natgillin/translations-raw huggingface dataset:
Sodium lauryl sulfate Titanium dioxide (E171) Indigo carmine (E132) Edible green ink
Ovojnica kapsule: 30 mg: želatina natrijev laurilsulfat titanijev dioksid (E171) indigo karmin (E132) zelena tinta, jestiva
What ARICLAIM looks like and contents of the pack ARICLAIM is a hard gastro-resistant capsule.
ARICLAIM je tvrda želučanootporna kapsula.
NAME OF THE MEDICINAL PRODUCT ARICLAIM 60 mg hard gastro-resistant capsules
ARICLAIM 60 mg tvrde želučanootporne kapsule
NAME OF THE MEDICINAL PRODUCT ARICLAIM 30 mg hard gastro-resistant capsules
ARICLAIM 30 mg tvrde želučanootporne kapsule
The main ingredient of ARICLAIM, duloxetine, is used in other medicines for other conditions:
Duloksetin, glavni sastojak lijeka ARICLAIM, nalazi se i u nekim drugim lijekovima koji se koriste za liječenje drugih stanja: • depresije, tjeskobe i inkontinencije mokraće
PARTICULARS TO APPEAR ON THE OUTER PACKAGING CARTONS FOR 30 MG HARD GASTRO-RESISTANT CAPSULES
KUTIJE ZA 30 MG TVRDE ŽELUČANOOTPORNE KAPSULE
• “Serotonin syndrome” (a rare reaction which may cause feelings of great happiness, drowsiness, clumsiness, restlessness, feeling of being drunk, fever, sweating or rigid muscles),
omamljenost, nespretnost, nemir, osjećaj opijenosti, vrućicu, znojenje ili ukočene mišiće),
A. MANUFACTURER(S) RESPONSIBLE FOR BATCH RELEASE B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE C. OTHER CONDITIONS AND REQUIREMENTS OF THE
UVJETI ILI OGRANIČENJA VEZANI UZ OPSKRBU I PRIMJENU
Duloxetine is very weakly excreted into human milk based on a study of 6 lactating patients, who did not breast feed their children.
Na temelju ispitivanja provedenog na 6 bolesnica u laktaciji koje nisu dojile svoju djecu pokazalo se da se duloksetin u majčino mlijeko izlučuje u vrlo maloj mjeri.
BATCH NUMBER Lot
BROJ SERIJE Broj serije
PARTICULARS TO APPEAR ON THE OUTER PACKAGING CARTONS FOR 60 MG HARD GASTRO-RESISTANT CAPSULES
KUTIJE ZA 60 MG TVRDE ŽELUČANOOTPORNE KAPSULE
Each capsule contains 60 mg of duloxetine (as hydrochloride).
KVALITATIVNI I KVANTITATIVNI SASTAV Jedna kapsula sadrži 60 mg duloksetina (u obliku duloksetinklorida).
Palpitations
FARMACEUTSKI
Each capsule contains 30 mg of duloxetine (as hydrochloride).
KVALITATIVNI I KVANTITATIVNI SASTAV Jedna kapsula sadrži 30 mg duloksetina (u obliku duloksetinklorida).
Very Rare disorder Ejaculation delayed disorder Sexual dysfunction Testicular pain
U otvorenom dugotrajnom nekontroliranom ispitivanju smanjenje boli u bolesnika koji su reagirali na
Musculoskeletal and connective tissue disorders
Poremećaji mišićno-koštanog sustava i vezivnog tkiva bol spazam mišića trzanje mišića trizmus
The concomitant use of ARICLAIM with selective, reversible MAOIs, like moclobemide, is not recommended (see section 4.4).
MAO, poput moklobemida (vidjeti dio 4.4).
- are taking medicines to treat depression (see ‘Other medicines and ARICLAIM') - are taking St. John's Wort, a herbal treatment (Hypericum perforatum) - have kidney disease - have had seizures (fits) - have had mania - suffer from bipolar disorder - have eye problems, such as certain kinds of glaucoma (increased pressure in the eye) - have a history of bleeding disorders (tendency to develop bruises) - are at risk of low sodium levels (for example if you are taking diuretics, especially if you are elderly) - are currently being treated with another medicine which may cause liver damage - are taking other medicines containing duloxetine (see ‘Other medicines and ARICLAIM')
- patite od bipolarnog poremećaja - imate probleme s očima poput određenih vrsta glaukoma (povišen očni tlak) - u povijesti bolesti imate poremećaje krvarenja (sklonost pojavi modrica)
Urine odour abnormal
• stezanje mišića čeljusti • neuobičajen miris mokraće
The treatment duration was up to 2 years.
Liječenje je trajalo do dvije godine.
The timetable for the implementation of the agreement is set out in Annex III.
Rok za provedbu sporazuma naznačen je u Prilogu III.
Spontaneous reports
Spontane prijave
Efficacy
Učinkovitost
• Respiratory events, mainly due to awareness of respiratory movements
• respiratorne nuspojave, uglavnom zbog svjesnosti respiratornih pokreta
The PRAC took in account the MAH's position.
PRAC je uzeo u obzir stav MAH-a.
The first Marketing Authorisation in the EU was granted in France on 10 December 1982.
Prvo odobrenje za stavljanje gotovog lijeka u promet u EU izdano je u Francuskoj 10. prosinca 1982.
In 50% of the cases, a neuropathy was also reported.
U 50% slučajeva zabilježena je i neuropatija.
Data from clinical trials
Podaci dobiveni iz kliničkih ispitivanja
In addition, the PRAC noted that the mechanism of these 2 adverse reactions remains unknown.
Osim toga, PRAC je istaknuo da mehanizam tih dviju nuspojava ostaje nepoznat.
The MAH has never performed trials or investigations to document/establish the mechanism of action of these adverse effects.
MAH nikad nije proveo ispitivanja ili istraživanja da bi dokumentirao/utvrdio mehanizam djelovanja tih nuspojava.
The mean time to onset for the cases reported was 5 months but time to onset was variable ranging from 15 days to 2,5 years.
Prosječno vrijeme pojavljivanja zabilježenih slučajeva bilo je pet mjeseci, no vrijeme pojavljivanja variralo je od 15 dana do 2,5 godine.
In the view of the negative benefit risk balance, patients will need to be switched to alternative therapies.
U pogledu negativne uravnoteženosti koristi i rizika, pacijenti će morati biti prebačeni na zamjenske terapije.
No effect was nor observed on pulmonary functional status.
Ni jedan učinak nije uočen vezano za plućni funkcionalni status.
However, no data supports the restrictive indication proposed by the MAH.
Međutim, ni jedan podatak ne podupire ograničenu indikaciju koju je predložio MAH.
Almitrine containing medicinal products for oral use are currently authorised in 3 European Member States (France, Poland and Portugal) and only marketed in France and Poland (see Annex I for the list of almitrine containing medicinal products for oral use authorised in the EU).
Medicinski proizvodi za oralnu primjenu koji sadrže almitrin trenutačno su odobreni u tri europske države članice (Francuska, Poljska i Portugal), a u promet su stavljeni samo u Francuskoj i Poljskoj (vidjeti Prilog I. za popis medicinskih proizvoda za oralnu primjenu koji sadrže almitrin odobrenih u EU).
In addition, France had concerns with regards to the benefit of almitrine in its approved indications.
Osim toga, Francuska je izrazila zabrinutost vezano za koristi almitrina u njegovim odobrenim indikacijama.
In November 2012 the French National Competent Authority considered that the above-mentioned major safety concerns were not fully controlled in clinical practice despite the risk minimisation measures in place.
U studenom 2012. francusko nacionalno nadležno tijelo zaključilo je da prethodno navedena ozbiljna pitanja sigurnosti nisu u potpunosti kontrolirana u kliničkoj praksi, usprkos mjerama smanjenja rizika koje su bile na snazi.
Scientific conclusions and grounds for the revocation of the marketing authorisations
Znanstveni zaključci i razlozi za opoziv odobrenja za stavljanje gotovog lijeka u promet
The PRAC is of the opinion that almitrine cannot be considered as an alternative to LTOT for which reduction in mortality has been achieved.
PRAC smatra da se almitrin ne može smatrati zamjenom za LTOT kod kojeg je postignuto smanjenje stope smrtnosti.
An important proportion of cases seems to have been reported with an outcome as not recovered during the period from September 2003 to December 2012 (5 cases of the 7 reported).
Čini se da je značajan dio slučajeva zabilježen s ishodom neoporavka tijekom razdoblja od rujna 2003. do prosinca 2012. (pet slučajeva od sedam prijavljenih).
Consideration that long-term oxygen therapy can be discontinued, delayed or even avoided with almitrine is not based on scientific or clinical evidence.
Razmatranja da se dugoročna terapija kisikom može prekinuti, odgoditi ili čak izbjeći uz primjenu almitrina ne temelji se na znanstvenim ili kliničkim dokazima.
Finally the PRAC noted that the current international consensus for the management of COPD and chronic hypoxemia (Global Initiative for Obstructive Lung Disease (GOLD) and other practical recommendation) does no longer refer to the use of almitrine.
PRAC je naposljetku primijetio da se trenutačni međunarodni konsenzus za upravljanje KOBP-om i kroničnom hipoksemijom (Globalna inicijativa za kroničnu opstruktivnu plućnu bolest (GOLD) i ostale praktične preporuke) više ne odnosi na primjenu almitrina.
Globally, an important proportion of cases had an outcome reported as not recovered or recovered with sequelae (489 cases out of the 2304 reported, i.e. 21.2%).
U globalnom smislu, u većem je dijelu slučajeva zabilježen ishod neoporavka ili oporavka s posljedicama (sequlae) (489 slučajeva od 2304 prijavljena slučaja, odnosno 21,2%).
The PRAC noted that weight loss reported led to almitrine discontinuation in 90,9% of the cases.
PRAC je istaknuo da je zabilježeni gubitak težine doveo do prekida primjene almitrina u 90,9% slučajeva.
Weight loss observed in patients with respiratory insufficiency is progressive.
Gubitak težine zabilježen u ispitanika s respiratornom insuficijencijom je progresivan.
The decrease in reporting of peripheral neuropathy mentioned by the MAH, is probably mainly related to the decrease in sales over the last 10 years.
Smanjenje zabilježenih slučajeva periferne neuropatije koje je naveo MAH vjerojatno je uglavnom povezano sa smanjenjem prodaje u posljednjih 10 godina.
Moreover, no data is available to support any benefit of almitrine in the restrictive indication proposed by the MAH (patient with PaO2: 55 mmHg< PaO2< 65 mmHg).
Štoviše, nisu dostupni podaci koji bi poduprli bilo koju korist almitrina u ograničenoj indikaciji koju predlaže MAH (ispitanik s PaO2: 55 mmHg < PaO2 < 65 mmHg).
In view of the 11 above mentioned published clinical studies, it is acknowledged that efficacy results among clinical studies are contradictory and extrapolations not feasible.
S obzirom na 11 navedenih objavljenih kliničkih ispitivanja, priznaje se da su rezultati učinkovitosti različitih kliničkih ispitivanja kontradiktorni i da ekstrapolacije nisu moguće.
Regarding weight loss, 795 cases were reported since launch, some of them severe.
Vezano za gubitak težine, od stavljanja lijeka u promet zabilježeno je 795 slučajeva, od kojih su neki bili ozbiljni.
Hypoxemia alone is not sufficient to explain severe weight loss reported with almitrine.
Sama hipoksemija nije dovoljna za objašnjenje ozbiljnog gubitka težine povezanog s almitrinom.
This was supported by the fact that cases of peripheral neuropathy continued to be reported from September 2003 to November 2012 despite the implemented minimisation measures (recommendation for a sequential scheme of administration and dose adjustment initially, followed by contra-indications and warnings).
Navedeno je poduprto činjenicom da su od rujna 2003. do studenog 2012. prijavljivani slučajevi periferne neuropatije, usprkos provedenim mjerama smanjenja rizika (preporuka za sekvencijalnu shemu primjene i prilagodbe prvotne doze, nakon čega slijede kontraindikacije i upozorenja).
The PRAC considered that many of the publications reported that a clinical benefit of oral almitrine could not be seen in terms of exacerbations or hospitalisation, exercise capacity, clinical outcome, survival, or quality of life.
PRAC je smatrao da je u mnogim publikacijama zabilježeno da klinička korist oralne primjene almitrina nije vidljiva u smislu egzacerbacija ili hospitalizacije, kapaciteta vježbanja, kliničkog ishoda, preživljavanja ili kvalitete života.
During the period September 2003 to December 2012, 20 cases of peripheral neuropathies were reported, suggesting that the risk minimisation measures are not able to prevent the occurrence of these reactions.
Tijekom razdoblja između rujna 2003. i prosinca 2012. zabilježeno je 20 slučajeva perifernih neuropatija, što ukazuje na to da mjere smanjenja rizika ne mogu spriječiti pojavljivanje navedenih nuspojava.
Spontaneous reports of peripheral neuropathies persist even after the introduction of sequential administration scheme.
Spontane prijave perifernih neuropatija zabilježene su i nakon uvođenja sheme sekvencijalne primjene.
In published clinical studies with continuous administration1234567, peripheral neuropathies and weight loss were encountered when the study duration was longer than 3 months, indicating that the duration of continuous exposure have played a role in their development.
U objavljenim kliničkim ispitivanjima sa stalnom primjenom,1234567, periferne neuropatije i gubitak težine zabilježeni su u slučajevima kad je trajanje ispitivanja bilo duže od tri mjeseca, ukazujući na to da je trajanje stalne izloženosti utjecalo na njihov razvoj.
Besides, the PRAC also noted that the knowledge in physiopatholigical mechanism and management of COPD (including life expectancy in COPD) has been considerably improved.
Osim toga, PRAC je također istaknuo značajan napredak znanja koje se odnosi na fiziopatološki mehanizam i upravljanje KOBP-om (uključujući očekivani životni vijek kod KOBP-a).
The PRAC noted that most cases of peripheral neuropathies reported from September 2003 to December 2012 were not recovered or recovered with sequelae.
PRAC je istaknuo da se većina slučajeva perifernih neuropatija zabilježenih od rujna 2003. do prosinca 2012. nije oporavila ili se oporavila s posljedicama.
One of the proposed further risk minimisation measures by the MAH was a restricted indication in patients with PaO2 between 55 mmHg and 65 mmHg or as adjuvant treatment to Long Term Oxygen Therapy (LTOT).
Jedna od predloženih daljnjih mjera smanjenja rizika MAH-a bila je restriktivna indikacija u ispitanika s PaO2 između 55 mmHG i 65 mmHg ili kao adjuvantno liječenje dugoročne terapije kisikom (LTOT).
The NCAs should undertake timely actions allowing an appropriate switching of patients to other therapeutic alternatives.
Nacionalna nadležna tijela trebala bi poduzeti pravovremene korake radi osiguranja odgovarajućeg prebacivanja pacijenata na ostale zamjenske terapije.
The doses of 100-200 mg of almitrine continuously were associated with a higher incidence of adverse effects and withdrawals compared to placebo.
Doze od 100 do 200 mg almitrina kontinuirano su bile povezivane s učestalijim štetnim događajima i ustezanjem u usporedbi s placebom.
Taken together, these clinical trials enrolled 2036 patients (1380 under almitrine, 656 under placebo).
Ukupno su navedena klinička ispitivanja uključivala 2036 ispitanika (1380 ih je primalo almitrin, a 656 placebo).
• Digestive events (nausea, burning sensation and sensation of epigastric heaviness, dyspepsia),
• probavne nuspojave (mučnina, žgaravica i osjećaj epigastrične težine, dispepsija)
Overall, a significant number of cases with outcomes reported as not recovered or recovered with sequelae is not acceptable to the PRAC.
Stoga PRAC značajan broj slučajeva s ishodom zabilježenim kao neoporavak ili oporavak s posljedicama smatra neprihvatljivim.
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.
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.
A total of 11 published clinical studies which became available after the initial Marketing Authorisation were reviewed.
Revidirano je ukupno 11 objavljenih kliničkih ispitivanja koja su postala dostupna nakon prvotnog odobrenja za stavljanje gotovog lijeka u promet.
France has taken a number of national regulatory actions to minimise the risk of these adverse reactions associated with almitrine for oral use.
Francuska je poduzela niz nacionalnih regulatornih koraka kako bi smanjila rizik navedenih nuspojava povezanih s almitrinom za oralnu primjenu.
This included data from the Member States and published literature data which became available since the original marketing authorisations and the MAH's response.
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.
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).
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).
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:
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:
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.
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).
Almitrine for oral use was studied in several clinical studies.
Almitrin za oralnu primjenu ispitivan je u nekoliko kliničkih ispitivanja.
This adverse effect was also clearly recognised in the trials comparing almitrine at high doses to placebo.
Ta je nuspojava također očito prepoznata u ispitivanjima koja uspoređuju almitrin u visokim dozama s placebom.
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.
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.
The reported reactions consisted mainly of peripheral neuropathy and weight loss.
Prijavljene nuspojave uglavnom su se odnosile na perifernu neuropatiju i gubitak težine.
The last trials, conducted with sequential treatment and following a double blind placebo controlled design, account for 366 patients.
Posljednja ispitivanja, tijekom kojih je provedeno sekvencijalno liječenje, nakon dvostruko slijepog, placebom kontroliranog nacrta ispitivanja, uključivala su 366 ispitanika.
Safety
Neškodljivost
In addition, the benefit claimed by the MAH that long-term oxygen therapy can be delayed with almitrine is not substantiated by supporting data.
Osim toga, tvrdnja MAH-a da dugoročna terapija kisikom može biti odgođena uz primjenu almitrina nije poduprta odgovarajućim podacima.
• 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.
• 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.
• 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).
• 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.).
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.
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.
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.
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.
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.
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.
The first trials, conducted with non-sequential treatment, account for 1670 patients (1006 following a double blind, placebo controlled design).
Prva ispitivanja, tijekom kojih je primijenjeno nesekvencijalno liječenje, uključivala su 1670 ispitanika (1006 nakon dvostruko slijepog, placebom kontroliranog nacrta ispitivanja).
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.
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.
In France, almitrine containing medicinal products for oral use have been under close monitoring due to serious adverse reaction .
U Francuskoj se medicinski proizvodi za oralnu primjenu koji sadrže almitrin pomno prate zbog ozbiljnih nuspojava.
Concerns have also been raised with regards to the potential risks of hepatobilary disorders, skin disorders and cytopenia with the use of oral almitrine.
Izražena je i zabrinutost vezano za moguće rizike poremećaja jetre i žuči, poremećaja kože i citopenije kod oralne primjene almitrina.
Risk minimisation measures (reduction of the dose and implementation of a sequential treatment scheme ) were implemented since the initial marketing authorisation.
Mjere smanjenja rizika (smanjenje doze i provedba sheme sekvencijalnog liječenja) provođene su od prvotnog odobrenja za stavljanje gotovog lijeka u promet.
No benefit has been demonstrated when almitrine was used as an adjuvant of that intervention.
Prilikom korištenja almitrina kao adjuvansa toj intervenciji nije zabilježena ikakva korist.