclesoroperatemachinerycanbeimpaired(see

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4.8Undesirableeffects

Theadverseevents/reactionsaredescribedaccordingtothefollowingfrequencyconvention:

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)

Clinicaltrialsdata

Thefollowingadversereactionshavebeenobservedincontrolledclinicaltrials.Itshouldbenotedthatinsome

instancesitcanbedifficulttodifferentiateadverseeventsfromsymptomsoftheunderlyingdisease.

Investigations

Common: Weightgain

Uncommon: Increasedhepaticenzymelevels,mainlytransaminases

Cardiacdisorders

Uncommon: Bradycardia

Nervoussystemdisorders

Verycommon: Extrapyramidaldisorderssuchastremor,rigidity,hypokinesia,hypersalivation,akathisia,dyskinesia.

Thesesymptomsaregenerallymildatoptimaldosagesandpartiallyreversiblewithout

discontinuationofamisulprideuponadministrationofantiparkinsonianagents.Theincidenceof

extrapyramidalsymptoms,whichisdose-related,remainsverylowinthetreatmentofpatientswith

dosesof50-300mg/day.

Common: Acutedystoniasuchasspasmtorticolis,oculogyriccrisis,trismus.Thisisreversiblewithout

discontinuationofamisulprideupontreatmentwithanantiparkinsonianagent.

Somnolence,dizziness

Uncommon: Tardivedyskinesiacharacterisedbyrhythmic,involuntarymovementsprimarilyofthetongueand/or

face,usuallyafterlongtermadministration.Antiparkinsoniantreatmentshouldnotbeusedasitis

ineffectiveormayinduceaggravationofthesymptoms.

Seizures

Gastrointestinaldisorders

Common: Gastrointestinaldisorderssuchasconstipation,nausea,vomiting,mouthdryness

Endocrinedisorders

Common: Amisulpridecausesanincreaseinplasmaprolactinlevels,reversibleafterdrugdiscontinuation.This

mayresultingalactorrhoea,amenorrhoeaormenstrualdisorders,gynaecomastia,breastpainor

enlargement,prolactinomaanderectiledysfunction.

Metabolismandnutritiondisorders

Uncommon: Hyperglycaemia(seesection4.4)

Vasculardisorders

Common: Hypotension

Immunesystemdisorders

Uncommon: Allergicreactions

Psychiatricdisorders

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Postmarketingdata

Inaddition,casesofthefollowingadverseevents/reactionswerespontaneouslyreportedaftermarketlaunch:

Cardiacdisorders

Notknown: QTprolongation,ventriculararrhythmiassuchastorsadedepointesandventriculartachycardia,

whichcanleadtofibrillationorcardiacarrestandsuddendeath(seesection4.4).

Nervoussystemdisorders

Notknown: Neurolepticmalignantsyndrome(seesection4.4)

Vasculardisorders

Notknown: Venousthromboembolism,includingpulmonaryembolism,sometimesfatal,anddeepvein

thrombosis

Skinandsubcutaneoustissuedisorders

Notknown: Angioedema,urticaria

Pregnancy,puerperiumandperinatalconditions

Notknown: Drugwithdrawalsyndromeneonatal(seesection4.6)

Generaldisorders

Rare: Acutewithdrawalsymptomsincludingnausea,vomitingandinsomniaafterabruptcessationofhigh

doses,alsorecurrenceofpsychoticsymptoms,emergenceofinvoluntarymovementdisorders(such

asakathisia,dystoniaanddyskinesia)(seesection4.4).

4.9Overdose

Symptoms

Experiencewithamisulprideinoverdoseislimited.Exaggerationoftheknownpharmacologicaleffectsoftheagent

havebeenreported.Theseincludedrowsinessandsedation,coma,hypotensionandextrapyramidalsymptoms.

Treatment

Incasesofacuteoverdose,thepossibilityofmultipleagentintakeshouldbeconsidered.Sinceamisulprideisweakly

dialysable,haemodialysisshouldnotbeusedtoeliminateit.Thereisnoknownspecificantidotetoamisulpride.

Appropriatesupportivemeasuresshouldthereforebeinstitutedinhospital,closesupervisionofvitalfunctionsand

cardiac(ECG)monitoringisrecommended(riskofprolongationofQTinterval).

Ifsevereextrapyramidalsymptomsoccur,anticholinergicagentsshouldbeadministered.

5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

Pharmacotherapeuticgroup: Antipsychotics,benzamides

ATCcode: N05AL05

AmisulpridebindsselectivelywithahighaffinitytohumandopaminergicD

receptorsubtypeswhereasitisdevoid

ofaffinityforD

,D

andD

receptorsubtypes.

Unlikeclassicalandotheratypicalneuroleptics,amisulpridehasnoaffinityforserotonin,-adrenergic,histamineH

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Athighdosesamisulprideblockspost-synapticD

receptorslocatedinthelimbicstructuresinpreferencetothosein

thestriatum.UnlikeclassicalneurolepticsitdoesnotinducecatalepsyandhypersensitivityofD

dopaminereceptors

doesnotdevelopafterrepeatedtreatment.Atlowdosesitpreferentiallyblockspre-synapticD

receptors,

producingdopaminereleaseresponsibleforitsdisinhibitoryeffects.

Thisatypicalpharmacologicalprofilemayexplainamisulpride'sclinicalefficacyagainstboththepositiveandnegative

symptomsofschizophrenicpsychoticdisordersanditsreducedtendencytoproduceextrapyramidaladverseeffects.

5.2Pharmacokineticproperties

Inhumans,amisulprideshowstwoabsorptionpeaksafteroraladministration:onewhichisattainedrapidly,onehour

post-dose,andasecondbetween3and4hoursafteradministration.Correspondingplasmaconcentrationsare39±3

and54±4ng/mlaftera50mgdose.

Thevolumeofdistributionis5.8l/kg.Asplasmaproteinbindingislow(16%),interactionsareunlikely.

Absolutebioavailabilityis48%.Amisulprideisweaklymetabolised:twoinactivemetabolites,accountingfor

approximately4%ofthedose,havebeenidentified.Thereisnoaccumulationofamisulprideanditspharmacokinetics

remainunchangedaftertheadministrationofrepeateddoses.Theeliminationhalf-lifeofamisulprideisapproximately

12hoursafteranoraldose.

Amisulprideiseliminatedunchangedintheurine.Fiftypercentofanintravenousdoseisexcretedviatheurine,of

which90%iseliminatedinthefirst24hours.Renalclearanceisintheorderof20l/hor330ml/min.

Acarbohydrate -richmeal(containing68%fluids)significantlydecreasestheAUC,T

andC

ofamisulpridebut

nochangeswereseenafterahigh -fatmeal.However,thesignificanceofthesefindingsinroutineclinicaluseisnot

known.

Hepaticinsufficiency

Sinceamisulprideisweaklymetabolised,dosereductionshouldnotbenecessaryinpatientswithhepaticinsufficiency.

Renalinsufficiency

Theeliminationhalf-lifeisincreasedinpatientswithrenalinsufficiencywhilesystemicclearanceisreducedbyafactor

of2.5to3.Theareaunderthecurve(AUC)ofamisulprideinmildrenalfailureincreasedtwo-foldandalmostten-fold

inmoderaterenalfailure.

Amisulprideisveryweaklydialysable.

Elderlypatients

Inelderlypatients(>65years),slightchangeswereobservedinthekineticprofile(10%increaseinAUC)whichare

probablyduetoage-relatedchangesinrenalfunction.

5.3Preclinicalsafetydata

Nospecificorgantoxicitywasidentifiedinchronictoxicitystudiesinratsreceiving200mg/kg/dayamisulprideand

dogsreceivingatmost120mg/kg/day.Apathy,lethargyandtremorwereobserved.Increasesincholesterolandlipid

valuesandtransienttachycardiaoccurredonlyindogs.

Animalstudiesindicateaninfluenceonembryofetalgrowthanddevelopment,butnoteratogenicpotential.Adequate

studiesontheeffectontheoffspringhavenotbeenperformed.

Carcinogenicitystudiesinmiceandratsrevealedanincreasedincidenceofmammary,pituitary,adrenalandendocrine

pancreatictumours.Theno-effectleveldosecouldnotbeestablished.Anincreasedincidenceoftumourswasobserved

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Theinductionoftumourscanbeexplainedbytheantidopaminergicandhyperprolactinaemiceffectsofamisulpride,

andtheparticularsensitivityofrodentstothesehormonalchanges.Theinductionmechanisminrodentsisknown.

6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

Lactosemonohydrate

Potatostarch

Hypromellose

Sodiumstarchglycolate(typeA)

Magnesiumstearate

6.2Incompatibilities

Notapplicable.

6.3Shelflife

4years

6.4Specialprecautionsforstorage

Thismedicinalproductdoesnotrequireanyspecialstorageconditions.

6.5Natureandcontentsofcontainer

TransparentPVC/PVdC–aluminiumblisters

1,10,20,30,50,5x50,60,90,100&120tablets.Hospitalpackwith500(10x50)tablets

Notallpacksizesmaybemarketed.

6.6Specialprecautionsfordisposal

Nospecialrequirements.

7MARKETINGAUTHORISATIONHOLDER

TevaPharmaB.V.

Computerweg10

3542DRUtrecht

TheNetherlands

8MARKETINGAUTHORISATIONNUMBER

PA749/75/2

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

Dateoffirstauthorisation:17thApril2009

10DATEOFREVISIONOFTHETEXT

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