natgillin/translations-raw huggingface dataset:
Der er påvist kemisk og fysisk stabilitet i 7 dage ved stuetemperatur og på køl (2-8 °C) i et koncentrationsområde på 0,15-0,83 mg/ml efter fortynding med natriumchlorid 9 mg/ml (0,9 %). 
Chemical and physical in-use stability has been demonstrated for seven days at room temperature and under refrigeration (2°C - 8°C) at a concentration range of 0.15 mg/ml to 0.83 mg/ml after dilution with sodium chloride 9 mg/ml (0.9%).
*ITT = intention to treat **Patienter, der var i live og i remission på tidspunktet for sidste opfølgning, indgik på dette tidspunkt i analysen. 
**Patients alive and in remission at the time of last follow up were censored at that time point for the analysis.
Der er indberettet alvorlige hepatotoksiske hændelser i et fase 1/2-kombinationsstudie med anvendelse af clofarabin til pædiatriske patienter med recidiveret eller refraktær akut leukæmi. 
Severe hepatotoxic events have been reported in a Phase 1/2 combination study of clofarabine in paediatric patients with relapsed or refractory acute leukaemia.
Clofarabin er en purin-nukleosid-antimetabolit. 
Clofarabine is a purine nucleoside anti-metabolite.
Patienterne skal informeres om at søge læge, hvis de får symptomer på svimmelhed, besvimelsesanfald eller nedsat urinproduktion. 
Patients should be instructed to seek medical advice if they experience symptoms of dizziness, fainting spells, or decreased urine output.
Endvidere besidder clofarabin større modstandsevne over for cellulær nedbrydning af adenosindeaminase og mindre modtagelighed for phosphorolytisk spaltning end andre aktive stoffer i denne klasse, mens clofarabintriphosphats affinitet til DNA-polymerase α og ribonukleotidreduktase svarer til eller overstiger affiniteten til deoxyadenosintriphosphat. 
In addition, clofarabine possesses greater resistance to cellular degradation by adenosine deaminase and decreased susceptibility to phosphorolytic cleavage than other active substances in its class whilst the affinity of clofarabine triphosphate for DNA polymerase α and ribonucleotide reductase is similar to or greater than that of deoxyadenosine triphosphate.
Fortæl din læge, hvis et af disse punkter passer på dig. 
Tell your doctor if any of these conditions apply to you.
Ivozall er et potent antineoplastisk middel, som kan have betydelige hæmatologiske og ikkehæmatologiske bivirkninger (se pkt. 
Ivozall is a potent antineoplastic agent with potentially significant haematological and non-haematological adverse reactions (see section 4.8).
Da clofarabin imidlertid ikke metaboliseres af cytochrom P450- (CYP-) enzymsystemet, er de renale eliminationsprocesser aktuelt ikke afdækket. 
However, as clofarabine is not detectably metabolised by the cytochrome P450 (CYP) enzyme system, pathways of non-renal elimination currently remain unknown.
Clofarabin metaboliseres ikke i påviselig grad via cytochrom P450-(CYP)-enzymsystemet. 
Clofarabine is not detectably metabolised by the cytochrome P450 (CYP) enzyme system.
Blødningshændelser er blevet observeret i forbindelse med trombocytopeni. 
Bleeding events have been observed in the setting of thrombocytopaenia.
Patienter, der tidligere har fået et hæmatopoietisk stamcelletransplantat (HSCT), kan have øget risiko for hepatotoksicitet, der tyder på veneokklusion (VOD), efter behandling med clofarabin (40 mg/m2), når det anvendes sammen med etoposid (100 mg/m2) og cyclophosphamid (440 mg/m2). 
Patients who have previously received a hematopoietic stem cell transplant (HSCT) may be at higher risk for hepatotoxicity suggestive of veno-occlusive disease (VOD) following treatment with clofarabine (40 mg/m2) when used in combination with etoposide (100 mg/m2) and cyclophosphamide (440 mg/m2).
Intravenøs infusion af clofarabin 52 mg/m2 gav samme eksponering inden for et stort vægtområde. 
Intravenous infusion of 52 mg/m2 clofarabine produced equivalent exposure across a wide range of weights.
En sammenhæng mellem eksponering for clofarabin eller clofarabintriphosphat og enten effekt eller toksicitet er ikke påvist hos denne population. 
No relationship between clofarabine or clofarabine triphosphate exposure and either efficacy or toxicity has been established in this population.
Endvidere havde 50/113 patienter, der fik clofarabin, svært forhøjet ALAT (mindst NCI-CTC-grad 3), 36/100 havde forhøjet ASAT og 15/114 patienter forhøjet bilirubin. 
In addition, 50/113 patients receiving clofarabine had at least severely (at least US NCI CTC Grade 3) elevated ALT, 36/100 elevated AST and 15/114 elevated bilirubin levels.
Procedurerne for korrekt håndtering af antineoplastiske midler skal overholdes. 
Procedures for proper handling of antineoplastic agents should be observed.
Hos rotter sås hjertepåvirkning, der svarede til kardiomyopati og fremstod som symptomer på hjerteinsufficiens efter gentagne behandlingscykler. 
Cardiac effects were observed in rats consistent with cardiomyopathy and contributed to signs of cardiac failure after repeated cycles of treatment.
13 tilfælde af tumorlysesyndrom, kapillær lækagesyndrom eller SIRS er blevet indberettet; SIRS (2 tilfælde, som begge blev anset for alvorlige), kapillær lækage-syndrom (4 tilfælde, hvoraf 3 blev anset for at være alvorlige og relaterede) og tumorlysesyndrom (7 tilfælde, hvoraf 6 blev anset for relaterede og 3 for at være alvorlige). 
Thirteen events of tumour lysis syndrome, capillary leak syndrome or SIRS have been reported; SIRS (2 events; both were considered to be serious), capillary leak syndrome (4 events; 3 of which were considered serious and related) and tumour lysis syndrome (7 events; 6 of which were considered related and 3 of which were serious).
Perikardiel ekssudation var imidlertid klinisk signifikant hos 2 patienter, som var noget hæmodynamisk kompromitterede. 
However, the pericardial effusion was clinically significant in 2 patients with some associated haemodynamic compromise.
Benigne, maligne og uspecificerede tumorer (inkl.cyster og polypper) og immunsystemet Administration af clofarabin medfører et hurtigt fald i perifere leukæmiceller. 
Neoplasms benign and malignant (including cysts and polyps) and Immune systems disorders Administration of clofarabine results in a rapid reduction in peripheral leukaemia cells.
Clofarabin bør omgående seponeres i tilfælde af voldsomme stigninger i kreatinin, leverenzymer og/eller bilirubin. 
Clofarabine should be discontinued immediately if substantial increases in creatinine, liver enzymes and/or bilirubin are observed.
Patienterne bør monitoreres for renal toksicitet og clofarabin bør seponeres om nødvendigt. 
Patients should be monitored for renal toxicity and clofarabine should be discontinued as necessary.
De hyppigst rapporterede bivirkninger var kvalme (61 % af patienterne), opkastning (59 %), febril neutropeni (35 %), hovedpine (24 %), udslæt (21 %), diarre (20 %), pruritus (20 %), pyreksi (19 %), palmar-plantar erytrodysæstesi-syndrom (15 %), træthed (14 %), angst (12 %), slimhindeinflammation (11 %) og flushing (11 %). 
Those most frequently reported were nausea (61% of patients), vomiting (59%), febrile neutropaenia (35%), headache (24%), rash (21%), diarrhoea (20%), pruritus (20%), pyrexia (19%), palmar-plantar erythrodysaesthesia syndrome (15%), fatigue (14%), anxiety (12%), mucosal inflammation (11%), and flushing (11%).
Glomerulonefropati rapporteredes hos rotter efter 3-5 gange større eksponering end det kliniske AUC efter 6 behandlingscykler med clofarabin. 
Glomerulonephropathy was reported in rats at exposure levels 3 to 5 fold higher than the clinical AUC after 6 dosing cycles of clofarabine.
Et fase II-, åbent, non-komparativt multicenterstudie med clofarabin blev udført for at bestemme total remission (TR) hos tungt behandlede patienter (≤ 21 år ved første diagnosticering) med recidiverende eller refraktær ALL defineret i henhold til fransk-amerikansk-britisk klassifikation. 
A multi-centre, phase II, open-label, non-comparative study of clofarabine was conducted to determine the overall remission (OR) rate in heavily pretreated patients (≤ 21 years old at initial diagnosis) with relapsed or refractory ALL defined using the French-American-British classification.
I tilfælde af en yderligere klinisk betydningsfuld infektion bør clofarabin seponeres, indtil infektionen er velkontrolleret, og den kan genoptages, hvis dosis reduceres med 25 %. 
In the event of a second clinically significant infection, clofarabine treatment should be withheld until the infection is clinically controlled and may be reinitiated at a 25% dose reduction.
Endvidere forhalede clofarabin tumorvækst og medførte i nogle tilfælde tumorregression hos en række humane og murine tumorxenoplantater implanteret hos mus. 
In addition, clofarabine delayed tumour growth and, in some cases, caused tumour regression in an assortment of human and murine tumour xenografts implanted in mice.
Clofarabin bør omgående seponeres, hvis patienten udviser nogle af de tidlige symptomer på SIRS, kapillær lækage-syndrom eller omfattende organdysfunktion, og passende understøttende behandling iværksættes. 
Clofarabine should be discontinued immediately if patients show early signs or symptoms of SIRS, capillary leak syndrome or substantial organ dysfunction and appropriate supportive measures instituted.
Farmakokinetiske populationsdata fra voksne og pædiatriske patienter tyder på, at patienter med stabil, moderat nyreinsufficiens (kreatininclearance 30 - < 60 ml/min), der får halv dosis, opnår en clofarabineksponering svarende til personer med normal nyrefunktion, som får standarddosis. 
Population pharmacokinetic data from adult and paediatric patients suggest that patients with stable moderate renal impairment (creatinine clearance 30 - < 60 ml/min) receiving a 50% dose reduction achieve similar clofarabine exposure to those with normal renal function receiving a standard dose.
Genotoksicitetsforsøg viste, at clofarabin ikke var mutagent i en tilbagemutationstest med bakterier, men var klastogent i en ikke-aktiveret kromosomal aberrationstest af ovarieceller fra kinesiske hamstere og i en in vivo-mikronukleustest hos rotter. 
Genotoxicity studies demonstrated that clofarabine was not mutagenic in the bacterial reverse mutation assay, but did induce clastogenic effects in the non-activated chromosomal aberration assay in Chinese Hamster Ovary (CHO) cells and in the in vivo rat micronucleus assay.
Hver æske indeholder 1 hætteglas. 
Each box contains 1 vial.
For at undgå væskemangel er det vigtigt at drikke rigeligt vand. 
It is important to drink plenty of water to avoid dehydration.
Inden indledning af hver cyklus skal legemsoverfladen beregnes ud fra patientens faktiske højde og vægt. 
Body surface area must be calculated using the actual height and weight of the patient before the start of each cycle.
Der er ingen erfaring fra kliniske studier hos pædiatriske patienter med nyreinsufficiens (defineret i kliniske undersøgelser som serum-kreatinin ≥ 2 x ULN for aldersgruppen), og clofarabin udskilles hovedsageligt via nyrerne. 
There is no clinical study experience in paediatric patients with renal insufficiency (defined in clinical studies as serum creatinine ≥ 2 x ULN for age) and clofarabine is predominately excreted via the kidneys.
Anvendelse til patienter med alvorlig nyreinsufficiens eller svært nedsat leverfunktion. 
Use in patients with severe renal insufficiency or severe hepatic impairment.
Tre patienter døde af bivirkninger, som af forsøgets investigator blev anset for at være relateret til clofarabin: Én patient døde af respirationshæmning, hepatocellulær skade og kapillær lækage-syndrom; én døde af vancomycinresistent Enterococcus-sepsis (VRE-sepsis) og multiorgansvigt; og én døde af septisk shock og multiorgansvigt. 
Three patients died of adverse events considered by the study investigator to be related to treatment with clofarabine: one patient died from respiratory distress, hepatocellular damage, and capillary leak syndrome; one patient from VRE sepsis and multi-organ failure; and one patient from septic shock and multi-organ failure.
Profylaktisk behandling med antiemetika bør overvejes. 
Prophylactic anti-emetic medicinal products should be considered.
Total overlevelse (uger) 
Overall Survival (weeks)
Til patienter med moderat nyreinsufficiens (kreatininclearance 30 - <60 ml/min) skal dosis reduceres med 50 % (se pkt. 
Patients with moderate renal impairment (creatinine clearance 30 - < 60 ml/min) require a 50% dose reduction (see section 5.2).
Hos rotter sås leverpåvirkning efter kronisk administration af clofarabin. 
Hepatic effects were observed in rats following chronic administration of clofarabine.
Clofarabins sikkerhed og effekt blev evalueret i et fase I, åbent, non-komparativt dosiseskaleringsstudie med 25 pædiatriske patienter med recidiverende eller refraktær leukæmi (17 ALL, 8 AML), som ikke havde opnået bedring med standardbehandling, eller som ikke kunne få anden behandling. 
The safety and efficacy of clofarabine were evaluated in a phase I, open-label, non-comparative, doseescalation study in 25 paediatric patients with relapsed or refractory leukaemia (17 ALL; 8 AML) who had failed standard therapy or for whom no other therapy existed.
Clofarabin var også virksomt mod hvilende lymfocytter og makrofager. 
It was also active against quiescent lymphocytes and macrophages.
Clofarabins farmakokinetik blev undersøgt hos 40 patienter mellem 2 og 19 år med recidiverende eller refraktær ALL eller AML. 
The pharmacokinetics of clofarabine were studied in 40 patients aged between 2 to 19 years old with relapsed or refractory ALL or AML.
Hvis du er forælder til et barn, som bliver behandlet med Ivozall, skal du fortælle lægen, hvis et af disse punkter passer på dit barn. 
If you are the parent of a child who is being treated with Ivozall, tell the doctor if any of them apply to your child.
MINDSTEKRAV TIL MÆRKNING PÅ SMÅ INDRE EMBALLAGER HÆTTEGLAS 
MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS VIAL LABEL
Du får medicinen via et drop - det vil sige som infusion gennem en lang tynd slange i en vene (drop), eller i en lille medicinsk enhed, der indsættes under huden (centralt venekateter), hvis du (eller dit barn) har fået indlagt et sådant. 
It will be given to you as an infusion through a long thin tube which goes into a vein (a drip), or into a small medical appliance that is inserted under the skin (port-a-cath) if you (or your child) have one implanted.
Knoglemarvssuppression må forventes. 
Suppression of bone marrow should be anticipated.
Begynd ikke at få Ivozall: - hvis du er allergisk (overfølsom) over for clofarabin eller et af de øvrige indholdsstoffer i dette lægemiddel (angivet i punkt 6); - hvis du ammer (se afsnittet 'Graviditet og amning'); - hvis du lider af en alvorlig lever- eller nyresygdom. 
Do not use Ivozall - - if you are allergic to clofarabine or any of the other ingredients of this medicine (listed in section 6); - if you are breast-feeding (please read the section “Pregnancy and breast-feeding” below); - if you have severe kidney or liver problems.
Disse patienter indgik i en enkelt fase I-undersøgelse (n = 12) eller to fase II-undersøgelser (n = 14 / n = 14) af sikkerhed og effekt, hvor de fik gentagne doser clofarabin som intravenøs infusion (se pkt. 
The patients were enrolled into a single phase I (n = 12) or two phase II (n = 14 / n = 14) safety and efficacy studies, and received multiple doses of clofarabine by intravenous infusion (see section 5.1).
Median tid til progression (uger)** 
Median time to progression (weeks)** (95% CI)
For instruktioner om fortynding af lægemidlet før administration, se pkt. 
For instructions on dilution of the medicinal product before administration (see section 6.6).
Almindelig: Kontusion 
Common: Contusion
Tre af disse tilfælde blev efterfølgende vurderet til at være relateret til clofarabin: perikardiel ekssudation (to tilfælde, hvoraf et var alvorligt) og pericarditis (et tilfælde, der ikke var alvorligt). 
Three of these events were subsequently assessed as being related to clofarabine: pericardial effusion (2 events; 1 of which was serious) and pericarditis (1 event; not serious).
ANVENDELSESMETODE Læs indlægssedlen inden brug 
METHOD OF ADMINISTRATION Read the package leaflet before use
CRp = Komplet remission uden fuldstændig normalisering af trombocyttal 
CRp = Complete remission in the Absence of Total Platelet Recovery
Hætteglas af type I-glas med en grå fluorpolymer-belagt klorobutyl-gummiprop, flip-off plombering af polypropylen og aluminiumsforsegling. 
Type I glass vial with grey chlorobutyl fluoropolymer coated rubber stopper, polypropylene flip-off cap and aluminium overseal.
Til patienter, hos hvem ANC holder sig < 0,5 × 109/l i over 4 uger efter start på den forudgående cyklus, anbefales det at reducere dosis til næste cyklus med 25 %. 
Should patients experience an ANC < 0.5 × 109/l for more than 4 weeks from the start of the last cycle, it is recommended that the dose for the next cycle be reduced by 25%.
Dosisreduktion hos patienter med hæmatologisk toksicitet 
Dose reduction for patients experiencing haematological toxicities
LÆGEMIDDELFORM OG INDHOLD (PAKNINGSSTØRRELSE) Koncentrat til infusionsvæske, opløsning 20 mg/20 ml 
PHARMACEUTICAL FORM AND CONTENTS Concentrate for solution for infusion 20 mg/20 ml
Almindelig: Hyperbilirubinæmi, gulsot, veneokklusion, stigninger i alanin- (ALAT)* og aspartat- (ASAT)* aminotransferaser, leversvigt Ikke almindelig: Hepatitis 
Common: Hyperbilirubinaemia, jaundice, veno-occlusive disease, increases in alanine (ALT)* and aspartate (AST)* aminotransferases, hepatic failure Uncommon: Hepatitis
50 % af patienterne fik mindst én bivirkning tilhørende hjerte organklassen. 
Fifty percent of patients experienced at least one cardiac disorders adverse reaction.
Almindelig: Overfølsomhed 
Common: Hypersensitivity
Leveren er et potentielt organ for clofarabintoksicitet, og 25,2 % af patienterne oplevede mindst ét tilfælde af bivirkninger fra lever- og galdeveje (se pkt. 
The liver is a potential target organ for clofarabine toxicity and 25.2% of patients experienced at least one hepato-biliary disorders adverse reaction (see sections 4.3 and 4.4).
Øvrige indholdsstoffer: Natriumchlorid og vand til injektionsvæsker. 
The other ingredients are sodium chloride and water for injections.
Clofarabins clearance synes at være langt hurtigere end den glomerulære filtrationshastighed, hvilket indikerer, at elimination via nyrerne foregår som filtration og tubulær sekretion. 
Clofarabine clearance rates appear to be much higher than glomerular filtration rates suggesting filtration and tubular secretion as kidney elimination mechanisms.
De fleste patienter, som responderer på clofarabin, opnår respons efter 1 - 2 behandlingscykler (se pkt. 
The majority of patients who respond to clofarabine achieve a response after 1 or 2 treatment cycles (see section 5.1).
• Nyre- og leverfunktion skal kontrolleres før og efter behandlingen samt i løbet af aktiv behandling. 
• Renal and hepatic function prior to, during active treatment and following therapy.
En patient afbrød behandlingen på grund af hyperbilirubinæmi grad 4, der blev anset for at være relateret til clofarabin, efter at have fået clofarabin 52 mg/m2/dag. 
One patient discontinued treatment due to grade 4 hyperbilirubinaemia considered as related to clofarabine after receiving 52 mg/m2/day clofarabine.
Patienter, der gennemgik transplantation under fortsat remission* CRp 
Patients who underwent transplant while in continued remission*
Plasmaproteinbinding Serum-albumin Elimination: 
Plasma protein binding Serum albumin Elimination: β half-life of clofarabine
Behandling af pædiatriske patienter med recidiverende eller refraktær akut lymfatisk leukæmi (ALL), efter at de har fået mindst to tidligere behandlingsregimer, og hos hvem ingen andre behandlingsformer forventes at kunne opnå et varigt respons. 
Treatment of acute lymphoblastic leukaemia (ALL) in paediatric patients who have relapsed or are refractory after receiving at least two prior regimens and where there is no other treatment option anticipated to result in a durable response.
Studiets hovedresultater for effekt gengives i tabellen nedenfor. 
The table below summarises the key efficacy results for this study.
Hovedstudiets effektresultater hos patienter (≤ 21 år ved første diagnosticering) med recidiverende eller refraktær ALL efter mindst to forudgående behandlingsregimer Responskategori 
Efficacy results from the pivotal study in patients (≤ 21 years old at initial diagnosis) with relapsed or refractory ALL after at least two prior regimens
Brug af anden medicin sammen med Ivozall 
Other medicines and Ivozall
Størstedelen af de rapporterede tilfælde var forbundet med trombocytopeni (se pkt. 
The majority of the cases were associated with thrombocytopaenia (see section 4.8).
En øget forekomst af fostertab efter implantation, reduceret føtal legemsvægt og reduceret kuldstørrelse sammen med et øget antal misdannelser (store eksterne misdannelser, bløde væv) og skeletale forandringer (inklusive forsinket ossifikation) rapporteredes hos rotter, der fik clofarabin i doser, som svarede til ca. 2-3 gange den kliniske eksponering (54 mg/m2/dag), og hos kaniner, der fik 12 mg/m2/dag. 
Increases in postimplantation loss, reduced foetal body weights and decreased litter sizes together with increases in the number of malformations (gross external, soft tissue) and skeletal alterations (including retarded ossification) were reported in rats receiving doses which produced approximately 2 to 3 fold the clinical exposure (54 mg/m2/day) and in rabbits receiving 12 mg/m2/day clofarabine.
Patienter med hjertesygdom eller patienter, som tager lægemidler, der er kendt for at påvirke blodtryk eller hjertefunktion, bør kontrolleres nøje under behandling med clofarabin (se pkt. 
Patients with cardiac disease and those taking medicinal products known to affect blood pressure or cardiac function should be closely monitored during treatment with clofarabine (see sections 4.5 and
EVENTUELLE ANDRE SÆRLIGE ADVARSLER Cytostatikum 
OTHER SPECIAL WARNING(S), IF NECESSARY Cytotoxic
ANVENDELSESMÅDE OG ADMINISTRATIONSVEJ(E) Intravenøs anvendelse efter fortynding Skal fortyndes før brug. 
METHOD AND ROUTE(S) OF ADMINISTRATION Intravenous use after dilution Dilute before use.
Instruktioner vedrørende håndtering 
Instructions for handling
Opbevaringsforhold efter fortynding af lægemidlet, se pkt. 
For storage conditions after dilution of the medicinal product, see section 6.3
Almindelig: Agitation, rastløshed, ændring i mental status 
Very common: Anxiety Common: Agitation, restlessness, mental status change
Stevens-Johnsons syndrom (SJS) og toksisk epidermal nekrolyse (TEN), herunder tilfælde med letalt udfald, er blevet rapporteret hos patienter, som bliver eller for nylig er blevet behandlet med clofarabin. 
Stevens - Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), including fatal cases, have been reported in patients who were receiving or had recently been treated with clofarabine.
De forgiftninger, der observeredes hos disse patienter, omfattede opkastning, hyperbilirubinæmi, forhøjede aminotransferaser og makulopapulært udslæt. 
The toxicities observed in these patients included vomiting, hyperbilirubinaemia, elevated transaminase levels and maculo-papular rash.
(6,7 til 12,6) 
(6.7 to 12.6)
Dosisreduktion hos patienter med ikke-hæmatologisk toksicitet: 
Dose reduction for patients experiencing non-haematological toxicities
Tilfælde af enterocolitis, herunder neutropenisk colitis, caecitis og C. difficile colitis, er blevet indberettet under behandling med clofarabin. 
Occurrences of enterocolitis, including neutropaenic colitis, caecitis, and C. difficile colitis, have been reported during treatment with clofarabine.
Clofarabin skal seponeres, hvis der forekommer udslæt med afskalning af huden eller bulløst udslæt, eller hvis der er mistanke om SJS eller TEN. 
Clofarabine must be discontinued for exfoliative or bullous rash, or if SJS or TEN is suspected.
LÆGEMIDLETS NAVN OG ADMINISTRATIONSVEJ(E) Ivozall 1 mg/ml sterilt koncentrat clofarabin 
NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION Ivozall 1 mg/ml sterile concentrate clofarabine