natgillin/translations-raw huggingface dataset:
Hvormed begrunder firmaet indikationen for bicalutamid, 150 mg, til lokalt avanceret prostatacancer på baggrund af den manglende statistisk signifikante fordel i total overlevelse og de betydelige bivirkninger?
How does the company justify the indication of bicalutamide 150 mg for locally advanced prostate cancer knowing the absence of statistically significant overall survival and the important side effects?
For dødsfald som følge af hjertesvigt vides bestemmelsen af dødsårsagen at være upålidelig, og der blev kun udført meget få obduktioner.
Regarding the heart failure deaths, the allocation of cause of death is known to be unreliable, and very few post-mortems were done.
Den øgede overlevelse hos patienter, der får strålebehandling mod lokalt avanceret sygdom, synes også at svare til resultaterne af tidligere undersøgelser, og en synergistisk virkning med strålebehandling er ret plausibel.
In addition, the survival advantage observed in patients with locally advanced disease receiving radiotherapy appears to be consistent with that seen in previous studies, and a synergistic effect with radiotherapy is plausible.
- Der gennemføres en ny farmakopidemiologisk undersøgelse med henblik på at skaffe bedre indsigt i den kardiovaskulære risiko.
- A new pharmacoepidemiological study(ies) should be undertaken to get a better understanding of cardiovascular risk.
EL - Grækenland Genepharm SA 18th klm Marathon Ave 153 44 Pallini Attiki
EL - Greece Genepharm SA 18th klm Marathon Ave 153 44 Pallini Attiki
Undersøgelsen var imidlertid positiv for endepunktet primær progressionsfri overlevelse, både samlet og i hver delgruppe af lokalt avanceret sygdom.
However, the EPC study was positive for the primary progression free survival (PFS) endpoint, both overall and in the locally advanced subgroups.
- Udvalget konkluderede på grundlag af de foreliggende oplysninger, at en sammenhæng mellem brugen af bicalutamid, 150 mg, og hjertesvigt ikke kan udelukkes, og derfor fandt det fortsat nødvendigt med nærmere undersøgelse af den kardiovaskulære morbiditet og mortalitet.
- In view of the available data, the CHMP concluded that a potential association between the use of bicalutamide 150 mg and heart failure cannot be ruled out and therefore considered that the need to further study cardiovascular morbidity and mortality remains.
Indehaver af markedsføringstilladelse
Marketing Authorisation Holders
På baggrund af betænkelighederne vedrørende sikkerheden og virkningen af bicalutamid, 150 mg, fandt de belgiske kompetente myndigheder, at det ville være i folkesundhedens interesse at revurdere risk/benefitforholdet.
In view of the concerns related to safety and efficacy for bicalutamide 150 mg the National Competent Authority (NCA) in Belgium considered it to be in the interest of public health to perform a new benefit/risk assessment.
I retningslinjerne fra EAU foreslås symptomerne behandlet med profylaktisk strålebehandling af brysterne, tamoxifen eller aromatasehæmmere, skønt disse midler ikke er godkendt til denne anvendelse.
EAU guidelines suggest the use of prophylactic breast radiation, tamoxifen or aromatase inhibitors to manage these symptoms, although they are not licensed in this use.
Sagen inkluderede samtlige påbegyndte ansøgninger om markedsføringstilladelse og eksisterende markedsføringstilladelser for lægemidler indeholdende 150 mg bicalutamid.
The scope of the referral included all pending Marketing Authorisation applications as well as all Marketing Authorisations for medicinal products containing 150 mg bicalutamide.
Hvordan udelukker firmaet, at bicalutamid, 150 mg, var medvirkende til den øgede mortalitet som følge af hjertesvigt i Casodex-armen i den kliniske undersøgelse af EPC?
How can the company rule out any role of bicalutamide 150 mg in the increased mortality due to heart failure in the Casodex arm of the EPC trial?
Det generelle udtryk "høj risiko" rummer bedre de store forskelle i lokal praksis og de uundgåelige ændringer i standardbehandlingen, foruden at det for den enkelte patient tager hensyn til de mange variable, der kan bidrage til risikoen for progression.
A more specific target population is hard to define from the EPC data, and the general term “high risk” better accommodates wide differences in local practice and inevitable changes in the standard of care, and takes into account the many variables in the individual patient which may contribute to risk of progression.
I indbringelsen blev der rejst følgende fire punkter: - den manglende fordel i total overlevelse, sammenholdt med bivirkningerne, ved "lokal avanceret prostatacancer" - statistiske betænkeligheder vedrørende multiplicitet - behandlingsstandarden for placebogruppen i de pågældende undersøgelser - antallet af dødsfald som følge af hjertesvigt.
The 4 issues raised in the referral concern the analyses of the Early Prostate Cancer Programme (EPC): - the lack of an overall survival benefit versus adverse events in ‘locally advanced prostate cancer'; - statistical concerns regarding multiplicity; - the standard of care for the placebo group in the relevant studies; - the number of deaths due to cardiac failure.
RMS konkluderede dengang, at Casodex (bicalutamid) 150 mg ikke burde anvendes til behandling af "lokaliseret" prostatacancer, men at risk/benefit-forholdet stadig var positivt for udvalgte patienter med "lokalt avanceret" prostatacancer, som umiddelbar behandling enten alene eller som adjuverende behandling til radikal prostatektomi eller strålebehandling.
At that time, the RMS concluded that Casodex (bicalutamide) 150 mg should not be used in the treatment of ‘localised' prostate cancer, however, it was concluded that the benefit/risk balance remained positive for selected patients in ‘locally advanced' prostate cancer, as immediate therapy either alone or as adjuvant to treatment by radical prostatectomy or radiotherapy.
Casodex (bicalutamid) 150 mg blev undersøgt til behandling af patienter med lokaliseret (T1-T2, N0 eller NX, M0) eller lokalt avanceret (T3-T4, N0, NX, N+, M0; T1-T2, N+, M0) ikke-metasteret prostatacancer i en kombineret analyse af 3 placebokontrollerede studier med i alt 8113 patienter.
CASODEX (Bicalutamide) 150 mg was studied as a treatment for patients with localised (T1-T2, N0 or NX, M0) or locally advanced (T3-T4, any N, M0; T1-T2, N+, M0) non-metastatic prostate cancer in a combined analysis of 3 placebo controlled double-blind studies in 8113 patients, where CASODEX was given as immediate hormonal therapy or as adjuvant to radical prostatectomy or radiotherapy, (primarily external beam radiation).
Bemærk: Dette bilag III (ændringer til produktresuméet) er identisk med det, der blev vedlagt Kommissionens afgørelse om den i henhold til artikel 31 indbragte sag vedrørende lægemidler indeholdende bicalutamid 150 mg. Teksten havde gyldighed på daværende tidspunkt.
Note: This Annex III (Amendments to the Summary of Product Characteristics) is the one that was Annexed to the Commission Decision on this Article 31 referral for bicalutamide 150 mg containing medicinal products.
ÆNDRINGER TIL PRODUKTRESUMEET
AMENDMENTS TO THE SUMMARY OF PRODUCT CHARACTERISTICS
ÆNDRINGER SOM SKAL INKLUDERES I DE RELEVANTE AFSNIT AF PRODUKTRESUMEET FOR PRODUKTER SOM INDEHOLDER 150 MG BICALUTAMID
AMENDMENTS TO BE INCLUDED IN THE RELEVANT SECTION OF THE SUMMARY OF PRODUCT CHARACTERISTICS FOR BICALUTAMIDE 150MG CONTAINING MEDICINAL PRODUCTS
De anmodede supplerende analyser af data fra EPC-undersøgelserne bekræfter, at der er øget risiko for dødsfald registreret som hjertesvigt (dog uden forhøjet total kardiovaskulær risiko) og øget risiko for urogenitale symptomer (herunder gynækomasti og smerter i brysterne), hovedsagelig i det første behandlingsår.
The requested additional analyses of the EPC trial data confirm an increased risk for deaths coded as heart failures (however, with no overall excess risk in the cardiovascular system), an increased risk of urogenital symptoms (including gynaecomastia and breast pain) mainly during the first year of intake, and further indicate the absence of an adverse effect on thromboembolic events during the follow-up (supported by a pattern of events inconsistent with hormonal effects).
Schwarzenbergplatz 7 1037 Wien
1037 Wien
- Udvalget fandt, at bicalutamid, 150 mg, er effektivt til behandling af lokal avanceret prostatacancer, men at indikationen bør indskrænkes til patienter med høj risiko for progression af sygdommen.
- The Committee considered that bicalutamide 150 mg is effective in the treatment of locally advanced prostate cancer; however the CHMP considered that the therapeutic indication should be restricted to treatment of patients at high risk of disease progression.
Generis Farmacêutica, S.A. Office Park da BelouraEdifício 4 Quinta da Beloura 2710-444 Sintra
Quinta da Beloura 2710-444 Sintra
Umiddelbart forekommer det indlysende, at patienter, der desuden har fået behandling med kurativt sigte, ved tillægsbehandling med bicalutamid ikke opnår så stor en forbedring af prognosen som andre patienter.
It seems intuitive that for good prognosis patients who have also received treatment of curative intent, the addition of bicalutamide might confer less benefit than in other patients.
- Resultaterne af den fjerde analyse af EPC-data indberettes til referencemedlemsstaten og til de nationale kompetente myndigheder i de stater, hvor bicalutamid, 150 mg, er godkendt.
- The outcome of the 4th analysis of the EPC data should be provided to the RMS and the NCAs where bicalutamide 150 mg is authorised.
Der skal udføres en ny farmakopidemiologisk undersøgelse som led i en godkendt risikostyringsplan med forpligtelse til at skaffe bedre indsigt i den kardiovaskulære risiko, efter at udtalelsen er afgivet.
A new pharmacoepidemiological study will be undertaken as part of an agreed Risk Management Plan (RMP), a post-opinion commitment to get a better understanding of cardiovascular risk.
Yderligere omfattede sagen kun indikationen lokalt avanceret prostata cancer baseret på EPC's kliniske udviklingsprogram og den direkte relaterede tekst i pkt.
Further, the referral concerned only the locally advanced prostate cancer indication based on the Early Prostate Cancer study programme, and the directly related wording in sections 4.1 and 5.1 of the SPC.
Undersøgelsens formål bliver at vurdere incidensen af hjertesvigt samt den kardiovaskulære morbiditet og mortalitet hos patienter med prostatacancer i forhold til den almindelige befolkning.
The aim of the study is to estimate the incidence of heart failure, cardiovascular morbidity and mortality in patients with prostate cancer, compared to the general population.
De godkendte indikationer er lokalt avanceret prostatacancer som umiddelbar behandling enten alene eller i kombination med anden behandling eller som adjuverende behandling til radikal prostatektomi eller strålebehandling.
Its authorised indications include the treatment of patients with locally advanced prostate cancer, as an immediate therapy either alone or as adjuvant to treatment by radical prostatectomy or radiotherapy.
1.09 (0.85 til 1.39)
1.09 (0.85 to 1.39)
AstraZeneca UK Ltd, 600 Capability Green Luton, Bedfordshire,
RO-Romania AstraZeneca UK Ltd, 600 Capability Green Luton, Bedfordshire,
Astra Zeneca Österreich GmbH
AT - Austria Astra Zeneca Österreich GmbH Schwarzenbergplatz 7
Reduktionen var tydeligst hos patientgrupper med højst risiko for sygdomsprogression.
A reduction in risk of objective disease progression was seen across most patient groups but was most evident in those at highest risk of disease progression.
0.81 (0.66 til 1.01)
0.81 (0.66 to 1.01)
0.65 (0.44 til 0.95)
0.65 (0.44 to 0.95)
20 Queen Frederiks Street, Office 301
20 Queen Frederiks Street, Office 301 1066 Nicosia, Cyprus
Ingers Industrial Solutions Bicaluplex
Ingers Industrial Solutions S.R.O.
Undersøgelsen skal desuden omfatte prostatacancer-undergrupper bestående af patienter, der behandles med bicalutamid, med GnRH-analoger, med orkiektomi eller med anden hormonbehandling.
Further, the study should include prostate cancer subgroups to include those on bicalutamide, and those treated with LHRH analogues, orchidectomy, and other hormonal therapies.
Hafnerstraße 211 8054 Graz
8054 Graz
Progressionsfri overlevelse ved lokal avanceret sygdom, fordelt på behandlingsundergrupper
Progression-free survival in locally advanced disease by therapy sub-group
5.1 i produktresuméet blev ændret med en bemærkning om, den optimale behandlingsstrategi for patienter med lav risiko for progression af sygdommen, navnlig i forbindelse med adjuverende behandling efter radikal prostatektomi, kan være at udskyde hormonbehandlingen, indtil der opstår tegn på progression af sygdommen.
Section 5.1 of the SPC was amended to note that the optimum medical strategy for a patient at low risk of disease progression, particularly in the adjuvant setting following radical prostatectomy, might be to defer hormonal therapy until signs that the disease is progressing.
4.1 Terapeutiske indikationer [Lægemiddelnavn] 150 mg er indiceret til behandling af lokalt avanceret prostatacancer med høj risiko for sygdomsprogression, enten som umiddelbar behandling alene eller som adjuverende behandling ved radikal prostatektomi eller ved strålebehandling (se afsnit 5.1).
4.1 Therapeutic indications [Invented name] 150mg is indicated either alone or as adjuvant to radical prostatectomy or radiotherapy in patients with locally advanced prostate cancer at high risk for disease progression (see section 5.1).
Resultaterne skal indberettes til referencemedlemsstaten og til de nationale kompetente myndigheder i de stater, hvor bicalutamid, 150 mg, er godkendt.
The results should be reported to the RMS and the NCAs where bicalutamide 150 mg is authorised.
Hændelser (%) hos placebo-patienter
Events (%) in placebo patients
Luomanportti 3 02200 Espoo
02200 Espoo
Resultaterne for progressionsfri overlevelse er gengivet nedenfor:
The PFS results are given again below:
Capability Green Luton, Bedfordshire, LU1 3LU, UK
600 Capability Green Luton, Bedfordshire LU1 3LU
0.60 (0.49 til 0.73)
0.60 (0.49 to 0.73)
0.75 (0.61 til 0.91)
0.75 (0.61 to 0.91)
Hændelser (%) hos Casodexpatienter
Events (%) in Casodex patients
Cancer-undergrupperne i undersøgelsen skal bestå af de patienter, der er i behandling med Casodex (bicalutamid) og dem, hvis behandling består i GnRHanaloger, orkiektomi eller anden hormonbehandling.
Further, the study will include prostate cancer subgroups to include those on Casodex (bicalutamide), and those treated with luteinizing hormone-releasing hormone (LHRH) analogues, orchidectomy, and other hormonal therapies.
0.56 (0.40 til 0.78)
0.56 (0.40 to 0.78)
Ved den oprindelige godkendelse af indikationen prostatacancer i tidligt stadium var data vedrørende total overlevelse for præliminære til at kunne analyseres, men det giver mening efterfølgende at analysere dette endepunkt i de samme undergrupper.
At the initial authorisation of the early prostate cancer indication, the data for overall survival were too immature to allow an analysis, however it makes sense to subsequently analyse this endpoint in the same subgroups, and there are favourable trends in overall survival for patients with locally advanced disease receiving Casodex (bicalutamide) alone, and for patients also receiving radiotherapy.
Klinikerne kan derfor skønne, at den optimale behandlingsstrategi for patienter med lav risiko for progression af sygdommen, navnlig i forbindelse med adjuverende behandling efter radikal prostatektomi, kan være at udskyde hormonbehandlingen, indtil der opstår tegn på progression af sygdommen."
Therefore, clinicians may decide that the optimum medical strategy for a patient at low risk of disease progression, particularly in the adjuvant setting following radical prostatectomy, may be to defer hormonal therapy until signs that the disease is progressing.
BEGRUNDELSE FOR ÆNDRINGEN AF PRODUKTRESUMÉET
GROUNDS FOR AMENDMENT OF THE SUMMARY OF PRODUCT CHARACTERISTICS Whereas
EL - Grækenland Astrazeneca SA 4 Theotocopoulou & Astronauton
EL - Greece Astrazeneca SA 4 Theotocopoulou & Astronauton 151 25 Marousi-Athens
Døde (%) placebopatienter
Deaths (%) in placebo patients
AstraZeneca AB Västra Mälarehamnen 9 SE-151 85 Södertälje
SE-151 85 Södertälje
EL - Grækenland Alvia SA 18th klm Athens-Marathon Ave
EL - Greece Alvia SA 18th klm Athens-Marathon Ave 153 44 Pallini Attiki
Ratiopharm Arzneimittel Vertriebs-GmbH Albert-Schweitzer Gasse 3 1140 Wien
Albert-Schweitzer Gasse 3
Sygdommens snigende forløb gør det vanskeligt at skaffe data for total overlevelse af patienter med prostatacancer i tidligt stadium.
It is difficult to obtain overall survival data in patients with early prostate cancer due to its insidious course.
Hvad angår tilstrækkeligheden af behandlingen i placebogruppen i EPC-undersøgelserne fandtes der ved påbegyndelse af undersøgelserne ingen bredt anerkendt standardbehandling ved lokal avanceret prostatacancer (hvilket stadig ikke er tilfældet).
With reference to the adequacy of treatment in the placebo group in the EPC studies, given that at the time of initiation of these studies there was no widely agreed standard of care in locally advanced prostate cancer (something which remains the case), the empirical design of the studies, which compared Casodex (bicalutamide) 150mg or placebo when given as an adjunct to “standard care” is considered reasonable.
Farma-APS, Produtos Farmacêuticos, S.A. Rua João de Deus, 19 Venda Nova 2700-487 Amadora
Venda Nova 2700-487 Amadora
Hos patienter med lokalt avanceret sygdom er fordelen mindre efter operation og når strålebehandlingen kan forventes at være kurativ.
Benefit is generally a function of risk progression and in patients with locally advanced disease; benefit is reduced after surgery or in cases where radiotherapy is likely to be curative.
- Udvalget konkluderede, at benefit/risk-forholdet for lægemidler indeholdende bicalutamid, 150 mg, til den godkendte indskrænkede indikation er gunstigt anbefalede CHMP opretholdelse af markedsføringstilladelserne for alle de produkter og udstedelse af markedsføringstilladelse for alle de ansøgninger, der er refereret til i bilag I til udtalelsen.
- The CHMP concluded that the benefit/risk balance of bicalutamide 150 mg containing medicinal products in the agreed restricted indication is favourable.
Peseri Trading Limited El Greco House 20 Queen Frederiks Street, Office 301
20 Queen Frederiks Street, Office 301 1066 Nicosia, Cyprus FI - Finland Peseri Trading Limited El Greco House
Af den årsag er det ikke favorabelt at anvende Casodex til patienter med lokaliseret prostatacancer.
In view of this, the benefit-risk profile for the use of CASODEX is not considered favourable in this group of patients.
AstraZeneca UK Limited Horizon Place 600 Capability Green Luton, Bedfordshire LU1 3LU
BG - Bulgaria AstraZeneca UK Ltd, 600 Capability Green Luton, Bedfordshire, LU1 3LU, UK
De skal være i overensstemmelse med ændringerne af de pågældende afsnit af produktresuméet, som fremgår af bilag III til udtalelsen.
As a consequence, the CHMP has recommended to maintain the Marketing Authorisations for all medicinal products and to grant Marketing Authorisations for all applications referred to in Annex I of the Opinion in accordance with the amendments to the relevant sections of the Summary of Product Characteristics, set out in Annex III of the Opinion.
AstraZeneca UK Limited Silk Road Business Park Macclesfield Cheshire SK10 2NA
SK - Slovakia AstraZeneca UK Limited Silk Road Business Park Macclesfield
Sagen omfattede hverken øvrige dele af produktresuméet eller øvrige godkendte indikationer for bicalutamid 150 mg.
Other aspects of the SPC and the other indication for bicalutamide 150 mg, which is approved in some EU member states, were not within the scope of the referral.
Bicalutamid "Genericon"
Bicalutamid CTArzneimittel
Medlemsstat
Germany
5.1, at for patienter med lokalt avanceret sygdom "var der en signifikant fordel for de patienter, som havde lokalt avanceret cancer prostatae.
The SPC has been amended accordingly and notes in section 5.1 that, for patients with locally advanced disease “A reduction in risk of objective disease progression… was most evident in those at highest risk of disease progression.
Analysepopulation Døde (%) Casodexpatienter
Overall survival in locally advanced disease by therapy sub-group Analysis population Deaths (%) in CASODEX patients
Bicalutamid CT-Arzneimittel 150 mg
Bicalutamida Prostec 150 mg
112 (4 x 28) tabletter (multipakning)
112 (4 x 28) tablets (multipack)
Særnavn Styrke Lægemiddelform Administration
Invented name Strength Pharmaceutical Form
Subkutan anvendelse Fyldt injektionssprøjte (glas) med on-body-injektor (Onpro-kit)
Solution for injection Subcutaneous use Pre-filled syringe (glass) with on body-injector (Onpro kit)
Subkutan anvendelse Fyldt injektionssprøjte (glas) uden blisterpakning
Solution for injection Subcutaneous use pre-filled syringe (glass) without blister
1 fyldt injektionssprøjte + on-body-injektor (Onprokit)
0.6 ml (10 mg/ml) 1 pre-filled syringe + on body injector (Onpro kit)
Subkutan anvendelse Fyldt injektionssprøjte (glas) med kanylebeskyttelse
Solution for injection Subcutaneous use pre-filled syringe (glass) with needle guard
Subkutan anvendelse Fyldt injektionssprøjte (glas) 0,6 ml (10 mg/ml)
0.6 ml (10 mg/ml) 1 pre-filled syringe with needle guard
1 flaske + 1 doseringssprøjte + 1 adaptor
1 bottle + 1 dosing syringe + 1 adapter
Oral anvendelse Blisterpakning (PVC/alu)
Blister (PVC/alu foil)
300 mg Filmovertrukne tabletter
Film-coated tablet
Oral opløsning Oral anvendelse Flaske (HDPE)
Bottle (HDPE)
Styrke Lægemiddelform Administration Emballage Indhold Pakningsstørrelse
Immediate Packaging
Dette gør det nemmere for Dem at foretage flere aktiviteter.
This will make it easier for you to do more activities.
• Efter anmodning fra det Europæiske Lægemiddelagentur.
• At the request of the European Medicines Agency.
Steady state hos frivillige nås inden for cirka 6 dage.
Steady state in volunteers is reached within about 6 days.
INR skal i alle tilfælde monitoreres regelmæssigt.
In all cases, INR should be monitored on a regular schedule.
(16%)) blev forbedret efter 12 ugers behandling.
(16%)) was improved after 12 weeks of treatment.
Rådgivning fra en hepatolog anbefales.
The advice of a hepatologist is recommended.
nedenfor);
below);
Den kan tages med eller uden mad uden hensyntagen til tidspunktet på dagen.
It may be taken with or without food and without regard to the time of day.
En NOAEL er ikke blevet fastlagt.
A NOAEL has not been established.
Tag ikke mere end én tablet om dagen.
Do not take more than one tablet each day.
• Hvis De er barn eller ung under 18 år.
• If you are a child or adolescent under 18 years old.
• Hvis De har eller har haft et alvorligt leverproblem.
• If you have or have had a serious liver problem;
Det er vigtigt, at disse prøver tages hver måned under behandlingen, selvom De ikke har symptomer.
It is important to have these tests every month during treatment, even if you do not have any symptoms at all.
Den afsluttende elimineringshalveringstid (t½) er 10 timer.
The terminal elimination half-life (t½) is 10 hours.
Deres læge vil rådgive Dem om egnet prævention.
Your doctor will advise you about suitable contraception.
Den absolutte biotilgængelighed af Thelin er mellem 70 og 100 %.
The absolute bioavailability of Thelin is between 70 and 100%.
Af hensyn til Deres sikkerhed er det yderst vigtigt, at De får taget regelmæssige blodprøver.
For your own safety, it is very important that you have regular blood tests.
Interaktion med et sådant lægemiddel kan derfor ikke udelukkes.
Therefore an interaction with such a drug cannot be excluded.
Dosis af denne medicin skal muligvis justeres af Deres læge;
The dose of these medicines may need to be adjusted by your doctor.
Median forskel fra placebo ( 95% CI)
Median Difference from Placebo (95% CI)
Skal skrives i braille-skrift på fremstillingstidspunktet.
To be written in braille at time of manufacture.
Mindre end 1 % af dosen udskilles som uændret aktivt stof.
Less than 1% of the dose is excreted as unchanged active ingredient.