natgillin/translations-raw huggingface dataset:
This risk of ulcerations was mainly established based on safety reports received in association with the marketed product.
Tveganje za razjede je bilo določeno predvsem na podlagi poročil o varnosti, prejetih v povezavi s trženim zdravilom.
However, the 5 mg dose although active in Japanese patients has shown to induce modest haemodynamic changes.
Čeprav je odmerek 5 mg pri japonskih bolnikih aktiven, povzroča skromne hemodinamske spremembe.
Section 4.4 - Special warnings and precautions for use Initially lack of glucose-6-phosphate-dehydrogenase was added as contraindication.
Poglavje 4.4 - Opozorila in posebni previdnostni ukrepi Prvotno je bilo med kontraindikacije dodano pomanjkanje glukoza-6-fosfat dehidrogenaze.
The effect on venous capacitance was less than with nitrates.
Učinek na vensko kapacitivnost je bil manjši kot pri uporabi nitratov.
Event counts were presented by the different daily doses in the previous Periodic Safety Update Report for nicorandil (reporting period 01-March-2010 to 28- February
Število dogodkov glede na različne dnevne odmerke je bilo predstavljeno v prejšnjem redno posodobljenem poročilu o varnosti zdravila za nikorandil (obdobje poročanja od 1. marca 2010 do 28. februarja 2013).
According to the Guideline on SmPC (dated September 2009), available information on pediatric patients should be summarised using some standard statements in section 4.2.
V skladu s smernicami za povzetek glavnih značilnosti zdravila (iz septembra 2009) je razpoložljive informacije o pediatričnih bolnikih treba povzeti z določenimi standardnimi navedbami v poglavju 4.2.
The daily dose in Asiatic patients cannot be extrapolated to the European patients; this is acknowledged by the CHMP.
Dnevnega odmerka za azijske bolnike ni mogoče ekstrapolirati na evropske, s čimer se je strinjal tudi odbor CHMP.
While the IONA study does not provide adequate support for a prevention indication, the totality of the data, including IONA, provide good support for the new symptomatic indication proposed above.
Medtem ko študija IONA ni zagotovila zadostnih dokazov za indikacijo, povezano s preprečevanjem, pa celokupni podatki, vključno s tistimi iz študije IONA, dobro utemeljujejo zgoraj predlagano novo indikacijo, povezano s simptomatskim zdravljenjem.
In general, it can be stated, that the treatment should be conducted with the lowest effective dose.
Na splošno velja, da je treba za zdravljenje uporabiti najmanjši učinkoviti odmerek.
The step of a retrospective assessment as part of the pharmacovigilance plan is a pre-requisite for a thorough understanding of the factors leading to the development of ulcerations.
Retrospektivna ocena v okviru načrta farmakovigilance je predpogoj za natančno razumevanje dejavnikov, ki vodijo do razvoja razjed.
The anti-ischemic activity of nicorandil seems to be comparable to that of diltiazem, nifedipine, nitrates and propranolol.
Zdi se, da je protiishemično delovanje nikorandila primerljivo z delovanjem diltiazema, nifedipina, nitratov in propranolola.
The CHMP considers that the DHPC should also inform about the main modifications of the product information following the outcome of this harmonisation procedure; this should be decided at national level by each competent authority, if deemed necessary.
Odbor CHMP je menil, da bi bilo treba v neposrednem obvestilu zdravstvene delavce seznaniti tudi z glavnimi spremembami informacij o zdravilu v skladu z izidom tega postopka uskladitve, posamezen pristojni organ pa mora na nacionalni ravni presoditi, ali je to potrebno.
No dose recommendation is proposed for prevention of CHD events and the product information was adapted accordingly.
Predlagana niso bila nobena priporočila za odmerjanje pri preprečevanju dogodkov KBS, zato so bile informacije o zdravilu ustrezno spremenjene.
The SG 002 study was an open label non-controlled study and EMD 034 study was a double-blind randomized cross over study.
Študija SG 002 je bila odprta nekontrolirana študija, EMD 034 pa dvojno slepa randomizirana navzkrižna študija.
As specified in the current ICH guidance on ”Ethnic factors in the acceptability of foreign clinical data” dated 1998 evaluation of the pharmacokinetics and pharmacodynamics and their comparability in the three major racial groups most relevant to the ICH regions (Asian, Black, Caucasian) is critical to the registration of medicines in the ICH regions.
Kot določajo trenutno veljavne smernice ICH z naslovom „Vpliv etničnih dejavnikov na sprejemljivost tujih kliničnih podatkov“ iz leta 1998, je ovrednotenje farmakokinetike in farmakodinamike in njune primerljivosti med tremi glavnimi rasnimi skupinami, ki so najpomembnejše za regije ICH (Azijci, temnopolti, belci), ključnega pomena za registracijo zdravil v regijah ICH.
Consequently, as none of the performed studies show efficacy at doses lower than 20 mg b.i.d., and as the toxicity is dose dependant and appears at 20 mg b.i.d., the indication should be restricted to second line treatment as recommended in section 4.1 for safety reasons.
Ker nobena od izvedenih študij ni pokazala učinkovitosti pri odmerkih, manjših od 20 mg dvakrat na dan, in da je toksičnost odvisna od odmerka ter se pojavi pri 20 mg dvakrat na dan, je treba indikacijo zaradi varnosti omejiti na zdravljenje drugega reda, kot je priporočeno v poglavju 4.1.
The statistically significant superiority of a single 5 mg dose over placebo was not considered as relevant evidence for efficacy after repeated dosing, as it was an acute administration only, and this was not the objective of the study.
Statistično značilna večja učinkovitost enkratnega odmerka 5 mg v primerjavi s placebom ni bila upoštevana kot ustrezen dokaz o učinkovitosti po večkratnem odmerjanju, saj je šlo zgolj za akutno odmerjanje, kar pa ni bil cilj študije.
Furthermore, the reduction of enddiastolic pressure and wall tension decreases the extravascular component of vascular resistance.
Poleg tega znižanje končnega diastoličnega tlaka in napetosti v stenah zmanjša ekstravaskularno komponento žilnega upora.
According to the risk management plan assessed separately in a worksharing procedure9, a DHPC emphasising the risk of ulceration is already planned to be disseminated in all member states.
V skladu z načrtom obvladovanja tveganj, ocenjenim ločeno med postopkom delitve dela9, je že predvideno, da se bo v vseh državah članicah razposlalo neposredno obvestilo zdravstvenim delavcem, v katerem bo poudarjeno tveganje za razjede.
Therefore, a contra-indication is not considered justified, however a warning statement is requested by the CHMP.
Ta kontraindikacija je bila zato ocenjena kot neutemeljena, kljub temu pa je odbor CHMP zahteval, da se vključi opozorilna navedba.
It is more likely to occur in patients with specific risk factors such as those receiving potassium supplements or potassium-sparing diuretics.
Večja verjetnost je, da se pojavi pri bolnikih z določenimi dejavniki tveganja, na primer pri tistih, ki prejemajo dodatke kalija ali diuretike, ki zadržujejo kalij.
In addition one of the following was also in force: left ventricular hypertrophy on the ECG, left ventricular ejection fraction ≤45%, or an end diastolic dimension of >55mm, age ≥65, diabetes, hypertension, peripheral vascular disease, or cerebrovascular disease.
Poleg tega je bil prisoten še eden od naslednjih dejavnikov: hipertrofija levega prekata na EKG-ju, iztisni delež levega prekata ≤ 45 % ali končni diastolični premer > 55 mm, starost ≥ 65 let, sladkorna bolezen, hipertenzija, periferna žilna bolezen ali cerebrovaskularna bolezen.
Furthermore Japanese studies with double blind randomised controlled design have used higher single doses, i.e., 10 or 30 mg nicorandil.
Poleg tega so v japonskih študijah, ki so bile zasnovane kot dvojno slepe randomizirane kontrolirane študije, uporabili večje enkratne odmerke, in sicer 10 ali 30 mg nikorandila.
The mechanism of action of nicorandil as a nicotinamide ester was clarified and the wording harmonised.
Dodano je bilo pojasnilo mehanizma delovanja nikorandila kot nikotinamidestra, besedilo pa usklajeno.
This should reflect that nicorandil should be used with caution in patients with glucose-6-phosphate-dehydrogenase deficiency as this may lead to methemoglobinemia based on the theoretical mechanism of triggering this process by metabolism of organic nitrates resulting in the formation of nitrites.
Ta mora opozarjati na to, da je treba nikorandil previdno uporabljati pri bolnikih s pomanjkanjem glukoza-6-fosfat dehidrogenaze, saj se lahko pojavi methemoglobinemija, ki naj bi jo v teoriji povzročal mehanizem, pri katerem ta proces sproži presnova organskih nitratov, ki povzroči nastanek nitritov.
This section was clarified by indicating that the tablets should not be removed from the blister strip until intake (with cross references to the sections 4.4 and 6.4) as they are affected by humidity and mentioning of the absence of effect with food intake.
V to poglavje sta bila dodana pojasnilo, da se lahko tablete zaradi vpliva vlage odstranijo iz pretisnega omota šele tik pred zaužitjem (s sklicem na poglavji 4.4 in 6.4), in navedba o odsotnosti učinka v primeru zaužitja skupaj s hrano.
Overall summary of the scientific evaluation of Ikorel and associated names, and Dancor and associated names (see Annex I)
Splošni povzetek znanstvenega vrednotenja zdravila Ikorel in povezanih imen ter zdravila Dancor in povezanih imen (glejte Prilogo I)
Nicorandil may induce hyperkalaemia.
Nikorandil lahko povzroči hiperkaliemijo.
Nicorandil has no direct effect on myocardial contractility.
Nikorandil nima neposrednega učinka na kontraktilnost miokardija.
However, two contraindications related to the risk of acute pulmonary oedema and hypovolemia were added in this section.
Sta pa bili v to poglavje dodani dve kontraindikaciji, povezani s tveganjem za akutni pljučni edem in hipovolemijo.
The impairment of fertility and the embryotoxicity and peri- and post-natal toxicity were clarified.
Dodano je bilo pojasnilo o vplivu na zmanjšano plodnost in o embriotoksičnosti ter perinatalni in postnatalni toksičnosti.
Due to the divergent national decisions taken by Member States (MS) concerning the authorisation of Ikorel and its associated names and Dancor and its associated names, these products were included in the list of products for Summary of Product Characteristics (SmPC) harmonisation, requested by the Coordination Group for Mutual Recognition and Decentralised ProceduresHuman (CMDh).
Zaradi razhajajočih se nacionalnih odločitev držav članic glede odobritve zdravila Ikorel in povezanih imen ter zdravila Dancor in povezanih imen so bila ta zdravila vključena na seznam zdravil za uskladitev povzetka glavnih značilnosti zdravila, ki jo je zahtevala Usklajevalna skupina za postopek z medsebojnim priznavanjem in decentralizirani postopek - zdravila za uporabo v humani medicini (CMDh).
The main objective criterion of efficacy was exercise capacity reported in terms of time to onset of angina, total exercise duration and time to 1 mm ST segment depression.
Glavno objektivno merilo učinkovitosti je bila telesna zmogljivost, o kateri so poročali glede na čas do pojava angine pektoris, skupno trajanje vadbe in čas do 1-mm znižanja spojnice ST.
It appears that most cases, beside GI ulcerations, were reported at a higher dose than 20 mg/day.
Zdi se, da so o večini primerov, tudi o razjedah v prebavilih, poročali pri uporabi odmerkov, večjih od 20 mg/dan.
The objectives are to quantify the rates of ulceration in patients treated with nicorandil (including but not restricted to gastrointestinal, skin, ocular, mucosal, anal sites; alone or in multiple locations), as well as subsequent erosion, perforation, haemorrhage, abscess formation, fistulae and delayed wound healing in a real world setting; together with identification of high risk subgroups, other risk factors, and a dose and time effect assessment.
Cilji so kvantificirati stopnje razjed pri bolnikih, zdravljenih z nikorandilom (med drugim razjede na enem ali več mestih v prebavilih, na koži, očeh, sluznici in v predelu anusa), ter posledične erozije, perforacije, krvavitve, nastanka abscesa, fistul in zapoznelega celjenja ran v resničnem okolju, poleg tega pa tudi opredeliti podskupine z visokim tveganjem in druge dejavnike tveganja ter oceniti vpliv odmerka in časa.
Several clinical studies1,2,3,4 in patients with angina pectoris have shown that treatment with nicorandil 10 and 20 mg twice daily prolongs the time to onset of ischemia during exercise and the total exercise duration.
Več kliničnih študij1,2,3,4, v katerih so sodelovali bolniki z angino pektoris, je pokazalo, da zdravljenje z 10 in 20 mg nikorandila dvakrat na dan podaljša čas do pojava ishemije med vadbo in skupno trajanje vadbe.
The CHMP was therefore of the view that the indication of cardiovascular prevention was not further supported.
Odbor CHMP je zato menil, da indikacija preprečevanje srčno-žilnih dogodkov ni več utemeljena.
The reduction in preload was proportionally more important than that of the afterload.
Zmanjšanje predobremenitve je bilo sorazmerno pomembnejše kot zmanjšanje sistoličnega bremena.
Ultimately, this results in an improved oxygen balance in the myocardium and improved blood flow in the post-stenotic areas of the myocardium.
Rezultat na koncu je izboljšano ravnovesje kisika v miokardiju in izboljšan dotok krvi v poststenotične predele miokardija.
Nicorandil has a direct effect on coronary arteries without leading to a steal phenomenon.
Nikorandil ima neposreden učinek na koronarne arterije, ne da bi pri tem povzročil kradežni pojav.
Others studies did not enrol patients with stable angina and thus are not relevant to evaluate its efficacy for the treatment of angina.
V druge študije niso vključili bolnikov s stabilno angino pektoris, zato niso primerne za oceno učinkovitosti nikorandila pri zdravljenju angine pektoris.
They have also been associated with damage to the distal small intestine and colon.
Prav tako so povezana s poškodbami distalnega tankega črevesa in debelega črevesa.
The Current Guidelines from the European Society of Cardiology (ESC) for the management of stable angina pectoris5 dated on 2013 provide the following recommendations for the use of nicorandil in pharmacological therapy to improve symptoms and/or reduce ischaemia in patients with stable angina:
Trenutno veljavne smernice Evropskega kardiološkega združenja (ESC) za zdravljenje stabilne angine pektoris5 iz leta 2013 vsebujejo naslednja priporočila za uporabo nikorandila pri farmakološkem zdravljenju za izboljšanje simptomov in/ali zmanjšanje ishemije pri bolnikih s stabilno angino pektoris:
Prevention of cardiovascular events in patients with stable coronary heart disease (CHD)
Preprečevanje srčno-žilnih dogodkov pri bolnikih s stabilno koronarno boleznijo srca (KBS)
With the current knowledge, the early diagnosis and the identification of nicorandil treatment as a possible cause to the emergence of ulceration are the best way to prevent more severe ulceration and to ensure recovery.
Glede na trenutno znanje sta zgodnja diagnoza in prepoznanje zdravljenja z nikorandilom kot možnega vzroka za pojav razjede najboljša načina, da se prepreči hujša razjeda in zagotovi okrevanje.
Caution is advised when nicorandil is used in combination with other medical products that may increase potassium levels (see sections 4.4 and 4.8).
Kadar se nikorandil uporablja v kombinaciji z drugimi zdravili, ki lahko zvišajo ravni kalija, se priporoča previdnost (glejte poglavji 4.4 in 4.8).
Available data on cardiovascular prevention may suggest a favourable effect of nicorandil in reducing cardiovascular risk, mainly by a reduction of hospitalisation.
Razpoložljivi podatki o preprečevanju srčno-žilnih dogodkov kažejo na ugoden učinek nikorandila na zmanjšanje srčno-žilnega tveganja, zlasti zaradi zmanjšanja hospitalizacij.
However, the CHMP is of the view that the level of the oxidation process may not be clinically relevant as only a single case of methemoglobinemia
Vendar je odbor CHMP menil, da raven oksidacije ni klinično pomembna, saj so pri uporabi nikorandila poročali o enem samem primeru methemoglobinemije.
Section 5.3 - Precllinical safety data
Poglavje 5.3 - Predklinični podatki o varnosti
There were no major discrepancies between the existing wordings in the different SmPCs.
V različnih povzetkih glavnih značilnosti zdravila ni bilo bistvenih razlik med obstoječimi besedili.
In addition, two hemodynamic studies (SG 002 and EMD 034) studied hemodynamic effects of single oral doses of nicorandil (40 mg, 60 mg, 80 mg) in a total of 21 pharmacodynamically evaluable patients with severe heart failure (N.Y.H.A.
Poleg tega so v dveh študijah hemodinamskih učinkov (SG 002 in EMD 034) proučili hemodinamske učinke enkratnih peroralnih odmerkov nikorandila (40 mg, 60 mg, 80 mg) pri skupno 21 bolnikih s hudim srčnim popuščanjem (razred II in IV po NYHA), ki jih je bilo mogoče ovrednotiti z vidika farmakodinamike.
Efficacy in the clinical programme was based on the measurement of anginal attack rates on exercise tests.
Učinkovitost v kliničnem programu je temeljila na merjenju stopnje preprečenih napadov angine pektoris na obremenitvenih testih.
The number of patients treated by nicorandil per dosage is unavailable; it is thus unknown whether a dose reduction would allow a reduction in ulceration without lack of efficacy.
Podatki o številu bolnikov, zdravljenih z določenim odmerkom nikorandila, niso na voljo, zato ni znano, ali bi lahko z zmanjšanjem odmerka zmanjšali število razjed in ohranili zadostno učinkovitost.
Nicorandil has dual pharmacological effects; activation of ATP-sensitive inward-rectifier potassium channels and (similar to nitroglycerin) increased production of nitric oxide.
Nikorandil ima dvojne farmakološke učinke - aktivira za ATP občutljive navznoter usmerjevalne kalijeve kanalčke in (podobno kot nitroglicerin) poveča nastajanje dušikovega oksida.
NSAIDs can cause clinically important damage of the gastrointestinal tract, increasing the incidence of bleeding in the upper gastrointestinal tract and of perforation, although serious complications and death are relatively infrequent.
Nesteroidna protivnetna zdravila lahko povzročijo klinično pomembne poškodbe prebavil in s tem povečajo incidenco krvavitev v zgornjih prebavilih ter perforacij, čeprav so resni zapleti in smrt relativno redki.
Efficacy of nicorandil on cardiovascular risk in patients with stable angina mainly lays on the pivotal study IONA6 and the supportive study by Nishimura7 (2009) which enrolled a too small number of patients to assess efficacy on morbi-mortality endpoints appropriately.
Učinkovitost nikorandila pri zmanjšanju srčno-žilnega tveganja pri bolnikih s stabilno angino pektoris v glavnem temelji na ključni študiji IONA6 in podporni študiji Nishimura7 (2009), v katerih je sodelovalo premajhno število bolnikov, da bi lahko ustrezno ocenili učinkovitost pri opazovanih dogodkih obolevnost in umrljivost.
Taking the above into account the CHMP was of the view that for the treatment of symptomatic stable angina, nicorandil should be considered in second line.
Odbor CHMP je ob upoštevanju navedenega zgoraj menil, da je treba pri zdravljenju simptomatske stabilne angine pektoris v drugem redu zdravljenja razmisliti o uporabi nikorandila.
However, the primary endpoint is weak as it includes the criterion “reduction of hospitalisation” which is subjective criteria for cardiovascular prevention in patient with coronary heart disease (CHD) patients with angina.
Vendar je primarni opazovani dogodek slab, saj vključuje merilo „zmanjšanje hospitalizacij“, kar je subjektivno merilo za oceno preprečevanja srčno-žilnih dogodkov pri bolnikih, ki imajo koronarno bolezen srca (KBS) z angino pektoris.
the CHMP was of the opinion that the benefit/risk ratio of Ikorel and associated names and Dancor and associated names is considered to be favourable.
je odbor CHMP menil, da se razmerje med koristmi in tveganji zdravila Okorel in povezanih imen ter zdravila Dancor in povezanih imen šteje za ugodno.
The half-life of 6 to 8 hours permits twice daily dosage, and total-daily dosages between 10 and 40 mg have been effective in patients with chronic stable angina.
Razpolovna doba 6 do 8 ur omogoča odmerjanje dvakrat na dan, pri čemer so pri bolnikih s kronično stabilno angino pektoris učinkoviti skupni dnevni odmerki od 10 do 40 mg.
The IONA study was conducted at a time when the standard of care of managing patient with CHD was different from that of present times in terms of revascularisation, antianginal strategies etc., and does not allow a conclusion regarding the prevention of cardiovascular events for CHD patients with angina.
Študija IONA je bila izvedena v času, ko je bila standardna oskrba pri zdravljenju bolnikov s KBS z vidika revaskularizacije, antianginioznih strategij itd. drugačna od današnje, zato ne omogoča zaključka glede preprečevanja srčno-žilnih dogodkov pri bolnikih, ki imajo KBS z angino pektoris.
The CHMP also recommended the information on the absence of pharmacodynamic interaction between nicorandil and acenocoumarol to be reflected in the SmPC with a cross reference to section 4.4 in order to refer the physician to the risk of ulcerations and associated bleeding.
Odbor CHMP je priporočil tudi, da se v povzetek glavnih značilnosti zdravila vključijo informacije o odsotnosti farmakodinamičnih interakcij med nikorandilom in acenokumarolom s sklicem na poglavje 4.4, da se zdravnike opozori na tveganje za razjede in posledične krvavitve.
In conclusion, based on the assessment of the MAHs' proposals and responses and following the discussions of the Committee, the CHMP adopted harmonised sets of product information documents of Ikorel and associate names and Dancor and associated names.
V zaključku je odbor CHMP na podlagi ocene predlogov in odgovorov imetnikov dovoljenja za promet z zdravilom ter razprave v odboru potrdil usklajene sklope dokumentov z informacijami o zdravilu za zdravilo Ikorel in povezana imena ter zdravilo Dancor in povezana imena.
The CHMP therefore requested the MAHs to include a statement mentioning that nicorandil should be used with caution in such a population.
Odbor CHMP je zato zahteval, da imetniki dovoljenja za promet z zdravilom vključijo navedbo, da je treba nikorandil pri tej populaciji uporabljati previdno.
The CHMP adopted a positive opinion recommending the variation to the terms of the marketing authorisations for which the summary of products characteristics, labelling and package leaflet as set out in Annex III of the CHMP opinion for Ikorel and associated names and Dancor and associated names (see Annex I).
Sprejel je pozitivno mnenje, v katerem je priporočil spremembo pogojev dovoljenj za promet z zdravili, za katera so povzetek glavnih značilnosti zdravila, označevanje in navodilo za uporabo opredeljeni v Prilogi III k mnenju odbora CHMP o zdravilu Ikorel in povezanih imenih ter zdravilu Dancor in povezanih imenih (glejte Prilogo I).
Coronary heart disease (CHD) patients
Bolniki s koronarno boleznijo srca (KBS)
Overall, nicorandil shows moderate efficacy to improve exercise capacity versus placebo and seems to be comparable to other anti-anginal therapies.
Na splošno se je nikorandil izkazal za zmerno učinkovitega pri izboljšanju telesne zmogljivosti v primerjavi s placebom in je primerljiv z drugimi zdravili proti angini pektoris.
Nicorandil has been shown to exert a direct effect on the coronary arteries, both on normal and stenotic segments, without leading to a steal phenomenon.
Dokazano je tudi, da ima nikorandil neposreden učinek na koronarne arterije, tako na normalne kot stenozne predele, ne da bi pri tem povzročil kradežni pojav.
However, the important identified risk of ulceration (gastrointestinal (GI), skin, mucosal, genital and ocular) and perforations, fistula and abscesses has been recognized and monitored since 1997.
Po drugi strani pa od leta 1997 opažajo in spremljajo pomembno ugotovljeno tveganje za razjede (v prebavilih, na koži, sluznici, spolovilih in očeh) in perforacijo, fistulo ter absces.