DDAVP DESMOPRESSIN

Main information

  • Trade name:
  • DDAVP DESMOPRESSIN
  • Dosage:
  • 0.2 Milligram
  • Pharmaceutical form:
  • Tablets
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug

Documents

Localization

  • Available in:
  • DDAVP DESMOPRESSIN
    Ireland
  • Language:
  • English

Status

  • Source:
  • HPRA - Health Products Regulatory Authority - Ireland
  • Authorization number:
  • PA1009/001/004
  • Authorization date:
  • 10-02-1999
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

IRISHMEDICINESBOARDACTS1995AND2006

MEDICINALPRODUCTS(CONTROLOFPLACINGONTHEMARKET)REGULATIONS,2007

(S.I.No.540of2007)

PA1009/001/004

CaseNo:2055991

TheIrishMedicinesBoardinexerciseofthepowersconferredonitbytheabovementionedRegulationsherebygrantsto

FerringIrelandLtd

UnitedDrugHouse,MagnaDrive,MagnaBusinessPark,CitywestRoad,Dublin24,Ireland

anauthorisation,subjecttotheprovisionsofthesaidRegulations,inrespectoftheproduct

DDAVP/Desmopressin0.2mgTablets

TheparticularsofwhicharesetoutinPartIandPartIIoftheattachedSchedule.Theauthorisationisalsosubjecttothegeneralconditionsas

maybespecifiedinthesaidRegulationsaslistedonthereverseofthisdocument.

Thisauthorisation,unlesspreviouslyrevoked,shallcontinueinforcefrom10/02/2009.

SignedonbehalfoftheIrishMedicinesBoardthis

________________

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PartII

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

DDAVP/Desmopressin0.2mgTablets

2QUALITATIVEANDQUANTITATIVECOMPOSITION

Eachtabletcontainsdesmopressinacetate0.2mgequivalenttodesmopressin178micrograms.

Excipients:Contains123.7mglactosemonohydrate.

Forafulllistofexcipients,seesection6.1.

3PHARMACEUTICALFORM

Tablets

White,roundconvextablet,withascorelineononefaceand“0.2”onthereverse.

Thescorelineisonlytofacilitatebreakingforeaseofswallowingandnottodivideintoequaldoses.

4CLINICALPARTICULARS

4.1TherapeuticIndications

4.2Posologyandmethodofadministration

Centraldiabetesinsipidus:

Dosageisindividualindiabetesinsipidusbutclinicalexperiencehasshownthatthetotaldailydosenormallyliesinthe

rangeof0.2to1.2mg.Asuitablestartingdoseinadultsandchildrenis0.1mgthreetimesdaily.Thisdosageregimen

shouldthenbeadjustedinaccordancewiththepatient'sresponse.Forthemajorityofpatients,themaintenancedoseis

0.1mgto0.2mgthreetimesdaily.Intheeventofsignsofwaterretention/hyponatraemiatreatmentshouldbe

interrupteduntilthepatienthasrecovered.

Primarynocturnalenuresis

Therecommendedinitialdoseis0.2mgatbedtime.Ifthisdoseisnotsufficientlyeffective,thedosemaybeincreased

upto0.4mg.Fluidrestrictionshouldbeobserved.

Intheeventofsignsorsymptomsofwaterretentionand/orhyponatraemia(headache,nausea/vomiting,weightgain,

and,inseverecases,convulsions)treatmentshouldbeinterrupteduntilthepatienthasfullyrecovered.Thesupervising

specialistshoulddecidewhetherornottorestarttreatmentinsuchapatient.Ifrestartingtreatmentstrictfluid

Forthediagnosisandtreatmentofcranialdiabetesinsipidusincludingpost-hypophysectomy

polyuria/polydipsiaandforthetreatmentofprimarynocturnalenuresisinpatients(from5to

65yearsofage)withnormalabilitytoconcentrateurine.

DDAVP/Desmopressintabletsareindicatedforthesymptomatictreatmentofnocturiain

adultsupto65yearsonly,associatedwithnocturnalpolyuria,i.e.nocturnalurineproduction

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DDAVP/Desmopressintabletsareintendedfortreatmentperiodsofupto3months.Theneedforcontinuedtreatment

shouldbereassessedbymeansofaperiodofatleastoneweekwithoutDDAVP/Desmopressintablets.

Nocturia:

Therecommendedinitialdoseis0.1mgatbedtime.

Ifthisdoseisnotsufficientlyeffectiveafteroneweek,thedosemaybeincreasedupto0.2mgandsubsequently0.4mg

byweeklydoseescalations.Fluidrestrictionshouldbeobserved.

Innocturiapatients,afrequency/volumechartshouldbeusedtodiagnosenocturnalpolyuriaforatleast2daysbefore

startingtreatment.Anight-timeurineproductionexceedingthefunctionalbladdercapacityorexceeding1/3ofthe24-

hoururineproductionisregardedasnocturnalpolyuria.Foodintakemayreducetheintensityanddurationofthe

antidiureticeffectatlowdosesofdesmopressin(seesection4.5).

Theinitiationoftreatmentintheelderly(patientsover65years)iscontraindicated.

Intheeventofsignsorsymptomsofwaterretentionand/orhyponatraemia(headache,nausea/vomiting,weightgain,

and,inseverecases,convulsions)treatmentshouldbeinterrupteduntilthepatienthasfullyrecovered.Whenrestarting

treatmentstrictfluidrestrictionshouldbeenforced(see4.4).Ifadequateclinicaleffectisnotachievedwithin4weeks

followingappropriatedosetitrationthemedicationshouldbediscontinued.

4.3Contraindications

DDAVP/Desmopressintabletsarecontraindicatedincasesof:

4.4Specialwarningsandprecautionsforuse

Useoftheproductshouldbeunderspecialistsupervisionwithappropriatefacilitiesavailableformonitoringand

interpretationofresponse.

Thisproductcontainslactosemonohydrate.

Patientswithrarehereditaryproblemsofgalactoseintolerance,theLapplactosedeficiencyorglucose-galactose

malabsorptionshouldnottakethismedicine.

Careshouldbetakenwithpatientswhohavereducedrenalfunctionand/orcardiovasculardiseaseorcysticfibrosis.

PatientsbeingtreatedforprimarynocturnalenuresisornocturiashoulddiscontinueDDAVP/DesmopressinTablets

duringanepisodeofvomitingand/ordiarrhoeauntiltheirfluidbalanceisonceagainnormal.

Whenusedforprimarynocturnalenuresisandnocturiaindications,thefluidintakemustbelimitedtoaminimumfrom

1hourbeforeuntil8hoursafteradministration.

Treatmentwithoutconcomitantreductionoffluidintakemayleadtowaterretentionand/orhyponatraemiawithor

withoutaccompanyingwarningsignsandsymptoms(headache,nausea/vomiting,weightgain,and,inseverecases,

1.Habitualorpsychogenicpolydipsia(resultinginaurineproductionexceeding40ml/kg/24hours).

2.Ahistoryofknownorsuspectedcardiacinsufficiencyandotherconditionsrequiringtreatmentwithdiuretics.

3.Moderateandsevererenalinsufficiency(creatinineclearancebelow50ml/min).

4.Knownhyponatraemia.

5.SyndromeofInappropriateAnti-diureticHormone(SIADH)secretion.

6.HypersensitivitytodesmopressinortoanyoftheexcipientsofDDAVP/Desmopressintablets.

7.Patientsovertheageof65forthetreatmentofprimarynocturnalenuresis.

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Precautions:

4.5Interactionwithothermedicinalproductsandotherformsofinteraction

SubstanceswhichareknowntoinduceSIADH,e.g.tricyclicantidepressants,selectiveserotoninereuptakeinhibitors,

chlorpromazineandcarbamazepine,maycauseanadditiveantidiureticeffectleadingtoanincreasedriskofwater

retention/hyponatraemia(see4.4).

NSAIDsmayinducewaterretention/hyponatraemia(see4.4).

Concomitanttreatmentwithloperamidemayresultina3-foldincreaseofdesmopressinplasmaconcentrations,which

mayleadtoanincreasedriskofwaterretention/hyponatraemia.Althoughnotinvestigated,otherdrugsslowing

intestinaltransportmighthavethesameeffect.

Itisunlikelythatdesmopressinwillinteractwithdrugsaffectinghepaticmetabolism,sincedesmopressinhasbeen

shownnottoundergosignificantlivermetabolismininvitrostudieswithhumanmicrosomes.However,formalinvivo

interactionstudieshavenotbeenperformed.Astandardised27%fatmealsignificantlydecreasedabsorption(rateand

extent)oforaldesmopressin.Nosignificanteffectwasobservedwithrespecttopharmacodynamics(urineproduction

orosmolality).Foodintakemayreducetheintensityanddurationoftheantidiureticeffectatloworaldosesof

desmopressin.

4.6Pregnancyandlactation

Pregnancy

CautionshouldbeexercisedwhenprescribingDDAVP/Desmopressintabletstopregnantwomen.

Dataonalimitednumber(n=53)ofexposedpregnanciesinwomenwithdiabetesinsipidusindicatenoadverseeffects

ofdesmopressinonpregnancyoronthehealthofthefoetus/newbornchild.Todate,nootherrelevantepidemiological

dataareavailable.Animalstudiesdonotindicatedirectorindirectharmfuleffectswithrespecttopregnancy,

embryonal/foetaldevelopment,parturitionorpostnataldevelopment.Therehavebeenrarereportsofmalformationsin

childrenborntomotherstreatedfordiabetesinsipidusduringpregnancy.

Lactation

ResultsfromanalysesofmilkfromnursingmothersreceivinghighdoseDesmopressin(300microgramsintranasal)

indicatethattheamountsofDesmopressinthatmaybetransferredtothechildareconsiderablylessthantheamounts

requiredtoinfluencediuresis.

4.7Effectsonabilitytodriveandusemachines

1.Severebladderdysfunctionandoutletobstructionshouldbeconsideredbeforestartingtreatment.

2.Elderlypatientsandpatientswithlowserumsodiumlevelsmayhaveanincreasedriskofhyponatraemia

thereforeDDAVP/Desmopressintabletsarecontraindicatedinthesepatients.

3.Treatmentwithdesmopressinshouldbeinterruptedduringacuteintercurrentillnessescharacterisedbyfluid

and/orelectrolyteimbalance(suchassystemicinfections,fever,andgastroenteritis),

4.Precautionstoavoidhyponatraemiaincludingcarefulattentiontofluidrestrictionandmorefrequentmonitoring

ofserumsodiummustbetakenincaseofconcomitanttreatmentwithdrugs,whichareknowntoinduceSIADH,

e.g.tricyclicantidepressants,selectiveserotoninereuptakeinhibitors,chlorpromazineandcarbamazepine,case

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4.8Undesirableeffects

Treatmentwithoutconcomitantreductionoffluidintakemayleadtowaterretention/hyponatraemiawithorwithout

accompanyingwarningsignsandsymptoms(headache,nausea/vomiting,decreasedserumsodium,weightgainandin

severecasesconvulsions).

Primarynocturnalenuresisanddiabetesinsipidus:

Postmarketingexperience:

Nocturia:

Inclinicaltrialsabout35%ofpatientsexperiencedadversedrugreactionsduringdose-titration.Themostfrequent

adversedrugreactionsduringdosetitrationwereheadache(15%),nausea(5%),abdominalpain(4%),hyponatraemia

(4%),dizziness(3%)anddrymouth(3%).Duringlong-termtreatment24%ofpatientsexperiencedadversedrug

reactions.Themostfrequentadversedrugreactionsinlongtermtreatmentwereheadache(6%),dizziness(3%),

peripheraloedema(3%),micturitionfrequency(2%),nausea(2%),andweightincrease(2%).

4.9Overdose

OverdoseofDDAVP/Desmopressintabletsleadstoaprolongeddurationofactionwithanincreasedriskofwater

retentionandhyponatraemia.

Treatment:

Althoughthetreatmentofhyponatraemiashouldbeindividualised,thefollowinggeneralrecommendationscanbe

Common(>1/100): General:Headache.

GI:Stomachpain,nausea.

Veryrare(<1/10,000):Hyponatraemia.

1.Veryrarecasesofemotionaldisturbancesinchildrenhavebeenreported.

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5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

Pharmacotherapeuticgroup:vasopressinandanalogues.

ATCcode:H01BA02.

DDAVP/Desmopressintabletscontaindesmopressin,astructuralanalogueofthenaturalpituitaryhormonearginine

vasopressin.ThedifferenceliesinthedesaminationofcysteineandsubstitutionofL-argininebyD-arginine.This

resultsinconsiderablylongerdurationofaction.Theuterotonicandvasopressoractionsareextremelylowinthe

dosagesclinicalused.

Clinicaltrialswithdesmopressintabletsinthetreatmentofnocturiashowedthefollowing:

Effectoftreatmentwithindividualoraldoseofdesmopressinbetween0.1and0.4mgduring3weeks,comparedwith

placebo(pooleddata).

Eightpercentofthepatientsinterruptedinthedesmopressindosetitrationphaseduetoadverseeffects,and2%inthe

1.areductionofatleast50%inthemeannumberofnocturnalvoidswasobtainedin39%ofpatientswith

desmopressincomparedto5%ofpatientswithplacebo(p<0.0001).

2.Themeannumberofvoidspernightdecreasedby44%withdesmopressincomparedto15%withplacebo

(p<0.0001).

3.Themediandurationoffirstundisturbedsleepperiodincreasedby64%withdesmopressincomparedto20%

withplacebo(p<0.0001).

4.Themeandurationoffirstundisturbedsleepperiodincreasedby2hourswithdesmopressincomparedto31

minuteswithplacebo(p<0.0001).

Desmopressin Placebo Statistical

Significance

Vs.placebo

Variable Mean

Baseline

Value Meanvalue

during3weeks

oftreatment Mean

Baseline

value Meanvalue

during3weeks

oftreatment

Numberof

nocturnalvoids 2.97(0.84)

1.68(0.86) 3.03(1.10) 2.54(1.05)

(p<0.0001)

Nocturnaldiuresis

rate(ml/min) 1.51(0.55) 0.87(0.34) 1.55(0.57) 1.44(0.57) (p<0.0001)

Durationoffirst

undisturbedsleep

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5.2Pharmacokineticproperties

Theabsolutebioavailabilityoforallyadministereddesmopressinvariesbetween0.08%and0.16%.Meanmaximum

plasmaconcentrationisreachedwithin2hours.Thedistributionvolumeis0.2-0.31/kg.Desmopressindoesnotcross

theblood-brainbarrier.Theoralterminalhalf-lifevariesbetween2.0and3.21hours.Desmopressinexhibitsa

moderatetohighvariabilityinbioavailability,bothwithinandbetweensubjects.Concomitantuseoffooddecreases

therateandextentofabsorptionby40%.

Inin-vitrohumanlivermicrosomepreparations,ithasbeenshownthatnosignificantamountofdesmopressinis

metabolisedintheliver,andthushumanlivermetabolisminvivoisnotlikelytooccur.

AfterIVinjection45%oftheamountofdesmopressincouldberecoveredintheurinewithin24hours.

FollowingoraladministrationofDesmopressinacetate,maximumplasmaconcentrationsareachievedwithinonehour.

ThedisappearanceofDesmopressinacetatefromplasmathenfollowsanexponentialdecreasewithhalf-lifeofabout2

hours.Therewasnostatisticaldifferenceinantidiureticresponsebetweenfastingandnon-fastingsubjects.

5.3Preclinicalsafetydata

Therearenopre-clinicaldataofrelevancetotheprescriberwhichareadditionaltothatalreadyincludedinother

sectionsoftheSPC.

6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

Lactosemonohydrate

Potatostarch

Povidone

Magnesiumstearate

6.2Incompatibilities

Notapplicable.

6.3ShelfLife

3years.

6.4Specialprecautionsforstorage

Donotstoreabove25 °

Storeintheoriginalpackageandkeepthebottletightlyclosedinordertoprotectfromlightandmoisture.

6.5Natureandcontentsofcontainer

Thetabletsaresuppliedina30mlHDPEbottle/PPclosurewithadesiccantcapsule.

Packsize:90tablets.

6.6Specialprecautionsfordisposalofausedmedicinalproductorwastematerialsderivedfrom

suchmedicinalproductandotherhandlingoftheproduct

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7MARKETINGAUTHORISATIONHOLDER

FerringIrelandLtd

UnitedDrugHouse

MagnaDrive

MagnaBusinessPark

CitywestRoad

Dublin24

Ireland

8MARKETINGAUTHORISATIONNUMBER

PA1009/1/4

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

Dateoffirstauthorisation:10February1994

Dateoflastrenewal:10February2009

10DATEOFREVISIONOFTHETEXT

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