FrancophonIA/ELRC3.0 huggingface dataset:
English: In the setting of long term use of this product in a large population, the frequency of adverse psychiatric effects and their consequences, as well as the cognitive effects, are unknown.
Slovenian: V obdobju dolgotrajne uporabe tega zdravila v večji populaciji pogostost neželenih psihiatričnih učinkov in njihovih posledic ter kognitivnih učinkov ni znana.
English: With regard to the general safety profile, the applicant pointed out that Qsiva is a combination of two approved drugs with long histories of use at higher doses and well established safety profiles of both components.
Slovenian: V zvezi s splošnim varnostnim profilom je predlagatelj poudaril, da je zdravilo Qsiva kombinacija dveh odobrenih zdravilnih učinkovin z dolgo zgodovino uporabe večjih odmerkov in dobro dokazanima varnostnima profiloma za obe sestavini.
English: Teratogenic risk - Topiramate has been associated with an increased risk of teratogenesis; however, topiramate has been approved for 16 years and is currently in widespread use within the EU for migraine prophylaxis and epilepsy, which requires treatment at higher doses.
Slovenian: Teratogeno tveganje - topiramat se povezuje s povečanim tveganjem za teratogenezo, kljub temu pa je že 16 let odobreno zdravilo in je v EU široko uporabljan za preprečevanje migrene in epilepsije, ki zahtevata zdravljenje z večjimi odmerki.
English: The probability of off-label use of this product outside the population covered by the claimed indication is expected to be high.
Slovenian: 4. je pričakovana verjetnost za nenamensko uporabo tega zdravila zunaj populacije, zajete v predlagani indikaciji, velika.
English: Reported rates for most CNS-related side effects were similar between the mid-dose and placebo.
Slovenian: Poročila o stopnjah večine stranskih učinkov, povezanih z osrednjim živčevjem, so bila za srednji odmerek in placebo podobna.
English: The frequency of adverse psychiatric effects and their consequences, in particular resulting from the topiramate component, is unknown in the setting of long term use of this product in a large population.
Slovenian: 2. je pogostost neželenih psihiatričnih učinkov in njihovih posledic, še posebej tistih, ki so posledica topiramata, v obdobju dolgotrajne uporabe tega izdelka v veliki populaciji, neznana.
English: Teratogenic risk - CHMP agreed that the risk from the teratogenic potential of Qsiva might be mitigated through the implementation of appropriate risk minimisation measures, which include a Pregnancy Prevention Plan (PPP), the principles of which should be consistent with that agreed across the EU for isotretinoin in 2003.
Slovenian: Teratogeno tveganje - odbor CHMP je soglašal, da je tveganje za teratogeni potencial zdravila Qsiva mogoče omiliti z uvedbo ustreznih ukrepov za zmanjšanje tveganja, ki vključujejo načrt za preprečevanje nosečnosti, tj. načela, ki naj bi bila skladna s sprejetimi načeli v vsej EU za izotretinoin leta 2003.
English: Further stability studies on PHEN beads and TPM beads stored in bulk were necessary in order to support a start of the shelf-life at the time of capsule filling.
Slovenian: Potrebne so bile nadaljnje stabilnostne študije s kroglicami fentermina in topiramata, skladiščenimi v razsutem stanju, s katerimi bi podprli začetek roka uporabnosti ob polnjenju v kapsule.
English: The supportive information on safety of phentermine from the literature provided by the applicant was considered by CHMP to be very limited due to factors such as only retrospective, cohort studies submitted, absence of a reliable control group, etc..
Slovenian: Odbor CHMP je presodil, da so podporne informacije o varnosti fentermina iz literature, ki jo je predložil predlagatelj, zelo omejene, saj so bile predložene le retrospektivne, kohortne študije brez zanesljive kontrolne skupine itd.
English: However, weight reducing agents with a mechanism of action with a detrimental influence on heart rate, such as Qsiva, or on other cardiovascular parameters, may require further exclusion of a harmful CV effect.
Slovenian: Vendar je za sredstva za zmanjševanje telesne mase, katerih mehanizem delovanja ima škodljiv učinek na srčni utrip, kakršnega ima tudi zdravilo Qsiva, ali na druge kardiovaskularne parametre, morda potrebna dodatna izključitev škodljivih kardiovaskularnih učinkov.
English: Even though there was no overall signal of an increased risk of cardiovascular events in the studies, the consequences of an increased heart rate in subjects with history of, or with ongoing cardiovascular disease, are unknown.
Slovenian: Čeprav v študijah niso opazili splošnih znamenj povečanega tveganja za kardiovaskularne dogodke, pa posledice povišanega srčnega utripa pri preiskovancih s prisotno kardiovaskularno boleznijo ali anamnezo take bolezni niso znane.
English: Therefore, the lack of power, and thus reliability, of the post-hoc analysis of cardiovascular events during the Qsiva clinical development program remains a major concern, since with a total number of 1526 patients of low CV risk treated for one year the expected rate of CV events is extremely low and thus of little significance for the assessment of the CV risk.
Slovenian: Zaradi pomanjkanja moči in s tem zanesljivosti post-hoc analize kardiovaskularnih dogodkov v času programa kliničnega razvoja zdravila Qsiva ostaja glavni zadržek, saj je ob skupnem številu 1526 bolnikov z majhnim kardiovaskularnim tveganjem, ki so bili zdravljeni eno leto, pričakovana stopnja kardiovaskularnih dogodkov izjemno nizka in zato majhnega pomena za oceno kardiovaskularnega tveganja.
English: The proposed removal of the top dose for the use of Qsiva does not alleviate the concerns.
Slovenian: Predlagan izbris največjega odmerka za uporabo zdravila Qsiva ne omili zadržkov.
English: Although the amount of phentermine in the high dose of Qsiva is half of that currently licensed for use as a single agent in the US and the UK, the addition of topiramate was shown to increase exposure to phentermine by 40% in the PK studies.
Slovenian: Čeprav je količina fentermina v velikem odmerku zdravila Qsiva le polovica količine, ki je trenutno odobrena za uporabo v monoterapiji v ZDA in Združenem kraljestvu, pa se je v farmakokinetičnih študijah izkazalo, da dodatek topiramata poveča izpostavljenost fenterminu za 40 %.
English: There remains uncertainty whether off-label use can be sufficiently mitigated by the measures proposed by the applicant.
Slovenian: Obstaja tudi negotovost, ali je nenamensko uporabo mogoče zadovoljivo omiliti z ukrepi, ki jih je predlagal predlagatelj.
English: There was a dose-dependent increase in the incidence of depression (3.8% in the mid dose group vs. 7.7% in the highest dose group, with 3.4% in the placebo group), anxiety (4.8% vs. 7.9%, respectively, with 2.6% in the placebo group), insomnia (6.8% vs. 10.8%, respectively, with 5.7% in the placebo group), paraesthesia (11.8% vs. 17.3%, respectively, with 1.2% in the placebo group) and cognitive disorders (5.0% vs. 7.6%, respectively, with 1.5% in the placebo group; mainly attention disturbances, memory impairment and language disorders).
Slovenian: Opazili so porast incidence depresije v odvisnosti od odmerka (3,8 % v skupini s srednjim odmerkom v primerjavi s 7,7 % v skupini z največjim odmerkom in 3,4 % v skupini s placebom), anksioznosti (4,8 % v primerjavi s 7,9 %, 2,6 % v skupini s placebom), nespečnosti (6,8 % v primerjavi z 10,8 %, 5,7 % v skupini s placebom), parestezije (11,8 % v primerjavi s 17,3 %, 1,2 % v skupini s placebom) ter kognitivnih motenj (5,0 % v primerjavi s 7,6 %, 1,5 % v skupini s placebom; predvsem motenj pozornosti, poslabšanega spomina in motenj govora).
English: Off-label use - The CHMP considers that Qsiva is expected to have a high probability of off-label use, particularly in patients with some nutritional disorders (e.g. bulimia, Binge Eating Disorder) as well as in psychiatric patients, paediatric populations, adults with high CV risk, and elderly patients.
Slovenian: Nenamenska uporaba - odbor CHMP pričakuje, da v zvezi z zdravilom Qsiva obstaja velika verjetnost za nenamensko uporabo, še posebej pri bolnikih z določenimi motnjami hranjenja (npr. bulimijo, kompulzivnim prenajedanjem) in psihiatričnih bolnikih, pediatričnih populacijah, odraslih z velikim kardiovaskularnim tveganjem ter pri starejših bolnikih.
English: Phentermine as amphetamine-like substance has a well known drug abuse potential.
Slovenian: Ker je fentermin amfetaminu podobna snov, ima dobro znan potencial za zlorabo.
English: A meta-analysis of cardiovascular events showed the population studied to be at a low risk of cardiovascular events.
Slovenian: Metaanaliza kardiovaskularnih dogodkov je pokazala, da je v proučevani populaciji tveganje za kardiovaskularne dogodke majhno.
English: The collection of psychiatry data with screening instruments such as QPH-9 and C-SSRS was found by CHMP to be inadequate since diagnostic instruments are more powerful and would be needed to reliably establish the clinical relevance and magnitude of the psychiatry adverse events (AEs) observed with Qsiva.
Slovenian: Nabor psihiatričnih podatkov s presejalnimi instrumenti, kot sta vprašalnika QPH-9 in C-SSRS, je po mnenju CHMP nezadosten, saj so diagnostični instrumenti močnejši in bi bili potrebni za zanesljivo ugotavljanje klinične pomembnosti ter obsega psihiatričnih neželenih učinkov, opaženih pri uporabi zdravila Qsiva.
English: While the CHMP acknowledged that this could improve the benefit/risk ratio, CHMP concluded that the proposed removal of the high dose from the application did not sufficiently alleviate the concerns of the CHMP both with regard to the psychiatric and cardiovascular safety profile (see points above), which remains for the lower doses.
Slovenian: Čeprav je odbor CHMP presodil, da bi to lahko izboljšalo razmerje med koristmi in tveganji, pa je sklenil, da predlagani izbris velikega odmerka iz vloge ne bi zadovoljivo odpravil njegovih zadržkov v zvezi s profiloma psihiatrične in kardiovaskularne varnosti (glejte zgornje točke), ki veljata za manjše odmerke.
English: Psychiatric safety - Although there was an increase in reports of psychiatric and cognitive symptoms with the top-dose of Qsiva, the majority of these events were of mild severity, occurred early in treatment, resolved spontaneously or with discontinuation of study drug.
Slovenian: Psihiatrična varnost - čeprav so opazili porast poročil o psihiatričnih in kognitivnih simptomih ob uporabi največjega odmerka zdravila Qsiva, je bila večina teh dogodkov blagih, pojavili pa so se predvsem v zgodnjem obdobju zdravljenja in so izzveneli spontano ali pa ob prekinitvi zdravljenja s proučevanim zdravilom.
English: The applicant further cited supportive CV safety data from published results of clinical studies with other sympathomimetic agents in other indications and from historical data with phentermine.
Slovenian: Predlagatelj je v nadaljevanju navedel podporne podatke o varnosti glede kardiovaskularnih bolezni iz objavljenih rezultatov kliničnih študij z drugimi simpatikomimetičnimi sredstvi v drugih indikacijah in iz preteklih podatkov s fenterminom.
English: Cardiovascular safety - According to the applicant, the only concern about a potential increase in CV risk arises from a small (1.6 bpm) dose-related increase in heart rate that differed significantly from placebo only with the top-dose, but not for the mid-dose, whereas blood pressure was consistently and significantly reduced by both the mid- and top-doses of Qsiva.
Slovenian: Kardiovaskularna varnost - predlagatelj meni, da edina skrb glede morebitnega povečanja tveganja za kardiovaskularne dogodke izhaja iz majhnega (1,6 utripa na minuto) pospešenja srčnega utripa, povezanega z odmerkom, ki se je bistveno razlikoval od placeba le pri največjem odmerku, ne pa pri srednjem odmerku, medtem ko se je krvni tlak konsistentno in bistveno znižal tako pri srednjem kot pri največjem odmerku zdravila Qsiva.
English: There were no outstanding issues on the quality of the active substances, however minor issues remained unresolved regarding the quality of the finished medicinal product: no process validation for the proposed production scale batch size had been performed, therefore the largest batch size that would have been accepted is that of the pilot scale batches.
Slovenian: V zvezi s kakovostjo zdravilnih učinkovin niso opazili izrazitih težav, v zvezi s kakovostjo končnega zdravila pa je ostalo nerešenih nekaj manjših težav: ker ni bila opravljena validacija postopka za predlagano velikost proizvodne serije, je največja sprejemljiva velikost serije velikost pilotnih serij.
English: The proposed RMP was assessed at the request of the CHMP by the Pharmacovigilance Risk Assessment Committee (PRAC).
Slovenian: Osnutek načrta za obvladovanje tveganja je na predlog odbora CHMP ocenil Odbor za oceno tveganja na področju farmakovigilance (PRAC).
English: The applicant emphasised that Qsiva is highly effective in achieving and maintaining weight loss in obese patients, of a magnitude greater than that of any other pharmacological treatment to date with expected improvement of cardiovascular, metabolic, and other outcomes, as well as demonstrated improvements in blood pressure, glycaemic control, lipids, quality of life, incidence of new onset type 2 diabetes and other outcomes.
Slovenian: Predlagatelj je poudaril, da je zdravilo Qsiva zelo učinkovito pri doseganju in vzdrževanju izgube telesne mase pri debelih bolnikih v večjem obsegu kot katero koli drugo dosedanje farmakološko zdravljenje, s pričakovanim izboljšanjem v kardiovaskularnih, presnovnih in drugih izidih ter z dokazanimi izboljšanji v krvnem tlaku, urejenosti glikemije, lipidih, kakovosti življenja, incidenci novo nastale sladkorne bolezni tipa 2 ter drugih izidih.
English: Outcomes using various accepted MACE composite endpoints in the Qsiva programme showed no increase in risk for any of these endpoints compared to placebo (hazard ratios <1.0).
Slovenian: Izidi z uporabo sestavljenih opazovanih dogodkov MACE (veliki neželeni srčni dogodki) v programu z zdravilom Qsiva niso pokazali nikakršnega povečanja tveganja za katerega koli od teh opazovanih dogodkov v primerjavi s placebom (razmerje tveganj < 1,0).
English: Qsiva has proven to be very effective in reducing body weight, with a mean weight loss from baseline of approximately 8 and 10% for the mid and high dose, respectively, in the first year.
Slovenian: Zdravilo Qsiva se je izkazalo kot zelo učinkovito pri zmanjševanju telesne mase s povprečno izgubo le-te od izhodišča približno 8 % za srednji in 10 % za veliki odmerek v prvem letu.
English: Following a request from the applicant at the time of the re-examination, the CHMP convened a Scientific Advisory Group (SAG) Diabetes Endocrinology with additional experts, inviting the experts to provide their views on the CHMP grounds for refusal, taking into account the applicant's response.
Slovenian: Ob ponovnem pregledu je odbor CHMP na predlagateljevo zahtevo sklical znanstveno svetovalno skupino za endokrinologijo sladkorne bolezni z dodatnimi strokovnjaki in pozval strokovnjake, naj ob upoštevanju predlagateljevega odgovora predložijo svoje mnenje o razlogih odbora CHMP za zavrnitev.
English: Psychiatric safety -Depression, anxiety and cognitive impairment were more commonly reported in patients treated with Qsiva than placebo.
Slovenian: Psihiatrična varnost - o depresiji, anksioznosti in poslabšanih kognitivnih funkcijah so pogosteje poročali pri bolnikih, ki so bili zdravljeni z zdravilom Qsiva, kot pri bolnikih, zdravljenih s placebom.
English: Known adverse events with the use of phentermine are palpitations, tachycardia, elevation of blood pressure, psychosis, CNS and gastrointestinal effects and with the use of topiramate paraesthesia, changes in taste, ocular disorders, psychiatric and cognitive disorders.
Slovenian: Znani neželeni dogodki ob uporabi fentermina so palpitacije, tahikardija, dvig krvnega tlaka, psihoza, učinki na osrednje živčevje in prebavila, ob uporabi topiramata pa parestezija, spremembe okušanja, očesna obolenja, psihiatrične in kognitivne motnje.
English: However, it was recognised that effectiveness of the PPP in clinical practice will be difficult to maintain in the long term use.
Slovenian: Odbor je izpostavil, da bo učinkovitost načrta za preprečevanje nosečnosti pri dolgotrajni uporabi v klinični praksi težko ohranjati.
English: The currently available cardiovascular outcome data for Qsiva remains inconclusive;
Slovenian: Trenutno razpoložljivi podatki o kardiovaskularnem izidu za zdravilo Qsiva ostajajo nedoločni;
English: In the view of the CHMP, any increase in heart rate can remain a concern with regard to CV risk.
Slovenian: Po mnenju odbora CHMP lahko vsakršno pospešenje srčnega utripa ostane zadržek, povezan s kardiovaskularnim tveganjem.
English: Cardiovascular safety - The CHMP had methodological concerns with regard to the quality of the data source (with dropout rates of about 40%, and lost to follow up rate above 10%) and the magnitude of the dose-dependent increase in heart rate (as heart rate measurement was not an end point in the Qsiva clinical program and no standardised methodology for accurate assessment was implemented).
Slovenian: Kardiovaskularna varnost - odbor CHMP je izrazil metodološke zadržke v zvezi s kakovostjo vira podatkov (stopnja izpada preskušancev iz študije je bila približno 40 %, stopnja prekinitve sodelovanja med sledenjem pa 10 %) in obsegom pospešenja srčnega utripa, povezanega z odmerkom (ker meritev srčnega utripa ni bila opazovani dogodek v kliničnem programu z zdravilom Qsiva in niso uvedli standardizirane metodologije za natančno ocenjevanje).
English: In the 1 year cohort the frequency of cardiac disorders (mostly palpitations and increase in heart rate) was higher in the Qsiva groups (4.2% and 4.7% in the mid dose and high dose group, respectively) compared to placebo (1.8%).
Slovenian: V enoletni kohorti je bila pogostnost srčnih bolezni (predvsem palpitacij in pospešenega srčnega utripa) večja v skupinah z zdravilom Qsiva (4,2 % v skupini s srednjim odmerkom in 4,7 % v skupini z velikim odmerkom) v primerjavi s placebom (1,8 %).
English: Qsiva should be prescribed by physicians experienced in the management of obesity and obesity-related co-morbidities.
Slovenian: Zdravilo Qsiva naj bi predpisovali zdravniki z izkušnjami pri obravnavi debelosti in z debelostjo povezanih bolezni.
English: The long term cardiovascular safety of Qsiva has not been sufficiently established.
Slovenian: 1. dolgoročna kardiovaskularna varnost zdravila Qsiva ni bila zadovoljivo dokazana.
English: The overall quality of the medicinal product was considered acceptable by the CHMP.
Slovenian: Odbor CHMP je presodil, da je splošna kakovost zdravila sprejemljiva.
English: Due to the inhibitory effect of topiramate on renal carbonic anhydrase, reductions in serum bicarbonate below 21 mEq/L were seen in 2.1%, 6.4% and 12.8% in the placebo, mid and high dose groups, and therefore are of concern in the targeted population.
Slovenian: Zaradi zaviralnega učinka topiramata na ledvično karbonsko anhidrazo so zaznali znižanje ravni serumskega bikarbonata pod 21 mEq/l pri 2,1 % v skupini s placebom, 6,4 % v skupini s srednjim odmerkom in 12,8 % v skupini z največjim odmerkom, kar predstavlja zadržek za uporabo pri ciljni populaciji.
English: The CHMP further considered that restricting prescribing to clinical settings where prescribing decisions can be informed by a multi-disciplinary clinical team that can assess both the physical and mental health of the patients and the appropriateness of treatment with Qsiva could help minimise the risks but had concerns about the feasibility of this practice in all EU member states.
Slovenian: Odbor CHMP je poleg tega presodil, da bi omejitev predpisovanja na klinična okolja, v katerih lahko odločitev za predpisovanje podkrepi večdisciplinarna klinična ekipa, ki lahko oceni telesno in duševno zdravje bolnika in ustreznost zdravljenja z zdravilom Qsiva, sicer lahko pomagala pri zmanjšanju tveganj,
English: The applicant's proposal to retain restricted prescribing (to physicians experienced in management of obesity and/or obesity-related co-morbidities) but to remove restricted distribution and dispensing requirements remained a concern to CHMP as this may still represent a broad prescriber base not limited to specialists.
Slovenian: Za odbor CHMP ostaja vprašljiv tudi predlagateljev predlog, naj se ohrani omejeno predpisovanje zdravila (na zdravnike z izkušnjami pri zdravljenju debelosti in z debelostjo povezanih bolezni) in ukine zahteva o omejeni distribuciji in izdajanju, saj to lahko še vedno predstavlja široko bazo predpisovalcev, ki ni omejena na specialiste.
English: The Applicant presented hazard ratios for major cardiovascular events in Qsiva-treated subjects.
Slovenian: Predlagatelj je predstavil razmerja tveganja za glavne kardiovaskularne dogodke pri preiskovancih, ki so bili zdravljeni z zdravilom Qsiva.
English: Pregnancies have been reported in rather high numbers in the clinical trial program raising concerns with regard to the teratogenic risk of the product when used in a less controlled real life setting.
Slovenian: V programu kliničnega preskušanja so poročali o precej velikem številu nosečnosti, zato so izpostavili zadržke glede teratogenega tveganja zdravila, kadar se uporablja v manj kontroliranih okoliščinah v realnem življenju.
English: Dropout rates for depression with Qsiva significantly outnumbered those with placebo; thus close surveillance in trials may have stopped progression to more severe symptoms.
Slovenian: Stopnje prekinitve sodelovanja preskušancev zaradi depresije ob uporabi zdravila Qsiva so bile bistveno višje kot ob uporabi placeba, zato je natančno spremljanje v preskušanjih morda preprečilo napredovanje do resnejših simptomov.
English: The applicant's claim that by applying the 3 month stopping rule for non-responders, the number of drop-outs due to neuropsychiatric AEs in the Qsiva group would not exceed those in the placebo group was questioned by CHMP.
Slovenian: Odbor CHMP je podvomil v predlagateljevo trditev, da z uporabo pravila o prenehanju zdravljenja po 3 mesecih pri osebah, ki se ne odzivajo na zdravljenje, število prekinitev sodelovanja zaradi nevropsihiatričnih neželenih učinkov v skupini, ki je prejemala zdravilo Qsiva, ne bi preseglo števila prekinitev v skupini s placebom.
English: In the view of the CHMP an unmet medical need in the treatment of patients with obesity is acknowledged.
Slovenian: Po mnenju odbora CHMP obstaja potreba po zdravilu za zdravljenje bolnikov s čezmerno telesno maso.
English: The Applicant addressed the need for effective contraception and the risk of teratogenesis in the SmPC and the RMP, which included a detailed healthcare provider checklist as well as patient education card.
Slovenian: Predlagatelj je v povzetku glavnih značilnosti zdravila in načrtu za obvladovanje tveganja obravnaval potrebo po učinkoviti kontracepciji in tveganje za teratogenezo, vključno s podrobnim seznamom za izvajalca zdravstvenih storitev in informativno kartico za bolnika.
English: During the re-examination procedure, the applicant proposed a further revised SmPC which forgoes the top dose of Qsiva, associated with the highest rate of psychiatric and cardiovascular adverse events.
Slovenian: Med postopkom ponovnega pregleda je predlagatelj predložil dodatno popravljeni povzetek glavnih značilnosti zdravila, v katerem največji odmerek zdravila Qsiva, povezan z najvišjo stopnjo psihiatričnih in kardiovaskularnih neželenih dogodkov, ni več naveden.
English: Therefore, the currently available cardiovascular outcome data for Qsiva was considered inconclusive and the long term cardiovascular safety of Qsiva has not been sufficiently established.
Slovenian: Zato so trenutno razpoložljive podatke o kardiovaskularnih izidih pri zdravilu Qsiva upoštevali kot nedoločne, dolgoročna varnost zdravila Qsiva za srce in ožilje pa ni bila zadovoljivo dokazana.