natgillin/translations-raw huggingface dataset:
Furthermore the PRAC agreed on additional pharmacovigilance activities and risk minimisation measures.
Poleg tega se je PRAC dogovoril o dodatnih dejavnostih farmakovigilance in ukrepih za zmanjšanje tveganja.
Cases possible related to flupirtine treatment, and with re-challenge reported, had reoccurrence or worsening of the symptoms in 93% of the cases.
Pri primerih, ki so bili verjetno povezani z zdravljenjem s flupirtinom in pri katerih so poročali o ponovni uporabi zdravila, so v 93 % primerov opazili ponoven pojav ali poslabšanje simptomov.
Overall summary of the scientific evaluation of flupirtine containing medicinal products by PRAC
Splošni povzetek znanstvenega vrednotenja zdravil, ki vsebujejo flupirtin, odbora PRAC
Flupirtine is available as 100 mg immediate release capsules, 400 mg modified release tablet, 75 mg and 150 mg suppositories and as solution for injection (100 mg).
Flupirtin je na voljo v obliki 100-miligramskih kapsul s takojšnjim sproščanjem, 400-miligramskih tablet s prirejenim sproščanjem, 75- in 150-miligramskih svečk ter raztopine za injiciranje (100 mg).
Flupirtine is a ‘selective neuronal potassium channel opener' (SNEPCO) that acts by reducing the excessive electrical activity that leads to many pain states.
Flupirtin je „selektivni odpiralec kalijevih kanalčkov v živčnih celicah“ (selective neuronal potassium channel opener - SNEPCO), ki deluje tako, da zmanjša prekomerno električno aktivnost v možganih, ki je vzrok za številne boleče motnje.
The PRAC also noted that according to the current scientific knowledge including the Note for Guidance on clinical investigation of medicinal products for treatment of nociceptive pain (CPMP/EWP/612/00) clinical data of at least 3 months for the treatment of mild to moderately severe chronic back pain is required.
PRAC je upošteval tudi, da so glede na trenutna znanstvena dognanja, ki vključujejo smernice za klinične raziskave zdravil za zdravljenje nociceptivne bolečine (CPMP/EWP/612/00), potrebni klinični podatki za najmanj 3 mesece zdravljenja blagih do zmerno hudih kroničnih bolečin v hrbtu.
Based on the above safety concerns and further to consideration of the current evidence of efficacy of flupirtine in the treatment of chronic and acute pain, the BfArM considered the benefit-risk not to be favourable in the treatment of chronic pain and potential favourable in acute pain subject to effective implementation of risk minimisation measures (e.g. limited duration of treatment, closely liver monitoring) and therefore on 28 February 2013 initiated an urgent union procedure under Article 107i of Directive 2001/83/EC.
Na podlagi zgoraj navedenih zadržkov, povezanih z varnostjo, in preučitve trenutno razpoložljivih podatkov o učinkovitosti flupirtina pri zdravljenju kroničnih in akutnih bolečin je BfArM menil, da razmerje med tveganji in koristmi pri zdravljenju kroničnih bolečin ni pozitivno, pri zdravljenju akutnih bolečin pa je lahko pozitivno pod pogojem, da se učinkovito izvajajo ukrepi za zmanjšanje tveganja (npr. omejeno trajanje zdravljenja, natančno spremljanje jeter), zato je dne 28. februarja 2013 sprožil nujni postopek Unije v skladu s členom 107i Direktive 2001/83/ES.
Overall, the oral and suppositories formulations are indicated for the treatment of acute and chronic pain while the injectable is indicated for short-term use for acute pain such as post-operative pain.
Na splošno so peroralne farmacevtske oblike in svečke indicirane za zdravljenje akutnih in kroničnih bolečin, medtem ko je raztopina za injiciranje indicirana za kratkoročno uporabo pri akutnih bolečinah, na primer po operaciji.
If liver function tests show pathological results your doctor will ask you to discontinue intake/use of <Product Name> immediately.
Če bo zdravnik pri preverjanju delovanja jeter opazil patološke spremembe, vam bo predlagal, da nemudoma prekinete jemanje/uporabo zdravila <ime zdravila>.
Detailed explanation for the differences from the PRAC recommendation
Podrobna obrazložitev odstopanj od priporočila PRAC
Most studies presented are in management of pain in short term use only and management of chronic pain is intended for long term use in most cases.
V večini predloženih študij so preučevali samo obvladovanje bolečin pri kratkoročni uporabi, medtem ko je v večini primerov za obvladovanje kroničnih bolečin potrebna dolgoročna uporaba.
For the treatment of acute pain, the PRAC recommended that the benefit still outweighs the hepatotoxicity risk when treatment with other analgesics (e.g. non-steroidal anti-inflammatory drugs, weak opioids) is contraindicated.
V zvezi z zdravljenjem akutnih bolečin je PRAC menil, da so koristi še vedno večje od tveganja za hepatotoksičnost, kadar je zdravljenje z drugimi analgetiki (npr. nesteroidnimi protivnetnimi zdravili, šibkimi opioidi) kontraindicirano.
Liver transplantation or fatal cases resulting from liver failure were seen after 3-5 weeks of treatment in 25% of the cases and the remaining after 60 days of treatment (information is only available from 8 cases of the total of 15 fatal cases).
Presaditev jeter ali smrtne primere zaradi odpovedi jeter so pri 25 % primerov zabeležili po 3-5 tednih zdravljenja, pri ostalih pa po 60 dneh zdravljenja (podatki so bili na voljo samo za 8 od skupno 15 primerov s smrtnim izidom).
These have been requested by PRAC for submission within the risk management plan.
PRAC je zahteval, da se gradivo predloži v okviru načrta za obvladovanje tveganja.
The PRAC considered that in the short term use studies, the efficacy of flupirtine in acute pain was at least comparable to the comparators.
PRAC je menil, da je bila v študijah kratkoročne uporabe učinkovitost flupirtina pri akutnih bolečinah vsaj primerljiva z učinkovitostjo primerjalnih zdravilnih učinkovin.
As part of the risk minimisation measures the PRAC recommended amendments to the product information for all flupirtine containing medicinal products.
PRAC je v sklopu ukrepov za zmanjšanje tveganja predlagal spremembo informacij o zdravilu za vsa zdravila, ki vsebujejo flupirtin.
Herrmann WM: Final report: Investigation of the long-term tolerability of the analgesic flupirtine in patients who require analgesics regularly over long periods of time.
Herrmann WM: Final report: Investigation of the long-term tolerability of the analgesic flupirtine in patients who require analgesics regularly over a long period of time.
The PRAC considered that a Direct healthcare professional communication (DHPC) was needed to communicate the outcome of the present review.
PRAC je menil, da je treba izdati neposredno obvestilo zdravstvenim delavcem (DHPC), da se jih seznani z izidom tega pregleda.
The PRAC noted that based on clinical and histological features, the hepatotoxicity of flupirtine may be immune-mediated and that hepatotoxicity associated with flupirtine treatment may be type B or idiosyncratic adverse drug reaction.
Odbor PRAC je upošteval, da bi lahko bila glede na klinične in histološke lastnosti hepatotoksičnost flupirtina imunsko pogojena in da bi bila lahko hepatotoksičnost, povezana z zdravljenjem s flupirtinom, neželeni učinek zdravila tipa B ali idiosinkratična reakcija.
The PRAC endorsed a Direct Healthcare Professional Communication (DHPC), to communicate the outcome of the present review to the healthcare professionals, in particular, the restricted indication and maximum duration of use and to highlight the risk of hepatotoxicity and the necessary measures needed to minimise this risk.
PRAC je odobril neposredno obvestilo zdravstvenim delavcem (Direct Healthcare Professional Communication - DHPC), da se jih seznani z izidom tega pregleda, zlasti z omejeno indikacijo ter najdaljšim trajanjem zdravljenja, in da se jih opozori na tveganje za hepatotoksičnost ter ukrepe, potrebne za zmanjšanje tega tveganja.
In view of the risks of hepatotoxicity the PRAC considered there was a need to recommend further risk minimisation measures to ensure the safety and effective use in acute pain.
V zvezi s tveganjem za hepatotoksičnost je PRAC menil, da bi bilo za zagotovitev varne in učinkovite uporabe pri akutnih bolečinah treba priporočiti dodatne ukrepe za zmanjšanje tveganja.
Most cases were reports of increased liver enzymes, jaundice, hepatitis or hepatic failure.
V večini primerov so poročali o povišanih jetrnih encimih, zlatenici, hepatitisu ali odpovedi jeter.
The CMDh having considered the PRAC recommendation dated 13 June 2013 pursuant to Article 107k(1) and (2) of Directive 2001/83/EC reached a position on the variation to the terms of the marketing authorisations of flupirtine containing medicinal products for which the relevant sections of the summary of product characteristics and package leaflet are set out in Annex III and subject to the conditions set out in Annex IV.
Skupina CMDh je na podlagi preučitve priporočila, ki ga je dne 13. junija 2013 v skladu s členom 107k(1) in (2) Direktive 2001/83/ES podal PRAC, sprejela stališče o spremembi pogojev dovoljenj za promet z zdravili, ki vsebujejo flupirtin, skladno z besedili ustreznih poglavij povzetka glavnih značilnosti zdravila in navodila za uporabo, opredeljenimi v Prilogi III, in pod pogoji, določenimi v Prilogi IV.
Another publication4 described six cases of flupirtine-induced liver injury, including one requiring liver transplantation.
V drugi publikaciji4 je opisanih šest primerov okvare jeter zaradi flupirtina, pri čemer je bila v enem primeru potrebna presaditev jeter.
However, three published studies1,2,3 reported elevated transaminases in 3%, 31% and 58.6% respectively, of the patients treated with flupirtine.
povišane vrednosti transaminaz pri 3 %, 31 % oziroma 58,6 % bolnikov, zdravljenih s flupirtinom.
Finally educational materials are necessary in order to clearly inform prescribers and patients on the hepatotoxicity risk associated with flupirtine and on the measures necessary to minimise the risk.
Poleg tega je potrebno tudi izobraževalno gradivo, s katerim se bo zdravnike, ki bodo predpisovali zdravilo, in bolnike natančno seznanilo s tveganjem za hepatotoksičnost, povezanim s flupirtinom, in ukrepi, potrebnimi za zmanjšanje tega tveganja.
The time to onset of liver failure observed in spontaneous reporting was 25 % for each of the cases after 2-3 weeks, after 3-8 weeks, after 8-13 weeks and after >13 weeks (information on time to onset was available in 35 cases of the total 49 cases).
Čas do pojava odpovedi jeter, zabeležen pri spontanih poročilih, je bil 2-3 tedne, 3-8 tednov, 8-13 tednov in > 13 tednov, pri čemer posamezen čas velja za 25 % primerov (podatki o času do pojava odpovedi so bili na voljo za 35 od skupno 49 primerov).
There were no reports of liver failure from published clinical trials.
V objavljenih kliničnih preskušanjih ni poročil o odpovedi jeter.
Scientific conclusions and grounds for variation to the terms of the marketing authorisations subject to conditions and detailed explanation for the differences from the PRAC recommendation
Znanstveni zaključki in podlaga za spremembo pogojev dovoljenj za promet z zdravili pod določenimi pogoji ter podrobna obrazložitev odstopanj od priporočila odbora PRAC
The PRAC, as a consequence, concluded that pursuant to Article 116 of Directive 2001/83/EC the riskbenefit balance for flupirtine containing medicinal products in the management of chronic pain is not favourable.
je PRAC zaključil, da v skladu s členom 116 Direktive 2001/83/ES razmerje med tveganji in koristmi za zdravila, ki vsebujejo flupirtin, pri obvladovanju kroničnih bolečin ni pozitivno.
Your doctor will test liver function every week during treatment with <Product Name> because increased liver enzyme levels, hepatitis and liver failure have been reported in association with flupirtine therapy.
Zdravnik bo v času zdravljenja z zdravilom <ime zdravila> vsak teden preverjal delovanje vaših jeter, saj so v povezavi z uporabo flupirtina poročali o povišanih ravneh jetrnih encimov, hepatitisu in odpovedi jeter.
Data on efficacy of flupirtine in the use of chronic pain is very limited.
Podatki o učinkovitosti flupirtina pri zdravljenju kroničnih bolečin, so zelo omejeni.
The exact wording recommended by the PRAC to relevant sections of the Summary of Product Characteristics (SmPC) and Package Leaflet (PIL) are found in Annex III of this recommendation.
Točno besedilo za zadevna poglavja povzetka glavnih značilnosti zdravila (SmPC) in navodila za uporabo, ki ga je priporočil PRAC, je navedeno v Prilogi III k temu priporočilu.
In addition, the frequency of the observed increase in hepato-biliary markers in clinical studies lead to a higher frequency of occurrence of these adverse drug reactions and consequently amendments to the products information in this regard.
Poleg tega je pogostost porasta označevalcev bolezni jeter, žolčnika in žolčevodov, opaženega v kliničnih študijah, povzročila večjo pojavnost teh neželenih učinkov zdravila, zato so potrebne spremembe informacij o zdravilu v zvezi s tem.
Furthermore the PRAC requested that the protocol of a Post Authorisation Safety Study (PASS) should be submitted within the risk management plan submission, to evaluate the effectiveness of the risk minimisation activities.
PRAC je nadalje zahteval, da se v okviru načrta za obvladovanje tveganja predloži študija varnosti zdravila v obdobju trženja (PASS), namenjena oceni učinkovitosti dejavnosti za zmanjšanje tveganja.
The PRAC also recommended that the MAH should submit a full risk management plan (RMP) within a certain timeframe.
Prav tako je priporočil, naj imetnik dovoljenja za promet z zdravilom v določenem časovnem okviru predloži celovit načrt za obvladovanje tveganja (RMP).
• The PRAC concluded that in view of the currently available safety data in order to maintain a favourable benefit/risk in the management of acute pain, flupirtine containing medicinal products should have treatment duration restricted to 2 weeks, contraindicated in patients with pre-existing liver disease.
• PRAC je na podlagi trenutno razpoložljivih podatkov o varnosti zaključil, da bi bilo treba za ohranitev pozitivnega razmerja med koristmi in tveganji pri obvladovanju akutnih bolečin trajanje zdravljenja z zdravili, ki vsebujejo flupirtin, omejiti na 2 tedna in uporabo kontraindicirati pri bolnikih z že obstoječo boleznijo jeter.
• The PRAC reviewed all available data from clinical and non-clinical studies, epidemiological studies, spontaneous reports and published literature on the safety and efficacy of flupirtine containing medicinal products, as well as stakeholders' submissions in particular with regards to the risk of hepatotoxicity.
• PRAC je pregledal vse razpoložljive podatke o varnosti in učinkovitosti zdravil, ki vsebujejo flupirtin, iz kliničnih in predkliničnih študij, epidemioloških študij, spontanih poročil in objavljene literature, ter podatke, ki so jih predložile zainteresirane strani, zlasti v povezavi s tveganjem za hepatotoksičnost;
7 Herrmann WM, Hiersemenzel R, Aigner M et al.: Die Langzeitverträglichkeit von Flupirtin.
Herrmann WM, Hiersemenzel R, Aigner M in sod.
The PRAC also agreed on the need of a risk management plan to be submitted together with a protocol for a drug utilisation study aiming to characterise prescribing practices during typical clinical use in representative groups of prescribers.
Prav tako se je PRAC dogovoril, da je treba skupaj z načrtom za obvladovanje tveganja predložiti tudi protokol za študijo uporabe zdravila, s katero bi razjasnili prakse pri predpisovanju med običajno klinično uporabo pri reprezentativni skupini zdravnikov, ki predpisujejo ta zdravila.
However, the CMDh considered that changes were necessary to the wording proposed in section 2 of the PL, in order to accurately reflect the PRAC recommended amendments to the SmPC section 4.3 “contraindications”.
Vendar pa je menila, da so potrebne spremembe besedila, predlaganega za 2. poglavje navodila za uporabo, ki bi natančno odražale spremembe, ki jih je PRAC priporočil za poglavje 4.3 „Kontraindikacije” v povzetku glavnih značilnosti zdravila.
During the period of 1999 to March 2013 a total of 136 reports of flupirtine drug induced liver injury (DILI, hepatic necrosis, liver failure including fatal cases) have been identified in spontaneous reporting and literature including 15 cases with fatal outcome.
V obdobju od leta 1999 do marca 2013 so iz spontanih poročil in literature ugotovili skupno 136 primerov okvar jeter, povezanih s flupirtinom (z zdravilom povzročena okvara jeter, nekroza jeter, odpoved jeter, vključno s smrtnimi primeri), od tega 15 primerov s smrtnim izidom.
• The PRAC is of the opinion that data from safety provide evidence for an increased risk of hepatotoxicity including cases with fatal outcome or resulted in liver transplantation when duration of treatment is longer than 2 weeks.
• PRAC meni, da je iz podatkov o varnosti razvidno, da se pri zdravljenju, ki traja več kot 2 tedna, poveča tveganje za hepatotoksičnost, pri čemer podatki vključujejo tudi primere, ki so se končali s smrtnim izidom ali presaditvijo jeter;
Also aiming minimisation of the hepatotoxicity risk associated with flupirtine, close monitoring of the liver function during treatment should be performed and its use contraindicated in patients with preexisting liver disease.
Za zmanjšanje tveganja za hepatotoksičnost, povezanega s flupirtinom, je treba v času zdravljenja opravljati tudi natančne preglede delovanja jeter in kontraindicirati uporabo pri bolnikih z že obstoječo boleznijo jeter.
It is acknowledged that the majority of cases included concomitant medication known to have potential for hepatic adverse reactions and that the combination of COX-2 inhibitors or NSAIDs with flupirtine may significantly increase the severity of the hepato-biliary reactions.
Ugotovljeno je bilo, da je večina primerov vključevala sočasno uporabo drugih zdravil z znanim tveganjem za neželene učinke na jetra in da lahko kombinacije zaviralcev COX-2 ali nesteroidnih protivnetnih zdravil in flupirtina znatno povečajo intenzivnost neželenih učinkov na jetra, žolčnik in žolčevode.
Overall conclusion and conditions to the Marketing Authorisations Having considered the overall submitted data provided by the MAHs in writing and in the oral explanation, the PRAC concluded that: a. the marketing authorisation holders should sponsor a post-authorisation safety study together with the follow up evaluation of the results of that study; b. the marketing authorisation holders should implement risk minimisation measures;
Splošni zaključki in pogoji dovoljenj za promet z zdravili Po preučitvi vseh podatkov, ki so jih v obliki pisne dokumentacije in ustnih obrazložitev predložili imetniki dovoljenj za promet z zdravili, je PRAC zaključil, da: a. morajo imetniki dovoljenj za promet z zdravili sponzorirati študijo o varnosti zdravila v obdobju trženja in nadaljnje vrednotenje rezultatov študije; b. morajo imetniki dovoljenj za promet z zdravili izvajati ukrepe za zmanjšanje tveganja; c. so potrebne spremembe dovoljenj za promet z zdravili.
Data from the literature as well as data from randomised clinical trials,,, showed an increment of markers for hepato-biliary impairment associated with the treatment of flupirtine.
Tako podatki iz literature kot tudi podatki iz randomiziranih kliničnih preskušanj1,2,3,4 so pokazali porast označevalcev bolezni jeter, žolčnika in žolčevodov, povezanih z zdravljenjem s flupirtinom.
Open study over 12 months, single blind subsequent observation period of 14 days (including an „Additional evaluation about a group of very old patients > 80 years“) Degussa-Report No. D-09998 / 75 057 C, (for publication see also below)
Open study over 12 months, single blind subsequent observation period of 14 days (including an „Additional evaluation about a group of very old patients > 80 years“).
Moreover, liver function should be kept under closely monitoring i.e. weekly during the treatment with flupirtine which should be discontinued upon symptoms and signals of liver disorders.
Prav tako je treba skrbno pregledovati delovanje jeter, in sicer enkrat na teden v času zdravljenja s flupirtinom, ki ga je treba ob pojavu simptomov in znakov bolezni jeter prekiniti.
The PRAC concluded that the benefit-risk balance for flupirtine containing medicinal products remains favourable in the treatment of acute pain subject to the agreed restrictions, contraindications, warnings, other changes to the product information and additional risk minimisation measures.
PRAC je zaključil, da je razmerje med tveganji in koristmi za zdravila, ki vsebujejo flupirtin, pri zdravljenju akutnih bolečin še vedno pozitivno, če se upoštevajo dogovorjene omejitve, kontraindikacije, opozorila, druge spremembe informacij o zdravilu in dodatni ukrepi za zmanjšanje tveganja.
A total of 330 hepatic and biliary disorders were reported post-marketing, of which 49 involved liver failure and 15 had a fatal outcome or resulted in liver transplantation.
V obdobju trženja so poročali o skupno 330 primerih bolezni jeter, žolčnika in žolčevodov; v 49 primerih je prišlo do odpovedi jeter, 15 pa se jih je končalo s smrtnim izidom ali presaditvijo jeter.
The amendments aim to reflect the restricted use of maximum of two weeks of treatment, consequently only for use in acute pain and when other analgesics are contraindicated.
na največ dva tedna ter posledično uporabo samo pri akutnih bolečinah in v primerih, ko so ostali analgetiki kontraindicirani.
Direct healthcare professional communication were agreed, together with the timelines for distribution and that a postauthorisation safety study as well as a drug utilisation study should be conducted.
Odbor se je dogovoril o neposrednem obvestilu zdravstvenim delavcem in rokih za njegovo razdelitev ter določil, da je treba izvesti študijo varnosti v obdobju trženja ter tudi študijo uporabe zdravila;
Since no cases of hepatotoxicity including cases with fatal outcome or which resulted in liver transplantation have been identified so far in the first two weeks of treatment, PRAC concluded that flupirtine use should be restricted to a maximum of two weeks.
Ker do sedaj v prvih dveh tednih zdravljenja niso zabeležili nobenih primerov hepatotoksičnosti, ki bi se končali s smrtnim izidom ali presaditvijo jeter, je PRAC zaključil, da bi moralo biti zdravljenje s flupirtinom omejeno na največ dva tedna.
If you observe any symptoms that may indicate hepatic damage during treatment with <Product Name> (e.g. loss of appetite, nausea, vomiting, abdominal discomfort, fatigue, dark urine, jaundice,
Če v času zdravljenja z zdravilom <ime zdravila> opazite katere koli simptome, ki bi lahko kazali na okvaro jeter (npr. izguba teka, slabost, bruhanje, nelagodje v trebuhu, utrujenost, temen urin, zlatenica, pruritus), morate prenehati jemati/uporabljati zdravilo <ime zdravila> in se takoj posvetovati z zdravnikom.
In view of the hepatotoxicity and very limited efficacy PRAC concluded that the benefit/risk for flupirtine containing medicinal products in the management of chronic pain is no longer favourable.
Ob upoštevanju hepatotoksičnosti in zelo omejene učinkovitosti je PRAC zaključil, da razmerje med tveganji in koristmi za zdravila, ki vsebujejo flupirtin, pri obvladovanju kroničnih bolečin ni več pozitivno.
[Oral pharmaceutical forms and suppositories] Do not <take><use><Product name> if you: suffer from pre-existing liver disease suffer from alcoholism concomitantly use other medicinal products known to cause drug induced liver injury.
[Peroralne farmacevtske oblike in svečke] Ne <jemljite><uporabljajte> zdravila <ime zdravila>, če: - imate že obstoječo bolezen jeter;
In addition, patients should have their liver function monitored after each full week of treatment and treatment should be stopped if there are signs of liver problems.
Poleg tega bi bilo treba v času zdravljenja vsak teden pregledati delovanje bolnikovih jeter in prekiniti zdravljenje, če bi se pojavili znaki težav z jetri;
[All pharmaceutical forms]
Opozorila in previdnostni ukrepi [Vse farmacevtske oblike]