natgillin/translations-raw huggingface dataset:
Faslodex 250 mg injektionsvæske, opløsning.
Faslodex 250 mg solution for injection
Faslodex er indiceret til behandling af postmenopausale kvinder med østrogen receptor positiv, lokal avanceret eller metastaseret brystcancer ved sygdomstilbagefald under eller efter adjuverende antiøstrogen behandling eller sygdomsprogression under behandling med et antiøstrogen.
Faslodex is indicated for the treatment of postmenopausal women with estrogen receptor positive, locally advanced or metastatic breast cancer for disease relapse on or after adjuvant anti-estrogen therapy or disease progression on therapy with an anti-estrogen.
Dosering Voksne kvinder (inklusive ældre)
4.2 Posology and method of administration
Den anbefalede dosis er 250 mg givet med 1 måneds interval.
Posology Adult females (including the elderly) The recommended dose is 250 mg at intervals of 1 month.
Faslodex anbefales ikke til børn eller unge, da sikkerhed og effekt ikke er fastlagt i denne aldersgruppe.
Paediatric patients Faslodex is not recommended for use in children or adolescents, as safety and efficacy have not been established in this age group.
Dosisjustering anbefales ikke til patienter med mild til moderat nedsat nyrefunktion (kreatinin clearance ≥ 30 ml/ min).
Renal impairment No dose adjustments are recommended for patients with mild to moderate renal impairment (creatinine clearance ≥ 30 ml/ min).
4. 4).
Safety and efficacy have not been evaluated in patients with severe renal impairment (creatinine clearance < 30 ml/ min), and, therefore, caution is recommended in these patients (see section 4.4).
Det er ikke nødvendigt at justere dosis hos patienter med mild til moderat nedsat leverfunktion.
Hepatic impairment No dose adjustments are recommended for patients with mild to moderate hepatic impairment.
Da eksponeringen af fulvestrant kan være øget, skal man anvende Faslodex med forsigtighed hos disse patienter. Der er ingen data vedrørende patienter med svært nedsat leverfunktion (se 4. 3, 4. 4 og 5. 2).
There are no data in patients with severe hepatic impairment (see sections 4.3, 4.4 and 5.2).
Administrationsmetode Faslodex skal administreres ved langsom intramuskulær injektion i balden.
Method of administration Faslodex should be administered by slow intramuscular injection into the buttock.
6. 6. for detaljeret administrationsinstruktion.
For detailed instructions for administration, see section 6.6.
2 4. 3 Kontraindikationer
4.3 Contraindications
Overfølsomhed over for det aktive stof eller over for et eller flere af hjælpestofferne.
Hypersensitivity to the active substance, or to any of the other excipients.
4. 4 og 5. 2).
Pregnancy and lactation (see section 4.6) Severe hepatic impairment (see sections 4.4 and 5.2).
Faslodex skal anvendes med forsigtighed til patienter med mild til moderat nedsat leverfunktion (se 4. 2, 4. 3 og 5. 2).
Faslodex should be used with caution in patients with mild to moderate hepatic impairment (see sections 4.2, 4.3 and 5.2).
Anvend Faslodex med forsigtighed til patienter med meget nedsat nyrefunktion (kreatinin clearance < 30 ml/ min) (Se 5. 2).
Faslodex should be used with caution in patients with severe renal impairment (creatinine clearance less than 30 ml/ min)
På grund af den intramuskulære administrationsvej skal Faslodex anvendes med forsigtighed ved behandling af patienter med blødningsdiatese, thrombocytpeni eller patienter i antikoagulationsbehandling.
Due to the intramuscular route of administration, Faslodex should be used with caution if treating patients with bleeding diatheses, thrombocytopenia or those taking anticoagulant treatment.
Thromboemboliske tilfælde ses ofte hos kvinder med avanceret brystcancer og er observeret i kliniske forsøg med Faslodex (se pkt.
Thromboembolic events are commonly observed in women with advanced breast cancer and have been observed in clinical trials with Faslodex (see section 4.8).
Der er ingen langtidsdata om effekten af fulvestrant på knogler.
There are no long-term data on the effect of fulvestrant on bone.
På grund af fulvestrants virkningsmekanisme, er der en potentiel risiko for osteoporosis.
Due to the mechanism of action of fulvestrant, there is a potential risk of osteoporosis.
Et klinisk interaktionsstudie med midazolam (substrat af CYP3A4) viste at fulvestrant ikke hæmmer CYP 3A4.
A clinical interaction study with midazolam (substrate of CYP3A4) demonstrated that fulvestrant does not inhibit CYP3A4.
Kliniske interaktionsstudier med rifampicin (en CYP 3A4 inducer) og ketoconazol (CYP 3A4 hæmmer) viste ingen klinisk relevant ændring i fulvestrant clearance.
Clinical interaction studies with rifampicin (inducer of CYP3A4) and ketoconazole (inhibitor of CYP3A4) showed no clinically relevant change in fulvestrant clearance.
Dosisjustering er derfor ikke nødvendig hos patienter, som får fulvestrant og CYP- 3A4 hæmmere eller inducere samtidig.
Dose adjustment is therefore not necessary in patients who are receiving fulvestrant and CYP3A4 inhibitors or inducers concomitantly.
4. 3).
Faslodex is contraindicated in pregnancy (see section 4.3).
Det er vist, at fulvestrant passerer placenta efter en enkelt intramuskulær dosis i rotte og kanin.
Fulvestrant has been shown to cross the placenta after single intramuscular doses in rat and rabbit.
5. 3).
Studies in animals have shown reproductive toxicity including an increased incidence of foetal abnormalities and deaths (see section 5.3).
Hvis graviditet indtræder samtidig med Faslodex behandling, skal patienten informeres om de mulige skadevirkninger på fostret og den potentielle risiko for afbrydelse af graviditeten.
If pregnancy occurs while taking Faslodex, the patient must be informed of the potential hazard to the foetus and potential risk for loss of pregnancy.
Det vides ikke, om fulvestrant udskilles i human brystmælk.
It is not known whether fulvestrant is excreted in human milk.
Med henblik på muligheden for potentielt alvorlige bivirkninger hos ammede børn på grund af fulvestrant, er amning kontraindiceret (se 4. 3).
Considering the potential for serious adverse reactions due to fulvestrant in breast-fed infants, lactation is contraindicated (see section 4.3).
Dog er asteni rapporteret som almindeligt under behandling med Faslodex.
Faslodex has no or negligible influence on the ability to drive or use machines.
Derfor skal patienter, som oplever denne bivirkning, være forsigtige, når de fører bil eller betjener maskiner.
However, since asthenia has been reported commonly with Faslodex, caution should be observed by those patients who experience this adverse reaction when driving or operating machinery.
Dette afsnit giver information baseret på alle bivirkninger fra kliniske forsøg, post- marketing- studier eller rapporterede spontane bivirkninger.
This section provides information based on all adverse reactions from clinical trials, post-marketing studies or spontaneous reports.
Cirka 47% af patienterne oplevede bivirkninger i det kliniske undersøgelsesprogram.
Approximately 47% of patients experienced adverse reactions in the clinical trial programme.
Imidlertid stoppede kun 0, 9% af patienterne behandlingen på grund af en bivirkning.
However, only 0.9% of patients stopped therapy because of an adverse reaction.
De hyppigst rapporterede bivirkninger er hedeture, kvalme og reaktioner ved injektionsstedet.
The most frequently reported adverse reactions are hot flushes, nausea, and injection site reactions.
Frekvensopdelingen er defineret i henhold til følgende:
Frequency groupings are defined according to the following convention:
Meget almindelig (≥1/ 10), Almindelig (≥1/ 100 til < 1/ 10), Ikke almindelig (≥1/ 1. 000 til < 1/ 100).
Very common (≥ 1/ 10), Common (≥ 1/ 100 to < 1/ 10), Uncommon (≥ 1/ 1,000 to < 1/ 100).
Inden for hver frekvensgruppering er bivirkningerne listet i rækkefølge med aftagende alvorlighed.
Within each frequency grouping adverse reactions are reported in order of decreasing seriousness.
Table 1 Bivirkninger
3 Table 1 Adverse Drug Reactions
Systemorganklasse
SOC
Nervesystemet Mave- tarm- kanalen
Nervous system disorders Gastrointestinal disorders
Hovedpine Opkastning, kvalme og diarré.
Headache Vomiting, nausea and diarrhoea
Nyrer og urinveje Hud og subkutane væv
Renal and urinary disorders
Urinvejsinfektioner Udslæt
Urinary tract infections
Rygsmerter
Rash
Metabolisme og ernæring
Musculoskeletal and connective tissue disorders
Anoreksi
Back pain
Vaskulære sygdomme Almene symptomer og reaktioner på administrationsstedet
Metabolism and nutrition disorders
Hedeture
Anorexia
Venøs thromboembolisme Asteni Reaktioner ved injektionsstedet inkl. smerte og inflammation1
Asthenia Injection site reactions including injection site pain and injection site inflammation1
Overfølsomhedsre - aktioner, inkl. angioødem og urticaria
Hypersensitivity reactions, including angioedema and urticaria
Lever - og galdevejslidelser Forplantning og bryst 1
Hepatobiliary disorders
Forhøjede lever enzymer2
Increased Hepatic Enzymes2
Vaginal blødning Vaginal moniliatis Leukorrhoea
Vaginal moniliasis Leukorrhea Vaginal haemorrhage
Smerter ved injektionsstedet er forbigående og forekommer hos 7% af patienterne (1% af injektionerne), når det gives som en enkelt injektion på 5 ml.
injection site reactions pain is transient 7% of patients (1% of injections) when given as a single 5 ml injection.
2 Hovedsageligt < 2xULN.
2 the vast majority < 2xULN
5. 3).
Animal studies suggest that no effects other than those related directly or indirectly to anti-estrogenic activity were evident with higher doses of fulvestrant (see section 5.3).
Antiøstrogener, ATC- kode:
L02BA03
L02BA03 4 Virkningsmekanisme Fulvestrant er en kompetitiv østrogen receptor (ER) - antagonist med en affinitet sammenlignelig med østradiol.
Mechanism of action Fulvestrant is a competitive estrogen receptor (ER) antagonist with an affinity comparable to estradiol.
Fulvestrant blokerer de trofiske østrogenvirkninger uden at have nogen partiel agonist - aktivitet (østrogenlignende).
Fulvestrant blocks the trophic actions of estrogens without any partial agonist (estrogen-like) activity.
Virkningsmekanismen hænger sammen med nedregulering af niveauet af østrogen receptor- protein.
The mechanism of action is associated with down-regulation of estrogen receptor protein levels.
Kliniske forsøg hos postmenopausale kvinder med primær brystcancer har vist, at fulvestrant nedregulerer ER protein signifikant i ER positive tumorer i forhold til placebo.
4 Clinical trials in postmenopausal women with primary breast cancer have shown that fulvestrant significantly down-regulates ER protein in ER positive tumours compared with placebo.
Der sås også en signifikant nedsat progesteron receptor- ekspression i overensstemmelse med en manglende intrinsic østrogen agonist effekt.
There was also a significant decrease in progesterone receptor expression consistent with a lack of intrinsic estrogen agonist effects.
To kliniske fase III forsøg blev gennemført med i alt 851 postmenopausale kvinder med avanceret brystcancer, som havde sygdomstilbagefald under, eller efter, adjuvant endokrin behandling, eller progression efter endokrin behandling for avanceret sygdom.
Clinical safety and efficacy in advanced breast cancer Two phase III clinical trials were completed in a total of 851 postmenopausal women with advanced breast cancer who had disease recurrence on or after adjuvant endocrine therapy or progression following endocrine therapy for advanced disease.
Disse studier sammenlignede sikkerhed og effekt ved administration af 250 mg fulvestrant månedligt versus daglig administration af 1 mg anastrozol (aromatase- hæmmer).
These trials compared the safety and efficacy of monthly administration of 250 mg fulvestrant versus the daily administration of 1 mg anastrozole (aromatase inhibitor).
Overordnet var fulvestrant, med en dosis på 250 mg månedligt, mindst lige så effektiv som anastrozol, når man så på tid til progression, objektiv respons og tid til død.
Overall, fulvestrant at the 250 mg monthly dose was at least as effective as anastrozole in terms of time to progression, objective response, and time to death.
Tid til progression var det primære endepunkt.
Time to progression was the primary endpoint.
Kombineret analyse af begge forsøg viste, at 83% af patienterne, som fik fulvestrant, progredierede i forhold til 85% af patienterne, der fik anastrozol.
Combined analysis of both trials showed that 83% of patients who received fulvestrant progressed, compared with 85% of patients who received anastrozole.
Hazard rationen for fulvestrant i forhold til anastrozol, med henblik på tid til progression, var 0, 95 (95% konfidens interval 0, 82- 1, 10).
The hazard ratio of fulvestrant to anastrozole for time to progression was 0.95 (95% CI 0.82 to 1.10).
Den objektive respons rate for fulvestrant var 19, 2% i forhold til 16, 5% for anastrozol.
The objective response rate for fulvestrant was 19.2% compared with 16.5% for anastrozole.
Den gennemsnitlige tid til død var 27, 4 måneder for patienter i behandling med fulvestrant og 27, 6 måneder for patienter i behandling med anastrozol.
The median time to death was 27.4months for patients treated with fulvestrant and 27.6 months for patients treated with anastrozole.
Hazard rationen for fulvestrant, i forhold til anastrozol for tid til død, var 1, 01 (95% konfidensinterval, 0, 86 til 1, 19).
The hazard ratio of fulvestrant to anastrozole for time to death was 1.01 (95% CI 0.86 to 1.19).
Analyse af resultater ud fra ER status viste at anvendelsen af fulvestrant bør forbeholdes patienter med ER positiv brystcancer.
Analysis of results by ER status showed that the use of fulvestrant should be restricted to patients with ER positive breast cancer.
5. 3).
Effects on the postmenopausal endometrium Preclinical data do not suggest a stimulatory effect of fulvestrant on the postmenopausal endometrium (see section 5.3).
Et forsøg på 2 uger med raske postmenopausale frivillige forsøgspersoner, behandlet med 20 μg ethinylestradiol dagligt, viste, at præmedicinering med 250 mg fulvestrant resulterede i en signifikant reduceret stimulation af det postmenopausale endometrium, sammenlignet med placebo, vurderet via ultralydsmålinger af endometriets tykkelse.
A 2-week study in healthy postmenopausal volunteers treated with 20 μ g per day ethinylestradiol showed that pre-treatment with 250 mg fulvestrant resulted in significantly reduced stimulation of the postmenopausal endometrium, compared to pre-treatment with placebo, as judged by ultrasound measurement of endometrium thickness
Der er ingen data vedrørende langtidseffekt for fulvestrant på det postmenopausale endometrium.
There are no data on the long-term effects of fulvestrant on the postmenopausal endometrium.
I to korttidsforsøg (1 og 12 uger) med præmenopausale patienter med godartet gynækologisk sygdom, blev der ikke observeret nogen signifikante forskelle i endometrie tykkelse mellem fulvestrant og placebo grupperne.
In two short-term studies (1 and 12 weeks) with premenopausal patients with benign gynaecologic disease, no significant differences in endometrial thickness were observed by ultrasound measuring between fulvestrant and placebo groups.
Der er ingen langtidsdata omkring effekten af fulvestrant på knogler.
Effects on bone There are no long-term data on the effect of fulvestrant on bone.
5 Efter administration af Faslodex som en langtidsvirkende intramuskulær injektion, absorberes fulvestrant langsomt, og maksimale plasmakoncentrationer (Cmax) opnås efter cirka 7 dage.
Absorption After administration of Faslodex long-acting as an intramuscular injection, fulvestrant is slowly absorbed and maximum plasma concentrations (Cmax) are reached after about 7 days.
Absorption fortsætter i over en måned, og månedlig administration fører til en cirka 2- foldig akkumulation.
Absorption continues for over one month, and monthly administration results in an approximate 2-fold accumulation.
Steady- state niveau opnås efter cirka 6 månedlige injektioner hvor den største del af akkumuleringen opnås efter 3- 4 doser.
Steady-state levels are reached after about 6 monthly injections, with the major part of the accumulation achieved after 3-4 doses.
Ved steady- state er fulvestrant plasmakoncentrationer bibeholdt indenfor et relativt smalt koncentrationsområde med en cirka 2- 3 foldig difference mellem maksimale og nedre koncentrationer.
At steady state, fulvestrant plasma concentrations are maintained within a relatively narrow range with approximately 2- to 3-fold difference between maximum and trough concentrations.
Efter intramuskulær administration er eksponeringen omtrentlig dosis- proportional i dosisintervallet 50- 250 mg.
After intramuscular administration, the exposure is approximately dose-proportional in the dose range 50 to 250 mg.
Fulvestrant distribueres omfattende og hurtigt.
Distribution Fulvestrant is subject to extensive and rapid distribution.
3- 5 l/ kg, tyder på, at distributionen fortrinsvis sker ekstravasculært.
The large apparent volume of distribution at steady state (Vdss) of approximately 3 to 5 l/ kg suggests that distribution is largely extravascular.
Fulvestrant er stærkt bundet (99%) til plasma- proteiner.
Fulvestrant is highly (99%) bound to plasma proteins.
Very low density lipoprotein (VLDL), low density lipoprotein (LDL) og high density lipoprotein (HDL) fraktioner er de primære bindende bestanddele.
Very low density lipoprotein (VLDL), low 5 density lipoprotein (LDL), and high density lipoprotein (HDL) fractions are the major binding components.
Metabolismen af fulvestrant er ikke fuldstændig undersøgt men involverer kombinationer af en række mulige biotransformationsveje, analog til endogene steroider.
Metabolism The metabolism of fulvestrant has not been fully evaluated, but involves combinations of a number of possible biotransformation pathways analogous to those of endogenous steroids.
Identificerede metabolitter (inkluderer 17- keton, sulphon, 3 sulphat 3 - og 17- glucoronid metabolitter) er enten mindre aktive eller viser tilsvarende aktivitet som fulvestrant i antiøstrogene modeller.
Identified metabolites (includes 17-ketone, sulphone, 3-sulphate, 3- and 17-glucuronide metabolites) are either less active or exhibit similar activity to fulvestrant in anti-estrogen models.
Studier, hvor der er anvendt humant levermateriale og rekombinante humane enzymer, indikerer, at CYP3A4 er det eneste P- 450 isoenzym, der er involveret i oxidation af fulvestrant, hvor veje, der ikke involverer P- 450, dog synes mere fremtrædende in vivo.
Studies using human liver preparations and recombinant human enzymes indicate that CYP3A4 is the only P450 isoenzyme involved in the oxidation of fulvestrant; however, non-P450 routes appear to be more predominant in vivo.
In vitro data indikerer at fulvestrant ikke hæmmer CYP450 isoenzymer.
In vitro data suggest that fulvestrant does not inhibit CYP450 isoenzymes.
Fulvestrant elimineres primært i metaboliseret form.
Elimination Fulvestrant is eliminated mainly in metabolised form.
Fulvestrant har en høj clearance, 11+ / - 1, 7 ml/ min/ kg, som tyder på en høj udskillelsesratio via leveren.
Fulvestrant has a high clearance, 11±1.7 ml/ min/ kg, suggesting a high hepatic extraction ratio.
Den terminale halveringstid (t1/ 2) efter intramuskulær administration er bestemt af absorbtionshastigheden og blev estimeret til at være 50 dage.
The terminal half-life (t1/ 2) after intramuscular administration is governed by the absorption rate and was estimated to be 50 days.
I en farmakokinetisk populationsanalyse af data fra fase III studier, var der ingen forskel i den farmakokinetiske profil for fulvestrant hvad angår alder (interval 33 til 89 år), vægt (40- 127 kg) eller race.
Special populations In a population pharmacokinetic analysis of data from phase III studies, no difference in fulvestrant’ s pharmacokinetic profile was detected with regard to age (range 33 to 89 years), weight (40-127 kg) or race.
Mild til moderat nedsat nyrefunktion påvirkede ikke farmakokinetikken for fulvestrant i klinisk relevant omfang.
Renal impairment Mild to moderate impairment of renal function did not influence the pharmacokinetics of fulvestrant to any clinically relevant extent.
Farmakokinetikken for fulvestrant er blevet undersøgt i et klinisk enkeltdosis- studie, der blev gennemført hos forsøgspersoner som havde mild til moderat nedsat leverfunktion, (Child- Pugh klasse A og B)..
Hepatic impairment The pharmacokinetics of fulvestrant has been evaluated in a single-dose clinical trial conducted in subjects with mild to moderate hepatic impairment (Child-Pugh class A and B).
Hos forsøgspersoner med nedsat leverfunktion sås en stigning i AUC på op til 2, 5 gange sammenlignet med raske forsøgspersoner.
There was up to about 2.5-fold increase in AUC in subjects with hepatic impairment compared to healthy subjects.
6 stigning i eksponering af denne størrelse at være veltolereret.
In patients administered Faslodex, an increase in exposure of this magnitude is expected to be well tolerated.
Forsøgspersoner med svært nedsat leverfunktion, (Child- Pugh klasse C, blev ikke undersøgt.
Subjects with severe hepatic impairment (Child-Pugh class C) were not evaluated.
Lokale reaktioner inklusiv myositis og granulomatom ved injektionsstedet blev tilskrevet vehiklet, men sværhedsgraden af myositis hos kaniner steg i takt med fulvestrant i forhold til saltkontrollen.
Local reactions, including myositis and granulomatoma at the injection site were attributed to the vehicle but the severity of myositis in rabbits increased with fulvestrant, compared to the saline control.
I intramuskulære flerdosis toksicitetsstudier med rotter og hunde, var den antiøstrogene aktivitet af fulvestrant årsag til de fleste observerede virkninger, specielt i hunkønnenes reproduktionssystem, men også i andre organer, som hos begge køn er følsomme overfor hormoner.
In toxicity studies with multiple intramuscular doses of fulvestrant in rats and dogs, the anti-estrogenic activity of fulvestrant was responsible for most of the effects seen, particularly in the female reproductive system, but also in other organs sensitive to hormones in both sexes.
I forsøg med hunde efter oral og intravenøs administration, sås påvirkninger af det cardiovaskulære system (svage stigninger af S- T segmentet i EKG [ved oral indgift], og hjertestop hos en hund [ved intravenøs indgift].
In dog studies following oral and intravenous administration, effects on the cardiovascular system (slight elevations of the S-T segment of the ECG [oral], and sinus arrest in one dog [intravenous]) were seen.
Disse forekom ved højere eksponeringsniveauer end ved patienter (Cmax > 40 gange) og er sandsynligvis af begrænset betydning for human sikkerhed ved den kliniske dosis.
These occurred at exposure levels higher than in patients (Cmax > 40 times) and are likely to be of limited significance for human safety at the clinical dose.
Fulvestrant påvirkede reproduktionen og embryo/ fosterudvikling i overensstemmelse med dets antiøstrogene aktivitet, ved doser svarende til den kliniske dosis.
Fulvestrant showed effects upon reproduction and embryo/ foetal development consistent with its anti-estrogenic activity, at doses similar to the clinical dose.
Hos rotter sås en reversibel nedsat kvindelig fertilitet og embryo- overlevelse, dyctocia samt en øget forekomst af fosterabnormaliteter inkl. fodrodsbøjning.
In rats, a reversible reduction in female fertility and embryonic survival, dystocia and an increased incidence of foetal abnormalities including tarsal flexure were observed.
Der blev observeret stigninger i placentavægt og foster post- implantationstab.
6 placental weight and post-implantation loss of foetuses were seen.
Der var en øget forekomst af foster variationer hos kaniner (forskydning bagud af bækkenringen og 27. præ- sakrale hvirvel).
There was an increased incidence of foetal variations in rabbits (backwards displacement of the pelvic girdle and 27 pre-sacral vertebrae).