natgillin/translations-raw huggingface dataset:
Hvis du tager anden medicin samtidig med Afinitor, skal din læge måske ændre dosis af Afinitor eller den anden medicin.
If you are taking other medicines at the same time as Afinitor, your doctor may need to change the dose of Afinitor or the other medicines.
I et randomiseret, dobbeltblindet multicenterstudie med patienter med funktionelle karcinoide tumorer blev Afinitor plus depotformulering af octreotid sammenlignet med placebo plus depotformulering af octreotid.
In a randomised, double-blind, multi-centre trial in patients with functional carcinoid tumours, Afinitor plus depot octreotide was compared to placebo plus depot octreotide.
Funktionelle karcinoide tumorer
Functional carcinoid tumours
• Unormale resultater af blodprøver for leverfunktionen (forhøjet alanin- og aspartat-aminotransferase)
• Abnormal results of liver blood tests (increased alanine and aspartate aminotransferase)
Baseret på resultaterne fra de to studier anbefales det at justere dosis hos patienter med nedsat leverfunktion (se pkt.
Based on the results of the two studies, dose adjustment is recommended for patients with hepatic impairment (see sections 4.2 and 4.4).
I understøttende analyser er der observeret positiv behandlingseffekt i alle undergrupper med undtagelse af undergruppen af patienter med primærtumor udgået fra ileum (ileum: HR=1,22 [95 % CI: 0,56-2,65]; ikke-ileum: HR=0,34 [95 % CI: 0,22-0,54]; lunge: HR=0,43 [95 % CI: 0,24-0,79]) (se figur 5).
In supportive analyses, positive treatment effect has been observed in all subgroups with the exception of the subgroup of patients with ileum as primary site of tumour origin (Ileum: HR=1.22 [95% CI: 0.56 to 2.65]; Non-ileum: HR=0.34 [95% CI: 0.22 to 0.54]; Lung: HR=0.43 [95% CI: 0.24 to 0.79]) (see Figure 5).
Everolimus har immunsuppressive egenskaber og kan prædisponere patienter for infektioner forårsaget af bakterier, svampe, vira eller protozoer, inklusive infektioner med opportunistiske patogener (se pkt.
Everolimus has immunosuppressive properties and may predispose patients to bacterial, fungal, viral or protozoan infections, including infections with opportunistic pathogens (see section 4.8).
dexamethason, et kortikosteroid, som bruges til behandling af en lang række tilstande, blandt andet forskellige betændelseslignende reaktioner og problemer med immunforsvaret.
dexamethasone, a corticosteroid used to treat a wide variety of conditions including inflammatory or immune problems.
Grad 4 Seponer behandlingen.
Grade 4 Discontinue treatment.
Everolimus 10 mg + exemestan: 7,82 måneder Placebo + exemestan: 3,19 måneder
Everolimus 10 mg + exemestane: 7.82 months Placebo + exemestane: 3.19 months
Table 6 RADIANT-4 - Resultater for progressionsfri overlevelse
Table 6 RADIANT-4 - Progression-free survival results
• Pludseligt opstået åndenød, brystsmerter eller ophostning af blod (kan være tegn på en blodprop i lungerne, en tilstand, der opstår, når en eller flere af arterierne i dine lunger tilstoppes)
• Sudden onset of shortness of breath, chest pain or coughing up blood (potential signs of pulmonary embolism, a condition that occurs when one or more arteries in your lungs become blocked)
Understøttende PFS-analyser var baseret på den lokale investigators vurdering.
Supportive PFS analysis was based on local investigator review.
Det Europæiske Lægemiddelagentur har dispenseret fra kravet om at fremlægge resultaterne af studier med Afinitor i alle undergrupper af den pædiatriske population med neuroendokrine tumorer udgået fra pancreas, neuroendokrine tumorer i thorax og ved renalcellekarcinom (se pkt.
The European Medicines Agency has waived the obligation to submit the results of studies with Afinitor in all subsets of the paediatric population in neuroendocrine tumours of pancreatic origin, thoracic neuroendocrine tumours and in renal cell carcinoma (see section 4.2 for information on paediatric use).
Der er rapporteret tilfælde af PJP/PCP med letal udgang hos patienter, der fik behandling med everolimus.
Cases of PJP/PCP, some with fatal outcome, have been reported in patients who received everolimus.
Hvis patienter har brug for samtidig administration af en moderat hæmmer af CYP3A4 eller PgP, kan det overvejes at reducere dosis til 5 mg eller 2,5 mg daglig.
If patients require co-administration of a moderate CYP3A4 or PgP inhibitor, dose reduction to 5 mg daily or 2.5 mg daily may be considered.
De store målorganer var reproduktionsorganer hos begge køn (tubulær testikeldegeneration, reduceret mængde sædvæske i bitestikel og uterin atrofi) hos flere arter; og lunger (stigning i alveolære makrofager) hos rotter og mus; pancreas (degranulering og vakuolation af eksokrine celler i henholdsvis aber og minigrise samt degenerering af øceller i aber), og øjne (uklarheder ved lentikulare anteriore suturlinier) hos rotter alene.
The major target organs were male and female reproductive systems (testicular tubular degeneration, reduced sperm content in epididymides and uterine atrophy) in several species; lungs (increased alveolar macrophages) in rats and mice; pancreas (degranulation and vacuolation of exocrine cells in monkeys and minipigs, respectively, and degeneration of islet cells in monkeys), and eyes (lenticular anterior suture line opacities) in rats only.
De bivirkninger, som hyppigst medførte seponering, var pneumonitis (inklusiv interstitiel lungesygdom), stomatitis, træthed og dyspnø.
The most common adverse reactions leading to discontinuation were pneumonitis (including interstitial lung disease), stomatitis, fatigue and dyspnoea.
Non-infektiøs pneumonitis (herunder interstitiel lungesygdom) har været rapporteret hyppigt hos patienter, der tog Afinitor (se pkt.
Non-infectious pneumonitis (including interstitial lung disease) has been frequently reported in patients taking Afinitor (see section 4.8).
På tidspunktet for den endelige OS-analyse var den mediane behandlingsvarighed med everolimus 24,0 uger (interval 1,0-199,1 uger).
At the time of the final OS analysis, the median duration of everolimus treatment was 24.0 weeks (range 1.0-199.1 weeks).
Moderat nedsat leverfunktion (Child-Pugh B): Den anbefalede startdosis er 5 mg daglig.
Moderate hepatic impairment (Child-Pugh B) - the recommended dose is 5 mg daily.
Censoreringstidspunkter Everolimus/Exemestan (n/N=80/104) Everolimus (n/N=74/103)
Everolimus/Exemestane (n/N=80/104) Everolimus (n/N=74/103)
Orale doser af everolimus på ≥0,1 mg/kg (ca. 4 % af AUC0-24h hos patienter, der fik en dosis på 10 mg daglig) til hunrotter, resulterede dog i en stigning i præ-implantationstab.
However, oral doses of everolimus in female rats at ≥0.1 mg/kg (approximately 4% of the AUC0-24h in patients receiving the 10 mg daily dose) resulted in increases in pre-implantation loss.
Censureringstid Everolimus (n/N = 155/277) Placebo (n/N = 111/139)
Censoring Times Everolimus (n/N = 155/277) Placebo (n/N = 111/139)
Den mediane varighed af blindet forsøgsbehandling var 40,4 uger for patienter, der fik Afinitor, og 19,6 uger for dem, der fik placebo.
The median duration of blinded treatment was 40.4 weeks for patients receiving Afinitor and 19.6 weeks for those receiving placebo.
I et fertilitetsstudie med hanrotter påvirkedes testikelmorfologien ved 0,5 mg/kg og derover, og sædcellemotilitet, antal sædceller og plasmatestosteronniveau faldt ved 5 mg/kg, hvilket medførte et fald i fertilitet hos hanrotterne.
In a male fertility study in rats, testicular morphology was affected at 0.5 mg/kg and above, and sperm motility, sperm head count, and plasma testosterone levels were diminished at 5 mg/kg which caused a reduction in male fertility.
På det nuværende tidspunkt er der ingen tilgængelige data vedrørende klinisk sikkerhed og effekt, som understøtter anbefaling af dosisjustering ved bivirkninger hos patienter med nedsat leverfunktion.
No clinical safety or efficacy data are currently available to support dose adjustment recommendations for the management of adverse reactions in patients with hepatic impairment.
I en farmakokinetisk populationsanalyse af 170 patienter med progressive massive tumorer sås der ingen signifikant effekt af kreatininclearance (25-178 ml/min) på everolimus' CL/F.
In a population pharmacokinetic analysis of 170 patients with advanced solid tumours, no significant influence of creatinine clearance (25-178 ml/min) was detected on CL/F of everolimus.
Forhøjet serumkreatinin, som regel let forhøjet, og proteinuri er rapporteret (se pkt.
Elevations of serum creatinine, usually mild, and proteinuria have been reported (see section 4.8).
Hos raske forsøgspersoner nedsatte måltider med højt fedtindhold eksponeringen for everolimus 10 mg (målt ved AUC) med 22% og peak-plasmakoncentrationen Cmax med 54%.
In healthy subjects, high fat meals reduced systemic exposure to everolimus 10 mg (as measured by AUC) by 22% and the peak plasma concentration Cmax by 54%.
Øvrige indholdsstoffer: butylhydroxytoluen , magnesiumstearat, lactosemonohydrat, hypromellose, crospovidon type A og vandfri lactose.
The other ingredients are butylhydroxytoluene, magnesium stearate, lactose monohydrate, hypromellose, crospovidone type A and lactose anhydrous.
Et enkeltarms-studie med postmenopausale brystkræftpatienter, der blev behandlet med Afinitor plus exemestan, tyder på, at en alkoholfri oral opløsning med kortikosteroid, administreret som mundskyllevæske i de første 8 ugers behandling, kan nedsætte forekomsten og alvorligheden af stomatitis (se pkt.
A single-arm study in postmenopausal breast cancer patients treated with Afinitor plus exemestane suggested that an alcohol-free corticosteroid oral solution, administered as a mouthwash during the initial 8 weeks of treatment, may decrease the incidence and severity of stomatitis (see section 5.1).
- fremskredne tumorer (kræftknuder) kaldet neuroendokrine tumorer, som stammer fra maven, tarmene, lungerne eller bugspytkirtlen.
advanced tumours called neuroendocrine tumours that originate from the stomach, bowels, lung or pancreas.
Det anbefales at monitorere nyrefunktionen, herunder måling af blodureanitrogen (BUN), urinprotein eller serumkreatinin, inden opstart af behandling med Afinitor og med jævne mellemrum herefter.
Monitoring of renal function, including measurement of blood urea nitrogen (BUN), urinary protein or serum creatinine, is recommended prior to the start of Afinitor therapy and periodically thereafter.
Hvis den moderate hæmmer seponeres, bør en udvaskningsperiode på mindst 2-3 dage (gennemsnitlig eliminationstid for de hyppigst anvendte moderate hæmmere) overvejes, før behandlingen fortsætter med den Afinitor-dosis, der blev anvendt før initiering af kombinationsbehandlingen.
If the moderate inhibitor is discontinued, consider a washout period of at least 2 to 3 days (average elimination time for most commonly used moderate inhibitors) before the Afinitor dose is returned to the dose used prior to initiation of the co-administration.
Afinitor er indiceret til behandling af inoperable eller metastaserende højt eller moderat differentierede neuroendokrine tumorer udgået fra pancreas hos voksne med progressiv sygdom.
Afinitor is indicated for the treatment of unresectable or metastatic, well- or moderately-differentiated neuroendocrine tumours of pancreatic origin in adults with progressive disease.
Den anbefalede dosis er 10 mg everolimus en gang dagligt.
The recommended dose is 10 mg everolimus once daily.
Effektresultaterne for det primære endepunkt var baseret på den endelige PFS-analyse (se tabel 6 og figur 4).
The efficacy results for the primary endpoint were obtained from the final PFS analysis (see Table 6 and Figure 4).
I det andet studie med 34 personer med forskellige grader af nedsat leverfunktion, der blev sammenlignet med personer med normal leverfunktion, var der 1,6 gange, 3,3 gange og 3,6 gange øget eksponering (dvs. AUC0-uendelig) hos personer med henholdsvis let (Child-Pugh A), moderat (Child-Pugh B) og svært nedsat leverfunktion (Child-Pugh C).
In the second study of 34 subjects with different impaired hepatic function compared to normal subjects, there was a 1.6-fold, 3.3-fold and 3.6-fold increase in exposure (i.e. AUC0-inf) for subjects with mild (Child-Pugh A), moderate (Child-Pugh B) and severe (Child-Pugh C) hepatic impairment, respectively.
• Tør hud, skællende hud, skader på huden
• Dry skin, skin exfoliation, skin lesions
Hvis behandlingen med induktor seponeres, bør en udvaskningsperiode på mindst 3-5 dage (passende tid til ophør af signifikant udtalt enzyminduktion) overvejes, før behandlingen fortsætter med den Afinitor-dosis, der blev anvendt før initiering af kombinationsbehandlingen.
If treatment with the inducer is discontinued, consider a washout period of at least 3 to 5 days (reasonable time for significant enzyme de-induction), before the Afinitor dose is returned to the dose used prior to initiation of the co-administration.
Genoptag behandlingen med 5 mg daglig.
Re-initiate treatment at 5 mg daily.
Hos patienter med progressive massive tumorer blev maksimum-koncentrationer (Cmax) af everolimus nået ved en mediantid på 1 time efter daglig administration af 5 og 10 mg everolimus fastende eller sammen med et let fedtfrit mellemmåltid.
In patients with advanced solid tumours, peak everolimus concentrations (Cmax) are reached at a median time of 1 hour after daily administration of 5 and 10 mg everolimus under fasting conditions or with a light fat-free snack.
Den mediane varighed af åben behandling var 47,7 uger blandt alle patienter; 67,1 uger for de 53 patienter, der blev randomiseret til everolimus, og som skiftede til open-label everolimus, og 44,1 uger hos de 172 patienter, der blev randomiseret til placebo, og som skiftede til open-label everolimus.
The median duration of open-label treatment was 47.7 weeks among all patients; 67.1 weeks in the 53 patients randomised to everolimus who switched to open-label everolimus and 44.1 weeks in the 172 patients randomised to placebo who switched to open-label everolimus.
Den estimerede HR var 1,27 (90 % CI: 0,95; 1,70) for sammenligningen af OS i everolimus alene-armen i forhold til everolimus + exemestan-armen.
The estimated HR was 1.27 (90% CI: 0.95, 1.70) for the comparison of OS in the everolimus alone arm relative to the everolimus + exemestane arm.
Overvej at genoptage behandlingen med 5 mg daglig.
Consider re-initiating treatment at 5 mg daily.
Kvinders frugtbarhed Der er observeret udeblivelse af menstruationen (amenoré) hos nogle kvinder, der får Afinitor.
Absence of menstrual periods (amenorrhoea) has been observed in some female patients receiving Afinitor.
10 tabletter 30 tabletter 90 tabletter
10 tablets 30 tablets 90 tablets
perikon (Hypericum perforatum)- et naturlægemiddel, der bruges til behandling af depression og andre tilstande.
St. John's wort (Hypericum perforatum), a herbal product used to treat depression and other conditions.
Hvis samtidig administration af en moderat CYP3A4- og/eller PgP-hæmmer eller induktor ikke kan undgås, kan det overvejes at foretage dosisjusteringer af Afinitor baseret på forventet AUC (se pkt.
If co-administration of a moderate CYP3A4 and/or PgP inhibitor or inducer cannot be avoided, dose adjustments of Afinitor can be taken into consideration based on predicted AUC (see section 4.5).
Der vil også blive taget blodprøver for at kontrollere din nyrefunktion (kreatinin-tal), leverfunktion (transaminase-tal), dit blodsukker og dit kolesteroltal, fordi disse tal også kan påvirkes af Afinitor.
Blood tests will also be carried out to check your kidney function (level of creatinine) and liver function (level of transaminases) and your blood sugar and cholesterol levels.
I kliniske studier og spontane rapporter modtaget efter markedsføring er angioødem blevet rapporteret med og uden samtidig behandling med ACE inhibitorer (se punkt 4.4).
In clinical trials and post-marketing spontaneous reports, angioedema has been reported with and without concomitant use of ACE inhibitors (see section 4.4).
Baseret på prækliniske fund kan fertiliteten hos hanner og hunner kompromitteres af behandling med everolimus (se pkt.
Based on non-clinical findings, male and female fertility may be compromised by treatment with everolimus (see section 5.3).
Den mediane behandlingsvarighed med exemestan var længere i everolimus + exemestan-gruppen: 29,5 uger (1,0-199,1) sammenlignet med 14,1 uger (1,0-156,0) i placebo + exemestan-gruppen.
The median duration of exemestane treatment was longer in the everolimus + exemestane group at 29.5 weeks (1.0-199.1) compared to 14.1 weeks (1.0-156.0) in the placebo + exemestane group.
Butylhydroxytoluen Magnesiumstearat Lactosemonohydrat Hypromellose Crospovidon type A Lactose, vandfri
Butylhydroxytoluene Magnesium stearate Lactose monohydrate Hypromellose Crospovidone type A Lactose anhydrous
Kvinder i den fertile alder/Kontraception til mænd og kvinder Kvinder i den fertile alder skal anvende yderst sikker kontraception (fx orale, injicerede eller implanterede ikke-østrogenholdige hormonale præventionsmetoder, progesteron-baserede kontraceptiva, hysterektomi, aflukning af æggeledere, fuldstændig afholdenhed, barriereprævention, intrauterin prævention [IUD] og/eller kvindelig/mandlig sterilisation) under behandlingen med everolimus og i op til 8 uger efter endt behandling.
Women of childbearing potential/Contraception in males and females Women of childbearing potential must use a highly effective method of contraception (e.g. oral, injected, or implanted non-oestrogen-containing hormonal method of birth control, progesterone-based contraceptives, hysterectomy, tubal ligation, complete abstinence, barrier methods, intrauterine device [IUD], and/or female/male sterilisation) while receiving everolimus, and for up to 8 weeks after ending treatment.
Figure 5 RADIANT-4 - Resultater for progressionsfri overlevelse i præ-specificerede undergrupper (uafhængig radiologisk vurdering)
Figure 5 RADIANT-4 - Progression free survival results by pre-specified patient subgroup (independent radiological review)
Inklusive (meget almindelig) pneumonitis, (almindelig) interstitiel lungesygdom, lungeinfiltration og (sjælden) pulmonal alveolær blødning, pulmonal toksicitet og alveolitis d
Includes (very common) pneumonitis, (common) interstitial lung disease, lung infiltration and (rare) pulmonary alveolar haemorrhage, pulmonary toxicity, and alveolitis d
Ritonavir, atazanavir, saquinavir, darunavir, indinavir, nelfinavir
Telithromycin, clarithromycin Nefazodone Ritonavir, atazanavir, saquinavir, darunavir, indinavir, nelfinavir
Vaccinationer Anvendelse af levende vacciner bør undgås under behandling med Afinitor (se pkt.
Vaccinations The use of live vaccines should be avoided during treatment with Afinitor (see section 4.5).
• Hovedpine, svimmelhed (tegn på forhøjet blodtryk, også kendt som hypertension)
• Headache, dizziness (sign of high blood pressure, also known as hypertension)
Afinitor er indiceret til behandling af patienter med progressiv renalcellekarcinom, hvis sygdom er progredieret under eller efter behandling med vaskulær endotel vækstfaktor (VEGF) målrettet terapi.
Afinitor is indicated for the treatment of patients with advanced renal cell carcinoma, whose disease has progressed on or after treatment with VEGF-targeted therapy.
Censureringstid
Censoring Times
Nedsat sårheling er en klasseeffekt af rapamycinderivater, inklusiv everolimus.
Impaired wound healing is a class effect of rapamycin derivatives, including everolimus.
I et post-marketing, enkeltarms-studie med postmenopausale kvinder med fremskreden brystkræft (N=92) blev der administreret topikal behandling med en alkoholfri oral opløsning med dexamethason 0,5 mg/5 ml som mundskyllevæske (4 gange daglig i de første 8 ugers behandling) til patienter ved opstart af behandling med Afinitor (10 mg/daglig) plus exemestan (25 mg/daglig) for at reducere forekomsten og alvorligheden af stomatitis.
In a post-marketing single-arm study in postmenopausal women with advanced breast cancer (N=92), topical treatment with dexamethasone 0.5 mg/5 ml alcohol-free oral solution was administered as a mouthwash (4 times daily for the initial 8 weeks of treatment) to patients at the time of initiating treatment with Afinitor (10 mg/day) plus exemestane (25 mg/day) to reduce the incidence and severity of stomatitis.
Samtidig behandling med Afinitor og potente hæmmere frarådes.
Concomitant treatment of Afinitor and potent inhibitors is not recommended.
Middelværdien af oral clearance (CL/F) for everolimus efter en daglig dosis på 10 mg var 24,5 l/t hos patienter med progressive solide tumorer.
Mean oral clearance (CL/F) of everolimus after 10 mg daily dose in patients with advanced solid tumours was 24.5 l/h.
Risiko-ratio p-værdi
Hazard ratio p value
Nedsat leverfunktion Let nedsat leverfunktion (Child-Pugh A): Den anbefalede startdosis er 7,5 mg daglig.
Hepatic impairment Mild hepatic impairment (Child-Pugh A) - the recommended dose is 7.5 mg daily.
• Træthed, stakåndethed, svimmelhed, bleg hud (tegn på lavt niveau af røde blodlegemer, der muligvis skyldes en type blodmangel, der kaldes pure red cell aplasia)
• Tiredness, breathlessness, dizziness, pale skin (signs of low level of red blood cells, possibly due to a type of anaemia called pure red cell aplasia)
De sekundære endepunkter omfattede total overlevelse (OS), total responsrate, sygdomskontrolrate, sikkerhed, ændring i livskvalitet (FACT-G) og tid til forværring af World Health Organisation performance-status (WHO PS).
Secondary endpoints included overall survival (OS), overall response rate, disease control rate, safety, change in quality of life (FACT-G) and time to World Health Organisation performance status (WHO PS) deterioration.
• Neglesygdomme, knækkede negle
• Nail disorders, breaking of your nails
Dosisjustering bør foretages, hvis patientens leverfunktion (Child-Pugh) ændres under behandlingen (se også pkt.
Dose adjustments should be made if a patient's hepatic (Child-Pugh) status changes during treatment (see also sections 4.4 and 5.2).
Moderate CYP3A4/PgP-hæmmere Erythromycin
Moderate CYP3A4/PgP inhibitors Erythromycin
I kliniske studier og post-marketing spontane rapporter er everolimus blevet forbundet med alvorlige tilfælde af hepatitis B reaktivering, inklusive letale tilfælde.
In clinical studies and post-marketing spontaneous reports, everolimus has been associated with serious cases of hepatitis B reactivation, including fatal outcome.
Øvrige sekundære formål inkluderede evalueringen af OS, objektiv responsrate, rate for klinisk fordel, sikkerhed, tid til forværring af ECOG performance, tid til forværring af QoL og tilfredshed med behandlingen (TSQM).
Other secondary objectives included the evaluation of OS, objective response rate, clinical benefit rate, safety, time to ECOG performance deterioration, time to QoL deterioration, and treatment satisfaction (TSQM).
Log-rank p værdi: <0,0001
Log-rank p value: <0.0001
Antal patienter med fortsat risiko Tid (måneder)
No. of patients still at risk Time (months) Afinitor
Sekundære endepunkter inkluderede sikkerhed, objektiv responsrate, responsvarighed og total overlevelse (OS).
Secondary endpoints included safety, objective response rate, response duration and overall survival (OS).
I alt blev 309 patienter randomiseret i en 1:1:1 ratio til kombinationen af everolimus (10 mg dagligt) + exemestan (25 mg dagligt) (n=104), everolimus alene (10 mg dagligt) (n=103) eller capecitabin (1250 mg/m2-dosis to gange dagligt i 2 uger, efterfulgt af en uges pause, 3 ugers cyklus) (n=102).
A total of 309 patients were randomised in a 1:1:1 ratio to the combination of everolimus (10 mg daily) + exemestane (25 mg daily) (n=104), everolimus alone (10 mg daily) (n=103), or capecitabine (1250 mg/m dose twice daily for 2 weeks followed by one week rest, 3-week cycle) (n=102).
Afinitor er kun anbefalet til behandling af patienter med stærkt nedsat leverfunktion (Child-Pugh C), hvis de potentielle fordele opvejer risiciene (se pkt.
Afinitor is only recommended for use in patients with severe hepatic impairment (Child-Pugh C) if the potential benefit outweighs the risk (see sections 4.2 and 5.2).