Abelcet

Main information

  • Trade name:
  • Abelcet 5 mg/mL Emulsion for infusion
  • Dosage:
  • 5 mg/mL
  • Pharmaceutical form:
  • Emulsion for infusion
  • Units in package:
  • Vial, glass, single dose, 20 mL
  • Class:
  • Prescription
  • Prescription type:
  • Prescription
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug
  • Manufactured by:
  • Xellia Pharmaceuticals ApS

Documents

Localization

  • Available in:
  • Abelcet 5 mg/mL Emulsion for infusion
    New Zealand
  • Language:
  • English

Therapeutic information

  • Therapeutic indications:
  • ABELCET is indicated for the treatment of invasive fungal disease caused by organisms susceptible to amphotericin B.

Other information

Status

  • Source:
  • Medsafe - Medicines Safety Authority - New Zealand
  • Authorization number:
  • 8914
  • Authorization date:
  • 30-04-1999
  • Last update:
  • 27-09-2017

Summary of Product characteristics: dosage,interactions,side effects

NewZealandData Sheet

ABELCET ®

(amphotericinlipidcomplex)solutionforinfusion

DESCRIPTION

ABELCET ® isa sterile,pyrogen-free suspension in isotonicsaline.Itconsistsof

amphotericin,ofwhich amphotericin Bisthemajorcomponent,inacomplexwith

phospholipids.Amphotericin isamacrocyclic,polyene,broad-spectrumantifungal

antibioticproducedbyStreptomycesnodosus.Thelipophilicmoietyofamphotericin

Ballowsmoleculesofthe drugto be complexed ina ribbon-like structure with the

phospholipids.

The chemicalstructureofamphotericin Bisasfollows:

CASNumber:1397-89-3

ABELCETissuppliedasa20mL suspension in avial.Each vialcontainsthe

equivalentof100mgofamphotericin B.Before infusion,thesuspension mustbe

filtered usingthefilterneedle provided (to remove anylarge particlespresent)and

thendiluted with 5.0%glucose injection,accordingto the Sectionbelowtitled,

Preparationofthe Suspension forInfusion.EachmLofABELCETsuspension

contains:

Amphotericin equivalentto amphotericinB 5.0 mg

Dimyristoylphosphatidylcholine 3.4 mg

Dimyristoylphosphatidylglycerol(asthesodiumand ammonium

salts) 1.5 mg

SodiumChloride 9.0 mg

WaterforInjections,sufficienttomake 1.0 mL

PHARMACOLOGY

Pharmacokinetics

Amphotericin Biscomplexedto phospholipidsinABELCET.The pharmacokinetic

propertiesofABELCETand conventionalamphotericin Bare different.Amphotericin

Bwhen administeredasABELCETisrapidlydistributed totissues.Limitedhuman

autopsydatashowed that,afteradministration ofABELCET,amphotericin Blevelsin

tissue were highestinthe liver,spleenand lung.Peakblood levelsofamphotericin B

were lowerafteradministration ofABELCETthanafteradministration ofequivalent

amountsofconventionaldrug.

Available data on the pharmacokineticsofamphotericin Bin wholebloodafterthe

administrationofABELCETinhumanssupportan initialrapidfallinthe

concentration ofamphotericin Bfromthe bloodfollowed bya longterminaldeclinein

concentration.However,thephysicochemicalcharacterofcirculatingamphotericin B

andthepharmacologicalsignificance ofthe levelofthedrugin bloodisnotknown.

The assayused tomeasure amphotericin Bin the bloodaftertheadministrationof

ABELCETdoesnotdistinguish amphotericinBthatiscomplexed with the

phospholipidsofABELCETfromamphotericin Bthatisuncomplexed.

The pharmacokineticsofamphotericin Baftertheadministration ofABELCETare

nonlinear.Volume ofdistributionand clearancefrombloodincreasewithincreasing

doseofABELCET,resultingin lessthanproportionalincreasesin blood

concentrationsofamphotericinBovera doserange of0.6to5mg/kg/day.The

pharmacokineticsofamphotericinBin wholeblood afterthe administrationof

ABELCETand amphotericin Bdesoxycholate are:

PharmacokineticParametersofAmphotericin BinWholeBlood in Patients

Administered MultipleDosesofABELCETorAmphotericin BDesoxycholate

Pharmacokinetic Parameter ABELCET

5mg/kg/dayfor

5-7days

Mean±SD Amphotericin B

0.6mg/kg/dayfor

42 days a

Mean±SD

PeakConcentration (µg/mL) 1.7 ±0.8(n=10) b 1.1 ±0.2(n=5)

ConcentrationatEndofDosingInterval

(µg/mL) 0.6 ±0.3(n=10) b 0.4 ±0.2(n=5)

Area UnderBlood Concentration-Time Curve

(AUC

0-24h )(µg*h/mL) 14 ±7 (n=14) b,c 17.1±5 (n=5)

Clearance (mL/h*kg) 436 ±188.5

(n=14) b,c 38 ±15 (n=5)

ApparentVolume ofDistribution(Vd

area )

(L/kg) 131 ±57.7 (n=8) c 5 ±2.8 (n=5)

Terminal EliminationHalf-Life (h) 173.4 ±78 (n=8) c 91.1±40.9 (n=5)

AmountExcreted in Urine Over24h After

LastDose (%ofdose) d 0.9 ±0.4(n=8) c 9.6 ±2.5(n=8)

a Datafrompatientswithmucocutaneousleishmaniasis.Infusion rate was0.25

mg/kg/h.

b Datafromstudiesinpatientswith cytologicallyproven cancerbeingtreated with

chemotherapyorneutropenicpatientswith presumedorprovenfungalinfection.

Infusion rate was2.5mg/kg/h.

cDatafrompatientswith mucocutaneousleishmaniasis.Infusion rate was4mg/kg/h.

dPercentageofdoseexcreted in 24 hoursafterlastdose.

The large volumeofdistributionand high clearance valuefromthebloodof

amphotericin Bafterthe administrationofABELCETprobablyreflectuptakeby

tissues.The longterminalelimination half-lifeprobablyreflectsa slowredistribution

fromtissues.Althoughamphotericin Bisexcretedslowly,there islittle accumulation

in theblood afterrepeateddosing.

Tissueconcentrationsofamphotericin Bhave been obtainedatautopsyfromone

hearttransplantpatientwho received ABELCETata doseof5.3mg/kg/dayforthree

consecutive daysimmediatelybeforedeath.The concentrationsofamphotericin B

(µg/g)reported were:290,spleen;222,lung;196,liver;7.6,lymphnode;6.9,kidney;

5,heart; 1.6,brain.The relationshipoftissueconcentrationsofamphotericinBtoits

biologicalactivitywhen administered asABELCETisunknown.

Microbiological Activity

Amphotericin B,theactive antifungalagentinABELCET,maybefungistaticor

fungicidal,dependingon itsconcentration and onfungalsusceptibility.Thedrug

probablyactsbybindingto ergosterolin thefungalcellmembrane causing

subsequentmembranedamage.Asa result,cellcontentsleakfromthefungalcell,

and ultimately,celldeath occurs.Bindingofthe drugto sterolsinhumancell

membranesmayresultin toxicity,although amphotericinBhasgreateraffinityfor

fungalergosterolsthanforthe cholesterolofhuman cells.

Amphotericin Bisactive againstmanyfungalpathogensin vitro,includingCandida

sp.,Cryptococcusneoformans,Aspergillussp.,Mucorsp.,Sporothrixschenckii,

Blastomycesdermatitidis,CoccidioidesimmitisandHistoplasma capsulatum.Most

strainsare inhibited byamphotericin Bconcentrationsof0.03 to 1.0mg/mL.

Amphotericin Bhaslittle orno activityagainstbacteriaorviruses.ABELCETshows

in vitro activityagainstAspergillussp.(n=3)andCandidasp.(n=10),with MICs

general ly<1μg/mL.DependinguponthespeciesandstrainofAspergillusand

Candidatested,significantinvitro differencesin susceptibilityto amphotericinB

havebeenreported(MICsrangingfrom0.1to>10μg/mL).However,standardised

techniquesforsusceptibilitytestingforantifungalagentshave notbeen established,

and resultsofsusceptibilitystudiesdo notnecessarilycorrelatewith clinicaloutcome.

Clinical Trials

Two randomised comparative studieswere conducted insystemicCandidaandin

cryptococcalmeningitis.Inaddition,a comparison wasmade ofopen-labeltreatment

ofpatientswith aspergillosiswith a retrospectivelyacquired controlgroup.In the

randomisedcomparative studyin patientswith invasive candidiasis(153 on 5

mg/kg/dayofABELCETvs.78on0.6to1.0mg/kg/dayofamphotericin B),the

overallresponse ratewas63%forABELCETvs68%foramphotericin B.Inthe

randomisedcomparative studyin patientswith cryptococcalmeningitis(21 on 5

mg/kg/dayofABELCETvs.17on 0.7mg/kg/dayofamphotericin B),theoverall

response rate(clinicalandmycologicalsuccess)was43%forABELCETvs47%for

amphotericin B.

Acomparison wasmade ofa group ofpatientswith aspergillosistreatedwith

ABELCETwith a retrospectivelyacquiredcontrolgroup ofpatientstreatedwith

amphotericin B.Patientsin the ABELCET-treatedgroup were given theproductfor

a varietyofreasonswhich includedfailureofamphotericin Boranothersystemic

antifungaltherapy,nephrotoxicitydue toamphotericinBoranotherdrug,renal

diseaseoracuteamphotericin Btoxicity.There were severaldifferencesin the

characteristicsofthe two groupsthatmayhave influenced the comparison.Overall

clinicalresponse rate (completeand partialresponse)was40%forABELCETvs20%

foramphotericin B.

Information to supportefficacyin otherfungalinfections,includingfusariosis,

coccidioidomycosis,zygomycosis andblastomycosis,is limited.

INDICATIONS

ABELCETisindicatedforthetreatmentofinvasive fungaldisease caused by

organismssusceptibleto amphotericin B(seeClinicalTrials).

CONTRAINDICATIONS

ABELCETiscontraindicatedin patientswith known hypersensitivityto anyofits

constituentsunless,intheopinion ofthe physician,the advantagesofusing

ABELCEToutweigh the riskofhypersensitivity.

PRECAUTIONS

Treatmentwith ABELCETrequireshospitalization and supervision bya physician.

Adverse reactionssimilarto thoseassociatedwith conventionalamphotericinBmay

occurwith ABELCET.Patientsshouldbemonitoredforanytype ofadverse reaction

associated with conventionalamphotericin B.Particularattentionshouldbe paid to

patientsreceivingnephrotoxicdrugsconcomitantlywith ABELCET.Renalfunction

shouldbemonitored closelyinthesepatients.

Anaphylactoid reactionsandasthma have been reportedin patientsgiven ABELCET.

Facilitiesforcardiopulmonaryresuscitationshouldbe readilyathand when

ABELCETisbeingadministered.*Ifsevere respiratorydistressand/oranaphylaxis

occurwith the infusionofABELCET,theinfusion shouldbe immediately

discontinued.The patientshouldnotreceivefurtherinfusionsofABELCET.*

Infusion HypersensitivityReactions

Infusion related reactions(suchaschillsandpyrexia)recordedfollowingthe

administrationofABELCEThave been generallymild ormoderate and have mainly

been recordedduringthefirst2daysofadministration.These reactionsnormally

abate afterafewdaysoftreatmentand consideration ofprecautionarymeasuresfor

thepreventionortreatmentofthese reactionsshould begiven to patientswho

received ABELCETtherapy.Routine dosesofacetylsalicylicacid,antipyretics(e.g.

paracetamol),antihistaminicandanti-emetictreatmentshave beenreported as

successfulintheirprevention ortreatment.

Systemicfungalinfections

Do notuseABELCETfortreatmentofcommon orsuperficial,clinicallyunapparent

fungalinfectionsthatare detectable onlybypositive skin orserologictests.

Use inPatientswithRenalImpairment

Since ABELCETisa potentiallynephrotoxicdrug,monitoringofrenalfunction should

be performedbefore initiatingtreatmentinpatientswith pre-existingrenaldiseaseor

who have alreadyexperiencedrenalfailure,and regularlyduringtherapy.In patients

with serioussystemicfungalinfectionsandcontraindicationsto conventional

amphotericin Bwho were treatedwith ABELCETrenalfunction remained stablein

50.5%ofpatients,improved in 21.8%and declined in24.4%after6weeksof

treatment.In the subpopulationofcaseswith baseline serumcreatinine levels

greaterthan 221µmol/L,themean serumcreatininedecreasedfrom339µmol/Lat

the startoftreatmentto 229 µmol/L after6weeksoftreatment.Renaldysfunction

thatdeveloped duringtreatmentwith conventionalamphotericin Bhasbeen shown

to stabilise orimprovefrequentlyduringsubsequentABELCETtreatment.

Usein Children

Systemicfungalinfectionsin childrenhave beentreated successfullywith ABELCET.

The dose to be given shouldbe calculatedusingthe same doseperkgofweightas

isusedto calculatetherecommendedadultdose.

Use inElderlyPatients

Systemicfungalinfectionsinelderlypatientshave been treated successfullywith

ABELCET.

Theadverse reactionprofile issimilartothatseen inadultslessthan 65 yearsofage,

with the exceptionofincreasesin serumcreatinine anddyspnoeaforboth ABELCET

and conventionalamphotericinBwhich werereported with a greaterfrequencyin

patients ≥65yearsofage.

The dose to be given shouldbe calculatedusingthe same doseperkgofweightas

isusedto calculatetherecommendeddose.

Use inRenalDialysis Patients

ABELCETshould be administered to renaldialysispatientsonlyafterthe completion

ofdialysis.Serumpotassiumandmagnesiumlevelsshouldbemonitored regularly.

ABELCETmaybe given topatientswith renalfailure atthe recommended adultdose.

Use inPregnancy(CategoryB3)

ConventionalamphotericinBhasbeenused successfullyto treatsystemicfungal

infectionsin pregnantwomen with noobviouseffecton thefoetus,butonlya small

numberofcaseshave been reported.Reproductive studiesofABELCETinrats

showed noevidenceofembryotoxicity,foetotoxicityorteratogenicityatplasma drug

exposuressimilarto those expectedtherapeutically.However,in rabbits,adose-

rangingteratogenicitystudy,butnotthe subsequentfullstudy,indicatedthat

ABELCETmayhave embryotoxicandfoetotoxiceffectsatestimatedplasma

exposures(based on C

)belowthose expected inpatients.Asuncertaintyremains

asto whetherornotABELCETcanaffectthedevelopingembryo/foetus,thedrug

shouldbeadministered topregnantwomenonlyforlife-threateningdiseasewhen

the likelybenefitexceedstheriskto motherand foetus.

Use inLactation

Itisnotknown whetherABELCETisexcretedin human milk,and there have been

no relevantstudiesinanimals.Asmanydrugsare excretedin human milkand can

be harmfultothe baby,treatmentoflactatingwomen with ABELCETisnot

recommended.

Carcinogenesis,Mutagenesisand ImpairmentofFertility

There have been no animalstudiesconducted toassessthecarcinogenicpotential

ofABELCET.Genemutation assaysinSalmonella typhimuriumandin mouse

lymphoma cellsin vitro were negative.Therewasno increasein theincidenceof

chromosomalaberrationsin Chinesehamsterovarycellsin vitro orin an invivo

micronucleustestinmice.There wasno effectonfertilityin ratsdosed with

ABELCETatup to 10mg/kg/dayamphotericin B(0.32timesthe recommended

humandose,based onbodysurface area).

Interactionswith OtherDrugs

The interactionofABELCETwith otherdrugshasnotbeen studied to date.However,

when administered concomitantly,thefollowingdrugsare known tointeractwith

conventionalamphotericin B;therefore thefollowingtreatmentsmayinteractwith

ABELCET.

Nephrotoxicdrugs

ABELCETisa potentiallynephrotoxicdrugand monitoringofrenalfunction is

recommended inpatientsreceivingnephrotoxicdrugsconcomitantly.Leukocyte

transfusions

Acutepulmonarytoxicityhasbeen reported inpatientsreceivingintravenous

conventionalamphotericin Band leukocyte transfusions.Conventionalamphotericin

Band leukocyte should notbe given concomitantly.

Zidovudine

In dogs,exacerbatedmyelotoxicityand nephrotoxicitywere observed when

ABELCET(1.5or5.0mg/kg/day)wasadministered concomitantlywith zidovudine

for30days.Ifconcomitanttreatmentwith both agentsisrequired,renaland

haematologicfunctionshouldbe closelymonitored.

Cyclosporin

PreliminarydatasuggestthatpatientsreceivingABELCETconcomitantlywith high

dosecyclosporinexperiencean increase inserumcreatinine.Thedata alsoindicate

thattheincrease in serumcreatinine iscaused bycyclosporin andnotABELCET.

Untilfurtherinformation isavailable,renalfunction shouldbemonitored closelyin

patientswho receive concomitanttreatmentwith both drugs.

Otherdrugs

Conventionalamphotericin Bhasbeen reported to interactwith antineoplasticagents,

corticosteroidsand corticotrophin (ACTH),digitalisglycosides,flucytosineand

skeletalmusclerelaxants.Cautionshould beexercised duringconcomitantuse with

ABELCET.

ADVERSEREACTIONS

ClinicalTrialData

Themostcommon clinicaladverse reactionshave been chillsandfever.

Premedication (e.g.paracetamol)maybe administeredfortheprevention ofinfusion

related adversereactions.

Adverse experiencesreported amongpatientswith invasive candidiasistreated with

ABELCET(n=153)oramphotericin B(n=78)in a comparative clinicaltrialare shown

in thetable below.Included arealladverse eventsoccurringwith an incidence rate

ofgreaterthan orequalto 5%.

StudyAI800-017

Invasive Candidiasis

AdverseEvents(Regardlessof Causality) GroupedbyBodySystem

withIncidence ≥5%

ABELCET

5.0 mg/kg/day AmphotericinB

0.6 mg/kg/day

Incidence ≥5%

BodySystem/Adverse Events n n

No.ofPatientsTreated 153 (%) 78 (%)

No.ofPatientsWho Reported AEs 149 78

Body asa Whole 116 (76) 57 (73)

Sepsis 38 (25) 14 (18)

Infection 32 (21) 19 (24)

Fever 30 (20) 13 (17)

Chills 19 (12) 3 (4)

AbdominalPain 18 (12) 15 (19)

Pain 15 (10) 9 (12)

GeneralisedOedema 12 (8) 9 (12)

ChestPain 12 (8) 6 (8)

Headache 9 (6) 8 (10)

InjectionSiteReaction 9 (6) 5 (6)

Asthenia 8 (5) 5 (6)

InjectionSiteHypersensitivity 2 (1) 6 (8)

CardiovascularSystem 99 (65) 42 (54)

Hypotension 49 (32) 15 (19)

StudyAI800-017

Invasive Candidiasis

AdverseEvents(Regardlessof Causality) GroupedbyBodySystem

withIncidence ≥5%

ABELCET

5.0 mg/kg/day AmphotericinB

0.6 mg/kg/day

Incidence ≥5%

Tachycardia 25 (16) 6 (8)

HeartArrest 15 (10) 13 (17)

Hypertension 13 (8) 8 (10)

HeartFailure 12 (8) 6 (8)

Atrial Fibrillation 10 (7) 4 (5)

Phlebitis 7 (5) 2 (3)

SupraventricularTachycardia 7 (5) 2 (3)

ElectrocardiogramAbnormal 5 (3) 8 (10)

Digestive System 92 (60) 50 (64)

Diarrhoea 26 (17) 12 (15)

Nausea 24 (16) 11 (14)

Vomiting 20 (13) 8 (10)

NauseaandVomiting 8 (5) 7 (9)

GastrointestinalHaemorrhage 10 (7) 3 (4)

Constipation 9 (6) 8 (10)

Anorexia 8 (5) 0

LiverFunctionTestsAbnormal 7 (5) 5 (6)

HaemicandLymphatic System 57 (37) 40 (51)

Anaemia 26 (17) 14 (18)

Leukocytosis 15 (10) 12 (15)

Thrombocytopenia 12 (8) 5 (6)

Blood Dyscrasia 6 (4) 1 (1)

ThromboplastinDecreased 6 (4) 5 (6)

Leukopenia 5 (3) 7 (9)

Cyanosis 1 (1) 5 (6)

MetabolicandNutritionalDisorders 110 (72) 65 (83)

Creatinine Increased 51 (33) 35 (45)

Hypokalaemia 41 (27) 15 (19)

Urea Increased 29 (19) 20 (26)

AlkalinePhosphatase Increased 25 (16) 16 (21)

Hypomagnesaemia 18 (12) 8 (10)

Acidosis 15 (10) 6 (8)

PeripheralOedema 15 (10) 9 (12)

Bilirubinaemia 14 (9) 7 (9)

Hyperkalaemia 12 (8) 6 (8)

Hypoxia 11 (7) 1 (1)

Hyperglycaemia 9 (6) 5 (6)

Hypernatraemia 9 (6) 5 (6)

Hyperphosphataemia 8 (5) 6 (8)

Hyponatraemia 8 (5) 5 (6)

Hyperchloraemia 6 (4) 5 (6)

StudyAI800-017

Invasive Candidiasis

AdverseEvents(Regardlessof Causality) GroupedbyBodySystem

withIncidence ≥5%

ABELCET

5.0 mg/kg/day AmphotericinB

0.6 mg/kg/day

Incidence ≥5%

SGPTIncreased 5 (3) 5 (6)

Hypoglycaemia 2 (1) 7 (9)

Nervous System 67 (44) 22 (28)

Confusion 16 (10) 4 (5)

Insomnia 12 (8) 5 (6)

Somnolence 12 (8) 5 (6)

Anxiety 11 (7) 3 (4)

Agitation 7 (5) 3 (4)

RespiratorySystem 99 (65) 56 (72)

Dyspnoea 37 (24) 26 (33)

PluralEffusion 24 (16) 5 (6)

LungDisorder 22 (14) 14 (18)

RespiratoryDisorder 19 (12) 9 (12)

Pneumonia 15 (10) 7 (9)

Hyperventilation 13 (8) 9 (12)

Asthma 11 (7) 3 (4)

LungOedema 10 (7) 3 (4)

Haemoptysis 9 (6) 1 (1)

RespiratoryFailure 9 (6) 9 (12)

Cough Increased 8 (5) 1 (1)

Pharyngitis 7 (5) 2 (3)

Apnoea 1 (1) 6 (8)

Skin&Appendages 41 (27) 25 (32)

Rash 12 (8) 13 (17)

Pruritus 7 (5) 2 (3)

SkinUlcer 5 (3) 5 (6)

UrogenitalSystem 72 (47) 40 (51)

Haematuria 29 (19) 16 (21)

UrinaryTractInfection 16 (10) 9 (12)

Pyuria 15 (10) 8 (10)

Oliguria 11 (7) 5 (6)

KidneyFunction Abnormal 9 (6) 5 (6)

KidneyFailure 7 (5) 6 (8)

UrinaryTractDisorder 1 (1) 4 (5)

Post-marketingData

Thefollowing additionalpost-marketingadversereactionsarelistedbelowasMedDRA

preferredtermsbysystemorganclassandfrequency.Frequenciesare defined as:

Verycommon(>1/10),Common(>1/100to ≤1/10),Uncommon(>1/1000and≤1/100),Rare

(>1/10,000 to ≤1/1,000),Veryrare(≥1/10,000)andNotknown(cannotbeestimatedfromthe

available data).

Systemorgan

class Adverse reaction Frequency

Investigations

Blood creatinine increased Verycommon

Blood alkalinephosphatise increased,blood urea increased Common

Cardiacdisorders

Tachycardia,cardiacarrhythmias,hypotension Common

Shock,cardiacarrest Uncommon

arrhythmia,asystole,bradycardia,haemorrhage Veryrare

Blood and lymphaticsystemdisorders

Thrombocytopenia Common

Pancytopenia Veryrare

Nervoussystem disorders

Headache,tremor Common

Convulsion,neuropathy Uncommon

Agitation,confusion,encephalopathy,stupor Veryrare

Respiratory,thoracicand mediastinaldisorders

Dyspnoea,asthma Common

Respiratoryfailure Uncommon

Hypoxia Veryrare

Bronchospasm Notknown

Gastrointestinaldisorders

Nausea,vomiting,abdominalpain Common

Gastrointestinalhaemorrhage,liverfunction abnormal,peritonitis Veryrare

Musculoskeletaland connective tissue disorders

Myalgia Uncommon

Myoclonus Veryrare

Renaland urinarydisorders

Renalimpairmentincluding renalfailure Common

Anuria,incontinence Veryrare

Hyposthenuria,Renaltubularacidosis Notknown

Skin and subcutaneoustissue disorders

Rash Common

Pruritis Uncommon

Dermatitisexfoliative Notknown

Metabolism and nutrition disorders

Hyperbilirubinaemia,hypokalaemia,Electrolyteimbalance

includingbloodpotassiumincreased,bloodmagnesium

decreased Common

Hypoglycaemia,hyperammonaemia Veryrare

Vasculardisorders

Hypertension,hypotension Common

Shock Uncommon

Generaldisordersand administration site conditions

Chills,pyrexia Verycommon

Injection sitereaction Uncommon

Vasodilation Veryrare

Immune system disorders

Anaphylacticresponse Uncommon

Hepatobiliarydisorders

Liverfunction testabnormal Common

Infusionhypersensitivityreactionshavebeenassociatedwithabdominalpain,nausea,

vomiting,myalgia,pruritus,maculopapularrash,fever,hypotension,shock,

bronchospasm,respiratoryfailure.

Renaltubularacidosishasbeenreportedincludinghyposthenuriaandelectrolyte

imbalancesuch asincreased potassiumand decreased magnesium.

Abnormalliverfunctiontestshavebeen reported withABELCETandother

amphotericin Bproductsassociated tootherfactorssuchasinfection,

hyperalimentation,concomitanthepatotoxicdrugsandgraft-versus-hostdisease.

DOSAGEANDADMINISTRATION

ABELCETisasterile,pyrogen-free suspension to be dilutedforintravenousinfusion

only.

Vialsare forsingle usein one patienton oneoccasiononly. Unused materialshould

be discarded. Aseptictechniquemustbe strictlyobserved throughouthandlingof

ABELCETsincenobacteriostaticagentorpreservative ispresent.

Dosage

The recommended dailydoseis5.0 mg/kggiven asa single infusion.Use ofother

doseshasnotbeen supported byadequateinformation.

An initialtestdoseof1.0mgshouldbeinfused intravenouslyover15 minutes.

Facilitiesforresuscitation shouldbe readilyathand.

ABELCETshould be administeredbyintravenousinfusion ata rateof2.5mg/kg/h.

Anin-line filtermaybe used forintravenousinfusion ofABELCET.The meanpore

diameterofthefiltershouldnotbe lessthan5.0microns.Forsevere systemic

infections,treatmentduration istypicallyatleast14 days.ABELCEThasbeen

administeredforaslongas11months,and cumulative doseshavebeen ashigh as

56.6gwithoutsignificanttoxicity.

Preparation oftheSuspension forInfusion

1.Allowthe suspensionto come to roomtemperature.Shake gentlyuntilthereis

no evidence ofanyyellowsedimentatthe bottomofthevial.

2.WithdrawtheappropriatedoseofABELCETfromthe requirednumberofvials

into asterile syringe usinga 17to19gauge needle.

3.Remove the needlefromthe syringe filled with ABELCETand replace with the

5 micron highflowfilterneedle provided with each vial.

4.Insertthefilterneedleofthe syringe into an IVbagcontaining5.0%glucose

injectionandemptythe contentsofthe syringe into thebagbymanual

pressureorvia an infusion pump.

Eachneedleprovidedwith a filtermayonlybe used tofilterthe contentsofone

bottleand anotherneedle mustbeusedwith eachnewbottle.The finalinfusion

concentration should be1 mg/mL.

Discard afterdilutionifthereisanyevidence offoreign materialin the solution.The

infusionisbestadministeredbymeansofaninfusionpump.

DONOTDILUTEWITH SALINESOLUTIONSOR MIXWITH OTHER DRUGSOR

ELECTROLYTES.ThecompatibilityofABELCETwith thesematerialshasnotbeen

established.Anexistingintravenousline should beflushed with 5.0%glucose

injectionbefore infusion ofABELCET,ora separateinfusion lineshouldbe used.

Toreducemicrobiologicalhazard,use assoon aspracticable afterpreparation.If

storageisnecessary,hold at2°Cto 8°Cfornotmorethan 24hours.Following

storage in IVbags,thereadyforuse ABELCETsuspensionmustbe vigorously

agitated priorto use.

OVERDOSAGE

Onepaediatricpatientreceived a single doseof13.1mg/kgononeoccasion,

withoutadverse effects.

Should an overdoseoccur,thepatientshouldbe treated asdeemedappropriateby

the physician.Inparticular,the cardio-pulmonary,renalandhepaticfunction aswell

asthe blood countandserumelectrolytesshouldbemonitoredandsupportive

measuresinitiated.

PRESENTATION

Amphotericin equivalenttoamphotericinB100mg/20mL;yellow,opaque

suspensionforinfusion;20mLvialswith filterneedlesareindividuallypackaged.

STORAGE

Store at2°Cto 8°C(Refrigerate.Do notfreeze).Protectfromlight.

MEDICINECLASSIFICATION

Prescription Medicine

FURTHER INFORMATION

ThisdatasheethasProvisionalConsentunderSection 23 ofthe MedicinesAct1981.

ABELCETisnotcurrentlymarketed in NewZealand.

NAMEANDADDRESS OFSPONSOR

PharmacyRetailingLimitedtradingasHealthcare Logistics

58 RichardPearse Drive

AirportOaks

Auckland,NewZealand

DATEOFPREPARATION

15 August2012

Document Outline

27-11-2018

Teva Pharmaceuticals USA Issues Voluntary Nationwide Recall of All Amlodipine/Valsartan Combination Tablets and Amlodipine/Valsartan/Hydrochlorothiazide Combination Tablets That Are Within Expiry

Teva Pharmaceuticals USA Issues Voluntary Nationwide Recall of All Amlodipine/Valsartan Combination Tablets and Amlodipine/Valsartan/Hydrochlorothiazide Combination Tablets That Are Within Expiry

Teva Pharmaceuticals has initiated a voluntary recall in the United States, to the patient level, of all lots of Amlodipine / Valsartan combination tablets and Amlodipine / Valsartan / Hydrochlorothiazide combination tablets (see table below) due to an impurity detected above specification limits in an active pharmaceutical ingredient (API) manufactured by Mylan India. The impurity found in Mylan’s valsartan API is known as N-nitroso-diethylamine (NDEA), which has been classified as a probable human carc...

FDA - U.S. Food and Drug Administration

29-8-2018

Hellolife, Inc. Issues Voluntary Worldwide Recall of Neuroveen, Respitrol, Thyroveev and Compulsin due to Possible Microbial Contamination

Hellolife, Inc. Issues Voluntary Worldwide Recall of Neuroveen, Respitrol, Thyroveev and Compulsin due to Possible Microbial Contamination

HelloLife, Inc. in Grand Rapids, MI is initiating a voluntary recall of four different products, Neuroveen, Respitrol, Thyroveev and Compulsin, within expiry, to the retail and consumer level due to possible microbial contamination. Neuroveen has been tested and found to be contaminated with Staphylococcus saprophyticus and Burkholderia cepacia. Compulsin has been identified as containing Burkholderia cepacia. Respitrol and Thyroveev are still pending bacterial identification. Each product being recalled...

FDA - U.S. Food and Drug Administration

23-7-2018

Flowers Foods Issues Voluntary Recall on Mrs. Freshley’s and Other Brands of Swiss Rolls and Captain John Derst’s Old Fashioned Bread

Flowers Foods Issues Voluntary Recall on Mrs. Freshley’s and Other Brands of Swiss Rolls and Captain John Derst’s Old Fashioned Bread

As a precautionary measure, Flowers Foods, Inc. (NYSE: FLO) is voluntarily recalling Swiss Rolls sold under the brand names Mrs. Freshley’s, Food Lion, H-E-B, Baker’s Treat, Market Square, and Great Value, distributed nationwide, and Captain John Derst’s Old Fashioned Bread distributed in Alabama, Florida, Georgia, North Carolina, and South Carolina, due to the potential presence of Salmonella in an ingredient, whey powder. The ingredient recall was initiated by a third-party whey powder manufacturer and...

FDA - U.S. Food and Drug Administration

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

24-5-2018

#ThrowBackThursday- May 24, 1977- Bureau of Medical Devices and Diagnostic Products renamed Bureau of Medical Devices and new Office of Small Manufacturers Assistance created, as required by law. #OnThisDay #FDAHistory

#ThrowBackThursday- May 24, 1977- Bureau of Medical Devices and Diagnostic Products renamed Bureau of Medical Devices and new Office of Small Manufacturers Assistance created, as required by law. #OnThisDay #FDAHistory

#ThrowBackThursday- May 24, 1977- Bureau of Medical Devices and Diagnostic Products renamed Bureau of Medical Devices and new Office of Small Manufacturers Assistance created, as required by law. #OnThisDay #FDAHistory

FDA - U.S. Food and Drug Administration