natgillin/translations-raw huggingface dataset:
Din læge vil overvåge dit blodtryk, mens du tager Votrient.
Your doctor will monitor your blood pressure while you are taking Votrient.
Patienternes performancestatus (ECOG) var ens i pazopanib-gruppen og i placebogruppen (ECOG 0: 42 % i forhold til 41 %, ECOG 1: 58 % i forhold til 59 %).
The performance status (ECOG) was similar between the pazopanib and placebo groups (ECOG 0: 42% vs. 41%, ECOG 1: 58% vs. 59%).
Blod og lymfesystem f
Blood and lymphatic system disorders f
Doseringsanbefalinger til patienter med nedsat leverfunktion er baseret på farmakokinetiske studier af pazopanib til patienter med varierende grader af hepatisk dysfunktion (se pkt.
Dosing recommendations in hepatically impaired patients are based on pharmacokinetic studies of pazopanib in patients with varying degrees of hepatic dysfunction (see section 5.2).
Symptomer på infektioner kan omfatte: - feber - influenza-lignende symptomer som fx hoste, træthed og kropssmerter, der ikke går væk - stakåndethed og/eller hvæsende vejrtrækning - smerter, når du tisser - rifter, hudafskrabninger eller sår der er røde, varme, hævede eller smertefulde Søg straks lægehjælp, hvis du får nogen af disse symptomer.
Symptoms of infections may include: - fever - flu-like symptoms such as cough, tiredness and body aches that do not go away - shortness of breath and/or wheezing - pain while urinating - cuts, scrapes or wounds that are red, warm, swollen or painful Seek medical help immediately if you get any of these symptoms.
Samlede data fra det pivotale STS-studie (VEG110727, n = 369) og det understøttende fase II-studie (VEG20002, n = 142) blev vurderet i den overordnede evaluering af sikkerhed og tolerabilitet af pazopanib (i alt n = 382) hos forsøgspersoner med STS (se pkt.
Pooled data from the pivotal STS study (VEG110727, n=369) and the supportive Phase II study (VEG20002, n=142) was evaluated in the overall evaluation of safety and tolerability of pazopanib (total safety population n=382) in subjects with STS (see section 5.1).
Tabel 7 Median steady-state farmakokinetik for pazopanib målt hos patienter med nedsat leverfunktion
Table 7 Median steady-state pazopanib pharmacokinetics measured in subjects with hepatic impairment.
PFS Samlet Median (måneder) (95 % konfidensinterval)
PFS Overall Median (months) (95% CI)
Uskarpt eller forringet syn
Blurry or impaired vision
Tabletterne må ikke deles eller knuses, da dette påvirker optagelsen af Votrient og kan øge risikoen for bivirkninger.
Do not break or crush the tablets as this affects the way the medicine is absorbed and may increase the chance of side effects.
Tabel 1 Dosisjusteringer ved lægemiddelinduceret nedsat leverfunktion
Table 1 Dose modifications for drug-induced hepatotoxicity
Pazopanib hæmmer uridin-diphosphatglukuronosyl-transferase 1A1- (UGT1A1-) enzymet in vitro.
Pazopanib is an inhibitor of the uridine diphosphoglucuronosyl-transferase 1A1 (UGT1A1) enzyme in vitro.
Størstedelen af disse tilfælde var palmoplantar erytrodysæstesi-syndrom d Venøs tromboembolisk bivirkning - inkluderer dyb venetrombose, lungeemboli og trombose-termer e
The majority of these cases were Palmar-plantar erythrodysaesthesia syndrome d Venous thromboembolic events - includes Deep vein thrombosis, Pulmonary embolism and Thrombosis terms e
Tabletovertræk Hypromellose Rød jernoxid (E 172) Macrogol 400
Tablet coating Hypromellose Iron oxide red (E172) Macrogol 400
66 % af patienterne i placebo-armen fik behandling efter studiet sluttede sammenlignet med 30 % af patienterne i pazopanib-armen.
Sixty-six per cent of placebo patients received post-study therapy compared to 30% of pazopanib patients.
Det anbefales at udføre urinanalyse ved behandlingsstart og periodisk i behandlingsforløbet, og patienterne skal monitoreres for tiltagende proteinuri.
Baseline and periodic urinanalysis during treatment is recommended and patients should be monitored for worsening proteinuria.
Dette kan være symptomer på en blodprop (trombe).
These could be signs of a blood clot in your body (thromboembolism).
Meget almindelig Leukopeni
Very common Leukopenia
Votrient kan forårsage blodpropper i dine blodårer, især i dine ben (dyb venetrombose eller DVT), som også kan bevæge sig til dine lunger (lungeemboli).
Deep vein thrombosis (DVT) and pulmonary embolism Votrient may cause blood clots in your veins, especially in your legs (deep vein thrombosis or DVT), which may also travel to your lungs (pulmonary embolism).
Votrient er indiceret til behandling af voksne patienter med udvalgte undertyper af avanceret bløddelssarkom (STS), der tidligere har fået kemoterapi for metastatisk sygdom eller haft progression inden for 12 måneder efter (neo-)adjuverende behandling.
Votrient is indicated for the treatment of adult patients with selective subtypes of advanced soft-tissue sarcoma (STS) who have received prior chemotherapy for metastatic disease or who have progressed within 12 months after (neo) adjuvant therapy.
Administration af pazopanib sammen med uridin-diphosphatglukuronosyl-transferase 1A1-substrater (UGT1A1-substrater) (f.eks. irinotecan) skal foretages med forsigtighed, da pazopanib hæmmer UGT1A1 (se pkt.
Concomitant administration of pazopanib with uridine diphosphate glucuronosyl transferase 1A1 (UGT1A1) substrates (e.g. irinotecan) should be undertaken with caution since pazopanib is an inhibitor of UGT1A1 (see section 4.5).
Grapefrugtjuice indeholder en hæmmer af CYP3A4 og kan også øge plasmakoncentrationen af pazopanib.
Grapefruit juice contains an inhibitor of CYP3A4 and may also increase plasma concentrations of pazopanib.
Hypotyroidisme 18 (5 %) 0
Common Hypothyroidism 18 (5%)
Resultater fra en farmakokinetisk model af populationen (data fra forsøgspersoner med kreatininclearance i intervallet 30,8 ml/minut til 150 ml/minut ved udgangsniveauet) indikerede, at nedsat nyrefunktion sandsynligvis ikke har en klinisk relevant effekt på pazopanibs farmakokinetik.
Results from population pharmacokinetic modelling (data from subjects with baseline CLCR values ranging from 30.8 ml/min to 150 ml/min) indicated that renal impairment is unlikely to have clinically relevant effect on pazopanib pharmacokinetics.
Tegn og symptomer på slagtilfælde kan omfatte: - følelsesløshed eller svaghed i den ene side af din krop - problemer med at tale - hovedpine - svimmelhed
Signs and symptoms of stroke may include: - numbness or weakness on one side of your body - difficulty talking - headache - dizziness
Pazopanibs sikkerhed og virkning ved STS blev undersøgt i et pivotalt fase III randomiseret, dobbelt-blindet, placebokontrolleret multicenterstudie (VEG 110727).
The efficacy and safety of pazopanib in STS were evaluated in a pivotal Phase III randomised, double-blind, placebo-controlled multicentre study (VEG110727).
I et fase II-studie, der omfattede 225 patienter med lokalt tilbagefald eller metastatisk clear celle renalcellekarcinom, var den objektive responsrate 35 %.
In a Phase II study of 225 patients with locally recurrent or metastatic clear cell renal cell carcinoma, objective response rate was 35% and median duration of response was 68 weeks, as per independent review.
I hver behandlingsgruppe var der en lidt større procentdel af forsøgspersoner med 2+ linjer af tidligere systemisk behandling mod avanceret sygdom (58 % og 55 % i henholdsvis placebo- og pazopanib-armen) sammenlignet med 0 og 1 linjer af tidligere systemisk behandling (42 % og 45 % i henholdsvis placebo- og pazopanib-armen).
In each treatment group, there was a slightly greater percentage of subjects in the 2+ lines of prior systemic therapy for advanced disease (58% and 55%, respectively, for placebo and pazopanib treatment arms) compared with 0 or 1 lines of prior systemic therapy (42% and 45%, respectively, for placebo and pazopanib treatment arms).
Ikke kendt (kan ikke estimeres ud fra forhåndenværende data): - en udvidelse og svækkelse af en blodårevæg eller en rift i en blodårevæg (aneurismer og arterielle dissektioner)
Not known (frequency cannot be estimated from the available data): - an enlargement and weakening of a blood vessel wall or a tear in a blood vessel wall
Pazopanib skal administereres mindst 1 time før eller 2 timer efter administration af korttidsvirkende antacidum.
Pazopanib should be administered at least 1 hour before or 2 hours after administration of short-acting antacids.
Votrient er indiceret til førstelinjebehandling af voksne patienter med avanceret renalcellekarcinom (RCC) og til RCC-patienter, som tidligere har fået cytokinbehandling for avanceret sygdom.
Votrient is indicated in adults for the first-line treatment of advanced renal cell carcinoma (RCC) and for patients who have received prior cytokine therapy for advanced disease.
Kliniske studier med pazopanib i kombination med pemetrexed (ikke-småcellet lungecancer [NSCLC]) og lapatinib (cervixcancer) blev afsluttet tidligere end planlagt pga. betænkelighed ved øget toksicitet og/eller mortalitet.
Clinical studies of pazopanib in combination with pemetrexed (non-small cell lung cancer [NSCLC]) and lapatinib (cervical cancer) were terminated early due to concerns over increased toxicity and/or mortality, and a safe and effective combination dose has not been established with these regimens.
Afbryd pazopanib, indtil aminotransferaserne vender tilbage til grad 1 eller udgangsniveauet.
Interrupt pazopanib until transaminases return to Grade 1 or baseline.
Letale bivirkninger, der blev anset for muligvis at være relateret til pazopanib, inkluderede gastrointestinal blødning, pulmonal blødning/hæmoptyse, abnorm leverfunktion, intestinal perforation og iskæmisk apopleksi.
Fatal events that were considered possibly related to pazopanib included gastrointestinal haemorrhage, pulmonary haemorrhage/haemoptysis, abnormal hepatic function, intestinal perforation and ischaemic stroke.
Tegn på, at din lever muligvis ikke fungerer korrekt, kan omfatte: - gulfarvning af din hud eller af det hvide i dine øjne (gulsot) - mørk urin - træthed - kvalme - opkastning - appetitløshed - smerter i højre side af dit maveområde (abdomen) - tendens til blå mærker
Signs that your liver may not be working properly may include: - yellowing of your skin or the whites of your eyes (jaundice) - dark urine - tiredness - nausea - vomiting - loss of appetite - pain on the right side of your stomach area (abdomen) - bruising easily
Karcinogenicitetsstudier med pazopanib af 2 års varighed viste et øget antal leveradenomer hos mus og duodenale adenokarcinomer hos rotter.
In two-year carcinogenicity studies with pazopanib, there were increased numbers of liver adenomas noted in mice and duodenal adenocarcinomas noted in rats.
Pazopanib er ikke undersøgt hos patienter med hæmoptyse og cerebral blødning eller klinisk signifikant gastrointestinal (GI) blødning inden for de sidste 6 måneder.
Pazopanib has not been studied in patients who had a history of haemoptysis, cerebral haemorrhage or clinically significant gastrointestinal (GI) haemorrhage in the past 6 months.
• Periodiske, opdaterede sikkerhedsindberetninger (PSUR'er)
Periodic Safety Update Reports
Meget almindelige bivirkninger, der kan ses i blod- eller urinprøver: - forhøjede leverenzymer - nedsat albumin i blodet - protein i urinen - nedsat antal blodplader (celler, der hjælper blodet til at størkne) - nedsat antal hvide blodlegemer
Very common side effects that may show up in your blood or urine tests: - increase in liver enzymes - decrease in albumin in the blood - protein in the urine - decrease in the number of blood platelets (cells that help blood to clot) - decrease in the number of white blood cells
Du må ikke tage Votrient sammen med mad, da det påvirker optagelsen af Votrient.
Don't take Votrient with food, as it affects the way the medicine is absorbed.
I juvenile toksicitetsstudier, hvor rotter i præ-afvænningsfasen fik pazopanib fra dag 9 til dag 14 efter fødslen, sås dødsfald og unormal organvækst/modning af nyrer, lunger, lever og hjerte ved en dosis på ca. 0,1 gang den kliniske eksponering, baseret på AUC hos voksne mennesker.
In juvenile toxicity studies, when pre-weaning rats were dosed from day 9 post partum through to day 14 post partum, pazopanib caused mortalities and abnormal organ growth/maturation in kidney, lung, liver and heart, at a dose approximately 0.1 times the clinical exposure based on AUC in adult humans.
Dysgeusi c
Very common Dysgeusia c
Baseret på sikkerheds- og tolerabilitetsdata anbefales det, at pazopanibdosis reduceres til 200 mg én gang daglig hos patienter med moderat nedsat leverfunktion (se pkt.
Based on safety and tolerability data, the dose of pazopanib should be reduced to 200 mg once daily in subjects with moderate hepatic impairment (see section 4.2).
Samtidig behandling med kraftige hæmmere af CYP3A4, P-glycoprotein (P-gp) eller brystcancer-resistent protein (BCRP) skal undgås på grund af risikoen for en øget pazopanib-eksponering (se pkt.
Concomitant treatment with strong inhibitors of CYP3A4, P-glycoprotein (P-gp) or breast cancer resistance protein (BCRP) should be avoided due to risk of increased exposure to pazopanib (see section 4.5).
Trombotisk mikroangiopati (TMA)
Thrombotic microangiopathy (TMA)
Fortæl det til lægen eller på apoteket, hvis du tager et eller flere af disse lægemidler.
Tell your doctor or pharmacist if you take any of these.
Perforering og fistler
Perforation and fistula
Ændring i hårfarve 404 (35 %) 1 (<1 %) 0 Palmoplantar erytrodysæestesi (PPE) (hånd-fodsyndrom)
Very common Hair colour change 404 (35%) 1 (<1%) Palmar-plantar erythrodysaesthesia syndrome
Brug ikke lægemidlet efter den udløbsdato, der står på pakningen efter EXP. Udløbsdatoen er den sidste dag i den nævnte måned.
Do not use this medicine after the expiry date (EXP) which is stated on the bottle and the carton.
Votrient kan forårsage løsning af eller rift i hinden bagerst i øjet (nethindeløsning eller rift i nethinden).
Votrient can cause separation or tear of the lining of the back part of the eye (retinal detachment or tear).
Dehydrering Ikke almindelig Hypomagnesiæmi
Common Dehydration Uncommon Hypomagnesaemia
Posterior reversibel encefalopati/reversibel posterior leukoencefalopatisyndrom †
Posterior reversible encephalopathy / reversible posterior leukoencephalopathy syndrome†
Dysgeusi, ageusi og hypogeusi d Fald i antallet af hvide blodlegemer, fald i neutrofil- og leukocyttallet e
Dysgeusia, ageusia and hypogeusia d White cell count decreased, neutrophil count decreased and leukocyte count decreased e
De fås i beholdere med 30 eller 60 tabletter.
They are supplied in bottles of 30 or 60 tablets.
Andre lægemidlers effekt på pazopanib
Effects of other medicinal products on pazopanib
Resultater fra en meta-analyse af pooled data fra kliniske studier med pazopanib, viser et forhøjet ALAT-niveau > 3 gange den øvre normalgrænse hos 126 ud af 895 patienter (14 %), der ikke fik statiner, sammenlignet med hos 11 ud af 41 patienter (27 %), der samtidig fik simvastatin (p = 0,038).
Results from a meta-analysis using pooled data from clinical studies with pazopanib show that ALT >3x ULN was reported in 126/895 (14%) of patients who did not use statins, compared with 11/41 (27%) of patients who had concomitant use of simvastatin (p = 0.038).
Nogle typer af medicin kan påvirke Votrients virkning eller øge sandsynligheden for, at du får bivirkninger.
Some medicines may affect how Votrient works or make it more likely that you'll have side effects.
Pazopanib skal administreres med forsigtighed sammen med andre orale BCRP- og P-gp-substrater.
Care should be taken when pazopanib is co-administered with other oral BCRP and P-gp substrates.
Lapatinibs hæmning af P-gp og/eller BCRP bidrog sandsynligvis til den øgede pazopanib-eksponering.
Inhibition of P-gp and/or BCRP by lapatinib likely contributed to the increased exposure to pazopanib.
Endvidere kan en hæmning af BCRP og P-gp i mave-tarmkanalen af pazopanib ikke udelukkes.
Furthermore, inhibition of BCRP and P-gp by pazopanib in the gastrointestinal tract cannot be excluded.
CYP3A4-, P-gp- og BCRP-hæmmere Pazopanib er et CYP3A4-, P-gp- og BCRP-substrat.
CYP3A4, P-gp, BCRP inhibitors Pazopanib is a substrate for CYP3A4, P-gp and BCRP.
TMA er rapporteret i kliniske studier med pazopanib som monoterapi, i kombination med bevacizumab og i kombination med topotecan (se pkt.
TMA has been reported in clinical studies of pazopanib as monotherapy, in combination with bevacizumab, and in combination with topotecan (see section 4.8).
Blodtrykket skal monitoreres og reguleres omgående ved en kombination af anti-hypertensiv behandling og dosistilpasning af pazopanib (pausering og genopstart med en reduceret dosis baseret på klinisk vurdering) (se pkt.
Blood pressure should be monitored and managed promptly using a combination of anti-hypertensive therapy and dose modification of pazopanib (interruption and re-initiation at a reduced dose based on clinical judgement) (see sections 4.2 and 4.8).
Administration af pazopanib sammen med måltider med et højt eller lavt fedtindhold resulterer i en 2-folds stigning i AUC og Cmax.
Administration of pazopanib with a high-fat or low-fat meal results in an approximately 2-fold increase in AUC and Cmax.
Samtidig administration med kraftige P-gp- eller BCRP-hæmmere kan også ændre eksponeringen for og fordelingen af pazopanib, herunder fordelingen i centralnervesystemet (CNS).
Co-administration with potent P-gp or BCRP inhibitors may also alter the exposure and distribution of pazopanib, including distribution into the central nervous systems (CNS).
Kardiel dysfunktion/hjerteinsufficiens
Cardiac dysfunction/Heart failure
Der skal udvises forsigtighed ved behandling af patienter med en kreatininclearance på under 30 ml/minut, da der ikke er erfaring med anvendelse af pazopanib hos denne patientpopulation.
Caution is advised in patients with creatinine clearance below 30 ml/min as there is no experience of pazopanib in this patient population.
Fødevarers indvirkning på pazopanib
Effect of food on pazopanib
Patienter med kendt eller formodet Gilberts syndrom med kun en let indirekte hyperbilirubinæmi og forhøjet ALAT >3 gange den øvre normalgrænse skal behandles efter anbefalingerne for isoleret forhøjet ALAT.
Patients with only a mild indirect hyperbilirubinaemia, known or suspected Gilbert's syndrome, and elevation in ALT >3 x ULN should be managed as per the recommendations outlined for isolated ALT elevations.
Hver behandlingsarm omfattede samme antal behandlingsnaive patienter som patienter, der tidligere var behandlet med cytokiner (53 % og 47 % i pazopanib-armen, 54 % og 46 % i placebo-armen).
A similar proportion of patients in each arm were treatment-naïve and cytokine pre-treated (53% and 47% in pazopanib arm, 54% and 46% in placebo arm).
Dit blodtryk vil blive målt, før du får Votrient, og mens du er i behandling.
Your blood pressure will be checked before you take Votrient and while you are taking it.
Fortæl altid lægen eller apotekspersonalet, hvis du bruger anden medicin eller har gjort det for nylig.
Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.
ILD, som kan være dødelig, er blevet rapporteret i forbindelse med pazopanib (se pkt.
ILD, which can be fatal, has been reported in association with pazopanib (see section 4.8).
Almindelige bivirkninger, der kan ses i dine blod- eller urinprøver: - nedsat aktivitet af skjoldbruskkirtlen - unormal leverfunktion - forhøjet bilirubin-niveau (et stof, der dannes af leveren) - forhøjet lipase-niveau (et fordøjelsesenzym) - forhøjet kreatinin-niveau (et stof, der dannes i musklerne) - ændringer i niveauet af andre stoffer/enzymer i blodet.
Common side effects that may show up in your blood or urine tests: - underactive thyroid gland - abnormal liver function - increase in bilirubin (a substance produced by the liver) - increase in lipase (an enzyme involved in digestion - increase in creatinine (a substance produced in muscles) - changes in the levels of other different chemicals / enzymes in the blood.
Samtidig brug af pazopanib og en kraftig CYP3A4-hæmmer bør undgås (se pkt.
Concomitant use of pazopanib with a strong CYP3A4 inhibitor should be avoided (see section 4.4).
De fås i beholdere med 30 eller 90 tabletter.
They are supplied in bottles of 30 or 90 tablets.
Investigatorerne indberettede sjældnere unormale laboratorieværdier som en bivirkning, end laboratorieværdi-tabellerne giver udtryk for.
Laboratory abnormalities were reported as adverse events less frequently by investigators than as indicated by laboratory value tables.
Hæmmere og induktorer af CYP3A4 kan derfor ændre metaboliseringen af pazopanib.
Therefore, inhibitors and inducers of CYP3A4 may alter the metabolism of pazopanib.
Samlede data fra det centrale RCC-studie (VEG105192, n = 290), det forlængede studie (VEG107769, n = 71), det understøttende fase II-studie (VEG102616, n = 225) og det randomiserede, ublindede, parallelgruppe fase III non-inferioritets studie (VEG108844, n = 557) blev vurderet i den overordnede evaluering af sikkerheden ved og tolerancen over for pazopanib (i alt n = 1149) hos forsøgspersoner med RCC (se pkt.
Pooled data from the pivotal RCC study (VEG105192, n=290), the extension study (VEG107769, n=71), the supportive Phase II study (VEG102616, n=225) and the randomised, open-label, parallel group Phase III non-inferiority study (VEG108844, n=557) were evaluated in the overall evaluation of safety and tolerability of pazopanib (total n=1149) in subjects with RCC (see section 5.1).
Samtidig behandling med induktorer af CYP3A4 skal undgås på grund af risikoen for en nedsat pazopanib-eksponering (se pkt.
Concomitant treatment with inducers of CYP3A4 should be avoided due to risk of decreased exposure to pazopanib (see section 4.5).
Forlængelse af QT-intervallet og torsades de pointes
QT prolongation and torsade de pointes
Administration af en knust 400 mg pazopanib-tablet øgede AUC(0-72) med 46 %, resulterede i en 2-folds stigning i Cmax og nedsatte tmax med ca. 2 timer sammenlignet med administration af en hel tablet.
Administration of a pazopanib 400 mg crushed tablet increased AUC(0-72) by 46% and Cmax by approximately 2 fold and decreased tmax by approximately 2 hours compared to administration of the whole tablet.
In vitro-forsøg tyder på, at pazopanib er et P-gp-substrat og et BCRP-substrat.
In vitro studies suggest that pazopanib is a substrate for P-gp and BCRP.
Almindelig Hyperbilirubinæmi Abnorm leverfunktion 29 (3 %) Hepatotoksicitet
Hyperbilirubinaemia 38 (3%) Hepatic function abnormal
HDPE-beholder med børnesikret låg af polypropylen, som indeholder enten 30 eller 90 tabletter.
HDPE bottles with polypropylene child resistant closures containing either 30 or 90 tablets.
I de tre mindste af disse 20 undergrupper oversteg hazad ratioens punktestimat 1,25; dvs. hos personer uden tidligere nefrektomi (n = 186, HR = 1,403, 95 % konfidensinterval (0,995-2,061)), med baseline-LDH > 1,5 x ULN (n = 68, HR = 1,72, 95 % konfidensinterval (0,943-3,139)), og MSKCC: lav risiko (n = 119, HR = 1,472, 95 % konfidensinterval (0,937-2,313)).
In the three smallest of these 20 subgroups, the point estimate of the hazard ratio exceeded 1.25; i.e. in subjects with no prior nephrectomy (n=186, HR=1.403, 95% CI (0.955, 2.061)), baseline LDH >1.5 x ULN (n=68, HR=1.72, 95% CI (0.943, 3.139)), and MSKCC: poor risk (n=119, HR=1.472, 95% CI (0.937, 2.313)).
Ødem b
Oedema b
Tabel 4 Samlede effektresultater fra RCC bedømt ved uafhængig vurdering (VEG105192)
Table 4 Overall efficacy results in RCC by independent assessment (VEG105192)