ALMIRID 5MG CAPSULES

Main information

  • Trade name:
  • ALMIRID 5MG CAPSULES
  • Dosage:
  • 5 Milligram
  • Pharmaceutical form:
  • Capsule
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug

Documents

Localization

  • Available in:
  • ALMIRID 5MG CAPSULES
    Ireland
  • Language:
  • English

Status

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

Summary of Product characteristics: dosage, interactions, side effects

PartII

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

Almirid5mgCapsules

2QUALITATIVEANDQUANTITATIVECOMPOSITION

Onecapsulecontains5mgof-dihydroergocryptinemesylate.

Forlistofexcipients,seesection6.1

3PHARMACEUTICALFORM

HardCapsule.

Ahardpink-redcapsulecontainingawhite–ivorywhitegranularpowder.

4CLINICALPARTICULARS

4.1TherapeuticIndications

TreatmentofadvancedParkinson’sdisease.Almirid istobeadministeredbyspecialistswithaccesstomonitoring

facilities.

4.2Posologyandmethodofadministration

Dosagemustbeadjustedaccordingtothepatient’sresponse.Theinitialrecommendeddosageis5mgtwiceaday.

Themaintenancedosageisgenerally60mg/day,andmaybeincreasedto120mg/day.Thisdosagecanbereached

graduallywithsuccessiveincreasesof10mg/dayeverytwoweeks.

Thehigherdosagescanbereachedbyadministeringthemultiscored20mgtablets,alsoavailableasAlmirid 20.If

Almirid isadministeredtogetherwithlevodopa,withorwithoutdecarboxylaseinhibitor,lowerdosageshouldbe

sufficient.Reductioninlevodopadosagemustbecarriedoutgraduallyuntiltheoptimaltherapeuticeffectisreached.

Irish Medicines Board

______________________________________________________________________________________________________________________

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-

goingpepticulcer,inviewoftheabsenceofexperimentalandsafetydata,shouldpreferablybegivenanalternative

treatment.

Duetothestructuralsimilaritywithergotderivatives,caremustbetakenintheadministrationofhighdosagesof

ALMIRID topatientswithmedicalhistoryofpsychoticdisturbances,severecardiovasculardiseases,pepticulceror

gastrointestinalbleeding.

-dihydroergocryptinehasbeenassociatedwithsomnolence,andotherdopamineagonistscanbeassociatedwith

suddensleeponsetepisodes,particularlyinpatientswithParkinson’sdisease.Patientsmustbeinformedofthisand

advisedtoexercisecautionwhiledrivingoroperatingmachinesduringtreatment.Patientswhohaveexperienced

somnolencemustrefrainfromdrivingoroperatingmachines.Furthermoreareductionofdosageorterminationof

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 30/09/2008 CRN 2038925 page number: 2

Pleuritisandpleuropulmonaryfibrosisareknowneffectsoflong-termtreatmentwithrelateddopaminergicsubstances.

Anyconnectionbetweentheseclinicalfindingsand-dihydroergocryptinemesylateisnotproved.Patientswith

pleuropulmonarysymptomsshouldbemonitoredandshouldbeencouragedtocontacttheirdoctorincaseofcoughing

anddyspnoea.

Patientswithrarehereditaryproblemsofgalactoseintolerance,theLapplactasedeficiencyorglucose-galactose

malabsorptionshouldnottakethismedicine.

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)shouldnotbeadministeredtogetherwitha-dihydroergocryptine

sincetheeffectsof-dihydroergocryptinemaybesubstantiallyincreased.

4.6Pregnancyandlactation

ALMIRID iscontraindicatedindocumentedorpresumedpregnancy.Sinceitinhibitslactation,itsuseis

contraindicatedduringbreast-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

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 30/09/2008 CRN 2038925 page number: 3

4.9Overdose

Accidentaloverdosecancausehypotension,nauseaandvomiting;inthiscase,intramuscularmetoclopramideshould

beusedasanantidote.Thepatientshouldbekeptsupinewitharterialbloodpressuremonitoring.

5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

Thetremor,bradykinesiaandstiffnessobservedinParkinson’sdiseaseareduetotheprogressivedegenerationofthe

dopaminergicneuronsoftheSubstantiaNigraandthenigrostriatalfibres.Thisleadstoalackofinhibitionofthe

cholinergicneuronsofthestriatumandthustotheextra-pyramidalsymptoms.-dihydroergocryptinebindsstronglyto

dopaminereceptorsresultinginstimulationofD

dopaminergicreceptorsintheSubstantiaNigraandCorpus

Striatum.Inaddition,-dihydroergocriptinepossessesapartialagonistactivityonD

receptors.Stimulationof

dopaminergicneuronsby-dihydroergocryptineattenuatestheextra-pyramidalmotorsymptomscharacteristicof

Parkinson’sdisease.

Animalstudieshavedemonstratedthattreatmentwith-dihydroergocryptineleadstorecoveryfromParkinson-like

symptomsinducedbythetoxinMPTPandpreventsneuronalcelldegenerationinducedbyoxidizingagents.

Thisneuroprotectiveactivityisadirectactionofdihydroergocryptineontheintracerebralcontentofreduced

glutathione,whichisanimportantendogenousfactor(scavenger)againstthecytotoxicityofhighlyreactiveoxygen

freeradicals.Freeradicalformationinthebrainisenhancedbyageing,byexcito-toxicstimulation,andincertain

degenerativediseaseslikeParkinson’sandAlzheimer’s.Thetreatmentwithdihydroergocryptineinducesasignificant

increaseinbrainreducedglutathione,throughactivationofantioxidantenzymes.

Throughtheabovemechanism,thedrugpreventstheneuronaldegenerationoftheSubstantiaNigrainducedbyMPTP

inexperimentalParkinson’sdisease.

5.2Pharmacokineticproperties

Thepharmacokineticsof-dihydroergocryptineareprobablybestdescribedbyreferencetoathreecomponentmodel.

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

Irish Medicines Board

______________________________________________________________________________________________________________________

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

6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

Capsulecontents

Maizestarch

Lactosemonohydrate

Microcrystallinecellulose

Magnesiumstearate

Capsuleshell

Erythrosine(E127)

Indigotin(E132)

Redferricoxide(E172)

Titaniumdioxide(E171)

Sodiumlaurilsulfate

Gelatin

6.2Incompatibilities

Noincompatibilityisreported,howeveritisinadvisabletomixwithotherdrugs.

6.3ShelfLife

4years.

6.4Specialprecautionsforstorage

Storebelow25 o

6.5Natureandcontentsofcontainer

Aluminiumblisters,coupledwithwhiteopaquePVCcontaining15capsules/blister,2blisters/carton.

6.6Specialprecautionsfordisposalofausedmedicinalproductorwastematerialsderivedfrom

suchmedicinalproductandotherhandlingoftheproduct

Nospecialrequirements.

7MARKETINGAUTHORISATIONHOLDER

PolichemS.A.,

50,ValFleuri,

L-1526,

Luxembourg.

8MARKETINGAUTHORISATIONNUMBER

Irish Medicines Board

______________________________________________________________________________________________________________________

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

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

Dateoffirstauthorisation:4February2000

Dateoflastrenewal:4February2005

10DATEOFREVISIONOFTHETEXT

Irish Medicines Board

______________________________________________________________________________________________________________________

Date Printed 30/09/2008 CRN 2038925 page number: 6