natgillin/translations-raw huggingface dataset:
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.
The relationship between fibrosis and serotoninergic receptor activation, particularly 5-HT2B receptors by ergot derivatives is extensively described in the literature. 
U literaturi je dostupan opsežan opis odnosa između fibroze i aktivacije serotoninergijskog receptora, posebice 5-HT2B receptora, derivatima ergota.
These co-suspected drugs are known to induce fibrosis. 
Poznato je da ovi lijekovi, koji mogu izazvati iste nuspojave, mogu uzrokovati fibrozu.
• The variation to the terms of the marketing authorisation for dihydroergotamine containing medicinal products referred to in Annex I, to delete the below indications from the Product Information (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 in the Product Information, when there are other therapeutic indications approved as part of their marketing authorisation: 
I kako bi se obrisale niže navedene indikacije (specifična formulacija indikacija može varirati od proizvoda do proizvoda i od države do države) kao i bilo koja relevantna referenca na ove indikacije, kada postoje druge terapijske indikacije odobrene kao dio njihovog odobrenja za stavljanje lijeka u promet: profilaksa migrenske glavobolje. ortostatska hipertenzija. simptomatsko liječenje vensko limfne insuficijencije.
The Committee concluded that the benefit-risk balance of dihydroergotamine containing products for oral use is not favourable pursuant to Article 116 of Directive 2001/83/EC for prophylaxis of migraine, for orthostatic hypotension and for symptomatic treatment of veno-lymphatic insufficiency. 
Direktive 2001/83/EC za profilaksu migrenske glavobolje, ortostatsku hipotenziju i za simptomatski liječenje vensko limfne insuficijencije.
• The suspension of the marketing authorisation for dihydroergotamine containing medicinal products referred to in Annex I in the event that no other indications are approved as part of their marketing authorisation. 
• Suspenzija odobrenja za stavljanje lijeka u promet za lijekove koji sadrže dihidroergotamin, a koji su navedeni u Dodatku
What does the black triangle mean? 
Što znači crni trokut?
For more information, visit www.ema.europa.eu 
Za više informacija posjetite www.ema.europa.eu
How to report side effects 
Kako prijavljivati nuspojave
Why are medicines monitored after they are approved? 
Zašto se lijekove prati nakon što su odobreni?
The European Union (EU) has introduced a new way of identifying medicines that are being monitored particularly closely. 
Europska unija (EU) uvela je novi postupak označavanja lijekova koje se posebno prati.
They may have other diseases and they may be taking other medicines. 
Ti bolesnici mogu imati druge bolesti i mogu uzimati druge lijekove.
This is generally because there is less information available about them compared with other medicines, for example because they are new on the market. 
To je općenito iz razloga što je o tom lijeku dostupno manje informacija nego o drugim lijekovima, primjerice jer su novi na tržištu.
It does not mean that the medicine is unsafe. 
To ne znači da lijek nije siguran za primjenu.
In a real-life setting, a larger and more diverse group of patients will use the medicine. 
U stvarnom životu veća i raznolikija skupina bolesnika koristit će lijek.
"This medicinal product is subject to additional monitoring." 
„Ovaj se lijek pod dodatnim praćenjem.”
It is therefore vital that the safety of all medicines continues to be monitored while they are on the market. 
Stoga je ključno nastaviti nadzor sigurnost svih lijekova dok su na tržištu.
Clinical trials usually involve a limited number of patients for a defined time period in controlled conditions. 
Klinička ispitivanja obično uključuju ograničeni broj bolesnika tijekom definiranog vremenskog razdoblja u kontroliranim uvjetima.
Only medicines whose benefits have been shown to be greater than their risks can be marketed. 
Samo lijekove za koje je dokazano da im je korist veća od rizika mogu može se staviti u promet.
This ensures that patients can access the treatments they need without being exposed to unacceptable side effects. 
To bolesnicima osigurava pristup potrebnom liječenju bez izlaganja neprihvatljivim nuspojavama.
You can report side effects to your doctor, pharmacist or nurse. 
Nuspojave možete prijaviti svom liječniku, ljekarniku ili medicinskoj sestri.
Examples of medicines under additional monitoring include new medicines authorised since the start of 2011 and medicines for which regulators require more studies to be carried out, e.g. on long-term use or on rare side effects seen in clinical trials. 
Primjeri lijekova koje se dodatno prati uključuju nove lijekove odobrene nakon početka 2011. godine i lijekove za koje nadležna tijelai službenici zahtijevaju provođenje dodatnih ispitivanja, primjerice o dugoročnoj upotrebi ili o rijetkim nuspojavama primijećenim u kliničkim ispitivanjima.
You should report any suspected side effects with a medicine you are taking, particularly if it displays the black triangle. 
Trebate prijaviti bilo koju sumnju na nuspojave lijeka koji uzimate, posebice ako je na lijeku prikazan crni trokut.
However, medicines with the black triangle are being monitored even more closely than others. 
Međutim, lijekove označene crnim trokutom prati se još intenzivnije od ostalih lijekova.
All medicines are carefully monitored after they are placed on the EU market. 
Svi se lijekovi pomno prate nakon stavljanja u promet u EU-u.
European regulatory authorities decide to authorise medicines after assessing the results of laboratory tests and clinical trials. 
Europska regulatorna tijela odlučuju odobriti lijekove nakon ocjene njihove koristi i rizika na temelju rezultata kliničkih ispitivanja i laboratorijskih testiranja.
These medicines have a black inverted triangle displayed in their package leaflet, together with a short sentence that reads: 
Ovi lijekovi na uputi imaju obrnuti crni trokut zajedno s kratkom rečenicom koja glasi:
By reporting side effects, you can help medicines regulators assess whether the benefits of a medicine remain greater than its risks. 
Prijavljivanjem nuspojava možete pomoći regulatornim tijelima nadležnim za lijekove procijeniti jesu li koristi lijeka veće od njegovih rizika.
Some less common side effects may only be apparent when a medicine has been used for a long time by a large number of people. 
Neke manje česte nuspojave mogu se uočiti samo nakon što veći broj osoba duže vrijeme koristi lijek.
You can also report side effects directly to your national medicines regulator, using the reporting system in your country. 
Nuspojave također možete prijaviti izravno nacionalnom regulatornom tijelu nadležnom za lijekove upotrebom sustava za prijavljivanje u Vašoj državi.
Information on how to do this can be found in the package leaflet of your medicine or on your national medicines regulator's website. 
Informacije o tome možete naći u uputi o lijeku ili na internetskim stranicama nacionalnog regulatornog tijela nadležnog za lijekove.
Visit your national medicines regulator at: www.mhra.gov.uk (United Kingdom) www.imb.ie (Ireland) www.medicinesauthority.gov.mt (Malta) 
www.halmed.hr
Pharmaceutical Form Route of Administration Packaging 
Farmaceutski oblik
Use immediately. 
Koristite odmah.
Repeat every 24 hours. 
Ponoviti svaka 24 sata.
It is not known whether they respond differently from younger subjects. 
Nije poznato reagiraju li oni drugačije od mlađih ispitanika.
If not coinciding with week 26 visit. 
Ako se ne poklapa s posjetom u 26. tjednu.
The product dissolves rapidly (within 2 minutes). 
Lijek se brzo otapa (unutar 2 minute).
Your doctor may need to treat you promptly for these reactions. 
Vaš liječnik će Vas možda trebati odmah liječiti zbog ovih reakcija.
Required units 
Potrebne jedinice
A-2304 Orth an der Donau Austria 
A-2304 Orth an der Donau Austrija
Your doctor may need to treat you promptly for these reactions (see section 2 ‘Warnings and precautions'). 
Vaš liječnik će Vas možda trebati odmah liječiti zbog ovih reakcija (vidjeti dio 2 "Upozorenja i mjere opreza").
You or somebody else might also administer RIXUBIS as an injection but only after receiving adequate training. 
Vi ili netko drugi također možete primijeniti RIXUBIS kao injekciju, ali tek nakon što ste prošli adekvatnu obuku.
This is of importance particularly when changing the laboratory and/or reagents used in the assay. 
To je naročito važno kada se mijenjaju laboratoriji i/ili reagensi upotrijebljeni u testu.