natgillin/translations-raw huggingface dataset:
Dette fund blev regelmæssigt bekræftet ved ultralyd ({X} 35% vs. tamoxifen 25%, p=0,04) og mammografi ({X} 34% vs. tamoxifen 16%, p<0,001).
This finding was consistently confirmed by ultrasound ({Invented Name} 35% vs tamoxifen 25%, P=0.04) and mammography ({Invented Name} 34% vs tamoxifen 16%, P<0.001).
Et dobbeltblindet studie (P024) blev udført hos 337 postmenopausale brystcancerpatienter tilfældigt allokeret til enten {X} 2,5 mg i 4 måneder eller tamoxifen i 4 måneder.
A double blind trial (P024) was conducted in 337 postmenopausal breast cancer patients randomly allocated either {Invented Name} 2.5 mg for 4 months or tamoxifen for 4 months.
Letrozol 2,5 mg var aminoglutethimid statistisk overlegen i perioden indtil progression (p=0,008), i perioden indtil behandlingssvigt (p=0,003) og i total overlevelse (p=0,002).
Letrozole 2.5 mg was statistically superior to aminoglutethimide for time to progression (P=0.008), time to treatment failure (P=0.003) and overall survival (P=0.002).
In vitro hæmmer letrozol CYP-isoenzymet 2A6 og - i moderat grad - 2C19, men den kliniske relevans er ukendt.
In vitro, letrozole inhibits the cytochrome P450 isoenzymes 2A6 and, moderately, 2C19, but the clinical relevance is unkown.
Endometriehyperplasi / endometriecancer
Endometrial hyperplasia / endometrial cancer
Median behandlingstid var 5 år for {X} og 3 år for placebo.
Median duration of treatment was 5 years for {Invented Name}, compared with 3 years for placebo.
Kvinder med osteoporose og/eller knoglebrud i anamnesen, eller som har en øget risiko for osteoporose, skal have målt knoglemineraldensiteten før påbegyndelse af adjuverende og forlænget adjuverende behandling og skal monitoreres for udvikling af osteoporose under og efter behandling med letrozol.
Women with a history of osteoporosis and/or fractures, or who are at increased risk of osteoporosis, should have their bone mineral density formally assessed prior to the commencement of adjuvant and extended adjuvant treatment and monitored during and following treatment with letrozole.
Effektresultater ved median opfølgning på 73 måneder (kun monoterapi-arme) Monoterapi-arm-analysen (MAA) langtidsopdatering af effekten af {X} monoterapi sammenlignet med tamoxifen-monoterapi (median varighed af adjuverende behandling: 5 år) vises i Tabel 5.
Results at a median follow-up of 73 months (monotherapy arms only) The Monotherapy Arms Analysis (MAA) long-term update of the efficacy of {Invented Name} monotherapy compared to tamoxifen monotherapy (median duration of adjuvant treatment: 5 years) is presented in Table 5.
Den eneste statistisk signifikante forskel opstod efter 2 år og var et større fald i BMD af hele hoften (median nedsættelse på 3,8% i letrozol-gruppen sammenlignet med 2,0% i placebogruppen).
The only statistically significant difference occurred at 2 years and was in total hip BMD (letrozole median decrease of 3.8% vs placebo median decrease of 2.0%).
Nogle bivirkninger er meget almindelige.
Some side effects are very common.
Ved adjuverende behandling og forlænget adjuverende behandling bør behandling med {X} fortsætte i 5 år, eller indtil tumor recidiverer, afhængigt af hvad der indtræffer først.
In the adjuvant and extended adjuvant setting, treatment with {Invented Name} should continue for 5 years or until tumour relapse occurs, whichever is first.
Det hæmmer aromataseenzymet ved kompetitiv binding til hæmgruppen i CYP-enzymet, hvilket resulterer i reduktion af østrogensyntesen i alle væv, hvor det forekommer.
It inhibits the aromatase enzyme by competitively binding to the haem of the aromatase cytochrome P450, resulting in a reduction of oestrogen biosynthesis in all tissues where present.
Tamoxifen, andre antiøstrogener eller østrogener kan nedsætte den farmakologiske virkning af letrozol.
Tamoxifen, other anti-oestrogens or oestrogen-containing therapies may diminish the pharmacological action of letrozole.
Der var ikke signifikant forskel i total overlevelse mellem de to behandlinger (p=0,2).
Overall survival was not significantly different between the 2 arms (P=0.2).
Tromboembolisk hændelse
Thromboembolic events
Ikke almindelig Angst (inklusive nervøsitet), irritabilitet Nervesystemet
Anxiety (including nervousness), irritability Nervous system disorders Common:
Tabletterne indeholder lactose, og {X} bør ikke anvendes til patienter med arvelig galactoseintolerans, en særlig form for arvelig lactasemangel (Lapp Lactase defiency) eller glucose/galactose malabsorption.
As the tablets contain lactose, {Invented Name} is not recommended for patients with rare hereditary problems of galactose intolerance, of severe lactase deficiency or of glucose-galactose malabsorption.
1 Justeret for brug af kemoterapi
Adjusted by chemotherapy use
Ikke almindelig Vægttab 1 Bivirkninger rapporteret alene ved metastaser.
Weight loss 1 Adverse drug reactions reported only in the metastatic setting
Det primære endepunkt var sygdomsfri overlevelse (DFS); sekundært endepunkt var tid til fjernmetastase (TDM), fjernmetastasefri overlevelse (DDFS), total overlevelse (OS), systemisk sygdomsfri overlevelse (SDFS), invasiv kontralateral brystcancer og tid til tilbagefald af brystcancer.
The primary endpoint was disease-free survival (DFS); secondary efficacy endpoints were time to distant metastasis (TDM), distant disease-free survival (DDFS), overall survival (OS), systemic disease-free survival (SDFS), invasive contralateral breast cancer and time to breast cancer recurrence.
Følgende tabeller giver information om signifikante forskelle mellem {X} versus tamoxifen ved monoterapi og i {X}-tamoxifen sekventielt behandlingsprogram:
The following tables provide information on significant differences in {Invented Name} versus tamoxifen monotherapy and in the {Invented Name}-tamoxifen sequential treatment therapy:
Ikke almindelig Tromboflebitis (inklusive overfladisk og dyb venetrombose), Sjælden
Thrombophlebitis (including superficial and deep vein thrombophlebitis)
Der blev ikke fundet klinisk relevante ændringer i plasmakoncentrationerne for cortisol, aldosteron, 11-deoxycortisol, 17-hydroxyprogesteron eller ACTH eller i plasmareninaktiviteten hos postmenopausale kvinder, der blev behandlet med en daglig dosis på 0,1-5 mg letrozol.
No clinically relevant changes were found in the plasma concentrations of cortisol, aldosterone, 11-deoxycortisol, 17-hydroxyprogesterone, and ACTH or in plasma renin activity among postmenopausal patients treated with a daily dose of letrozole 0.1 to 5 mg.
• Forlænget adjuverende behandling af hormonafhængig invasiv tidlig brystcancer hos postmenopausale kvinder, som forud har fået adjuverende standardbehandling med tamoxifen i 5 år.
• Extended adjuvant treatment of hormone-dependent invasive breast cancer in postmenopausal women who have received prior standard adjuvant tamoxifen therapy for 5 years.
Hos raske postmenopausale kvinder nedsætter enkeltdoser af letrozol på 0,1 mg, 0,5 mg og 2,5 mg serum-estron og serum-estradiol med henholdsvis 75%, 78% og 78% fra baseline.
In healthy postmenopausal women, single doses of 0.1 mg, 0.5 mg, and 2.5 mg letrozole suppress serum oestrone and oestradiol by 75%, 78% and 78% from baseline, respectively.
- Gul hud og øjne, kvalme, appetitløshed, mørkfarvet urin (tegn på leverbetændelse).
Yellow skin and eyes, nausea, loss of appetite, dark-coloured urine (signs of hepatitis).
• Førstevalgsbehandling til postmenopausale kvinder med hormonafhængig fremskreden brystcancer.
• First-line treatment in postmenopausal women with hormone-dependent advanced breast cancer.
Nedsat nyrefunktion {X} er ikke undersøgt hos et tilstrækkeligt antal patienter med kreatininclearance < 10 ml/min.
Renal impairment {Invented Name} has not been investigated in a sufficient number of patients with a creatinine clearance lower than 10 ml/min.
Dødsfald4
Deaths4
I det andet studie var responsraten mellem letrozol 2,5 mg og aminoglutethimid ikke signifikant forskellig (p=0,06).
In the second study, the response rate was not significantly different between letrozole 2.5 mg and aminoglutethimide (P=0.06).
Der var statistisk signifikant forskel mellem de to behandlingsarme for hændelser markeret med *.
Events marked * were statistically significantly different in the two treatment arms.
Nogle bivirkninger er almindelige.
Some side effects are common.
Tabel 4 Primær analyse: Sygdomsfri og total overlevelse ved en median opfølgningtid på 26 måneder og en median opfølgningstid på 60 måneder (ITT-population)
Table 4 Primary Core Analysis: Disease-free and overall survival,at a median follow-up of 26 months and at median follow-up of 60 months (ITT population)
Perioden indtil progression var ikke signifikant forskellig mellem letrozol 2,5 mg og megestrolacetat (p=0,07).
Time to progression was not significantly different between letrozole 2.5 mg and megestrol acetate (P=0.07).
Neo-adjuverende behandling
Neoadjuvant treatment
Farmakologisk virker letrozol ved at reducere østrogenproduktionen ved aromatasehæmning.
The pharmacological action of letrozole is to reduce oestrogen production by aromatase inhibition.
Plasmakoncentrationen i steady state er ca. 7 gange højere end koncentrationen målt efter en enkeltdosis på 2,5 mg, medens den er 1,5-2 gange højere end steady state-værdier skønnet ud fra koncentrationsmåling efter en enkelt dosis.
Plasma concentrations at steady state are approximately 7 times higher than concentrations measured after a single dose of 2.5 mg, while they are 1.5 to 2 times higher than the steady-state values predicted from the concentrations measured after a single dose, indicating a slight non-linearity in the pharmacokinetics of letrozole upon daily administration of 2.5 mg.
Ved forlænget adjuverende behandling opstod der knoglebrud og osteporose hos signifikant flere patienter behandlet med {X} (knoglebrud 10,4% og osteoporose 12,2%) sammenlignet med placebo (henholdsvis 5,8% og 6,4%).
In the extended adjuvant setting, significantly more patients treated with {Invented Name} experienced bone fractures or osteoporosis (bone fractures, 10.4% and osteoporosis, 12.2%) than patients in the placebo arm (5.8% and 6.4%, respectively).
Ikke almindelig Øget urineringsfrekvens Det reproduktive system og mammae Almindelig
Increased urinary frequency Reproductive system and breast disorders Common:
• Adjuverende behandling af postmenopausale kvinder med hormonreceptor-positiv invasiv tidlig brystcancer.
• Adjuvant treatment of postmenopausal women with hormone receptor positive invasive early breast cancer.
{X} kan give anledning til tab af knoglemasse (osteoporose), da det nedsætter mængden af østrogen i din krop.
{Invented Name} may cause thinning or wasting of your bones (osteoporosis) due to the reduction of oestrogens in your body.
hvilket er den eneste problemstilling vedrørende sikkerheden ved human anvendelse, som kan uddrages fra dyrestudierne.
Preclinical observations were confined to those associated with the recognised pharmacological action, which is the only safety concern for human use derived from animal studies.
Ikke almindelig Døsighed, søvnløshed, hukommelsessvækkelse, dysæstesi (inklusive paræstesi, hypæstesi), smagsforstyrrelser, cerebrovaskulær hændelse
Somnolence, insomnia, memory impairment, dysaesthesia (including paraesthesia, hypoaesthesia), taste disturbance, cerebrovascular accident
Tabel 2 Adjuverende {X} monoterapi versus tamoxifen monoterapi - bivirkninger med signifikante forskelle
Table 2 Adjuvant {Invented Name} monotherapy versus tamoxifen monotherapy - adverse events with significant differences
Anoreksi, øget appetit Psykiske forstyrrelser Almindelig
Anorexia, appetite increase
Progressionstiden var signifikant længere og responsrater signifikant højere for letrozol uafhængigt af, om der var givet adjuverende antiøstrogen-behandling eller ej. Progressionstiden var signifikant længere for letrozol uafhængigt af det dominerende sygdomssted.
Time to progression was significantly longer, and response rate significantly higher for letrozole irrespective of whether adjuvant anti-oestrogen therapy had been given or not.
Myalgi, knoglesmerter1, osteoporose, knoglebrud.
Myalgia, bone pain1, osteoporosis, bone fractures
Rapporteringsperioden inkluderer behandlingsperioden plus 30 dage efter behandlingsophør Procenter i parentes indikerer hændelsesfrekvenser på enhvert tidspunkt efter randomisering, inklusive behandlingsperiode efter studiet.
Percentages in parentheses indicate event frequencies any time after randomisation, including post study treatment period.
Kontakt lægen eller apoteket, før du tager {X} - hvis du lider af en alvorlig nyresygdom - hvis du lider af en alvorlig leversygdom - hvis du lider af knogleskørhed (osteoporose) eller tidligere har haft knoglebrud (se også
Warnings and precautions Talk to your doctor or pharmacist before taking {Invented Name} if you have a severe kidney disease, if you have a severe liver disease, if you have a history of osteoporosis or bone fractures (see also “Follow-up during {Invented Name} treatment” in section 3).
Det primære endepunkt var sygdomsfri overlevelse defineret som intervallet mellem randomisering og første forekomst af lokoregionalt tilbagefald, fjernmetastase eller kontralateral brystcancer.
The primary endpoint was disease-free survival, defined as the interval between randomisation and the earliest occurrence of loco-regional recurrence, distant metastasis, or contralateral breast cancer.
Samtidig administration af tamoxifen, andre antiøstrogener eller østrogener skal undgås, da disse stoffer kan nedsætte den farmakologiske virkning af letrozol (se pkt.
Co-administration of {Invented Name} with tamoxifen, other anti-oestrogens or oestrogen-containing therapies should be avoided as these substances may diminish the pharmacological action of letrozole (see section 4.5).
Da træthed og svimmelhed kan forekomme hos patienter i behandling med {X}, og døsighed er rapporteret som en ikke almindelig bivirkning, bør der udvises forsigtighed ved bilkørsel og betjening af maskiner.
Since fatigue and dizziness have been observed with the use of {Invented Name} and somnolence has been reported uncommonly, caution is advised when driving or using machines.
Effekter på knoglerne {X} er et potent østrogen-supprimerende stof.
Bone effects {Invented Name} is a potent oestrogen-lowering agent.
88,2 ± 7,6% af radioaktiviteten genfundet i urin og 3,8 ± 0,9% i fæces.
labelled letrozole to healthy postmenopausal volunteers, 88.2 ± 7.6% of the radioactivity was recovered in urine and 3.8 ± 0.9% in faeces.
Angioødem, toksisk epidermal nekrolyse, erythema multiforme Knogler, led, muskler og bindevæv Meget almindelig Artralgi
Angioedema, toxic epidermal necrolysis, erythema multiforme Musculoskeletal and connective tissue disorders Very common:
Letrozol er en meget specifik aromatasehæmmer.
Letrozole is highly specific in inhibiting aromatase activity.
Letrozol N=2.582
Letrozole N=2582
Ved adjuverende behandling blev der udover de bivirkninger, der er præsenteret i Tabel 2, rapporteret følgende bivirkninger for henholdsvis {X} og tamoxifen (ved median behandlingsvarighed på 60 måneder plus 30 dage): operationskrævende angina (1,0% vs. 1,0%); hjertesvigt (1,1% vs. 0,6%); hypertension (5,6% vs. 5,7%); cerebrovaskulær hændelse/transitorisk cerebral iskæmi (2,1% vs.
In the adjuvant setting, in addition to the date presented in Table 2, the following adverse events were reported for {Invented Name} and tamoxifen, respectively (at median treatment duration of 60 months plus 30 days): angina requiring surgery (1.0% vs. 1.0%); cardiac failure (1.1% vs. 0.6%); hypertension (5.6% vs. 5.7%); cerebrovascular accident/transient ischaemic attack (2.1% vs. 1.9%).
Alopeci, udslæt (inklusive erytematøst, makulopapuløst og psoriasislignende udslæt samt udslæt med blærer), tør hud.
Alopecia, rash (including erythematous, maculopapular, psoriaform, and vesicular rash), dry skin
3 Protokol-definition af hændelser ved sygdomsfri overlevelse: lokoregionalt tilbagefald, fjernmetastaser eller kontralateral brystcancer.
Protocol definition of disease-free survival events: loco-regional recurrence, distant metastasis or contralateral breast cancer.
To velkontrollerede kliniske studier blev udført, hvor to doser letrozol (0,5 mg og 2,5 mg) blev sammenlignet med henholdsvis megestrolacetat og aminoglutethimid hos postmenopausale kvinder med fremskreden brystcancer, som tidligere havde været i behandling med antiøstrogener.
Two well-controlled clinical trials were conducted comparing two letrozole doses (0.5 mg and 2.5 mg) to megestrol acetate and to aminoglutethimide, respectively, in postmenopausal women with advanced breast cancer previously treated with anti-oestrogens.
Ved forlænget adjuverende behandling med {X} (median behandlingstid 5 år) henholdsvis placebo (median behandlingstid 3 år) blev der rapporteret operationskrævende angina (0,8% vs. 0,6%), forekomst eller forværring af angina (1,4% vs. 1,0%), myokardieinfarkt (1,0% vs. 0,7%), tromboembolisk hændelse* (0,9% vs. 0,3%), apopleksi/transitorisk cerebral iskæmi* (1,5% vs. 0,8%).
In the extended adjuvant setting for {Invented Name} (median duration of treatment 5 years) and placebo (median duration of treatment 3 years), respectively: angina requiring surgery (0.8% vs. 0.6%); new or worsening angina (1.4% vs. 1.0%); myocardial infarction (1.0% vs. 0.7%); thromboembolic event* (0.9% vs. 0.3%); stroke/transient ischaemic attack* (1.5% vs. 0.8%) were reported.
Et kontrolleret dobbeltblindet studie sammenlignede {X} (letrozol) 2,5 mg med tamoxifen 20 mg som første-linje-behandling til postmenopausale kvinder med fremskreden brystcancer.
One controlled double-blind trial was conducted comparing {Invented Name} (letrozole) 2.5 mg to tamoxifen 20 mg as first-line therapy in postmenopausal women with advanced breast cancer.
RR= Relativ risiko; KI = konfidensinterval 1 Da studiet blev afblindet i 2003, skiftede 1.551 patienter fra placebo-armen (60% af dem, der var egnet til at skifte - dvs. sygdomsfri) til letrozol med en median på 31 måneder efter randomisering.
When the study was unblinded in 2003, 1551 patients in the randomised placebo arm (60% of those eligible to switch, i.e. who were disease-free) switched to letrozole at a median 31 months after randomisation.
Tabel 3 Sekventiel behandling versus {X} monoterapi - bivirkninger med signifikante forskelle
Table 3 Sequential treatment versus {Invented Name} monotherapy - adverse events with significant differences
Dette medfører, at væksten af kræftceller eller spredningen af kræftceller til andre dele af kroppen stoppes eller hæmmes.
As a consequence tumour cells slow or stop growing and/or spreading to other parts of the body.
{ X} N=453
{Invented Name} N=453
- Lægen har ordineret {X} til dig personligt.
This medicine has been prescribed for you only.
Tag ikke {X} - hvis du er allergisk over for letrozol eller et af de øvrige indholdsstoffer (angivet i punkt 6).
Do not take {Invented Name} if you are allergic to letrozole or to any of the other ingredients of this medicine (listed in section 6), if you still have periods, i.e. if you have not yet gone through the menopause,
LÆGEMIDLETS NAVN {Lægemidlets (sær)navn} og relaterede navne (Se bilag I) styrke lægemiddelform [Se bilag I - Udfyldes nationalt]
NAME OF THE MEDICINAL PRODUCT {Invented name} and associated names (see Annex I) strength pharmaceutical form [See Annex I - To be completed nationally]
Hos postmenopausale kvinder med fremskreden brystcancer nedsætter daglige doser på 0,1-5 mg plasmakoncentrationen af estradiol, estron og estronsulfat med 75-95% fra baseline hos alle behandlede patienter.
In postmenopausal patients with advanced breast cancer, daily doses of 0.1 mg to 5 mg suppressed plasma concentration of oestradiol, oestrone, and oestrone sulphate by 75-95% from baseline in all patients treated.
2 624 (40%) patienter, som selektivt blev krydset over til letrozol, efter tamoxifen-armen blev afblindet i 2005.
Adjusted by chemotherapy use (yes/no) 624 (40%) patients selectively crossed to letrozole after tamoxifen arm unblinded in 2005
Dosisjustering af {X} er ikke nødvendig hos patienter med nedsat nyrefunktion, hvis kreatininclearance er ≥ 10 ml/min.
No dosage adjustment of {Invented Name} is required for patients with renal insufficiency with creatinine clearance ≥10 ml/min.
Rate for sygdomsfri overlevelse efter 5 år Fjernmetastase Hændelser
5-year DFS rate Distant metastases Events
Censoreret analyse af total overlevelse3
Censored analysis of OS3
Monoterapi-arm-analyse: Sygdomsfri og total overlevelse ved median opfølgning på 73 måneder (ITT-population)
Table 5 Monotherapy Arms Analysis: Disease-free and overall survival at a median follow-up of 73 months (ITT population)
Anafylaktisk reaktion Metabolisme og ernæring Meget almindelig Hyperkolesterolæmi Almindelig
Anaphylactic reaction Metabolism and nutrition disorders Very common:
- Øvrige indholdsstoffer [Udfyldes nationalt] Udseende og pakningsstørrelser [Udfyldes nationalt]
The other ingredients are [To be completed nationally] What {Invented Name} looks like and contents of the pack [To be completed nationally]
{X} er kontraindiceret under graviditeten (se pkt.
{Invented Name} is contraindicated during pregnancy (see sections 4.3 and 5.3).
BMD i lændehvirvlerne (L2-L4) viste et mediant fald på 4,1% for letrozol sammenlignet med en median øgning på 0,3% for tamoxifen.
At 24 months there was a statistically significant difference in the primary end-point; the lumbar spine BMD (L2-L4) showed a median decrease of 4.1% for letrozole compared to a median increase of 0.3% for tamoxifen.
Den sædvanlige dosis er 1 tablet daglig.
The usual dose is one tablet of {Invented Name} to be taken once a day.
Tæt opfølgning er nødvendig hos patienter med svært nedsat leverfunktion (Child-Pugh C) (se pkt.
Patients with severe hepatic impairment (Child-Pugh C) require close supervision (see sections 4.4 and 5.2).
Sygdomsfri overlevelse Hændelser
Disease-free survival Events
Kvalme, dyspepsi1, obstipation, abdominalsmerter, diarré, opkastning Ikke almindelig Mundtørhed, stomatitis1
Nausea, dyspepsia1, constipation, abdominal pain, diarrhoea, vomiting
Det symptom, der generede flest patienter i begge behandlingsarme (men signifikant oftere i {X}armen end i placebo-armen), var muskelsmerter.
The symptom that bothered most patients in both treatment arms was aching muscles, with a statistically significant difference in favour of placebo.
62 måneder median opfølgning
Median follow-up 62 months
Der blev ikke fundet ændringer i plasmakoncentrationen af androgener (androstendion og testosteron) hos raske postmenopausale kvinder efter administration af enkeltdoser på 0,1 mg, 0,5 mg og 2,5 mg letrozol eller i plasmakoncentrationen af androstendion hos postmenopausale patienter i behandling med daglige doser på 0,1-5 mg.
No changes were noted in plasma concentrations of androgens (androstenedione and testosterone) among healthy postmenopausal women after 0.1 mg, 0.5 mg, and 2.5 mg single doses of letrozole or in plasma concentrations of androstenedione among postmenopausal patients treated with daily doses of 0.1 mg to 5 mg, indicating that the blockade of oestrogen biosynthesis does not lead to accumulation of androgenic precursors.