natgillin/translations-raw huggingface dataset:
Metaanalyserne fra to studier omfattende 480 patienter med prostata- karcinom uden metastaser (M0), som ikke var blevet behandlet før, blev anvendt.
The effectiveness of bicalutamide 150 mg in the treatment of patients with locally advanced prostatic carcinoma without metastases, for whom primary treatment with hormones was indicated, was evaluated separately using the meta-analysis of two studies comprising 480 patients with prostatic carcinoma without metastases (M0) who had not been treated before.
Der var ingen signifikant forskel i overlevelse (RR=1, 05 (KI=0, 81- 1, 36), p=0, 669) eller i intervallet indtil progression (RR=1, 20 (KI 0, 96- 1, 51), p=0, 107) mellem gruppen, som blev behandlet med bicalutamid 150 mg og gruppen, som blev behandlet med kastration.
There was no significant difference in survival (HR=1.05 (CI=0.81-1.36), p=0.669) or in the interval until progression (HR=1.20 (CI 0.96-1.51), p=0.107) between the group treated with bicalutamide 150 mg and the group treated with castration.
Der blev observeret en generel tendens til forbedret livskvalitet ved behandling med bicalutamid 150 mg i forhold til kastration; undergrupperne som frembragte disse data, viste signifikant større sexlyst (p=0, 029) og udholdenhed (p=0, 046).
A general trend with respect to quality of life in favour of bicalutamide 150 mg in comparison with castration was observed; the subgroups that provided these data showed significantly higher sexual appetence (p=0.029) and fitness (p=0.046).
Kombinerede analyser af 2 kliniske studier, der omfattede 805 patienter med metastatisk prostata - karcinom, som ikke var blevet behandlet før og med en forventet mortalitet på 43%, viste at behandlingen med bicalutamid 150 mg er mindre effektiv end kastration i forhold til overlevelsestiden (RR=1, 30[ konfidensinterval 1, 04 – 1, 65]).
Combined analysis of 2 clinical studies comprising 805 patients with metastatic prostatic carcinoma, who had not been treated before with expected mortality 43%, showed that the treatment with bicalutamide 150 mg is less effective than castration as for the survival time (HR = 1.30 [confidence interval 1.04 – 1.65]).
11 ETIKETTERING
11 LABELLING
12 Den gældende tekst til etikettering er den endelige version der er fastlagt ved behandling i koordinationsgruppen.
12 The valid labelling text is the final version achieved during the Coordination group procedure.
13 INDLÆGSSEDDEL
13 PACKAGE LEAFLET
14 Den gældende tekst til indlægsseddel er den endelige version der er fastlagt ved behandling i koordinationsgruppen med følgende ændringer.
14 The valid package leaflet is the final version achieved during the Coordination group procedure with the following amendments:
BICALUTAMIDS VIRKNING OG HVAD DU SKAL BRUGE DET TIL
WHAT BICALUTAMIDE IS AND WHAT IT IS USED FOR
Bicalutamid tilhører gruppen af antiandrogener.
Bicalutamide belongs to the group of anti-androgens.
15 BILAG IV
15 ANNEX IV
16 BETINGELSER FOR MARKEDSFØRINGSTILLADELSEN
16 CONDITIONS OF THE MARKETING AUTHORISATION
De nationale kompetente myndigheder sikrer med referencemedlemsstaten (RMS) som koordinerende instans, at indehaverne af markedsføringstilladelserne opfylder følgende betingelser:
National Competent Authorities, coordinated by the Reference Member State (RMS), shall ensure that the following conditions are fulfilled by the Marketing Authorisation Holders:
- Ud over den rutinemæssige lægemiddelovervågning foretages forstærket overvågning og
- In addition to routine pharmacovigilance activities, identified and potential risks highlighted for
opfølgning af konstaterede og potentielle risici vedrørende hjerteinsufficiens, leversvigt, interstitiel lungesygdom og brystcancer samt af indberettede graviditeter hos partnere til patienter, der er i behandling med bicalutamid.
hepatic failure, interstitial lung disease, breast cancer, and reports concerning pregnancy in partners of patients taking bicalutamide.
London, den 22. november 2007 EMEA/ 433691/ 2007
London, 22 November 2007 EMEA/ 433691/ 2007
Bicaluplex og tilknyttede navne
OPINION FOLLOWING AN ARTICLE 29(4)1 REFERRAL FOR Bicaluplex and associated names
Ingers Industrials Solutions s. r. o indgav ansøgninger om gensidig anerkendelse af Bicaluplex og tilknyttede navne, 150 mg, filmovertrukket tablet, på grundlag af den markedsføringstilladelse, som Den Tjekkiske Republik udstedte den 30. november 2005.
Ingers Industrials Solutions s. r. o submitted applications for mutual recognition of Bicaluplex and associated names, 150 mg, film-coated tablet on the basis of the marketing authorisation granted by Czech Republic on 30 November 2005.
Der er identificeret væsentlige forskelle med hensyn til benefit/ risk- forholdet for produktet.
Significant differences have been identified with regard to the benefit/ risk ratio of the product.
Det drejer sig om to indikationer (behandling af lokalt fremskreden prostatakarcinom uden metastaser, hvor kirurgisk kastration eller anden form for medicinsk indgreb ikke er indiceret eller ikke kan anbefales, og monoterapi i initialbehandlingen eller som supplement til strålebehandling eller radikal prostatektomi hos patienter med prostatakarcinom (T3- T4, på ethvert stadium N, M0), hvilket blev anset for at udgøre et alvorligt problem for folkesundheden.
This refers to two indications (treatment of locally advanced prostatic carcinoma without metastases, for which surgical castration or other type of medical intervention is not indicated or unacceptable; and as monotherapy in early treatment or as an adjunct to treatment with radiotherapy or radical prostatectomy in patients with prostatic carcinoma (T3-T4, any Stage N, M0) and this was considered to be of serious public health concern.
På baggrund af alle de forelagte oplysninger og den faglige drøftelse i udvalget var CHMP på sit møde i september 2007 af den opfattelse, at benefit/ risk- forholdet er gunstigt for Bicaluplex og tilknyttede navne, at de indsigelser, der er rejst af Tyskland, ikke bør forhindre udstedelse af en markedsføringstilladelse, og at referencemedlemsstatens produktresumé, etikettering og indlægsseddel bør ændres.
During their September 2007 meeting, the CHMP, in the light of the overall data submitted and the scientific discussion within the Committee, was of the opinion that the benefit/ risk ratio is favourable for Bicaluplex and associated names, that the objections raised by Germany should not prevent the granting of a Marketing Authorisation and that the Summary of Product Characteristics, labelling and package leaflet of the Reference Member State should be amended.
Der blev vedtaget en positiv udtalelse ved konsensus den 20. september 2007.
A positive opinion was adopted by consensus on 20 September 2007.
1 Artikel 29, stk.
The final opinion was converted into a Decision by the European Commission on 22 November 2007.
(44- 20) 74 18 84 00 Fax (44- 20) 74 18 86 13 E- mail: mail@ emea. europa. eu http: // www. emea. europa. eu ©EMEA 2007 Reproduction and/ or distribution of this document is authorised for non commercial purposes only provided the EMEA is acknowledged Den endelige udtalelse blev omdannet til en afgørelse truffet af Europa- Kommissionen den 22. november 2007.
(44-20) 74 18 84 00 Fax (44-20) 74 18 86 13 E-mail: mail@emea. europa. eu http: / /www. emea. europa. eu ©EMEA 2007 Reproduction and/ or distribution of this document is authorised for non commercial purposes only provided the EMEA is acknowledged
London, den 16. august 2007 EMEA/ 378451/ 2007
London, 16 August 2007 EMEA/ 378451/ 2007
SAMMENDRAG AF UDTALELSEN VEDRØRENDE INDBRINGELSEN I HENHOLD TIL ARTIKEL 31 I RÅDETS DIREKTIV 2001/ 83/ EØF, MED SENERE ÆNDRIN - GER, FOR
SUMMARY INFORMATION ON REFERRAL OPINION PURSUANT TO ARTICLE 31 OF COUNCIL DIRECTIVE 2001/ 83/ EC, AS AMENDED, FOR
Bicalutamid, 150 mg, markedsføres i EU efter nationale ansøgninger og ansøgninger i henhold til den gensidige anerken - delsesprocedure.
Bicalutamide 150 mg is marketed in the EU following national and Mutual Recognition application procedures.
De godkendte indikationer er lokal avance - ret 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.
Den 27. juli 2006 foretog Belgien en indbringelse for EMEA i henhold til artikel 31 i direktiv 2001/ 83/ EF, med senere ændringer.
On 27 July 2006, Belgium presented a referral to the EMEA under Article 31 of Directive 2001/ 83, as amended.
Begrundelsen for indbringelsen fremgik af en gennemgang af risk/ benefit- profilen af lægemidler indeholdende bicalutamid, 150 mg.
The reasons for referral concerned a review of the benefit/ risk profile of medicinal products containing bicalutamide 150 mg.
- den manglende fordel i total overlevelse, sammenholdt med bivirkningerne, ved "lokal avanceret prosta -
- the lack of an overall survival benefit versus adverse events in ‘ locally advanced prostate cancer’;
- statistiske betænkeligheder vedrørende multiplicitet,
- statistical concerns regarding multiplicity;
- behandlingsstandarden for placebogruppen i de pågældende undersøgelser,
- the standard of care for the placebo group in the relevant studies;
- antallet af dødsfald som følge af hjertesvigt.
- the number of deaths due to cardiac failure.
Ud - valget vedtog derfor den 24. maj 2007 en udtalelse, der anbefaler opretholdelse eller, i givet fald, udste - delse af markedsføringstilladelse, med ændringer i de relevante punkter af produktresumeet, for produkter indeholdende bicalutamid, 150 mg.
Based on evaluation of the available data and the Rapporteurs’ assessment reports, the CHMP considered that the benefit/ risk profile of bicalutamide 150 mg-containing medicinal products remains favourable, and therefore adopted an opinion on 24 May 2007 recommending the maintenance or the granting, as appropriate, of the Marketing Authorisations with amendments to the relevant sections of the Summary of Product Characteristics, for bicalutamide 150 mg-containing medicinal products.
På baggrund af de foreliggende oplysninger konkluderede CHMP, at en sammenhæng mellem brugen af bicalutamid, 150 mg, og hjertesvigt ikke kan udelukkes, og fandt derfor, at der fortsat er behov for nær - mere at undersøge 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.
(44- 20) 74 18 84 00 Fax (44- 20) 74 18 86 68 E- mail: mail@ emea. europa. eu http: // www. emea. europa. eu ©. EMEA 2007 Reproduction and/ or distribution of this document is authorised for non commercial purposes only provided the EMEA is acknowledged Listen over de berørte produktnavne findes i bilag I.
(44-20) 74 18 84 00 Fax (44-20) 74 18 86 68 E-mail: mail@emea. eu. int http: / /www. emea. eu. int ©. EMEA 2006 Reproduction and/ or distribution of this document is authorised for non commercial purposes only provided the EMEA is acknowledged * Note:
Oplysningerne i nærværende dokument og de tilhørende bilag afspejler udelukkende CHMP' s udtalelse af 24. maj 2007.
The information given in this document and Annexes reflect only the CHMP Opinion dated 24 May 2007.
De kompetente myndigheder fører løbende opsyn med produktet.
The Member States’ competent authorities will continue to keep the product under regular review.
FORTEGNELSE OVER LÆGEMIDLERNES NAVNE, LÆGEMIDDELFORM, STYRKE, INDGIVELSESVEJ, ANSØGERE, INDEHAVERE AF MARKEDSFØRINGSTILLADELSER I MEDLEMSSTATERNE
LIST OF THE NAMES, PHARMACEUTICAL FORM, STRENGTH OF THE MEDICINAL PRODUCTS, ROUTE OF ADMINISTRATION, APPLICANTS, MARKETING AUTHORISATION HOLDERS IN THE MEMBER STATES
1 Markedsføringstilladelsesindehavere
1 Marketing Authorisation Holders
filmovertrukne tabletter
film-coated tablet
150 mg
Bicalutamid "Genericon" 150 mg
150 mg
Bicalutanorm "Genericon" 150 mg
Ratiopharm Arzneimittel Vertriebs- GmbH Albert- Schweitzer Gasse 3 1140 Wien
Ratiopharm Arzneimittel Vertriebs- GmbH Albert-Schweitzer Gasse 3 1140 Wien
150 mg
Bicalutamid-ratiopharm 150 mg
150 mg
Casodex 150 mg
Ingers Industrial Solutions
Ingers Industrial Solutions S. R. O.
Bicaluplex
BRNO Jeneweinova 51a
150 mg
Bicaluplex 150 mg
2 Medlemsstat
2 Member State
Indehaver af markedsføringstilladelse S. R. O.
Marketing Authorisation Holder
CY - Cypern
617 00 Brno CY - Cyprus
EL - Grækenland
EL - Greece
AstraZeneca Oy
AstraZeneca Oy Luomanportti 3 02200 Espoo
3 Medlemsstat
3 Member State
Indehaver af markedsføringstilladelse Luomanportti 3 02200 Espoo
Marketing Authorisation Holder
Bicalutamid CT- Arzneimittel
Bicalutamid CT- Arzneimittel
150 mg
Bicalutamid Ribosepharm 150 mg
150 mg
Bicavan 150 mg
150 mg
Bikalutamidi Synthon 150 mg
150 mg
Bicalutamid Alternova 150 mg
Peseri Trading Limited El Greco House
Peseri Trading Limited El Greco House
150 mg
Alidex 150 mg
4 Medlemsstat
4 Member State
Indehaver af markedsføringstilladelse 20 Queen Frederiks Street, Office 301 1066 Nicosia, Cyprus
Marketing Authorisation Holder
FI - Finland
20 Queen Frederiks Street, Office 301 1066 Nicosia, Cyprus FI - Finland
FI - Finland
20097 Hamburg, Germany FI - Finland
AstraZeneca 1, place Renault 92844 Rueil- Malmaison Cedex
AstraZeneca 1, place Renault 92844 Rueil-Malmaison Cedex
IS - Island
H-2045 IS - Iceland
LT - Lithaun
LT - Lithuania
LU - Luxemborg
LU - Luxembourg
NV AstraZeneca SA 110 rue E.
NV AstraZeneca SA 110 rue E.
Van Ophem B- 1180 Bruxelles Belgium
Van Ophem B-1180 Bruxelles Belgium
AstraZeneca UK Limited Silk Road Business Park Macclesfield Cheshire SK10 2NA United Kingdom
PL - Poland AstraZeneca UK Limited
PT - Portugal
Silk Road Business Park Macclesfield Cheshire SK10 2NA United Kingdom PT - Portugal
RO- Romænien
RO-Romania
SK – Slovakiet
SK – Slovakia
AstraZeneca UK Limited Silk Road Business Park Macclesfield Cheshire SK10 2NA
AstraZeneca UK Limited Silk Road Business Park Macclesfield Cheshire SK10 2NA United Kingdom
SL - Slovenien
SL - Slovenia
SV - Sverige
Invented name
AstraZeneca AB Västra Mälarehamnen 9 SE- 151 85 Södertälje
AstraZeneca AB Västra Mälarehamnen 9 SE-151 85 Södertälje
10 FAGLIGE KONKLUSIONER
10 SCIENTIFIC CONCLUSIONS
Pkt.
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.
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.
Efter egen gennemgang af disse oplysninger i 2004 og som følge af de resulterende betænkeligheder ved risk/ benefit- forholdet for bicalutamid 150 mg ved lokalt avanceret prostatacancer suspenderede de belgiske tilsynsmyndigheder i august 2005 den nationale markedsføringstilladelse for Casodex (bicalutamid), 150 mg.
Following their own review of these data carried out in 2004 and due to their resulting concerns over the benefit/ risk balance of bicalutamide 150 mg in locally advanced prostate cancer, the Belgian Regulatory Authority suspended their national Marketing Authorisation for Casodex (bicalutamide) 150 mg in August 2005.
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/ benefit - forholdet.
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.
Belgien indbragte derfor den 27. juli 2006 sagen for CHMP til vurdering i henhold til artikel 31 i direktiv 2001/ 83/ EF, med senere ændringer.
Therefore, Belgium referred the issue on 27 July 2006 for consideration by CHMP under Article 31 of Directive 2001/ 83/ EC, as amended.
I indbringelsen blev der rejst følgende fire punkter:
The 4 issues raised in the referral concern the analyses of the Early Prostate Cancer Programme (EPC):
- den manglende fordel i total overlevelse, sammenholdt med bivirkningerne, ved "lokal avanceret
- the lack of an overall survival benefit versus adverse events in ‘ locally advanced prostate cancer’;
- statistiske betænkeligheder vedrørende multiplicitet
- statistical concerns regarding multiplicity;
- behandlingsstandarden for placebogruppen i de pågældende undersøgelser
- the standard of care for the placebo group in the relevant studies;
På grundlag af de rejste betænkeligheder blev der til ansøgerne/ indehaverne af markedsføringstilladelserne stillet følgende spørgsmål, som indgik i den række spørgsmål fra CHMP, hvis besvarelse var grundlag for CHMP' s revurdering af risk/ benefit- forholdet:
Based on the concerns raised, the following questions were posed to the Applicants/ MAHs as part of the consolidated CHMP List of Questions, the responses to which were the basis of the CHMP reassessment of the benefit/ risk balance:
1 / 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?
1/ 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?
2 / Hvormed begrunder firmaet den manglende korrektion for test for multiplicitet i analysen af resultaterne for EPC?
2/ How does the company justify the absence of adjustment for tests of multiplicity in the analysis of the EPC results?
3 / Hvormed begrunder firmaet, at placeboarmen ikke fik fornøden behandling svarende til den nuværende behandlingsstandard, og hvorfor blev dette ikke taget i betragtning ved analyse af resultaterne ved EPC?
3/ How does the company justify that the placebo arm did not receive an adequate treatment according to the present standard of care and why this is not taken into account in the analysis of the EPC results?
4 / 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?
4/ 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?
11 Sagen inkluderede samtlige påbegyndte ansøgninger om markedsføringstilladelse og eksisterende markedsføringstilladelser for lægemidler indeholdende 150 mg bicalutamid.
Further, the referral concerned only
Yderligere omfattede sagen kun indikationen lokalt avanceret prostata cancer baseret på EPC’ s kliniske udviklingsprogram og den direkte relaterede tekst i pkt.
11 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.
Risk/ benefit- overvejelser
Benefit/ Risk considerations
Da EPC- programmet blev indledt for mere end otte år siden, var målet at dokumentere fordelen af tidlig behandling med bicalutamid i forhold til placebo, anvendt som monoterapi eller adjuverende terapi til operation eller strålebehandling.
When the EPC programme was initiated more than 8 years ago, the aim was to document the benefit of early bicalutamide therapy versus placebo as monotherapy or adjuvant therapy to surgery or radiotherapy.
EPC- undersøgelsen var empirisk opbygget, dvs. at den generelt sammenlignede Casodex (bicalutamid) med behandlingsstandarden i hver af de pågældende regioner.
The EPC study was an empirical design, that is to say, it generally compared Casodex (bicalutamide) to the standard of care in each region involved.
Der ses herved ses en gunstig tendens i total overlevelse ved lokalt avanceret sygdom, både når Casodex (bicalutamid) anvendes alene og i tilslutning til strålebehandling.
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.
Hvad angår det rejste spørgsmål om multiplicitet, anses det for hensigtsmæssigt at analysere undergrupperne statistisk, da dette har medvirket til at indsnævre indikationen til patienter med et gunstigere risk/ benefit - forhold for bicalutamid 150 mg.
As regards the multiplicity issue raised, it is considered appropriate to look at subgroups from a statistical viewpoint, as they have helped to narrow the indication to patients with a more favourable benefit/ risk balance for bicalutamide 150 mg.
Hændelser (%) hos Casodex -
Events (%) in Casodex patients
Hændelser (%) hos
Events (%) in placebo patients
(95% SI)
Hazard ratio (95% CI)
Watchful waiting Strålebehandling Radikal prostatektomi
Watchful waiting Radiotherapy Radical prostatectomy
58% og 69% progression hos patienter, der ikke desuden blev opereret eller fik strålebehandling).
In particular, there is a statistically significant and clinically meaningful improvement in progression-free survival in the patients with locally advanced prostate cancer who received Casodex (bicalutamide) as compared to placebo (58% versus 69% progressors in patients who were not receiving adjuvant surgery or radiotherapy).
Det empiriske design af de undersøgelser, hvor Casodex (bicalutamid), 150 mg, blev sammenlignet med placebo som adjuverende behandling til "standardbehandling", må derfor anses for at være rimeligt.
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.
Ingen af EPC- undersøgelserne forlangte, at placebogruppen skulle forholdes behandling indtil klinisk progression af sygdommen.
12 None of the EPC trials mandated that treatment be withheld from patients in the placebo group until clinical progression.
Ved påbegyndelse af aktiv behandling er medianværdien af PSA- niveauet i hver undergruppe over tærskelværdierne i de nuværende retningslinjer fra European Association of Urology (EAU).
The median PSA levels on initiation of active therapy for each subgroup are above the thresholds in current European Association of Urology (EAU) guidance.
I de kliniske undersøgelser forekom denne bivirkning i svær grad hos omkring 5% af patienterne.
In the clinical studies this was severe in around 5% of patients.