AMISULPRIDE

Main information

  • Trade name:
  • AMISULPRIDE Tablets 200 Milligram
  • Dosage:
  • 200 Milligram
  • Pharmaceutical form:
  • Tablets
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug

Documents

Localization

  • Available in:
  • AMISULPRIDE Tablets 200 Milligram
    Ireland
  • Language:
  • English

Status

  • Source:
  • HPRA - Health Products Regulatory Authority - Ireland
  • Authorization number:
  • PA1046/013/003
  • Authorization date:
  • 29-10-2004
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

PartII

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

Amisulpride200 mg Tablets

2QUALITATIVEANDQUANTITATIVECOMPOSITION

Amisulpride200mg pertablet.

Forexcipients, see6.1.

3PHARMACEUTICALFORM

Tablet

Whiteto off-whitescored tablets.

4CLINICALPARTICULARS

4.1TherapeuticIndications

Amisulprideisindicated forthetreatmentofacuteand chronicschizophrenicdisorders, in which positivesymptoms

(such asdelusions, hallucinations, thoughtdisorders)and/ornegativesymptoms(such asblunted affect, emotionaland

socialwithdrawal)areprominent, including patientscharacterised by predominantnegativesymptoms.

4.2Posologyandmethodofadminstration

Foracutepsychoticepisodes, oraldosesbetween 400 mg/dayand 800 mg/day arerecommended. Dosesabove800

mg/day havenotbeen associated with greaterefficacy and haveinduced higherratesofextrapyramidalsymptoms.No

specifictitration isrequired when initiating thetreatmentwith Amisulpride. Dosesshould beadjusted according to

individualresponse.

Forpatientswith mixed positiveand negativesymptoms, dosesshould beadjusted to obtain optimalcontrolofpositive

symptoms.

Maintenancetreatmentshould beestablished individually with theminimally effectivedose.

Forpatientscharacterised by predominantnegativesymptoms, oraldosesbetween 50 mg/day and 300mg/day are

recommended. Dosesshould beadjusted individually.

Amisulprideshould beadministered b.i.d. fordosesabove400mg.

Elderly:

Thesafety ofAmisulpridehasbeen examined in alimited numberofelderly patients. Amisulprideshould beused with

particularcaution becauseofapossiblerisk ofhypotension orsedation.Reduction indosagemayalso berequired

becauseofrenalinsufficiency.

Children:

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Renalinsufficiency:

Amisulprideiseliminated by therenalroute. Inrenalinsufficiency, thedoseshould bereduced to halfin patientswith

creatinineclearance(CR

)between 30-60 ml/min and to athird in patientswith CR

between 10-30 ml/min.

Asthereisno experiencein patientswith severerenalimpairment(CR

<10 ml/min)particularcareisrecommended

in thesepatients.

Hepaticinsufficiency:

Sincethedrug isweakly metabolised adosagereduction should notbenecessary.

4.3Contraindications

Hypersensitivity to theactiveingredientorto otheringredientsoftheproduct.

Concomitantprolactin-dependenttumourse.g. pituitary gland prolactinomasand breastcancer.

Phaeochromocytoma.

Children up to puberty.

Lactation.

4.4Special warningsandprecautionsforuse

Aswithotherneuroleptics, NeurolepticMalignantSyndrome, characterized by hyperthermia, musclerigidity,

autonomicinstability and elevated CPK, may occur. In theeventofhyperthermia, particularly with high daily doses, all

antipsychoticdrugsincluding Amisulprideshould bediscontinued.

Amisulprideiseliminated by therenalroute. Incasesofsevererenalinsufficiency orrenaldialysis, thedoseshould be

decreased and intermittenttreatmentshould beconsidered (seeSection 4.2).

Amisulpridecan lowertheseizurethreshold. Thereforepatientswith ahistory ofseizuresshould beclosely monitored

during Amisulpridetherapy.

In elderlypatients, Amisulpride, likeotherneuroleptics, should beused with particularcaution becauseofapossible

risk ofhypotension orsedation.Reduction indosagemayalso berequired becauseofrenalinsufficiency.

Aswithotherantidopaminergicagents, caution should bealso exercised when prescribing Amisulprideto patientswith

Parkinson’sdiseasesinceitmay causeworsening ofthedisease. Amisulprideshould beused only ifneuroleptic

treatmentcannotbeavoided.

Amisulprideshould beprescribed with caution in patientswith thesefactorsand patientswith cardiovasculardisorders

which may predisposeto prolongation oftheQTinterval.

Avoid concomitantprescription ofotherantipsychotics.

Acutewithdrawalsymptomsincluding nausea, vomiting and insomniahavebeen rarely described afterabruptcessation

ofhigh dosesofantipsychoticdrugs. Recurrenceofpsychoticsymptomsmay also occur, and theemergenceof

involuntary movementdisorders(such asakathisia, dystoniaand dyskinesia)havebeen reported. Therefore, gradual

withdrawalisadvisable.

4.5Interactionwithothermedicinalproductsandotherformsofinteraction

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Caution should beexercised with theconcomitantadministrationofdrugssuchas:

CNSdepressantsincluding narcotics, anaesthetics, analgesics, sedativeH

antihistamines, barbiturates,

benzodiazepinesand otheranxiolyticdrugs, clonidineand derivatives.

Antihypertensivedrugsand otherhypotensivemedications.

Amisulpridemay opposetheeffectofdopamineagonistse.g. bromocriptine, ropinirole.

Dopamineagonists(e.g. levodopa)sinceitmay attenuatetheiraction.

4.6Pregnancyandlactation

Pregnancy

In animals, amisulpridedid notshowdirectreproductivetoxicity. Adecreasein fertility linked to thepharmacological

effectsofthedrug (prolactin mediated effect)wasobserved. No teratogeniceffectsofamisulpridewerenoted.

Thesafety ofamisulprideduring human pregnancy hasnotbeen established. Therefore, useofthedrug isnot

recommended during pregnancy unlessthebenefitsjustify thepotentialrisks.

Lactation

Itisnotknownwhetheramisulprideisexcreted in breastmilk, breast-feeding isthereforecontra-indicated.

4.7Effectsonabilitytodriveandusemachines

Even used asrecommended, Amisulpridemayaffectreaction timeso thattheability to drivevehiclesoroperate

machinery can beimpaired.

4.8Undesirableeffects

Thefollowing adverseeffectshavebeen observed in controlled clinicaltrials.Itshould benoted thatin someinstances

itcan bedifficultto differentiateadverseeventsfromsymptomsoftheunderlying disease.

Common adverseeffects(5-10%):insomnia, anxiety, agitation.

Lesscommon adverseeffects(0.1-5%):somnolence, gastrointestinaldisorderssuch asconstipation, nausea, vomiting,

dry mouth.

In common with otherneuroleptics:

Amisulpridecausesan increasein plasmaprolactin levelswhich isreversibleafterdrug discontinuation. Thismay

resultin galactorrhoea, amenorrhoea, gynaecomastia, breastpain, orgasmicdysfunction and impotence.

Weightgain may occurundertherapy with Amisulpride.

Acutedystonia(spasmtorticolis, oculogyriccrisis, trismus)may appear. Thisisreversiblewithoutdiscontinuation of

Amisulprideupon treatmentwith an antiparkinsonian agent.

Extrapyramidalsymptomsmay occur:tremor, rigidity, hypokinesia, hypersalivation, akathisia. Thesesymptomsare

generally mild atoptimaldosagesand partially reversiblewithoutdiscontinuation ofAmisulprideupon administration

ofantiparkinsonian medication. Theincidenceofextrapyramidalsymptomswhich isdoserelated, remainsvery lowin

thetreatmentofpatientswith predominantly negativesymptomswith dosesof50-300 mg/day.

Tardivedyskinesiacharacterised by rhythmic, involuntary movementsprimarily ofthetongueand/orfacehavebeen

reported, usually afterlong termadministration. Antiparkinsonian medication isineffectiveormay induceaggravation

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Cardiovasculardisorders

Hypotension and bradycardiahavebeen reported occasionally.

Very rarecasesofQTprolongation and ofventriculararrhythmiassuch asoftorsadedepointes, ventricular

tachycardia, which may resultin ventricularfibrillation orcardiacarrest, havebeen reported. Very rarecasesofsudden

death havebeen reported.

Allergicreactionsand casesofseizureshavebeen reported occasionally.

RarecasesofNeurolepticMalignantSyndromehavebeen reported (seespecialwarningsand specialprecautionsfor

use).

4.9Overdose

Experiencewith amisulpridein overdosageislimited. Exaggeration oftheknown pharmacologicaleffectsofthedrug

havebeen reported. Theseincludedrowsinessand sedation, coma, hypotension and extrapyramidalsymptoms.

In casesofacuteoverdosage, thepossibility ofmultipledrug intakeshould beconsidered. Sinceamisulprideisweakly

dialysed, haemodialysisshould notbeused to eliminatethedrug.Thereisno specificantidoteto amisulpride.

Appropriatesupportivemeasuresshould thereforebeinstituted, closesupervisionofvitalfunctionsand cardiac

monitoring isrecommended untilthepatientrecovers.

Ifsevereextrapyramidalsymptomsoccur, anticholinergicagentsshould beadministered.

5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

Pharmacotherapeuticgroup:Antipsychotics

ATCCode:N05AL05

Amisulpridebindsselectively with ahigh affinity to human dopaminergicD

receptorsubtypeswhereasitisdevoid

ofaffinity forD

and D

receptorsubtypes.

Unlikeclassicaland atypicalneuroleptics, amisulpridehasno affinityforserotonin,-adrenergic,histamineH

and

cholinergicreceptors. In addition, amisulpridedoesnotbind to sigmasites.

In animals, athigh dosesitblockspost-synapticD

receptorslocated in thelimbicstructuresin preferenceto thosein

thestriatum. Unlikeclassicalneurolepticsitdoesnotinducecatalepsy andhypersensitivity ofD

dopaminereceptors

doesnotdevelop afterrepeated treatment. Atlowdosesitpreferentially blockspre-synapticD

receptors,

producing dopaminereleaseresponsibleforitsdisinhibitory effects.

Thisatypicalpharmacologicalprofilemay explain amisulpride’santipsychoticeffectathigherdosesthrough post-

synapticdopaminereceptorblockadeand itsefficacy againstnegativesymptoms, atlowerdoses, through pre-synaptic

dopaminereceptorblockade. In addition, thereduced tendency ofamisulprideto produceextrapyramidalsideeffects

may berelated to itspreferentiallimbicactivity.

In clinicalstudiesincluding schizophrenicpatientswith acuteexacerbations, amisulpridesignificantly alleviated

secondary negativesymptoms.

5.2Pharmacokineticproperties

In man, amisulprideshowstwo absorption peaks:onewhich isattained rapidly, onehourpost-doseand asecond

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50mg dose.

Thevolumeofdistribution is5.8l/kg.Asplasmaprotein binding islow(16%)drug interactionsareunlikely.

Absolutebioavailability is48%.Amisulprideisweakly metabolised:two inactivemetabolites, accounting for

approximately 4%ofthedose, havebeen identified.Thereisno accumulation ofamisulprideand itspharmacokinetics

remain unchanged aftertheadministration ofrepeated doses. Theelimination half-lifeofamisulprideisapproximately

12 hoursafteran oraldose.

Amisulprideiseliminated unchanged in theurine. Fifty percentofan intravenousdoseisexcreted viatheurine, of

which 90%iseliminated in thefirst24 hours. Renalclearanceisin theorderof20 l/h or330 ml/min.

Acarbohydraterich meal(containing 68%fluids)significantly decreasestheAUCs, T

and C

ofamisulpridebut

no changeswereseen afterahigh fatmeal.However, thesignificanceofthesefindingsin routineclinicaluseisnot

known.

Hepaticinsufficiency:sincethedrug isweakly metabolised adosagereduction should notbenecessary in patientswith

hepaticinsufficiency.

Renalinsufficiency:Theelimination half-lifeisunchanged in patientswith renalinsufficiency whilesystemic

clearanceisreduced by afactorof2.5 to 3.TheAUCofamisulpridein mild renalfailureincreased twofold and

almosttenfold in moderaterenalfailure(seechapter4.2 fordosing recommendations).Experienceishoweverlimited

and thereisno datawith dosesgreaterthan 50 mg.

Amisulprideisvery weakly dialysed.

Limited pharmacokineticdatain elderly subjects(>65 years)showthata10-30%riseoccursin C

and AUC

afterasingleoraldoseof50 mg.No dataareavailableafterrepeatdosing.

5.3Preclinical safetydata

An overallreviewofthecompleted safety studiesindicatesthatamisulprideisdevoid ofany general, organ-specific,

teratogenic, mutagenicorcarcinogenicrisk.Changesobserved in ratsand dogsatdosesbelowthemaximumtolerated

doseareeitherpharmacologicaleffectsoraredevoid ofmajortoxicologicalsignificanceundertheseconditions.

Compared with themaximumrecommended dosagesin man, maximumtolerated dosesare2 and 7 timesgreaterinthe

rat(200 mg/kg/day)and dog (120 mg/kg/day)respectively in termsofAUC. No carcinogenicrisk, relevantto man,

wasidentified in themouse(up to 120 mg/kg/day)and in therat(up to 240 mg/kg/day), corresponding fortheratto 1.5

to 4.5 timestheexpected human AUC.

Reproductivestudiesperformed in therat, rabbitand mousedid notshowany teratogenicpotential.

6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

Potato starch

Lactosemonohydrate

Methylcellulose

Colloidalhydrated silica

Magnesiumstearate

6.2Incompatibilities

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6.3ShelfLife

3 years.

6.4Special precautionsforstorage

No specialprecautions.

6.5Natureandcontentsofcontainer

PVC/aluminiumfoilblisterpackscontaining 30, 60, 90, 120 or150 tablets.

Notallpack sizesmay bemarketed.

6.6Instructionsforuseandhandling

No specialrequirements.

7MARKETINGAUTHORISATIONHOLDER

Winthrop PharmaceuticalsUKLimited

OneOnslowStreet

Guildford

Surrey

GU1 4YS

United Kingdom

Trading as:

Winthrop Pharmaceuticals

POBox 611

Guildford

Surrey

GU1 4YS

United Kingdom

8MARKETINGAUTHORISATIONNUMBER

PA1046/13/3

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

Dateoffirstauthorisation: 08 August2003

10DATEOFREVISIONOFTHETEXT

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