FrancophonIA/ELRC3.0 huggingface dataset:
English: The CHMP thoroughly assessed the detailed grounds for re-examination submitted by the applicant for the use of Alcover granules in the long-term maintenance of alcohol abstinence in AD patients with a very high Drinking Risk Level (VH-DRL) and the treatment of acute alcohol withdrawal syndrome (AWS) and took into consideration the outcome of the consultation of an ad-hoc expert group on 4 October 2017.
Slovenian: Odbor CHMP je temeljito ovrednotil podrobno opisane razloge za ponovno preučitev, ki jih je predložil predlagatelj, pri uporabi zdravila Alcover v obliki zrnc pri dolgoročnem vzdrževanju abstinence od alkohola pri bolnikih, odvisnih od alkohola, z zelo visoko stopnjo tveganja za zlorabo alkohola in pri zdravljenju akutnega alkoholnega odtegnitvenega sindroma ter je pri tem upošteval izid posvetovanja ad hoc strokovne skupine, ki je potekalo 4. oktobra 2017.
English: The trials submitted with active arm comparators (Gate 1, Nava 2007, Addolorato 1999 and Nimmerrichter 2002) had several methodological flaws such as open label, small sample size, heterogeneity in the studies' population, lack of protocol or defined primary endpoints, assessment of large number of outcomes, and long enrolment period, which lead to conclusions based on post-hoc analysis that do not provide sufficient evidence to establish the efficacy for the use of sodium oxybate granules in the treatment of AWS.
Slovenian: Predložena preskušanja z aktivnimi primerjalnimi skupinami (Gate 1, Nava 2007, Addolorato 1999 in Nimmerrichter 2002) so imela več metodoloških pomanjkljivosti, kot so odprta zasnova, majhna velikost vzorca, heterogenost študijskih populacij, odsotnost protokola ali opredeljenih primarnih opazovanih dogodkov, ocenjevanje velikega števila izidov in dolgo obdobje vključevanja, kar je privedlo do zaključkov na podlagi post-hoc analize, ki ne zagotavljajo zadostnih dokazov za potrditev učinkovitosti uporabe natrijevega oksibata v obliki zrnc pri zdravljenju alkoholnega odtegnitvenega sindroma.
English: In order to further mitigate these risks in the clinical practice, the applicant has proposed additional risk minimization measures in addition to the warnings/guidance in the product information; dose reduction at the end of treatment to prevent risk of withdrawal; inpatient setting in the treatment of AWS; warnings and guidance in case of concomitant alcohol consumption, and implementation of a restricted prescribing, controlled distribution system and a packaging containing only 4 days treatment.
Slovenian: Za nadaljnje obvladovanje teh tveganj v klinični praksi je predlagal dodatne ukrepe za zmanjševanje tveganj poleg opozoril/navodil v informacijah v zdravilu, in sicer zmanjšanje odmerka na koncu zdravljenja za preprečitev tveganja za odtegnitvene težave, hospitalizacijo pri zdravljenju alkoholnega odtegnitvenega sindroma, opozorila in navodila v primeru sočasnega uživanja alkohola ter uvedbo omejenega predpisovanja, nadzorovanega sistema distribucije in pakiranja, ki vsebuje količino zdravila za štiridnevno zdravljenje.
English: Evaluation of patients' compliance was regarded as important.
Slovenian: Kot pomembno so ocenili ovrednotenje bolnikovega upoštevanja navodil pri jemanju zdravila.
English: While the methodological challenges to run a randomised clinical trial in this field were acknowledged by the experts, they recommended the conduction of a prospective, multicentre placebo-controlled, feasible study in order to confirm the results in the subpopulation of interest.
Slovenian: Strokovnjaki so sicer priznali metodološke izzive pri izvedbi randomiziranega kliničnega preskušanja na tem področju, vendar so za potrditev rezultatov v želeni podpopulaciji priporočili izvedbo prospektivne, multicentrične, s placebom nadzorovane študije.
English: The Committee concluded that in the absence of demonstration of efficacy for Alcover granules in sachets, the benefit-risk balance of this medicinal product is not favourable in the proposed indications.
Slovenian: je odbor zaključil, da zaradi pomanjkanja dokazov o učinkovitosti zdravila Alcover zrnca v vrečkah razmerje med tveganji in koristmi za to zdravilo pri predlaganih indikacijah ni ugodno.
English: There was a consensus among the experts on the clinical unmet need in the management of maintenance of abstinence from alcohol, and the need for more pharmacological treatment alternatives in this setting.
Slovenian: Strokovnjaki so se strinjali, da pri vzdrževanju abstinence od alkohola obstaja neizpolnjena klinična potreba in da je pri tej indikaciji potrebnih več možnosti farmakološkega zdravljenja.
English: Overall, the CHMP maintains its initial opinion that the results of the submitted clinical studies are not sufficient to establish the efficacy of Alcover (sodium oxybate) granules in the maintenance of alcohol abstinence and treatment of alcohol withdrawal syndrome (AWS) as there are several drawbacks in the design of these clinical studies, including open-label designs, small sample size, choice of patient population and absence of clearly defined, statistically significant outcomes, DRL not being recorded at baseline, low dose of comparator, and lack of assessment of effects on seizures or delirium as the most concerning events in alcohol withdrawal.
Slovenian: Odbor CHMP ohranja svoje prvotno mnenje, da rezultati predloženih kliničnih študij ne zadoščajo za potrditev učinkovitosti zdravila Alcover (natrijev oksibat) v obliki zrnc pri vzdrževanju abstinence od alkohola in zdravljenju alkoholnega odtegnitvenega sindroma, saj ima zasnova teh študij več pomanjkljivosti, kot so odprta zasnova, majhna velikost vzorca, izbira populacije bolnikov in odsotnost jasno opredeljenih, statistično značilnih izidov, nebeleženje izhodiščne stopnje tveganja za zlorabo alkohola, majhen odmerek primerjalnega zdravila ter odsotnost ocenjevanja učinkov na epileptične napade ali delirij, kar sta najbolj zaskrbljujoča dogodka pri odtegnitvi od alkohola.
English: With regards to the indication alcohol withdrawal syndrome (AWS), the efficacy of sodium oxybate granules in Very High DRL patients has also not been established.
Slovenian: V zvezi z indikacijo za alkoholni odtegnitveni sindrom učinkovitost natrijevega oksibata v obliki zrnc pri bolnikih z zelo visoko stopnjo tveganja za zlorabo alkohola prav tako ni bila ugotovljena.
English: The applicant Debrégeas & Associés (D&A) submitted an application for marketing authorisation (MAA) for Alcover 750 mg, 1250 mg and 1750 mg through the Decentralised Procedure (DCP) under the legal basis of Article 8(3) of Directive 2001/83/EC, as a full-mixed application for the treatment of long-term maintenance of alcohol abstinence and alcohol withdrawal syndrome in alcohol-dependent adult patients.
Slovenian: Predlagatelj, družba Debrégeas & Associés (D&A), je predložil vlogo za pridobitev dovoljenja za promet z zdravilom za zdravilo Alcover 750 mg, 1250 mg in 1750 mg po decentraliziranem postopku na pravni podlagi člena 8(3) Direktive 2001/83/ES.
English: In light of the above and the identified risks related to the product, the CHMP was of the opinion that the benefit-risk balance for Alcover granules in sachets, and associated names is not favourable.
Slovenian: Glede na zgoraj navedeno in glede na ugotovljena tveganja, povezana z zdravilom, je odbor CHMP presodil, da razmerje med tveganji in koristmi zdravila Alcover zrnca v vrečkah in povezanih imen ni ugodno.
English: A design focusing on either of these endpoints with only supplementary data on the other might be acceptable.
Slovenian: podatki o drugem pa bi bili le dopolnilni.
English: • The Committee reviewed the totality of the data provided by the applicant in writing and in the oral explanations and related to the efficacy and safety of Alcover and associated names, 750 mg, 1250 mg, 1750 mg granules in sachets in the proposed indications for the maintenance of alcohol abstinence and the treatment of alcohol withdrawal syndrome; The Committee also considered the grounds submitted by the applicant within the re-examination procedure, and the views from an ad-hoc expert group.
Slovenian: • odbor je pregledal vse podatke, ki jih je predložil predlagatelj v pisni in ustni obrazložitvi, povezane z učinkovitostjo in varnostjo zdravila Alcover in povezanih imen, 750 mg, 1 250 mg, 1 750 mg zrnca v vrečkah, pri predlaganih indikacijah za vzdrževanje abstinence od alkohola in zdravljenje alkoholnega odtegnitvenega sindroma.
English: The applicant has proposed two prospective Post-Authorisation Efficacy Studies (PAES) to confirm the efficacy of sodium oxybate in the treatment of AWS in alcohol dependent patients and its longterm benefits in the maintenance of alcohol abstinence.
Slovenian: Predlagatelj je za potrditev učinkovitosti natrijevega oksibata pri zdravljenju alkoholnega odtegnitvenega sindroma pri bolnikih, odvisnih od alkohola, in njegovih dolgoročnih koristih pri vzdrževanju abstinence od alkohola predlagal dve prospektivni študiji učinkovitosti po odobritvi.
English: In conclusion, further to the initial assessment and the re-examination procedure, the CHMP maintains its initial opinion that the benefit-risk balance of this medicinal product is not favourable in both of the proposed indications.
Slovenian: Zaključki odbora CHMP Po začetnem ocenjevanju in postopku ponovnega pregleda odbor CHMP ohranja svoje prvotno mnenje, da razmerje med koristmi in tveganjem za to zdravilo pri nobeni od predlaganih indikacij ni ugodno.
English: There were several drawbacks in the design of these studies, including small sample size, choice of patient population and absence of clearly defined, statistically significant outcomes, and although some of the studies showed trends to positive results, there were also some that were clearly failed studies.
Slovenian: Pri zasnovi teh študij je bilo več pomanjkljivosti, vključno z majhno velikostjo vzorca, izbiro populacije bolnikov in odsotnostjo jasno opredeljenih, statistično značilnih izidov.
English: The meta-analysis that included GATE 2, SMO032/10/03, Gallimberti 1992 and Di Bello 1995 have several methodological flaws and quality concerns such as GATE 2 did not evaluate the population of interest; SMO032/10/03 trial included only a subset of High/Very High DRL patients and failed to meet its primary endpoint; Gallimberti trial did not report primary endpoint or follow-up time; Di Bello had a very small sample size (total n=17) and failed to specify the primary endpoint.
Slovenian: V študiji GATE 2 na primer niso ovrednotili želene populacije, preskušanje SMO032/10/03 je vključevalo le podskupino bolnikov z visoko/zelo visoko stopnjo tveganja za zlorabo alkohola in ni doseglo primarnega opazovanega dogodka, v Gallimbertijevem preskušanju niso poročali o primarnem opazovanem dogodku in času spremljanja, v Di Bellovi študiji pa je bila velikost vzorca zelo majhna (skupni n = 17) in primarni opazovani dogodek ni bil opredeljen.
English: The Gallimberti 1989 trial was the only placebo-controlled RCT to evaluate sodium oxybate in the treatment of AWS, which had a small sample (n=11 oxybate vs n= 12 placebo), that evaluated the first 7 hours of treatment, showing favourable results for the active arm.
Slovenian: Vzorec je bil majhen (n = 11 za oksibat v primerjavi z n = 12 za placebo), vrednotili so prvih sedem ur zdravljenja, rezultati v aktivno zdravljeni skupini pa so bili ugodni.
English: Referring to the results in abstinence rate from study SMO032/10/03, Gallimberti 1992, GATE 2 and Di Bello 1995, apart from different study designs, post-hoc chosen patient groups, different study duration, it cannot be concluded whether continuous abstinence was measured, and whether responders (a posteriori defined as completers with a DRL<high or who did not relapse to heavy drinking) are actually the group of people aimed at with full abstinence in mind.
Slovenian: razen različnih zasnov študij, naknadno izbranih skupin bolnikov in različnega trajanja študij, ni mogoče zaključiti, ali so izmerili neprekinjeno abstinenco in ali so odzivni bolniki (naknadno opredeljeni kot bolniki z manj kot visoko stopnjo tveganja za zlorabo alkohola ali tisti, ki se niso vrnili k hudi zlorabi alkohola) dejansko tista skupina ljudi, ki naj bi bila ciljna skupina za popolno abstinenco.
English: Talk to your doctor.
Slovenian: Posvetujte se z zdravnikom.
English: • Postpone start of consolidation course.
Slovenian: • Odložite začetek konsolidacijskega cikla.
English: • Infections (including serious infections)
Slovenian: • okužbe (vključno z resnimi okužbami)
English: Frequency unknown (frequency cannot be estimated from the available data):
Slovenian: Neznana pogostnost (pogostnosti iz razpoložljivih podatkov ni mogoče oceniti):
English: Second induction (if required)
Slovenian: Druga indukcija (če je potrebna)
English: g. Based on Fisher's exact test.
Slovenian: Na podlagi Fisherjevega natančnega testa.
English: As with all therapeutic proteins, there is potential for immunogenicity.
Slovenian: Kot pri vseh terapevtskih beljakovinah obstaja možnost imunogenosti.
English: Grade 3/4
Slovenian: Stopnja 3/4
English: Patients should be monitored for hepatotoxicity as recommended in section 4.4.
Slovenian: Bolnike je treba spremljati glede hepatotoksičnosti, kot je priporočeno v poglavju 4.4.
English: The median study size was 15 patients, with a range of 5-105 patients.
Slovenian: Mediana velikost študije je bila 15 bolnikov z razponom 5-105 bolnikov.
English: Age, race, and gender
Slovenian: Starost, rasa in spol
English: Some infections may be serious and may be life-threatening.
Slovenian: Nekatere okužbe so lahko resne in življenjsko ogrožajoče.
English: DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION Date of first authorisation: 19 April 2018
Slovenian: Datum prve odobritve: 19. april 2018
English: Not reported
Slovenian: niso poročali
English: The detection of ADAs is highly dependent on the sensitivity and specificity of the assay.
Slovenian: Zaznavanje ADA je zelo odvisno od občutljivosti in specifičnosti preskusa.
English: Day 1 (as per standard medical practice)
Slovenian: do 7. dne na 1. dan (v skladu z običajno medicinsko prakso)
English: d: Within 30 days from the last dose of MYLOTARG.
Slovenian: d: V 30 dneh po zadnjem odmerku zdravila MYLOTARG.
English: MYLOTARG will be stored by the health professionals at the hospital or clinic.
Slovenian: Zdravilo MYLOTARG bodo shranili zdravstveni delavci v bolnišnici ali kliniki.
English: Therefore, caution should be exercised when driving or operating machines.
Slovenian: Zato je med vožnjo ali upravljanjem strojev potrebna previdnost.
English: Other side effects may include:
Slovenian: Drugi neželeni učinki so lahko:
English: Pharmacokinetics in specific groups of subjects or patients
Slovenian: Farmakokinetika pri posebnih skupinah preskušancev ali bolnikov
English: Tell your doctor or nurse if you are taking, have recently taken, or might take any other medicines.
Slovenian: Obvestite zdravnika ali medicinsko sestro, če jemljete, ste pred kratkim jemali ali pa boste morda začeli jemati katerokoli drugo zdravilo.
English: Monitoring only total bilirubin may not identify all patients at risk of VOD/SOS.
Slovenian: Če spremljate samo celokupni bilirubin, morda ne boste odkrili vseh bolnikov, pri katerih obstaja tveganje za VOD/SOS.
English: • Calculate the required volume of the reconstituted solution needed to obtain the appropriate dose according to patient body surface area.
Slovenian: • Izračunajte potreben volumen rekonstituirane raztopine, da dobite ustrezen odmerek glede na bolnikovo telesno površino.
English: Warnings and precautions When you first receive this medicine and during the course of treatment, tell your doctor or nurse if you:
Slovenian: Opozorila in previdnostni ukrepi Ko zdravilo prejmete prvič in med zdravljenjem, obvestite zdravnika ali medicinsko sestro, če:
English: • Your doctor may lower your dose based on your response to treatment.
Slovenian: • Zdravnik lahko zmanjša odmerek glede na vaš odziv na zdravljenje.
English: MYLOTARG must not to be used in children and adolescents under 15 years of age because limited data are available in this population.
Slovenian: Zdravila MYLOTARG ne smemo uporabljati pri otrocih in mladostnikih, mlajših od 15 let, saj so podatki za to populacijo omejeni.
English: Immediately contact your doctor if you experience any of the following serious side effects (see also section 2 “What you need to know before you are given MYLOTARG”):
Slovenian: Nemudoma obvestite zdravnika, če se vam pojavi kateri od naslednjih resnih neželenih učinkov (glejte tudi poglavje 2 "Kaj morate vedeti, preden boste prejeli zdravilo MYLOTARG"):
English: • are allergic to gemtuzumab ozogamicin or any of the other ingredients of this medicine (listed in section 6).
Slovenian: • ste alergični na gemtuzumab ozogamicin ali katerokoli sestavino tega zdravila (navedeno v poglavju 6).
English: The relevance of these animal findings to humans is uncertain.
Slovenian: Pomen teh ugotovitev pri živalih za ljudi je negotov.
English: Increased embryolethality was also observed in the presence of maternal toxicity.
Slovenian: Zvečano smrtnost zarodkov so opazili tudi ob prisotnosti toksičnosti za mater.
English: Limitations of this analysis include the small sample size of some studies, heterogeneity of the studies, and the lack of control data in this setting.
Slovenian: Omejitve te analize vključujejo majhno velikost vzorca v nekaterih študijah, raznolikost študij in pomanjkanje kontrolnih podatkov v zadevnih okoliščinah.
English: *Including fatal outcome.
Slovenian: Vključno s primeri s smrtnim izidom.
English: The primary endpoint was event-free survival (EFS).
Slovenian: Primarni opazovani dogodek je bilo preživetje brez dogodkov (EFS - Event-Free Survival).
English: Five (3.8%) of these VOD reactions occurred within 28 days of any dose of gemtuzumab ozogamicin.
Slovenian: Pet (3,8 %) od teh reakcij VOD se je pojavilo v 28 dneh po kateremkoli odmerku gemtuzumab ozogamicina.
English: Treatment of MYLOTARG overdose should consist of general supportive measures.
Slovenian: Zdravljenje prevelikega odmerjanja zdravila MYLOTARG mora obsegati splošne podporne ukrepe.
English: Do not use this medicine after the expiry date which is stated on the vial label and carton after EXP.
Slovenian: Tega zdravila ne smete uporabljati po datumu izteka roka uporabnosti, ki je naveden na nalepki viale in škatli poleg oznake ''EXP''.
English: Definitive conclusions cannot be drawn between the presence of antibodies and potential impact on efficacy and safety due to the limited number of patients with positive ADAs.
Slovenian: Dokončni zaključki glede prisotnosti protiteles in možnem vplivu na učinkovitost in varnost zaradi omejenega števila bolnikov s pozitivnim izvidom na ADA niso mogoči.
English: For these reasons, comparison of incidence of antibodies to gemtuzumab ozogamicin with the incidence of antibodies to other products may be misleading.
Slovenian: Zato je primerjava pojavnosti protiteles proti gemtuzumab ozogamicinu s pojavnostjo protiteles proti drugim zdravilom lahko zavajajoča.
English: Determination of PK parameters for unconjugated calicheamicin was limited due to the low systemic concentration levels.
Slovenian: Določanje farmakokinetičnih parametrov za nekonjugirani kaliheamicin je bilo zaradi nizkih sistemskih koncentracij omejeno.
English: This includes the time required for reconstitution, dilution, and administration.
Slovenian: To vključuje čas, potreben za rekonstitucijo, redčenje in uporabo.
English: The overall minimum and maximum ages range from 0 years to 22.3 years, with an overall median age of 8.7 years at the time of treatment.
Slovenian: Celokupni razpon najnižje in najvišje starosti je bil od 0 let do 22,3 leta, celokupna mediana starost v času zdravljenja pa je bila 8,7 leta.
English: The mITT population included all patients who were randomised, unless withdrawal of consent prior to start of treatment and were analysed according to initial randomisation arm.
Slovenian: V populacijo mITT so vključili vse randomizirane bolnike, razen če so bolniki pred začetkom zdravljenja preklicali privolitev, analizirali pa so jih v skladu z začetno randomizirano skupino.
English: ***Frequency is based on laboratory values (Grade per NCI CTCAE v4.03).
Slovenian: Pogostnost temelji na laboratorijskih vrednostih (stopnja po NCI CTCAE v4.03).
English: Few patients (13.7%) had low CD33 expression (less than 30% of blasts).
Slovenian: Pri nekaj bolnikih (13,7 %) je bilo izražanje CD33 nizko (manj kot 30 % blastov).
English: Most studies were in the compassionate use setting (70.6%).
Slovenian: Večino študij so izvajali v sklopu sočutne uporabe zdravila (70,6 %).
English: Use appropriate aseptic technique for the reconstitution and dilution procedures.
Slovenian: Za postopke rekonstitucije in redčenja uporabite ustrezno aseptično tehniko.
English: Patients who experienced remission were also eligible for allogeneic transplantation.
Slovenian: Bolniki, pri katerih je prišlo do remisije, so bili primerni tudi za alogensko presaditev.
English: Response rate (by Investigator)
Slovenian: Stopnja odziva (po oceni raziskovalca)
English: • Decreased appetite
Slovenian: • pomanjkanje apetita
English: Single doses higher than 9 mg/m2 in adults were not tested.
Slovenian: Enkratnih odmerkov, večjih od 9 mg/m2, pri odraslih niso preskušali.
English: Based on the primary definition of EFS: event dates (induction failure, relapse, or death) determined by investigator assessment.
Slovenian: Na podlagi primarne definicije EFS: datumi dogodkov (neuspešna indukcija, ponovitev bolezni ali smrt) po oceni raziskovalca.
English: MYLOTARG has moderate influence on the ability to drive and use machines.
Slovenian: Zdravilo MYLOTARG ima zmeren vpliv na sposobnost vožnje in upravljanja strojev.
English: Protect from light and do not freeze.
Slovenian: Zaščitite pred svetlobo in ne zamrzujte.
English: The infusion line does not need to be protected from light.
Slovenian: Infuzijske cevke ni treba zaščititi pred svetlobo.
English: If you are pregnant or breast-feeding, think you may be pregnant, or are planning to have a baby, ask your doctor or pharmacist for advice before you are given this medicine.
Slovenian: Če ste noseči ali dojite, menite, da bi lahko bili noseči ali načrtujete zanositev, se posvetujte z zdravnikom ali farmacevtom, preden prejmete to zdravilo.
English: The median time from the last gemtuzumab ozogamicin dose to onset of VOD was 9 days (range: 2-298 days).
Slovenian: Mediani čas od zadnjega odmerka gemtuzumab ozogamicina do pojava VOD je bil 9 dni (razpon: 2298 dni).
English: MYLOTARG must not be used during pregnancy unless the potential benefit to the mother outweighs the potential risks to the foetus.
Slovenian: Zdravila MYLOTARG se ne sme uporabljati med nosečnostjo, razen če morebitna korist za mater odtehta morebitna tveganja za plod.
English: Patients should be monitored for signs and symptoms of TLS and treated according to standard medical practice.
Slovenian: Bolnike je treba spremljati glede znakov in simptomov TLS in jih zdraviti v skladu z običajno medicinsko prakso.
English: • Infections (signs of a low number of white blood cells known as neutrophils) Some infections may be serious and can be due to viruses, bacteria, or other causes that may be life-threatening.
Slovenian: • Okužbe (znaki majhnega števila belih krvnih celic, imenovanih nevtrofilci) Nekatere okužbe so lahko resne in so lahko posledica virusov, bakterij ali drugih vzrokov, ki so lahko življenjsko ogrožajoči.
English: c: Rates across studies were estimated using inverse variance weighting with fixed effects.
Slovenian: c: Deleže v študijah so ocenjevali z obtežitvijo študij s fiksnimi učinki z inverzno varianco.
English: There is no information regarding the presence of gemtuzumab ozogamicin or its metabolites in human milk, the effects on the breast-fed child, or the effects on milk production.
Slovenian: Ni podatkov o prisotnosti gemtuzumab ozogamicina ali njegovih presnovkov v materinem mleku, učinkih na dojenega otroka ali učinkih na nastajanje mleka.