natgillin/translations-raw huggingface dataset:
Implementation of the agreement by the Member States (submission of the variation by the Marketing Authorisation Holder): 
Izvajanje sporazuma s strani držav članic (predložitev spremembe s strani imetnika dovoljenja za promet z zdravilom):
20 February 2014 
20. februar 2015
The procedure started on 20 September 2007. 
Postopek se je začel 20. septembra 2007.
Ref. EMEA/CHMP/384879/2008 
: EMEA/CHMP/554691/2008
A Decision was issued by the European Commission on 7 October 2008. 
Evropska komisija je odločbo izdala 7. oktobra 2008.
London, 8 October 2008 Doc. 
London, 8. oktober 2008 Sklic dok.
The Marketing Authorisation Holder provided supplementary information on 28 January 2008 and 28 April 2008. 
Imetnik dovoljenja za promet z zdravilom je priskrbel dodatne informacije 28. januarja 2008 in 28. aprila 2008.
Risperdal Consta and associated names is an anti-psychotic, indicated for the maintenance treatment of schizophrenia in patients currently stabilised with oral antipsychotics. 
Zdravilo Risperdal Consta in z njim povezana imena je antipsihotično zdravilo, indicirano za vzdrževalno zdravljenje shizofrenije pri bolnikih, katerih stanje je trenutno stabilizirano s peroralnimi antipsihotiki.
It is available as prolonged release powder and solvent for suspension for intramuscular use. 
Zdravilo je na voljo v obliki praška s podaljšanim sproščanjem in vehikla za suspenzijo za intramuskularno uporabo.
COMMITTEE FOR MEDICINAL PRODUCTS FOR HUMAN USE (CHMP) OPINION FOLLOWING AN ARTICLE 30 REFERRAL FOR Risperdal Consta and associated names International Non-Proprietary Name (INN): risperidone 
ODBOR ZA ZDRAVILA ZA UPORABO V HUMANI MEDICINI (CHMP) MNENJE V ZVEZI Z NAPOTITVIJO V SKLADU S ČLENOM 30 ZA Risperdal Consta in z njim povezana imena Mednarodno nelastniško ime (INN): risperidon
The basis for referral was that there were divergences in the Summaries of Product Characteristics (SPC) of Risperdal Consta and associated names approved across EU Member States, with respect to the indication, the special warnings and precautions for use and the interaction with other medicinal products and other forms of interaction. 
Osnova za napotitev so bile razlike med povzetki glavnih značilnosti zdravila Risperdal Consta in z njim povezanih imen v državah članicah EU pri indikacijah, posebnih opozorilih in previdnostnih ukrepih ter medsebojnem delovanju z drugimi zdravili in drugih vrstah interakcij.
On 24 July 2007 the European Commission presented to the EMEA a referral under Article 30 of Directive 2001/83/EC, as amended, in order to harmonise the nationally authorised Summaries of Product Characteristics (SPC), Labelling and Package Leaflet of the medicinal product Risperdal Consta and associated names. 
Evropska komisija je dne 24. julija 2007 agenciji EMEA predložila napotitev v skladu s členom 30 Direktive 2001/83/ES, kakor je bila spremenjena, da bi uskladila nacionalno odobrene povzetke glavnih značilnosti zdravila, označevanje in navodilo za uporabo zdravila Risperdal Consta in z njim povezana imena.
The list of product names concerned is given in Annex I. The scientific conclusions are provided in Annex II together with the amended SPC, Labelling and Package Leaflet in Annex III. 
Seznam zadevnih imen zdravil je naveden v Dodatku I. Znanstveni zaključki so navedeni v Dodatku II, skupaj s spremenjenim povzetkom glavnih značilnosti zdravila, označevanjem in navodilom za uporabo v Dodatku III.
During its July 2008 meeting, the CHMP, in the light of the overall submitted data and the scientific discussion within the Committee, was of the opinion that the proposal for the harmonisation of the SPC, Labelling and Package Leaflet was acceptable and that they should be amended. 
CHMP je med zasedanjem julija 2008 glede na vse predložene podatke in znanstveno razpravo v Odboru sprejel mnenje, da je predlog za uskladitev povzetkov glavnih značilnosti zdravila, označevanja in navodila za uporabo sprejemljiv in da bi bilo treba navedene dokumente spremeniti.
This medicinal product belongs to the list of products identified in 2007 for SPC harmonisation. 
To zdravilo spada na seznam zdravil, katerih povzetke glavnih značilnosti zdravila je treba po ugotovitvah iz leta 2007 uskladiti.
The CHMP gave a positive opinion on 24 July 2008 recommending the harmonisation of the SPC, Labelling and Package Leaflet for Risperdal Consta and associated names. 
V CHMP so podali pozitivno mnenje 24. julija 2008, s katerim so priporočili uskladitev povzetkov glavnih značilnosti zdravila, označevanja in navodila za uporabo za zdravilo Risperdal Consta in z njim povezana imena.
Most of them received only one infusion. 
Večina od njih je prejela samo eno infuzijo.
The majority of patients were female. 
Večina bolnikov je bila ženskega spola.
The majority of studies were retrospective. 
Večina študija je bila retrospektivnih.
Published literature was also provided. 
Predložena je bila tudi objavljena literatura.
In about 80% of the cases, the outcome of pregnancy was unknown. 
Pri približno 80 % primerov izid nosečnosti ni bil znan.
Therefore, no conclusions on safety can be drawn from these studies alone. 
Zaključkov o varnosti zato samo iz teh študij ni mogoče izpeljati.
These reactions may be damaging, uncomfortable, or occasionally fatal. 
Te reakcije so lahko škodljive, neprijetne in v nekaterih primerih smrtne.
Risk minimisation measures and other pharmacovigilance activities 
Ukrepi za zmanjšanje tveganja in druge dejavnosti farmakovigilance
The following analyses were performed on spontaneous or solicited cases, medically confirmed or not, recorded until 15 December 2011. 
Naslednje analize so izvedli na spontanih ali spodbujenih primerih, medicinsko potrjenih ali ne, ki so jih zabeležili do 15. decembra 2011.
Twenty-two clinical studies were submitted. 
Predloženih je bilo dvaindvajset kliničnih študij.
• The Committee considered the procedure under Article 31 of Directive 2001/83/EC for intravenous iron containing medicinal products. 
• Odbor je obravnaval napotitev v skladu s členom 31 Direktive 2001/83/ES za intravenska zdravila, ki vsebujejo železo;
This recommendation was also advised by the PRAC during the consultation requested by the CHMP. 
To priporočilo je med posvetovanjem na zahtevo CHMP izdal tudi PRAC.
Overall summary of the scientific evaluation of intravenous iron containing medicinal products (see Annex I) 
Splošni povzetek znanstvenega vrednotenja intravenskih zdravil, ki vsebujejo železo (glejte Prilogo I)
A total of 33 publications reporting on the safety of LMWID were identified. 
Upoštevanih je bilo skupno 33 publikacij, ki so poročale o varnosti LMWID.
The majority of cases were reported as serious (366/587; 62%). 
Večina primerov je bila zabeleženih kot resnih (366/587; 62 %).
For some cases (108 out of 168) the time-to-onset of the reaction was reported. 
Pri nekaterih primerih (108 od 168) so poročali o času do pojava reakcije.
Predisposition to an allergy or known asthma may result in a more severe reaction. 
Nagnjenost k alergijam ali znana astma lahko povzročita resnejšo reakcijo.
All studies have been performed applying a protocol not including a test dose. 
Vse študije so bile izvedene z uporabo protokola brez testnega odmerka.
Data provided regarding safety in pregnancy and intestinal absorption disorder was very limited. 
Predloženi podatki glede varnosti v nosečnosti in motnje absorpcije v črevesju so bili zelo omejeni.
Anti-allergic treatment was reported for 94/168 cases. 
O antialergijskem zdravljenju so poročali pri 94 od 168 primerov.
The test-dose does not seem to prevent the occurrence of severe reactions. 
Zdi se, da testni odmerek ne prepreči pojava resnih reakcij.
Test dose 
Testni odmerek
Among all studies provided, only one life-threatening reaction was reported (Michael, et al 2002). 
Pri vseh predloženih študijah so poročali o samo eni življenjsko ogrožajoči reakciji (Michael, in sod.
Cytotoxicity is mediated throughout the formation of reactive oxygen species (ROS). 
Citotoksičnost se posreduje skozi celoten postopek oblikovanja reaktivnih kisikovih zvrsti (reactive oxygen species − ROS).
This corresponds to a hypersensitivity events frequency rate of 0.060%, which is lower than the frequency rate found in clinical trials. 
To ustreza 0,060-odstotni stopnji pogostnosti preobčutljivostnih dogodkov, kar je nižje od stopnje pogostnosti v kliničnih preskušanjih.
Two of these 3 anaphylactoid reactions occurred in patients with Crohn's disease. 
Dve od teh 3 anafilaktoidnih reakcij sta se pojavili pri bolnikih s Crohnovo boleznijo.
Within the on-going clinical studies only two serious adverse reactions have been reported. 
V potekajočih kliničnih študijah so poročali o samo dveh resnih neželenih reakcijah.
In about one third of the total cases (223/846), the patients recovered after drug withdrawal. 
Približno ena tretjina vseh bolnikov (223/846) si je po odtegnitvi zdravila opomogla.
When outcome is known, most patients recovered without sequelae (94.8%). 
Kjer je bil izid znan, si je večina bolnikov opomogla brez posledic (94,8 %).
In approximately 90% of the cases in which the time to onset was reported the reaction occurred within the first 10 minutes of administration, and in about one third it occurred during the test dose. 
Pri približno 90 % primerov, pri katerih so poročali o času do pojava, se je reakcija pojavila v prvih 10 minutah po dajanju, pri približno eni tretjini pa med testnim odmerkom.
So the CHMP conclusions are applicable to all the iron complexes assessed in this referral. 
Zaključki CHMP zato veljajo za vse komplekse železa, ocenjene v tej napotitvi.
In summary, there is only very limited data on safety from clinical studies. 
Povzamemo lahko, da so iz kliničnih študij na voljo le zelo omejeni podatki o varnosti.
In later stages of pregnancy the intravenous iron preparations may be given but after careful consideration of the risks involved for the mother and foetus. 
V poznih fazah nosečnosti se pripravki intravenskega železa lahko dajejo, vendar po skrbnem premisleku tveganj za mater in zarodek.
The majority of cases were classified as grade III (53%) followed by grade II (32%). 
Večina primerov je bila razvrščena kot stopnja III (53 %), ki ji je sledila stopnja II (32 %).
As the conclusions of this assessment were mainly drawn from the post-marketing data, differentiation between these iron complexes in terms of hypersensitivity reactions could not be identified. 
Ker so bili zaključki te ocene večinoma izpeljani iz podatkov v obdobju trženja, razlik med temi kompleksi železa glede preobčutljivostnih reakcij ni bilo mogoče določiti.
19 pregnant women presented at least one anaphylactic reaction. 
19 nosečnic je doživelo vsaj eno anafilaktično reakcijo.
A total of 236 cases of hypersensitivity reactions were reported (mainly grade I and II). 
Zabeleženih je bilo skupno 236 primerov preobčutljivostnih reakcij (v glavnem stopnje I in II).
A fatal case was also reported. 
Poročali so tudi o enem primeru s smrtnim izidom.
Hypersensitivity (also called allergic reactions) refers to undesirable reactions produced by the normal immune system, including allergies and autoimmunity. 
Preobčutljivost (imenovana tudi alergijske reakcije) se nanaša na neželene reakcije, ki jih sproži normalni imunski sistem, vključno z alergijami in avtoimunsko boleznijo.
However the discussion of the existing preclinical data did not clear the immunogenic point, therefore the existing pre-clinical data do not allow for any firm conclusions; the CHMP conclusions were reached based on clinical and pharmacovigilance data. 
Ker pa v razpravi o obstoječih predkliničnih podatkih vprašanja imunogenosti niso bila pojasnjena, obstoječi predklinični podatki ne omogočajo izpeljave nobenih zanesljivih zaključkov; CHMP je svoje zaključke zato podal na osnovi kliničnih in farmakovigilančnih podatkov.
In conclusion, regarding post-marketing data, 317 cases of hypersensitivity were reported (frequency rate 0.0022%). 
Skratka, v podatkih v obdobju trženja so zabeležili 317 primerov preobčutljivosti (stopnja pogostnosti 0,0022 %).
The majority of cases were reported as serious and five cases were reported with a primary event within the immune system disorders. 
Večina primerov je bila zabeležena kot resnih in pri petih primerih so zabeležili primarni dogodek znotraj motenj imunskega sistema.
The Committee concluded that there was need for further risk minimisation measures such as information to patients and healthcare professionals. 
• Odbor je zaključil, da so potrebni dodatni ukrepi za zmanjšanje tveganja, na primer informacije za bolnike in zdravstvene delavce.
In two cases, no symptoms were reported and it was not reported whether treatment of the reaction was provided nor was the time to onset other than the day of the event reported, making it difficult to classify these events. 
Pri dveh primerih niso zabeležili nobenih simptomov in niso zabeležili, ali je bilo zagotovljeno zdravljenje reakcije in ali je bil čas do pojava drugačen od dneva, ko je bil dogodek zabeležen, zato je bilo te dogodke težko razvrstiti.
In view of the above, on 7 December 2011 France requested the CHMP under Article 31 of Directive 2001/83/EC to assess the above concerns regarding hypersensitivity and its impact on the benefit-risk balance for iron intravenous containing medicinal products, and to give its opinion on measures necessary to ensure the safe and effective use, and on whether the marketing authorisation for these products should be maintained, varied, suspended or withdrawn. 
Na podlagi zgoraj navedenega je Francija 7. decembra 2011 v skladu s členom 31 Direktive 2001/83/ES zaprosila CHMP, naj prouči zgoraj omenjene zadržke glede preobčutljivosti in njen vpliv na razmerje med tveganji in koristmi za intravenska zdravila, ki vsebujejo železo, ter poda mnenje glede ukrepov, potrebnih za zagotovitev varne in učinkovite uporabe, in o tem, ali bi bilo treba dovoljenje za promet s temi zdravili ohraniti, spremeniti, začasno umakniti ali preklicati.
Instead caution should be exercised in each iron administration even in the cases of repeated administrations. 
Namesto tega je pri dajanju železa potrebna previdnost, tudi pri primerih ponovljenih odmerkov.
Thirty-two of 88 patients experienced a reaction at injection site. 
Pri dvaintridesetih od 88 bolnikov so zabeležili reakcijo na mestu injiciranja.
In only one case, the onset was reported as a late-occurring event (onset after one day). 
Pri enem primeru so pojav zabeležili kot pozno pojavljeni dogodek (ki se je pojavil po enem dnevu).
A total of 168 cases were reported with a primary event within the System Organ Class (SOC) of immune system disorders (28.6%) including 147 serious. 
Poročali so o skupno 168 primerih s primarnim dogodkom znotraj organskega sistema motenj imunskega sistema (28,6 %), vključno s 147 resnimi primeri.
In conclusion the post-marketing data are in accordance with the known safety profile of ferric carboxymaltose. 
Podatki v obdobju trženja so v skladu z znanim varnostnim profilom železove karboksimaltoze.
One of these cases was an anaphylactoid reaction, and another was a probable serious allergic reaction. 
Eden od teh je bila anafilaktoidna reakcija, druga pa verjetna resna alergijska reakcija.
The CHMP concluded that the information on test dose is not appropriate as it may give false reassurance to the healthcare professionals. 
CHMP je zaključil, da informacije o testnem odmerku niso ustrezne, saj lahko dajejo zdravstvenim delavcem napačno zagotovilo.
Of these, one was reported as non-serious and four as serious. 
Od teh so zabeležili en primer, ki ni bil resen, in štiri resne primere.
For one patient, the event of hypersensitivity occurred after the first and the second injection. 
Pri enem bolniku se je preobčutljivost pojavila po prvem in drugem injiciranju.
All five patients made full recovery. 
Vseh pet bolnikov si je v celoti opomoglo.
Analysis on the severity of the hypersensitivity post marketing cases showed 33 cases of the 178 serious cases required hospitalization, 31 cases of the 178 serious cases were of a life-threatening nature, from which 6 patients presented with a history of allergy. 
Analize resnosti primerov preobčutljivosti v obdobju trženja so pokazale, da je bila v 33 primerih od 178 resnih primerov potrebna hospitalizacija in da je bilo 31 primerov od 178 resnih primerov življenjsko ogrožajoče narave, od katerih je imelo 6 bolnikov alergijo v anamnezi.
In addition the CHMP stressed that these products should not be given to pregnant women in the first trimester of pregnancy; treatment should be confined to second or third trimester, if the benefit is clearly judged to outweigh the potential risks for both the mother and the foetus. 
CHMP je prav tako poudaril, da teh zdravil ni dovoljeno dajati nosečnicam v prvem trimesečju nosečnosti; zdravljenje je treba omejiti na drugo ali tretje trimesečje, če so po skrbnem premisleku koristi večje od potencialnih tveganj za mater in zarodek;
A total of 1649 cases including 546 serious and 1103 non-serious cases corresponding to 6179 ADRs were recorded. 
Zabeležili so skupno 1 649 primerov, vključno s 546 resnimi primeri in 1 103 primeri, ki niso bili resni, kar ustreza 6 179 neželenim reakcijam.
Among 20 patients who presented a reaction of grade IV, six (6) patients died. 
Od 20 bolnikov, pri katerih so zabeležili reakcijo stopnje IV, jih je šest (6) umrlo.
In conclusion the CHMP recommended that no test dose is administered for any of the intravenous containing iron products. 
CHMP je zato priporočil, da se testni odmerek ne daje za nobena intravenska zdravila, ki vsebujejo železo.
Over all studies, 36 hypersensitivity events occurring in 35 patients were reported. 
V vseh študijah so poročali o skupno 36 preobčutljivostnih dogodkih pri 35 bolnikih.
The CHMP discussed the potential that patients with allergies (notably type 1-allergies) may have an increased risk of serious allergic reactions to intravenous iron. 
CHMP je razpravljal o morebitnem potencialu bolnikov z alergijami (zlasti alergijami tipa 1) za povečano tveganje resnih alergijskih reakcij na intravensko železo.
Out of these 6 patients, 5 patients died from a non-allergic reaction a few days after the last injection (e.g. complications of amputation, septic shock, bronchopulmonary disease complication, rhabdomyolysis and pulmonary embolism). 
Od teh 6 bolnikov jih je 5 umrlo zaradi nealergijske reakcije nekaj dni po zadnjem injiciranju (npr. zapleti pri amputaciji, septični šok, zapleti pri bronhopulmonarni bolezni, rabdomioliza in pljučna embolija).
Some of the assessed parenteral iron containing products have a recommendation for a test dose to be administered prior to the final administration. 
Pri nekaterih ocenjenih parenteralnih zdravilih, ki vsebujejo železo, se pred končnim dajanjem priporoča dajanje testnega odmerka.
A total of 34 grade III (14.4%) and 2 grade IV (0.8%) were reported. 
Zabeleženih je bilo skupno 34 primerov stopnje III (14,4 %) in 2 primera stopnje IV (0,8 %).
Of note, hypotension, nausea, vomiting and cramps are often symptoms associated with haemodialysis. 
Opomnimo, da so hipotenzija, navzeja, bruhanje in krči pogosto simptomi, povezani s hemodializo.
Further, a test-dose might give the prescriber a feeling of false assurance that an allergic reaction is unlikely to happen. 
Poleg tega lahko daje testni odmerek zdravniku, ki predpiše zdravilo, napačno zagotovilo, da se alergijska reakcija verjetno ne bo pojavila.
The most frequent AEs experienced by patients in all treatment groups were hypotension (48.7%), nausea (31.9%), vomiting (22.1%) and cramps. 
Najpogostejši neželeni učinki, ki so jih zabeležili pri bolnikih v vseh zdravljenih skupinah, so bili hipotenzija (48,7 %), navzeja (31,9 %), bruhanje (22,1 %) in krči.
In 8 cases of the total 51 life-threatening cases (15.7%; 8/51 cases, one graded as Grade IV), the patient presented with a history of allergy. 
V 8 primerih od skupno 51 življenjsko ogrožajočih primerov (15,7 %; 8/51 primerov, eden razvrščen kot stopnja IV) so imeli bolniki alergijo v anamnezi.
Among the 846 cases with allergic reaction, 55 patients (6.5%) received a dose-test of sodium ferric gluconate prior to the first IV infusion. 
Med 846 primeri z alergijskimi reakcijami je 55 bolnikov (6,5 %) prejelo testni odmerek natrijevega železovega glukonata pred prvo i.v.
According to the MAH, of 9 fatal cases of hypersensitivity reactions reported, six (1.9%, 6/317) were considered to be related. 
Po podatkih imetnika dovoljenja za promet z zdravilom so od 9 zabeleženih smrtnih primerov preobčutljivostnih reakcij menili, da jih je bilo šest (1,9 %, 6/317) povezanih.
In iron deficiency anaemia there were three publications with no anaphylactoid reactions reported. 
O anemiji zaradi pomanjkanja železa so govorile tri publikacije, v katerih niso poročali o nobenih anafilaktoidnih reakcijah.
Other groups of patients included home total parenteral nutrition, those unable to tolerate or respond to oral iron, children with inflammatory bowel disease (IBD), patients with cancer, and pregnant women. 
Med druge skupine bolnikov so spadali bolniki s popolno parenteralno prehrano na domu, bolniki, ki peroralnega železa niso prenašali ali se nanj niso odzivali, otroci z vnetno boleznijo črevesja, bolniki z rakom ter nosečnice.
Of these all patients recovered. 
Od teh so se vsi bolniki opomogli.
All serious cases reported with a primary event other than within the immune system disorders has been reviewed according to the common terminology criteria for adverse events (CTCAE) grade III-V in order not to oversee any severe potential allergic reactions (n=219 additional cases). 
Vse resne primere s primarnim dogodkom, ki ni spadal med motnje imunskega sistema, so pregledali po enotnih terminoloških merilih neželenih dogodkov (CTCAE) stopnje III−V, da ne bi spregledali nobenih morebitnih resnih alergijskih reakcij (n = 219 dodatnih primerov).
One of the ways to classify the hypersensitivity reactions is according to Ring and Messmer1 definition. 
Eden od načinov razvrščanja preobčutljivostnih reakcij je razvrščanje po definiciji Ring in Messmer1.
Over 8,000 patients have been included/treated across all arms in these clinical trials, of whom almost half (N=4,048) received iron sucrose either as the test product or as the reference (comparator) therapy. 
V teh kliničnih preskušanjih je bilo v vseh krakih vključenih/zdravljenih več kot 8 000 bolnikov, od katerih jih je skoraj polovica (N = 4 048) prejela železov saharat kot testno zdravilo ali kot referenčno (primerjalno) zdravljenje.
Iron(III) isomaltoside 1000 
Železov (III) izomaltozid 1000
This is out of around 260 patients being included in clinical studies regarding iron (III) isomaltoside 1000 (studies that also assessed safety parameters). 
To je bilo med približno 260 bolniki, ki so sodelovali v kliničnih študijah glede železovega (III) izomaltozida 1000 (v študijah so ocenili tudi varnostne parametre).
However, due to very limited exposure in utero to sodium ferric gluconate the risk for neonates of developing any abnormality seems unlikely. 
Vendar je zaradi zelo omejene izpostavljenosti in utero natrijevemu železovemu glukonatu tveganje novorojenčkov za razvoj kakršnih koli anomalij malo verjetno.
Six cases were classified as grade V and all led to a fatal outcome due to cardiac arrest, hypotension, or circulatory failure. 
Šest primerov je bilo razvrščenih kot stopnja V in so se končali s smrtnim izidom zaradi zastoja srca, hipotenzije ali cirkulatorne odpovedi.
In the 3% of cases where sodium ferric gluconate was re-administered, the patients experienced the same type of ADRs, mainly allergic reactions without aggravation of the symptoms. 
Pri 3 % primerov, ki so prejeli ponovni odmerek natrijevega železovega glukonata, so bolniki doživeli enako vrsto neželenih reakcij, v glavnem alergijske reakcije brez poslabšanja simptomov.
For pregnancy specifically, as oral iron may be well tolerated in the first trimester of the pregnancy, the CHMP advised that the intravenous iron complexes are not given to pregnant women in the early stages. 
Ker se v nosečnosti peroralno železo dobro prenaša v prvem trimesečju, je CHMP glede nosečnosti predlagal, da se kompleksov intravenskega železa ne uporablja pri nosečnicah v zgodnjih fazah.