natgillin/translations-raw huggingface dataset:
Følgende kan øge risikoen for bivirkninger med Afinitor: ketoconazol, itraconazol, voriconazol eller fluconazol og andre lægemidler til behandling af svampeinfektioner.
The following may increase the risk of side effects with Afinitor: ketoconazole, itraconazole, voriconazole, or fluconazole and other antifungals used to treat fungal infections.
Afinitor indeholder lactose
Afinitor contains lactose
• hævelse i ansigtet, læberne, tungen eller halsen
• swelling of the face, lips, tongue or throat
Grad 2 Hvis toksiciteten tolereres, er dosisjustering ikke nødvendig.
Grade 2 If toxicity is tolerable, no dose adjustment required.
Tag ikke Afinitor hvis du er allergisk over for everolimus, beslægtede stoffer som fx sirolimus eller temsirolimus eller et af de øvrige indholdsstoffer i Afinitor (angivet i punkt 6).
Do not take Afinitor if you are allergic to everolimus, to related substances such as sirolimus or temsirolimus, or to any of the other ingredients of this medicine (listed in section 6).
Everolimus bør ikke anvendes under graviditet eller til kvinder i den fertile alder, der ikke anvender kontraception.
Everolimus is not recommended during pregnancy and in women of childbearing potential not using contraception.
Du kan derfor risikere af få en infektion, mens du tager Afinitor.
Therefore, you may be at risk of getting an infection while you are taking Afinitor.
Hos patienter med progressive massive tumorer var Vd 191 l for det synlige centrale kompartment og 157 l for det synlige perifere kompartment.
In patients with advanced solid tumours, Vd was 191 l for the apparent central compartment and 517 l for the apparent peripheral compartment.
Understøttende PFS-analyser var baseret på en uafhængig, central radiologisk vurdering.
Supportive PFS analyses were based on an independent central radiology review.
Afinitor kan påvirke evnen til at føre motorkøretøj og betjene maskiner i mindre eller moderat grad.
Afinitor may have a minor or moderate influence on the ability to drive and use machines.
* Se også undersektion ”Beskrivelse af udvalgte bivirkninger”
Very common Weight decreased * See also subsection “Description of selected adverse reactions”
Den samlede sikkerhedsprofil i dette studie var i overensstemmelse med den etablerede sikkerhedsprofil for everolimus til behandling af onkologiske sygdomme og tuberøst sklerosekompleks (TSC) med undtagelse af en let forhøjet forekomst af oral candidiasis, der blev rapporteret hos 2,2 % (2/92) af patienterne.
The overall safety profile in this study was consistent with that established for everolimus in the oncology and tuberous sclerosis complex (TSC) settings, with the exception of a slightly increased frequency of oral candidiasis which was reported in 2.2% (n=2/92) of patients.
Afinitor kan muligvis påvirke kvinders frugtbarhed.
Afinitor may have an impact on female fertility.
Everolimus nedsætter blodtilførslen til kræftknuden og hæmmer væksten og spredningen af kræftceller.
Everolimus reduces the blood supply to the tumour and slows down the growth and spread of cancer cells.
Ca. 20% af everolimus-koncentrationen i fuldblod er begrænset til plasma hos cancerpatienter, der får everolimus 10 mg/dag.
Approximately 20% of the everolimus concentration in whole blood is confined to plasma in cancer patients given everolimus 10 mg/day.
95% CI [0,27, 0,45] Log-rank p værdi = <0,001 Kaplan-Meier medianer Afinitor : 11,04 måneder Placebo : 4,60 måneder
95% CI [0.27, 0.45] Log-rank p value = <0.001 Kaplan-Meier medians Afinitor : 11.04 months Placebo : 4.60 months
I en farmakokinetisk populationsevaluering af cancerpatienter sås ingen signifikant alderspåvirkning (27-85 år) på oral clearance af everolimus.
In a population pharmacokinetic evaluation in cancer patients, no significant influence of age (27-85 years) on oral clearance of everolimus was detected.
Tabel 7 RECORD-1 - Resultater for progressionsfri overlevelse
Table 7 RECORD-1 - Progression-free survival results
Bedste totale respons (%) (95% CI) Objektiv responsrate b n/a d e
Best overall response (%) (95% CI) Objective response rate b
• Følelse af svaghed eller træthed
• Feeling weak or tired
Studiet nåede ikke sit primære effektendepunkt (progressionsfri overlevelse [PFS]), og interimanalysen af den totale overlevelse (overall survival OS) favoriserede numerisk armen med placebo plus depot-octreotid.
The study did not meet the primary efficacy endpoint (progression-free-survival [PFS]) and the overall survival (OS) interim analysis numerically favoured the placebo plus depot octreotide arm.
Det primære formål med studiet var at estimere HR for PFS for everolimus + exemestan versus everolimus alene.
The primary objective of the study was to estimate the HR of PFS for everolimus + exemestane versus everolimus alone.
Nedsat nyrefunktion efter transplantation (kreatininclearance 11-107 ml/min) påvirkede ikke everolimus' farmakokinetik hos transplantationspatienter.
Post-transplant renal impairment (creatinine clearance range 11-107 ml/min) did not affect the pharmacokinetics of everolimus in transplant patients.
Steady-state-farmakokinetik
Steady-state pharmacokinetics
AUC ↓63% (interval 0-80%) Cmax ↓58% (interval 10-70%)
AUC ↓63% (range 0-80%) Cmax ↓58% (range 10-70%)
Hvis det er tilfældet, kan det være, at din læge skal ordinere en anden Afinitor-dosis.
If this is the case, your doctor may need to prescribe a different dose of Afinitor.
Resultaterne for det sekundære endepunkt OS var ikke konsistente med det primære endepunkt PFS, da der blev observeret en trend, der favoriserer everolimus alene-armen.
Results of the secondary endpoint OS were not consistent with the primary endpoint PFS, with a trend observed favouring the everolimus alone arm.
Der sås ingen statistisk signifikant behandlingsrelateret forskel i overlevelse (hazard ratio 0,87; konfidensinterval: 0,65-1,17; p=0,177).
No statistically significant treatment-related difference in overall survival was noted (hazard ratio 0.87; confidence interval: 0.65-1.17; p=0.177).
Mens Afinitor tages, skal man være på vagt over for symptomer og tegn på infektion: hvis der stilles en infektionsdiagnose, skal der omgående iværksættes hensigtsmæssig behandling, og afbrydelse eller ophør med Afinitor-behandlingen skal overvejes.
While taking Afinitor, be vigilant for symptoms and signs of infection; if a diagnosis of infection is made, institute appropriate treatment promptly and consider interruption or discontinuation of Afinitor.
Stærkt nedsat leverfunktion (Child-Pugh C): Afinitor er kun anbefalet hvis de ønskede fordele opvejer risiciene.
Severe hepatic impairment (Child-Pugh C) - Afinitor is only recommended if the desired benefit outweighs the risk.
hvis du skal vaccineres, mens du tager Afinitor.
if you need to receive a vaccine while taking Afinitor.
I begge arme fik 58% af patienterne systemisk behandling op til studiet.
Fifty-eight percent of the patients in both arms received prior systemic therapy.
Behandling med Afinitor bør initieres og superviseres af læger med erfaring inden for cancerterapi.
Treatment with Afinitor should be initiated and supervised by a physician experienced in the use of anticancer therapies.
Hvis diagnosen invasiv systemisk svampeinfektion stilles, skal Afinitor-behandlingen omgående og permanent seponeres, og patienten skal behandles med et passende antimykotisk lægemiddel.
If a diagnosis of invasive systemic fungal infection is made, the Afinitor treatment should be promptly and permanently discontinued and the patient treated with appropriate antifungal therapy.
Interaktion - Ændring i Everolimus AUC/Cmax Geometrisk gennemsnitsratio (observeret interval)
Interaction - Change in Everolimus AUC/Cmax Geometric mean ratio (observed range)
Patienterne blev stratificeret ifølge Memorial Sloan-Kettering Cancer Center (MSKCC)-prognosescorings-systemet (grupperne favorabel vs. middel vs. dårlig risiko) og tidligere cancerterapi (1 vs. 2 tidligere VEGFR-TKI'er).
Patients were stratified according to Memorial Sloan-Kettering Cancer Center (MSKCC) prognostic score (favourable- vs. intermediate- vs. poor-risk groups) and prior anticancer therapy (1 vs. 2 prior VEGFR-TKIs).
Progressionsfri overlevelse (PFS), dokumenteret ved brug af RECIST (Response Evaluation Criteria in Solid Tumours) og vurderet via en blindet, uafhængig central gennemgang, var det primære endepunkt.
Progression-free survival, documented using RECIST (Response Evaluation Criteria in Solid Tumours) and assessed via a blinded, independent central review, was the primary endpoint.
Der blev taget højde for demografien (median alder 58 år, 55% mænd, 78,5% kaukasier).
Demographics were well balanced (median age 58 years, 55% male, 78.5% Caucasian).
Everolimus nedsætter niveauer af VEGF (vascular endothelial growth factor), som potentierer tumorangiogene processer.
Everolimus reduces levels of vascular endothelial growth factor (VEGF), which potentiates tumour angiogenic processes.
Kvinder i den fødedygtige alder skal bruge yderst sikker prævention under behandlingen.
Women who could potentially become pregnant should use highly effective contraception during treatment.
Overgang til open-label Afinitor-behandling efter sygdomsprogression for patienter, der var allokeret til placebo, slørede muligheden for at detektere behandlingsrelateret forskel i total overlevelse.
Crossover to open-label Afinitor following disease progression for patients allocated to placebo confounded the detection of any treatment-related difference in overall survival.
Samtidig administration af everolimus og depot-octreotid øgede Cmin for octreotid med en geometrisk middelratio (everolimus/placebo) på 1,47.
Co-administration of everolimus and depot octreotide increased octreotide Cmin with a geometric mean ratio (everolimus/placebo) of 1.47.
Der var ingen tegn på nyretoksicitet hos aber eller minigrise.
There was no indication of kidney toxicity in monkeys or minipigs.
Afinitor er et lægemiddel mod kræft, som indeholder det aktive stof everolimus.
Afinitor is an anticancer medicine containing the active substance everolimus.
Diagnosen non-infektiøs pneumonitis skal overvejes hos patienter med uspecifikke respiratoriske tegn og symptomer såsom hypoksi, pleuraekssudat, hoste eller dyspnø, og hos hvem infektiøse, neoplastiske eller andre ikke-medicinske årsager er blevet udelukket ved hjælp af passende undersøgelser.
A diagnosis of non-infectious pneumonitis should be considered in patients presenting with non-specific respiratory signs and symptoms such as hypoxia, pleural effusion, cough or dyspnoea, and in whom infectious, neoplastic and other non-medicinal causes have been excluded by means of appropriate investigations.
Kaplan-Meier-medianer Everolimus/Exemestan: 36,57 [28,71;42,29] uger Everolimus: 29,43 [24,00;31,29] uger
Kaplan-Meier medians Everolimus/Exemestane: 36.57 [28.71;42.29] weeks Everolimus: 29.43 [24.00;31.29] weeks
Håndtering af stomatitis kan derfor inkludere profylaktisk og/eller terapeutisk brug af topikale behandlinger, som fx en alkoholfri oral opløsning med kortikosteroid som mundskyllevæske.
Management of stomatitis may therefore include prophylactic and/or therapeutic use of topical treatments, such as an alcohol-free corticosteroid oral solution as a mouthwash.
Lokaliserede og systemiske infektioner, herunder pneumoni, andre bakterielle infektioner, invasive svampeinfektioner, såsom aspergillose, candidiasis eller PJP/PCP og virale infektioner inklusive reaktivering af hepatitis B virus, er beskrevet hos patienter, der tager Afinitor.
Localised and systemic infections, including pneumonia, other bacterial infections, invasive fungal infections such as aspergillosis, candidiasis or PJP/PCP and viral infections including reactivation of hepatitis B virus, have been described in patients taking Afinitor.
Den estimerede HR for sammenligningen af OS i everolimus + exemestan kombinations-armen i forhold til capecitabin-armen var 1,33 (90 % CI: 0,99; 1,79).
The estimated HR for the comparison of OS in the everolimus + exemestane combination arm relative to capecitabine arm was 1.33 (90% CI: 0.99, 1.79).
Efter administration af everolimus til patienter med progressive massive tumorer var steady-state-AUC0-τ dosisproportional i området 5 til 10 mg daglig dosis.
After administration of everolimus in patients with advanced solid tumours, steady-state AUC0-τ was dose-proportional over the range of 5 to 10 mg daily dose.
Vaskulære sygdomme Almindelig Hæmoragi b, hypertension
Common Haemorrhage b, hypertension
Eksponering af everolimus var øget i patienter med let (Child-Pugh A), moderat (Child-Pugh B) og stærkt (Child-Pugh C) nedsat leverfunktion (se pkt.
Exposure to everolimus was increased in patients with mild (Child-Pugh A), moderate (Child-Pugh B) and severe (Child-Pugh C) hepatic impairment (see section 5.2).
Det kunne ikke påvises, om dette havde en klinisk signifikant effekt på virkningsresponset for everolimus hos patienter med progressive neuroendokrine tumorer.
A clinically significant effect on the efficacy response to everolimus in patients with advanced neuroendocrine tumours could not be established.
Hvis du tager en eller flere af dem, vil din læge måske ændre din behandling til en anden medicin eller ændre din dosis af Afinitor.
If you are taking any of them, your doctor may switch you to a different medicine, or may change your dose of Afinitor.
Fortæl det straks til din læge, hvis du oplever nogen af disse bivirkninger, da det kan have livstruende konsekvenser.
If you experience any of these side effects, tell your doctor immediately as this might have life-threatening consequences.
Kaplan-Meier medianer Everolimus: 4,90 måneder Placebo: 1,87 måneder
Kaplan-Meier medians Everolimus: 4.90 months Placebo: 1.87 months
Moderstoffet sporedes ikke i urin eller fæces.
The parent substance was not detected in urine or faeces.
Sikkerhedsprofilen er baseret på de samlede data fra 2.879 patienter, der blev behandlet med Afinitor i elleve kliniske studier bestående af fem randomiserede, dobbeltblindede, placebokontrollerede fase III-studier og seks open-label (ublindet) fase I og fase II-studier, som var relaterede til de godkendte indikationer.
The safety profile is based on pooled data from 2,879 patients treated with Afinitor in eleven clinical studies, consisting of five randomised, double-blind, placebo controlled phase III studies and six open-label phase I and phase II studies, related to the approved indications.
- fremskreden nyrekræft (fremskreden renalcellekarcinom), hvor andre behandlinger (såkaldt VEGF-rettet behandling) ikke har kunnet standse din sygdom.
advanced kidney cancer (advanced renal cell carcinoma), where other treatments (so-called “VEGF-targeted therapy”) have not helped stop your disease.
Tabel 1 Anbefalinger for dosisjustering af Afinitor
Table 1 Afinitor dose adjustment recommendations
Dyrestudier har påvist reproduktionstoksicitet, herunder embryotoksicitet og føtotoksicitet (se pkt.
Studies in animals have shown reproductive toxicity effects including embryotoxicity and foetotoxicity (see section 5.3).
Patienter i placebo-armen overgik ikke til everolimus på tidspunktet for progression.
Patients in the placebo arm did not cross-over to everolimus at the time of progression.
Resultatet af den endelige PFS-analyse med 154 hændelser, observeret baseret på lokal investigator-vurdering, viste en estimeret HR på 0,74 (90 % CI: 0,57; 0,97) til fordel for everolimus + exemestan-armen i forhold til everolimus-armen.
The result of the final PFS analysis with 154 PFS events observed based on local investigator assessment showed an estimated HR of 0.74 (90% CI: 0.57, 0.97) in favour of the everolimus + exemestane arm relative to everolimus arm.
Det vigtigste sekundære formål var at estimere HR for PFS for everolimus + exemestan versus capecitabin.
The key secondary objective was to estimate the HR of PFS for everolimus + exemestane versus capecitabine.
Neuroendokrine tumorer udgået fra pancreas
Neuroendocrine tumours of pancreatic origin
Der skal udvises forsigtighed, når Afinitor tages i kombination med oralt administrerede CYP3A4-substrater med et snævert terapeutisk vindue på grund af risiko for lægemiddelinteraktioner.
Caution should be exercised when Afinitor is taken in combination with orally administered CYP3A4 substrates with a narrow therapeutic index due to the potential for drug interactions.
Afinitor kan øge risikoen for problemer med sårheling.
Afinitor may increase the risk of problems with wound healing.
Afinitor anvendes til behandling af voksne patienter med: - fremskreden hormonreceptorpositiv brystkræft hos postmenopausale kvinder, hvor andre behandlinger (såkaldte "ikke-steoide aromatasehæmmere") ikke længere er i stand til at holde sygdommen under kontrol.
Afinitor is used to treat adult patients with: hormone receptor-positive advanced breast cancer in postmenopausal women, in whom other treatments (so called “non-steroidal aromatase inhibitors”) no longer keep the disease under control.
For alle analyserede undergrupper (alder, sensitivitet for tidligere hormonbehandling, antallet af involverede organer, status for læsioner i knogler alene ved baseline og tilstedeværelse af visceral metastase samt på tværs af store demografiske og prognostiske undergrupper) sås en positiv behandlingsvirkning med everolimus + exemestan med en estimeret risiko-ratio (HR) versus placebo + exemestan på mellem 0,25 og 0,60.
For all analysed subgroups (age, sensitivity to prior hormonal therapy, number of organs involved, status of bone-only lesions at baseline and presence of visceral metastasis, and across major demographic and prognostic subgroups) a positive treatment effect was seen with everolimus + exemestane with an estimated hazard ratio (HR) versus placebo + exemestane ranging from 0.25 to 0.60.
Farmakoterapeutisk klassifikation: Antineoplastiske stoffer, andre antineoplastiske stoffer, proteinkinasehæmmere, ATC-kode: L01XE10
Pharmacotherapeutic group: Antineoplastic agents, other antineoplastic agents, protein kinase inhibitors, ATC code: L01XE10
Antal patienter stadig i risiko
Number of Patients still at Risk
Patienter i placebo + exemestan-armen overgik ikke til everolimus på progressiontidspunktet.
Patients in the placebo + exemestane arm did not cross over to everolimus at the time of progression.
Afinitor kan skade dit ammede barn.
Afinitor could harm your breast-fed baby.
Det skal du vide, før du begynder at tage Afinitor
What you need to know before you take Afinitor
Non-infektiøs pneumonitis er en klasseeffekt af rapamycinderivater inklusive everolimus.
Non-infectious pneumonitis is a class effect of rapamycin derivatives, including everolimus.
Almindelig Forhøjet aspartataminotransferase, forhøjet alaninaminotransferase Hud og subkutane væv
Common Aspartate aminotransferase increased, alanine aminotransferase increased Skin and subcutaneous tissue disorders
Hyperglykæmi er rapporteret (se pkt.
Hyperglycaemia has been reported (see section 4.8).
Hvis du har taget for mange Afinitor-tabletter Hvis du har taget for mange Afinitor-tabletter, eller hvis andre ved et uheld har taget dine tabletter, skal du straks tage til lægen eller på hospitalet.
If you have taken too much Afinitor, or if someone else accidentally takes your tablets, see a doctor or go to a hospital immediately.
• Hævelse af arme, hænder, fødder, ankler eller andre dele af kroppen (tegn på vand i kroppen)
• Swelling of arms, hands, feet, ankles or other part of the body (signs of oedema)
Ved svære og/eller uacceptable bivirkninger kan dosisreduktion og/eller midlertidig afbrydelse af behandlingen være påkrævet.
Management of severe and/or intolerable suspected adverse reactions may require dose reduction and/or temporary interruption of Afinitor therapy.
Perikon (Hypericum Perforatum)
St John's Wort (Hypericum perforatum)
De patienter, som var randomiseret til at få placebo, kunne derefter få open-label Afinitor.
Those randomised to placebo were then able to receive open-label Afinitor.
Samtidig behandling med potente CYP3A4-hæmmere resulterer i dramatisk øgede plasmakoncentrationer af everolimus (se pkt.
Concomitant treatment with potent CYP3A4 inhibitors result in dramatically increased plasma concentrations of everolimus (see section 4.5).
Risikorate (95 % CI) fra stratificeret Cox-model
Hazard ratio (95% CI) from stratified Cox model
Et interaktionsstudie med raske forsøgspersoner viste, at samtidig administration af en oral dosis midazolam, et sensitivt CYP3A-testsubstrat, og everolimus resulterede i en stigning på 25% i Cmax og på 30% i AUC(0-inf) for midazolam.
An interaction study in healthy subjects demonstrated that co-administration of an oral dose of midazolam, a sensitive CYP3A substrate probe, with everolimus resulted in a 25% increase in midazolam Cmax and a 30% increase in midazolam AUC(0-inf).
Middel risiko
Intermediate risk
Everolimus' sikkerhed, tolerabilitet og farmakokinetik blev vurderet i to enkeltdosisstudier med Afinitor-tabletter hos 8 og 34 personer med nedsat leverfunktion i forhold til personer med normal leverfunktion.
The safety, tolerability and pharmacokinetics of everolimus were evaluated in two single oral dose studies of Afinitor tablets in 8 and 34 subjects with impaired hepatic function relative to subjects with normal hepatic function.
Nogle mundskyllevæsker og geler kan gøre sår værre, så du skal tale med din læge, før at du starter på behandling.
Some mouthwashes and gels can make ulcers worse, so do not try anything without checking with your doctor first.
Nogle af disse infektioner har været alvorlige (har fx ført til sepsis, respirations- eller leversvigt), og i nogle tilfælde letale.
Some of these infections have been severe (e.g. leading to sepsis, respiratory or hepatic failure) and occasionally fatal.
Hvis Afinitor tages med orale CYP3A4-substrater med et snævert terapeutisk vindue (fx pimozid, terfenadin, astemizol, cisaprid, quinidin eller sekalealkaloider), skal patienten monitoreres for de bivirkninger, der er beskrevet i produktinformationen for det orale CYP3A4-substrat (se pkt.
If Afinitor is taken with orally administered CYP3A4 substrates with a narrow therapeutic index (e.g. pimozide, terfenadine, astemizole, cisapride, quinidine or ergot alkaloid derivatives), the patient should be monitored for undesirable effects described in the product information of the orally administered CYP3A4 substrate (see section 4.5).
Dyslipidæmi (inklusive hyperkolesterolæmi og hypertriglyceridæmi) er rapporteret.
Dyslipidaemia (including hypercholesterolaemia and hypertriglyceridaemia) has been reported.
Afinitor kan øge mængden af sukker i blodet og forværre sukkersyge.
Afinitor may increase blood sugar levels and worsen diabetes mellitus.
Demografien var velafbalanceret (poolet median-alder [61 år; fra 27 til 85], 78% mænd, 88% kaukasiere, antal tidligere VEGFR-TKI-behandlinger [1-74%, 2-26%]).
Demographics were well balanced (pooled median age [61 years; range 27-85], 78% male, 88% Caucasian, number of prior VEGFR-TKI therapies [1-74%, 2-26%]).
Stomatitis, herunder mundsår og oral mucositis, er den hyppigst rapporterede bivirkning hos patienter, der blev behandlet med Afinitor (se pkt.
Stomatitis, including mouth ulcerations and oral mucositis, is the most commonly reported adverse reaction in patients treated with Afinitor (see section 4.8).
• Hævelse eller/og smerter i ét af benene, ofte i læggen, rødme eller varm hud i det berørte område (tegn på blokering af en blodåre (vene) i benene pga. en blodprop)
• Swelling and/or pain in one of the legs, usually in the calf, redness or warm skin in the affected area (signs of blockade of a blood vessel (vein) in the legs caused by blood clotting)
• Unormale resultater af blodprøver for nyrefunktionen (forhøjet kreatinin)
• Abnormal results of renal blood tests (increased creatinine)
Blod og lymfesystem Meget almindelig
Blood and lymphatic system disorders Very common Anaemia
Effektresultaterne for det primære endepunkt blev indhentet fra den endelige PFS-analyse (se tabel 4 og figur 1).
The efficacy results for the primary endpoint were obtained from the final PFS analysis (see Table 4 and Figure 1).