Idarubicinhydrochlorid "Accord"

Primær information

  • Handelsnavn:
  • Idarubicinhydrochlorid "Accord" 20 mg injektionsvæske, opløsning
  • Dosering:
  • 20 mg
  • Lægemiddelform:
  • injektionsvæske, opløsning
  • Brugt til:
  • Mennesker
  • Medicin typen:
  • Allopatiske stof

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Lokation

  • Fås i:
  • Idarubicinhydrochlorid "Accord" 20 mg injektionsvæske, opløsning
    Danmark
  • Sprog:
  • dansk

Andre oplysninger

Status

  • Kilde:
  • Lægemiddelstyrelsen - Danish Medicines Agency
  • Autorisationsnummer:
  • 57742
  • Sidste ændring:
  • 22-02-2018

Produktresumé

11. januar 2017

PRODUKTRESUMÉ

for

Idarubicinhydrochlorid "Accord", injektionsvæske, opløsning

0.

D.SP.NR.

30284

1.

LÆGEMIDLETS NAVN

Idarubicinhydrochlorid "Accord"

2.

KVALITATIV OG KVANTITATIV SAMMENSÆTNING

Hver ml opløsning indeholder 1 mg idarubicinhydrochlorid.

Hvert hætteglas med 5 ml indeholder 5 mg idarubicinhydrochlorid.

Hvert hætteglas med 10 ml indeholder 10 mg idarubicinhydrochlorid.

Hvert hætteglas med 20 ml indeholder 20 mg idarubicinhydrochlorid.

Alle hjælpestoffer er anført under pkt. 6.1.

3.

LÆGEMIDDELFORM

Injektionsvæske, opløsning

Klar, orangerødlig opløsning uden synlige suspenderede partikler.

pH: 3-4,5.

4.

KLINISKE OPLYSNINGER

4.1

Terapeutiske indikationer

Cytotoksisk og antimitotisk stof.

Voksne

Til behandling af akut myeloid leukæmi (også kendt som AML), til remissionsinduktion

i ubehandlede patienter eller til remissionsinduktion i recidiverende eller refraktære

patienter.

Til andetvalgsbehandling af recidiverende akut lymfoblastær leukæmi (ALL).

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Side 1 af 13

Børn

Til førstevalgsbehandling af akut myeloid leukæmi (AML), i kombination med

cytarabin, til remissionsinduktion.

Til andetvalgsbehandling af recidiverende akut lymfoblastær leukæmi (ALL).

Idarubicinhydrochlorid "Accord" kan anvendes i kombination med kemoterapiregimer med

andre cytotoksiske stoffer (se pkt. 4.2).

4.2

Dosering og indgivelsesmåde

Dosering

Dosering er sædvanligvis beregnet på baggrund af kroppens overfladeareal (mg/m

). Til

intravenøs brug.

Akut myeloid leukæmi (AML)

Voksne

Ved akut myeloid leukæmi hos voksne er den anbefalede dosis 12 mg/m

intravenøst

daglig i 3 dage i kombination med cytarabin. En anden dosisplan, der kan anvendes til

behandling af akut myeloid leukæmi som enkeltstof eller i kombinationsterapi, er 8 mg/m

intravenøst daglig i 5 dage.

Børn

Det anbefalede dosisinterval er 10-12 mg/m

intravenøst daglig i 3 dage i kombination med

cytarabin.

Akut lymfocytisk leukæmi (ALL)

Voksne

Som enkeltstof er den foreslåede dosis 12 mg/m

intravenøst daglig i 3 dage.

Børn

Som enkeltstof er den foreslåede dosis 10 mg/m

intravenøst daglig i 3 dage

Bemærk: Dette er kun generelle retningslinjer. Se individuelle protokoller for nøjagtig

dosering.

Alle ovennævnte doseringsregimer bør tage højde for patientens hæmatologiske status og

dosering af andre cytotoksiske lægemidler, når anvendt i kombination hermed.

Administration

Intravenøs administration af idarubicin bør udføres meget omhyggeligt. Det anbefales, at

idarubicin administreres over en periode på 5 til 10 minutter via en infusionsslange med en

fritløbende intravenøs infusion af 0,9 % natriumchlorid. Denne teknik mindsker risikoen

for tromboflebitis eller perivenøs ekstravasation, som kan føre til alvorlig lokal cellulitis,

vesikation og vævsnekrose. Direkte intravenøs injektion anbefales ikke på grund af

risikoen for ekstravasation, som kan forekomme selv om en passende blodmængde

aspireres i kanylen.

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4.3

Kontraindikationer

Overfølsomhed over for idarubicin eller over for et eller flere af hjælpestofferne anført i

pkt. 6.1

Overfølsomhed over for antracykliner eller antracenedioner

Alvorligt nedsat leverfunktion

Alvorligt nedsat nyrefunktion

Svær kardiomyopati

Nyligt myokardieinfarkt

Alvorlige arytmier

Vedvarende myelosuppression

Tidligere behandling med maksimale kumulative doser af idarubicin og/eller andre

antracykliner og antracenedioner (se pkt. 4.4)

Amning bør stoppes under behandling med dette lægemiddel (se pkt. 4.6).

4.4

Særlige advarsler og forsigtighedsregler vedrørende brugen

Generelt

Idarubicin bør kun anvendes, når behandlingen forestås af læger med særligt kendskab til

cytoksisk kemoterapi. Dette sikrer, at en hurtig og effektiv behandling af svære

komplikationer i forbindelse med disse lidelser og/eller behandling af dem (f.eks. blødning,

alvorlige infektioner) kan udføres.

Patienterne skal være kommet sig helt over akutte toksiske symptomer efter tidligere

cytostatikabehandling (f.eks. stomatitis, neutropeni, trombocytopeni og almene

infektioner), før behandling med idarubicin påbegyndes.

Hjertefunktion

Kardiotoksicitet er en kendt risiko ved antracyklinbehandling. Dette kan manifestere sig

som tidlige (dvs. akutte) eller sene (dvs. forsinkede) hændelser.

Tidlige (akutte) hændelser

Tidlig kardiotoksicitet forårsaget af idarubicin består hovedsagligt af sinustakykardi

og/eller EKG ændringer, såsom ikke specifik ST-T-segmentændring. Der er også

rapporteret takyarytmi, herunder ventrikulær ekstrasystoli og ventrikulær takykardi,

bradykardi og atrioventrikulært blok og grenblok. Disse hændelser forudsiger sædvanligvis

ikke efterfølgende udvikling af forsinket kardiotoksicitet. De er sjældent af klinisk

betydning og giver generelt ikke anledning til afbrydelse af behandlingen med idarubicin.

Sene (forsinkede) hændelser

Forsinket kardiotoksicitet udvikles sædvanligvis sent i behandlingsforløbet eller inden for

2-3 måneder efter afslutning af behandlingen. Der er også rapporteret om sene hændelser

adskillige måneder eller år efter afsluttet behandling. Forsinket kardiomyopati manifesterer

sig ved nedsat venstre ventrikels uddrivningsfraktion (LVEF) og/eller symptomer på

kronisk hjerteinsufficiens, såsom dyspnø, lungeødem, sænkningsødem, kardiomegali,

hepatomegali, oliguri, ascites, pleuraeffusion og galoprytme. Der er også rapporteret om

subakutte hændelser som perikardit/myokardit. Livstruende kronisk hjerteinsufficiens er

den mest alvorlige form for antracyklininduceret kardiomyopati og repræsenterer den

kumulative dosisbegrænsende toksicitet for lægemidlet.

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Der er ikke defineret en kumulativ dosisbegrænsning for idarubicin indgivet intravenøst.

Imidlertid er der set idarubicinrelateret kardiomyopati hos 5 % af de patienter, som blev

behandlet med kumulative intravenøse doser på 150 til 290 mg/m

. De tilgængelige data

for patienter, der er behandlet med kumulative doser på i alt op til 400 mg/m

idarubicin

peroralt antyder, at der er en lille mulighed for kardiotoksicitet.

Hjertefunktionen skal vurderes inden behandlingsstart med idarubicin og skal monitoreres

nøje under behandlingen for at minimere risikoen for alvorlig hjerteinsufficiens. Risikoen

kan reduceres ved regelmæssig overvågning af venstre ventrikels uddrivningsfraktion

(LVEF) under behandlingen, med hurtig afbrydelse af idarubicin ved det første tegn på

nedsat funktion. De mest specifikke metoder til gentagen vurdering af hjertefunktionen

(evaluering af LVEF) omfatter kardiescintigrafi eller ekkokardiografi. Det anbefales at

vurdere hjertefunktionen ved baseline ved hjælp af EKG og enten

kardiescintigrafi/myokardiescintigrafi eller ekkokardiografi, især hos patienter med

risikofaktorer for øget kardiotoksicitet.

Gentagne kardiescintigrafiske eller ekkokardiografiske bestemmelser af LVEF bør udføres,

især ved behandling med høje, kumulative antracyklindoser. Samme teknik til vurdering af

LVEF bør anvendes under hele opfølgningen.

Risikofaktorer for kardiotoksicitet omfatter aktiv eller latent kardiovaskulær sygdom,

tidligere eller samtidig mediastinal/perikardiel strålebehandling, tidligere behandling med

andre antracykliner eller antracenedioner samt samtidig brug af lægemidler med

hæmmende virkning på hjertekontraktiliteten eller kardiotoksiske lægemidler (f.eks.

trastuzumab). Antracykliner, herunder idarubicin, bør ikke administreres i kombination

med andre kardiotoksiske lægemidler, medmindre patientens hjertefunktion monitoreres

omhyggeligt (se pkt. 4.5). Patienter, som bliver behandlet med antracykliner efter afsluttet

behandling med andre kardiotoksiske lægemidler, især dem med lang halveringstid,

herunder trastuzumab, kan også have forøget risiko for udvikling af kardiotoksicitet.

Halveringstiden for trastuzumab er ca. 28-38 dage, og det kan forblive i kredsløbet i op til

27 uger. Antracyklinbaseret terapi bør derfor undgås i op til 24 uger efter ophør med

behandling med trastuzumab, hvis muligt. Det anbefales at monitorere hjertefunktionen

omhyggeligt, hvis antracykliner anvendes tidligere end 27 uger efter ophørt behandling

med trastuzumab.

Hjertefunktionen skal monitoreres omhyggeligt hos patienter, som får høje kumulative

doser og hos patienter med risikofaktorer. Kardiotoksicitet pga. idarubicin kan dog opstå

ved lavere kumulative doser med eller uden tilstedeværelse af risikofaktorer.

Hos spædbørn og børn kan der forekomme større modtagelighed for antracyklininduceret

kardiotoksicitet, og hjertefunktionen bør derfor vurderes over en længere periode.

Toksiciteten af idarubicin og andre antracykliner eller antracenedioner er sandsynligvis

additiv.

Hæmatologisk toksicitet

Idarubicin er en potent hæmmer af knoglemarven. Alle patienter, som får terapeutiske

doser af idarubicin, får alvorlig knoglemarvssuppression.

Før og under hver behandlingscyklus med idarubicin bør blodbilledet monitoreres,

herunder differentialtælling af hvide blodlegemer.

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Leukopeni og/eller granulocytopeni (neutropeni) er den mest dominerende manifestation af

idarubicins hæmatologiske toksicitet og er den mest almindelige akutte dosisbegrænsende

toksicitet ved dette lægemiddel.

Leukopeni og neutropeni er sædvanligvis alvorlig. Desuden kan der også ses

trombocytopeni og anæmi. Neutrofile celler og trombocytter når sædvanligvis nadir 10-14

dage efter lægemiddeladministration, men normaliseres i de fleste tilfælde i løbet af den

tredje uge. I fasen med alvorlig knoglemarvssuppression, er der rapporteret om dødsfald på

grund af infektioner og/eller hæmoragi.

De kliniske konsekvenser af alvorlig knoglemarvssuppression omfatter feber, infektioner,

sepsis/septikæmi, septisk chok, hæmoragi, vævshypoksi eller dødsfald. Hvis der opstår

febril neutropeni, anbefales det at behandle med IV-antibiotika.

Sekundær leukæmi

Sekundær leukæmi, med eller uden en præleukæmisk fase, er rapporteret hos patienter

behandlet med antracykliner, herunder idarubicin. Sekundær leukæmi er mere almindelig,

når sådanne lægemidler gives i kombination med DNA-ødelæggende antineoplastiske

midler, når patienterne er blevet kraftigt præmedicineret med cytostatika, eller ved

dosiseskalering af antracyklin. Disse typer leukæmi kan have en latenstid på 1-3 år.

Gastrointestinal påvirkning

Idarubicin er emetisk. Mucositis (hovedsagelig stomatitis, sjældnere øsofagit) forekommer

generelt tidligt efter administration af idarubicin og kan i alvorlige tilfælde udvikles til

ulceration af slimhinden i løbet af få dage. De fleste patienter oplever bedring i 3.

behandlingsuge.

Der er lejlighedsvis set episoder med alvorlige gastrointestinale bivirkninger (som

perforering eller blødning) hos patienter, der får oral idarubicin. Disse patienter havde akut

leukæmi eller har haft andre patologier i anamnesen eller har fået medicin, som er kendt

for at give gastrointestinale komplikationer. Hos patienter med aktiv gastrointestinal

sygdom, som har en øget risiko for blødning og/eller perforering, må lægen overveje

fordelen af behandling med oral idarubicin mod risikoen.

Lever og nyrefunktion

Da nedsat lever- og nyrefunktion kan påvirke dispositionen af idarubicin, bør lever- og

nyrefunktionen derfor evalueres med konventionelle kliniske laboratorieundersøgelser

(med serumbilirubin og serumcreatinin som indikatorer) før og under behandlingen. I en

række kliniske fase III-forsøg var behandling med idarubicin kontraindiceret, hvis bilirubin

og/eller serumkreatininniveauerne oversteg 2,0 mg/dl. For andre antracykliner anvendes

generelt en 50 % dosisreduktion, hvis bilirubinniveauerne er i et område mellem 1,2-2,0

mg/dl.

Reaktioner på injektionsstedet

Injektion i små blodkar eller tidligere injektioner i samme vene kan føre til flebosklerose.

Ved at følge den anbefalede administrationsprocedure kan risikoen for flebitis/tromboflebit

minimeres på injektionsstedet.

Ekstravasation

Ekstravasation af idarubicin ved intravenøs injektion kan forårsage lokal smerte, alvorlig

vævsbeskadigelse (blæredannelse, alvorlig cellulit) og nekrose. Ved tegn eller symptomer

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på ekstravasation under intravenøs administration af idarubicin skal lægemiddelinfusionen

omgående stoppes.

I tilfælde med ekstravastation kan dexrazoxan anvendes til at forhindre eller reducere

vævsbeskadigelse.

Tumorlysesyndrom

Idarubicin kan inducere hyperurikæmi pga. den omfattende purin-katabolisme som følge af

kraftigt henfald af neoplastiske celler (tumorlysesyndrom). Urinsyreindhold i blodet,

kalium, calcium, phosphat og kreatinin bør evalueres efter initialbehandling.

Tumorlysesyndrom kan minimeres ved væsketilførsel, alkalisering af urin og profylaktisk

behandling med allopurinol for at forhindre hyperurikæmi.

Immunosuppressive virkninger/øget modtagelighed for infektioner

Administration af levende eller levende svækkede vacciner (som gul feber) til patienter,

der er immunkompromitterede pga. kemoterapeutika, herunder idarubicin, kan medføre

alvorlige eller fatale infektioner. Patienter, der bliver behandlet med idarubicin, bør ikke

vaccineres med en levende vaccine. Uskadeliggjorte eller inaktiverede vacciner kan

anvendes, men patientens immunrespons på denne type vaccine kan dog være nedsat.

Det reproduktive system

Mænd, der er i behandling med idarubicinhydrochlorid, tilrådes at anvende sikker

antikonception under behandlingen. Hvis det er relevant og tilgængeligt, bør der søges

rådgivning om opbevaring af sæd på grund af irreversibel infertilitet forårsaget af

behandling (se pkt. 4.6).

Andet

Som ved andre cytostatika er der set enkelte tilfælde af tromboflebit og

tromboembolifænomen, herunder lungeemboli, ved brug af idarubicin.

Lægemidlet kan forårsage rødlig farvning af urinen i 1-2 dage efter indgift, og patienter

bør gøres opmærksomme på dette faktum.

4.5

Interaktion med andre lægemidler og andre former for interaktion

Idarubicin er en potent knoglemarvshæmmer, og kombinationsbehandling med andre

kemoterapeutika med tilsvarende virkning kan forvente at inducere additiv

knoglemarvshæmmende effekt (se pkt. 4.4). Samtidig behandling med idarubicin i

kombinationskemoterapi og andre potentielle kardiotoksiske stoffer, såvel som den

samtidige behandling med andre kardioaktive lægemidler (f.eks. calciumkanalblokkere)

kræver monitorering af hjertefunktionen under hele behandlingen.

Samtidig anvendelse af lægemidler, der ændrer nyre- eller leverfunktionen, kan påvirke

idarubicins metabolisme, farmakokinetik og terapeutisk effekt og/eller toksicitet (se pkt.

4.4).

Additiv myelosuppression kan forekomme, når strålebehandling samtidig gives med eller

inden for 2-3 uger før behandling med idarubicin.

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Samtidig brug frarådes

Levende, svækkede vacciner: Risiko for mulig fatal systematisk sygdom. Risikoen er

forhøjet hos personer, som allerede er immunsupprimerede af deres underliggende

sygdom.

En inaktiveret vaccine bør anvendes, hvis tilgængelig (polio).

Ved kombination af orale antikoagulantia og kemoterapi mod cancer kræves hyppigere

monitorering af INR (International Normalised Ratio), da risikoen for en interaktion ikke

kan udelukkes.

Ciclosporin A: Samtidig anvendelse af ciclosporin A som eneste kemosensibilisator øgede

markant idarubicin AUC (1,78 gange) og idarubicinol AUC (2,46 gange) hos patienter med

akut leukæmi. Den kliniske relevans for denne interaktion er ukendt.

En dosisjustering kan blive relevant hos nogle patienter.

4.6

Graviditet og amning

Fertilitet

Idarubicin kan forårsage kromosomskader i humane spermatozoer. Derfor bør mænd, som

er i behandling med idarubicin, anvende sikker kontraception i op til 3 måneder efter endt

behandling (se pkt. 4.4).

Graviditet

Idarubicins embryotoksiske potentiale er påvist i både in vitro- og in vivo-undersøgelser.

Der er dog ikke nogen tilstrækkelige eller velkontrollerede undersøgelser af gravide

kvinder. Kvinder i den fertile alder bør rådgives om ikke at blive gravide under

behandlingen og bør anvende sikker kontraception under behandlingen. Idarubicin bør kun

anvendes under graviditet, hvis den potentielle fordel for moderen opvejer den potentielle

risiko for fostret. Patienten skal underrettes om den potentielle risiko for fostret. Hvis det er

hensigtsmæssigt og tilgængeligt, bør patienter, der ønsker at få børn efter behandlingens

afslutning, modtage genetisk rådgivning først.

Amning

Det vides ikke, om idarubicin eller dets metabolitter udskilles i modermælk. Mødre bør

ikke amme under behandling med idarubicinhydrochlorid.

4.7

Virkninger på evnen til at føre motorkøretøj eller betjene maskiner

Ikke mærkning.

Virkningen af idarubicin på evnen til at føre motorkøretøj eller betjene maskiner er ikke

blevet systematisk evalueret.

4.8

Bivirkninger

Liste over bivirkninger

Bivirkningerne er opdelt efter følgende hyppigheder: Meget almindelig (≥ 1/10),

almindelig (≥ 1/100 til < 1/10), ikke almindelig (≥ 1/1.000 til < 1/100), sjælden (≥ 1/10.000

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til < 1/1.000), meget sjælden (< 1/10.000), ikke kendte (kan ikke estimeres ud fra

forhåndenværende data).

Infektioner og parasitære sygdomme

Meget almindelig: Infektioner

Ikke almindelig: Sepsis, septikæmi

Benigne, maligne og uspecificerede tumorer (inkl. cyster og polypper)

Ikke almindelig: Sekundære leukæmier (akut myeloid leukæmi og myelodysplastisk

syndrom)

Blod og lymfesystem

Meget almindelig: Anæmi, svær leukopeni og neutropeni, trombocytopeni

Ikke kendte: Pancytopeni

Immunsystemet

Meget sjælden: Anafylaksi

Det endokrine system

Meget almindelig: Anoreksi

Ikke almindelig: Dehydrering

Metabolisme og ernæring

Ikke almindelig: Hyperurikæmi

Ikke kendte: Tumorlysesyndrom

Nervesystemet

Sjælden: Cerebral blødning

Hjerte

Almindelig: Bradykardi, sinus takykardi, takyarytmi, asymptomatiske reduktioner i venstre

ventrikels uddrivningsfraktion, kongestivt hjertesvigt, kardiomyopati (se pkt. 4.4 i forhold

til associerede tegn og symptomer)

Ikke almindelig: EKG-abnormaliteter (f.eks. ikke-specifikke ST-segmentforandringer),

myokardieinfarkt

Meget sjælden: Pericarditis, myokarditis, atrioventrikulær blok og grenblok

Vaskulære sygdomme

Almindelig: Blødninger, lokal flebitis, tromboflebitis

Ikke almindelig: Shock

Meget sjælden: Tromboembolis, rødme

Mave-tarm-kanalen

Meget almindelig: Kvalme, opkastning, mukosit/stomatitis, diarré, mavesmerter eller

brændende fornemmelse

Almindelig: Gastrointestinal blødning, mavesmerter

Ikke almindelig: Øsofagitis, colitis (inklusive svær enterocolitis/neutropenisk enterocolitis

med perforation)

Meget sjælden: Gastriske erosioner eller sår

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Lever og galdeveje

Almindelig: Stigning i leverenzymer og bilirubin

Hud og subkutane væv

Meget almindelig: Alopeci

Almindelig: Hududslæt, kløe, overfølsomhed af strålebehandlet hud (”radiation recall

reaction”)

Ikke almindelig: Hyperpigmentering af hud og negle, urticaria, cellulitis (muligvis

alvorlig), vævsnekrose

Meget sjælden: Akral erytem

Ikke kendte: Lokal reaktion

Nyrer og urinveje

Meget almindelig: Rødfarvning af urin i 1-2 dage efter behandling

Almene symptomer og reaktioner på administrationsstedet

Meget almindelig: Feber, hovedpine, kulderystelser

Beskrivelse af udvalgte bivirkninger

Hæmatopoietisk system

Den mest udtalte bivirkning ved behandling med idarubicin er udtalt

knoglemarvsdepression. Dette er dog nødvendigt for eradikation af leukæmiske celler (se

pkt. 4.4).

Kardiotoksicitet

Livstruende hjertesvigt er den alvorligste form for antracyklininduceret kardiomyopati og

repræsenterer den kumulative dosisbegrænsende lægemiddeltoksicitet (se pkt. 4.4).

Mave-tarm-kanalen

Stomatitis og i alvorlige tilfælde ulcerationer af slimhinden, dehydrering forårsaget af svær

opkastning og diarré; risiko for perforering af kolon osv.

Reaktioner på administrationsstedet

Phlebitis/trombophlebitis og forebyggende forholdsregler diskuteret i pkt. 4.2 i

produktresuméet; utilsigtet paravenøs infiltration kan forårsage smerte, svær cellulitis og

vævsnekrose.

Andre bivirkninger

Hyperurikæmi

Forebyggelse af symptomer ved hydrering, alkalinisering af urinen og profylakse med

allupurinol kan minimere de potentielle komplikationer forbundet med tumorlysesyndrom.

Pædiatrisk population

Bivirkninger er ens hos voksne og børn undtagen en større modtagelighed for antracyklin-

induceret kardiotoksicitet hos børn (se pkt. 4.4).

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Indberetning af formodede bivirkninger

Når lægemidlet er godkendt, er indberetning af formodede bivirkninger vigtig. Det

muliggør løbende overvågning af benefit/risk-forholdet for lægemidlet. Læger og

sundhedspersonale anmodes om at indberette alle formodede bivirkninger via:

Lægemiddelstyrelsen

Axel Heides Gade 1

DK-2300 København S

Websted: www.meldenbivirkning.dk

E-mail: dkma@dkma.dk

4.9

Overdosering

Meget høje doser idarubicin kan forventes at forårsage akut myokardietoksicitet inden for

24 timer og alvorlig myelosuppression i løbet af 1-2 uger. Der er med antracykliner set

forsinket hjertesvigt i op til flere måneder efter overdosis.

Patienter, som behandles oralt med idarubicin, bør observeres for mulig gastrointestinal

blødning og alvorlig beskadigelse af gastrointestinalkanalen.

4.10

Udlevering

5.

FARMAKOLOGISKE EGENSKABER

5.0

Terapeutisk klassifikation

ATC-kode: L 01 DB 06. Cytotoksiske antibiotika. Anthracycliner og beslægtede stoffer.

5.1

Farmakodynamiske egenskaber

Idarubicin er et DNA-interkalerende antracyklin, der interagerer med enzymet

topoisomerase II og har en hæmmende effekt på nukleinsyresyntesen. Modifikationen af

position 4 af antracyklinstrukturen giver stoffet en høj lipofilicitet, som resulterer i en

forøget frekvens af cellulær optagelse sammenlignet med doxorubicin og daunorubicin.

Idarubicin har vist sig at have en højere styrke mht. daunorubicin og til at være et effektivt

stof mod murin leukæmivirus og lymfomer, både ved intravenøs administration og ved oral

indtagelse. In vitro-studier af humane og murine antracyklinresistente celler har vist en

lavere grad af krydsresistens over for idarubicin sammenlignet med doxorubicin og

daunorubicin. Kardiotoksicitetsstudier hos dyr har indikeret, at idarubicin har et bedre

terapeutisk indeks end daunorubicin og doxorubicin. Hovedmetabolitten, idarubicinol, har i

in vitro- og in vivo-studier vist antitumoral aktivitet i eksperimentelle modeller. Hos rotten

er idarubicinol, når administreret i samme doser som det oprindelige lægemiddel, tydeligt

mindre cardiotoksisk end idarubicin.

5.2

Farmakokinetiske egenskaber

Efter oral administration af 10 til 60 mg/m

idarubicin til voksne blev idarubicin hurtigt

absorberet med de maksimale plasmakoncentrationer på 4-12,65 ng/ml opnået på 1 til 4

timer efter dosering. Den terminale halveringstid var 12,7 ± 6,0 timer (gennemsnit ± SD).

Efter intravenøs administration af idarubicin til voksne var den terminale halveringstid

13,9 ± 5,9 timer, svarende til den der blev observeret efter oral administration.

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Efter i.v.-administration metaboliseres idarubicin i stor udstrækning til den aktive

metabolit, idarubicinol, som elimineres langsomt med en plasmahalveringstid på 41-69

timer. Lægemidlet udskilles gennem nyrerne og med galden, hovedsagelig som

idarubicinol.

Studier af cellulære (kerneholdige celler og blodceller i knoglemarven)

lægemiddelkoncentrationer hos patienter med leukæmi har vist, at maksimale cellulære

idarubicinkoncentrationer nås få minutter efter injektion.

Idarubicin- og idarubicinolkoncentrationer i kerneholdige celler og blodceller i

knoglemarven er mere end hundrede gange så høje som plasmakoncentrationerne.

Idarubicins eliminationshastighed i plasma og celler var næsten sammenlignelig med den

terminale halveringstid på ca. 15 timer. Idarubicinols terminale halveringstid i celler var

ca. 72 timer.

Pædiatrisk population

Farmakokinetiske målinger hos 7 pædiatriske patienter, der blev behandlet med intravenøs

idarubicin i doser på 15-40 mg/m

i 3 dage, viste en median halveringstid på 8,5 timer

(interval: 3,6-26,4 timer) for idarubicin. Den aktive metabolit idarubicinol blev

akkumuleret under de 3 dages behandling og udviste en median halveringstid på 43,7 timer

(interval: 27,8 -131 timer).

I et andet studie, hvor 15 pædiatriske patienter blev behandlet med oral idarubicin i doser

på 30-50 mg/m

i 3 dage, var idarubicins maksimale plasmakoncentration 10,6 ng/ml

(interval: 2,7-16,7 ng/ml ved en dosis på 40 mg/m

). Median halveringstid af idarubicin var

9,2 timer (interval: 6,4-25,5 timer).

Der sås signifikant akkumulering af idarubicinol i 3-dages behandlingsperioden. Den

observerede halveringstid for idarubicin, efter i.v. administration hos pædiatriske patienter,

svarer til den for oral administration hos pædiatriske patienter.

Da idarubicin C

efter oral administration er den samme hos børn og voksne, tyder det

på, at der ikke er forskel på absorptionskinetik hos børn og voksne.

Efter både oral og intravenøs administration er idarubicins halveringstid forskellig hos

børn og voksne:

Totalclearance på 30-107,9 l/time/m

hos voksne er højere end totalclearance på

18-33 l/time/m

hos den pædiatriske population. Selvom idarubicin har et meget stort

fordelingsvolumen hos både voksne og børn, som tyder på stor vævsbinding, kan den

kortere halveringstid og lavere totalclearance ikke udelukkende forklares ved det

tilsyneladende mindre distributionsvolumen hos børn sammenlignet med voksne.

5.3

Prækliniske sikkerhedsdata

LD50 (middelværdier) af intravenøs idarubicin var 4,4 mg/kg hos mus, 2,9 mg/kg hos

rotter og ca. 1,0 mg/kg hos hunde. Efter en enkelt intravenøs administration var det

væsentlige målorgan blod- og lymfesystemet og i hundenes tilfælde også det

gastrointestinale system. De toksiske effekter hos rotter og hunde er blevet undersøgt efter

gentagen intravenøs administration af idarubicin. Målorganerne for intravenøs idarubicin

hos de ovennævnte dyrearter var blod- og lymfesystem, mavetarmkanalen, nyrer, lever og

kvindelige og mandlige kønsorganer.

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Side 11 af 13

I relation til hjertet, viser kardiotoksicitets- og subakutte undersøgelser, at intravenøs

idarubicin kun var mildt til moderat kardiotoksisk i dødelige doser, hvorimod doxorubicin

og daunorubicin forårsager udpræget myokardiel svækkelse selv i ikke-dødelige doser.

Idarubicin var genotoksisk i de fleste af in vitro eller in vivo undersøgelserne. Intravenøs

idarubicin var toksisk for de reproduktive organer og embryotoksisk og teratogent hos

rotter. Der blev ikke påvist nogen bemærkelsesværdige effekter hos hverken mødre eller

afkom af rotter, der blev tildelt doser på op til 0,2 mg/kg/dag i de perinatale og postnatale

perioder. Det vides ikke, om stoffet udskilles i human modermælk. Ligesom med andre

antracykliner og cytostatika er intravenøs idarubicin kræftfremkaldende hos rotter. I et

tolerancestudie hos hunde blev hudnekrose som følge af ekstravasation observeret.

6.

FARMACEUTISKE OPLYSNINGER

6.1

Hjælpestoffer

Glycerol

Saltsyre, koncentreret

Natriumhydroxid (til justering af pH)

Vand til injektionsvæsker

6.2

Uforligeligheder

Idarubicin må ikke have længere tids kontakt med en alkalisk opløsning, da dette kan

medføre nedbrydning af lægemidlet. Idarubicinhydrochlorid må ikke blandes med heparin,

da dette kan medføre udfældning. Dette lægemiddel må ikke blandes med andre

lægemidler end dem, der er anført under pkt. 6.6.

6.3

Opbevaringstid

2 år.

Efter åbning skal indholdet anvendes med det samme.

6.4

Særlige opbevaringsforhold

Opbevares i køleskab (2 °C - 8 °C).

Opbevares i den originale emballage for at beskytte mod lys.

6.5

Emballagetyper og pakningsstørrelser

Farveløst type I hætteglas med chlorobutylgummiprop, forseglet med en aluminiumshætte

med en orange flip-off hætte i plastik.

Pakningsstørrelser

1 hætteglas med 5 ml injektionsvæske, opløsning.

1 hætteglas med 10 ml injektionsvæske, opløsning.

1 hætteglas med 20 ml injektionsvæske, opløsning.

Ikke alle pakningsstørrelser er nødvendigvis markedsført.

6.6

Regler for destruktion og anden håndtering

Idarubicinhydrochlorid "Accord" opløsning må kun indgives intravenøst via en

infusionsslange med en fritløbende intravenøs infusion af 0,9 % natriumchlorid over en

periode på 5 til 10 minutter.

57742_spc.docx

Side 12 af 13

Denne fremgangsmåde mindsker risikoen for tromboflebitis og perivenøs ekstravasation,

som kan føre til alvorlig lokal cellulitis og nekrose. Phlebosclerosis kan skyldes injektion i

små vener eller gentagne injektioner i samme vene.

De følgende forsigtighedsregler er fastlagt pga. det aktive stofs toksicitet.

Lægemidlet må kun håndteres af personer, som er trænet i håndtering af cytostatika.

Gravide kvinder skal udelukkes fra at arbejde med dette lægemiddel.

Personer, der håndterer dette lægemiddel, skal bære beskyttende beklædning: briller,

overtrækstøj, engangshandsker og -masker.

Der skal etableres et arbejdsområde med en overflade, der er beskyttet med

absorberende papir, der er plastbelagt på den ene side

Alle genstande, der anvendes til administration eller rengøring, inklusive handsker, skal

lægges i en særlig beholder til højrisikoaffald beregnet til forbrænding ved høje

temperaturer.

Spild eller lækage behandles med 1 % natriumhypokloritopløsning, og derefter med vand.

Artikler brugt til rengøring skal bortskaffes som angivet ovenfor.

Utilsigtet kontakt med øjne og hud skal behandles straks med skylning med rigeligt vand,

sæbe og vand eller natriumbikarbonatopløsning. Det kan være nødvendigt at søge

lægehjælp. Al ubrugt opløsning skal bortskaffes.

Ikke anvendt lægemiddel samt affald heraf og alle de materialer, der blev anvendt til

rekonstituering, fortynding og administration, skal bortskaffes i henhold til hospitalets

procedure for cytotoksiske stoffer og i henhold til lokale retningslinjer for farligt affald.

7.

INDEHAVER AF MARKEDSFØRINGSTILLADELSEN

Accord Healthcare Limited

Sage House, 319 Pinner Road

North Harrow, Middlesex HA1 4HF

Storbritannien

8.

MARKEDSFØRINGSTILLADELSESNUMMER (NUMRE)

5 mg/5 ml:

57740

10 mg/10 ml:

57741

20 mg/20 ml:

57742

9.

DATO FOR FØRSTE MARKEDSFØRINGSTILLADELSE

11. januar 2017

10.

DATO FOR ÆNDRING AF TEKSTEN

57742_spc.docx

Side 13 af 13

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Review of the existing maximum residue levels for fluquinconazole according to Article 12 of Regulation (EC) No 396/2005

Review of the existing maximum residue levels for fluquinconazole according to Article 12 of Regulation (EC) No 396/2005

Published on: Wed, 12 Sep 2018 00:00:00 +0200 According to Article 12 of Regulation (EC) No 396/2005, EFSA has reviewed the maximum residue levels (MRLs) currently established at European level for the pesticide active substance fluquinconazole. Considering the information provided by Member States, neither EU uses nor import tolerances are currently authorised for fluquinconazole within the European Union. Furthermore, no MRLs are established by the Codex Alimentarius Commission (codex maximum residue ...

Europe - EFSA - European Food Safety Authority Publications

11-9-2018

Risk assessment of substances used in food supplements: the example of the botanical Gymnema sylvestre

Risk assessment of substances used in food supplements: the example of the botanical Gymnema sylvestre

Published on: Tue, 28 Aug 2018 00:00:00 +0200 Botanicals and preparations derived from these are among the substances frequently added to foods and food supplements, yet the safety of many botanicals has not been systematically assessed. In the context of the EU‐FORA fellowship programme, the fellow performed an assessment on the safety of the botanical Gymnema sylvestre, in accordance with EFSA's guidance on the assessment of safety of botanicals. Although preparations of G. sylvestre are marketed as f...

Europe - EFSA - European Food Safety Authority Publications

11-9-2018

Modelling of inactivation through heating for quantitative microbiological risk assessment (QMRA)

Modelling of inactivation through heating for quantitative microbiological risk assessment (QMRA)

Published on: Mon, 27 Aug 2018 00:00:00 +0200 EFSA regards the household as a stage in the food chain that is important for the final number of food‐borne infections. The fate of a pathogen in the private kitchen largely depends on consumer hygiene during preparation of food and on its proper cooking, especially in the case of meat. Unfortunately, detailed information on the microbiological survival in meat products after heating in the consumer kitchen is lacking. The aim of the study was to improve th...

Europe - EFSA - European Food Safety Authority Publications

11-9-2018

Assessment of occupational and dietary exposure to pesticide residues

Assessment of occupational and dietary exposure to pesticide residues

Published on: Mon, 27 Aug 2018 00:00:00 +0200 Plant protection products (PPPs) are pesticides containing at least one active substance that drives specific actions against pests (diseases). PPPs are regulated in the EU and cannot be placed on the market or used without prior authorisation. EFSA assesses the possible risks of the use of active substances to humans and environment. Member States decide whether or not to approve their use at EU level. Furthermore, Member States decide at national level on ...

Europe - EFSA - European Food Safety Authority Publications

4-9-2018

Outcome of the consultation with Member States and EFSA on the basic substance application for milk for use in plant protection as fungicide

Outcome of the consultation with Member States and EFSA on the basic substance application for milk for use in plant protection as fungicide

Published on: Mon, 03 Sep 2018 00:00:00 +0200 The European Food Safety Authority (EFSA) was asked by the European Commission to provide scientific assistance with respect to the evaluation of applications received by the European Commission concerning basic substances. In this context, EFSA's scientific views on the specific points raised during the commenting phase conducted with Member States and EFSA on the basic substance application for milk are presented. The context of the evaluation was that req...

Europe - EFSA - European Food Safety Authority Publications

1-9-2018

Multiple “Dr. King’s” homeopathic and “Natural Pet” veterinary products recalled due to potential microbial contamination

Multiple “Dr. King’s” homeopathic and “Natural Pet” veterinary products recalled due to potential microbial contamination

Health Canada is advising consumers and pet owners not to use homeopathic and veterinary products made by King Bio Inc. and labeled as "Dr. King's," "Dr King's Natural Pet" or "Natural Pet." These products may pose a health risk to people and pets, especially children, pregnant women and those with compromised immune systems, because of potential microbial contamination. According to the United States Food and Drug Administration, high levels of microbial contamination were identified at the manufacturin...

Health Canada

1-9-2018

Acknowledgement:EFSA  wishes  to  thank  the  rapporteur  Member  State  Denmark  for  thepreparatory work on this scientific output.Suggested citation:EFSA (European Food Safety Authority), Brancato A, Brocca D, Carrasco Cabrera L,De Lentdecker C, Erdos

Acknowledgement:EFSA wishes to thank the rapporteur Member State Denmark for thepreparatory work on this scientific output.Suggested citation:EFSA (European Food Safety Authority), Brancato A, Brocca D, Carrasco Cabrera L,De Lentdecker C, Erdos

Published on: Fri, 31 Aug 2018 00:00:00 +0200 According to Article 12 of Regulation (EC) No 396/2005, EFSA has reviewed the maximum residue levels (MRLs) currently established at European level for the pesticide active substance napropamide. To assess the occurrence of napropamide residues in plants, processed commodities, rotational crops and livestock, EFSA considered the conclusions derived in the framework of Directive 91/414/EEC as well as the European authorisations reported by Member States (incl...

Europe - EFSA - European Food Safety Authority Publications

1-9-2018

Review of the existing MRLs for fenbuconazole

Review of the existing MRLs for fenbuconazole

Published on: Fri, 31 Aug 2018 00:00:00 +0200 According to Article 12 of Regulation (EC) No 396/2005, EFSA has reviewed the maximum residue levels (MRLs) currently established at European level for the pesticide active substance fenbuconazole. To assess the occurrence of fenbuconazole residues in plants, processed commodities, rotational crops and livestock, EFSA considered the conclusions derived in the framework of Directive 91/414/EEC, the MRLs established by the Codex Alimentarius Commission as well...

Europe - EFSA - European Food Safety Authority Publications

30-8-2018

National summary reports on pesticide residue analysis performed in 2016

National summary reports on pesticide residue analysis performed in 2016

Published on: Tue, 07 Aug 2018 00:00:00 +0200 In accordance with Article 31 of Regulation (EC) No 396/2005, European Union (EU) Member States have to communicate to the European Food Safety Authority (EFSA) the results of their official controls on pesticide residues in food. In the framework of this communication, the EU Member States, Iceland and Norway provided a short summary report outlining the main findings of the control activities during the reference year. This technical report is the compilat...

Europe - EFSA - European Food Safety Authority Publications

29-8-2018

Review of the existing maximum residue levels for sintofen according to Article 12 of Regulation (EC) No 396/2005

Review of the existing maximum residue levels for sintofen according to Article 12 of Regulation (EC) No 396/2005

Published on: Tue, 28 Aug 2018 00:00:00 +0200 According to Article 12 of Regulation (EC) No 396/2005, EFSA has reviewed the maximum residue levels (MRLs) currently established at European level for the pesticide active substance sintofen. To assess the occurrence of sintofen residues in plants, processed commodities, rotational crops and livestock, EFSA considered the conclusions derived in the framework of Commission Regulation (EC) No 33/2008, as well as the European authorisations reported by Member ...

Europe - EFSA - European Food Safety Authority Publications

29-8-2018

Review of the existing maximum residue levels for prochloraz according to Article 12 of Regulation (EC) No 396/2005

Review of the existing maximum residue levels for prochloraz according to Article 12 of Regulation (EC) No 396/2005

Published on: Mon, 27 Aug 2018 00:00:00 +0200 According to Article 12 of Regulation (EC) No 396/2005, EFSA has reviewed the maximum residue levels (MRLs) currently established at European level for the pesticide active substance prochloraz. To assess the occurrence of prochloraz residues in plants, processed commodities, rotational crops and livestock, EFSA considered the conclusions derived in the framework of Directive 91/414/EEC, the MRLs established by the Codex Alimentarius Commission as well as th...

Europe - EFSA - European Food Safety Authority Publications

29-8-2018

Modification of the existing maximum residue levels for prohexadione in various oilseeds

Modification of the existing maximum residue levels for prohexadione in various oilseeds

Published on: Mon, 27 Aug 2018 00:00:00 +0200 In accordance with Article 6 of Regulation (EC) No 396/2005, the applicant BASF SE submitted a request to the competent national authority in France to modify the existing maximum residue levels (MRL) for the active substance prohexadione in linseeds, poppy seeds, sunflower seeds, rape seeds, mustard seeds and gold of pleasure seeds. The data submitted in support of the request were found to be sufficient to derive MRL proposals for all oilseeds under consid...

Europe - EFSA - European Food Safety Authority Publications

29-8-2018

Review of the existing maximum residue levels for napropamide according to Article 12 of Regulation (EC) No 396/2005

Review of the existing maximum residue levels for napropamide according to Article 12 of Regulation (EC) No 396/2005

Published on: Fri, 24 Aug 2018 00:00:00 +0200 According to Article 12 of Regulation (EC) No 396/2005, EFSA has reviewed the maximum residue levels (MRLs) currently established at European level for the pesticide active substance napropamide. To assess the occurrence of napropamide residues in plants, processed commodities, rotational crops and livestock, EFSA considered the conclusions derived in the framework of Directive 91/414/EEC as well as the European authorisations reported by Member States (incl...

Europe - EFSA - European Food Safety Authority Publications

29-8-2018

Explanatory note on the determination of newly expressed protein levels in the context of genetically modified plant applications for EU market authorisation

Explanatory note on the determination of newly expressed protein levels in the context of genetically modified plant applications for EU market authorisation

Published on: Mon, 20 Aug 2018 00:00:00 +0200 Genetically modified organisms are subject to a risk assessment and regulatory approval before entering the European market. According to legislation (Directive 2001/18/EC, Regulation (EC) No 1829/2003 and Regulation (EU) No 503/2013) and the EFSA guidance documents on the risk assessment of food and feed from genetically modified (GM) plants and on the environmental risk assessment of GM plants, applicants need to perform a molecular characterisation of any...

Europe - EFSA - European Food Safety Authority Publications

29-8-2018

Setting of import tolerances for mandestrobin in strawberries and table and wine grapes

Setting of import tolerances for mandestrobin in strawberries and table and wine grapes

Published on: Thu, 16 Aug 2018 00:00:00 +0200 In accordance with Article 6 of Regulation (EC) No 396/2005, the applicant Sumitomo Chemical Agro Europe SAS submitted a request to the competent national authority in Austria to set an import tolerance for the active substance mandestrobin in strawberries, table grapes and wine grapes. The data submitted in support of the request were found to be sufficient to derive maximum residue level (MRL) proposals for the crops under consideration. Adequate analytica...

Europe - EFSA - European Food Safety Authority Publications

29-8-2018

Modification of the existing maximum residue levels for fluoxastrobin in oilseeds

Modification of the existing maximum residue levels for fluoxastrobin in oilseeds

Published on: Mon, 13 Aug 2018 00:00:00 +0200 In accordance with Article 6 of Regulation (EC) No 396/2005, the applicant Arysta LifeSciences SAS submitted a request to the competent national authority in the United Kingdom to modify the existing maximum residue levels (MRL) for the active substance fluoxastrobin in certain oilseeds. The data submitted in support of the request were found to be sufficient to derive MRL proposals for the oilseeds for which a modification was requested. Adequate analytical...

Europe - EFSA - European Food Safety Authority Publications

29-8-2018

Review of the existing maximum residue levels for myclobutanil according to Article 12 of Regulation (EC) No 396/2005

Review of the existing maximum residue levels for myclobutanil according to Article 12 of Regulation (EC) No 396/2005

Published on: Mon, 13 Aug 2018 00:00:00 +0200 According to Article 12 of Regulation (EC) No 396/2005, EFSA has reviewed the maximum residue levels (MRLs) currently established at European level for the pesticide active substance myclobutanil. To assess the occurrence of myclobutanil residues in plants, processed commodities, rotational crops and livestock, EFSA considered the conclusions derived in the framework of Commission Regulation (EC) No 33/2008, the MRLs established by the Codex Alimentarius Com...

Europe - EFSA - European Food Safety Authority Publications

29-8-2018

Evaluation of data concerning the necessity of bromoxynil as herbicide to control a serious danger to plant health which cannot be contained by other available means, including non‐chemical methods

Evaluation of data concerning the necessity of bromoxynil as herbicide to control a serious danger to plant health which cannot be contained by other available means, including non‐chemical methods

Published on: Mon, 13 Aug 2018 00:00:00 +0200 EFSA was requested by the European Commission to provide scientific assistance under Article 31 of Regulation (EC) No 178/2002 regarding the evaluation of data concerning the necessity of bromoxynil as a herbicide to control a serious danger to plant health which cannot be contained by other available means including non‐chemical methods, in accordance with Article 4(7) of Regulation (EC) No 1107/2009. In this context, EFSA organised a commenting phase with ...

Europe - EFSA - European Food Safety Authority Publications

29-8-2018

Grant agreement for piloting the Framework Partnership Agreement between the National data provider organisations in Slovakia and EFSA – Final report

Grant agreement for piloting the Framework Partnership Agreement between the National data provider organisations in Slovakia and EFSA – Final report

Published on: Tue, 07 Aug 2018 00:00:00 +0200 Presented document is the final report of the project GA/EFSA/DATA/2017/01: “Strategic Partnership with Slovakia on Data Quality (Pilot project)”. The report describes national processes and tools in order to implement internal validation and quality control of collected data according to EFSA requirements. A description of the data transmission processes from the National Databases to the EFSA databases, terminology, data mapping and data transformations fo...

Europe - EFSA - European Food Safety Authority Publications

28-8-2018

Accord Healthcare Inc. Issues Voluntary Nationwide Recall of Hydrochlorothiazide Tablets USP 12.5 Mg Due to Labeling Mix-up

Accord Healthcare Inc. Issues Voluntary Nationwide Recall of Hydrochlorothiazide Tablets USP 12.5 Mg Due to Labeling Mix-up

A 100 count bottle of Hydrochlorothiazide Tablets USP 12.5 mg has been found to contain 100 Spironolactone Tablets USP 25 mg. Since the individual lot, PW05264, of the product is involved in a potential mix-up of labeling, Accord is recalling this individual lot from the market.

FDA - U.S. Food and Drug Administration

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

25-9-2018

Pelgraz (Accord Healthcare Limited)

Pelgraz (Accord Healthcare Limited)

Pelgraz (Active substance: pegfilgrastim) - Centralised - Authorisation - Commission Decision (2018)6288 of Tue, 25 Sep 2018 European Medicines Agency (EMA) procedure number: EMEA/H/C/003961/0000

Europe -DG Health and Food Safety

24-9-2018

Lenalidomide Accord (Accord Healthcare Limited)

Lenalidomide Accord (Accord Healthcare Limited)

Lenalidomide Accord (Active substance: lenalidomide) - Centralised - Authorisation - Commission Decision (2018)6237 of Mon, 24 Sep 2018 European Medicines Agency (EMA) procedure number: EMEA/H/C/4857

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

7-8-2018

Accofil (Accord Healthcare Limited)

Accofil (Accord Healthcare Limited)

Accofil (Active substance: Filgrastim) - Centralised - Yearly update - Commission Decision (2018)5428 of Tue, 07 Aug 2018

Europe -DG Health and Food Safety

7-8-2018

Memantine Accord (Accord Healthcare Limited)

Memantine Accord (Accord Healthcare Limited)

Memantine Accord (Active substance: memantine) - Centralised - Renewal - Commission Decision (2018)5421 of Tue, 07 Aug 2018 European Medicines Agency (EMA) procedure number: EMEA/H/C/2766/R/10

Europe -DG Health and Food Safety

6-8-2018

Zoledronic acid Accord (Accord Healthcare Limited)

Zoledronic acid Accord (Accord Healthcare Limited)

Zoledronic acid Accord (Active substance: zoledronic acid) - Centralised - Yearly update - Commission Decision (2018)5386 of Mon, 06 Aug 2018

Europe -DG Health and Food Safety