natgillin/translations-raw huggingface dataset:
Bivirkninger rapporteret hos mindst 5% af patienterne i nogle af behandlingsgrupperne - studie 11213 for nyrecellecancer (se studie 1 under pkt.
Adverse reactions reported in at least 5% of patients in any treatment group – study 11213 in renal cell carcinoma (see study 1 in section 5.1).
5. 1).
System organ
Organklasse- system
class Metabolism and
Fortrukket term
Preferred term
grad alle grader
all grades grade 3 grade 4 all grades grade 3 grade 4
Metabolisme og
nutrition disorders Nervous system
3% 0%
0%
0%
12% 2% < 1% 1% < 1% 6% 0% 0% 2% 0% 38% 2% 0% 9% < 1% 16% < 1% 0% 12% < 1% 10% < 1% 0% 6% < 1% 6% 0% 0% 3% 0%
0% 0%
0% 0% 0% 0% 0% 0%
diarré
rash alopecia hand foot syndrome**
0%
28% < 1% 0% 9% < 1% 25% < 1% 0% 3% 0% 19% 4% 0% 3% 0%
0%
0% 0% 0%
kvalme opkastning forstoppelse
pruritus erythema dry skin skin exfoliation
0% 0% 0%
17% < 1% 0% 4% 0% 15% 0% 0% 4% 0% 11% 0% 0% 2% 0% 7% < 1% 0% 2% 0%
0% 0% 0%
0% 0% 0% 0%
udslæt alopecia håndflade- fodsål
Musculoskeletal and connective
< 1% < 1%
arthralgia
0% 0%
6% < 1% 0% 3% 0%
0% 0%
tissue disorders General disorders and
syndrom **
pain in extremity fatigue
0%
6% < 1% 0% 2% 0% 15% 2% 0% 11% < 1%
< 1% 0% 0% < 1%
0%
0% 0% 0% 0%
6 Table 2:
4% 4% 2% 2%
System organ
0% 0% 0% 0%
Preferred
0% 0% 0% 0%
Nexavar N= 297
Knogler, led, muskler og bindevæv
Placebo N= 302
artralgi smerte i
class Metabolism and
6%
term
< 1%
all grades
0%
grade 3
3%
grade 4 all grades grade 3
0%
grade 4
0%
nutrition disorders
ekstremiteter
anorexia
Almene symptomer og reaktioner på
gastrointestinal disorders
træthed
diarrhoea nausea abdominal
3%
5%
< 1%
1%
2% 1% < 1% < 1%
subcutaneous
0%
0% 2% 0%
0%
tissue disorders
alopecia udslæt pruritus tør hud
alopecia rash pruritus dry skin
0% < 1% 0% 0%
0% < 1% 0% 0%
0% 0% 0% 0%
0% 2% 0% 0% 8% 0% 0% 7% < 1% 0% 4% 0%
< 1%
< 1% 13% 3%
administrationsstedet Undersøgelser Luftveje, thorax og
administration site conditions
asteni vægttab
asthenia
6% 9%
6%
1% 2%
1%
< 1% 0%
< 1% 2% < 1%
2% < 1% < 1% 0%
0%
0% 0%
weight
mediastinum
Respiratory, thoracic and
hæshed
decreased
5%
2%
0%
0% < 1% 0%
Tabellen er inddelt i organklassesystemet (i MedDRA) og i frekvens.
Adverse reactions reported in multiple clinical trials are listed below in Table 3, by system organ class (in MedDRA) and frequency.
Meget almindelig (≥ 1/ 10), almindelig (≥ 1/ 100 til, < 1/ 10), ikke almindelig (≥ 1/ 1. 000 til, < 1/ 100).
Frequencies are defined as: very common (≥ 1/ 10), common (≥ 1/ 100, < 1/ 10), uncommon (≥ 1/ 1,000, < 1/ 100).
7 Tabel 3:
7 Table 3:
Alle bivirkninger rapporteret hos patienter i multiple kliniske studier
All adverse reactions reported in patients in multiple clinical trials
Organklassesystem Infektioner og parasitære sygdomme
Infections and infestations
Meget almindelig ≥1/ 10
≥ 1/ 10
Almindelig ≥1/ 100, < 1/ 10
≥ 1/ 100, < 1/ 10
Ikke almindelig ≥1/ 1, 000, < 1/ 100 follikulitis infektion
≥ 1/ 1,000, < 1/ 100 folliculitis infection
lymfopeni
lymphopenia
leukopeni neutropeni anæmi trombocytopeni
leucopenia neutropenia anaemia thrombocytopenia
overfølsomheds - reaktioner (inklusive hudreaktioner og urtikaria)
hypersensitivity reactions (including skin reactions and urticaria)
hypotyreoidisme
hypothyroidism
hyponatriæmi dehydrering
hyponatraemia dehydration
depression
depression
Nervesystemet Øre og labyrint Hjerte
Nervous system disorders Ear and labyrinth disorders
perifer sensorisk neuropati tinnitus
peripheral sensory neuropathy tinnitus
reversibel posterior leukoencefalopati * myokardieiskæmi og myokardieinfarkt * kongestiv hjertesvigt *
reversible posterior leukoencephalopathy*
blødning( inkl. gastrointestinal *, luftvejsblødning * og cerebral blødning *) hypertension
haemorrhage (inc. gastrointestinal*, respiratory tract* and cerebral haemorrhage*) hypertension
hypertensiv krise
hypertensive crisis*
rhinorré
rhinorrhoea
Mave- tarm- kanalen
Gastrointestinal disorders Hepatobiliary disorders
diarré kvalme opkastning
diarrhoea nausea vomiting
forstoppelse stomatitis (inklusive tør mund og glossodyni) dyspepsi dysfagi
constipation stomatitis (including dry mouth and glossodynia) dyspepsia dysphagia
stigning i bilirubin og gulsot cholecystitis cholangitis
gastro oesophageal reflux disease pancreatitis gastritis gastrointestinal perforations* increase in bilirubin and jaundice cholecystitis cholangitis
Hud og subkutane væv
8 System organ class
hududslæt alopeci håndflade- fodsål syndrom ** erytem pruritus
Very
Knogler, led, muskler og bindevæv
Common Common
artralgi myalgi
Uncommon
Almindelig ≥1/ 100, < 1/ 10 nyresvigt
≥ 1/ 100, < 1/ 10
Ikke almindelig ≥1/ 1, 000, < 1/ 100
≥ 1/ 1,000, < 1/ 100
gynækomasti
gynaecomastia
træthed smerter (inklusive mund, abdomen, skelet, tumorsmerter og hovedpine)
fatigue pain (including mouth, abdominal, bone, tumour pain and headache)
asteni feber influenzalignende sygdom
asthenia fever influenza like illness
forhøjet amylase forhøjet lipase
increased amylase increased lipase
vægttab forbigående stigning af transaminaser
weight decreased transient increase in transaminases
forbigående stigning af alkalinfosfatase i blodet unormal INR protrombinniveau unormalt
transient increase in blood alkaline phosphatase, INR abnormal, prothrombin level abnormal
** Håndflade- fodsål syndrom svarende til palmar- plantar erytrodysæstesi syndrom i MedDRA
* The adverse reactions may have a life-threatening or fatal outcome. ** hand foot syndrome corresponds to palmar plantar erythrodysaesthesia syndrome in MedDRA
Afvigelser i laboratorieundersøgelser Rapporter om øget lipase og amylase var meget almindelige.
Laboratory test abnormalities Increased lipase and amylase were very commonly reported.
Stigninger af lipase CTCAE Grad 3 eller 4 forekom hos 11% og 9% af patienterne i Nexavargruppen i henholdsvis studie 1 (nyrecellecancer) og studie 3 (levercellecancer) sammenlignet med 7% og 9% af patienterne i placebogruppen.
CTCAE Grade 3 or 4 lipase elevations occurred in 11% and 9% of patients in the Nexavar group in study 1 (RCC) and study 3 (HCC), respectively, compared to 7% and 9% of patients in the placebo group.
Stigningerne af amylase CTCAE Grad 3 eller 4 blev rapporteret hos 1% og 2% af patienterne i Nexavargruppen i henholdsvis studie 1 og studie 3, sammenlignet med 3% af patienterne i hver placebogruppe.
CTCAE Grade 3 or 4 amylase elevations were reported in 1% and 2% of patients in the Nexavar group in study 1 and study 3, respectively, compared to 3% of patients in each placebo group.
Klinisk pankreatitis blev rapporteret hos 2 ud af 451 patienter behandlet med Nexavar (CTCAE Grad 4) i studie 1, 1 ud af 297 patienter behandlet med Nexavar i studie 3 (CTCAE grad 2) og 1 ud af 451 patienter (CTCAE Grad 2) i placebogruppen i studie 1.
Clinical pancreatitis was reported in 2 of 451 Nexavar treated patients (CTCAE Grade 4) in study 1, 1 of 297 Nexavar treated patients in study 3 (CTCAE Grade 2), and 1 of 451 patients (CTCAE Grade 2) in the placebo group in study 1.
Hypofosfatæmi var et meget almindeligt laboratoriefund, som blev observeret hos 45% og 35% af patienterne, der blev behandlet med Nexavar sammenlignet med 12% og 11% hos placebopatienter i henholdsvis studie 1 og studie 3.
Hypophosphataemia was a very common laboratory finding, observed in 45% and 35% of Nexavar treated patients compared to 12% and 11% of placebo patients in study 1 and study 3, respectively.
I studie 1 forekom hypofosfatæmi CTCAE Grad 3 (1 - 2 mg/ dl) hos 13% af patienterne behandlet med Nexavar og hos 3% af patienterne i placebogruppen, i studie 3 hos 11% af patienterne behandlet med Nexavar og hos 2% af patienterne i placebogruppen.
CTCAE Grade 3 hypophosphataemia (1 – 2 mg/ dl) in study 1 occurred in 13% of Nexavar treated patients and 3% of patients in the placebo group, in study 3 in 11% of Nexavar treated patients and 2% of patients in the placebo group.
Der var ingen rapporterede tilfælde af CTCAE Grad 4 hypofosfatæmi (< 1 mg/ dl) hos hverken Nexavar - eller placebopatienter i studie 1, og 1 tilfælde i placebogruppen i studie 3.
There were no cases of CTCAE Grade 4 hypophosphataemia (< 1 mg/ dl) reported in either Nexavar or placebo patients in study 1, and 1 case in the placebo group in study 3.
Ætiologien om hypofosfatæmi associeret med Nexavar er ikke kendt.
The aetiology of hypophosphataemia associated with Nexavar is not known.
CTCAE Grad 3 eller 4 laboratorieafvigelser forekommer hos ≥ 5% af Nexavarbehandlede patienter og inkluderer lymfopeni og neutropeni.
CTCAE Grade 3 or 4 laboratory abnormalities occurring in ≥ 5% of Nexavar treated patients included lymphopenia and neutropenia.
Der findes ingen specifik behandling for overdosering af Nexavar.
There is no specific treatment for Nexavar overdose.
Bivirkningerne observeret ved denne dosis var primært diarré og dermatologiske tilfælde.
The adverse events observed at this dose were primarily diarrhoea and dermatological events.
Ved mistanke om overdosering bør administrering af Nexavar ophøre og understøttende behandling om nødvendigt gives.
In the event of suspected overdose Nexavar should be withheld and supportive care instituted where necessary.
Proteinkinase- hæmmere, ATC- kode:
Protein kinase inhibitors, ATC code:
Sorafenib er en multikinasehæmmer, som har vist både anti- proliferativ og anti- angiogenetiske egenskaber in vitro og in vivo.
Sorafenib is a multikinase inhibitor which has demonstrated both anti-proliferative and anti- angiogenic properties in vitro and in vivo.
Virkningsmekanisme og farmakodynamiske effekter Sorafenib er en multikinasehæmmer, som nedsætter proliferationen af tumorceller in vitro.
Mechanism of action and pharmacodynamic effects Sorafenib is a multikinase inhibitor that decreases tumour cell proliferation in vitro.
Sorafenib hæmmer aktiviteten af målfaktorer, som findes i tumorceller (CRAF, BRAF, V600E BRAF, c- KIT og FLT- 3) og i tumorens kar (CRAF, VEGFR- 2, VEGFR- 3 og PDGFR- β).
Sorafenib inhibits the activity of targets present in the tumour cell (CRAF, BRAF, V600E BRAF, c-KIT, and FLT-3) and in the tumour vasculature (CRAF, VEGFR-2, VEGFR-3, and PDGFR-ß).
RAF- kinaser er serin/ threonin- kinaser, hvorimod c- KIT, FLT- 3, VEGFR- 2, VEGFR- 3 og PDGFR- β er receptor- tyrosinkinaser.
RAF kinases are serine/ threonine kinases, whereas c-KIT, FLT-3, VEGFR-2, VEGFR-3, and PDGFR-ß are receptor tyrosine kinases.
Klinisk effekt Den kliniske sikkerhed og effekt af Nexavar er undersøgt hos patienter med levercellecancer (HCC) og hos patienter med fremskreden nyrecellecancer (RCC).
The clinical safety and efficacy of Nexavar have been studied in patients with hepatocellular carcinoma (HCC) and in patients with advanced renal cell carcinoma (RCC).
Levercellecancer Studie 3 (studie 100554) var et fase III, internationalt, multicenter, randomiseret, dobbeltblindt, placebo- kontrolleret studie med 602 patienter med levercellecancer.
Hepatocellular carcinoma Study 3 (study 100554) was a Phase III, international, multi-centre, randomised, double blind, placebo-controlled study in 602 patients with hepatocellular carcinoma.
Demografi og baseline sygdomskarakteristika var sammenlignelige mellem Nexavar - og placebogruppen med hensyn til ECOG status (status 0:
Demographics and baseline disease characteristics were comparable between the Nexavar and the placebo group with regard to ECOG status (status 0:
54% vs 54%; status 1:
54%; status 1:
38% vs 39%; status 2:
39%; status 2:
7%), TNM stadie (stadie I: < 1% vs < 1%; stadie II:
7%), TNM stage (stage I: < 1% vs. < 1%; stage II:
10. 4% vs 8. 3%; stadie III:
8.3%; stage III:
37. 8% vs 43. 6%; stadie IV:
43.6%; stage IV:
50. 8% vs 46. 9%), og BCLC stadie (stadie B:
46.9%), and BCLC stage (stage B:
18. 1% vs 16. 8%; stadie C:
16.8%; stage C:
81. 6% vs 83. 2%; stadie D: < 1% vs 0%).
0%).
Denne OS analyse viste en statistisk signifikant fordel for Nexavar i forhold til placebo for OS (HR:
This OS analysis showed a statistically significant advantage for Nexavar over placebo for OS (HR:
0. 69, p = 0. 00058, se tabel 4).
0.69, p = 0.00058, see Table 4).
I de præspecificerede stratificeringsfaktorer (ECOG status, tilstedeværelse eller fravær af makroskopisk vaskulær invasion og / eller ekstrahepatisk tumorspredning) var den relative risiko konsekvent til fordel for Nexavar i forhold til placebo.
In the prespecified stratification factors (ECOG status, presence or absence of macroscopic vascular invasion and/ or extrahepatic tumour spread) the hazard ratio consistently favoured Nexavar over placebo.
Undergruppeanalyserne tydede på en potentiel mindre udtalt behandlingseffekt for undergrupperne med patienter under 65 år og de med en metastaserende sygdom.
The descriptive subgroup analysis suggested a potentially less pronounced treatment effect for the subgroups of patients below 65 years of age and those with metastatic disease.
Tabel 4:
10 Table 4:
Effektresultater fra studie 3 (studie 100554) i levercellecancer
Efficacy Results from study 3 (study 100554) in hepatocellular carcinoma
Total overlevelse (OS) [median, uger (95% CI)]
Overall Survival (OS) [median, weeks (95% CI)]
46. 3 (40. 9, 57. 9)
46.3 (40.9, 57.9)
34. 4 (29. 4, 39. 4)
34.4 (29.4, 39.4)
0. 00058 *
0.00058*
0. 69 (0. 55, 0. 87)
0.69 (0.55, 0.87)
Tid til progression (TTP) [median, uger (95% CI)] **
Time to Progression (TTP) [median, weeks (95% CI)]**
24. 0 (18. 0, 30. 0)
24.0 (18.0, 30.0)
12. 3 (11. 7, 17. 1)
12.3 (11.7, 17.1)
0. 000007
0.000007
0. 58 (0. 45, 0. 74)
0.58 (0.45, 0.74)
CI=Konfidensinterval, HR=Relativ risiko (Nexavar overfor placebo) * Statistisk signifikant da p- værdien var under den præspecificerede O’ Brien Fleming stoppegrænse på 0. 0077 ** Uafhængig radiologisk redegørelse
CI=Confidence interval, HR=Hazard ratio (Nexavar over placebo) *statistically significant as the p-value was below the prespecified O’ Brien Fleming stopping boundary of 0.0077 **independent radiological review
10 Nyrecellecancer Sikkerheden og effekten af Nexavar ved behandling af fremskreden nyrecellecancer (RCC) blev undersøgt i to kliniske studier.
Renal cell carcinoma The safety and efficacy of Nexavar in the treatment of advanced renal cell carcinoma (RCC) were investigated in two clinical studies:
Studie 1 (studie 11213) var et fase III, multicenter, randomiseret, dobbeltblind, placebo- kontrolleret studie med 903 patienter.
Study 1 (study 11213) was a Phase III, multi-centre, randomised, double blind, placebo-controlled study in 903 patients.
Kun patienter med klar fremskreden nyrecellecancer og lav og mellem risiko MSKCC (Memorial Sloan Kettering Cancer Center) var inkluderet.
Only patients with clear cell renal carcinoma and low and intermediate risk MSKCC (Memorial Sloan Kettering Cancer Center) were included.
Cirka halvdelen af patienterne havde præstationskapacitet svarende til ECOG 0, og halvdelen af patienterne var i den lave MSKCC- prognosegruppe.
Approximately half of the patients had an ECOG performance status of 0, and half of the patients were in the low risk MSKCC prognostic group.
PFS blev evalueret ved blindet uafhængig radiologisk undersøgelse ved brug af RECIST- kriterier.
PFS was evaluated by blinded independent radiological review using RECIST criteria.
PFS- analysen var udført på 342 resultater hos 769 patienter.
The PFS analysis was conducted at 342 events in 769 patients.
Den gennemsnitlige PFS var 167 dage for patienter randomiseret til Nexavar sammenlignet med 84 dage for placebopatienter (HR = 0, 44; 95% CI:
The median PFS was 167 days for patients randomised to Nexavar compared to 84 days for placebo patients (HR = 0.44; 95% CI:
Alder, MSKCC- prognosegruppe, ECOG PS og tidligere behandling påvirkede ikke størrelsen af behandlingens effekt.
Age, MSKCC prognostic group, ECOG PS and prior therapy did not affect the treatment effect size.
Den nominelle alfa- værdi for denne analyse var 0, 0094.
The nominal alpha value for this analysis was 0.0094.
Den gennemsnitlige overlevelse var 19, 3 måneder for patienter randomiseret til Nexavar sammenlignet med 15, 9 måneder for placebopatienterne (HR = 0, 77; 95% CI:
The median survival was 19.3 months for patients randomised to Nexavar compared to 15.9 months for placebo patients (HR = 0.77; 95% CI:
Patienter med stabil sygdom i behandling med Nexavar var randomiseret til placebo eller fortsat behandling med Nexavar.
Patients with stable disease on therapy with Nexavar were randomised to placebo or continued Nexavar therapy.
Progressionsfri overlevelse hos patienter med RCC var signifikant længere i Nexavargruppen (163 dage) end i placebogruppen (41 dage) (p = 0, 0001, HR = 0, 29).
Progression-free survival in patients with RCC was significantly longer in the Nexavar group (163 days) than in the placebo group (41 days) (p = 0.0001, HR = 0.29).
Efter administration af Nexavar tabletter er den gennemsnitlige, relative biotilgængelighed 38 - 49% ved sammenligning med en oral opløsning.
After administration of Nexavar tablets the mean relative bioavailability is 38 - 49% when compared to an oral solution.
3 timer.
Following oral administration sorafenib reaches peak plasma concentrations in approximately 3 hours.
Når sorafenib gives samtidig med et måltid med højt fedtindhold reduceres absorptionen med 30% sammenlignet med administration til fastende tilstand.
When given with a high-fat meal sorafenib absorption was reduced by 30% compared to administration in the fasted state.
In vitro er bindingen til human plasmaproteiner 99, 5%.
In vitro binding of sorafenib to human plasma proteins is 99.5%.
Gentagen dosering med Nexavar i 7 dage resulterede i en 2, 5 - til 7- gange akkumulering sammenlignet med en enkeltdosis.
Multiple dosing of Nexavar for 7 days resulted in a 2.5- to 7-fold accumulation compared to single dose administration.
Metabolisme og elimination:
11 Metabolism and elimination:
25 - 48 timer.
The elimination half-life of sorafenib is approximately 25 - 48 hours.
70 - 85% af de cirkulerende analyserede metabolitter i plasmaet ved steady state.
Sorafenib accounts for approximately 70 - 85% of the circulating analytes in plasma at steady state.
Den cirkulerende hovedmetabolit af sorafenib i plasma, pyridin N- oxid, viser in vitro den samme effekt som den for sorafenib.
The main circulating metabolite of sorafenib in plasma, the pyridine N-oxide, shows in vitro potency similar to that of sorafenib.
9 - 16% af de cirkulerende analyserede metabolitter ved steady state.
This metabolite comprises approximately 9 - 16% of circulating analytes at steady state.
Heraf blev 77% af dosis udskilt via fæces, og 19% af dosis blev udskilt via urinen som glucuroniderede metabolitter.
Following oral administration of a 100 mg dose of a solution formulation of sorafenib, 96% of the dose was recovered within 14 days, with 77% of the dose excreted in faeces, and 19% of the dose excreted in urine as glucuronidated metabolites.
Uomdannet sorafenib, som udgjorde 51% af dosis, blev fundet i fæces men ikke i urinen, hvilket indikerer, at biliær udskillelse af uomdannet lægemiddel kan medvirke til eliminationen af sorafenib.
Unchanged sorafenib, accounting for 51% of the dose, was found in faeces but not in urine, indicating that biliary excretion of unchanged drug might contribute to the elimination of sorafenib.
11 Farmakokinetik i specielle populationer:
Pharmacokinetics in special populations:
Analyser af demografiske data viser, at der ikke er nogen relation mellem farmakokinetik og alder (op til 65 år), køn eller kropsvægt.
Analyses of demographic data suggest that there is no relationship between pharmacokinetics and age (up to 65 years) gender or body weight.
Børn:
Paediatric Population:
I fire fase- I kliniske studier var steady state eksponering af sorafenib ens hos patienter med mild til moderat nedsat nyrefunktion sammenlignet med eksponeringen af patienter med normal nyrefunktion.
In four Phase I clinical trials, steady state exposure to sorafenib was similar in patients with mild or moderate renal impairment compared to the exposures in patients with normal renal function.
I et klinisk farmakologistudie (enkeltdosis på 400 mg sorafenib) blev der ikke observeret nogen sammenhæng mellem sorafenibeksponering og nyrefunktion hos forsøgspersoner med normal nyrefunktion, mild, moderat eller svært nedsat nyrefunktion.
In a clinical pharmacology study (single dose of 400 mg sorafenib), no relationship was observed between sorafenib exposure and renal function in subjects with normal renal function, mild, moderate or severe renal impairment.
Hos patienter med levercellecancer og mild til moderat nedsat leverfunktion var eksponeringsgraderne sammenlignelige med eksponeringsgraden, som blev observeret hos patienter uden nedsat leverfunktion.
In hepatocellular carcinoma patients with mild or moderate hepatic impairment, exposure values were comparable and within the range of exposures observed in patients without hepatic impairment.
Der er ingen data for patienter med Child- Pugh C (svært) nedsat leverfunktion.
There are no data for patients with Child-Pugh C (severe) hepatic impairment.
Sorafenib elimineres hovedsageligt via leveren og eksponering kan være øget i disse patientpopulationer.
Sorafenib is mainly eliminated via the liver, and exposure might be increased in this patient population.
Toksicitetsstudier med gentagen dosering viste forandringer (degenerationer og regenerationer) i forskellige organer ved eksponering under den forventede kliniske eksponering (baseret på AUC - sammenligninger).
Repeat-dose toxicity studies revealed changes (degenerations and regenerations) in various organs at exposures below the anticipated clinical exposure (based on AUC comparisons).
Sorafenib var ikke genotoksisk i Ames test eller i mikronukleus- testen in vivo på mus.
Sorafenib was not genotoxic in the Ames test or in the in vivo mouse micronucleus assay.
Et intermediat fra fremstillingsprocessen, som også findes i den endelige lægemiddelsubstans (< 0, 15%), var positiv for mutagenese i en in vitro test på bakterieceller (Ames test).
One intermediate in the manufacturing process, which is also present in the final drug substance (< 0.15%), was positive for mutagenesis in an in vitro bacterial cell assay (Ames test).
Den sorafenibbatch, der blev testet i standardserien af genotoksicitetstudierne, inkluderede desuden 0, 34% PAPE.
Furthermore, the sorafenib batch tested in the standard genotoxicity battery included 0.34% PAPE.
Der er ikke udført nogen specifikke studier med sorafenib på dyr for at evaluere effekten på fertilitet.
12 No specific studies with sorafenib have been conducted in animals to evaluate the effect on fertility.
12 Sorafenib har vist sig at være embryotoksisk og teratogent, når det administreres til rotter og kaniner ved eksponering under den kliniske eksponering.
Sorafenib has been shown to be embryotoxic and teratogenic when administered to rats and rabbits at exposures below the clinical exposure.
Croscarmellosenatrium Cellulose, mikrokrystallinsk Hypromellose Natriumlaurilsulfat Magnesiumstearat
Core: croscarmellose sodium microcrystalline cellulose hypromellose sodium laurilsulfate magnesium stearate
Hypromellose Macrogol (3350) Titanoxid (E 171) Jernoxid (E 172)
Coating: hypromellose macrogol (3350) titanium dioxide (E 171) ferric oxide red (E 172)
112 (4 x 28) tabletter i transparente (PP/ Aluminium) blister.
112 (4 x 28) tablets in transparent (PP/ Aluminium) blister packs.
Bayer Schering Pharma AG 51368 Leverkusen Tyskland
Bayer Schering Pharma AG 51368 Leverkusen Germany
En revideret Risk Management Plan, baseret på CHMPs Guideline on Risk Management Systems for Medicinal Products for Human Use, skal indsendes samtidigt med PSUR, inden for 60 dage efter en vigtig (Pharmacovigilance - eller risikominimering) milepæl er nået, eller på det tidspunkt, hvor resultaterne fra et forsøg er tilgængelige, eller efter anmodning fra den ansvarlige myndighed.
An updated Risk Management Plan, as per the CHMP Guideline on Risk Management Systems for medicinal products for human use, should be submitted at the same time as the PSURs, within 60 days of an important (Pharmacovigilance or Risk minimisation) milestone being reached or when the results of a study becoming available or at the request of the Competent authority.
YDRE KARTON
{OUTER CARTON}
20 MINDSTEKRAV TIL MÆRKNING PÅ BLISTERKORT ELLER BLISTERSTRIPS
20 MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS
Nexavar 200 mg tabletter Sorafenib
Nexavar 200 mg tablets Sorafenib