natgillin/translations-raw huggingface dataset:
The double-blind, randomised, placebo-controlled studies were old and generally not carried out with the current up-to-date methodology.
Dvostruko slijepa, randomizirana, placebom kontrolirana ispitivanja bila su zastarjela i načelno nisu provedena u skladu s aktualnom, suvremenom metodologijom.
For the indication “symptomatic treatment of veno-lymphatic insufficiency” very few studies have been conducted.
Za indikaciju „simptomatsko liječenje vensko limfne insuficijencije“ proveden je vrlo mali broj ispitivanja.
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.
Načelno, mišljenje je CHMP-a da niti jedna situacija ne može opravdati izlaganje bolesnika riziku od fibroze i ergotizma uzimajući u obzir vrlo ograničene podatke o djelotvornosti.
The open label study (Wenzel-E et al, 1989) that became available after the granting of the initial marketing authorisation discusses the use of dihydroergotamine in venous insufficiency.
Otvoreno ispitivanje (Wenzel-E et al, 1989.), koje je postalo dostupno nakon izdavanja prvotnog odobrenja za stavljanje lijeka u promet, razmatra uporabu dihidroergotamina za vensku insuficijenciju.
Ergot derivatives are recognised as being capable of inducing fibrosis, in particular heart valve fibrosis.
Prepoznata je sposobnost derivata ergota za induciranje fibroze, a posebice fibroze srčanog zaliska.
• Ancillary treatment of visual acuity decrease and visual field disturbances presumably of vascular origin
• pomoćno liječenje smanjenja oštrine vida i poremećaja vidnoga polja za koje se pretpostavlja da su vaskularnog porijekla
Based on the clinical experience the group considered that dihydroergotamine has only been used rarely for the treatment of orthostatic hypotension with no clear benefit to the patients.
Na temelju kliničkog iskustva grupa je smatrala da se dihidroegotamin koristio samo rijetko za liječenje ortostatske hipotenzije bez jasne koristi za bolesnike.
To conclude, ergotism is an adverse reaction of ergot derivative drugs well-known to occur in a context of overdose or interaction.
Zaključno, ergotizma je nuspojava lijekova koji sadrže derivate ergota, za koju je poznato da nastupa u kontekstu predoziranja ili interakcije.
Overall, 8 cases of fibrotic adverse reactions from a French survey conducted in 2011 and 50 cases among the 75 cases reported by the MAHs have been considered as potentially related to dihydroergotamine including 24 with no confounding factor.
Načelno se za 8 slučaja fibrotičkih nuspojava iz francuskog ispitivanja provedenog 2011. godine i 50 slučajeva od 75 slučaja, koje su prijavili nositelji odobrenja, smatralo da su potencijalno povezani s dihidroergotaminom, uključujući 24 slučaja sa čimbenikom zabune.
After 4 months of treatment, the attack frequency decreased by 2.0 ± 1.6 (-60.0%) with dihydroergotamine versus 1.7 ± 1.5 (-48.8%) with placebo (p = 0.014 for the relative variations).
Nakon 4 mjeseca liječenja učestalost napadaja smanjila se za 2,0 + 1,6 (-60,0 %) s dihidroergotaminom u odnosu na 1,7 + 1,5 (-48,8%) s placebom (p=0,014 za relativne varijacije).
Based on the clinical experience the group considered that no special population exists that could benefit from the treatment with this active substance in the prophylaxis of migraine headache.
Na temelju kliničkog iskustva grupa smatra da ne postoji posebna populacija koja bi imala koristi od liječenja s ovom djelatnom tvari u profilaksi migrenske glavobolje.
Therefore, even if it is highly pharmacologically plausible that ergot derivatives acting as 5HT2B receptor agonists may induce "serotonergic" valve disease similar to that induced by carcinoid tumours or fibrotic lesions of other tissues, it must be remembered that some ergot derivatives are not 5-HT2B receptor agonists.
Stoga, čak i ako je farmakološki vrlo plauzibilno da derivati ergota, koji djeluju kao agonisti 5-HT2B receptora, mogu inducirati „serotonergijsku“ bolest zaliska sličnu onoj koju induciraju karcinoidni tumori ili fibrotičke lezije drugih tkiva, treba upamtiti da pojedini derivati ergota nisu agonisti 5-HT2B receptora.
Overall, the varying affinity for serotoninergic receptors with the different ergot derivatives and the therapeutic doses used may explain the differences observed for notification rates for the fibrotic reactions.
Ukupno gledano, varirajući afinitet serotoninskih receptora s različitim derivatima ergota i terapijskim dozama koje se koriste, može objasniti razlike uočene u prijavljenim stopama za fibrotičke reakcije.
Moreover, safety data provided by some MAHs are incomplete (gap between reviewing period and marketing period of the product) and it cannot be excluded that cases reported with their products are lacking.
Nadalje, podaci o sigurnosti koje su dostavili nositelji odobrenja nisu bili potpuni (vremenski odmak između razdoblja pregleda i razdoblja stavljanja lijeka u promet) te se ne može isključiti da ne nedostaju slučajevi prijavljeni s njihovim lijekovima.
In conclusion, the studies provided by the MAHs were not carried out with up-to-date methodology.
Zaključno, ispitivanja koja su proveli nositelji odobrenja nisu provedena u skladu sa suvremenom metodologijom.
The efficacy of dihydroergotamine in the acute treatment of migraine attack is not within the scope of this referral and will not be discussed.
Djelotvornost dihidroergotamina u akutnom liječenju napadaja migrene nije predmetom ovog postupka upućivanja i neće se razmatrati.
The literature data indicate a possible efficacy of oral dihydroergotamine in migraine prophylaxis, but definite scientific proof remains weak.
Bibliografski podaci ukazuju na moguću djelotvornost oralnog dihidroergotamina u profilaksi migrene, no konačan znanstveni dokaz i dalje je neuvjerljiv.
The authorised oral doses seem to have weak or null efficacy due to the low bioavailability of the drug.
Čini se da su odobrene oralne doze imale slabo ili nikakvo djelovanje zbog male bioraspoloživosti lijeka.
A review of all other available data (i.e. literature data, pre-clinical data, and other clinical data including epidemiological studies) that were relevant to evaluate the risk of fibrosis was provided where possible.
Ako je bilo moguće dostavljen je pregled svih drugih dostupnih podataka (odnosno bibliografskih podataka, predkliničkih podataka, i ostalih podataka uključujući epidemiološka ispitivanja), koji su relevantni za ocjenu rizika fibroze.
In these studies, dihydroergotamine seems to have some efficacy only by injection route or at doses higher than the authorised dose.
Čini se da je u ovim ispitivanjima dihidroegotamin djelovao u određenoj mjeri samo na putu injekcije ili pri dozama većima od odobrene doze.
Some symptoms related to ergotism may be confounded with migraine symptoms and thus not reported as an adverse drug reaction.
Određeni simptomi povezani s ergotizmom mogli su biti zamijenjeni s migrenskim simptomima te stoga nisu prijavljeni kao nuspojave na lijek.
− Is not favourable for orthostatic hypotension.
nije povoljan za ortostatsku hipotenziju.
With regard to the risk of ergotism, the review of cases provided by the MAHs was not exhaustive and the methodology used to retrieve cases of ergotism was unclear for most of the MAHs.
Vezano uz rizik od ergotizma, pregled slučajeva koje su dostavili nositelji odobrenja nisu bili iscrpni i metodologija koja se koristila za pronalazak slučajeva ergotizma bila je nejasna za većinu nositelja odobrenja.
However, a total of 134 cases of ergostim or symptoms potentially related to ergotism have been reported by the MAHs.
No, nositelji odobrenja prijavili su ukupno 134 slučaja ergotizma ili simptoma potencijalno povezanih s ergotizmom.
The marketing authorisation holders (MAHs) submitted all available efficacy data from clinical trials and observational studies, including data that became available since the granting of the initial marketing authorisation.
Nositelji odobrenja za stavljanje lijeka u promet (nositelji odobrenja) dostavili su sve dostupne podatke o djelotvornosti iz kliničkih ispitivanja i opservacijskih ispitivanja, uključujući i podatke koji su postali dostupni od trenutka izdavanja prvotnog odobrenja za stavljanje lijeka u promet.
With regard to the reported cases, the CHMP noted the problem of under-reporting for this product considering the period that it is on the market.
Vezano uz prijavljene slučajeve, CHMP uočio je problem s nedostatnim prijavljivanjem za ovaj lijek, ako se uzme u obzir razdoblje tijekom kojeg je lijek u prometu.
Likewise, the efficacy of dihydroergotamine administered by subcutaneous, intramuscular or intravenous injection or intranasal spray is not within the scope of this referral and will be not discussed.
Podjednako tako, djelotvornost dihidroergotamina koji se primjenjuje potkožnom, intramišićnom ili intravenoznom injekcijom ili sprejem za nos nije predmetom ovog postupka upućivanja i neće se razmatrati.
In addition, it was the IV formulation of the product that was used and not the oral formulation that is in the scope of this referral procedure.
Nadalje, korištena je intravenozna formulacija lijeka, a ne oralna formulacija koja je predmetom postupka upućivanja.
For all products the concomitant use of CYP3A inhibitors is contraindicated with dihydroergotamine (section 4.5) and for others the concomitant use of vasonconstrictive agent is also contraindicated.
Za sve je lijekove kontraindicirana istovremena uporaba CYP3A inhibitora s dihidroergotaminom (dio 4.5), te je za druge kontraindicirana istovremena uporaba s vazokonstriktivnim sredstvom.
Moreover, given the seriousness of ergotism and its consequences (sequelae, need for surgery, amputation), the young age of the patients with symptoms of ergotism and the short time to onset of the reaction, the safety profile of dihydroergotamine is highly questionable.
Nadalje, uzimajući u obzir ozbiljnost ergotizma i njegovih posljedica (sekvele, potrebe za kirurškim zahvatom, amputacije), mlada dob bolesnika sa simptomima ergotizma i kratko vrijeme pojave reakcije, vrlo je upitan sigurnosni profil dihidroergotamina.
Systolic blood pressure of the placebo and the dihydroergotamine group differed already at baseline.
Sistolički krvni tlak placebo grupe i grupe koja je uzimala dihidroegotamin razlikovao se već u osnovnoj vrijednosti.
Agonism to 5-HT2B receptors induces a proliferative response and mitogenicity of the cells expressing this receptor leading to fibrogenesis.
Agonizam 5-HT2B receptora inducira proliferativan odgovor i mitogenost stanica, koju ispoljava ovaj receptor, što rezultira fibrogenezom.
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 treatment of orthostatic hypotension.
Nadalje, znanstvena savjetodavna grupa (SAG) sazvana je u prosincu 2012. godine na zahtjev CHMPa, tijekom koje su stručnjaci, na temelju svojeg kliničkog iskustva, raspravljali igra li ova tvar značajnu ulogu u liječenju ortostatske hipotenzije.
On the efficacy side for the indication “prophylaxis of migraine headache” data derive from a few randomised, double-blind, placebo-controlled studies or double-blind non placebo-controlled and open label studies, the majority of which was conducted after the granting of the initial marketingauthorisation.
Vezano uz pitanje djelotvornosti za indikaciju „profilaksa migrenske glavobolje“, podaci potječu iz nekoliko randomiziranih, dvostruko slijepih, placebom kontroliranih ispitivanja ili dvostruko slijepih placebom nekontroliranih otvorenih ispitivanja, od kojih je većina provedena nakon izdavanja prvotnog odobrenja za stavljanje lijeka u promet.
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 prophylaxis of migraine headache.
Nadalje, znanstvena savjetodavna grupa (SAG) sazvana je u prosincu 2012. godine na zahtjev CHMPa, tijekom koje su stručnjaci, na temelju svojeg kliničkog iskustva, raspravljali igra li ova tvar značajnu ulogu u profilaksi migrenske glavobolje.
In the only recent, large study with appropriate design (double-blind, placebo-controlled, 5-month treatment study) (PROMISE study) that became available after the granting of the initial marketing authorisation, the evidence for efficacy of dihydroergotamine in the prevention of migraine has not been demonstrated as there was no statistically significant difference between dihydroergotamine and placebo.
U jedinom novijem, velikom ispitivanju odgovarajućeg dizajna (dvostruko slijepo, placebom kontrolirano ispitivanje 5-mjesečnog liječenja) (ispitivanje PROMISE), koje je postalo dostupno nakon izdavanja prvotnog odobrenja za stavljanje lijeka u promet, nije pružen dokaz djelotvornosti dihidroergotamina u prevenciji migrene s obzirom da nije bilo statistički značajne razlike između dihidroergotamina i placeba.
• Adverse drug reactions with a substance marketed for a long time are generally less reported
• se nuspojave s tvari stavljenom u promet za dugoročno uzimanje načelno manje prijavljuju,
Moreover, the number of cases reported with a contraindicated concomitant drug reveals that information in the SmPC is not sufficient to avoid an exposition of the patient to the serious risk of ergotism.
Nadalje, broj prijavljenih slučajeva s kontraindiciranim istovremenim lijekovima otkriva da informacije sadržane u sažetku opisa svojstava lijekova nisu dostatne kako bi se izbjeglo izlaganje bolesnika ozbiljnog rizika ergotizma.
There is little evidence from double-blind, placebo-controlled clinical trials and no uniform picture of the efficacy of oral ergotamine compared to placebo or other substances in the prevention of migraine emerges from these studies since studies reported both positive and negative results.
Postoji malo dokaza iz dvostrukih slijepih, placebom kontroliranih kliničkih ispitivanja, te jednoobrazna slika djelotvornosti oralnog ergotamina u usporedbi s placebom ili drugim tvarima u prevenciji migrene ne proizlazi iz ovih ispitivanja s obzirom da su ispitivanja prijavila pozitivne i negativne rezultate.
The frequency of attacks of migraine (the primary efficacy criteria) was not statistically significant (dihydroergotamine group (-1.84 ± 1.55) vs. placebo group (-1.67 ± 1.49) (p=0.220)).
Učestalost napadaja migrene (primarni kriterij djelotvornosti) nije bila statistički značajna (grupa koja je primala dihidroergotamin (-1,84 + 1,55) u donosu na grupu koja je primala placebo (-1,67 + 1,49) (p=0,220)).
• Ancillary treatment of Raynaud's syndrome
• pomoćno liječenje Raynaudovog sindroma
Therefore, other mechanisms inducing fibrosis cannot be excluded, which suggests a causal link between fibrosis and agonism of 5-HT2A and 5-HT1B receptors and also plausible effect on serotonin transporter.
Stoga, se ne mogu isključiti drugi mehanizmi koji induciraju fibrozu, što nagovještava kauzalnu vezu između fibroze i agonizma 5-HT2A i 5-HT1B receptora, te također plauzibilan učinak na serotoninski prijenosnik.
The CHMP also stated that the study population, consisting only of drug induced orthostatic hypotension patients, is not representative to conclude on the efficacy of dihydroergotamine in the total population of orthostatic hypotension patients.
CHMP je također naveo da populacija ispitivanja, koja se sastojala samo od bolesnika oboljelih od ortostatske hipotenzije inducirane lijekom, nije reprezentativna za donošenje zaključaka o djelotvornosti dihidroegotamina u ukupnoj populaciji bolesnika oboljelih od ortostatske hipotenzije.
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
Dodatak II Znanstveni zaključci i razlozi za izmjenu uvjeta odobrenja za stavljanje lijeka u promet ili suspenziju odobrenja za stavljanje lijeka u promet, ovisno o slučaju, uzimajući u obzir odobrene indikacije za svaki lijek
However, given the number of cases reported with dihydroergotamine, with symptoms related to ergotism (despite probable lacking cases) even when dihydroergotamine is used as recommended (no overdosage, no contraindicated drug, and short time treatment), the high pharmacological plausibility and a suggestive chronology in most of the cases, it is considered that patients are exposed to a high risk of ergotism when treated with dihydroergotamine.
No, s obzirom na broj slučajeva prijavljenih s dihidroergotaminom, za simptome povezane s ergotizmom (usprkos izglednim manjkavim slučajevima), čak i ako se dihidroergotamin koristi kako je preporučeno (bez predoziranja, bez kontraindiciranih lijekova i kratko vrijeme liječenja), visoku farmakološku plauzibilnost i sugestivnu kronologiju u većini slučajeva, smatra se da su bolesnici izloženi velikom riziku od ergotizma prilikom liječenja dihidroergotaminom.
In the preventive treatment of migraine, dihydroergotamine is administered orally for long term.
U slučaju preventivnog liječenja migrene, dihidroergotamin primjenjuje se oralno tijekom dugog vremenskog razdoblja.
In addition, given that fibrosis is a serious life threatening reaction, observed after long duration of treatment with dihydroergotamine (a drug used in indications requiring long duration of treatment) this has an impact on the benefit-risk balance of the products.
Uz to, s obzirom da je fibroza ozbiljna reakcija opasna po život, uočena nakon dugotrajnog liječenja dihidroergotaminom (lijek koji se koristi za indikacije koje zahtijevaju dugotrajno liječenje), ovo ima učinak na profil omjera koristi i rizika lijekova.
• Orthostatic hypotension
• ortostatska hipotenzija
The efficacy of dihydroergotamine in the prevention of migraine in this study has not been demonstrated taking into account that there was no statistically significant difference between dihydroergotamine and placebo with respect to the reduction of the frequency of migraine attacks (the primary efficacy criterion) in the overall population.
Djelotvornost dihidroergotamina u prevenciji migrene u ovom ispitivanju nije prikazana uzimajući u obzir da ne postoji statistički značajna razlika između dihidroergotamina i placeba s obzirom na smanjenje učestalosti napadaja migrene (primarni kriterij djelotvornosti) u ukupnoj populaciji.
Overall summary of the scientific evaluation of dihydroergotamine containing medicinal products (see Annex I)
Cjelokupan sažetak znanstvene ocjene lijekova koji sadrže dihidroergotamin (vidjeti Dodatak I)
Some of them were conducted with the intravenous administration which is not in the scope of this referral procedure for dihydroergotamine.
Pojedina su ispitivanja provedena intravenoznom primjenom, što nije predmetom ovog postupka upućivanja za dihidroergotamin.
The CHMP noted the position of several MAHs that there is not enough evidence to support an indication of oral dihydroergotamine in the symptomatic treatment of veno-lymphatic insufficiency and was of the opinion that no scientific conclusion can be drawn regarding the efficacy of dihydroergotamine based on these study results.
CHMP je naglasio stav nekoliko nositelja odobrenja da ne postoji dovoljno dokaza koji idu u prilog indikaciji oralnog dihidroergotamina za simptomatsko liječenje vensko limfne insuficijencije, te je mišljenja da se znanstveni zaključci ne mogu donijeti u svezi djelotvornosti dihidroergotamina na temelju ovih ispitivanja.
• Symptomatic treatment of chronic pathological cognitive and neurosensorial impairment in elderly
• simptomatsko liječenje kroničnog patološkog kognitivnog i neurosenzoričkog oštećenja u starijih osoba (isključujući Alzheimerovu bolest i druge demencije)
To conclude, given the cases reported for a reaction difficult to diagnose early (delayed symptoms) and probably under reported, the use of the drug at an approved dosage, added to a plausible pharmacological profile, dihydroergotamine is considered to be strongly associated with a risk of fibrotic reactions.
Zaključno, s obzirom na teško rano dijagnosticiranje (kasni simptomi) slučajeva prijavljenih za reakciju i vjerojatno su premalo prijava, te uporabu lijeka u odobrenoj dozi, uz plauzibilan farmakološki profil, dihidroergotamin se smatra usko povezanim s rizikom od fibrotičke reakcije.
− Is not favourable for prophylaxis of migraine headache.
nije povoljan za profilaksu migrenske glavobolje.
Although significant reduction in venous capacity, capillary flow of erythrocytes and peak flow of reactive hyperemia were demonstrated, due to a very small study group, the uncontrolled design and other methodological limitations, the CHMP could not draw any conclusion on the efficacy of dihydroergotamine.
Iako je demonstrirano značajno smanjenje u venskom kapacitetu, kapilarnom protoku eritrocita i vršnom protoku reaktivne hiperemije, CHMP nije mogao donijeti zaključak o djelotvornosti dihidroergotamina zbog vrlo male grupe na kojoj je provedeno ispitivanje, nekontroliranog dizajna i drugih metodoloških ograničenja.
The CHMP also noted the position of several MAHs that there is not enough evidence to support an indication of oral dihydroergotamine in orthostatic hypotension.
CHMP je također napomenuo stajalište nekoliko nositelja odobrenja da ne postoji dovoljno dokaza koji podržavaju indikaciju oralnog dihidroegotamina za ortostatsku hipotenziju.
Grounds for the suspension/variation to the terms of the marketing authorisations
Razlozi za suspenziju/varijaciju uvjeta odobrenja za stavljanje lijeka u promet Budući da
No significant improvement over placebo was observed in the subset of patients with unaffected QOL.
U podgrupi bolesnika s nepromijenjenim QOL nije uočeno značajno poboljšanje u odnosu na placebo.
In the only recent, large study with appropriate design (PROMISE study) there was no statistically significant difference between dihydroergotamine and placebo with respect to the reduction of the frequency of migraine attacks (the primary efficacy criterion) in the overall population.
U jedinom novijem, velikom ispitivanju odgovarajućeg dizajna (ispitivanje PROMISE) nema statistički značajne razlike između dihidroergotamina i placeba s obzirom na smanjenje učestalosti napadaja migrene (primarni kriterij djelotvornosti) u ukupnoj populaciji.
These included restricting the therapeutic indications, recommending close monitoring of patients and the issuing of a DHPC.
CHMP je razmotrio prijedlog nositelja odobrenja za mjere za smanjivanje rizika, koje uključuju ograničavanje terapijskih indikacija, preporuku pažljivog praćenja bolesnika i izdavanje pisma upućenog zdravstvenim djelatnicima.
• The Committee considered that the benefit-risk balance of oral dihydroergotamine containing products:
• Povjerenstvo smatra da omjer koristi i rizika lijekova koji sadrže oralni dihidroergotamin:
The number of patients included was small and the duration of treatment was too short and the clinical efficacy parameters used are not in line with the European Guidelines on clinical investigation of medicinal products for the treatment of migraine.
Korišteni parametri kliničke djelotvornosti nisu u skladu s Europskim smjernicama za kliničko istraživanju lijekova koji se koriste za liječenje migrene.
• Symptomatic treatment of veno-lymphatic insufficiency
• simptomatsko liječenje vensko limfne insuficijencije
For the percentage of responders (61.1% in the dihydroergotamine group vs. 55.9% in the placebo group) the difference was not statistically significant.
Razlika nije bilo statistički značajna za određeni postotak odgovarača (61,1% u grupi koja je primala dihidroergotamin u odnosu na 55,9% u grupi koja je primala placebo).
• Prophylaxis of migraine headache
• profilaksa migrenske glavobolje
In some published literature, they are considered as aetiology of retroperitoneal fibrosis (P. Meier et al, La fibrose rétropéritonéale, une maladie inflammatoire méconnue.
Meier et al, La fibrose rétropéritonéale, une maladie inflammatoire méconnue.
− Is not favourable for symptomatic treatment of veno-lymphatic insufficiency.
nije povoljan za simptomatsko liječenje vensko limfne insuficijencije.