natgillin/translations-raw huggingface dataset:
Taking into account the limited information presented from these studies (only summary of these studies were provided), the unclear inclusion/exclusion criteria and statistical analyses employed, no conclusion can be drawn from the data provided.
Glede na omejene podatke iz teh študij (predloženi so bili samo povzetki teh študij), nejasna merila za vključitev/izključitev in uporabljene statistične metode ni mogoče podati zaključkov.
Moreover, recent cases were identified during the French survey conducted in 2011, which show that the risk minimisation measures currently in place are not sufficient to prevent the development of fibrotic reactions.
Poleg tega so v francoski raziskavi, opravljeni leta 2011, odkrili nove primere, kar kaže, da trenutni ukrepi za zmanjševanje tveganja niso zadostni za preprečevanje razvoja fibrotičnih reakcij.
Most of the studies that became available after the granting of the initial marketing authorisation were very old and of poor methodological quality, notably non-randomised and with a low number of patients.
Večina teh študij, ki so bile objavljene po odobritvi prvotnega dovoljenja za promet z zdravilom, je bilo zelo starih in s slabo kakovostjo metodologije, večinoma nerandomizirane in z majhnim številom bolnikov.
• The Committee considered the procedure under Article 31 of Directive 2001/83/EC for ergot derivatives containing medicinal products.
• odbor je obravnaval napotitveni postopek v skladu s členom 31 Direktive 2001/83/ES za zdravila, ki vsebujejo derivate ergot-alkaloidov;
Indeed, this publication described the metaanalysis of 13 double-blind, placebo-controlled, randomised studies performed by the Cochrane Collaboration in 2001.
Ta publikacija je opisala metaanalizo 13 dvojno slepih, s placebom nadzorovanih, randomiziranih študij, ki jo je leta 2001 opravila organizacija Cochrane Collaboration.
However, provision of information on these events is insufficient to avoid that some patients develop fibrosis and ergotism during treatment.
Vendar navedba informacij o teh dogodkih ni zadostna, da bi lahko med zdravljenjem preprečili razvoj fibroze in ergotizma pri nekaterih bolnikih.
The CHMP has considered the totality of the available data on the safety and efficacy of nicergoline.
CHPM je upošteval vse razpoložljive podatke glede varnosti in učinkovitosti nicergolina.
Nicergoline was also given to 17 patients with migraines for prevention of attacks (Prusinski, Wiad.Lek, 1984).
Nicergolin so dajali tudi 17 bolnikom z migrenami za preprečevanje napadov (Prusinski, Wiad.Lek 1984).
• The Committee is of the opinion that the evidence for clinically significant efficacy of nicergoline in the currently assessed indications is very limited, and therefore the potential benefit for patients in these indications is outweighed by the identified risk.
• odbor meni, da so dokazi o klinično pomembni učinkovitosti nicergolina v zvezi s trenutno ocenjevanimi indikacijami izredno omejeni, zato je zgoraj omenjeno tveganje večje od morebitne koristi za bolnike v zvezi s temi indikacijami;
• The Committee considered that a potential causal association between fibrotic reactions or ergotism and nicergoline cannot be excluded.
• odbor je menil, da morebitne vzročne povezave med fibrotičnimi reakcijami ali ergotizmom in nicergolinom ni mogoče izključiti.
For the indication “prophylaxis of migraine headache” the available data in migraine headache are from open label studies in a small number of patients (40 and 17 patients).
Pri indikaciji „preprečevanje migrenskega glavobola“ so na voljo podatki za migrenski glavobol iz odprtih študij z majhnim številom bolnikov (40 in 17 bolnikov).
The main localisation of fibrosis is preferentially pulmonary area and also retroperitoneal and cardiac area.
Glavno mesto fibroze je večinoma pljučno območje, prav tako pa tudi retroperitonealno in srčno območje.
Therefore, the CHMP was of the opinion that it is not possible to rule out the possibility that these actually correspond to the development of ergotism.
Odbor CHMP je zato sklenil, da ni mogoče izključiti možnosti, da so ti simptomi dejansko povezani z razvojem ergotizma.
Overall, the study designs were adequate (randomised, double-blind, placebo-controlled), diagnoses were established according classification criteria at the time of the studies, primary efficacy scales were defined a priori (MMSE, SCAG, ADAS-Cog).
Na splošno so bile zasnove študij primerne (randomizirane, dvojno slepe, s placebom nadzorovane), diagnoze pa so bile postavljene skladno s klasifikacijskimi merili, veljavnimi v času študij, lestvice za primarno učinkovitost pa so bile opredeljene a priori (MMSE, SCAG, ADAS-Cog).
From the approved indications of the nicergoline containing medicinal products the ones that are in the scope of this referral procedure and are approved in at least one Member State are the following (specific wording of the indication may vary from product to product):
Od odobrenih indikacij za zdravila, ki vsebujejo nicergolin, so indikacije, ki spadajo v sklop tega napotitvenega postopka in so odobrene v vsaj eni državi članici, naslednje (natančno besedilo za indikacijo se lahko med zdravili razlikuje):
The improvement, when documented, was observed between 3 and 10 months after nicergoline discontinuation, without corticoid treatment in four cases.
Dokumentirano izboljšanje so opazili od 3 do 10 mesecev po prekinitvi uporabe nicergolina, v štirih primerih brez zdravljenja s kortikosteroidi.
The studies submitted have assessed nicergoline for oral or parenteral use and had heterogeneous efficacy endpoints such as: sensitivity to cold, peripheral blood flow, walking distance, pain, quality of life.
Predložene študije so ocenjevale peroralno ali parenteralno uporabo nicergolina in so uporabile heterogene opazovane dogodke za učinkovitost, kot so: občutljivost za mraz, periferni krvni pretok, prehojena razdalja, bolečina, kakovost življenja.
• Fibrosis is also a slow and insidious reaction that occurs after a long period of treatment and with delayed diagnosis
• je fibroza počasna in zahrbtna reakcija, ki se pojavi dolgo časa po zdravljenju, diagnoza pa je navadno zapoznela.
The majority of them had been previously treated with various anti-migraine drugs like dihydroergotamine, pizotifen and propranolol with unsatisfactory effects.
Večina od njih se je predhodno neuspešno zdravila z različnimi zdravili proti migreni, kot so dihidroergotamin, pizotifen in propranolol.
Therefore, the group was of the opinion that there is not a clearly defined population, which unsatisfactorily responds to standard migraine prophylaxis treatment, where there is a therapeutic need for this substance as alternative/last line treatment.
Skupina je zato zaključila, da ni jasno opredeljene populacije, ki se nezadostno odziva na standardno preprečevanje migrene, kadar obstaja terapevtska potrebna po uporabi te učinkovine kot alternativnega/zadnjega zdravljenja.
The group highlighted that the claimed indication is not used anymore in the clinical practice and that from a clinical viewpoint there is no evidence at present that there is a therapeutic need for this active substance in the treatment of cognitive and neurosensorial impairment in the elderly.
Skupina je izpostavila, da se navedena indikacija v klinični praksi ne uporablja več, zato s kliničnega vidika trenutno ni dokazov, da obstaja terapevtska potreba po tej zdravilni učinkovini pri zdravljenju kognitivne in nevrosenzorične okvare pri starejših.
• The Committee considered that the benefit-risk balance of nicergoline containing products:
• odbor je menil, da razmerje med tveganji in koristmi pri zdravilih, ki vsebujejo nicergolin:
The CHMP noted that an under-notification of the adverse events can also be suspected given that:
Odbor CHMP je omenil, da je lahko prav tako prisoten sum na preredko poročanje neželenih dogodkov, saj:
Fourty (40) patients with migraine were assessed in an open clinical study that became available after the initial marketing authorisation was granted (Prusinski, Wiad.Lek, 1984).
Štirideset (40) bolnikov z migreno so ocenili v odprti klinični študiji, ki je bila objavljena po odobritvi prvotnega dovoljenja za promet z zdravilom (Prusinski, Wiad.Lek 1984).
Scientific conclusions and grounds for variation to the terms of the marketing authorisations or suspension of the marketing authorisations, as applicable, taking into consideration the approved indications for each product
Znanstveni zaključki in podlaga za spremembo pogojev dovoljenj za promet z zdravilom ali začasni umik dovoljenj za promet z zdravilom, kot je ustrezno, pri čemer so se upoštevale odobrene indikacije za posamezno zdravilo
The CHMP considered the MAH's proposal for risk minimisation measures: the inclusion of information related to fibrosis and ergotism in section 4.4 of the Summary of Product Characteristics.
Odbor CHMP je obravnaval predlog imetnika dovoljenja za promet z zdravilom glede ukrepov za zmanjšanje tveganja: vključitev informacij, povezanih s fibrozo in ergotizmom, v poglavje 4.4 Povzetka glavnih značilnosti zdravila.
Four cases of fibrotic events were excluded from the analysis.
Iz analize so izključili štiri primere fibrotičnih dogodkov.
Overall, the CHMP was of the opinion that no situation could justify exposing a patient to risk of fibrosis and ergotism considering the very limited data on efficacy.
Na splošno je odbor CHMP menil, da nobene okoliščine ne upravičijo izpostavitve bolnika tveganju za fibrozo in ergotizem, saj so podatki o učinkovitosti zelo omejeni.
• The suspension of the marketing authorisation for nicergoline containing medicinal products referred to in Annex I in the event that no other indications are approved as part of their marketing authorisation.
• začasni umik dovoljenja za promet z zdravili iz Priloge I, ki vsebujejo nicergolin, če se kot del njihovega dovoljenja za promet z zdravilom ne odobrijo druge indikacije.
Regarding cases of pulmonary reactions, the emerging number of cases and the improvement observed after nicergoline discontinuation in 10 cases with no confounding factor is in favour of a causal role of nicergoline, especially in 5 cases in which improvement was also confirmed by radiography or scanner.
Vedno večje število primerov pljučnih reakcij in izboljšanje, opaženo po prekinitvi uporabe nicergolina pri 10 bolnikih brez sočasnih dejavnikov, podpirata vzročno vlogo nicergolina, predvsem pri 5 primerih, pri katerih se je izboljšanje potrdilo tudi z radiografijo ali slikanjem.
Ninety (90) cases were found to contain terms potentially indicative of symptoms or ergotism, such as paraesthesia, formication, tingling, intestinal/cerebrovascular/peripheral/tongue ischaemia, angina pectoris, coronaropathy, thoracic pain, nausea, vomiting, diarrhoea, abdominal pain, cold sensation, thrombosis, stroke, gangrene, necrosis, vasoconstriction/vasospasm, cyanosis, myalgia, muscular cramps, pain in extremities, vertigo, hypoaesthesia, numbness, headache, confusion, hallucinations.
Devetdeset (90) primerov vsebuje izraze, ki lahko kažejo na simptome ergotizma, kot so parestezija, mravljinčenje, ščemenje, intestinalna/cerebrovaskularna/periferna ishemija, ishemija jezika, angina pektoris, koronaropatija, bolečina v prsnem košu, navzea, bruhanje, diareja, bolečina v trebuhu, občutek mrazenja, tromboza, kap, gangrena, nekroza, vazokonstrikcija/vazospazem, cianoza, mialgija, mišični krči, bolečina v okončinah, vertigo, hipoestezija, otopelost, glavobol, zmedenost, halucinacije.
Therefore, despite the positive conclusions of the authors regarding the progression of visual acuity under a treatment with nicergoline, the CHMP considered that, in the absence of a comparison to a placebo control, no reliable conclusion can be drawn from these clinical results which referred to heterogeneous data based on small series of patients of various eye conditions.
Kljub pozitivnim zaključkom avtorjev glede izboljšanja ostrine vida pri zdravljenju z nicergolinom je odbor CHMP menil, da zaradi odsotnosti primerjave s kontrolo s placebom ni mogoče podati zanesljivih zaključkov na podlagi teh kliničnih rezultatov, ki so se nanašali na različne podatke in temeljili na majhnem številu bolnikov z različnimi očesnimi obolenji.
Among the 21 remaining cases, an association between nicergoline and the fibrotic event or potential fibrotic event could not be excluded.
Pri preostalih 21 primerih ni bilo mogoče izključiti povezave med nicergolinom in fibrotičnim dogodkom ali morebitnim fibrotičnim dogodkom.
In addition, given that fibrosis is a serious life threatening reaction, observed after long duration of treatment with nicergoline (a drug used in indications requiring long duration of treatment), this has an impact on the benefit-risk profile of the products.
Ker je fibroza resna, smrtno nevarna reakcija, ki se pojavi po dolgem času od zdravljenja z nicergolinom (zdravilom, ki se uporablja z indikacijami, ki zahtevajo dolgotrajnega zdravljenja), ima to vpliv na profil razmerja med tveganji in koristmi teh zdravil.
For the indication “ancillary treatment of Raynaud's syndrome”, the submitted studies did not really assess nicergoline in patients with this specific indication, but were rather conducted in patients with peripheral arteriopathy.
Pri indikaciji „dodatno zdravljenje Raynaudovega sindroma“ predložene študije niso dejansko ocenile nicergolina pri bolnikih z zadevno indikacijo, ampak so bile opravljene pri bolnikih s periferno arteriopatijo.
However, the CHMP considered whether some of these studies could be used in support of the indication “ancillary treatment of intermittent claudication in symptomatic peripheral arterial occlusive disease (PAOD Stage II)”.
Kljub temu je odbor CHMP presodil, ali se lahko nekatere od teh študij uporabijo kot podpora za indikacijo „dodatno zdravljenje intermitentne klavdikacije pri simptomatski periferni arterijski okluzivni bolezni (PAOD stadij II)“.
Nicergoline is a semisynthetic ergoline derivative that seems to have an action: (i) as an α1adrenoceptor antagonist, it induces vasodilation and increases arterial blood flow; (ii) it enhances cholinergic and catecholaminergic neurotransmitter function; (iii) it inhibits platelet aggregation; (iv) it promotes metabolic activity, resulting in increased utilization of oxygen and glucose; and (v) it has neurotrophic and antioxidant properties.
Nicergolin je polsintetični derivat ergolina, ki domnevno deluje: kot antagonist α1-adrenoreceptorjev, povzroča vazodilatacijo in poveča arterijski krvni pretok, ii) poveča delovanje holinergičnih ter kateholaminergičnih nevrotransmitorjev, iii) zavira agregacijo trombocitov, iv) spodbuja delovanje presnove, s čimer poveča izkoristek kisika in glukoze ter v) ima nevrotropne in antioksidacijske lastnosti.
In conclusion, the CHMP was of the opinion that a couple of studies have some positive findings in the populations tested but considering the inadequate methodology, the reliability and the clinical relevance of the results is questionable.
Odbor CHMP je zaključil, da imata dve študiji nekaj pozitivnih ugotovitev pri preiskovani populaciji, vendar sta zanesljivost in klinični pomen rezultatov zaradi pomanjkljive metodologije vprašljiva.
This Cochrane review on efficacy of nicergoline was performed in patients with mild to moderate dementia and is therefore also outside the scope of the procedure.
Ta pregled učinkovitosti nicergolina je organizacija Cochrane opravila pri bolnikih z blago do zmerno demenco, zato je zunaj sklopa tega napotitvenega postopka.
• The variation to the terms of the marketing authorisation for nicergoline containing medicinal products referred to in Annex I, to delete the below indications (specific wording of the indication may vary from product to product and from country to country) as well as any relevant reference to these indications, when there are other therapeutic indications approved as part of their marketing authorisation:
• spremembo pogojev dovoljenja za promet z zdravili iz Priloge I, ki vsebujejo nicergolin, tako da se iz informacij o zdravilu izbrišejo spodaj navedene indikacije (natančno besedilo za indikacijo se lahko med zdravili in državami razlikuje) ter druge zadevne reference na te indikacije, kadar so kot del dovoljenja za promet z zdravilom odobrene druge terapevtske indikacije:
Regarding ergotism, there were no cases identified in the MAH's safety database reporting the preferred term ergotism associated with nicergoline.
V varnostni zbirki podatkov imetnika dovoljenja za promet z zdravilom ni bilo nobenih primerov, ki bi poročali o prednostnem izrazu ergotizem, povezan z nicergolinom.
For the indication “ancillary treatment of intermittent claudication in symptomatic peripheral arterial occlusive disease (PAOD Stage II)” no data were submitted and as a result was considered as unsupported by the CHMP.
Za indikacijo „dodatno zdravljenje intermitentne klavdikacije pri simptomatski periferni arterijski okluzivni bolezni (PAOD stadij II)“niso bili predloženi nobeni podatki, zato je odbor CHMP menil, da ni utemeljena.
The MAHs considers that the most comprehensive review of nicergoline efficacy was completed in a meta-analysis performed in 2008 by Winblad et al.
Imetniki dovoljenj za promet z zdravilom menijo, da je bil najobsežnejši pregled učinkovitosti nicergolina opravljen v metaanalizi, ki so jo leta 2008 izvedli Winblad in sodelavci.
The MAH further provided information on six clinical comparative studies in senile cerebral insufficiency and a short description of a non-comparative study and three observational studies in support of the efficacy of nicergoline in a specific indication “symptomatic treatment of mild cognitive impairment of vascular origin in the elderly”.
Imetnik dovoljenja za promet z zdravilom je prav tako predložil podatke šestih kliničnih primerjalnih študij senilne cerebralne insuficience in kratek opis neprimerjalne študije ter treh opazovalnih študij, ki naj bi podprle učinkovitost nicergolina pri zadevni indikaciji „simptomatsko zdravljenje blage kognitivne okvare žilnega izvora pri starejših“.
The CHMP noted that none of the studies was designed to address the specific indication under question (symptomatic treatment of chronic pathological cognitive and neurosensorial impairment in elderly (excluding Alzheimer's disease and other dementia)), and that the data is further weakened by publication biases and changes in the understanding of proper criteria for current diagnoses.
CHMP je ugotovil, da nobena od teh študij ni bila načrtovana za obravnavo zadevne indikacije (simptomatsko zdravljenje kronične patološke kognitivne in nevrosenzorične okvare pri starejših (izključujoč Alzheimerjevo bolezen in druge oblike demence)) in da je kredibilnost podatkov dodatno zmanjšana zaradi pristranskosti publikacij ter sprememb v razumevanju ustreznih meril za trenutne diagnoze.
In addition, a scientific advisory group (SAG) was convened in December 2012 at the request of the CHMP during which the experts discussed, based on their clinical experience, whether this substance plays a role in the symptomatic treatment of chronic pathological cognitive and neurosensorial impairment in elderly (excluding Alzheimer's disease and other dementia).
Znanstveno svetovalna skupina je na pobudo odbora CHMP decembra 2012 sklicala sestanek, na katerem so strokovnjaki na podlagi svojih kliničnih izkušenj razpravljali o tem, ali ima ta učinkovina vlogo pri simptomatskem zdravljenju kronične patološke kognitivne in nevrosenzorične okvare pri starejših (izključujoč Alzheimerjevo bolezen in druge oblike demence).
For the indications “ancillary treatment of visual acuity decrease and visual field disturbances presumably of vascular origin” and “acute retinopathies of vascular origin” the CHMP noted that positive clinical results (in particular regarding the progression of visual acuity) were described mainly in one open long-term study in the context of an ambulatory ophthalmological practice that involved 213 patients with heterogeneous pathologies (e.g. retina degeneration, inflammatory diseases of the retina and of the optic nerve, venous and arterial vessels occlusions, glaucoma, etc) (Hasslinger, 1986).
Pri indikacijah „dodatno zdravljenje zmanjšane ostrine vida in motenj vidnega polja, za katere se domneva, da so žilnega izvora“ in „akutna retinopatija žilnega izvora“ je odbor CHMP opazil, da so bili pozitivni klinični rezultati (predvsem glede izboljšanja ostrine vida) večinoma opisani v eni odprti dolgotrajni študiji v sklopu ambulantne oftalmološke prakse, ki je vključevala 213 bolnikov z različnimi patologijami (npr. degeneracija mrežnice, vnetne bolezni mrežnice in optičnega živca, venske ter arterijske okluzije, glavkom itd.) (Hasslinger 1986).
The Committee concluded that the benefit-risk balance of nicergoline containing products is not favourable pursuant to Article 116 of Directive 2001/83/EC for symptomatic treatment of chronic pathological cognitive and neurosensorial impairment in elderly (excluding Alzheimer's disease and other dementia), for ancillary treatment of intermittent claudication in symptomatic peripheral arterial occlusive disease (PAOD Stage II), for ancillary treatment of Raynaud's syndrome, for ancillary treatment of visual acuity decrease and visual field disturbances presumably of vascular origin, for acute retinopathies of vascular origin and for prophylaxis of migraine headache.
Odbor je zaključil, da skladno s členom 116 Direktive 2001/83/ES razmerje med tveganji in koristmi pri zdravilih, ki vsebujejo nicergolin, ni ugodno za simptomatsko zdravljenje kronične patološke kognitivne in nevrosenzorične okvare pri starejših (izključujoč Alzheimerjevo bolezen in druge oblike demence), dodatno zdravljenje intermitentne klavdikacije pri simptomatski periferni arterijski okluzivni bolezni (PAOD stadij II), dodatno zdravljenje Raynaudovega sindroma, dodatno zdravljenje zmanjšane ostrine vida in motenj vidnega polja, za katere se domneva, da so žilnega izvora, akutno retinopatijo žilnega izvora in preprečevanje migrenskega glavobola.
• Adverse drug reaction with a substance marketed for a long time is generally less reported
• se o neželenem učinku pri učinkovini, ki je v prometu dolgo časa, navadno poroča redkeje;
These data were considered insufficient by the CHMP to conclude on a beneficial efficacy of nicergoline in the prophylaxis of migraine headache.
Odbor CHMP je menil, da so ti podatki nezadostni, da bi lahko sklepali o koristni učinkovitosti nicergolina pri preprečevanju migrenskih glavobolov.
The CHMP was of the opinion that overall based on these data there is some evidence of positive effects of nicergoline on cognition and behaviour in patients with senile cerebral insufficiency of different origins.
CHMP je menil, da je na splošno v teh podatkih nekaj dokazov za pozitivne učinke nicergolina na kognicijo in vedenje pri bolnikih s senilno cerebralno insuficienco različnega izvora, vendar klinični pomen ni znan.
• Symptomatic treatment of veno-lymphatic insufficiency
• Simptomatsko zdravljene veno-limfatične insuficience.
This does not exactly reflect the indication supported by the MAH.
To pa se ne nanaša natančno na indikacijo, za podporo katere je imetnik dovoljenja za promet z zdravilom predložil podatke.
The CHMP concluded that, as result, no conclusion on efficacy of nicergoline as “symptomatic treatment of chronic pathological cognitive and neurosensorial impairment in elderly (excluding Alzheimer's disease and other dementia)” can be drawn from the data provided.
CHMP je zaključil, da posledično iz predloženih podatkov ni mogoče sklepati na učinkovitost nicergolina pri „simptomatskem zdravljenju kronične patološke kognitivne in nevrosenzorične okvare pri starejših (izključujoč Alzheimerjevo bolezen in druge oblike demence)“.
− Is not favourable for prophylaxis of migraine headache.
− ni ugodno za preprečevanje migrenskega glavobola.
− Is not favourable for symptomatic treatment of chronic pathological cognitive and neurosensorial impairment in elderly (excluding Alzheimer's disease and other dementia).
− ni ugodno za simptomatsko zdravljenje kronične patološke kognitivne in nevrosenzorične okvare pri starejših (izključujoč Alzheimerjevo bolezen in druge oblike demence),