natgillin/translations-raw huggingface dataset:
The neoadjuvant (pre-operative) treatment indication represented the major deviation across the nationally approved SmPCs, as it was approved in some member states in 2001 but the application was withdrawn in others, primarily because neoadjuvant endocrine treatment was not a validated concept at the time and because the results of the pivotal adjuvant study were not yet available.
Indikacija neoadjuvantnega (predoperativnega) zdravljenja je predstavljala glavno odstopanje v vseh povzetkih glavnih značilnosti zdravila, odobrenih na nacionalni ravni, saj je bila v nekaterih državah članicah odobrena leta 2001, druge pa so vlogo umaknile zlasti zato, ker takrat neoadjuvantno endokrino zdravljenje ni bil potrjen koncept in ker še ni bilo na voljo rezultatov ključne dopolnilne študije.
The CHMP noted the pivotal study for the adjuvant treatment indication, BIG 1-98, coordinated by the collaborative group IBCSG (International Breast Cancer Study Group) and the parent organization BIG (Breast International Group), which specifically excluded patients who did not have a confirmed diagnosis of invasive breast cancer.
CHMP je upošteval študijo BIG 1-98, ki je ključna za indikacijo adjuvantnega zdravljenja, in sta jo uskladili Mednarodna skupina za raka dojk IBCSG (International Breast Cancer Study Group) in krovna organizacija BIG (Breast International Group), pri čemer je študija izrecno izključevala bolnice brez potrjene diagnoze invazivnega raka dojke.
Because doubling the exposure to letrozole is not linked to safety concerns and because under-exposure should be avoided as efficacy has been shown to be dose dependent, the CHMP concluded that no dose adjustment is needed in patients with severe hepatic impairment, but that a warning should be inserted in section 4.4.
Ker dvakratna izpostavljenost letrozolu ni povezana s tveganjem za varnost, in ker se je treba premajhni izpostavljenosti izogibati, saj je bilo dokazano, da je učinkovitost odvisna od odmerka, je CHMP sklenil, da pri bolnikih s hudo okvaro jeter odmerka ni treba prilagajati, vendar je v poglavje 4.4 treba vnesti opozorilo.
A statement on the absence of studies on the use of Femara in male breast cancer was also added.
Prav tako so dodali izjavo o odsotnosti študij o uporabi zdravila Femara za raka dojke pri moških.
Letrozole inhibits the enzyme involved in the synthesis of oestrogens, which are required for proper embryo and foetal development.
Letrozol zavira encim, ki sodeluje pri sintezi estrogenov, ki so potrebni za pravilen razvoj zarodka in ploda.
Scientific conclusions and grounds for amendment of the summary of product characteristics, labelling and package leaflet presented by the European Medicines Agency
Znanstveni zaključki in podlaga za spremembo povzetka glavnih značilnosti zdravila, označevanja in navodila za uporabo, ki jih je predstavila Evropska agencija za zdravila
In addition, letrozole is not considered to have a narrow therapeutic index.
Poleg tega se letrozol ne uvršča med zdravila z ozkim terapevtskim indeksom.
For the remaining sections, the CHMP adopted a harmonised wording in line with the nationally approved SmPCs, although minor revisions were made.
Za ostala poglavja je CHMP sprejel usklajeno besedilo, skladno s povzetki glavnih značilnosti zdravila, ki so odobreni na nacionalni ravni, čeprav je naredil manjše popravke.
Femara was included in the list of products for Summary of Product Characteristics (SmPC) harmonisation, due to the divergent national decisions taken by Member States concerning the authorisation of the above-mentioned product.
Zdravilo Femara je bilo vključeno na seznam zdravil za uskladitev povzetka glavnih značilnosti zdravila zaradi različnih nacionalnih odločitev držav članic glede dovoljenja za promet z omenjenim zdravilom.
Regarding the pre-operative use of letrozole if receptor status is negative or unknown, the CHMP considered a contraindication to be unnecessary, as this is already sufficiently explained in Section 4.4.
Če je status receptorjev negativen ali neznan, je CHMP glede predoperativne uporabe letrozola menil, da kontraindikacija ni potrebna, saj je to že dovolj pojasnjeno v poglavju 4.4.
A statement recommending against the use of Femara for patients with problems of galactose intolerance, severe lactase deficiency or glucose-galactose malabsorption was also added.
Dodana je bila tudi izjava, ki odsvetuje uporabo zdravila Femara za bolnike z intoleranco za galaktozo, hudim pomanjkanjem laktaze ali malabsorpcijo glukoze/galaktoze.
In the absence of clinical trials, the CHMP therefore concluded that the safety and efficacy of Femara in this population is not established.
Ker ni bilo kliničnih preskušanj, je CHMP zaključil, da varnost in učinkovitost zdravila Femara pri tej populaciji nista dokazani.
Regarding use in elderly, the CHMP did not consider dose adjustment to be required, based on analyses of efficacy and safety conducted for all pivotal studies with Femara.
Glede uporabe pri starejših je CHMP menil, da prilagoditev odmerka ni potrebna, kar je ugotovil na podlagi analize učinkovitosti in varnosti, izvedene za vse ključne študije za zdravilo Femara.
The CHMP instead included a warning in Section 4.4 stating that safety data in patients with significant organ impairment are lacking.
Zato je CHMP v poglavje 4.4 raje vključil opozorilo, ki navaja, da ni dovolj podatkov o varnosti za bolnike s hudo okvaro organov.
The CHMP noted that while elimination of metabolites is expected to be slower in patients with renal impairment, the available data show that this did not affect the safety profile and did not alter pharmacokinetics in patients with severe renal impairment.
CHMP je ugotovil, da je sicer izločanje presnovkov po pričakovanjih počasnejše pri bolnikih z ledvično okvaro, vendar razpoložljivi podatki kažejo, da to ni vplivalo na varnostni profil zdravila in ni spremenilo farmakokinetike pri bolnikih s hudo okvaro ledvic.
As a result, efficacy was suboptimal and high rates of menopausal symptoms such as hot flushes occurred, as their perimenopausal status was insufficient to suppress the feedback loop of oestrogen synthesis.
Zaradi tega je bila učinkovitost suboptimalna in so se pojavili številni simptomi menopavze, kot so vročinski oblivi, saj njihov perimenopavzni status ni zadoščal za zaviranje encimov, ki sodelujejo pri sintezi estrogenov.
Regarding bone effects, the CHMP reviewed data from studies showing that long-term use of Femara is associated with a significantly higher rate of osteoporosis and a significantly higher rate of bone fractures than tamoxifen (adjuvant setting) or placebo (extended adjuvant setting).
Glede učinkov na kosti je CHMP pregledal podatke iz študij, ki kažejo, da je dolgoročna uporaba zdravila Femara povezana z bistveno višjo stopnjo osteoporoze in bistveno višjo stopnjo zlomov kosti kot pri tamoksifenu (adjuvantnem zdravljenju) ali placebu (podaljšanem adjuvantnem zdravljenju).
The CHMP considered the term “hormone-dependent” to be justified, as letrozole has no efficacy in hormone receptor negative breast cancer.
CHMP je menil, da je izraz „hormonsko odvisen“ upravičen, saj letrozol ni učinkovit pri raku dojke z negativnimi hormonskimi receptorji.
Finally, the CHMP inserted a statement advising against the co-administration of Femara with tamoxifen, other anti-oestrogens or oestrogens.
Nazadnje je CHMP dodal izjavo, ki odsvetuje sočasno uporabo zdravila Femara z tamoksifenom, drugimi antiestrogeni ali estrogeni.
Regarding male breast cancer, the CHMP noted the absence of clinical trials or specific systematic investigation on the use of Femara in male breast cancer.
Glede raka dojke pri moških je CHMP ugotovil, da ni kliničnih preskušanj ali posebne sistematične preiskave o uporabi zdravila Femara za raka dojke pri moških.
For Section 5.1Pharmacodynamic Properties, the wording was substantially shortened to focus on information relevant to the prescriber for the approved indications.
Za poglavje 5.1 - Farmakodinamične lastnosti je bilo besedilo močno skrajšano, da so poudarjene informacije za odobrene indikacije, ki so pomembne za zdravnika, ki to zdravilo predpisuje.
The CHMP also clarified the contraindications for pregnancy and breast-feeding, making the information more visible and included a contraindication for known hypersensitivity to letrozole or to any of the excipients.
CHMP je pojasnil tudi kontraindikacije med nosečnostjo in dojenjem, tako da so podatki bolj vidni, in vključil kontraindikacije za znano preobčutljivost na letrozol ali katero koli pomožno snov.
The CHMP also considered information on the treatment duration with tamoxifen to be justified, based on studies in which letrozole was administered after 5 years of adjuvant tamoxifen.
CHMP je prav tako menil, da je upravičen tudi podatek o trajanju zdravljenja s tamoksifenom, ki temelji na študijah, v katerih so letrozol dajali po 5 letih adjuvantnega zdravljenja s tamoksifenom.
Regarding renal impairment, the CHMP noted that there is very limited information about patients whose creatinine clearance is below 10 ml/min and therefore agreed on a precaution for these patients.
Glede ledvične okvare je CHMP ugotovil, da obstaja zelo malo podatkov za bolnike z očistkom kreatinina pod 10 ml/min, zato je soglašal, da je pri teh bolnikih potrebna previdnost.
Femara contains letrozole, an aromatase inhibitor which inhibits the conversion of androgens to oestrogens.
Zdravilo Femara vsebuje letrozol, zaviralec aromataze, ki zavira pretvorbo androgenov v estrogene.
The CHMP considered the indication to be well-established and that confirmation of postmenopausal endocrine status of women before initiation of treatment is justified for both efficacy and safety reasons, as studies have shown that women with induced menopausal status may not be of postmenopausal endocrine status.
CHMP je menil, da je indikacija dobro utemeljena in da je potrditev pomenopavznega endokrinega statusa žensk pred začetkom zdravljenja upravičena tako zaradi učinkovitosti kot tudi varnosti, saj so študije pokazale, da ženske z induciranim menopavznim statusom morda nimajo pomenopavznega endokrinega statusa.
Regarding neoadjuvant treatment, recent studies investigating duration of therapy show higher response rates and more patients becoming suitable for BCS at 4-8 months, with very little incremental benefit beyond that and that the minimum duration is 4-6 months.
Glede neoadjuvantnega zdravljenja so najnovejše študije, ki so raziskovale trajanje zdravljenja, pokazale večjo stopnjo odzivnosti in več bolnic, ki so po 4-8 mesecih postale primerne za ohranitveno operacijo dojke, po tem obdobju pa je bila korist le malo večja, in da traja zdravljenje vsaj 4-6 mesecev.
The CHMP was also of the opinion that there is a concern of reduced efficacy of letrozole in premenopausal or perimenopausal women.
CHMP je menil tudi, da obstaja pomislek glede zmanjšane učinkovitosti letrozola pri ženskah pred menopavzo ali v perimenopavzi.
Letrozole is thus predicted to have a potential for adverse effects on the embryo-foetus, as confirmed by studies in pregnant rats and rabbits.
Zato se predvideva, da ima lahko Letrozol neželene učinke za zarodek ali plod, kar je bilo potrjeno v študijah na brejih podganah in kunkah.
Regarding hepatic impairment, the CHMP considered that a strict contraindication is not appropriate for letrozole, which is a potentially life-saving treatment with a relatively benign safety profile.
Glede okvare jeter je CHMP menil, da stroga kontraindikacija ni primerna za zdravljenje z letrozolom, ki lahko rešuje življenja in ima relativno benigen varnostni profil.
The CHMP concluded that no specific warnings or dose adjustments recommendations are needed for patients with CrCl  10 ml/min.
CHMP je zaključil, da pri bolnicah z očistkom kreatinina  10 ml/min niso potrebna posebna opozorila ali priporočila glede prilagoditve odmerkov.
The CHMP noted the absence of adequate clinical trials in pregnant women and that isolated cases of birth defects have been reported in pregnant women exposed to Femara, while nonclinical studies have shown that letrozole is embryotoxic and foetotoxic.
CHMP je ugotovil, da ni ustreznih kliničnih preskušanj pri nosečnicah in da so poročali o posameznih primerih prirojenih napak pri nosečnicah, ki so bile izpostavljene zdravilu Femara, medtem ko so predklinične študije pokazale, da je letrozol embriotoksičen in fetotoksičen.
Femara is approved for a number of indications related to the treatment of breast cancer in postmenopausal women with disease progression.
Zdravilo Femara je odobreno za številne indikacije, ki so povezane z zdravljenjem napredovalega raka dojke pri ženskah po menopavzi.
Regarding renal impairment, the CHMP noted the available pharmacokinetics report and observed that letrozole is mainly cleared by the hepatic metabolism, with renal clearance reported to be less than 5%.
Glede ledvične okvare je CHMP preučil razpoložljivo farmakokinetično poročilo in ugotovil, da se letrozol v glavnem izloča z jetrno presnovo, poročani ledvični očistek pa je manj kot 5 %.
The CHMP reviewed the potential for interaction of a number of substances, including cimetidine and anti-cancer agents, as well as the role played by CYP2A6 and CYP3A4 in the metabolism of letrozole.
Poglavje 4.5 - Medsebojno delovanje z drugimi zdravili in druge oblike interakcij CHMP je pregledal možnosti za medsebojno delovanje številnih snovi, vključno s cimetidinom in zdravili proti raku, pa tudi vlogo, ki jo imata CYP2A6 in CYP3A4 v presnovi letrozola.
Regarding hepatic impairment, the CHMP noted that studies have shown that Femara is safe in mild to moderate hepatic insufficiency but that there is limited experience of use in patients with severely impaired hepatic function, non-cancer patients with liver cirrhosis and/or Child-Pugh stage C liver insufficiency.
Glede okvare jeter je CHMP ugotovil, da so študije pokazale, da je zdravilo Femara varno pri blagi do zmerni jetrni insuficienci, da pa je malo izkušenj z uporabo pri bolnikih s hudo okvaro delovanja jeter, nerakavih bolnikih s cirozo jeter in/ali jetrno insuficienco razreda C po razvrstitvi Child-Pugh.
The CHMP also noted the limitations of the pregnancy prevention tools and therefore considered that postmenopausal status must be fully established before initiation of and during treatment of Femara and that Femara should not be used in women when postmenopausal status is not fully established.
CHMP je opozoril tudi na omejitev sredstev za preprečevanje nosečnosti, zato je menil, da je treba pred začetkom in med zdravljenjem z zdravilom Femara dokončno ugotoviti pomenopavzni status in da ženske, ki nimajo dokončno ugotovljenega pomenopavznega statusa, ne smejo uporabljati zdravila Femara.
Regarding premenopausal endocrine status, the CHMP noted that although no clinical trials testing the safety or efficacy of Femara in premenopausal women have been conducted, there are safety reasons for not treating premenopausal or even perimenopausal women with letrozole.
Glede predmenopavznega endokrinega statusa je CHMP ugotovil, da čeprav niso bila izvedena klinična preskušanja za varnost ali učinkovitost zdravila Femara pri ženskah pred menopavzo, obstajajo varnostni razlogi proti zdravljenju žensk pred menopavzo ali celo v perimenopavzi z letrozolom.
“Section 4.1 - Therapeutic indications
„Poglavje 4.1 - Terapevtske indikacije
Regarding hepatic impairment, the CHMP noted that no signal was raised regarding the safety of Femara in patients with severe impairment of hepatic function.
Glede okvare jeter je CHMP ugotovil, da ni bilo opozorilnega znaka v zvezi z varnostjo zdravila Femara pri bolnikih s hudo okvaro delovanja jeter.
The CHMP concluded that there are significant safety concerns warranting a contraindication in premenopausal women, specifically in women of premenopausal endocrine status.
CHMP je zaključil, da obstajajo resna tveganja glede varnosti, ki utemeljujejo kontraindikacijo pri ženskah pred menopavzo, zlasti pri ženskah s predmenopavznim endokrinim statusom.
The adverse drug reactions table was structured according to the SmPC guideline and several ADRs were relocated under more appropriate system organ class.
Razpredelnica neželenih učinkov zdravila je bila oblikovana v skladu s smernicami za povzetek glavnih značilnosti zdravila, poleg tega pa je bilo več neželenih učinkov prestavljenih v ustreznejši razred organskega sistema.
The CHMP considered this indication to be well-established and noted that the wording was consistent with the wording in the nationally approved SmPCs.
CHMP je menil, da je ta indikacija dobro utemeljena, in opazil, da je besedilo skladno z besedilom povzetkov glavnih značilnosti zdravila, odobrenih na nacionalni ravni.
The CHMP introduced a warning regarding postmenopausal endocrine status, as studies have shown sub-optimal efficacy and increased frequency and severity of adverse events in women with perimenopausal status.
Poglavje 4.4 - Posebna opozorila in previdnostni ukrepi CHMP je predstavil opozorilo o pomenopavznem endokrinem statusu, saj so študije pokazale suboptimalno učinkovitost in večjo pogostnost in resnost neželenih dogodkov pri ženskah s perimenopavznim statusom.
The CHMP defined the target patient population as women of established postmenopausal status and patients with ER-positive tumours, patients whose tumours are HER-2 (Human Epidermal Growth Factor Receptor 2) negative and patients who are unable to tolerate or who refuse to take neoadjuvant chemotherapy as well as patient for whom immediate surgery is not an option.
CHMP je za ciljno populacijo bolnikov opredelil ženske z določenim pomenopavznim statusom in bolnice s ER-pozitivnimi tumorji, bolnice s HER-2 (Human Epidermal Growth Factor Receptor 2) negativnimi tumorji, bolnice, ki neoadjuvantne kemoterapije ne prenašajo ali jo zavračajo, ter bolnice, za katere takojšnja operacija ne pride v poštev.
4) Advanced breast cancer after relapse or disease progression, in women with natural or artificially induced postmenopausal endocrine status, who have previously been treated with anti-oestrogens.
4) Napredovali rak dojke po ponovitvi ali napredovanju bolezni pri ženskah z naravno ali umetno sproženim pomenopavznim endokrinim statusom, ki so se že zdravile z antiestrogeni.
Advanced breast cancer after relapse or disease progression, in women with natural or artificially induced postmenopausal endocrine status, who have previously been treated with antioestrogens.
• Napredovali rak dojke po ponovitvi ali napredovanju bolezni pri ženskah z naravno ali umetno sproženim pomenopavznim endokrinim statusom, ki so se že zdravile z antiestrogeni.
2) Extended adjuvant treatment of hormone-dependent invasive breast cancer in postmenopausal women who have received prior standard adjuvant tamoxifen therapy for 5 years.
2) Podaljšano adjuvantno zdravljenje hormonsko odvisnega invazivnega raka dojke pri ženskah po menopavzi, ki so predhodno 5 let prejemale standardno adjuvantno obliko zdravljenja s tamoksifenom.
3) First-line treatment in postmenopausal women with hormone-dependent advanced breast cancer.
3) Prva linija zdravljenja pri pomenopavznih ženskah s hormonsko odvisnim napredovalim rakom dojke.
In addition, it is essential to avoid pregnancy during letrozole therapy because of the risk of embryotoxicity and foetotoxicity.
Poleg tega je zaradi nevarnosti embriotoksičnosti in fetotoksičnosti pomembno, da ženska med terapijo letrozola ne zanosi.
5) Neo-adjuvant treatment of postmenopausal women with hormone receptor positive, HER-2 negative breast cancer where chemotherapy is not suitable and immediate surgery not indicated.
5) Neoadjuvantno zdravljenje HER-2 negativnega raka dojke s pozitivnimi hormonskimi receptorji pri pomenopavznih ženskah, pri katerih kemoterapija ni primerna in takojšnja operacija ni indicirana.
Extended adjuvant treatment of hormone-dependent invasive breast cancer in postmenopausal women who have received prior standard adjuvant tamoxifen therapy for 5 years.
• Podaljšano adjuvantno zdravljenje hormonsko odvisnega invazivnega raka dojke pri ženskah po menopavzi, ki so predhodno 5 let prejemale standardno adjuvantno obliko zdravljenja s tamoksifenom.
• the scope of the referral was the harmonisation of the summary of products characteristics, labelling and package leaflet
• je bil namen napotitve uskladitev povzetka glavnih značilnosti zdravila, označevanja in navodila za uporabo,
The CHMP therefore concluded that the current data, including long-term follow-up information, is sufficient to support the neoadjuvant (pre-operative) treatment indication for Femara, in particular with the aim to down-size hormone receptor-positive tumours to allow BCS or to allow inoperable tumours to become operable.
CHMP je pregledal vse razpoložljive podatke in menil, da je letrozol glede na tamoksifen pokazal značilno boljšo stopnjo kliničnega odziva, mamografskega odziva, odziva z ultrazvokom dojk in stopnjo ohranitvene operacije dojke CHMP je zato sklenil, da trenutni podatki za zdravilo Femara, vključno z dolgoročnimi informacijami o spremljanju, zadoščajo za podporo indikacije neoadjuvantnega (predoperativnega) zdravljenja, zlasti z namenom zmanjšanja tumorjev s pozitivnimi hormonskimi receptorji, da se omogoči ohranitvena operacija dojke ali operacijo tumorjev, ki jih prej ni bilo mogoče operirati.
Neo-adjuvant treatment of postmenopausal women with hormone receptor positive, HER-2 negative breast cancer where chemotherapy is not suitable and immediate surgery not indicated.
• Neoadjuvantno zdravljenje HER-2 negativnega raka dojke s pozitivnimi hormonskimi receptorji, pri pomenopavznih ženskah, pri katerih kemoterapija ni primerna in takojšnja operacija ni indicirana.
First-line treatment in postmenopausal women with hormone-dependent advanced breast cancer.
• Prva linija zdravljenja pri pomenopavznih ženskah s hormonsko odvisnim napredovalim rakom dojke.
Grounds for amendment of the summary of product characteristics, labelling and package leaflet
Razlogi za dopolnilo povzetka glavnih značilnosti zdravila, označevanje in navodila za uporabo
1) Adjuvant treatment of postmenopausal women with hormone receptor positive invasive early breast cancer.
1) Adjuvantno zdravljenje zgodnjega invazivnega raka dojke s pozitivnimi hormonskimi receptorji pri ženskah po menopavzi.
The CHMP also noted that the wording was consistent with the wording in most nationally approved SmPCs.
CHMP je opazil tudi, da je bilo besedilo skladno z besedilom v večini povzetkov glavnih značilnosti zdravila, odobrenih na nacionalni ravni.
The CHMP also noted that the wording was largely consistent with the nationally approved SmPCs.
CHMP je opazil tudi, da je besedilo večinoma skladno z besedilom v povzetkih glavnih značilnosti zdravila, odobrenih na nacionalni ravni.
• the summary of products characteristic, labelling and package leaflet proposed by the marketing authorisation holders have been assessed based on the documentation submitted and the scientific discussion within the Committee the CHMP has recommended the amendment of the marketing authorisations for which the summary of product characteristics, labelling and package leaflet are set out in Annex III for Femara and associated names (see Annex I).
je CHMP priporočil dopolnitev dovoljenj za promet z zdravilom, katerih povzetek glavnih značilnosti zdravila, označevanje in navodilo za uporabo (glejte Prilogo I) so navedeni v Prilogi III za zdravilo Femara in z njim povezana imena.
Efficacy has not been demonstrated in patients with hormone receptor negative breast cancer.”
Učinkovitost ni bila dokazana pri bolnicah z rakom dojke z negativnimi hormonskimi receptorji.“ Poglavje 4.2 - Odmerjanje in način uporabe
Adjuvant treatment of postmenopausal women with hormone receptor positive invasive early breast cancer.
• Adjuvantno zdravljenje zgodnjega invazivnega raka dojke s pozitivnimi hormonskimi receptorji pri ženskah po menopavzi.
28 June 2013
28. junij 2013
The company that applied for authorisation is Laboratoires SMB s.a.
Vlogo za pridobitev dovoljenja je predložila družba Laboratoires SMB s.a.
The effects of Labazenit were first tested in experimental models before being studied in humans.
Učinki zdravila Labazenit so bili najprej preskušeni na poskusnih modelih, nato pa so jih raziskali pri ljudeh.