natgillin/translations-raw huggingface dataset:
Desuden tyder de på, at der ikke er nogen ugunstig indflydelse på tromboemboliske hændelser i opfølgningsperioden (hvilket underbygges af, at bivirkningsmønsteret ikke er konsistent med hormonale virkninger).
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).
Resultaterne af endnu en klinisk undersøgelse, en ajourført litteraturgennemgang og en ajourført gennemgang af sikkerhedsdatabasen.
With reference to heart failure mortality, the MAHs have submitted a limited amount of new data since this issue was last assessed, namely results from a further clinical study, an updated literature review and an updated review of their safety database.
For størstedelen af patienterne med hjertesvigt var der konfunderende faktorer ved patientens indtræden i undersøgelsen, og for samtlige dødsfald tilskrevet hjertesvigt var investigatorernes kausalitetsvurdering "uden sammenhæng".
The majority of patients with heart failure had confounding factors at study entry, and the causality assessment of investigators for all deaths ascribed to heart failure was “ not related”.
Tromboemboliske hændelser kan dog ikke helt "udelukkes" som medvirkende til den øgede kardiovaskulære mortalitet.
However, it is not possible to entirely “ rule out” thromboembolic events as contributory explanation of increased cardiovascular mortality.
Undersøgelsens formål bliver at vurdere incidensen af hjertesvigt samt kardiovaskulær 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.
Cancer- undergrupperne i undersøgelsen skal bestå af de patienter, der er i behandling med Casodex (bicalutamid) og dem, hvis behandling består i GnRH - analoger, 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.
Den fjerde analyse af EPC- data vil ligeledes blive fremlagt, når den foreligger.
The 4th analysis of the EPC data will also be provided when available.
Disse data støtter
In conclusion, the heart failure data remain a concern and are inconclusive, but do not significantly alter the benefit/ risk balance in locally advanced prostate cancer patients.
13 imidlertid udvalgets standpunkt, dvs. at indikationen bør indskrænkes til udvalgte patienter med lokalt avanceret prostatacancer og høj risiko for progression af sygdommen.
However, these data do support the Committee’ s position that the indication should be restricted to selected patients with locally advanced prostate cancer at high risk of disease progression.
Udvælgelsen af sådanne patienter kan tænkes baseret på kriterier som PSA- niveau, Gleason- score og sygdomsstadium.
How such patients are identified could be based on criteria such as PSA levels, Gleason score and stage of disease.
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.
Produktresuméet er ændret i overensstemmelse hermed, og det bemærkes i produktresuméet under pkt.
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.
5. 1, at for patienter med lokalt avanceret sygdom "var der en signifikant fordel for de patienter, som havde lokalt avanceret cancer prostatae.
Therefore, clinicians may
Afsnit 5. 1 i produktresuméet indeholder også et sammendrag af effektresultaterne fra EPC- undersøgelsen.
13 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 .” Section 5.1 of the SPC also includes a summary of the efficacy results from the EPC study.
Udvalget behandlede indbringelsen i henhold til artikel 31 i Rådets direktiv 2001/ 83/ EF, med senere ændringer, for lægemidler indeholdende bicalutamid, 150 mg.
The Committee considered the referral made under article 31 of Directive 2001/ 83/ EC, as amended, for medicinal products containing bicalutamide 150 mg.
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.
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.
Udvalget konkluderede, at benefit/ risk- forholdet for lægemidler indeholdende bicalutamid, 150 mg, til den godkendte indskrænkede indikation er gunstigt -
The CHMP concluded that the benefit/ risk balance of bicalutamide 150 mg containing medicinal products in the agreed restricted indication is favourable.
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.
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.
15 ÆNDRINGER SOM SKAL INKLUDERES I DE RELEVANTE AFSNIT AF PRODUKTRESUMEET FOR PRODUKTER SOM INDEHOLDER 150 MG BICALUTAMID
15 AMENDMENTS TO BE INCLUDED IN THE RELEVANT SECTION OF THE SUMMARY OF PRODUCT CHARACTERISTICS FOR BICALUTAMIDE 150MG CONTAINING MEDICINAL PRODUCTS
[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).
[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).
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).
Casodex blev givet som umiddelbar hormonterapi eller som adjuvans til radikal prostatektomi eller strålebehandling (hovedsagelig ekstern stråling).
At 7.4 years median follow up, 27.4% and 30.7% of all CASODEX and placebo-treated patients, respectively, had experienced objective disease progression.
Den behandlende læge må derfor tage stilling til, om den optimale behandlingsstrategi, for patienter med lav risiko for progression, er at udskyde hormonal behandling, indtil der er tegn på sygdomsprogression, specielt i forhold til efterfølgende radikal prostatektomi.
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.
Ved 7, 4- årsmedianen var der ingen forskel i overlevelse, dødeligheden var 22, 9% (HR = 0, 99 CI 0, 91 til 1, 09).
No overall survival difference was seen at 7.4 years median follow up with 22.9% mortality (HR=0.99; 95% CI 0.91 to1.09).
Progressionsfri overlevelse i lokalt avanceret sygdom opdelt terapigruppe.
Progression-free survival in locally advanced disease by therapy sub-group
Hazard ratio (95% CI)
Events (%) in Events (%) in placebo Hazard ratio CASODEX patients patients (95% CI)
Watchful waiting Strålebehandling
Watchful waiting Radiotherapy
193/ 335 (57. 6) 222/ 322 (68. 9) 66/ 161 (41. 0) 86/ 144 (59. 7)
193/ 335 (57.6) 222/ 322 (68.9) 0.60 (0.49 to 0.73) 66/ 161 (41.0) 86/ 144 (59.7) 0.56 (0.40 to 0.78)
179/ 870 (20. 6)
179/ 870 (20.6)
213/ 849 (25. 1)
213/ 849 (25.1)
0. 75 (0. 61 til 0. 91)
0.75 (0.61 to 0.91)
overlevelse i lokalt avanceret sygdom opdelt efter terapigruppe.
Overall survival in locally advanced disease by therapy sub-group
Døde (%) Casodex - Døde (%) placebo - Hazard ratio patienter patienter (95% CI)
Deaths (%) in Deaths (%) in placebo Hazard ratio CASODEX patients patients (95% CI)
164/ 335 (49. 0) 183/ 322 (56. 8) 0. 81 (0. 66 til 1. 01) 49/ 161 (30. 4) 61/ 144 (42. 4) 0. 65 (0. 44 til 0. 95)
164/ 335 (49.0) 183/ 322 (56.8) 0.81 (0.66 to 1.01) 49/ 161 (30.4) 61/ 144 (42.4) 0.65 (0.44 to 0.95)
137/ 870 (15. 7)
137/ 870 (15.7)
122/ 849 (14. 4)
122/ 849 (14.4)
1. 09 (0. 85 til 1. 39)
1.09 (0.85 to 1.39)
Hos disse patienter var der også en tendens til formindsket overlevelse i
In these patients there was also a trend toward decreased survival compared with
16 forhold til de patienter, der fik placebo (HR = 1, 16; 95% CI 0, 99 til 1, 37).
16 placebo patients (HR=1.16; 95% CI 0.99 to 1.37).
17 BILAG IV
17 ANNEX IV
18 De nationale kompetente myndigheder sikrer med referencemedlemsstaten som koordinerende instans, at indehaverne af markedsføringstilladelserne opfylder følgende betingelser:
18 National Competent Authorities (NCA), coordinated by the Reference Member State (RMS), shall ensure that the following conditions are fulfilled by the Marketing Authorisation Holders:
- Der gennemføres en ny farmakopidemiologisk undersøgelse med henblik på at skaffe bedre indsigt i
- A new pharmacoepidemiological study(ies) should be undertaken to get a better understanding of
den kardiovaskulære risiko.
cardiovascular risk.
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 should be to estimate the incidence of heart failure, cardiovascular morbidity and mortality in patients with prostate cancer, compared to the general population.
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.
- Resultaterne af den fjerde analyse af EPC- data indberettes til referencemedlemsstaten og til de
- The outcome of the 4th analysis of the EPC data should be provided to the RMS and the NCAs where
nationale kompetente myndigheder i de stater, hvor bicalutamid, 150 mg, er godkendt.
bicalutamide 150 mg is authorised.
- Alle indehavere af markedsføringstilladelser skal ud over den rutinemæssige lægemiddelovervågning
- For all MAHs, in addition to routine pharmacovigilance activities, identified and potential risks
foretage forstærket overvågning og opfølgning af følgende konstaterede og potentielle risici:
highlighted for increased monitoring and follow-up should include:
Hjertesvigt Leversvigt Interstitiel lungesygdom Brystkræft Indberetninger vedrørende graviditet hos partnere til patienter, der får bicalutamid
Heart failure Hepatic failure Interstitial lung disease Breast cancer Reports concerning pregnancy in partners of patients taking bicalutamide
FORTEGNELSE OVER LÆGEMIDLERNES NAVNE, LÆGEMIDDELFORM, STYRKE, INDGIVELSESVEJE, ANSØGERE, I MEDLEMSSTATERNE
LIST OF THE NAMES, PHARMACEUTICAL FORM, STRENGTH OF THE MEDICINAL PRODUCT, ROUTES OF ADMINISTRATION, APPLICANTS IN THE MEMBER STATES
1 Medlemsstat
1 Member State EU/ EEA
Box 552 2003 RN Haarlem, Nederlandene
Box 552 2003 RN Haarlem, The Netherlands
15 U (USP) / hætteglas
15 U (USP)/ vial
Pulver til Intramuskulær anvendelse injektionsvæske, Subkutan anvendelse opløsning Intravenøs anvendelse Intraarteriel anvendelse Intrapleural anvendelse Intraperitoneal anvendelse Lokal anvendelse
Intramuscular injection Subcutaneous injection Intravenous administration Intra-arterial administration Intra-pleural injection Local injection
Pulver til injektionsvæske, opløsning
powder for solution for injection
Intramuskulær anvendelse Subkutan anvendelse Intravenøs anvendelse Intraarteriel anvendelse Intrapleural anvendelse Intraperitoneal anvendelse Lokal/ Intratumoral anvendelse
Intramuscular injection Subcutaneous injection Intravenous administration Intra-arterial administration Intra-pleural injection Intraperitoneal administration Local/ Intratumoral injections
Intramuskulær anvendelse Subkutan anvendelse Intravenøs anvendelse Intraarteriel anvendelse Intrapleural anvendelse
Intramuscular injection Subcutaneous injection Intravenous administration Intra-arterial administration Intra-pleural injection Intraperitoneal administration Local/ Intratumoral injections
2 Medlemsstat
2
Lægemiddelform Indgivelsesvej Intraperitoneal anvendelse Lokal/ Intratumoral anvendelse
Pharmaceutical Route of administration Form
Bleomicina TEVA, 15 U 15 U (USP) / polvere per soluzione hætteglas iniettabile
Bleomicina TEVA, 15 U 15 U (USP)/ vial polvere per soluzione iniettabile
Intramuskulær anvendelse Subkutan anvendelse Intravenøs anvendelse Intraarteriel anvendelse Intrapleural anvendelse
Intramuscular injection Subcutaneous injection Intravenous administration Intra-arterial administration Intra-pleural injection Intraperitoneal administration
Indehaver af
Member State EU/ EEA
Ansøger Navn
Marketing Authorisation Holder
Indgivelsesvej
(Invented) Name
markedsførings tilladelse
Pharmaceutical Form
Intraperitoneal anvendelse Lokal/ Intratumoral anvendelse
Route of administration Local/ Intratumoral injections
(koncentrati on
Content (concentrati on)
Luxemborg
Luxembourg
15U poudre pour solution hætteglas injectable
BLEOMYCINE TEVA 15 U (USP)/ vial 15U poudre pour solution injectable
injektionsvæske, opløsning
powder for solution for injection
Subkutan anvendelse Intravenøs anvendelse Intraarteriel anvendelse Intrapleural anvendelse Lokal/ Intratumoral anvendelse
Intramuscular injection Subcutaneous injection Intravenous administration Intra-arterial administration Intra-pleural injection Local/ Intratumoral injections
hætteglas
15 U (USP)/ vial
Bleomycine 15 U (USP), 15 U (USP) / poeder voor oplossing hætteglas voor injectie
Bleomycine 15 U (USP), 15 U (USP)/ vial poeder voor oplossing voor injectie
Bleomycin Teva, Pulver 15 U (USP) / og væske til hætteglas injeksjonsvæske,
Bleomycin Teva, Pulver 15 U (USP)/ vial og væske til injeksjonsvæske, oppløsning
Intramuskulær anvendelse Subkutan anvendelse Intravenøs anvendelse
Intramuscular injection Subcutaneous injection Intravenous administration Intra-arterial administration Intra-pleural injection Intraperitoneal administration Local/ Intratumoral injections
15 U (USP) / hætteglas
Bleomycin Teva 15 U (USP)/ vial
Medlemsstat
Member State EU/ EEA
Ansøger Nederlandene
(Invented) Name
Lægemiddelform Indgivelsesvej Intrapleural anvendelse Intraperitoneal anvendelse Lokal/ Intratumoral anvendelse
Route of administration Intraperitoneal administration Local/ Intratumoral injections
Bleomicin Teva 15 U (USP), prašek za raztopino za injiciranje
Bleomicin Teva 15 U (USP), praš ek za raztopino za injiciranje
Bleomicina Teva 15 UI polvo para solución inyectable EFG
Bleomicina Teva 15 UI polvo para solución inyectable EFG
5 European Medicines Agency
5 ANNEX II
7 Westferry Circus, Canary Wharf, London, E14 4HB, UK Tel.
6 SCIENTIFIC CONCLUSIONS
Bleomycins virkning ligger i indskydningen i enkelte og dobbelte DNA- strenge, således at der opstår sprængninger i disse strenge, hvilket hæmmer celledeling, vækst og DNA- syntese.
The effect of bleomycin rests on intercalation with single and double strands of DNA, resulting in single and double strand ruptures, which inhibit cell division, growth and DNA synthesis.
Bleomycin påvirker desuden i mindre grad RNA - og proteinsyntese.
In a lower degree bleomycin also affects the RNA and protein synthesis.
Behandling med bleomycin finder næsten altid sted i kombination med andre cytostatiske midler og/ eller strålebehandling.
The administration of bleomycin almost always takes place in combination with other cytostatic drugs and/ or radiation therapy.
- Pladecellekarcinomer i hoved og hals
- Squamous cell carcinoma of Head and neck (SCCHN)
- Pladecellekarcinomer i ydre kønsdele: peniscancer, cancer i livmoderhalsen
- Squamous cell carcinoma of external genitalia: penile carcinoma, cervix carcinoma.
- (Non -) Hodgkins lymfomer og andre maligne lymfomer
- (Non-)Hodgkin´s lymphoma and other malignant lymphomas
- Testikelcancer
- Testis carcinoma
- Interpleural behandling af malign pleural effusion
- Intrapleural therapy of malignant pleural effusion.
Da vurderingen af benefit/ risk- forholdet ved disse indikationer var negativ for det oprindelige produkt, og da indikationerne som følge heraf blev fjernet fra listen over indikationer for alle bleomycinprodukter i Tyskland, blev indikationerne betragtet som nye indikationer, og Tyskland skønnede, at de forelagte oplysninger var utilstrækkelige til, at der kunne udstedes en markedsføringstilladelse for de foreslåede nye indikationer.
Because the benefit/ risk assessment for these indications was negative for the originator product and because the indications were consequently deleted from the authorised indications for all bleomycin-containing products in Germany, the indications were regarded as new indications, and the objecting member state considered that the submitted data was insufficient for granting a marketing authorisation for the proposed new indications.
Da der ikke kunne opnås enighed, indbragte CMD( h) sagen for CHMP.
Because consensus could not be reached, the CMD(h) referred the procedure to the CHMP.
CHMP bemærkede, at bleomycin har været anvendt klinisk siden 1960' erne, hvilket forklarer det manglende kliniske udviklingsprogram.
The CHMP noted that bleomycin is in clinical use since the 1960ies, thereby explaining the lack of a clinical development programme.
En række undersøgelser og publikationer viser dog tydeligt, at bleomycin har en virkning.
Most of the presented data describe bleomycin as component of multi- drug chemotherapy including cisplatin and therefore the individual contribution of bleomycin cannot be unequivocally determined, however a number of studies and publications clearly indicate that bleomycin demonstrates efficacy.
Hvad angår indikationen hoved- hals- cancer, er CHMP af den opfattelse, at selv om bleomycin har åbenlyse ulemper som følge af stoffets toksicitet (lungebetændelse, pulmonar fibrose, stomatitis og hudforandringer), er bleomycin stadig relevant i (neoadjuvant) behandling af sygdommen.
Regarding the indication in Head and Neck cancer, the CHMP is of the opinion that although bleomycin has obvious disadvantages related to its toxicity (pulmonitis, pulmonary fibrosis, stomatitis and skin changes), there is still a role for bleomycin in (neoadjuvant) treatment of the disease.
Der ses en helbredelsesrate på 34% ved andetvalgsbehandling samt forbedret lokoregional kontrol og overlevelse hos patienter med fremskreden hoved- hals- cancer ved hjælp af samtidig postoperativ strålebehandling og kemoterapeutisk behandling med mitomycin C og bleomycin.
In addition to the documentation already provided during the decentralised procedure, supporting a modest but certain role for bleomycin in the treatment of SCCHN, a number of recent reports support the role of bleomycin in conjunction with other chemotherapeutic moieties, identifying both a recovery ratio (RR) of 34% in second line treatment and the improvement of loco-regional control and survival in patients with advanced HNC through concomitant postoperative radio- and chemotherapeutical treatment with mitomycin C and bleomycin.
Hvad angår indikationen i epidermoide karcinomer i de ydre kønsdele, bemærkede CMPH, at bleomycin stadig anvendes ved livmoderhalskræft, og det blev besluttet, at selv om den kliniske virkning er beskeden ved denne indikation såvel som ved peniscancer, har adskillige nylige forsøg
Regarding the indication in Epidermoid carcinoma of external genitalia, the CHMP noted that bleomycin is currently still in use in cervical cancer, and it was agreed that although the clinical efficacy is modest in
7 påvist bleomycins betydning ved anvendelse til disse indikationer.
7 this indication, as well as in penile cancer, several recent trials have illustrated the significance of bleomycin in these indications.
Kombinationen af bleomycin, vindesin, mitomycin C og cisplatin hos patienter med tilbagevendende og/ eller metastatiske pladecellekarcinomer i livmoderhalsen er for nyligt blevet påvist at have en positiv virkning på overlevelse, og en fase II- undersøgelse påviste bleomycin som en del af et klinisk relevant alternativt behandlingsregime til cisplatin hos patienter med tilbagevendende livmoderhalskræft.
The combination of bleomycin, vindesine, mitomycin C and cisplatin in patients with recurrent and/ or metastatic squamous cell carcinoma of the cervix was recently shown to be of benefit with regards to survival and a phase II study showed bleomycin to be part of a clinically relevant alternative treatment regimen for cisplatin, in patients with recurrent cervical cancer.
CMPH bemærkede, at bleomycin stadig anvendes og også nævnes i aktuelle behandlingsvejledninger i Europa og Nordamerika, eksempelvis i forbindelse med pladecellekarcinomer i hoved og hals:
The CHMP also noted that bleomycin is still in use and also mentioned in current treatment guidelines in Europe and North America, such as the SCCHN:
2, 2008 (HCCN, USA), "CCO (Cancer Care Ontario) Formulary", revideret i 2006/ 2007, samt "Guidelines on penile cancer" (marts 2004) fra European Association of Urology.
Practice Guidelines in Oncology-v.2.2008 (HCCN, USA), the CCO (Cancer Care Ontario) Formulary, revised 2006/ 2007, and the Guidelines on penile cancer (March 2004) of the European Association of Urology.
Sluttelig konkluderede CHMP, at virkningen opvejer produktets toksicitet, og at benefit/ risk- forholdet er positivt.
In conclusion, the CHMP considered that this efficacy outweighs the toxicity of the product, and that the benefit/ risk balance is positive.
Bleomycin er beregnet til behandling af:
Bleomycin is intended for the treatment of: