ALMIRID 20MG TABLETS

Main information

  • Trade name:
  • ALMIRID 20MG TABLETS
  • Dosage:
  • 20 Milligram
  • Pharmaceutical form:
  • Tablets
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug

Documents

Localization

  • Available in:
  • ALMIRID 20MG TABLETS
    Ireland
  • Language:
  • English

Status

  • Source:
  • HPRA - Health Products Regulatory Authority - Ireland
  • Authorization number:
  • PA1005/001/002
  • Authorization date:
  • 04-02-2000
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

PartII

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

Almirid20mgTablets.

2QUALITATIVEANDQUANTITATIVECOMPOSITION

Onetabletcontains20mgof-dihydroergocryptinemesylate.

Forexcipients,see6.1

3PHARMACEUTICALFORM

Tablet.

Awhitetooff-whitemultiscoredtablet.

4CLINICALPARTICULARS

4.1TherapeuticIndications

TreatmentofadvancedParkinson’sdisease.Almirid istobeadministeredbyspecialistswithaccesstomonitoring

facilities.

4.2Posologyandmethodofadministration

Dosagemustbeadjustedaccordingtothepatient’sresponse.ItissuggestedthattreatmentshouldbeginwithAlmirid

5.Theinitialrecommendeddosageis5mgtwiceaday.Themaintenancedosageisgenerally60mg/day,andmay

beincreasedto120mg/day,thisdosagecanbereachedgraduallywithsuccessiveincreasesof10mg/dayevery

twoweeks.

IfAlmirid isadministeredtogetherwithlevodopa,withorwithoutdecarboxylaseinhibitor,lowerdosageshouldbe

sufficient.Reductioninlevodopadosagemustbecarriedoutgraduallyuntiltheoptimaltherapeuticeffectisreached.

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Date Printed 30/09/2008 CRN 2038925 page number: 1

4.3Contraindications

Documentedindividualhypersensitivitytotheproduct.

Documentedorpresumedpregnancyandpaediatricuse.

Duetothehighrateoflivermetabolism,thedrugiscontraindicatedinsevereliverfailure.

Withregardtoitsinhibitoryeffectonlactation,theuseofthedrugiscontraindicatedduringbreast-feeding

4.4Specialwarningsandprecautionsforuse

Inparkinsonianpatientswithgalactorrhoea,prolactindependentamenorrhoea,menstrualdisturbancesoracromegaly,

treatmentwithAlmirid caneliminatethepre-existingsterility.Therefore,womenatriskofpregnancymustadopt

sometypeofnon-hormonalcontraceptive.Acromegalicpatientswithapositivehistoryofpepticulcerorwithon-going

pepticulcer,inviewoftheabsenceofexperimentalandsafetydata,shouldpreferablybegivenanalternative

treatment.

Duetothestructuralsimilaritywithergotderivatives,caremustbetakenintheadministrationofhighdosagesof

Almirid topatientswithmedicalhistoryofpsychoticdisturbances,severecardiovasculardiseases,pepticulceror

gastrointestinalbleeding.

-dihydroergocryptinehasbeenassociatedwithsomnolence,andotherdopamineagonistscanbeassociatedwith

suddensleeponsetepisodes,particularlyinpatientswithParkinson’sdisease.Patientsmustbeinformedofthisand

advisedtoexercisecautionwhiledrivingoroperatingmachinesduringtreatment.Patientswhohaveexperienced

somnolencemustrefrainfromdrivingoroperatingmachines.Furthermoreareductionofdosageorterminationof

therapymaybeconsidered.

Pleuritisandpleuropulmonaryfibrosisareknowneffectsoflong-termtreatmentwithrelateddopaminergicsubstances.

Anyconnectionbetweentheseclinicalfindingsand-Dihydroergocryptinemesylateisnotproved.Patientswith

pleuropulmonarysymptomsshouldbemonitoredandshouldbeencouragedtocontacttheirdoctorincaseofcoughing

anddyspnoea.

Patientswithrarehereditaryproblemsofgalactoseintolerance,theLapplactasedeficiencyorglucose-galactose

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4.5Interactionwithothermedicinalproductsandotherformsofinteraction

-dihydroergocryptinecounteractstheactivityofanti-dopaminergicagents,suchasneuroleptics.

Thepossibleinteractionof-dihydroergocryptinewithhypotensivedrugscannotbeexcluded.Particularcaremustbe

giventopatientsbeingtreatedwithotherergotalkaloids,ordrugsactiveonarterialbloodpressure,withregardtoa

possibleenhancingeffect.Thisisparticularlyimportantinelderlypatients.

-dihydroergocryptineissubjecttofirst-passmetabolismbytheisoenzymeCYP3A4ofCytochromeP450.A

pharmacokineticstudyinhealthysubjectsshowedthat,withconcomitantadministrationoferythromycin,serumlevels

of-dihydroergocryptineanditsmetabolitesaresignificantlyincreased.Duetothisfactthereispotentiallyan

increasedriskofsideeffects.Therefore,duringconcomitantadministrationwithdrugsthatinhibitCYP3A4,thedose

of-dihydroergocryptinemustbeadjusted.Thismustbeconsideredeachtimeconcomitanttreatmentisproposed.

Macrolideantibiotics(forexampleerythromycin)shouldnotbeadministeredtogetherwith-dihydroergocryptine

sincetheeffectsof-dihydroergocryptinemaybesubstantiallyincreased.

4.6Pregnancyandlactation

Almirid iscontraindicatedindocumentedorpresumedpregnancy.Sinceitinhibitslactation,itsuseiscontraindicated

duringbreast-feeding.

4.7Effectsonabilitytodriveandusemachines

Intheeventofhypotensivereactionsshownbycertainpatientsespeciallyduringtheearlydaysoftreatment,particular

caremustbetakenduringdrivingandoperatingmachines.

Patientsbeingtreatedwith-dihydroergocryptineandpresentingwithsomnolencemustbeinformedtorefrainfrom

drivingorengaginginactivitieswhereimpairedalertnessmayputthemselvesorothersatriskofseriousinjuryor

death(e.g.operatingmachines)unlesspatientshaveovercomesuchexperiencesofsomnolence(seealsosection4.4,

Specialwarningsandprecautionsforuse)

4.8Undesirableeffects

-dihydroergocryptineisassociatedwithsomnolence.

Duringclinicaltrialssomepatientscomplainedofnausea,vomiting,gastralgia,gastricburning,dyspepsia,

constipation,dizziness,hypotension,posturalhypotension,faintness,asthenia,sleepiness,anxiety,headacheand

tachycardia.

Sideeffectsgenerallyoccurduringtheearlydaysoftherapy,andtheyareshort-lasting.Someeffectsaredose-related

andmaybeeliminatedthroughareductionofthedosage.

Rarely,skinrashwasobserved.Insuchacaseitissuggestedtowithdrawthetreatmentandconsultaphysician.

Incaseofcombinedtreatmentwithlevodopa,thefrequencyofsideeffectssuchasgastralgia,pyrosis,faintness,and

headachewasincreased.Appearanceofoedemaandhallucinationshasbeenreported.

4.9Overdose

Accidentaloverdosecancausehypotension,nauseaandvomiting;inthiscase,intramuscularmetoclopramideshould

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5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

Thetremor,bradykinesiaandstiffnessobservedinParkinson’sdiseaseareduetotheprogressivedegenerationofthe

dopaminergicneuronsoftheSubstantiaNigraandthenigrostriatalfibres.Thisleadstoalackofinhibitionofthe

cholinergicneuronsofthestriatumandthustotheextra-pyramidalsymptoms.-dihydroergocryptinebindsstronglyto

dopaminereceptorsresultinginstimulationofD

dopaminergicreceptorsintheSubstantiaNigraandCorpusStriatum.

Inaddition,-dihydroergocryptinepossessesapartialagonistactivityonD

receptors.Stimulationofdopaminergic

neuronsby-dihydroergocryptineattenuatestheextra-pyramidalmotorsymptomscharacteristicofParkinson’s

disease.

Animalstudieshavedemonstratedthattreatmentwith-dihydroergocryptineleadstorecoveryfromParkinson-like

symptomsinducedbythetoxinMPTPandpreventsneuronalcelldegenerationinducedbyoxidizingagents.

Thisneuroprotectiveactivityisadirectactionofdihydroergocryptineontheintracerebralcontentofreduced

glutathione,whichisanimportantendogenousfactor(scavenger)againstthecytotoxicityofhighlyreactiveoxygen

freeradicals.Freeradicalformationinthebrainisenhancedbyageing,byexcito-toxicstimulation,andincertain

degenerativediseaseslikeParkinson’sandAlzheimer’s.Thetreatmentwithdihydroergocryptineinducesasignificant

increaseinbrainreducedglutathione,throughactivationofantioxidantenzymes.Throughtheabovemechanism,the

drugpreventstheneuronaldegenerationoftheSubstantiaNigrainducedbyMPTPinexperimentalParkinson’s

disease.

5.2Pharmacokineticproperties

Thepharmacokineticsof-dihydroergocryptineareprobablybestdescribedbyreferencetoathreecomponent

model.Thereisalinearrelationshipbetweendose,concentration,andeffect.

-dihydroergocryptineisrapidlyabsorbedfollowingoraladministration.Peakplasmalevelsareobservedafter30to

120minutes.Proteinbindingisapproximately50%.Approximately97%of-dihydroergocryptineismetabolisedby

theliver.Theabsoluteoralbioavailabilityofthedrugisapproximately2.4%ofthedose.Themeanbiologicalhalflife

isapproximately12hours.-dihydroergocryptineisexcretedinthefaeces.

Steadystateisrapidlyachievedfollowingadministrationofthedrugtwotothreetimesperday.Noaccumulation

phenomenahavebeenobservedinpatientsreceivingchronictherapy.

5.3Preclinicalsafetydata

OralLD

was4384.6and > 5000mg/kginmiceandrats,respectively.IntravenousLD

was192.3and50.7mg/kg

inthesamespecies.Inthelongtermoraltoxicitytestsperformedinratsandmonkeys,-dihydroergocryptinewaswell

toleratedparticularlyinmonkeys,evenatdosesmuchhigherthanthedailytherapeuticdosesadministeredinman.The

drugimpairsfertilityinrats,andreproductivetoxicityatdosesstartingfrom18mg/kg/day,hasbeenobserved.This

occursasaresultoftheprolactin-loweringactivity.Reproductivetoxicityhasalsobeenobservedinrabbitswithdoses

of18mg/kg/day.However,thisdoseiswellinexcessofthemaximumdailydoseforuseinman.Mutagenicitytests

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Date Printed 30/09/2008 CRN 2038925 page number: 4

6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

Lactosemonohydrate

Microcrystallinecellulose

Croscarmellosesodium

Magnesiumstearate

Povidone

6.2Incompatibilities

Noincompatibilityisreported,howeveritisinadvisabletomixwithotherdrugs.

6.3ShelfLife

4years.

6.4Specialprecautionsforstorage

Storebelow25 o

6.5Natureandcontentsofcontainer

Aluminiumblisters,coupledwithwhiteopaquePVCcontaining10tablets/blisterstrip.Cartonscontaining2,3or6

blisterstrips.

Notallpacksizesmaybemarketed.

6.6Specialprecautionsfordisposalofausedmedicinalproductorwastematerialsderivedfrom

suchmedicinalproductandotherhandlingoftheproduct

Nospecialrequirements.

7MARKETINGAUTHORISATIONHOLDER

PolichemS.A.,

50,ValFleuri,

L-1526,

Luxembourg.

8MARKETINGAUTHORISATIONNUMBER

PA1005/001/002

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

Dateoffirstauthorisation:04February2000

Dateoflastrenewal:04February2005

10DATEOFREVISIONOFTHETEXT

Irish Medicines Board

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Date Printed 30/09/2008 CRN 2038925 page number: 5