natgillin/translations-raw huggingface dataset:
(95% CI) p-value BSC = best supportive care, CI = confidence interval, ORR = objective response rate (patients with complete response or partial response), OS = overall survival time, PFS = progression-free survival time 
NPO = najboljši podporni oskrbi, IZ = interval zaupanja; ORR (objective response rate) = objektivna stopnja odgovora (bolniki s popolnim odgovorom ali delnim odgovorom); OS (overall survival) = celokupno preživetje, PFS (progression-free survival time) = čas preživetja brez napredovanja bolezni
OS months, median (95% CI) Hazard Ratio (95% CI) p-value PFS months, median (95% CI) 
OS meseci, mediana (95-odstotni IZ) razmerje tveganja (95-odstotni IZ) vrednost p PFS meseci, mediana (95-odstotni IZ)
Vascular disorders Uncommon: 
Pogostnost neznana:
BN 
NPO
Citric acid monohydrate Sodium hydroxide Water for injections 
6.1 Seznam pomožnih snovi natrijev klorid glicin polisorbat 80 citronska kislina monohidrat natrijev hidroksid voda za injekcije
What Erbitux is used for 
Za kaj uporabljamo zdravilo Erbitux
Posology 
Predzdravljenje
OS months, median (95% CI) Hazard Ratio (95% CI) p-value PFS months, median (95% CI) Hazard Ratio (95% CI) p-value ORR 
OS meseci, mediana (95-odstotni IZ) razmerje tveganja (95-odstotni IZ) vrednost p PFS meseci, mediana (95-odstotni IZ) razmerje tveganja (95-odstotni IZ) vrednost p ORR
Radiation therapy + cetuximab 
Radioterapija in cetuksimab
How to store Erbitux 
Shranjevanje zdravila Erbitux
• dizziness 
• luščenje
Do not breast-feed your baby during the period over which you are being treated with Erbitux and for two months after the last dose. 
V času, ko se zdravite z zdravilom Erbitux, in še dva meseca po zadnjem odmerku zdravila ne smete dojiti.
Intravenous use. 
Način uporabe
NN: 
Občasni:
A doctor experienced in the use of anticancer medicines will supervise your Erbitux therapy. 
Zdravljenje z zdravilom Erbitux bo potekalo pod nadzorom zdravnika, ki ima izkušnje z uporabo zdravil proti raku.
Hepatobiliary disorders Very common: 
Očesne bolezni Pogosti:
Connect the infusion line to the syringe and start the infusion after priming the line with Erbitux or sterile sodium chloride 9 mg/mL (0.9%) solution. 
Po polnjenju linije z zdravilom Erbitux ali sterilno raztopino natrijev klorid 9 mg/ml (0,9%) raztopina za injiciranje lahko začnete z infundiranjem zdravila.
ORR 
Lot
5 (5 x 1) vials (multipack) 
5 (5 pakiranj po 1) vial (skupno pakiranje)
10 (2 x 5) pre-filled pens (multipack) 
10 (2 pakiranji po 5) napolnjenih injekcijskih peresnikov (skupno pakiranje)
1 pre-filled pen + 7 NovoFine Plus needles 
1 napolnjen injekcijski peresnik + 7 igel NovoFine Plus
The CHMP considered the following: 
Odbor CHMP je upošteval naslednje:
These concerns were raised with the applicant during the procedure but were never adequately addressed. 
O teh zadržkih je bil predlagatelj med postopkom obveščen, vendar niso bili nikoli zadovoljivo razrešeni.
Grounds for re-examination 
Razlogi za ponovni pregled
The CHMP is of the opinion that pursuant to Article 12 of Regulation (EC) No 726/2004, the safety of the above mentioned medicinal product is not properly or sufficiently demonstrated. 
odbor CHMP meni, da na podlagi člena 12 Uredbe (ES) št. 726/2004 varnost zadevnega zdravila ni ustrezno ali zadovoljivo dokazana.
It is only being approved for short term periods of treatment (less than three months) and its long term cardiac toxicity is unknown. 
Uporaba zdravila je bila odobrena le za kratkotrajna obdobja zdravljenja (manj kot tri mesece), njegova dolgoročna toksičnost za srce pa ni znana.
as the safety of the above mentioned medicinal product was not sufficiently demonstrated, the applicant submitted detailed grounds for the re-examination of the grounds for refusal. 
Ker varnost zgoraj navedenega zdravila ni bila zadovoljivo prikazana, je predlagatelj predložil podrobne razloge za ponoven pregled razlogov za zavrnitev.
The applicant presented in their submission the following grounds for re-examination: 
Predlagatelj je v svoji predloženi dokumentaciji predstavil naslednje razloge za ponovni pregled:
Another concern was the feasibility to exclude patients with moderate depression from treatment. 
Drug zadržek pa je predstavljala izvedljivost izključitve bolnikov z zmerno depresijo iz zdravljenja.
Overall summary of the scientific evaluation of Qsiva 
Splošni povzetek znanstvenega vrednotenja zdravila Qsiva
Additionally, the Committee noted that the actual patient numbers treated with the recommended mid dose were limited. 
Poleg tega je odbor opozoril, da je bilo dejansko število bolnikov, zdravljenih s priporočenim srednjim odmerkom, omejeno.
The applicant addressed specifically the CHMP´s four initial principal grounds for refusal: 
Predlagatelj je posebej obravnaval štiri začetne temeljne razloge odbora CHMP za zavrnitev: 1.
There is remaining uncertainty whether the updated risk minimisation measures as proposed by the applicant could effectively prevent such off-label use. 
Ostaja negotovost, ali bi posodobljeni ukrepi za zmanjšanje tveganja, kot jih je predlagal predlagatelj, lahko učinkovito preprečili nenamensko uporabo,
However, due to the voluntary nature of the registry the expected participation was considered to be low and hence its capacity to minimise off-label use remained uncertain. 
Zaradi prostovoljne narave registra pa je pričakovati nizko udeležbo, zato njegov potencial za zmanjševanje nenamenske uporabe ostaja vprašljiv.
Although these showed no obvious increased frequency of events with treatment, the data are of limited value as the duration of follow-up was relatively short and the total number of events was small. 
Čeprav niso pokazali očitne povečane pogostnosti teh dogodkov ob zdravljenju, imajo ti podatki omejeno vrednost, saj je bilo sledenje relativno kratko, skupno število dogodkov pa majhno.
In addition, patient registry and drug utilization study was proposed to be conducted to repeatedly evaluate the effectiveness of these measures. 
Poleg tega je predlagal uvedbo registra bolnikov in študije uporabe zdravila, s katerima bi trajno ocenjevali učinkovitost teh ukrepov.
The effect was similar in examined subpopulations, but experience in older subjects and patients with cardiovascular disease was very limited. 
Učinek je bil podoben v preučevanih podpopulacijah, izkušnje s starejšimi preiskovanci in bolniki z kardiovaskularnimi obolenji pa so bile zelo omejene.
Treatment with Qsiva 7.5/46 mg and 15/92 mg for 28 and 56 weeks resulted in clinically relevant reductions of body weight, with a maximum effect after approx. 36-40 weeks of treatment. 
Zdravljenje z zdravilom Qsiva 7,5/46 mg in 15/92 mg v obdobju 28 in 56 tednov je povzročilo klinično pomembno zmanjšanje telesne mase z največjim učinkom po približno 36−40 tednih zdravljenja.
However, no additional weight loss was seen in the second year, rather there was a mean weight gain in all groups. 
V drugem letu pa niso opazili dodatne izgube telesne mase, pač pa povprečno pridobivanje telesne mase v vseh skupinah.
Topiramate is known as a teratogenic substance causing congenital malformations. 
Topiramat je znan kot teratogena snov, ki povzroča prirojene okvare.
• Safety issues 
• Vidiki varnosti
With regard to reported cases of suicidal ideation in patients treated with Qsiva during the clinical studies, regular assessments in this regard would be required. 
Glede na poročanje o samomorilnih mislih bolnikov, zdravljenih z zdravilom Qsiva v kliničnih študijah, bi bile v zvezi s tem potrebna redna ocenjevanja.
Importantly, there were no increases in major depression diagnoses (by PHQ-9 questionaire), emergent antidepressant use, or suicidality (by C-SSRS questionaire) in the programme. 
Pomembno je, da niso opazili povečanja v diagnozah velikih depresivnih motenj (po vprašalniku PHQ-9), novi uporabi antidepresivov ali samomorilnosti (po vprašalniku C-SSRS) v programu.
The proposed patient registry was considered a key component to gather long term data on the safety of Qsiva and on the effectiveness of the risk minimisation measures, especially in relation to off-label use. 
Predlagani register bolnikov je bil upoštevan kot ključna komponenta za zbiranje dolgoročnih podatkov o varnosti zdravila Qsiva in učinkovitosti ukrepov za zmanjšanje tveganja, še posebej v zvezi z nenamensko uporabo.
• Quality issues 
• Vidiki kakovosti
The specification of the finished product was to be revised based on the batch data results and a second identity test method included for each drug substance. 
Specifikacijo končnega izdelka naj bi pregledali na podlagi rezultatov podatkov o seriji in na podlagi druge metode identifikacijskega preskusa, ki naj bi bila vključena za vsako osnovno učinkovino.
Therefore, the CHMP has recommended the refusal of the granting of the marketing authorisation for Qsiva. 
Zato je odbor CHMP priporočil zavrnitev izdaje dovoljenja za promet z zdravilom Qsiva.
The magnitude of the weight loss was larger compared to previously approved weight reducing agents. 
Obseg izgubljene telesne mase je bil v primerjavi s predhodno odobrenimi sredstvi za zmanjšanje telesne mase večji.
Many of these adverse events were also reported with Qsiva as a fixed-dose combination of phentermine/topiramate in four pivotal Phase III studies and two supportive Phase II studies. 
O mnogih od teh neželenih učinkov so poročali tudi ob uporabi zdravila Qsiva kot kombinaciji fiksnih odmerkov fentermina/topiramata v štirih ključnih študijah 3. faze in dveh podpornih študijah 2. faze.
Existing data from phentermine use has major limitations and cannot be extrapolated with regard to conclusions on the safety profile of Qsiva. 
Obstoječi podatki o uporabi fentermina imajo velike omejitve in jih ni mogoče ekstrapolirati v povezavi z zaključki o varnostnem profilu zdravila Qsiva.
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. 
V obdobju dolgotrajne uporabe tega zdravila v večji populaciji pogostost neželenih psihiatričnih učinkov in njihovih posledic ter kognitivnih učinkov ni znana.
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. 
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.
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. 
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.
The probability of off-label use of this product outside the population covered by the claimed indication is expected to be high. 
4. je pričakovana verjetnost za nenamensko uporabo tega zdravila zunaj populacije, zajete v predlagani indikaciji, velika.
Reported rates for most CNS-related side effects were similar between the mid-dose and placebo. 
Poročila o stopnjah večine stranskih učinkov, povezanih z osrednjim živčevjem, so bila za srednji odmerek in placebo podobna.
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. 
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.
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. 
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.
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. 
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.
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.. 
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.
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. 
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.
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. 
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.
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. 
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.
The proposed removal of the top dose for the use of Qsiva does not alleviate the concerns. 
Predlagan izbris največjega odmerka za uporabo zdravila Qsiva ne omili zadržkov.
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. 
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 %.
There remains uncertainty whether off-label use can be sufficiently mitigated by the measures proposed by the applicant. 
Obstaja tudi negotovost, ali je nenamensko uporabo mogoče zadovoljivo omiliti z ukrepi, ki jih je predlagal predlagatelj.
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). 
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).
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. 
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.
Phentermine as amphetamine-like substance has a well known drug abuse potential. 
Ker je fentermin amfetaminu podobna snov, ima dobro znan potencial za zlorabo.
A meta-analysis of cardiovascular events showed the population studied to be at a low risk of cardiovascular events. 
Metaanaliza kardiovaskularnih dogodkov je pokazala, da je v proučevani populaciji tveganje za kardiovaskularne dogodke majhno.
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. 
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.
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. 
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.
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. 
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.
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. 
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.
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. 
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.
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. 
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.
The proposed RMP was assessed at the request of the CHMP by the Pharmacovigilance Risk Assessment Committee (PRAC). 
Osnutek načrta za obvladovanje tveganja je na predlog odbora CHMP ocenil Odbor za oceno tveganja na področju farmakovigilance (PRAC).
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. 
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.
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). 
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).
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. 
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.