natgillin/translations-raw huggingface dataset:
Det vil sige, at stoffet blokerer nogle bestemte enzymer, der kaldes proteinkinaser.
This means that it blocks some specific enzymes, known as protein kinases.
Desuden findes de i de blodkar, der forsyner svulsterne, og er her medvirkende ved dannelse af nye blodkar.
These enzymes can be found in some receptors on the surface of cancer cells, where they are involved in the growth and spread of cancer cells, and in the blood vessels that supply the tumours, where they are involved in the development of new blood vessels.
Nexavar virker ved at nedsætte kræftcellernes væksthastighed og afskære blodforsyningen, der holder kræftcellernes vækst i gang.
Nexavar works by slowing down the rate of growth of cancer cells and cutting off the blood supply that keeps cancer cells growing.
Virkningen af Nexavar ved hepatocellulært karcinom blev undersøgt i en hovedundersøgelse, som omfattede 602 patienter, og virkningen ved fremskredent renalcellecarcinom blev undersøgt i en hovedundersøgelse, som omfattede 903 patienter, hos hvem behandling med én type kræftmedicin 7 Westferry Circus, Canary Wharf, London E14 4HB, UK Tel.
In both studies, Nexavar was compared with placebo (a dummy treatment) in a double-blind manner 7 Westferry Circus, Canary Wharf, London E14 4HB, UK Tel.
(44- 20) 74 18 84 00 Fax (44- 20) 74 18 84 16 E- mail: mail@ emea. europa. eu http: // www. emea. eu. int ©EMEA 2007 Reproduction and/ or distribution of this document is authorised for non commercial purposes only provided the EMEA is acknowledged ikke længere havde nogen virkning.
(44-20) 74 18 84 00 Fax (44-20) 74 18 84 16 E-mail: mail@emea. europa. eu http: / /www. emea. europa. eu ©EMEA 2007 Reproduction and/ or distribution of this document is authorised for non commercial purposes only provided the EMEA is acknowledged (neither the doctor nor the patient knew which treatment the patient was receiving).
I begge undersøgelser blev Nexavar sammenlignet med placebo (en virkningsløs behandling) i en dobbeltblind undersøgelse (hverken læge eller patient havde kendskab til, hvilken behandling patienten fik).
Nexavar was more effective than placebo in lengthening the overall survival of the patients.
Den vigtigste målestok for virkningen i undersøgelsen af hepatocellulært karcinom var patientens samlede overlevelsestid.
In the study of hepatocellular carcinoma, the patients taking Nexavar survived for an average of 10.7 months, compared with 7.9 months in those taking placebo.
Hovedmålestokken for virkningen i undersøgelsen af fremskredent renalcellecarcinom var patientens samlede overlevelse, og hvor længe patienterne overlevede uden forværring af deres sygdom.
Time until disease got worse was longer in patients treated with Nexavar (167 days, around five and a half months) than those who took placebo (84 days, around three months), based on data from 726 patients.
I de kliniske undersøgelser var de hyppigste bivirkninger (der optrådte hos mere end 1 ud af 10 patienter) lymfopeni (lavt antal lymfocytter, en form for hvide blodlegemer), hypophosphatæmi (lav mængde fosfat i blodet), hæmorrhagi (blødning), hypertension (forhøjet blodtryk), diarré, kvalme og opkastninger, udslæt, hårtab, "hånd- fod- syndromet" (udslæt på og smerte i håndfladerne og fodsålerne), rødme, kløe, træthed, smerter og forhøjet amylase og lipase (enzymer, der produceres i pancreas).
In clinical studies, the most common side effects with Nexavar (seen in more than 1 patient in 10) were lymphopenia (low levels of lymphocytes, a type of white blood cell), hypophosphataemia (low levels of phosphate in the blood), haemorrhage (bleeding), hypertension (high blood pressure), diarrhoea, nausea (feeling sick), vomiting, rash, alopecia (hair loss), ‘ hand foot syndrome’ (rash and pain on the palms and soles), erythema (redness), pruritus (itchiness), fatigue (tiredness), pain, and increased amylase and lipase (enzymes produced by the pancreas).
Den fuldstændige liste over de indberettede bivirkninger ved Nexavar fremgår af indlægssedlen.
For the full list of all side effects reported with Nexavar, see the Package Leaflet.
Nexavar bør ikke anvendes til patienter, der kan være overfølsomme (allergiske) over for sorafenib eller andre af indholdsstofferne.
Nexavar should not be used in people who may be hypersensitive (allergic) to sorafenib or any of the other ingredients.
Der skal udvises forsigtighed ved anvendelse sammen med andre lægemidler.
Caution is needed when it is taken with other medicines.
Fortegnelsen over de lægemidler, der kan vekselvirke med Nexavar, fremgår af indlægssedlen.
See the Package Leaflet for the list of the medicines that may interact with Nexavar.
Udvalget for Humanmedicinske Lægemidler (CHMP) konkluderede, at fordelene ved Nexavar er større end risiciene ved behandling af hepatocellulært karcinom og fremskredent renalcellecarcinom hos patienter, hos hvem tidligere interferon alfa - eller interleukin- 2- baseret behandling har været uden resultat, eller som skønnes uegnede til denne behandling.
The Committee for Medicinal Products for Human Use (CHMP) decided that Nexavar’ s benefits are greater than its risks for the treatment of hepatocellular carcinoma, and of advanced renal cell carcinoma in patients who have failed prior interferon alfa or interleukin-2 based therapy, or who are considered unsuitable for such therapy.
The Committee recommended that Nexavar be given marketing authorisation.
The Committee recommended that Nexavar be given marketing authorisation.
Andre oplysninger om Nexavar:
Other information about Nexavar:
Europa- Kommissionen udstedte en markedsføringstilladelse med gyldighed i hele Den Europæiske Union for Nexavar til Bayer HealthCare AG den 19. juli 2006.
The European Commission granted a marketing authorisation valid throughout the European Union for Nexavar to Bayer HealthCare AG on 19 July 2006.
Sammendraget af udtalelsen fra Udvalget til Lægemidler til Sjældne Sygdommeom Nexavar kan ses her (hepatocellulært carcinom) og her (renalcellecarcinom).
The summaries of opinion of the Committee for Orphan Medicinal Products for Nexavar are available here (hepatocellular carcinoma) and here (renal cell carcinoma).
Den fuldstændige EPAR for Nexavar kan ses i sin helhed her.
The full EPAR for Nexavar can be found here.
Dette sammendrag er sidst opdateret i 11- 2007.
This summary was last updated in 11-2007.
Blister (PP/ Alu)
Blister (PP/ alu)
Hver filmovertrukket tablet indeholder 200 mg sorafenib (som tosylat).
Each film-coated tablet contains 200 mg of sorafenib (as tosylate).
Røde, runde, bikonvekse filmovertrukne tabletter, mærket med Bayerkors på den ene side og ” 200 ” på den anden.
Red, round, biconvex film-coated tablets, debossed with Bayer cross on one side and "200" on the other side.
5. 1).
Hepatocellular carcinoma Nexavar is indicated for the treatment of hepatocellular carcinoma (see section 5.1).
Nyrecellecancer Nexavar er indiceret til behandling af patienter med fremskreden nyrecellecancer, hvor tidligere interferon- alfa - og interleukin- 2- baseret behandling ikke har hjulpet, eller hvor en sådan behandling ikke er blevet vurderet passende.
Renal cell carcinoma Nexavar is indicated for the treatment of patients with advanced renal cell carcinoma who have failed prior interferon-alpha or interleukin-2 based therapy or are considered unsuitable for such therapy.
Behandling med Nexavar bør overvåges af en læge, som har erfaring med brugen af anticancerbehandling.
Nexavar treatment should be supervised by a physician experienced in the use of anticancer therapies.
Den anbefalede dosis til voksne er 400 mg (to tabletter á 200 mg) to gange dagligt (ækvivalent med en total daglig dosis på 800 mg).
The recommended dose of Nexavar in adults is 400 mg (two tablets of 200 mg) twice daily (equivalent to a total daily dose of 800 mg).
Det anbefales, at Nexavar tabletter administreres uden mad eller med et måltid med lavt til moderat fedtindhold.
It is recommended that sorafenib should be administered without food or with a low or moderate fat meal.
Hvis patienten insisterer på at indtage et måltid med højt fedtindhold, bør sorafenibtabletterne indtages mindst 1 time før eller 2 timer efter måltidet.
If the patient intends to have a high-fat meal, sorafenib tablets should be taken at least 1 hour before or 2 hours after the meal.
Dosisjustering:
Posology adjustments:
Forekomst af mistænksomme bivirkninger kan kræve midlertidig afbrydelse eller dosisreduktion af Nexavarbehandlingen.
Management of suspected adverse drug reactions may require temporary interruption or dose reduction of Nexavar therapy.
4. 4).
When dose reduction is necessary, the Nexavar dose should be reduced to two tablets of 200 mg once daily (see section 4.4).
Sikkerheden og effekten hos børn og unge (< 18 år) har ikke været undersøgt.
The safety and efficacy in children and adolescents (< 18 years) have not been studied.
5. 3.).
Nexavar is not recommended for use in children and adolescents due to a lack of data on safety and efficacy (see section 5.3).
Der kræves ingen dosisreduktion hos ældre (patienter over 65 år).
No dose adjustment is required in the elderly (patients above 65 years of age).
2 Nedsat nyrefunktion:
2 Renal impairment:
Der kræves ingen dosisreduktion for patienter med mild, moderat eller svært nedsat nyrefunktion.
No dose adjustment is required in patients with mild, moderate or severe renal impairment.
5. 2).
No data is available in patients requiring dialysis (see section 5.2).
Patienter med nedsat nyrefunktion bør overvåges med hensyn til væske - og elektrolytbalance.
Monitoring of fluid balance and electrolytes in patients at risk of renal dysfunction is advised.
Der kræves ingen dosisreduktion for patienter med Child Pugh A og B (mild til moderat) nedsat leverfunktion.
No dose adjustment is required in patients with Child Pugh A and B (mild to moderate) hepatic impairment.
4. 4 og 5. 2).
No data is available on patients with Child Pugh C (severe) hepatic impairment (see section 4.4 and 5.2).
Dermatologisk toksicitet:
Dermatological toxicities:
Håndflade- fodsål hudreaktion (palmar- plantar erythrodysæstesi) og hududslæt er de mest almindelige bivirkninger af Nexavar.
Hand-foot skin reaction (palmar-plantar erythrodysaesthesia) and rash represent the most common adverse drug reactions with Nexavar.
Hududslæt og håndflade- fodsål hudreaktion er af CTC (Common Toxicity Criteria) grad 1 og 2 og optræder oftest i løbet af de første seks uger af behandlingen med Nexavar.
Rash and hand-foot skin reaction are usually CTC (Common Toxicity Criteria) Grade 1 and 2 and generally appear during the first six weeks of treatment with Nexavar.
4. 8).
Management of dermatological toxicities may include topical therapies for symptomatic relief, temporary treatment interruption and/ or dose modification of Nexavar, or in severe or persistent cases, permanent discontinuation of Nexavar (see section 4.8).
Hypertension:
Hypertension:
Et øget antal tilfælde af arteriel hypertension blev observeret hos patienter, der blev behandlet med Nexavar.
An increased incidence of arterial hypertension was observed in Nexavar-treated patients.
Hypertensionen var ofte mild til moderat, den optrådte tidligt i behandlingsforløbet og kunne behandles med antihypersiv standardbehandling.
Hypertension was usually mild to moderate, occurred early in the course of treatment, and was amenable to management with standard antihypertensive therapy.
4. 8).
In cases of severe or persistent hypertension, or hypertensive crisis despite institution of antihypertensive therapy, permanent discontinuation of Nexavar should be considered (see section 4.8).
Øget risiko for blødning kan opstå efter administration af Nexavar.
An increased risk of bleeding may occur following Nexavar administration.
4. 8).
If any bleeding event necessitates medical intervention it is recommended that permanent discontinuation of Nexavar should be considered (see section 4.8).
Hjerteiskæmi og/ eller infarkt:
Cardiac ischaemia and/ or infarction:
5. 1) var forekomsten af tilfælde med hjerteiskæmi/ hjerteinfarkt, som opstod som følge af behandling, større i Nexavargruppen (2, 9%) sammenlignet med placebogruppen (0, 4%).
In a randomised, placebo-controlled, double-blind study (study 1, see section 5.1) the incidence of treatment-emergent cardiac ischaemia/ infarction events was higher in the Nexavar group (2.9%) compared with the placebo group (0.4%).
5. 1), var forekomsten af tilfælde med hjerteiskæmi/ hjerteinfarkt 2. 7% hos Nexavarpatienterne sammenlignet med 1. 3% hos placebogruppen.
In study 3 (see section 5.1), the incidence of treatment-emergent cardiac ischaemia/ infarction events was 2.7% in Nexavar patients compared with 1.3% in the placebo group.
4. 8).
Temporary or permanent discontinuation of Nexavar should be considered in patients who develop cardiac ischaemia and/ or infarction (see section 4.8).
Gastrointestinal perforation:
Gastrointestinal perforation:
Gastrointestinal perforation er en ikke almindeligt forekommende bivirkning, og er indberettet for under 1% af de patienter, der blev behandlet med sorafenib.
Gastrointestinal perforation is an uncommon event and has been reported in less than 1% of patients taking sorafenib.
I nogle tilfælde havde dette ikke forbindelse med en synlig intraabdominal tumor.
In some cases this was not associated with apparent intra- abdominal tumor.
4. 8).
Sorafenib therapy should be discontinued (see section 4.8).
Der findes ingen tilgængelige data vedrørende patienter med Child- Pugh C (svært) nedsat leverfunktion.
No data is available on patients with Child Pugh C (severe) hepatic impairment.
4. 2 og 5. 2).
Since sorafenib is mainly eliminated via the hepatic route exposure might be increased in patients with severe hepatic impairment (see section 4.2 and 5.2).
Samtidig warfarinbehandling:
Warfarin co-administration:
Sjældent forekommende blødninger eller stigning i International Normalized Ratio (INR) er rapporteret hos nogle patienter, der har taget warfarin samtidig med Nexavarbehandling.
Infrequent bleeding events or elevations in the International Normalised Ratio (INR) have been reported in some patients taking warfarin while on Nexavar therapy.
4. 5 og 4. 8).
Patients taking concomitant warfarin or phenprocoumon should be monitored regularly for changes in prothrombin time, INR or clinical bleeding episodes (see sections 4.5 and 4.8).
3 Sårhelingskomplikationer:
3 Wound healing complications:
Midlertidig afbrydelse af Nexavarbehandlingen anbefales af forsigtighedsmæssige årsager til patienter, som skal gennemgå større kirurgiske indgreb.
Temporary interruption of Nexavar therapy is recommended for precautionary reasons in patients undergoing major surgical procedures.
Derfor bør beslutningen om genoptagelse af Nexavarbehandlingen efter større kirurgiske indgreb baseres på klinisk vurdering af tilstrækkelig sårheling.
Therefore, the decision to resume Nexavar therapy following a major surgical intervention should be based on clinical judgement of adequate wound healing.
Erfaringen med Nexavar til ældre patienter er begrænset.
The experience with the use of Nexavar in elderly patients is limited.
Nyrecellecancer:
Renal cell carcinoma:
5. 1); og benefit- risk for disse patienter er ikke blevet evalueret.
High Risk Patients, according to MSKCC (Memorial Sloan Kettering Cancer Center) prognostic group, were not included in the phase III clinical study in renal cell carcinoma (see study 1 in section 5.1); and benefit-risk in these patients has not been evaluated.
Lægemiddelsinteraktioner:
Drug-drug interactions:
4. 5).
Caution is recommended when administering Nexavar with compounds that are metabolised/ eliminated predominantly by the UGT1A1 (e. g. irinotecan) or UGT1A9 pathways (see section 4.5).
4. 5).
Caution is recommended when sorafenib is co-administered with docetaxel (see section 4.5).
Inducere af metabolismeenzymer:
Inducers of metabolic enzymes:
Administration af rifampicin i 5 dage før administration af en engangsdosis af sorafenib resulterede i en gennemsnitsreduktion på 37% i sorafenibs AUC.
Administration of rifampicin for 5 days before administration of a single dose of sorafenib resulted in an average 37% reduction of sorafenib AUC.
Andre inducere med CYP3A4- aktivitet og/ eller glucuronidation (f. eks.
Other inducers of CYP3A4 activity and/ or glucuronidation (e. g.
Hypericum perforatum også kendt som Johannesurt, phenytoin, carbamazepin, phenobarbital og dexamethason) kan også øge metabolismen af sorafenib og dermed nedsætte sorafenibkoncentrationer.
John’ s wort, phenytoin, carbamazepine, phenobarbital, and dexamethasone) may also increase metabolism of sorafenib and thus decrease sorafenib concentrations.
CYP3A4- hæmmer:
CYP3A4 inhibitors:
Disse data tyder på, at kliniske farmakokinetiske interaktioner mellem sorafenib og CYP3A4- hæmmere ikke foreligger.
These data suggest that clinical pharmacokinetic interactions of sorafenib with CYP3A4 inhibitors are unlikely.
CYP2C9- substrater:
CYP2C9 substrates:
Sorafenib hæmmede CYP2C9 in vitro.
Sorafenib inhibited CYP2C9 in vitro.
Det kan ikke udelukkes, at sorafenib kan øge koncentrationerne af samtidig administrerede substrater af CYP2C9.
It cannot be excluded that sorafenib may increase the concentrations of concomitantly administered substrates of CYP2C9.
Den samtidige behandling med Nexavar og warfarin, et CYP2C9- substrat, frembragte ingen ændringer i gennemsnit PT- INR sammenlignet med placebo.
The concomitant treatment with Nexavar and warfarin, a CYP2C9 substrate, did not result in changes in mean PT-INR compared to placebo.
4. 4).
However, patients taking warfarin or phenprocoumon should have their INR checked regularly (see section 4.4).
CYP2B6 og CYP2C8 substrater:
CYP2B6 and CYP2C8 substrates:
Sorafenib hæmmede CYP2B6 og CYP2C8 in vitro, men den kliniske relevans af denne hæmning er ikke blevet evalueret.
Sorafenib inhibited CYP2B6 and CYP2C8 in vitro, but the clinical relevance of this inhibition has not been evaluated.
Det kan ikke udelukkes, at sorafenib kan øge koncentrationerne af samtidig administrerede substrater af CYP2C8 (f. eks. bupropion, cyclophosphamid, efavirenz, ifosfamid, methadon) og CYP2C8 (f. eks paclitaxel, amodiaquin, repaglinid).
It cannot be excluded that sorafenib may increase the concentrations of concomitantly administered substrates of CYP2B6 (e. g. bupropion, cyclophosphamide, efavirenz, ifosfamide, methadone) and CYP2C8 (e. g. paclitaxel, amodiaquine, repaglinide).
UGT1A1 og UGT1A9 substrater:
UGT1A1 and UGT1A9 substrates:
Sorafenib hæmmede glucuronidation via UGT1A1 og UGT1A9 in vitro.
In vitro, sorafenib inhibited glucuronidation via UGT1A1 and UGT1A9.
4. 4).
The clinical relevance of this finding is unknown (see below and section 4.4).
CYP- isoformselektive substrater:
CYP isoforms selective substrates:
Samtidig administration af sorafenib og midazolam, dextrometorfan eller omeprazol, som er substrater for cytokrom CYP3A4, CYP2D6 og CYP2C919, henholdsvis, forandrede ikke eksponeringen af disse substanser.
Concomitant administration of sorafenib and midazolam, dextromethorphan or omeprazole, which are substrates for cytochromes CYP3A4, CYP2D6 and CYP2C19 respectively, did not alter the exposure of these agents.
Dette viser, at sorafenib hverken er en hæmmer eller en inducer for disse cytokrom- P450 isoenzymer.
This indicates that sorafenib is neither an inhibitor nor an inducer of these cytochrome P450 isoenzymes.
In vivo studier af CYP- enzyminduktion:
4 In vitro studies of CYP enzyme induction:
CYP1A2 - og CYP3A4- aktiviteter blev ikke ændret efter behandling af opdyrkede humane hepatocytter med sorafenib, hvilket indikerer, at sorafenib sandsynligvis ikke inducerer CYP1A2 og CYP3A4.
CYP1A2 and CYP3A4 activities were not altered after treatment of cultured human hepatocytes with sorafenib, indicating that sorafenib is unlikely to be an inducer of CYP1A2 and CYP3A4.
4 P- gp- substrater:
P-gp-substrates:
Sorafenib har vist sig at hæmme transportproteinet p- glycoprotein (P- pg) in vitro.
In vitro, sorafenib has been shown to inhibit the transport protein p-glycoprotein (P- gp).
Øget plasmakoncentrationer af P- pg- substrater, så som digoxin, kan ikke udelukkes ved samtidig behandling med sorafenib.
Increased plasma concentrations of P-gp substrates such as digoxin cannot be excluded with concomitant treatment with sorafenib.
Kombination med andre antineoplastiske lægemidler:
Combination with other anti-neoplastic agents:
Disse inkluderer gemcitabin, oxaliplatin, doxorubicin og irinotecan.
In clinical studies Nexavar has been administered with a variety of other anti-neoplastic agents at their commonly used dosing regimens including gemcitabine, oxaliplatin, doxorubicin, and irinotecan.
Sorafenib påvirker ikke farmakokinetikken for gemcitabin eller oxaliplatin.
Sorafenib had no effect on the pharmacokinetics of gemcitabine or oxaliplatin.
Samtidig behandling med Nexavar og doxorubicin resulterede i en 21% stigning af AUC for doxorubicin.
Concomitant treatment with Nexavar resulted in a 21% increase in the AUC of doxorubicin.
Nexavar, der blev givet samtidigt med irinotecan, hvis aktive metabolit SN- 38 metaboliseres yderligere af UGT1A1- systemet, gav en 67 - 120% stigning i AUC for SN- 38 og en 26 - 42% stigning i AUC for irinotecan.
When administered with irinotecan, whose active metabolite SN-38 is further metabolised by the UGT1A1 pathway, there was a 67 - 120% increase in the AUC of SN-38 and a 26 - 42% increase in the AUC of irinotecan.
4. 4).
The clinical significance of these findings is unknown (see section 4.4).
Samtidig administration af docetaxel (75 eller 100 mg/ m2 administreret en gang hver 21. dag) og sorafenib (200 mg to gange daglig eller 400 mg to gange daglig på dag 2 til og med 19 i en 21- dags cyklus med en 3 dages pause i doseringen omkring administrationen af docetaxel) resulterede i en 36 - 80% stigning i AUC for docetaxel og en 16 - 32% øgning af Cmax for docetaxel.
Docetaxel (75 or 100 mg/ m2 administered once every 21 days) when co-administered with sorafenib (200 mg twice daily or 400 mg twice daily administered on Days 2 through 19 of a 21-day cycle with a 3-day break in dosing around administration of docetaxel) resulted in a 36-80% increase in docetaxel AUC and a 16-32% increase in docetaxel Cmax.
4. 4).
Caution is recommended when sorafenib is co-administered with docetaxel (see section 4.4).
Der foreligger ikke tilstrækkelige data om brugen af sorafenib hos gravide kvinder.
There are no data on the use of sorafenib in pregnant women.
På rotter blev det vist, at sorafenib og dens metabolitter passerer placenta og sorafenib forventes at skade fostret.
In rats, sorafenib and its metabolites were demonstrated to cross the placenta and sorafenib is anticipated to cause harmful effects on the foetus.
Nexavar bør ikke anvendes under graviditet, medmindre det er klart nødvendigt og efter nøje overvejelse af moderens behov og risikoen for fostret.
Nexavar should not be used during pregnancy unless clearly necessary, after careful consideration of the needs of the mother and the risk to the foetus.
Kvinder i den fødedygtige alder skal bruge effektiv prævention under behandlingen.
Women of childbearing potential must use effective contraception during treatment.
5. 3).
Results from animal studies further indicate that sorafenib can impair male and female fertility (see section 5.3).
Det vides ikke, om sorafenib udskilles i human modermælk.
It is not known whether sorafenib is excreted in human milk.
Eftersom sorafenib kan skade barnets vækst og udvikling, (se pkt.
In animals, sorafenib and/ or its metabolites were excreted in milk.
4. 3).
Because sorafenib could harm infant growth and development (see section 5.3), women must not breast-feed during sorafenib treatment.
Der er intet, der tyder på, at Nexavar påvirker evnen til at føre bil eller betjene maskiner.
There is no evidence that Nexavar affects the ability to drive or to operate machinery.
De mest almindelige bivirkninger var diarré, udslæt, alopeci og håndflade- fodsål syndrom (svarende til palmar- plantar errytrodysæstesi syndrom i MedDRA).
The most common adverse reactions were diarrhoea, rash, alopecia and hand-foot syndrome (corresponds to palmar plantar erythrodysaesthesia syndrome in MedDRA).