Amirol

Main information

  • Trade name:
  • Amirol 25 mg Film coated tablet
  • Dosage:
  • 25 mg
  • Pharmaceutical form:
  • Film coated tablet
  • Units in package:
  • Blister pack, PVC/Al, 50 tablets, 50 tablets
  • Class:
  • Prescription
  • Prescription type:
  • Prescription
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug
  • Manufactured by:
  • R.L. Fine Chem

Documents

Localization

  • Available in:
  • Amirol 25 mg Film coated tablet
    New Zealand
  • Language:
  • English

Other information

Status

  • Source:
  • Medsafe - Medicines Safety Authority - New Zealand
  • Authorization number:
  • 13492
  • Authorization date:
  • 01-04-2008
  • Last update:
  • 27-09-2017

Summary of Product characteristics: dosage,interactions,side effects

AMIROL

Amitriptylinehydrochloride

Name ofMedicine

Amirol 10 Filmcoatedtablets10mg

Amirol 25 Filmcoatedtablets25mg

Presentation

AMIROL10mgtabletsareblue,filmcoatedbiconvextablets,9/32"diameter.Eachtabletcontains

10mg amitriptyline hydrochloride.

AMIROL25mgtabletsareyellow,filmcoatedbiconvextablets,9/32"diameter.Eachtabletcontains

25mg amitriptylinehydrochloride.

Forbothstrengthsdonothalvetablet,doseequivalentwhenthetabletisdividedhasnotbeen

established.

Uses

Actions

Amitriptylineisapotentantidepressantwithsedativeproperties.Themechanismofactioninhumans

isnotknown.Itisnotamonoamineoxidaseinhibitoranditdoesnotactprimarilybystimulationofthe

centralnervoussystem. Inbroad clinicaluse amitriptylinehasbeenfoundtobewelltolerated.

Amitriptylineinhibitsthemembranepumpmechanismresponsibleforuptakeofnorepinephrineand

serotonininadrenergicandserotonergicneurons.Pharmacologicallythisactionmaypotentiateor

prolongneuronalactivitysincereuptakeofthesebiogenicaminesisimportantphysiologicallyin

terminatingtransmittingactivity.Thisinterferencewiththereuptakeofnorepinephrineand/orserotonin

isbelievedbysome to underlie theantidepressant activityofamitriptyline.

Pharmacokinetics

Absorption

Appearsinplasmawithin30to60minutesafteroralingestionand5to10minutesafterintramuscular

injection. Approximately62% ofthe radioactive dosesof 14

C wasrecovered in humanurineafter oralor

intravenousadministration.Plasmalevelsareverylowwithbroadpeaksrangingfrom2-12hoursafter

administration.

Metabolism

Inonestudy,12normalsubjectsreceived25mgofamitriptylinet.i.d.;plasmaamitriptylinelevelswere

maximal(62 ± 20 ng/ml)at4hourspost therapy. Inanother studyin which 12 normalsubjectsreceived

25mg amitriptylinet.i.d.for 2 weeks, the plasma half-life averaged30hours.

Studiesinhumansfollowingoraladministrationof 14 C-labelledmedicineindicatedthatamitriptylineis

rapidlyabsorbedandmetabolised.Radioactivityoftheplasmawaspracticallynegligible,although

significantamountsofradioactivityappearedintheurineby4to6hoursandone-halftoone-thirdof

themedicinewasexcreted within 24 hours.

AmitriptylineismetabolisedbyN-demethylationandbridgehydroxylationinhumans,rabbit,andrat.

Virtuallytheentiredoseisexcretedasglucuronideorsulphateconjugateofmetabolites,withlittle

unchangedmedicineappearing in theurine. Othermetabolicpathwaysmaybeinvolved.

Excretion

Urine

Followinganintravenousdose,anaveragetotalof62.9%ofradioactivitywasexcretedin7days,with

25.1%beingexcretedinthefirst24hours.Followingoraladministration,anaveragetotalof63.0%of

radioactivitywasexcreted in 7days, with27.0% excreted in thefirst 24 hours.

Faeces

Followingoraladministration 14

C-labelledtablets,excretionofradioactivitywascalculatedtobe10.5%

(average)over7days;afterintravenousadministration,anaverageof12.7%wasrecoveredinthe

faecesin 7days.

Bile

Animalstudiesshowthatamitriptylineand itsmetabolitesare excreted in thebile.

Milk

Inonereport,following100mg/dayoforalamitriptyline,levelsof135-151ng/mlwerefoundinthe

breast milkofalactatingpatient.

Indications

AMIROLisrecommended for thetreatment ofdepression.

Dosage andAdministration

Depression

DosageConsiderations

Dosageshouldbeinitiatedatalowlevelandincreasedgradually,notingcarefullytheclinicalresponse

and anyevidence ofintolerance.

OralDosage.

Do nothalve tablet,dose equivalent when thetabletisdivided hasnot been established.

InitialAdult Dosagefor Outpatients

75mgofamitriptylineadayindivideddosesisusuallysatisfactory.Ifnecessary,thismaybeincreased

toatotalof150mgaday.Increasesaremadepreferablyinthelateafternoonand/orbedtimedoses.

Thesedativeeffectisusuallyrapidlyapparent.Theantidepressantactivitymaybeevidentwithin3or4

daysor maytake up to 30 daystodevelopadequately.

Alternatemethodsofinitiatingtherapyin outpatientsare tobegin therapywith50to100mg amitriptyline

preferablyintheeveningoratbedtime;thismaybeincreasedby25to50mgasnecessarytoatotalof

150mgperday.Initiatetherapywithone75mgcapsuleortabletpreferablyintheeveningor at bedtime

and increase,ifnecessary, totwo,or onein themorningand onein theevening.

Dosagefor Hospitalised Patients

100mgadaymayberequiredinitially.Thiscanbeincreasedgraduallyto200mgadayifnecessary.A

smallnumberofhospitalisedpatientsmayneedasmuch as300mg aday.

Dosagefor ElderlyPatients

Ingeneral,lowerdosagesarerecommendedforthesepatients.Inthoseelderlypatientswhomaynot

toleratehigherdoses,50mgdailymaybesatisfactory.Therequireddailydosemaybeadministered

eitherasdivided dosesor asasingle dose preferablyin theeveningor at bedtime.

AdolescentDepression

Notrecommendedforuseinadolescentpatients13-18yearsofageforthetreatmentofdepression,

unlessunderthe supervisionofaspecialist.

MaintenanceDosage

Theusualmaintenancedoseis50to100mgamitriptylineperday.Formaintenancetherapy,thetotal

dailydosagemaybegiveninasingledosepreferablyintheeveningoratbedtime.Whensatisfactory

improvementhasbeenreached,dosageshouldbereducedtothelowestamountthatwillmaintain

reliefofsymptoms.Itisappropriatetocontinuemaintenancetherapy3monthsorlongertolessenthe

possibilityofrelapse.

PlasmaLevels

Becauseofthewidevariationintheabsorptionanddistributionoftricyclicantidepressantsinbody

fluids,itisdifficulttodirectlycorrelateplasmalevelsandtherapeuticeffect.However,determinationof

plasmalevelsmaybeusefulinidentifyingpatientswhoappeartohavetoxiceffectsandmayhave

excessivelyhighlevels,orthoseinwhomlackofabsorptionornoncomplianceissuspected.

Adjustmentsindosageshouldbemadeaccordingtothepatient'sclinicalresponseandnotonthe

basisofplasma levels.

Contraindications

Amitriptylineiscontraindicated for thetreatment ofdepressionin patients12yearsofage

and under.

Amitriptylineiscontraindicated for thetreatment ofnocturnalenuresis.

Amitriptylineiscontraindicated in patientswhohave shown prior hypersensitivitytoit.

It should notbegivenconcomitantlywitha monoamineoxidase inhibitingcompound.

Hyperpyreticcrises, severe convulsions, anddeathshave occurredin patientsreceiving

tricyclicantidepressant andmonoamineoxidase inhibitingmedicinessimultaneously. When

it isdesiredtosubstitute amitriptylinefor a monoamineoxidase inhibitor, a minimumof14

daysshould be allowedtoelapse after thelatter isdiscontinued. Amitriptylineshould then

beinitiated cautiouslywithgradualincrease in dosage untiloptimumresponse isachieved.

Thismedicineiscontraindicatedfor use during theacuterecoveryphase following

myocardialinfarction.

SeeUse in PregnancyunderWarningsand Precautions.

Warnings and Precautions

ClinicalWorsening and SuicideRisk

PatientsofanyagewithMajorDepressiveDisordermayexperienceworseningoftheirdepression

and/ortheemergenceofsuicidalideationandbehaviour(suicidality),whetherornottheyaretaking

antidepressantmedications,andthisriskmaypersist untilsignificant remissionoccurs. Patientsshould

becloselymonitored,especiallyatthebeginningoftherapyorwhenthedoseischanged,untilsuch

improvement occurs.

Therehasbeenalong-standingconcernthatsomeantidepressantsmayhavearoleintheemergence

ofsuicidalityinsomepatients.Thepossibleriskofincreasedsuicidalityinpatientsappliestoall

classesofantidepressantmedicines,asavailabledataarenotadequatetoexcludethisriskforany

antidepressant.Therefore,considerationshouldbegiventochangingthetherapeuticregimen,

includingpossiblydiscontinuingthemedication,inpatientswhosedepressionispersistentlyworseor

whoseemergentsuicidalityissevere,abruptinonset,orwasnotpartofthepatient'spresenting

symptoms.Generally,whenstoppinganantidepressant,dosesshouldbetaperedratherthanstopped

abruptly.

Thefollowingsymptoms,anxiety,agitation,panicattacks,insomnia,irritability,hostility

(aggressiveness),impulsivity,akathisia(psychomotorrestlessness),hypomania,andmania,have

beenreportedinadultandpaediatricpatientsbeingtreatedwithantidepressantsformajordepressive

disorderaswellasforotherindications,bothpsychiatricandnon-psychiatric.Althoughacausallink

betweentheemergenceofsuchsymptomsandeithertheworseningofdepressionand/orthe

emergenceofsuicidalimpulseshasnotbeenestablished,considerationshouldbegiventochanging

thetherapeuticregimen,includingpossiblydiscontinuingthemedication,inpatientsforwhomsuch

symptomsare severe, abrupt in onset,or were not part ofthe patient'spresentingsymptoms.

Becauseofthepossibilityofco-morbiditybetweenmajordepressivedisorderandotherpsychiatricand

non-psychiatricdisorders,thesameprecautionsobservedwhentreatingpatientswithmajor

depressivedisordershouldbeobservedwhentreatingpatientswithotherpsychiatricandnon-

psychiatricdisorders.

Maniaand Bipolar Disorder

Amajordepressiveepisodemaybetheinitialpresentationofbipolardisorder.Itisgenerallybelieved

(thoughnotestablishedincontrolledtrials)thattreatingsuchanepisodewithanyantidepressantalone

mayincreasethelikelihoodofamixed/manicepisodeinpatientsatriskforbipolardisorder.Priorto

initiatingtreatmentwithanantidepressant,patientsshouldbeadequatelyscreenedtodetermineifthey

areatriskforbipolardisorder.Itshouldbenotedthatamitriptylineisnotapprovedforuseintreating

bipolar depression.

Information for Patientsand Families

Patientsandtheirfamiliesshouldbealertedabouttheneedtomonitorfortheemergenceofanxiety,

agitation,panicattacks,insomnia,irritability,hostility,impulsivity,akathisia,hypomania,mania,

worseningofdepression,andsuicidalideation,especiallyearlyduringantidepressanttreatment.Such

symptomsshouldbereportedtothepatient'sdoctor,especiallyiftheyaresevere,abruptinonset,or

were not part ofthe patient'spresentingsymptoms.

Thepatienthastherighttotreatmentmeetingappropriateethicalandprofessionalstandards,andthe

patientneedstobefullyinformedwithfrankdiscussionofrisk/benefitissuesrelatingtothemedicines

efficacyand safetywhen usedin thetreatment regimenproposed.

General

Amitriptylineshouldbeusedwithcautioninpatientswithahistoryofseizures,inpatientswithimpaired

liverfunctionand,becauseofitsatropine-likeaction,inpatientswithahistoryofurinaryretention,or

withnarrowangle glaucoma orincreasedintraocular pressure. Inpatientswithnarrow-angle glaucoma,

evenaveragedosesmayprecipitate an attack.

There hasbeenareport offataldysrhythmia occurring aslateas56hoursafter amitriptylineoverdose.

Discontinue themedicineseveraldaysbefore elective surgeryifpossible.

Hyperpyrexiahasbeenreportedwhentricyclicantidepressantsareadministeredwithanticholinergic

agentsor withneurolepticmedicines, particularlyduringhot weather.

Themedicinemayimpairalertnessinsomepatients;operationofautomobilesandotheractivities

made hazardousbydiminished alertnessshould be avoided.

Cardiovascular Disorders

Amitriptylineshouldbeusedwithcautioninpatientswithcardiovasculardisease,includingheart

failure,conductiondisorders,(e.g.AVblockgradesItoIII),orarrhythmias.CardiovascularandECG

monitoringshouldbeundertakeninsuchpatients.AnECGshouldbeperformedpriortostarting

treatment,atsteadystate,afteranincreaseindoseorafterstartinganypotentiallyinteracting

medicine.

Tricyclicantidepressantmedicines,includingamitriptyline,particularlywhengiveninhighdoses,have

beenreportedtoproduceQTcprolongation,arrhythmias(includingTorsadesdepointes-TdP),sinus

tachycardia,andprolongationoftheconductiontime.MyocardialInfarctionandstrokehavebeen

reported withmedicinesofthisclass(SeeAdverse Events).

AmitriptylineshouldbeusedwithcautioninpatientswithriskfactorsforQTcprolongation/TdP

includingcongenitallongQTsyndrome,age>65years,femalesex,structuralheartdisease/LV

dysfunction,medicalconditionssuchasrenalorhepaticdisease,useofmedicinesthatinhibitthe

metabolismofamitriptyline,andtheconcomitantuseofotherQTcprolongingmedicines(see

Interactions). Hypokalaemia andhypomagnesaemia should be correctedprior to treatment.

ConsiderationshouldbegiventostoppingamitriptylinetreatmentorreducingthedoseiftheQTc

intervalis>500msor increasesby>60ms.

EndocrineDisorders

Closesupervisionisrequiredwhenamitriptylineisgiventohyperthyroidpatientsorthosereceiving

thyroid medications.

CentralNervousSystemDisorders

Whenamitriptylineisusedtotreatthedepressivecomponentofschizophrenia,psychoticsymptoms

maybeaggravated.

Paranoiddelusions,withorwithoutassociatedhostility,maybeexaggerated.Inanyofthese

circumstances,itmaybeadvisabletoreducethedoseofamitriptylineortouseamajortranquillising

medicine, such asperphenazine, concurrently.

Use in Pregnancy

Amitriptylineshouldonlybeusedinpregnancyifconsiderednecessary,takingintoaccounttherisksof

untreateddepression, andunderthe close supervisionofaphysician.

Epidemiologicalstudieshavesuggestedanincreasedriskofcongenitalabnormalitiesassociatedwith

use oftricyclicantidepressantsin pregnancy.

Neonatesshouldbeobservedifmaternaluseofamitriptylinehascontinuedintothelaterstagesof

pregnancy, particularlyintothe third trimester.

Neonatesexposedtotricyclicantidepressants,lateinthethirdtrimesterhaveshoweddrugwithdrawal

symptomssuchasdyspnoea,lethargy,colicirritability,hypotensionorhypertensionandtremoror

spasms.

Epidemiologicaldatasuggeststhattheuse oftricyclicantidepressantsin pregnancymaybeassociated

withanincrease in pre-termdelivery.

NursingMothers

Amitriptylineisdetectableinbreastmilk.Becauseofthepotentialforseriousadversereactionsin

infantsfromamitriptyline,adecisionshouldbemadewhethertodiscontinuenursingordiscontinuethe

medicine.

AdverseEffects

Note:Includedinthelistingwhichfollowsareafewadversereactionswhichhavenotbeenreported

withthisspecificmedicine.However,pharmacologicalsimilaritiesamongthetricyclicantidepressant

medicinesrequire that each ofthe reactionsbeconsideredwhen amitriptylineisadministered.

Cardiovascular

Hypotension,syncope,hypertension,tachycardia,palpitation,myocardialinfarction,arrhythmias

(includingventriculartachycardia,ventricularfibrillationandTorsadesdepointes),,stroke,ECG

changes(includingQTcprolongation,non-specificSTandTwavechanges,andAVconduction

disorderssuch asheart block, bundle branch blockand widened QRScomplex).

CNSand Neuromuscular

Confusionalstates;disturbedconcentration;disorientation;delusions;hallucinations;excitement;

anxiety;restlessness;drowsiness;insomnia;nightmares;numbness;tingling,andparesthesiasofthe

extremities;peripheralneuropathy;incoordination;ataxia;tremors;coma;seizures;alterationinEEG

patterns;extrapyramidalsymptoms,includingabnormalinvoluntarymovementsand tardive dyskinesia;

dysarthria;tinnitus.

Anticholinergic

Drymouth,blurredvision,mydriasis,disturbanceofaccommodation,increasedintraocularpressure,

constipation, paralyticileus, hyperpyrexia,urinaryretention, dilatationofurinarytract.

Allergic

Skinrash,urticaria, photosensitization, oedema offace andtongue.

Haematologic

Bone marrow depression including agranulocytosis, leukopenia, eosinophilia, purpura,

thrombocytopenia.

Gastrointestinal

Nausea,epigastricdistress,vomiting,anorexia,stomatitis,peculiartaste,diarrhoea,parotidswelling,

blacktongue, rarelyhepatitis(includingaltered liver functionand jaundice).

Endocrine

Testicularswellingandgynecomastiainthemale,breastenlargementandgalactorrheainthefemale,

increasedordecreasedlibido,impotence,elevationorloweringofbloodsugarlevels,syndromeof

inappropriateADH (antidiuretichormone) secretion.

Other

Dizziness,weakness,fatigue,headache,weightgainorloss,oedema,increasedperspiration,urinary

frequency, mydriasis, drowsiness, alopecia.

WithdrawalSymptoms

Abruptcessationoftreatmentafterprolongedadministrationmayproducenausea,headache,and

malaise.Gradualdosagereductionhasbeenreportedtoproduce,withintwoweeks,transient

symptomsincludingirritability,restlessness,anddreamandsleepdisturbance.Thesesymptomsare

notindicativeofaddiction.Rareinstanceshavebeenreportedofmaniaorhypomaniaoccurringwithin

2-7 daysfollowingcessationofchronictherapywithtricyclicantidepressants.

AdverseEffects-CasualRelationshipUnknown

Thefollowingadditionaladverseeffectshavebeenreported;however,acasualrelationshiptotherapy

withamitriptylinehasnot been established.

BodyasaWhole

Lupus-like syndrome (migratoryarthritis, positive ANAand rheumatoid factor).

Interactions

Medicinesthat can prolong theQTcinterval

TheriskofQTcprolongationand/orventriculararrhythmias(e.g.torsadesdepointes)isincreasedwith

concomitantuseofothermedicineswhichprolongtheQTcinterval(e.g.someantipsychoticsand

antibiotics).Pleasecheckthedatasheetofothermedicinesadministeredforinformationontheir

effectsonthe QTinterval.

Fluoxetine

FluoxetinemarkedlyinhibitsCytochromeP4502D6,whichisinvolvedinthemetabolismofanumber

oftricyclicantidepressantsincludingamitriptyline.Patientsshouldbemonitoredforincreased

antidepressantplasmalevelsandtoxicitywhenfluoxetineisusedconcurrently.Adjustmentofthe

antidepressant dosage maybenecessary.

OtherAntidepressantMedicines

Thepotencyofamitriptylineissuchthatadditionofotherantidepressantmedicinesgenerallydoesnot

resultinanyadditionaltherapeuticbenefit.Untowardreactionshavebeenreportedafterthecombined

useofantidepressantagentshavingvaryingmodesofactivity.Accordingly,combineduseof

amitriptylinehydrochlorideandotherantidepressantmedicinesshouldbeundertakenonlywithdue

recognitionofthepossibilityofpotentiationand witha thoroughknowledgeofthe pharmacologyofboth

medicines.Therehavebeennoreportsofuntowardeventswhenpatientsreceivingamitriptylinewere

changedimmediatelytoprotriptylineor vice versa.

Guanethidine

Amitriptylinemayblockthe antihypertensive actionofguanethidineor similarlyactingcompounds.

AnticholinergicAgents/SympathomimeticMedicines

Whenamitriptylineisgivenwithanticholinergicagentsorsympathomimeticmedicines,including

epinephrinecombinedwithlocalanaesthetics,closesupervisionandcarefuladjustmentofdosageare

required.Paralyticileusmayoccurinpatientstakingtricyclicantidepressantsincombinationwith

anticholinergic-typemedicines.

Cimetidine

Cimetidineisreported to reduce hepaticmetabolismofcertain tricyclicantidepressants.

CentralNervousSystemDepressants

AmitriptylinemayenhancetheresponsetoalcoholandtheeffectsofbarbituratesandotherCNS

depressants.Cautionisadvisedifpatientsreceivelargedosesofethchlorvynolconcurrently.Transient

deliriumhasbeenreportedinpatientswhoweretreatedwith1gofethchlorvynoland75-150mgof

amitriptyline.

Disulfiram

Deliriumhasbeenreported withconcurrent administrationofamitriptylineand disulfiram.

ElectroshockTherapy

Concurrentadministrationofamitriptylineandelectroshocktherapymayincreasethehazardsof

therapy. Such treatment should be limitedtopatientsfor whomit isessential.

Overdosage

Cardiovascular

Cardiovascularsystem:hypotension,tachycardia,QTcprolongation,arrhythmias(includingTorsades

depointes), conductiondisorders, shock, heart failure, in veryrare casescardiacarrest.

Manifestations

Highdosesmaycausetemporaryconfusion,disturbedconcentration,ortransientvisualhallucinations.

Over-dosagemaycausedrowsiness;hypothermia;tachycardiaandotherarrhythmicabnormalities,

suchasbundlebranchblock;ECGevidenceofimpairedconduction;congestiveheartfailure;dilated

pupils;disordersofocularmotility;convulsions;severehypotension;stupor;comaand

polyradiculoneuropathy; constipation.

Othersymptomsmaybeagitation,hyperactivereflexes,musclerigidity,vomiting,hyperpyrexia,orany

ofthose listedunderAdverse Effects.

Allpatientssuspectedofhavingtakenanoverdoseshouldbeadmittedtoahospitalassoonas

possible.Treatmentissymptomaticandsupportive.Emptythestomachasquicklyaspossibleby

emesisfollowedbygastriclavageuponarrivalatthehospital.Followinggastriclavage,activated

charcoalmaybeadministered.Twentyto30gofactivatedcharcoalmaybegiveneveryfourtosix

hoursduringthefirst24to48hoursafteringestion.AnECGshouldbetakenandclosemonitoringof

cardiacfunctioninstitutedifthereisanysignofabnormality.Maintainanopenairwayandadequate

fluid intake;regulatebodytemperature.

Theintravenousadministrationof1-3mgofphysostigminesalicylatehasbeenreportedtoreversethe

symptomsoftricyclicantidepressantpoisoning.Becausephysostigmineisrapidlymetabolised,the

dosageofphysostigmineshouldberepeatedasrequiredparticularlyiflife-threateningsignssuchas

arrhythmias,convulsionsanddeepcomarecurorpersistaftertheinitialdoseofphysostigmine.

Because physostigmineitselfmaybetoxic, it isnot recommended forroutineuse.

Standardmeasuresshouldbeusedtomanagecirculatoryshockandmetabolicacidosis.Cardiac

arrhythmiasmaybetreatedwithneostigmine,pyridostigmine,orpropranolol.Shouldcardiacfailure

occur,theuseofdigitalisshouldbeconsidered.Closemonitoringofcardiacfunctionofnotlessthan

five daysisadvisable.

Anticonvulsantsmaybegiventocontrolconvulsions.AmitriptylineincreasestheCNSdepressant

actionbutnottheanticonvulsantactionofbarbiturates;therefore,aninhalationanaesthetic,diazepam,

or paraldehydeisrecommended for controlofconvulsions.

Dialysisisofnovaluebecause oflowplasma concentrationsofthe medicine.

Sinceoverdosageisoftendeliberate,patientsmayattemptsuicidebyothermeansduringtherecovery

phase.Deathsbydeliberateor accidentaloverdosage have occurredwiththisclassofmedicine.

Pharmaceutical Precautions

Store below25°C.

Medicine Classification

PrescriptionMedicine

Package Quantities

AMIROL10mg tablets: Blister packsof30 tablets.

AMIROL25mg tablets: Blister packsof30tablets.

Further Information

Nil.

Name andAddress

AFTPharmaceuticalsLtd

POBox33-203

Takapuna

AUCKLAND

Telephone: (09)488-0232

Facsimile:(09)488-0234

Date of Preparation

January2013

28-11-2018

Prenoxad 1 mg/mL solution for injection (naloxone hydrochloride)

Prenoxad 1 mg/mL solution for injection (naloxone hydrochloride)

Update - medicine shortage

Therapeutic Goods Administration - Australia

22-1-2019


Orphan designation: Doxorubicin hydrochloride (in heat-sensitive liposomes), Treatment of hepatocellular carcinoma, 23/02/2011, Positive

Orphan designation: Doxorubicin hydrochloride (in heat-sensitive liposomes), Treatment of hepatocellular carcinoma, 23/02/2011, Positive

Orphan designation: Doxorubicin hydrochloride (in heat-sensitive liposomes), Treatment of hepatocellular carcinoma, 23/02/2011, Positive

Europe - EMA - European Medicines Agency

11-1-2019


Opinion/decision on a Paediatric investigation plan (PIP): Octenidine (dihydrochloride), decision type: , therapeutic area: , PIP number: P/0240/2018

Opinion/decision on a Paediatric investigation plan (PIP): Octenidine (dihydrochloride), decision type: , therapeutic area: , PIP number: P/0240/2018

Opinion/decision on a Paediatric investigation plan (PIP): Octenidine (dihydrochloride), decision type: , therapeutic area: , PIP number: P/0240/2018

Europe - EMA - European Medicines Agency

13-12-2018


Overview of comments received on 'Pegylated liposomal doxorubicin hydrochloride concentrate for solution 2 mg/ml product-specific bioequivalence guidance' (EMA/CHMP/800775/2017)

Overview of comments received on 'Pegylated liposomal doxorubicin hydrochloride concentrate for solution 2 mg/ml product-specific bioequivalence guidance' (EMA/CHMP/800775/2017)

Overview of comments received on 'Pegylated liposomal doxorubicin hydrochloride concentrate for solution 2 mg/ml product-specific bioequivalence guidance' (EMA/CHMP/800775/2017)

Europe - EMA - European Medicines Agency

13-12-2018


Pegylated liposomal doxorubicin hydrochloride concentrate for solution 2 mg/ml product-specific bioequivalence guidance

Pegylated liposomal doxorubicin hydrochloride concentrate for solution 2 mg/ml product-specific bioequivalence guidance

Pegylated liposomal doxorubicin hydrochloride concentrate for solution 2 mg/ml product-specific bioequivalence guidance

Europe - EMA - European Medicines Agency

11-12-2018


Epinephrine mepivacaine hydrochloride, mepivacaine norepinephrine, mepivacaine: List of nationally authorised medicinal products - PSUSA/00001979/201803

Epinephrine mepivacaine hydrochloride, mepivacaine norepinephrine, mepivacaine: List of nationally authorised medicinal products - PSUSA/00001979/201803

Epinephrine mepivacaine hydrochloride, mepivacaine norepinephrine, mepivacaine: List of nationally authorised medicinal products - PSUSA/00001979/201803

Europe - EMA - European Medicines Agency

28-11-2018


Opinion/decision on a Paediatric investigation plan (PIP): Fenfluramine (hydrochloride), decision type: , therapeutic area: , PIP number: P/0177/2018

Opinion/decision on a Paediatric investigation plan (PIP): Fenfluramine (hydrochloride), decision type: , therapeutic area: , PIP number: P/0177/2018

Opinion/decision on a Paediatric investigation plan (PIP): Fenfluramine (hydrochloride), decision type: , therapeutic area: , PIP number: P/0177/2018

Europe - EMA - European Medicines Agency

28-11-2018


Opinion/decision on a Paediatric investigation plan (PIP): Mexiletine (hydrochloride), decision type: , therapeutic area: , PIP number: P/0210/2018

Opinion/decision on a Paediatric investigation plan (PIP): Mexiletine (hydrochloride), decision type: , therapeutic area: , PIP number: P/0210/2018

Opinion/decision on a Paediatric investigation plan (PIP): Mexiletine (hydrochloride), decision type: , therapeutic area: , PIP number: P/0210/2018

Europe - EMA - European Medicines Agency

28-11-2018

Econor (Elanco GmbH)

Econor (Elanco GmbH)

Econor (Active substance: Valnemulin hydrochloride) - Centralised - Transfer Marketing Authorisation Holder - Commission Decision (2018)8038 of Wed, 28 Nov 2018 European Medicines Agency (EMA) procedure number: EMEA/V/C/42/T/54

Europe -DG Health and Food Safety

28-11-2018


Opinion/decision on a Paediatric investigation plan (PIP): ( 2R)-2-Amino-1-[3-( {2-[p-( 4-{3-[ (3,S-diamino-6-chloro-2-pyrazinyl)ca rbonyl ]guanidino }butyl )phenoxy ]ethyl}{ 3-[ ( 2R)-2-am ino-6-guanidinohexanoyla mino] propyl }amino )propylamino ]-6-gu

Opinion/decision on a Paediatric investigation plan (PIP): ( 2R)-2-Amino-1-[3-( {2-[p-( 4-{3-[ (3,S-diamino-6-chloro-2-pyrazinyl)ca rbonyl ]guanidino }butyl )phenoxy ]ethyl}{ 3-[ ( 2R)-2-am ino-6-guanidinohexanoyla mino] propyl }amino )propylamino ]-6-gu

Opinion/decision on a Paediatric investigation plan (PIP): ( 2R)-2-Amino-1-[3-( {2-[p-( 4-{3-[ (3,S-diamino-6-chloro-2-pyrazinyl)ca rbonyl ]guanidino }butyl )phenoxy ]ethyl}{ 3-[ ( 2R)-2-am ino-6-guanidinohexanoyla mino] propyl }amino )propylamino ]-6-guanidino-1-hexanone hexahydrochloride, decision type: , therapeutic area: , PIP number: P/0134/2018

Europe - EMA - European Medicines Agency

28-11-2018


Opinion/decision on a Paediatric investigation plan (PIP): naloxone (hydrochloride), decision type: , therapeutic area: , PIP number: P/0146/2018

Opinion/decision on a Paediatric investigation plan (PIP): naloxone (hydrochloride), decision type: , therapeutic area: , PIP number: P/0146/2018

Opinion/decision on a Paediatric investigation plan (PIP): naloxone (hydrochloride), decision type: , therapeutic area: , PIP number: P/0146/2018

Europe - EMA - European Medicines Agency

27-11-2018


Opinion/decision on a Paediatric investigation plan (PIP): (R)-2-amino-3-phenylpropylcarbamate hydrochloride (solriamfetol), decision type: , therapeutic area: , PIP number: P/0207/2018

Opinion/decision on a Paediatric investigation plan (PIP): (R)-2-amino-3-phenylpropylcarbamate hydrochloride (solriamfetol), decision type: , therapeutic area: , PIP number: P/0207/2018

Opinion/decision on a Paediatric investigation plan (PIP): (R)-2-amino-3-phenylpropylcarbamate hydrochloride (solriamfetol), decision type: , therapeutic area: , PIP number: P/0207/2018

Europe - EMA - European Medicines Agency

26-11-2018

Wakix (Bioprojet Pharma)

Wakix (Bioprojet Pharma)

Wakix (Active substance: Pitolisant hydrochloride) - Centralised - Yearly update - Commission Decision (2018)7974 of Mon, 26 Nov 2018

Europe -DG Health and Food Safety

21-11-2018

EU/3/18/2082 (Takeda Pharma A/S)

EU/3/18/2082 (Takeda Pharma A/S)

EU/3/18/2082 (Active substance: 5-{(1R,2R)-2-[(cyclopropylmethyl)amino]cyclopropyl}-N-(tetrahydro-2H-pyran-4-yl)thiophene-3-carboxamide monohydrochloride) - Orphan designation - Commission Decision (2018)7791 of Wed, 21 Nov 2018 European Medicines Agency (EMA) procedure number: EMA/OD/040/18

Europe -DG Health and Food Safety

13-11-2018

EU/3/17/1836 (Zogenix GmbH)

EU/3/17/1836 (Zogenix GmbH)

EU/3/17/1836 (Active substance: Fenfluramine hydrochloride) - Transfer of orphan designation - Commission Decision (2018)7576 of Tue, 13 Nov 2018 European Medicines Agency (EMA) procedure number: EMA/OD/233/16/T/01

Europe -DG Health and Food Safety

13-11-2018

EU/3/13/1219 (Zogenix GmbH)

EU/3/13/1219 (Zogenix GmbH)

EU/3/13/1219 (Active substance: Fenfluramine hydrochloride) - Transfer of orphan designation - Commission Decision (2018)7575 of Tue, 13 Nov 2018 European Medicines Agency (EMA) procedure number: EMA/OD/140/13/T/01

Europe -DG Health and Food Safety

1-11-2018

Dexdomitor (Orion Corporation)

Dexdomitor (Orion Corporation)

Dexdomitor (Active substance: dexmedetomidine hydrochloride) - Centralised - Yearly update - Commission Decision (2018)7380 of Thu, 01 Nov 2018

Europe -DG Health and Food Safety

31-10-2018

Evista (Daiichi Sankyo Europe GmbH)

Evista (Daiichi Sankyo Europe GmbH)

Evista (Active substance: Raloxifene hydrochloride) - Centralised - Yearly update - Commission Decision (2018)7342 of Wed, 31 Oct 2018

Europe -DG Health and Food Safety

26-9-2018

Sileo (Orion Corporation)

Sileo (Orion Corporation)

Sileo (Active substance: Dexmedetomidine hydrochloride) - Centralised - Yearly update - Commission Decision (2018)6325 of Wed, 26 Sep 2018

Europe -DG Health and Food Safety

10-8-2018

Brinavess (Correvio)

Brinavess (Correvio)

Brinavess (Active substance: vernakalant hydrochloride) - Centralised - Transfer Marketing Authorisation Holder - Commission Decision (2018)5523 of Fri, 10 Aug 2018 European Medicines Agency (EMA) procedure number: EMEA/H/C/1215/T/31

Europe -DG Health and Food Safety

30-7-2018

Segluromet (Merck Sharp and Dohme B.V.)

Segluromet (Merck Sharp and Dohme B.V.)

Segluromet (Active substance: ertugliflozin / metformin hydrochloride) - Centralised - Transfer Marketing Authorisation Holder - Commission Decision (2018)5103 of Mon, 30 Jul 2018 European Medicines Agency (EMA) procedure number: EMEA/H/C/4314/T/2

Europe -DG Health and Food Safety

30-7-2018

Ceplene (Noventia Pharma Srl)

Ceplene (Noventia Pharma Srl)

Ceplene (Active substance: Histamine dihydrochloride) - Centralised - Renewal - Commission Decision (2018)5116 of Mon, 30 Jul 2018 European Medicines Agency (EMA) procedure number: EMEA/H/C/796/R/36

Europe -DG Health and Food Safety

23-7-2018

Optruma (Eli Lilly Nederland B.V.)

Optruma (Eli Lilly Nederland B.V.)

Optruma (Active substance: Raloxifene hydrochloride) - Centralised - Yearly update - Commission Decision (2018)4893 of Mon, 23 Jul 2018

Europe -DG Health and Food Safety

12-7-2018

Econor (Elanco Europe Ltd)

Econor (Elanco Europe Ltd)

Econor (Active substance: Valnemulin hydrochloride) - Centralised - Yearly update - Commission Decision (2018)4580 of Thu, 12 Jul 2018

Europe -DG Health and Food Safety

11-7-2018

Ariclaim (Eli Lilly Nederland B.V.)

Ariclaim (Eli Lilly Nederland B.V.)

Ariclaim (Active substance: duloxetine hydrochloride) - Centralised - Withdrawal - Commission Decision (2018)4515 of Wed, 11 Jul 2018

Europe -DG Health and Food Safety

5-7-2018

Scientific guideline:  Draft pegylated liposomal doxorubicin hydrochloride concentrate for solution 2 mg/ml product-specific bioequivalence guidance, draft: consultation open

Scientific guideline: Draft pegylated liposomal doxorubicin hydrochloride concentrate for solution 2 mg/ml product-specific bioequivalence guidance, draft: consultation open

This document provides product-specific guidance on the demonstration of the bioequivalence of pegylated liposomal doxorubicin hydrochloride concentrate for solution 2 mg/ml.

Europe - EMA - European Medicines Agency

3-7-2018

Efficib (Merck Sharp and Dohme B.V.)

Efficib (Merck Sharp and Dohme B.V.)

Efficib (Active substance: sitagliptin / metformin hydrochloride) - Centralised - Transfer Marketing Authorisation Holder - Commission Decision (2018) 4254 of Tue, 03 Jul 2018 European Medicines Agency (EMA) procedure number: EMEA/H/C/896/T/90

Europe -DG Health and Food Safety

3-7-2018

Ristfor (Merck Sharp and Dohme B.V.)

Ristfor (Merck Sharp and Dohme B.V.)

Ristfor (Active substance: sitagliptin / metformin hydrochloride) - Centralised - Transfer Marketing Authorisation Holder - Commission Decision (2018) 4249 of Tue, 03 Jul 2018 European Medicines Agency (EMA) procedure number: EMEA/H/C/1235/T/77

Europe -DG Health and Food Safety

3-7-2018

Velmetia (Merck Sharp and Dohme B.V.)

Velmetia (Merck Sharp and Dohme B.V.)

Velmetia (Active substance: sitagliptin / metformin hydrochloride) - Centralised - Transfer Marketing Authorisation Holder - Commission Decision (2018) 4252 of Tue, 03 Jul 2018 European Medicines Agency (EMA) procedure number: EMEA/H/C/862/T/93

Europe -DG Health and Food Safety

3-7-2018

Janumet (Merck Sharp and Dohme B.V.)

Janumet (Merck Sharp and Dohme B.V.)

Janumet (Active substance: sitagliptin / metformin hydrochloride) - Centralised - Transfer Marketing Authorisation Holder - Commission Decision (2018) 4251 of Tue, 03 Jul 2018 European Medicines Agency (EMA) procedure number: EMEA/H/C/861/T/90

Europe -DG Health and Food Safety

29-6-2018

EU/3/18/2028 (BioCryst UK Ltd)

EU/3/18/2028 (BioCryst UK Ltd)

EU/3/18/2028 (Active substance: (R)-1-(3-(aminomethyl) phenyl)-N-(5-((3-cyanophenyl)(cyclopropylmethylamino)methyl)-2-fluorophenyl)-3-(trifluoromethyl)-1H-pyrazole-5-carboxamide dihydrochloride) - Orphan designation - Commission Decision (2018)4173 of Fri, 29 Jun 2018 European Medicines Agency (EMA) procedure number: EMA/OD/003/18

Europe -DG Health and Food Safety

14-6-2018

Kuvan (BioMarin International Limited)

Kuvan (BioMarin International Limited)

Kuvan (Active substance: sapropterin dihydrochloride) - Centralised - Yearly update - Commission Decision (2018)3859 of Thu, 14 Jun 2018

Europe -DG Health and Food Safety

12-6-2018

EU/3/10/811 (Celgene Europe B.V.)

EU/3/10/811 (Celgene Europe B.V.)

EU/3/10/811 (Active substance: N-tert-butyl-3-[(5-methyl-2-{[4-(2-pyrrolidin-1-ylethoxy)phenyl]amino}pyrimidin-4-yl)amino] benzenesulfonamide dihydrochloride monohydrate) - Transfer of orphan designation - Commission Decision (2018)3809 of Tue, 12 Jun 2018 European Medicines Agency (EMA) procedure number: EMA/OD/092/10/T/03

Europe -DG Health and Food Safety

12-6-2018

EU/3/10/810 (Celgene Europe B.V.)

EU/3/10/810 (Celgene Europe B.V.)

EU/3/10/810 (Active substance: N-tert-butyl-3-[(5-methyl-2-{[4-(2-pyrrolidin-1-ylethoxy)phenyl]amino}pyrimidin-4-yl)amino] benzenesulfonamide dihydrochloride monohydrate) - Transfer of orphan designation - Commission Decision (2018)3808 of Tue, 12 Jun 2018 European Medicines Agency (EMA) procedure number: EMA/OD/084/10/T/03

Europe -DG Health and Food Safety

12-6-2018

EU/3/10/794 (Celgene Europe B.V.)

EU/3/10/794 (Celgene Europe B.V.)

EU/3/10/794 (Active substance: N-tert-butyl-3-[(5-methyl-2-{[4-(2-pyrrolidin-1-ylethoxy)phenyl]amino}pyrimidin-4-yl)amino] benzenesulfonamide dihydrochloride monohydrate) - Transfer of orphan designation - Commission Decision (2018)3803 of Tue, 12 Jun 2018 European Medicines Agency (EMA) procedure number: EMA/OD/069/10/T/03

Europe -DG Health and Food Safety

12-6-2018

EU/3/11/888 (Gilead Sciences Ireland UC)

EU/3/11/888 (Gilead Sciences Ireland UC)

EU/3/11/888 (Active substance: N-(cyanomethyl)-4-(2-{[4-(morpholin-4-yl)phenyl]amino}pyrimidin-4-yl)benzamide, dihydrochloride salt) - Transfer of orphan designation - Commission Decision (2018)3802 of Tue, 12 Jun 2018 European Medicines Agency (EMA) procedure number: EMA/OD/152/10/T/03

Europe -DG Health and Food Safety

12-6-2018

EU/3/11/887 (Gilead Sciences Ireland UC)

EU/3/11/887 (Gilead Sciences Ireland UC)

EU/3/11/887 (Active substance: N-(cyanomethyl)-4-(2-{[4-(morpholin-4-yl)phenyl]amino}pyrimidin-4-yl)benzamide, dihydrochloride salt) - Transfer of orphan designation - Commission Decision (2018)3801 of Tue, 12 Jun 2018 European Medicines Agency (EMA) procedure number: EMA/OD/020/11/T/03

Europe -DG Health and Food Safety

12-6-2018

EU/3/11/886 (Gilead Sciences Ireland UC)

EU/3/11/886 (Gilead Sciences Ireland UC)

EU/3/11/886 (Active substance: N-(cyanomethyl)-4-(2-{[4-(morpholin-4-yl)phenyl]amino}pyrimidin-4-yl)benzamide, dihydrochloride salt) - Transfer of orphan designation - Commission Decision (2018)3799 of Tue, 12 Jun 2018 European Medicines Agency (EMA) procedure number: EMA/OD/019/11/T/03

Europe -DG Health and Food Safety