Adin

Main information

  • Trade name:
  • Adin 0.2 mg Tablet
  • Dosage:
  • 0.2 mg
  • Pharmaceutical form:
  • Tablet
  • Units in package:
  • Bottle, plastic, 30mL HDPE bottle, PP cap - 30 tablets, 30 tablets
  • Class:
  • Prescription
  • Prescription type:
  • Prescription
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug
  • Manufactured by:
  • PolyPeptide Laboratories AB

Documents

Localization

  • Available in:
  • Adin 0.2 mg Tablet
    New Zealand
  • Language:
  • English

Other information

Status

  • Source:
  • Medsafe - Medicines Safety Authority - New Zealand
  • Authorization number:
  • 12189
  • Authorization date:
  • 23-08-2005
  • Last update:
  • 27-09-2017

Summary of Product characteristics: dosage,interactions,side effects

NEWZEALANDDATASHEET

ADIN ®

TABLETS

Desmopressinacetate

Presentation

ADIN ®

0.1mg:Eachtabletcontainsdesmopressinacetate0.1mgequivalenttodesmopressin

(freebase)0.089mg.White,ovalandconvextabletswithasinglescoreandmarked“0.1”onone

side.

ADIN ®

0.2mg:Eachtabletcontainsdesmopressinacetate0.2mgequivalenttodesmopressin

(freebase)0.178mg.White,roundandconvextabletswithasinglescoreandmarked“0.2”on

oneside.

Thescorelineisonlytofacilitatebreakingforeaseofswallowingandnottodivideintoequal

doses.

ForafulllistofexcipientsseePharmaceuticalPrecautions.

Uses

Actions

ADIN ®

tabletscontaindesmopressin,astructuralanalogueofthenaturalpituitaryhormone

argininevasopressin.ThedifferenceliesinthedesaminationofcysteineandsubstitutionofL-

argininebyD-arginine.Thisresultsinaconsiderablylongerdurationofactionandacomplete

lackofpressoreffectinthedosagesclinicallyused.Desmopressinisapotentcompoundwithan

valueof1.6pg/mL,fortheantidiureticeffect.Afteroraladministration,aneffectlastingfrom

6to14hoursormorecanbeexpected.

Clinicaltrialswithdesmopressintabletsinthetreatmentofnocturiashowedthefollowing:

Areductionofatleast50%inthemeannumberofnocturnalvoidswasobtainedin39%of

patientswithdesmopressincomparedto5%ofpatientswithplacebo(p<0.0001).

Themeannumberofvoidspernightdecreasedby44%withdesmopressincomparedto15%

withplacebo(p<0.0001).

Themediandurationoffirstundisturbedsleepperiodincreasedby64%withdesmopressin

comparedto20%withplacebo(p<0.0001).

Themeandurationoffirstundisturbedsleepperiodincreasedby2hourswithdesmopressin

comparedto31minuteswithplacebo(p<0.0001).

Effectoftreatmentwithindividualoraldoseofdesmopressinbetween0.1and0.4mg

during3weeks,comparedwithplacebo(pooleddata)

Desmopressin Placebo Statistical

significance

vsplacebo

Variable Mean

baseline

value Meanvalue

during3

weeksof

treatment Mean

baseline

value Meanvalue

during3

weeksof

treatment

Numberof

nocturnal

voids 2.97(0.84) 1.68(0.86) 3.03(1.10) 2.54(1.05) P<0.0001

Nocturnal

diuresisrate

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

-2-

Durationof

first

undisturbed

sleepperiod

(min) 152(51) 270(95) 147(54) 178(70) P<0.0001

Eightpercentofthepatientsinterruptedinthedesmopressindosetitrationphaseduetoadverse

effects,and2%inthesubsequentdouble-blindphase(0.63%ondesmopressinand1.45%on

placebo).

Pharmacokinetics

TheabsolutebioavailabilityofADIN ®

tabletsis0.16%withanSDof0.17%.Meanmaximum

plasmaconcentrationisreachedwithin2hours.Concomitantuseoffooddecreasestherateand

extentofabsorptionby40%.

Distribution

Thedistributionofdesmopressinisbestdescribedbyatwo-compartmentdistributionmodelwith

avolumeofdistributionduringtheeliminationphaseof0.3-0.5L/kg.

Biotransformation

Theinvitrometabolismofdesmopressinhasnotbeenstudied.Invitrohumanlivermicrosome

metabolismstudiesofdesmopressinhaveshownthatnosignificantamountismetabolizedinthe

liverbythecytochromeP450system.Thushumanlivermetabolisminvivobythecytochrome

P450systemisunlikelytooccur.TheeffectofdesmopressinonthePKofotherdrugsislikelyto

beminimalduetoitslackofinhibitionofthecytochromeP450drugmetabolizingsystem.

Elimination

Thetotalclearanceofdesmopressinhasbeencalculatedto7.6L/hr.Theterminalhalf-lifeof

desmopressinisestimatedtobe2.8hours.Inhealthysubjectsthefractionexcretedunchanged

was52%(44%-60%).

Linearity/non-linearity

Therearenoindicationsofnon-linearitiesinanyofthepharmacokineticparametersof

desmopressin.

Characteristicsinspecificgroupsofpatients

RenalImpairment

DependingonthedegreeofrenalimpairmenttheAUCandhalf-lifeincreasedwiththeseverityof

therenalimpairment.Inpatientswithmoderateandsevererenalimpairment(creatinine

clearancebelow50mL/min)desmopressiniscontraindicated.

HepaticImpairment

Nostudiesperformed.

Children

ThepopulationpharmacokineticsofADIN ®

tabletshasbeenstudiedinchildrenwithPNEandno

significantdifferencefromadultsweredetected.

Indications

ADIN ®

tabletsareindicatedforthetreatmentofcentraldiabetesinsipidus.

ADIN ®

tabletsareindicatedforthetreatmentofprimarynocturnalenuresisinpatients(from5

yearsofage)withnormalabilitytoconcentrateurine.

ADIN ®

tabletsareindicatedforthesymptomatictreatmentofnocturiainadults,associatedwith

nocturnalpolyuria,i.e.nocturnalurineproductionexceedingbladdercapacity.

-3-

DosageandAdministration

General

Thetabletmaybedividedtoeasetheintakebutbothtablethalvesmustbetakenatthesame

occasion.

Foodintakemayreducetheintensityanddurationoftheantidiureticeffectatlowdosesof

desmopressin(seeInteractions).

Intheeventofsignsorsymptomsofwaterretentionand/orhyponatraemia(headache,

nausea/vomiting,weightgain,and,inseverecases,convulsions)treatmentshouldbeinterrupted

untilthepatienthasfullyrecovered.Whenrestartingtreatmentstrictfluidrestrictionshouldbe

enforced(seeWarningsandPrecautions).

Ifadequateclinicaleffectisnotachievedwithin4weeksfollowingappropriatedosetitrationthe

medicationshouldbediscontinued.

Centraldiabetesinsipidus

Dosageisindividualindiabetesinsipidusbutclinicalexperiencehasshownthatthetotaldaily

dosenormallyliesintherangeof0.2to1.2mg.Asuitablestartingdoseinadultsandchildrenis

0.1mgthreetimesdaily.Thisdosageregimenshouldthenbeadjustedinaccordancewiththe

patient’sresponse.Forthemajorityofpatients,themaintenancedoseis0.1mgto0.2mgthree

timesdaily.

Primarynocturnalenuresis

Therecommendedinitialdoseis0.2mgatbedtime.Ifthisdoseisnotsufficientlyeffective,the

dosemaybeincreasedupto0.4mg.Fluidrestrictionshouldbeobserved.ADIN ®

tabletsare

intendedfortreatmentperiodsofupto3months.Theneedforcontinuedtreatmentshouldbe

reassessedbymeansofaperiodofatleastoneweekwithoutADIN ®

tablets.

Nocturia

Innocturiapatients,afrequency/volumechartshouldbeusedtodiagnosenocturnalpolyuriafor

atleast2daysbeforestartingtreatment.Anight-timeurineproductionexceedingthefunctional

bladdercapacityorexceeding1/3ofthe24-hoururineproductionisregardedasnocturnal

polyuria.

Therecommendedinitialdoseis0.1mgatbedtime.Ifthisdoseisnotsufficientlyeffectiveafter

oneweek,thedosemaybeincreasedupto0.2mgandsubsequently0.4mgbyweeklydose

escalations.Fluidrestrictionshouldbeobserved.

SpecialPopulations

ElderlyPatients:

Theinitiationoftreatmentintheelderlyisnotrecommended.Shouldphysiciansdecidetoinitiate

desmopressintreatmentinthesepatientsthenserumsodiumshouldbemeasuredbefore

beginningthetreatmentand3daysafterinitiationorincreaseindosageandatothertimesduring

treatmentasdeemednecessarybythetreatingphysician.

RenalImpairment:SeeContraindications.

HepaticImpairment:SeeWarningsandPrecautions.

PaediatricPopulation:

ADIN ®

tabletisindicatedinCentralDiabetesInsipidusandPrimaryNocturnalEnuresis(see

Indications).Doserecommendationsarethesameasinadults.

-4-

Contraindications

ADIN ®

tabletsarecontraindicatedincasesof:

Habitualorpsychogenicpolydipsia(resultinginaurineproductionexceeding40ml/kg/24

hours)

Ahistoryofknownorsuspectedcardiacinsufficiencyandotherconditionsrequiringtreatment

withdiuretics

Moderateandsevererenalinsufficiency(creatinineclearancebelow50ml/min)

Knownhyponatraemia

SyndromeofinappropriateADHsecretion(SIADH)

Hypersensitivitytotheactivesubstanceortoanyoftheexcipients.

WarningsandPrecautions

Warnings

Whenusedforprimarynocturnalenuresisandnocturiaindications,thefluidintakemustbe

limitedtoaminimumfrom1hourbeforeuntilthenextmorning(atleast8hours)after

administration.Treatmentwithoutconcomitantreductionoffluidintakemayleadtowater

retentionand/orhyponatraemiawithorwithoutaccompanyingwarningsignsandsymptoms

(headache,nausea/vomiting,weightgain,and,inseverecases,convulsions).Allpatientsand,

whenapplicable,theirguardiansshouldbecarefullyinstructedtoadheretothefluidrestrictions.

Thisproductcontainslactosemonohydrate.Patientswithrarehereditaryproblemsofgalactose

intolerance,theLapplactasedeficiencyorglucose-galactosemalabsorptionshouldnottakethis

medicine.

Precautions

Severebladderdysfunctionandoutletobstructionshouldbeconsideredbeforestarting

treatment.

Elderlypatientsandpatientswithserumsodiumlevelsinthelowerrangeofnormalmayhavean

increasedriskofhyponatraemia.

Treatmentwithdesmopressinshouldbeinterruptedduringacuteintercurrentillnesses

characterisedbyfluidand/orelectrolyteimbalance(suchassystemicinfections,fever,

gastroenteritis).

Precautionsmustbetakeninpatientsatriskforincreasedintracranialpressure.

Desmopressinshouldbeusedwithcautioninpatientswithconditionscharacterizedbyfluid

and/orelectrolyteimbalance.

Precautionstoavoidhyponatraemiaincludingcarefulattentiontofluidrestrictionandmore

frequentmonitoringofserumsodiummustbetakenincaseofconcomitanttreatmentwith

medicines,whichareknowntoinduceSIADH,e.g.tricyclicantidepressants,selectiveserotonin

reuptakeinhibitors,chlorpromazineandcarbamazepine,casesofconcomitanttreatmentwith

NSAIDs.

Useinpregnancyandlactation

Pregnancy

Dataonalimitednumber(n=53)ofexposedpregnanciesinwomenwithdiabetesinsipidusas

wellasdataonalimitednumber(n=54)ofexposedpregnanciesinwomenwithvonWillebrand

diseaseindicatenoadverseeffectsofdesmopressinonpregnancyoronthehealthofthe

foetus/newbornchild.Todate,nootherrelevantepidemiologicaldataareavailable.Animal

-5-

studiesdonotindicatedirectorindirectharmfuleffectswithrespecttopregnancy,

embryonal/foetaldevelopment,parturitionorpostnataldevelopment.

Cautionshouldbeexercisedwhenprescribingtopregnantwomen.

Fertilitystudieshavenotbeendone.Invitroanalysisofhumancotyledonmodelshaveshown

thatthereisnotransplacentaltransportofdesmopressinwhenadministeredattherapeutic

concentrationcorrespondingtorecommendeddose.

Breastfeeding

Resultsfromanalysesofmilkfromnursingmothersreceivinghighdosedesmopressin(300µg

intranasal),indicatethattheamountsofdesmopressinthatmaybetransferredtothechildare

considerablylessthantheamountsrequiredtoinfluencediuresis.

Effectsonabilitytodriveandusemachines

ADIN ®

tabletshavenoornegligibleinfluenceontheabilitytodriveandusemachines.

AdverseEffects

Summaryofthesafetyprofile

Themostseriousadversereactionwithdesmopressinishyponatraemia,whichmaycause

headache,abdominalpain,nausea,vomiting,weightincrease,dizziness,confusion,malaise,

memoryimpairment,vertigo,fallsandinseverecasesconvulsionsandcoma.Themajorityof

adultstreatedfornocturiawhodevelophyponatraemiahavedevelopedlowserumsodiumafter

threedaysofdosing.Inadultstheriskofhyponatraemiaincreaseswiththeincreasingdoseof

desmopressinandtheriskhasbeenfoundtobemoreprominentinwomen.

Inadultsthemostcommonlyreportedadversereactionduringtreatmentwasheadache(12%).

Othercommonadversereactionswerehyponatraemia(6%),dizziness(3%),hypertension(2%)

andgastrointestinaldisorders(nausea(4%),vomiting(1%),abdominalpain(3%),diarrhoea(2%)

andconstipation(1%)).Lesscommonisaninfluenceofthesleeppattern/consciousnesslevel

presentingitselfase.g.insomnia(0.96%),somnolence(0.4%)orasthenia(0.06%).Anaphylactic

reactionshavenotbeenseeninclinicaltrialsbutspontaneousreportshavebeenreceived.

Inchildrenthemostcommonlyreportedadversereactionduringtreatmentwasheadache(1%),

lesscommonwerepsychiatricdisorders(affectlability(0.1%),aggression(0.1%),anxiety

(0.05%),moodswings(0.05%),nightmare(0.05%))whichgenerallyabatedaftertreatment

discontinuationandgastrointestinaldisorders(abdominalpain(0.65%),nausea(0.35%),vomiting

(0.2%)anddiarrhoea(0.15%)).Anaphylacticreactionshavenotbeenseeninclinicaltrialsbut

spontaneousreportshavebeenreceived.

Tabulatedsummaryofadversereactions

Adults

Basedonthefrequencyofadversedrugreactionsreportedinclinicaltrialswithoral

desmopressinconductedinadultsfortreatmentofNocturia(N=1557)combinedwiththepost

marketingexperienceforalladultindications(includingCentralDiabetesInsipidus).Reactions

onlyseenpostmarketinghavebeenaddedinthe‘Notknown’-frequencycolumn.

MedDRAOrganClass Very

Common

(>10%) Common

(1-10%) Uncommon

(0.1-1%) Rare

(0.1-0.01%) Notknown

Immunesystemdisorders - - - - Anaphylactic

reaction

Metabolismandnutrition

disorders - Hyponatraemia* - - Dehydration**,

Hypernatraemia**

Psychiatricdisorders - - Insomnia Confusionalstate* -

Nervoussystemdisorders Headache* Dizziness* Somnolence,

Paraesthesia - Convulsions*,

Asthenia**,

Coma*

Eyedisorders - - Visualimpairment - -

-6-

Earandlabyrinthdisorders - - Vertigo* - -

Cardiacdisorders - - Palpitations - -

Vasculardisorders - Hypertension Orthostatic

hypotension - -

Respiratory,thoracicand

mediastinaldisorders - - Dyspnoea - -

Gastrointestinaldisorders - Nausea*,

Abdominalpain*,

Diarrhoea,

Constipation,

vomiting* Dyspepsia,(HLT)

Flatulence,

bloatingand

distension - -

Skinandsubcutaneous

tissuedisorders - - Sweating,

Pruritus,Rash,

Urticaria Dermatitisallergic

Musculoskeletaland

connectivetissue

disorders - - Musclespasms,

Myalgia - -

Renalandurinary

disorders - (HLT)Bladder

andurethral

symptoms - - -

Generaldisordersand

administrationsite

conditions - (HLT)Oedema,

Fatigue Malaise*,Chest

pain,Influenza

likeillness - -

Investigations - - Weight

increased*,

Hepaticenzyme

increased,

Hypokalaemia - -

*Hyponatraemiamaycauseheadache,abdominalpain,nausea,vomiting,weightincrease,dizziness,confusion,malaise,

memoryimpairment,vertigo,falls,convulsionsandcoma

**OnlyseenintheCDIindication

Childrenandadolescents

Basedonthefrequencyofadversedrugreactionsreportedinclinicaltrialswithoral

desmopressinconductedinchildrenandadolescentsfortreatmentofPrimaryNocturnalEnuresis

(N=1923).Eventsonlyseeninpostmarketinghavebeenaddedinthe‘Notknown’frequency

column.

MedDRAOrganClass Very

Common

(>10%) Common

(1-10%) Uncommon

(0.1-1%) Rare

(0.1-0.01%) Notknown

Immunesystemdisorders - - - - Anaphylactic

reaction

Metabolismandnutrition

disorders - - - - Hyponatraemia****

Psychiatricdisorders - - Affectlability**,

Aggression*** (HLT)Anxiety

symptoms,

Nightmare*,Mood

swings* Abnormal

behaviour,

Emotional

disorder,

Depression,

Hallucination,

Insomnia

Nervoussystemdisorders - Headache - Somnolence Disturbancein

attention,

Psychomotor

hyperactivity,

Convulsions*

Vasculardisorders - - - Hypertension -

Respiratory,thoracicand

mediastinaldisorders - - - - Epistaxis

Gastrointestinaldisorders - - Abdominalpain,

Nausea,Vomiting,

Diarrhoea - -

Skinandsubcutaneous

tissuedisorders - - - - Rash,Dermatitis

allergic,Sweating,

Urticaria

Renalandurinary

disorders - - (HLT)Bladder

andurethral

symptoms - -

Generaldisordersand

administrationsite

conditions - - Oedema

peripheral,

Fatigue Irritability -

*Hyponatraemiamaycauseheadache,abdominalpain,nausea,vomiting,weightincrease,dizziness,confusion,malaise,

memoryimpairment,vertigo,falls,convulsionsandcoma

**Postmarketingreportedequallyinchildrenandadolescents(<18years)

***Postmarketingalmostexclusivelyreportedinchildrenandadolescents(<18years)

****Postmarketingreportedprimarilyinchildren(<12years)

-7-

Descriptionofselectedadversereactions

Themostseriousadversereactionwithdesmopressinishyponatraemia,whichmaycause

headache,abdominalpain,nausea,vomiting,weightincrease,dizziness,confusion,malaise,

memoryimpairment,vertigo,fallsandinseverecasesconvulsionsandcoma.Thecauseofthe

potentialhyponatraemiaistheanticipatedantidiureticeffect.Thehyponatraemiaisreversible

andinchildrenitisoftenseentooccurinrelationtochangesindailyroutinesaffectingfluid

intakeand/orperspiration.Inadultstudysubjectstreatedfornocturia,themajorityofthose

developinglowserumsodium,developedthiswithinthefirstdaysoftreatmentorinrelationto

doseincrease.

Inbothadultsandchildrenspecialattentionshouldbepaidtotheprecautionsaddressedin

WarningsandPrecautions.

Interactions

SubstanceswhichareknowntoinduceSIADH,e.g.tricyclicantidepressants,selectiveserotonin

reuptakeinhibitors,chlorpromazineandcarbamazepineaswellassomeantidiabeticsofthe

sulfonylureagroupparticularlychlorpropamide,maycauseanadditiveantidiureticeffectleading

toanincreasedriskofwaterretention/hyponatremia(seeWarningsandPrecautions).

NSAIDsmayinducewaterretention/hyponatraemia(seeWarningsandPrecautions).

Concomitanttreatmentwithloperamidemayresultina3-foldincreaseofdesmopressinplasma

concentrations,whichmayleadtoanincreasedriskofwaterretention/hyponatraemia.Although

notinvestigated,otheragentsslowingintestinaltransportmighthavethesameeffect.

Itisunlikelythatdesmopressinwillinteractwithagentsaffectinghepaticmetabolism,since

desmopressinhasbeenshownnottoundergosignificantlivermetabolismininvitrostudieswith

humanmicrosomes.However,formalinvivointeractionstudieshavenotbeenperformed.

TheconcomitantuseoffooddecreasestherateandextentofabsorptionofADIN ®

tabletsby

40%.Nosignificanteffectwasobservedwithrespecttopharmacodynamics(urineproductionor

osmolality).

Foodintakemayreducetheintensityanddurationoftheantidiureticeffectatloworaldosesof

ADIN ®

tablets.

Overdosage

OverdoseofADIN ®

tabletsleadstoaprolongeddurationofactionwithanincreasedriskofwater

retentionandhyponatremia.

Treatment

Althoughthetreatmentofhyponatremiashouldbeindividualised,thefollowinggeneral

recommendationscanbegiven:Discontinuethedesmopressintreatmentandinstitutefluid

restriction,andsymptomatictreatmentifnecessary.

PharmaceuticalPrecautions

Listofexcipients

Lactosemonohydrate

Potatostarch

Povidone

Magnesiumstearate

Incompatibilities

Notapplicable.

-8-

Shelf-life

3years.

Specialprecautionsforstorage

Donotstoreabove25°C.

Keepthecontainertightlyclosed,anddonotremovethedesiccantcapsulefromthecap.

MedicineClassification

PrescriptionMedicine.

PackageQuantities

Thetabletsarepresentedinthefollowingcontainers:

30mlHDPEbottle/PPclosurewithadesiccantcapsuleinpacksizesof30and100tablets

FurtherInformation

Preclinicalsafetydata

Non-clinicaldatarevealnospecialhazardforhumansbasedonconventionalstudiesofsafety

pharmacology,repeateddosetoxicity,genotoxicity,toxicitytoreproduction.

Carcinogenicitystudieshavenotbeenperformedwithdesmopressin,becauseitisveryclosely

relatedtothenaturally-occurringpeptidehormone.

Instructionsforuse/handling

Nospecialrequirements.

NameandAddress

FerringPharmaceuticalsA/S

NZdistributor:

Pharmaco(NZ)Ltd

POBox4079

Auckland

Telephone:(09)377-3336

DateofPreparation

20September2011

(CCDS2010/07Vers5)

There are no safety alerts related to this product.

29-6-2018

EU/3/18/2033 (Real Regulatory Limited)

EU/3/18/2033 (Real Regulatory Limited)

EU/3/18/2033 (Active substance: Codon-optimised human ornithine transcarbamylase mRNA complexed with lipid-based nanoparticles) - Orphan designation - Commission Decision (2018)4178 of Fri, 29 Jun 2018 European Medicines Agency (EMA) procedure number: EMA/OD/022/18

Europe -DG Health and Food Safety