Acetadote

Main information

  • Trade name:
  • Acetadote 20 % Solution for injection
  • Dosage:
  • 20 %
  • Pharmaceutical form:
  • Solution for injection
  • Units in package:
  • Vial, glass, Type 1, bromobutyl rubber stopper with filp-top cap 30ml vials, 4 dose units
  • Class:
  • Prescription
  • Prescription type:
  • Prescription
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug
  • Manufactured by:
  • Moehs Catalana SL

Documents

Localization

  • Available in:
  • Acetadote 20 % Solution for injection
    New Zealand
  • Language:
  • English

Therapeutic information

  • Therapeutic indications:
  • As an antidote for paracetamol poisoning: Acetadote Injection is indicated in the treatment of paracetamol overdose to protect against hepatotoxicity.

Other information

Status

  • Source:
  • Medsafe - Medicines Safety Authority - New Zealand
  • Authorization number:
  • 14491
  • Authorization date:
  • 25-05-2010
  • Last update:
  • 27-09-2017

Summary of Product characteristics: dosage,interactions,side effects

NewZealandData Sheet

ACETADOTE ® INJECTION

NAMEOFTHEMEDICINE

Acetylcysteine

ChemicalName: (2R)-2-(acetylamino)-3-sulphanylpropanoicacid.

StructuralFormula:

MolecularFormula: C5H9NO3S

MolecularWeight: 163.2

CASRegistryNumber: 616-91-1

DESCRIPTION

Acetylcysteineisawhite,crystallinepowderwithaslightaceticodour.Itissolublein

waterand alcoholandpracticallyinsoluble inchloroform,dichloromethaneand ether.

Acetadote®Injectioncontainsacetylcysteine,WaterforInjectionsandsodium

hydroxideforpHadjustment.

PHARMACEUTICALFORM

ConcentrateforSolutionforInfusion.

INDICATIONS

N-acetylcysteineisindicatedforthetreatmentofparacetamoloverdose inpatients:

Whopresentwithin15hoursafteranacuteoverdosewithaplasmaparacetamol

onorabovealinejoiningpointsof150mg/Lat4hand20mg/Lat15h(see

nomogrambelow).Or

Whohavetakenmorethan200mg/kgor10g(whicheverisless)ofsustained

releaseparacetamolorhaveoneoftwoserumparacetamollevelstakenfour

hoursapartonorabovealinejoiningpointsof150mg/mLat4hand20mg/mLat

15h (seemnomogrambelow).Or

Whohavetakenacuteoverdoseofparacetamolwithopiatesormedicineswith

anticholinergiceffectsandhaveoneoftwoserumparacetamollevelstakenfour

hoursapartonorabovealinejoiningpointsof150mg/mLat4hrand20mg/mLat

15h(seenomogrambelow).Or

Wherethereanydoubtoverthetimeofanacuteoverdose,irrespectiveofplasma

paracetamollevelOr

Whopresentmorethan15hoursafteranoverdosewithabnormalliver

biochemistry(INR>1.3 and/orALT>150)offulminanthepaticfailureor

Whohavetakenastaggeredoverdoseirrespectiveofplasmaparacetamollevel.

Staggeredisdefinedasanoverdoseof200mg/kgor10g(whicheverisless)over

asingle24hourperiodor150mg/kgof6g(whicheverisless)per24hourperiod

foratleast48hours.

PlasmaParacetamolNomogram

POSOLOGYANDMETHODOFADMINISTRATION

Acetylcysteineshouldbeadministeredbyintravenousinfusionpreferablyusingglucose5%

astheinfusionfluid.SodiumChloride0.9%solutionmaybeusedifGlucose5%isnot

suitable.

Themajorityofpatientsshouldbetreatedwiththethreeinfusionschedule.Howeversome

patientsmayrequireprolonged treatment.

Patientswhohavetakenverylargeoverdoses(eg,50gofparacetamol),co-ingestedopiates

ormedicineswithanticholinergiceffects,orhavetakenmodifiedreleaseparacetamolshould

beassessedattheendofthenormaldoseschedule.Treatmentshouldbecontinueduntil

aminotransferase levelsare improving,INR is1.3orlessand thereisnoacidosis.

DoseinAdults

AcetadoteInjectionisinfused inthreeintravenousinfusionscontainingdifferent

doses.Thiswillgive atotaldose of300milligrams/kg ofacetylcysteineinfusedover

20hours.

INITIALINFUSION:An initialdose of150milligrams/kg ofacetylcysteinedilutedin

200 mLof5%glucosesolution and infusedover60minutes.

SECONDINFUSION.The initialinfusionisfollowedbya continuous infusionof50

milligrams/kgofacetylcysteinein 500mLof5%glucose solution overthenext4

hours.

THIRDINFUSION.Thesecondinfusionisfollowedbya continuousinfusionof100

milligrams/kgofacetylcysteinein1000mL of5%glucose solutionoverthe next16

hours.

Toreducemicrobiologicalhazard,useassoon aspracticable afterdilution.Ifstorage

isnecessary,hold at2°to 8°Cfornotmorethan24hours.

Thedose shouldbecalculatedusingthepatient’sactualweighttoaceilingof110kgfor

obesepatients.

Regimen Dose1 Dose2 Dose3

Fluid 200ml5%glucoseor sodium

chloride0.9% 500ml5%glucoseor

sodiumchloride0.9% 1000ml5%glucoseor

sodiumchloride0.9%

Duration

of

Infusion 60minutes 4hours 16hours

Medicine

Dose 150mg/kgN-acetylcysteine 50mg/kgN-acetylcysteine 100mg/kgN-acetylcysteine

Patient

weight 1 Dose Ampoule

volume 2 Infusion

rate Dose Ampoule

volume 2 Infusion

rate Dose Ampoule

volume 2 Infusion

rate

kg mg mL mL/h mg mL mL/h mg mL mL/h

40-49 6750 34 234 2250 12 128 4500 23 64

50-59 8250 42 242 2750 14 129 5500 28 64

60-69 9750 49 249 3250 17 129 6500 33 65

70-79 11250 57 257 3750 19 130 7500 38 65

80-89 12750 64 264 4250 22 131 8500 43 65

90-99 14250 72 272 4750 24 131 9500 48 66

100-109 15750 79 279 5250 27 132 10500 53 66

>110 16500 83 283 5500 28 132 11000 55 66

Dose calculationsare basedon theweight in the middleofthe band

Ampoulevolume hasbeenroundedupto the nearestwhole number

Dosein Children

Childrenshouldbetreatedwiththesamedosesandregimenasadults;howeverthequantity

ofintravenousfluidusedmustbemodifiedtotakeintoaccountageandweightasfluid

overload isa potentialdanger.

Thefullcourseoftreatmentwithacetylcysteineincludesthreeconsecutiveintravenous

infusions.

INITIALINFUSION:Aninitialdoseof150milligrams/kgofAcetylcysteinegivenasa50mg/ml

solutionatarateof3ml/kg/h.

SECONDINFUSION:50milligrams/kgofAcetylcysteineoverthenext4hours.Givenasa

6.25mg/mlsolutionata rate of2ml/kg/h

THIRDINFUSION:100milligrams/kgofAcetylcysteineoverthenext16hours.Givenasa

6.25mg/mlsolutionata rate of1ml/kg/h.

Thedose shouldbecalculatedusingthepatient’sactualweight.Determinethetotal

volume ofsolution neededfromthe table.

Preparationofthe solution

Initialinfusion:Topreparea50mg/mlsolution,diluteeach10mlampouleofacetylcysteine

(200mg/ml)with 30mlglucose 5% orsodiumchloride 0.9% toa totalvolume of40ml.

Secondinfusion:Topreparea6.25mg/mlsolution,diluteeach10mlampouleof

acetylcysteine(200mg/ml)with310mlglucose5%orsodiumchloride0.9%togiveatotal

volume of320ml.

Thirdinfusion.Topreparea6.25mg/mlsolution,diluteeach10mlampouleofacetylcysteine

(200mg/ml)with310mlglucose 5% orsodiumchloride0.9% to give atotalvolume of320ml.

Regimen Dose1 Dose2 Dose3

Medicinedose 150mg/kgN-acetylcysteine 50mg/kgN-acetylcysteine 100mg/kgN-acetylcysteine

Durationof

infusion 1hour 4hours 16hours

Infusion

concentration 50mg/ml 6.25mg/ml 6.25mg/ml

Rateof

infusion 3ml/kg/h 2ml/kg/h 1ml/kg/h

Patientweight Dose Rateof

infusion Total

infusion

volume Dose Rateof

infusion Total

infusion

volume Dose Rateof

infusion Total

infusion

volume

kg mg mL/h mL mg mL/h mL mg mL/h mL

1 150 3 3 50 2 8 100 1 16

2 300 6 6 100 4 16 200 2 32

3 450 9 9 150 6 24 300 3 48

4 600 12 12 200 8 32 400 4 64

5 750 15 15 250 10 40 500 5 80

6 900 18 18 300 12 48 600 6 96

7 1050 21 21 350 14 56 700 7 112

8 1200 24 24 400 16 64 800 8 128

9 1350 27 27 450 18 72 900 9 144

10-14 1875 38 38 625 25 100 1250 13 208

15-19 2625 53 53 875 35 140 1750 18 288

20-24 3375 68 68 1125 45 180 2250 23 368

25-29 4125 83 83 1375 55 220 2750 28 448

30-34 4875 98 98 1625 65 260 3250 33 528

35-39 5625 113 113 1875 75 300 3750 38 608

Forexampleforachildweighing12kg,38mlofsolutionisrequiredfordose/infusion1,100ml

fordose/infusion2and200mlfordose/infusion3.Dose1isinfusedat38ml/hover60mins,

dose 2isinfusedat25ml/handdose 3at13ml/h.

Acetylcysteineisnotcompatiblewithrubberandsomemetals,particularly,iron,copperand

nickel.Acetylcysteine200mg/mlInjectioncanbeusedsatisfactorilywithsiliconerubberand

plastic.

CONTRAINDICATIONS

Therearenocontraindicationstothetreatmentofparacetamoloverdosewith

acetylcysteine.

SPECIALWARNINGANDPRECAUTIONSFORUSE

Managementof ParacetamolOverdosage

Itshould benotedthat,afteraningestion ofapotentiallyfataldose ofparacetamol,

thepatientmayappearrelativelywellinitiallyand mayevencontinue normal

activitiesfora dayortwo beforetheonsetofhepaticfailure.Hepatic damageis

morelikelytooccurwith alowerdosage ofparacetamolinpatientswhohave a

historyofchronicalcoholorenzyme-inducingdrug ingestion(e.g.,isoniazid,

rifampicin,anticonvulsantsincludingcarbamazepine,phenytoin,phenobarbitone,

primidone,sodiumvalproate).

Patientsare notoriouslyunreliable astotheamountofparacetamolingestedandthe

time ofingestion.Hepaticnecrosisispreventable iftreatmentcanbeinstitutedwithin

10to12hoursofparacetamolingestion.

Note:Liverdamagemaynotbebiochemicallyapparentfor24to48hoursafter

ingestion.

Hepatic necrosishas been seenfollowingingestionof6 gramsofparacetamol,

and deathwith15grams.

Patient presenting within 15hoursof ingestion

Give activatedcharcoal(1 to2 grams/kg)ifitiswithin 1hourofparacetamol

ingestion,andthepatient'sconsciousstate isnotimpaired.Intheeventofoverdose

with sustainedrelease paracetamolactivatedcharcoalmaybeusefulafter1 hourof

ingestion.

Plasmaparacetamollevelsshould beobtained no earlierthan 4hoursafteringestion

oftheparacetamoloverdose.Concentrationsdetermined priortothistimearenot

reliable forassessingpotentialhepatotoxicity.Ifthetimeofingestionisunknown,

paracetamollevelsshould bemeasuredimmediately.

Measurementsofplasma liverenzymes and bilirubin levels,and coagulationstudies,

should beperformedassoon aspossible afteradmission.Blood urea,electrolytes,

glucose and blood gasesshould beobtained.Thelaboratorymeasurementsare

used tomonitorhepaticand renalfunctionand electrolyte balance.An ECGshould

also beperformed.

Do notdelayacetylcysteinetherapywhile awaitingtheresultsofplasma assays.

Oncetheresultsbecomeavailable,treatmentmaybediscontinuediftheinitial

concentrationisbelowthe nomogramreference line.

Do notdiscontinue acetylcysteinetherapyiftheinitiallevelisabove thereference

lineand subsequentlevelsfallbelowthereference line.

Patientspresentingmorethan15hoursafter ingestion

Plasma paracetamol, bilirubin,AST, ALTlevelsandINR shouldbedeterminedurgently.

PatientswithINR>1.3and/orALT>150shouldbetreated.Furtheradviceshouldbesought

fromthe NewZealandPoisonsCentre.

Anaphylactoidreactions

Anaphylactoidhypersensitivityreactionsoccurwithacetylcysteine,particularlywiththeinitial

loadingdose.Thepatientshouldbecarefullyobservedduringthisperiodforsignsofan

anaphylactoidreaction.Nausea,vomiting,flushing,skinrash,pruritusandurticariaarethe

mostcommonfeatures,butmoreseriousanaphylactoidreactionshavebeenreportedwhere

thepatientdevelopsangioedema,bronchospasm,respiratorydistress,tachycardiaand

hypotension.Inveryrarecasesthesereactionshavebeenfatal.Thereissomeevidencethat

patientswithahistoryofatopyandasthmamaybeatincreasedriskofdevelopingan

anaphylactoid reaction.

Mostanaphylactoidreactionscanbemanagedbytemporallysuspendingtheacetylcysteine

infusion,administeringappropriatesupportivecare,antihistaminesandbronchodilatorsand

restartingatalowerinfusionrate.Onceananaphylactoidreactionisundercontrol,the

infusioncannormallyberestartedataninfusionrateof50mg/kgover4hours,followedby

thefinal16 hourinfusion(100mg/kg over16hours).

Inpatientswhohavepreviouslyexperiencedananaphylactoidreactionwithacetylcysteine

considerationshouldbegiventopre-treatmentwithanIVantihistamine15minutesbefore

startingtheacetylcysteineinfusion.

Coagulation

Changesinhaemostaticparametershavebeenobservedinassociationwithacetylcysteine

treatment,someleadingtodecreasedprothrombintime,butmostleadingtoasmallincrease

inprothrombintime(INR).Anisolatedincreaseinprothrombin(INR)timeupto1.3attheend

ofa21hourcourseofacetylcysteinewithoutanelevatedtransaminaseactivitydoesnot

requirefurther monitoring ortreatment withacetylcysteine.

Fluidandelectrolytes

Usewithcautioninchildren,patientsrequiringfluidrestrictionorthosewhoweighlessthan

<40kgbecauseoftheriskoffluidoverloadwhichmayresultinhyponatraemiaandseizures

whichmaybelifethreatening(seeposologyandmethodofadministrationfordosing

guidelines).

Each10mlofN-acetylcysteineforInfusioncontains322.6mgsodium.Tobetakeninto

considerationwithpatientsonacontrolled sodiumdiet.

Usein Renal/HepaticImpairedPatients

CautionshouldbetakenwhenadministeringAcetylcysteineinpatientswithhepaticorrenal

failure,sincethereislittledatarelatingtotheeffectsofAcetylcysteineinimpairedrenal

and/orhepaticfunction.Thedecisiontoadministershouldbepassedonarisk/benefit

assessment for theindividualsubject.

Inthepresenceofhepaticfailureduetoparacetamoloverdosethedegreeofexistingliver

damageandthepossibleriskassociatedwiththeadministrationofAcetylcysteineshouldbe

considered.

PregnancyandLactation

UseinPregnancy

CategoryB2

Therewasnoevidenceofteratogenicityinlimitedstudiesinratsandrabbitsfollowing

administrationofAcetylcysteineduringtheperiodofgestationatdosesupto1.2timesthe

maximumclinicaldose,onabodysurfaceareabasis.Therearenowell-controlledstudiesin

pregnantwomenbutexperiencedoesnotincludeanypositiveevidenceofadverseeffectsto

thefoetus.

Usein Lactation

Therewasnoevidenceofadverseeffectsinalimitedstudyinratsfollowingadministrationof

acetylcysteineduringlategestationandlactationat60%ofthemaximumclinicaldose,ona

bodysurfaceareabasis.Itisnotknownwhetheracetylcysteineand/oritsmetabolitesare

excretedinmilk.Therearenodataontheuseofacetylcysteineinlactatingwomenand

therefore breastfeeding isnotrecommended duringtreatment.

ImpairmentofFertility

There wasevidence ofeffectsonfertilityinmaleratsgivenAcetylcysteineatdosesupto60%

ofthemaximumclinicaldose,onabodysurfaceareabasis.Noeffectswereobservedat

doses15%themaximumclinicaldose,on abodysurface areabasis.

Carcinogenicity,Mutagenicity

CarcinogenicityassayshavenotbeenperformedwithAcetylcysteine.Inrats,noevidenceof

carcinogenicitywasreportedfollowing18monthsofdailydietaryadministrationof

Acetylcysteine at60%ofthe maximumclinicaldose,on abodysurface areabasis.

Noevidenceofmutagenicitywasobtainedinlimitedgenemutationassayswith

Acetylcysteine.ThepotentialforAcetylcysteinetocausechromosomaldamagehasnotbeen

investigated.

Interactionwithothermedicinalproducts andotherforms ofinteraction.

There are no knowninteractions.

Effects onLaboratoryTests

Acetylcysteinemaycauseafalse-positivereactionwithreagentdipsticktestsforurinary

ketones.

Effects onAbilitytoDriveandUseMachines

Acetylcysteineispresumedtobesafesinceitisunlikelytoproduceaneffectthatmayimpair

thepatient'sabilitytoconcentrateandreactandthereforenotconstituteariskintheabilityto

drive and usemachines.

UndesirableEffects

Intravenousadministrationofacetylcysteine,especiallyinthelargedosesneededtotreat

paracetamoloverdose,mayresult in nausea,vomitingandother gastrointestinalsymptoms.

Anaphylactoidreactionshavebeenreportedfollowingintravenousadministrationof

acetylcysteine.Bronchospasmmayoccurinconjunctionwithageneralizedanaphylactic

reaction.Othersymptomsincludeairwayobstruction(bronchospasm),angioedema,

dyspnoea,hypotension,shock,tachycardia,urticaria,andinjectionsitereaction(including

rash).Thesereactionsoccurmostcommonlyeitherduring,orattheendoftheperiodofthe

loadingdoseinfusion,andmayinfactbedose-related.Sincetheseanaphylactic-like

reactionsusuallyoccur following the loading dose,carefulmonitoring isrecommended.

There have beenrareinstancesofdeath.

Thefollowingadverse effectshave been reported:

Bloodandlymphatic system disorders:Thrombocytopenia

Immune system disorders:Anaphylactoid reaction

Metabolism andnutritiondisorders:Acidosis

Psychiatric disorders:Anxiety

Nervous system disorders:Syncope,generalized seizure

Eye disorders:Blurredvision, eyepain

Cardiac disorders:Cyanosis, tachycardia,bradycardia,cardiacarrest, extrasystoles

Vasculardisorders:Flushing,hypotension,hypertension,vasodilation

Respiratory,thoracicandmediastinaldisorders:Dyspnoea,respiratoryarrest,

bronchospasm, coughing,stridor

Gastrointestinaldisorders:Vomiting,nausea

Hepatobiliarydisorders:Deteriorationofliver function

Skinandsubcutaneoustissuedisorders:Angioedema,urticaria,rash(erythematousand

maculopapular), sweating,oedema periorbital

Musculoskeletal andconnective tissue disorders:Arthralgia

Generaldisordersandadministrationsiteconditions:Malaise,rigors,injectionsite

reaction, chest pain,facialpain,face oedema

Investigations:Raisedtemperature,changesinprothrombintime(INR)(usuallyincreased).

HypokalaemiaandECGchangeshavebeennotedinpatientswithparacetamolpoisoning

irrespectiveofthetreatmentgiven.Monitoringofplasmapotassiumconcentrationistherefore

recommended.

OVERDOSAGE

Symptoms

Symptomsfollowingoverdosage with acetylcysteinehave beensimilartothose of

anaphylactoid reactionsnotedunder“ADVERSEEFFECTS”,buttheymaybemore

severe.Hypotensionappearsto beespeciallyprominent.There isalso atheoretical

riskofhepaticencephalopathy.

Treatment

There is nospecifictreatment.Generalsupportive measuresshould becarriedout.

Ithasbeensuggestedthatgeneralisedreactionsto acetylcysteinecanbetreated

with intravenousinjection ofan antihistamine,and infusionofacetylcysteineshould

betemporarilystopped butcanberestartedataslowerratewithoutfurtherreaction.

PHARMACOLOGY

Pharmacokinetics

AcetylcysteineistheN-acetylderivativeofthenaturallyoccurringaminoacid,L-

cysteine,andisdeacetylatedinthelivertocysteine,oroxidisedtoothermetabolites

suchasN-acetylcystineorN,N-diacetylcystine.Theparentcompoundand

metabolitesmaybepresentintheplasmaeitherfreeorproteinbound.Renal

clearanceaccountsforabout30%oftotalbodyclearance.Followingintravenous

administration,meanterminalhalfliveshavebeencalculatedtobe1.95and5.58

hoursrespectivelyforreducedandtotalacetylcysteine.

Pharmacodynamics

Paracetamolismetabolisedintheliver,mainlybyconjugationwithglucuronideand

sulphate.ItisalsometabolisedbycytochromeP450toformareactive,potentially

toxicmetabolite.Thismetaboliteisnormallydetoxifiedbyconjugationwithhepatic

glutathione,toformnon-toxicderivatives.Inparacetamoloverdosage,the

glucuronideandsulphateconjugationpathwaysaresaturated,sothatmoreofthe

toxicmetaboliteisformed.Ashepaticglutathionestoresaredepleted,thistoxic

metabolitemaybindtohepatocyteproteins,leadingtolivercelldamageand

necrosis.Acetylcysteineisasulphydryl(SH)groupdonor,andmayprotecttheliver

fromdamagebyrestoringdepletedhepatic-reducedglutathionelevels,orbyacting

asanalternativesubstrateforconjugationwith,andthusdetoxificationof,thetoxic

paracetamolmetabolite.

CLINICALSTUDIES

ObservationalStudy –paediatricpatients

Anopen-label,observationalstudyconductedinthegreaterNewcastlearea,New

SouthWales,Australia,documentedtreatmentforpaediatricpatientswhopresented

withaparacetamoloverdoseduringa16yearperiodfromJanuary1987toJanuary

2003.Thisstudywas primarilyconsideredasafetystudy.

Datafrom148paediatricpatients,withanagerangeof2monthsto15years(this

correspondsto186cases)wereevaluated.Twentythree(23)outof148paediatric

patientsweregivenintravenousacetylcysteinetreatmentonatleastoneadmission.

Ofthese,14paediatricpatientsintheagegroup12to<16years(9.5%ofthe

group),receivedacetylcysteinewithin8hoursofingestingparacetamolonatleast

oneadmission.Therewasadelayofatleast8hoursfor9paediatricpatientsinthis

agegroup(6.1%ofthegroup).Oneotherpaediatricpatientintheagegroup2to<5

yearsofage(0.7%ofthegroup),receivedacetylcysteinewithadelayofatleast8

hoursonatleastone admission.

Ofthe23patientswhoreceivedintravenousacetylcysteinetreatment,3patients

(13%)experiencedanadversereaction(anaphylactoidreaction,rashandflushing,

transienterythema).Therewerenodeathsofpaediatricpatients.Noneofthe

paediatricpatientsreceivingintravenousacetylcysteinedevelopedhepatotoxicity,

whilsttwopatientsnotreceivingintravenousacetylcysteinediddevelop

hepatotoxicity.Thenumberofpaediatricpatientsexaminedinthisstudyistoosmall

toprovideastatisticallysignificantfindingforefficacy,however,theresultsappearto

beconsistenttothoseobservedin adults.

SafetyStudy

Arandomized,open-label,multi-centreclinicalstudywasconductedinAustraliato

comparetheratesofanaphylactoidreactionsbetweentworatesofinfusionforthe

intravenousacetylcysteineloadingdose.Onehundredandninesubjectswere

randomizedtoa15minuteinfusionrateand71subjectswererandomizedtoa60

minuteinfusionrate.Theloadingdosewas150mg/kg,followedbyamaintenance

doseof50mg/kgover4hoursandthen100mg/kgover16hours.Ofthe180

patientsexaminedinthisstudy,27%weremaleand73%werefemale.Agesranged

from15to83years,with themeanage being29.9 years(+13.0).

Withinthefirst2hoursfollowingintravenousacetylcysteineadministration,17%ofall

patientsdevelopedananaphylactoid reaction(18%inthe15-minutetreatmentgroup;

14%inthe60-minutetreatmentgroup)(SeePRECAUTIONS).Asubgroupof58

subjects(33inthe15-minutetreatmentgroup;25inthe60-minutetreatmentgroup)

wastreatedwithin8hoursofparacetamolingestion.Nohepatotoxicityoccurred

withinthissubgroup;howeverwith95%confidence,thetruehepatotoxicityrates

couldrangefrom0%to9%forthe15-minutetreatmentgroupandfrom0%to12%

forthe60-minutetreatmentgroup.

PRESENTATIONANDSTORAGECONDITIONS

AcetadoteInjectionisaclear,colourless,sterile,pyrogenfreeaqueoussolution of

acetylcysteine(N-acetyl-mercapto-alanine)with apHofapproximately6.0to 7.5.

AcetadoteInjectionissuppliedin vialscontaining6gofacetylcysteinein 30 mL

(acetylcysteine200 mg/mL)forintravenousadministration.Itisavailable in packsof

4 vials.

AUSTRnumber159242

Phebracode:INJ159

AcetadoteInjectionisintendedforintravenousadministration,followingdilution in5%

glucose solution.

Eachvialcontains acetylcysteine6 gin30mL.Whiletheconcentrationof

acetylcysteineinAcetadoteInjectionisexactlythesameasin other

acetylcysteineinjectable products,eachvialdoes containthreetimes the

quantityoftheactive ingredient;thatis,6gin 30mLforAcetadote,as

comparedto 2gin10mLforotheracetylcysteineinjectableproducts.

In addition,eachvialcontains thefollowinginactive ingredients:sodiumhydroxide

(pHadjustment),andWaterforInjections.

Productisforsingle usein one patientonly.Discardanyresidue.

Storetheunopenedvialbelow25°C.Protectfromlight.

Toreducemicrobiologicalhazard,useassoon aspracticable afterdilution.Ifstorage

isnecessary,hold at2°Cto8°Cfornotmorethan24hours.

POISONSCHEDULEOFTHEMEDICINE

S4:PrescriptionOnlyMedicine.

PACKAGEQUANTITIES

Each30mlvialcontains6gAcetylcysteine

Eachpackcontains4x30mlvials

FURTHERINFORMATION

Nil

NAMEANDADDRESS

AFTPharmaceuticalsLtd

POBox33-203

Takapuna

Auckland

Ph (09)488 0232

Fax(09)4880234

E:mailcustomer.service@aftpharm.com

DATEOFPREPARATION

Oct2013

3-10-2018

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EU/3/18/2065 (SFL Regulatory Services GmbH)

EU/3/18/2065 (SFL Regulatory Services GmbH)

EU/3/18/2065 (Active substance: Obiltoxaximab) - Orphan designation - Commission Decision (2018)5735 of Tue, 28 Aug 2018 European Medicines Agency (EMA) procedure number: EMA/OD/080/18

Europe -DG Health and Food Safety

28-8-2018

EU/3/18/2060 (Biogen Idec Limited)

EU/3/18/2060 (Biogen Idec Limited)

EU/3/18/2060 (Active substance: Adeno-associated viral vector serotype hu68 containing the human SMN1 gene) - Orphan designation - Commission Decision (2018)5732 of Tue, 28 Aug 2018 European Medicines Agency (EMA) procedure number: EMA/OD/065/18

Europe -DG Health and Food Safety

28-8-2018

EU/3/18/2064 (Bayer AG)

EU/3/18/2064 (Bayer AG)

EU/3/18/2064 (Active substance: Copanlisib) - Orphan designation - Commission Decision (2018)5734 of Tue, 28 Aug 2018 European Medicines Agency (EMA) procedure number: EMA/OD/071/18

Europe -DG Health and Food Safety

28-8-2018

EU/3/18/2069 (Professor Marjukka MyllArniemi)

EU/3/18/2069 (Professor Marjukka MyllArniemi)

EU/3/18/2069 (Active substance: Tilorone) - Orphan designation - Commission Decision (2018)5738 of Tue, 28 Aug 2018 European Medicines Agency (EMA) procedure number: EMA/OD/039/18

Europe -DG Health and Food Safety

28-8-2018

EU/3/18/2063 (IQVIA RDS Ireland Limited)

EU/3/18/2063 (IQVIA RDS Ireland Limited)

EU/3/18/2063 (Active substance: CD34+ haematopoietic stem and progenitor cells with CD3+ T-cells) - Orphan designation - Commission Decision (2018)5733 of Tue, 28 Aug 2018 European Medicines Agency (EMA) procedure number: EMA/OD/088/18

Europe -DG Health and Food Safety

28-8-2018

EU/3/18/2068 (Novo Nordisk A/S)

EU/3/18/2068 (Novo Nordisk A/S)

EU/3/18/2068 (Active substance: Somapacitan) - Orphan designation - Commission Decision (2018)5741 of Tue, 28 Aug 2018 European Medicines Agency (EMA) procedure number: EMA/OD/041/18

Europe -DG Health and Food Safety

28-8-2018

EU/3/18/2061 (Pharma Gateway AB)

EU/3/18/2061 (Pharma Gateway AB)

EU/3/18/2061 (Active substance: Autologous glioma tumour cells treated with antisense molecule directed against the insulin-like growth factor type 1 receptor) - Orphan designation - Commission Decision (2018)5739 of Tue, 28 Aug 2018 European Medicines Agency (EMA) procedure number: EMA/OD/049/18

Europe -DG Health and Food Safety

28-8-2018

EU/3/18/2067 (Omeros London Limited)

EU/3/18/2067 (Omeros London Limited)

EU/3/18/2067 (Active substance: Recombinant human monoclonal antibody against mannan-binding lectin-associated serine protease-2) - Orphan designation - Commission Decision (2018)5737 of Tue, 28 Aug 2018 European Medicines Agency (EMA) procedure number: EMA/OD/044/18

Europe -DG Health and Food Safety

27-8-2018

Beromun (BELPHARMA s.a.)

Beromun (BELPHARMA s.a.)

Beromun (Active substance: Tasonermin (Tumor Necrosis Factor alfa-1a)) - Centralised - Transfer Marketing Authorisation Holder - Commission Decision (2018)5699 of Mon, 27 Aug 2018 European Medicines Agency (EMA) procedure number: EMEA/H/C/206/T/40

Europe -DG Health and Food Safety

1-8-2018

Inflectra (Pfizer Europe MA EEIG)

Inflectra (Pfizer Europe MA EEIG)

Inflectra (Active substance: Infliximab) - Centralised - Transfer Marketing Authorisation Holder - Commission Decision (2018)5206 of Wed, 01 Aug 2018 European Medicines Agency (EMA) procedure number: EMEA/H/C/2778/T/64

Europe -DG Health and Food Safety

23-3-2018

EU/3/18/1998 (Blue-Reg Europe)

EU/3/18/1998 (Blue-Reg Europe)

EU/3/18/1998 (Active substance: Patidegib) - Orphan designation - Commission Decision (2018)1887 of Fri, 23 Mar 2018 European Medicines Agency (EMA) procedure number: EMA/OD/206/17

Europe -DG Health and Food Safety