natgillin/translations-raw huggingface dataset:
I kliniske undersøgelser absorberes ruxolitinib hurtigt efter oral administration med maksimal plasmakoncentration (Cmax) ca. 1 time efter indtagelse af dosis. 
In clinical studies, ruxolitinib is rapidly absorbed after oral administration with maximal plasma concentration (Cmax) achieved approximately 1 hour post-dose.
Ruxolitinib er evalueret i studier af sikkerhedsfarmakologi, gentagen dosis-toksicitet, genotoksicitet, reproduktionstoksicitet og i et carcinogenicitetsstudie. 
Ruxolitinib has been evaluated in safety pharmacology, repeated dose toxicity, genotoxicity and reproductive toxicity studies and in a carcinogenicity study.
Bivirkningerne under kliniske undersøgelser (Tabel 1) er ordnet efter MedDRA-systemorganklasser. 
Adverse drug reactions from clinical studies (Table 1) are listed by MedDRA system organ class.
Derfor forventes der ikke en stigning i eksponeringen af CYP3A4-substrater ved kombination med ruxolitinib. 
Therefore, no increase in exposure of CYP3A4 substrates is anticipated when combining them with ruxolitinib.
Bedste tilgængelige behandling (N=72) 
Best available therapy (N=72)
Blod og lymfesystem b,d 
Blood and lymphatic system disorders b,d
Frekvens for MF patienter Frekvens for PV patienter 
Frequency category for PV patients
MF og PV er myeloproliferative neoplasier, som man ved er forbundet med dysreguleret JAK1- og JAK2-signalering. 
MF and PV are myeloproliferative neoplasms known to be associated with dysregulated JAK1 and JAK2 signalling.
Dog skal patienterne overvåges nøje for cytopeni, når der påbegyndes behandling med en moderat CYP3A4-hæmmer. 
However, patients should be closely monitored for cytopenias when initiating therapy with a moderate CYP3A4 inhibitor.
Fravær af indikation for flebotomi blev defineret som bekræftet HCT på >45%, dvs. mindst 3 procentpoint højere end HCT ved baseline eller en bekræftet HCT på >48% alt efter, hvilken der var lavest. 
Phlebotomy eligibility was defined as a confirmed HCT of >45%, i.e. at least 3 percentage points higher than the HCT obtained at baseline or a confirmed HCT of >48%, depending on which was lower.
Clearance var 12,7 l/t hos PV-patienter med en inter-individuel variation på 42%, og der var tilsyneladende ingen forbindelse mellem oral clearance og køn, patientalder eller race baseret på en populationsfarmakokinetisk evaluering hos PVpatienter. 
Clearance was 12.7 l/h in PV patients, with a 42% inter-subject variability and no relationship was apparent between oral clearance and gender, patient age or race, based on a population pharmacokinetic evaluation in PV patients.
Substanser transporteret af P-glykoprotein eller andre transportere Ruxolitinib kan hæmme P-glykoprotein og brystcancer-resistent protein (BCRP) i tarmen. 
Substances transported by P-glycoprotein or other transporters Ruxolitinib may inhibit P-glycoprotein and breast cancer resistance protein (BCRP) in the intestine.
Ved PV skal behandlingen også afbrydes, hvis hæmoglobin er under 8 g/dl. 
In PV, treatment should also be interrupted when haemoglobin is below 8 g/dl.
- Bivirkninger er set under behandling eller op til 28 dage efter endt behandling. 
- ADRs reported are on treatment or up to 28 days post treatment end date.
Den mediane eksponeringsvarighed for Jakavi i den randomiserede studieperiode var 7,85 måneder (0,03 til 7,85 måneder). 
The median duration of exposure to Jakavi during the randomised study periods was 7.85 months (range 0.03 to 7.85 months).
Blødning (enhver blødning inklusive intrakraniel og gastrointestinal blødning, blå mærker og andre blødninger) 
Bleeding (any bleeding including intracranial, and gastrointestinal bleeding, bruising and other bleeding)
Demografi og sygdomskarakteristika ved baseline var sammenlignelige mellem de to behandlingsarme. 
Baseline demographics and disease characteristics were comparable between the two treatments arms.
Disse enzymer formidler signaleringen af flere cytokiner og vækstfaktorer, som er vigtige for hæmatopoese og immunfunktion. 
These mediate the signalling of a number of cytokines and growth factors that are important for haematopoiesis and immune function.
Den forventede orale clearance var 17,7 l/time hos kvinder og 22,1 l/time hos mænd med en inter-individuel variation blandt MF-patienter på 39%. 
The predicted oral clearance was 17.7 l/h in women and 22.1 l/h in men, with 39% inter-subject variability in MF patients.
90429 Nürnberg 
D-90429 Nuremberg
Interaktioner, der medfører dosisreduktion af ruxolitinib 
Interactions resulting in dose reduction of ruxolitinib
- Nefazodon, medicin som bruges til behandling af depression. 
- Nefazodone, a medicine to treat depression.
BAT blev bestemt af investigatoren fra patient til patient og inkluderede hydroxycarbamid (59,5%), interferon/pegyleret interferon (11,7%), anagrelid (7,2%), pipobroman (1,8%) og observation (15,3%). 
BAT was selected by the investigator on a patient-bypatient basis and included hydroxyurea (59.5%), interferon/pegylated interferon (11.7%), anagrelide (7.2%), pipobroman (1.8%) and observation (15.3%).
Derfor forventes det ikke, at den kontraceptive effekt af denne kombination vil blive kompromitteret ved administration sammen med ruxolitinib. 
Therefore, it is not anticipated that the contraceptive efficacy of this combination will be compromised by co-administration of ruxolitinib.
Frekvens er baseret på bivirkningsdata. 
Frequency is based on adverse event data.
Ruxolitinib er et stof tilhørende klasse 1 ifølge det biofarmaceutiske klassifikationssystem med høj permeabilitet, høj solubilitet og hurtig opløsning. 
Ruxolitinib is a Biopharmaceutical Classification System (BCS) class 1 compound, with high permeability, high solubility and rapid dissolution characteristics.
Det er uvist om den øgede metaboliteksponering har betydning for den kliniske sikkerhed. 
It is unknown whether the increased metabolite exposure is of safety concern.
Trombocyttransfusioner kan dog være klinisk indiceret. 
However, platelet transfusions may be required as clinically indicated.
Frakturer og tidlig aflivning af rotter blev observeret ved doser på ≥30 mg/kg/dag, når behandlingen startede på dag 7 postnatalt. 
Fractures and early termination of rats were observed at doses ≥30 mg/kg/day when treatment was started on postnatal day 7.
Ved PV skal dosisreduktion også overvejes, hvis hæmaglobin falder til under 12 g/dl, og dosisreduktion anbefales, hvis det falder til under 10 g/dl. 
In PV, dose reductions should also be considered if haemoglobin decreases below 12 g/dl and is recommended if it decreases below 10 g/dl.
Bortset fra knogleudvikling, var virkningerne af ruxolitinib hos juvenile rotter sammenlignelig med dem hos voksne rotter. 
Other than bone development, the effects of ruxolitinib in juvenile rats were similar to those in adult rats.
Doserne kan titreres under hensyntagen til sikkerhed og effekt. 
Doses may be titrated based on safety and efficacy.
Det kan også overvejes at justere dosis eller afbryde behandlingen hos patienter, der udvikler anæmi. 
Dose modifications or interruption for patients developing anaemia may also be considered.
Ruxolitinib var ikke karcinogent i den transgene Tg.rasH2-musemodel. 
Ruxolitinib was not carcinogenic in the Tg.rasH2 transgenic mouse model.
Enzym-induktorer 
Enzyme inducers
Anæmi, trombocytopeni og neutropeni er dosisrelaterede virkninger. 
Anaemia, thrombocytopenia and neutropenia are dose-related effects.
Dette kan inkludere anamnese, mulig tidligere kontakt med tuberkulose og/eller relevant screening fx lungerøntgen, tuberkulintest og/eller interferon-gamma frigørelsesassay som passende. 
This can include medical history, possible previous contact with tuberculosis, and/or appropriate screening such as lung x-ray, tuberculin test and/or interferon-gamma release assay, as applicable.
I en farmakokinetisk evaluering var der hos en population af MF-patienter tilsyneladende ingen sammenhæng mellem oral clearance og patienternes alder eller race. 
In a population pharmacokinetic evaluation in MF patients, no relationship was apparent between oral clearance and patient age or race.
Kvinder i den fertile alder skal anvende sikker kontraception under behandling med Jakavi. 
Women of child-bearing potential should use effective contraception during the treatment with Jakavi.
Virkningsstudie efter godkendelse (PAES) for at opnå langtidsdata for effekt og sikkerhed for ruxolitinib, inklusive (sen) opnåelse af respons, varighed af (forskellige) respons, såvel som incidensen af bivirkninger inklusive hæmatologisk transformation og sekundær malignitet fra studie B2301. 
Post-Authorisation efficacy study to provide long-term efficacy and safety data of ruxolitinib including (late) achievement of response, duration of (various) responses, as well as incidence of AEs including haematological transformation and second malignancies from the study B2301.
Dosis blev herefter justeret individuelt hos patienterne baseret på tolerabilitet og effekt med en maksimal dosis på 25 mg to gange dagligt. 
Doses were then adjusted in individual patients based on tolerability and efficacy with a maximum dose of 25 mg twice daily.
Hvis du har spørgsmål om, hvor længe du skal tage Jakavi, så tal med din læge eller apoteket. 
If you have questions about how long to take Jakavi, talk to your doctor or pharmacist.
Det anbefales at patienter, der har vist en grad af klinisk forbedring, ophører med ruxolitinibbehandlingen, hvis de bevarer en øgning i længden af milten på 40% sammenlignet med baselinestørrelse (ca. svarende til en 25% øgning i miltvolumen) og ikke længere har konkret forbedring af sygdomsrelaterede symptomer. 
It is recommended that, for patients who have demonstrated some degree of clinical improvement, ruxolitinib therapy be discontinued if they sustain an increase in their spleen length of 40% compared with baseline size (roughly equivalent to a 25% increase in spleen volume) and no longer have tangible improvement in disease-related symptoms.
Eksponeringsmaginer var dog lave sammenlignet med den højest kliniske dosis og resultaterne har derfor begrænset relevans hos mennesker. 
However, the exposure margins compared to the highest clinical dose were low and the results are therefore of limited relevance for humans.
Myelofibrose 
Myelofibrosis
Ruxolitinib metaboliseres hovedsagelig af CYP3A4 (>50%) med yderligere bidrag fra CYP2C9. 
Ruxolitinib is mainly metabolised by CYP3A4 (>50%), with additional contribution from CYP2C9.
Jakavi anvendes til behandling af voksne patienter med en forstørret milt eller med symptomer, der er relateret til myelofibrose, en sjælden form for blodkræft. 
Jakavi is used to treat adult patients with an enlarged spleen or with symptoms related to myelofibrosis, a rare form of blood cancer.
De fleste patienter havde fået mindst to flebotomier i de sidste 24 uger inden screening. 
Most patients (>80%) had received at least two phlebotomies in the last 24 weeks prior to screening.
Ruxolitinib var ikke mutagent eller klastogent. 
Ruxolitinib was not mutagenic or clastogenic.
I den bedst tilgængelige terapi-arm fik 47% af patienterne hydroxycarbamid og 16% glukokortikoider. 
In the best available therapy arm, 47% of patients received hydroxyurea and 16% of patients received glucocorticoids.
Når du stopper med at tage Jakavi, kan myelofibrose-symptomerne komme tilbage. 
When you stop taking Jakavi, the myelofibrosis symptoms may come back.
Jakavi kan lindre symptomerne, reducere miltens størrelse og nedsætte mængden af røde blodlegemer hos patienter med polycythæmia vera ved selektivt at blokere enzymer, som kaldes Janus-associerede kinaser (JAK1 og JAK2), og således potentielt nedsætte risikoen for alvorlige komplikationer i blod- eller blodkar. 
Jakavi can relieve the symptoms, reduce spleen size and the volume of red blood cells produced in patients with polycythaemia vera by selectively blocking enzymes called Janus Associated Kinases (JAK1 and JAK2), thus potentially reducing the risk of serious blood or vascular complications.
Hydroxypropylcellulose, 300 til 600 cps Lactosemonohydrat 
Hydroxypropylcellulose 300 to 600 cps Lactose monohydrate
Tal med din læge eller apotekspersonalet, mens du behandles med Jakavi - hvis du oplever uventede blå mærker og/eller blødninger, usædvanlig træthed, åndenød under motion eller i hvile, usædvanlig bleg hud eller hyppige infektioner (dette er tegn på blodsygdomme). 
Talk to your doctor or pharmacist during your treatment with Jakavi - if you experience unexpected bruising and/or bleeding, unusual tiredness, shortness of breath during exercise or at rest, unusually pale skin, or frequent infections (these are signs of blood disorders).
Medianværdien af Cmax faldt moderat (24%), mens middelværdien af AUC var næsten uændret (4% forøgelse) efter dosering sammen med et måltid med højt fedtindhold. 
The mean Cmax was moderately decreased (24%) while the mean AUC was nearly unchanged (4% increase) on dosing with a high-fat meal.
Polycytæmia vera er en sygdom i knoglemarven, hvor knoglemarven producerer for mange røde blodlegemer. 
Polycythaemia vera is a disorder of the bone marrow, in which the marrow produce too many red blood cells.
Det vides ikke, om den Janus associerede kinase (JAK) hæmning af ruxolitinib reducerer effekten af de hæmatopoietiske vækstfaktorer eller om de hæmatopoietiske vækstfaktorer påvirker effekten af ruxolitinib (se pkt. 
It is not known whether the Janus Associated Kinase (JAK) inhibition by ruxolitinib reduces the efficacy of the haematopoietic growth factors or whether the haematopoietic growth factors affect the efficacy of ruxolitinib (see section 4.4).
Myelofibrose er en sygdom i knoglemarven, hvor marven erstattes af arvæv. 
Myelofibrosis is a disorder of the bone marrow, in which the marrow is replaced by scar tissue.
Årsagerne til dysreguleringen menes at omfatte høje niveauer af cirkulerende cytokiner, som aktiverer JAK-STAT-signalvejen, gain of function-mutationer, som for eksempel JAK2V617F, og undertrykkelse af negative reguleringsmekanismer. 
The basis for the dysregulation is believed to include high levels of circulating cytokines that activate the JAK-STAT pathway, gain-of-function mutations such as JAK2V617F, and silencing of negative regulatory mechanisms.
Når blodtallene igen er over disse niveauer, kan doseringen genoptages med 5 mg to gange dagligt og gradvist øges på grundlag af omhyggelig monitorering af komplet blodtælling inklusive differentialtælling. 
After recovery of blood counts above these levels, dosing may be re-started at 5 mg twice daily and gradually increased based on careful monitoring of complete blood cell count, including a white blood cell count differential.
Brug ikke lægemidlet efter den udløbsdato, der står på yderkarton eller blister efter EXP. Udløbsdatoen er den sidste dag i den nævnte måned. 
Do not use this medicine after the expiry date which is stated on the carton or blister after “EXP”.
Tilsvarende havde patienter med PV forhøjede inflammatoriske markører ved baseline, og disse markører faldt efter behandling med ruxolitinib. 
Similarly, patients with PV also presented with baseline elevations in inflammatory markers and these markers were decreased following treatment with ruxolitinib.
Ved uge 32 opnåede 49% og 64% af patienterne behandlet med ruxolitinib en ≥50% reduktion i henholdsvis TSS-14 og TSS-5, sammenlignet med kun 5% og 11% af patienterne behandlet med BAT. 
At week 32, 49% and 64% of patients treated with ruxolitinib achieved a ≥50% reduction in TSS-14 and TSS-5, respectively, compared to only 5% and 11% of patients on BAT.
Farmakoterapeutisk klassifikation: Antineoplastiske stoffer, proteinkinasehæmmere, ATC-kode: L01XE18 
Pharmacotherapeutic group: Antineoplastic agents, protein kinase inhibitors, ATC code: L01XE18
Eksponeringsmarginerne var dog lave sammenlignet med den højeste kliniske dosis og resultaterne har derfor begrænset relevans for mennesker (se pkt. 
However, the exposure margins compared to the highest clinical dose were low and the results are therefore of limited relevance for humans (see section 5.3).
3 (>5-20 x ULN) 
c grade 3 (> 5x - 20 x ULN)
Disse dosisanbefalinger er baseret på simulationer, og enhver dosisjustering ved nyresygdom i slutstadiet skal efterfølges af omhyggelig monitorering af sikkerhed og effekt hos den individuelle patient. 
These dose recommendations are based on simulations and any dose modification in ESRD should be followed by careful monitoring of safety and efficacy in individual patients.
Der blev ikke observeret teratogenicitet hos rotter og kaniner. 
Teratogenicity was not observed in rats or rabbits.
Seponering af behandling pga. bivirkninger, uden hensyn til kausalitet, blev observeret hos 2,2% af patienterne. 
Discontinuation due to adverse events, regardless of causality, was observed in 2.2% of patients.
Den maksimale anbefalede startdosis til disse patienter er 5 mg to gange dagligt, og der bør udvises forsigtighed med hensyn til titrering. 
The maximum recommended starting dose in these patients is 5 mg twice daily and the patients should be titrated cautiously.
Du må ikke amme, mens du tager Jakavi. 
Do not breast-feed while taking Jakavi.
Det Europæiske Lægemiddelagentur har dispenseret fra kravet om at fremlægge resultaterne af studier med Jakavi i alle undergrupper af den pædiatriske population ved behandling af MF og PV (se pkt. 
The European Medicines Agency has waived the obligation to submit the results of studies with Jakavi in all subsets of the paediatric population for the treatment of MF and PV (see section 4.2 for information on paediatric use).
Forbedringer i opfattelsen af behandlingsfordele ved uge 32 var også højere hos patienter behandlet med ruxolitinib (78% mod 33%). 
Improvement in perception of treatment benefit was also higher in patients treated with ruxolitinib at week 32 (78% versus 33%).
Patienter med et hæmoglobinniveau under 10,0 g/dl i begyndelsen af behandlingen har i løbet af behandlingen en højere risiko for udvikling af et hæmoglobinniveau, der er under 8,0 g/dl sammenlignet med patienter med et højere baseline hæmoglobinniveau (79,3% vs. 30%). 
Patients with a haemoglobin level below 10.0 g/dl at the beginning of the treatment have a higher risk of developing a haemoglobin level below 8.0 g/dl during treatment compared to patients with a higher baseline haemoglobin level (79.3% versus 30.1%).
Ikke metaboliseret lægemiddel er den fremherskende forbindelse i humant plasma og udgør ca. 60% af det cirkulerende lægemiddel. 
Parent compound is the predominant entity in human plasma, representing approximately 60% of the drug-related material in circulation.
En forlænget opfølgningsperiode for patienter behandlet med ruxolitinib viste ingen tegn på en stigning i sepsis-tilfælde over tid. 
An extended follow-up of patients treated with ruxolitinib showed no trends towards an increase in the rate of sepsis over time.
Hvis effekten anses for utilstrækkelig, og blodtallene er passende, kan dosis øges med maksimalt 5 mg to gange dagligt op til en maksimaldosis på 25 mg to gange dagligt. 
If efficacy is considered insufficient and blood counts are adequate, doses may be increased by a maximum of 5 mg twice daily, up to the maximum dose of 25 mg twice daily.
Derfor må du ikke stoppe med at tage Jakavi uden først at have talt med lægen om det. 
Therefore, you should not stop taking Jakavi without discussing it with your doctor.
Efter afbrydelse af eller ophør med Jakavi kan myelofibrosesymptomerne vende tilbage over en periode på ca. en uge. 
Following interruption or discontinuation of Jakavi, symptoms of MF may return over a period of approximately one week.
Anæmi og trombocytopeni CTCAE grad 3 og 4 blev rapporteret hos henholdsvis 1,1% og 
Anaemia or thrombocytopenia CTCAE grade 3 and 4 were reported in respectively 1.1% or 3.3%.
Baseret på studier med raske forsøgspersoner blev der ikke observeret relevante forskelle i ruxolitinibs farmakokinetik med hensyn til køn eller race. 
Based on studies in healthy subjects, no relevant differences in ruxolitinib pharmacokinetics were observed with regard to gender and race.
Reduceret knogletilvækst blev observeret ved doser på ≥5 mg/kg/dag, når behandlingen startede på dag 7 postnatalt (sammenlignelig med humane nyfødte) og på ≥15 mg/kg/dag, når behandlingen startede på dag 14 eller 21 postnatalt (sammenlignelig med humane småbørn på 1-3 år). 
Reduced bone growth was observed at doses ≥5 mg/kg/day when treatment started on postnatal day 7 (comparable to human newborn) and at ≥15 mg/kg/day when treatment started on postnatal days 14 or 21 (comparable to human infant, 1-3 years).
De vigtigste sekundære endepunkter inkluderede andelen af patienter, som opnåede det primære endepunkt og forblev progressionsfri ved uge 48, såvel som andelen af patiener, der opnåede fuldstændig hæmatologisk remission ved uge 32. 
Key secondary endpoints included the proportion of patients who achieved the primary endpoint and remained free from progression at week 48, as well as the proportion of patients achieving complete haematological remission at week 32.
I PV-populationen blev CTCAE grad 3 og 4 rapporteret hos 2,7%, mens frekvensen var 42,56% for MF-patienter. 
In the PV population, the CTCAE grade 3 and 4 events were reported in 2.7%, while in the MF patients the frequency was 42.56%.
Tabel 3 Procentdel af patienter med ≥35% reduktion fra baseline i miltvolumen ved JAK mutationsstatus (sikkerhed) 
Table 3 Percentage of patients with ≥35% reduction from baseline in spleen volume by JAK mutation status (safety set)
Forhøjet aspartataminotransferase b 
Raised aspartate aminotransferase b
I studier med juvenile rotter medførte administration af ruxolitinib påvirkninger af vækst- og knogle parametre. 
In juvenile rat studies, administration of ruxolitinib resulted in effects on growth and bone measures.
En radiografisk undersøgelse af hele kroppen hos rotter har vist, at ruxolitinib ikke trænger igennem blod-hjernebarrieren. 
A whole body autoradiography study in rats has shown that ruxolitinib does not penetrate the blood-brain barrier.
Disse var alle grad 1 eller 2 med undtagelse af ét tilfælde af grad 3 forhøjet alaninaminotransferase. 
These were all CTCAE grade 1 and 2 with the exception of one CTCAE grade 3 raised alanine aminotransferase event.
Ud af 301 patienter havde 111 (36,9%) et baselinetrombocytniveau på mellem 100.000/mm og 200.000/mm 3, og 190 patienter (63,1%) havde et baseline-trombocytniveau >200.000/mm 
Of 301 patients, 111 (36.9%) had a baseline platelet count of between 100,000/mm and 200,000/mm and 190 (63.1%) had a baseline platelet count of
Følgende kan nedsætte virkningen af Jakavi: - Avasimib, medicin som bruges til behandling af hjertesygdom. 
The following may reduce the effectiveness of Jakavi: - Avasimibe, a medicine to treat heart disease.
Et randomiseret, åbent, aktivt kontrolleret fase 3-studie (RESPONSE) er gennemført med 222 patienter med PV, som var refraktære over for eller ikke tålte hydroxycarbamid, defineret ved Europæisk Leukæmi Nets (ELN) internationale arbejdsgruppes publicerede kriterier. 
A randomised, open-label, active-controlled phase 3 study (RESPONSE) was conducted in 222 patients with PV who were resistant to or intolerant of hydroxyurea defined based on the European LeukemiaNet (ELN) international working group published criteria.
Hvis du afbryder behandlingen med Jakavi, kan dine myelofibrose-relaterede symptomer vende tilbage. 
If you interrupt your treatment with Jakavi your myelofibrosis-related symptoms may come back.
Patienterne skal monitoreres nøje (fx to gange om ugen) for cytopeni, og dosis skal titreres under hensyntagen til sikkerhed og effekt (se pkt. 
Patients should be closely monitored (e.g. twice weekly) for cytopenias and dose titrated based on safety and efficacy (see section 4.2).
Målorganer, som er forbundet med ruxolitinibs farmakologiske aktivitet i gentagne dosisstudier, omfatter knoglemarv og perifert blod og lymfevæv. 
Target organs associated with the pharmacological action of ruxolitinib in repeated dose studies include bone marrow, peripheral blood and lymphoid tissues.