FrancophonIA/ELRC3.0 huggingface dataset:
English: • Digestive events (nausea, burning sensation and sensation of epigastric heaviness, dyspepsia),
Croatian: • probavne nuspojave (mučnina, žgaravica i osjećaj epigastrične težine, dispepsija)
English: Overall, a significant number of cases with outcomes reported as not recovered or recovered with sequelae is not acceptable to the PRAC.
Croatian: Stoga PRAC značajan broj slučajeva s ishodom zabilježenim kao neoporavak ili oporavak s posljedicama smatra neprihvatljivim.
English: Therefore, in accordance with Articles 31 and 32 of Directive 2001/83/EC, the PRAC recommends the revocation of the marketing authorisations of the marketing authorisations for all medicinal products referred to in Annex I.
Croatian: Stoga, u skladu s člancima 31. i 32. Direktive 2001/83/EZ, PRAC preporučuje opoziv odobrenja za stavljanje gotovog lijeka u promet za sve medicinske proizvode navedene u Prilogu I.
English: A total of 11 published clinical studies which became available after the initial Marketing Authorisation were reviewed.
Croatian: Revidirano je ukupno 11 objavljenih kliničkih ispitivanja koja su postala dostupna nakon prvotnog odobrenja za stavljanje gotovog lijeka u promet.
English: France has taken a number of national regulatory actions to minimise the risk of these adverse reactions associated with almitrine for oral use.
Croatian: Francuska je poduzela niz nacionalnih regulatornih koraka kako bi smanjila rizik navedenih nuspojava povezanih s almitrinom za oralnu primjenu.
English: This included data from the Member States and published literature data which became available since the original marketing authorisations and the MAH's response.
Croatian: Navedeno je uključivalo podatke iz država članica i objavljene literature koji su postali dostupni nakon prvotnog odobrenja za stavljanje gotovog lijeka u promet i odgovora MAH-a.
English: PRAC noted that in the clinical trials with results in favour of almitrine, effect of almitrine could have been overestimated as a high rate of patients withdrew predominantly in the almitrine group as compared to placebo (Voisin and al, 1987 and in most of all the clinical trials).
Croatian: PRAC je istaknuo da je u kliničkim ispitivanjima s rezultatima u korist almitrina učinak almitrina možda precijenjen jer se veliki broj ispitanika povukao uglavnom iz grupe koja je primala almitrin u usporedbi s grupom koja je primala placebo (Voisin et al, 1987. i u većini kliničkih ispitivanja).
English: In addition to peripheral neuropathies with abnormal sensations in the lower limb or paraesthesia and weight loss up to -6%, in the publications reporting clinical studies with continuous administration, the following adverse events were also more frequent in the almitrine groups:
Croatian: Osim perifernih neuropatija s neuobičajenim osjećajem u donjim ekstremitetima ili paraestezije i gubitka težine do -6%, u publikacijama o kliničkim ispitivanjima sa stalnom primjenom, u grupama koje su primale almitrin također su zabilježene sljedeće učestalije nuspojave:
English: The uncertainties relating to the mechanisms of action implying the vasoconstriction of pulmonary vasculature (which is inverse to the beneficial effect of LTOT on pulmonary arterial pressure) was noted by the PRAC.
Croatian: PRAC je istaknuo nesigurnosti povezane s mehanizmima djelovanja koji ukazuju na vazokonstrikciju plućne vaskulature (što je suprotno pozitivnom učinku LTOT-a na plućni arterijski pritisak).
English: Almitrine for oral use was studied in several clinical studies.
Croatian: Almitrin za oralnu primjenu ispitivan je u nekoliko kliničkih ispitivanja.
English: This adverse effect was also clearly recognised in the trials comparing almitrine at high doses to placebo.
Croatian: Ta je nuspojava također očito prepoznata u ispitivanjima koja uspoređuju almitrin u visokim dozama s placebom.
English: However, the PRAC noted that weight loss reported with almitrine could occur faster and be more severe than what is commonly observed in chronic respiratory insufficiency.
Croatian: Međutim, PRAC je napomeno da bi gubitak težine povezan s almitrinom mogao postati učestaliji i teži od onoga obično zabilježenog u slučajevima kronične respiratorne insuficijencije.
English: The reported reactions consisted mainly of peripheral neuropathy and weight loss.
Croatian: Prijavljene nuspojave uglavnom su se odnosile na perifernu neuropatiju i gubitak težine.
English: The last trials, conducted with sequential treatment and following a double blind placebo controlled design, account for 366 patients.
Croatian: Posljednja ispitivanja, tijekom kojih je provedeno sekvencijalno liječenje, nakon dvostruko slijepog, placebom kontroliranog nacrta ispitivanja, uključivala su 366 ispitanika.
English: Safety
Croatian: Neškodljivost
English: In addition, the benefit claimed by the MAH that long-term oxygen therapy can be delayed with almitrine is not substantiated by supporting data.
Croatian: Osim toga, tvrdnja MAH-a da dugoročna terapija kisikom može biti odgođena uz primjenu almitrina nije poduprta odgovarajućim podacima.
English: • The PRAC therefore concluded, in view of the available data, that the risks of serious peripheral neuropathy and weight loss adverse reactions associated with the use of almitrine-containing medicinal products for oral administration in the treatment of respiratory failure with hypoxemia related to obstructive bronchitis outweigh the limited benefits.
Croatian: • PRAC je, stoga, zaključio, s obzirom na dostupne podatke, da su rizici od nuspojava ozbiljne periferne neuropatije i gubitka težine povezanih s korištenjem medicinskih proizvoda za oralnu primjenu koji sadrže almitrin u liječenju respiratornih poremećaja i hipoksemije povezane s opsktruktivnim bronhitisom značajniji od ograničene koristi.
English: • The PRAC considered the procedure under Article 31 of Directive 2001/83/EC resulting from pharmacovigilance data, for almitrine containing products for oral administration (see Annex I).
Croatian: • PRAC je razmotrio postupak u skladu s člankom 31. Direktive 2001/83/EZ na temelju podataka o farmakovigilanciji, za proizvode za oralnu primjenu koji sadrže almitrin (vidjeti Prilog I.).
English: The CMDh, having considered the PRAC recommendation dated 16 May 2013 pursuant to Article 107k(1) and (2) of Directive 2001/83/EC, reached an agreement on the revocation of the marketing authorisations of almitrine containing products for oral use.
Croatian: CMDh je, nakon razmatranja preporuke PRAC-a od 16. svibnja 2013. u skladu sa stavcima 1. i 2. članka 107k Direktive 2001/83/EZ, postigao sporazum o opozivu odobrenja za stavljanje lijeka u promet za proizvode za oralnu primjenu koji sadrže almitrin.
English: Even if occurrence of peripheral neuropathy in COPD patients with associated conditions could be considered as a confounding factor, the occurrence of cases with positive rechallenge with almitrine during the post-marketing experience is strongly in favour of a causal relationship between almitrine and peripheral neuropathies.
Croatian: Čak i kad bi se pojavljivanje periferne neuropatije u ispitanika s KOBP-om s povezanim stanjima moglo smatrati pratećim čimbenikom, pojavljivanje slučajeva s pozitivnom ponovnom primjenom almitrina nakon stavljanja lijeka u promet izrazito podupire uzročnu vezu između almitrina i perifernih neuropatija.
English: On 27 November 2012 France informed the European Medicines Agency, pursuant to Article 31 of Directive 2001/83/EC, of their consideration to review the benefit risk balance of almitrine for oral use in the treatment of chronic respiratory diseases resulting from the evaluation of data relating to pharmacovigilance.
Croatian: Francuska je, u skladu s člankom 31. Direktive 2001/83/EZ, obavijestila Europsku agenciju za lijekove (EMA) o razmatranju revizije uravnoteženosti koristi i rizika almitrina za oralnu primjenu u liječenju kroničnih respiratornih bolesti na temelju ocjene podataka vezanih za farmakovigilanciju.
English: The first trials, conducted with non-sequential treatment, account for 1670 patients (1006 following a double blind, placebo controlled design).
Croatian: Prva ispitivanja, tijekom kojih je primijenjeno nesekvencijalno liječenje, uključivala su 1670 ispitanika (1006 nakon dvostruko slijepog, placebom kontroliranog nacrta ispitivanja).
English: The PRAC considered the risk minimisations measures already implemented (reduction of the dose and implementation of a sequential treatment scheme) to mitigate the risk of neuropathies and weight loss.
Croatian: PRAC je razmotrio mjere smanjenja rizika koje se već provode (smanjenje doze i provedba sheme sekvencijalnog liječenja) da bi se smanjio rizik od neuropatija i gubitka težine.
English: In France, almitrine containing medicinal products for oral use have been under close monitoring due to serious adverse reaction .
Croatian: U Francuskoj se medicinski proizvodi za oralnu primjenu koji sadrže almitrin pomno prate zbog ozbiljnih nuspojava.
English: Concerns have also been raised with regards to the potential risks of hepatobilary disorders, skin disorders and cytopenia with the use of oral almitrine.
Croatian: Izražena je i zabrinutost vezano za moguće rizike poremećaja jetre i žuči, poremećaja kože i citopenije kod oralne primjene almitrina.
English: Risk minimisation measures (reduction of the dose and implementation of a sequential treatment scheme ) were implemented since the initial marketing authorisation.
Croatian: Mjere smanjenja rizika (smanjenje doze i provedba sheme sekvencijalnog liječenja) provođene su od prvotnog odobrenja za stavljanje gotovog lijeka u promet.
English: No benefit has been demonstrated when almitrine was used as an adjuvant of that intervention.
Croatian: Prilikom korištenja almitrina kao adjuvansa toj intervenciji nije zabilježena ikakva korist.
English: • The PRAC considered, based on the assessment of the impact of risk minimisation measures already implemented (reduction of the dose and implementation of a sequential treatment scheme) and on the published literature, that the additional risk minimisation measures proposed by the Marketing Authorisation Holder and discussed during the assessment would not be able to adequately reduce the risks of serious adverse reactions to a clinically acceptable level.
Croatian: • PRAC je uzeo u obzir, na temelju ocjene učinka mjera smanjenja rizika koje se već provode (smanjenje doze i provedba sheme sekvencijalnog liječenja) i objavljene literature, da dodatne mjere smanjenja rizika koje predlaže nositelj odobrenja za stavljanje lijeka u promet (MAH) i o kojima je raspravljano tijekom postupka ocjene neće biti u mogućnosti primjereno smanjiti rizike od ozbiljnih nuspojava na klinički prihvatljivoj razini.
English: Further risk minimisation measures such as additional amendments to the product information (restriction of the indication and contra-indications), communication material (dear Health Care Professional Communication) and restricted prescription were also considered during the discussions.
Croatian: Daljnje mjere smanjenja rizika poput dodatnih izmjena podataka o proizvodu (ograničenje indikacija i kontraindikacija), komunikacijskog materijala (komunikacija sa zdravstvenim radnikom) i ograničenih recepata također su razmotrene tijekom rasprava.
English: During the assessment, the MAH confirmed that all the available data have been provided and that they will not be able to provide any further data to demonstrate the clinical benefit of oral almitrine in in the management of chronic hypoxemia in COPD.
Croatian: Tijekom ocjene, MAH je potvrdio da su izneseni svi dostupni podaci i da neće biti u mogućnosti osigurati dodatne podatke koji bi pokazali kliničku korist oralne primjene almitrina u upravljanju kroničnom hipoksemijom kod KOBP-a.
English: No published data focusing on the proper mechanism of almitrine in the occurrence of those adverse events was provided by the MAH.
Croatian: MAH nije dostavio ikakve objavljene podatke vezane za ispravan mehanizam almitrina kod pojavljivanja navedenih štetnih događaja.
English: • The PRAC considered that the available efficacy data, including data which became available since the initial marketing authorisation, showed only very limited clinical efficacy of almitrine in its approved indications.
Croatian: • PRAC je uzeo u obzir da su dostupni podaci o učinkovitosti, uključujući podatke koji su postali dostupni nakon prvotnog odobrenja za stavljanje gotovog lijeka u promet, pokazali samo izuzetno ograničenu kliničku učinkovitost almitrina u njegovim odobrenim indikacijama.
English: With regards to peripheral neuropathy, a total of 2304 cases of peripheral neuropathy have been spontaneously reported in patients exposed to almitrine since the launch of the product (from 1983 to December 2012).
Croatian: Što se tiče periferne neuropatije, u ispitanika izloženih almitrinu od stavljanja proizvoda u promet (od 1983. do prosinca 2012.) spontano je prijavljeno ukupno 2304 slučaja periferne neuropatije.
English: Further risk minimisation measures, as proposed by the MAH, such as additional amendments to the product information (restriction of the indication and contra-indications), communication material (dear Health Care Professional Communication) and restricted prescription (restriction to one month for pneumologists and hospital's use) were also considered during the discussions.
Croatian: Daljnje mjere smanjenja rizika, prema prijedlogu MAH-a, poput dodatnih izmjena podataka o proizvodu (restrikcija indikacija i kontraindikacija), komunikacijskog materijala (komunikacija sa zdravstvenim radnikom) i restriktivnih recepata (restrikcija na jedan mjesec za pulmologe i bolničku primjenu) također su razmotrene tijekom rasprava.
English: In addition to publications of clinical studies, the PRAC reviewed post marketing data provided by the MAH.
Croatian: Osim publikacija kliničkih ispitivanja, PRAC je revidirao podatke MAH-a zabilježene nakon stavljanja gotovog lijeka u promet.
English: Among the clinical studies in Chronic Obstructive Pulmonary Disease (COPD) patients, only those with more than 30 patients treated with therapeutic doses of almitrine for at least 3-month were selected for an efficacy and safety overview.
Croatian: U slučaju kliničkih ispitivanja ispitanika s kroničnom opstruktivnom plućnom bolesti (KOBP), za reviziju učinkovitosti i neškodljivosti odabrana su samo ona s više od 30 ispitanika liječenih terapijskim dozama almitrina kroz najmanje tri mjeseca.
English: • The PRAC took into account the MAH's position that all the available data have been provided and that there was no possibility to provide additional data for the demonstration of the clinical benefit of oral almitrine in chronic obstructive pulmonary disease (COPD).
Croatian: • PRAC je uzeo u obzir stav MAH-a da su svi dostupni podaci izneseni i da ne postoji mogućnost pružanja dodatnih podataka radi pokazivanja kliničke koristi oralne primjene almitrina kod kronične opstruktivne bolesti pluća (KOBP).
English: Long-term use of almitrine bismesylate is currently recommended at a dose level of 50 to 100 mg per day with limitation of the dose at 50 mg per day in patients with body weight less than 50 kg. After 3-month treatment, maintenance therapy of the sequential type is recommended: a 1-month interval for every 2 months treatment.
Croatian: Dugoročna primjena almitrin bismesilata trenutačno je preporučena u dozi od 50 do 100 mg na dan s ograničenjem doze od 50 mg na dan u pacijenata tjelesne težine manje od 50 kg.
English: Important weight losses and peripheral neuropathies which can potentially not recover or lead to sequelae, are still reported with almitrine despite risk minimisation measures in place for several years.
Croatian: neuropatije, kod kojih postoji mogućnost neoporavka ili posljedica, i dalje se prijavljuju vezano za almitrin usprkos mjerama smanjenja rizika koje su na snazi nekoliko godina.
English: Despite sequential doses regimen and amendments in the SmPC, the PRAC noted serious cases of neuropathy and weight loss continued to be reported, including some cases with positive rechallenge, and leading sometimes to sequelae.
Croatian: Usprkos propisanim sekvencijalnim dozama i izmjenama SmPC-a, PRAC je zapazio ozbiljne slučajeve neuropatije i gubitka težine koji se i dalje prijavljuju, ponekad s pozitivnom ponovnom primjenom, ponekad s posljedicama.
English: Respir Dis 1986; 69(Suppl 146):685-693 (PE10387)
Croatian: Eur J Respir Dis 1986; 69(Suppl 146):685-693 (PE10387)
English: Overall, based on the available published data and data from spontaneous reports, the PRAC considers that almitrine use is associated with serious cases of peripheral neuropathy, some with positive rechallenge, and weight loss.
Croatian: Sveukupno, na temelju dostupnih objavljenih podataka i podataka spontanih prijava, PRAC smatra da je primjena almitrina povezana s ozbiljnim slučajevima periferne neuropatije, uz pozitivnu ponovnu primjenu u pojedinim slučajevima, i gubitkom težine.
English: The PRAC therefore concluded that the benefit-risk balance of almitrine containing medicinal products for oral administration is not favourable.
Croatian: PRAC je stoga zaključio da uravnoteženost koristi i rizika medicinskih proizvoda za oralnu primjenu koji sadrže almitrin nije povoljna.
English: • The PRAC considered the totality of the data available for almitrine containing products for oral administration in relation to the risk of peripheral neuropathy and weight loss.
Croatian: • PRAC je razmotrio ukupne dostupne podatke vezane za proizvode za oralnu primjenu koji sadrže almitrin u vezi s rizikom od periferne neuropatije i gubitka težine.
English: Based on the published literature and post marketing data, the PRAC is of the view that the risk minimisation measures proposed by the MAH would not be able to adequately reduce the risks of serious adverse reactions to a clinically acceptable level: any additional communication on risks of neuropathies and weight loss, already well known to prescribers, would not contribute to a safer use of the product.
Croatian: Na temelju objavljene literature i podataka dobivenih nakon stavljanja gotovog lijeka u promet, PRAC smatra da mjere smanjenja rizika koje je predložio MAH ne bi mogle primjereno smanjiti rizike od ozbiljnih nuspojava na klinički prihvatljivu razinu: bilo kakva dodatna komunikacija o rizicima vezanima za neuropatije i gubitak težine, s kojima su liječnici koji propisuju lijekove već upoznati, ne bi doprinijela sigurnoj primjeni proizvoda.
English: The PRAC is of the view that the risk minimisation measures proposed by the MAH would not be able to adequately reduce the risks of serious adverse reactions to a clinically acceptable level: any additional communication on risks of neuropathies and weight loss, already well known to prescribers, would not contribute to a safer use of the product.
Croatian: PRAC smatra da mjere smanjenja rizika koje je predložio MAH ne bi mogle primjereno smanjiti rizike od ozbiljnih nuspojava na klinički prihvatljivu razinu: bilo kakva dodatna komunikacija o rizicima vezanim za neuropatije i gubitak težine, s kojima su liječnici koji propisuju lijekove već upoznati, ne bi doprinijela sigurnijoj primjeni proizvoda.
English: Further to the review of the available efficacy data, including data which became available since the initial marketing authorisation, the PRAC concluded that the available data only showed very limited efficacy of oral almitrine in its approved indications which does not translate in evidence of a benefit for patients in the current context of the therapeutic strategy and knowledge acquired in respiratory diseases.
Croatian: Nastavno na reviziju dostupnih podataka o učinkovitosti, uključujući podatke koji su postali dostupni nakon prvotnog odobrenja za stavljanje gotovog lijeka u promet, PRAC je zaključio da su dostupni podaci pokazali samo izuzetno ograničenu učinkovitost oralne primjene almitrina u njegovim odobrenim indikacijama što se ne smatra dokazom koristi za pacijente u trenutačnom kontekstu terapijske strategije i znanja stečenog vezano za respiratorne bolesti.
English: Based on the above, the PRAC considered that the available efficacy data, including data which became available since the initial marketing authorisation, showed only very limited efficacy of oral almitrine in its approved indications which does not translate in evidence of a benefit for patients in the current context of the therapeutic strategy and knowledge acquired in respiratory diseases.
Croatian: Na temelju prethodno navedenog, PRAC je smatrao da su dostupni podaci o učinkovitosti, uključujući podatke koji su postali dostupni nakon prvotnog odobrenja za stavljanje lijeka u promet, pokazali samo izuzetno ograničenu učinkovitost oralne primjene almitrina u njegovim odobrenim indikacijama što se ne smatra dokazom koristi za pacijente u trenutačnom kontekstu terapijske strategije i znanja stečenog vezano za respiratorne bolesti.
English: Effects of Almitrine bismesylate on arterial blood gases in patients with chronic obstructive pulmonary disease and moderate Hypoxaemia: A Multicentre, Randomised, Double-Blind, Placebo- Controlled Study.Resp.
Croatian: Effects of Almitrine bismesylate on arterial blood gases in patients with chronic obstructive pulmonary disease and moderate Hypoxaemia: A Multicentre, Randomised, Double-Blind, Placebo- Controlled Study.Resp. 2003 ; 70 : 275-283 (PE32001)
English: Overall summary of the scientific evaluation of Almitrine containing medicinal products for oral use by PRAC
Croatian: Cjelokupni sažetak PRAC-ove znanstvene ocjene medicinskih proizvoda za oralnu primjenu koji sadrže almitrin
English: Almitrine bismesylate is indicated in patients with respiratory failure with hypoxemia related to obstructive bronchitis.
Croatian: Almitrin bismesilat (almitrine bismesylate) izdaje se pacijentima s respiratornim problemima i hipoksemijom povezanom s opstruktivnim bronhitisom.
English: Sequential treatment with low dose Almitrine bismesylate in hypoxaemic chronic obstructive airways disease.
Croatian: Two years treatment with Almitrine bismesylate in patients with hypoxic chronic obstructive airways disease.
English: Pneumology 1998 Mar;52(3):121-7 (PE24412) Weitzenblum E., Arnaud F., Bignon J., Boutin C., Brune J., Castaing Y., Courty G., Derenne J.P., Duroux P., Freour P., Muir J.F., Paramelle B., Philip-Joet F., Poirier R., Pouget J., Senant J., Tonnel A.. Sequential administration of a reduced dose of Almitrine in patients with chronic obstrutive lung disease.
Croatian: Pneumology 1998 Mar;52(3):121-7 (PE24412) 11 Weitzenblum E., Arnaud F., Bignon J., Boutin C., Brune J., Castaing Y., Courty G., Derenne J.P., Duroux P., Freour
English: Based on the data from clinical studies and post-marketing experience, the two main safety concerns with almitrine are peripheral neuropathy and weight loss.
Croatian: Podaci kliničkih ispitivanja i iskustva nakon stavljanja lijeka u promet pokazali su da su periferna neuropatija i gubitak težine dva glavna pitanja neškodljivosti vezana za almitrin.
English: The PRAC, as a consequence, concluded that pursuant to Article 116 of Directive 2001/83/EC the risk-benefit balance for almitrine containing products for oral administration is not favourable.
Croatian: Direktive 2001/83/EZ uravnoteženost koristi i rizika za proizvode za oralnu primjenu koji sadrže almitrin nije povoljna.
English: Ansquer J.C., Bertrand A., Blaive B., Charpin J., Chretien J., Decroix G., Kalb J.C., Lissac J., Michel F.B., Morere P., Paramelle B., Pariente R., Perrin-Fayolle M., Rochemaure J., Sadoul P., Voisin C. The therapeutic value and acceptability of Vectarion 50 mg coated tablets (Almitrine bismesylate) at the dose of 100 mg per day.
Croatian: Ansquer J.C., Bertrand A., Blaive B., Charpin J., Chretien J., Decroix G., Kalb J.C., Lissac J., Michel F.B., Morere P., Paramelle B., Pariente R., Perrin-Fayolle M., Rochemaure J., Sadoul P., Voisin C.