natgillin/translations-raw huggingface dataset:
On 18 March 2008, Bioenvision Ltd, a wholly owned subsidiary of Genzyme Corporation, officially notified the Committee for Medicinal Products for Human Use (CHMP) that it wishes to withdraw its application for a change to the marketing authorisation for Evoltra.
Bioenvision Ltd, podružnica v popolni lasti družbe Genzyme Corporation, je dne 18. marca 2008 uradno obvestila Odbor za zdravila za uporabo v humani medicini (CHMP), da želi umakniti vlogo za spremembo dovoljenja za promet z zdravilom Evoltra.
It belongs to the group of anti-cancer medicines called ‘antimetabolites'.
Spada v skupino zdravil proti raku, ki jim pravimo „antimetaboliti“.
The study did not compare Evoltra with any other treatment.
V študiji zdravila Evoltra niso primerjali z nobenim drugim zdravljenjem.
It is used when the disease has not responded to, or has come back (relapsed), after at least two other treatments, and when no other treatment is expected to work.
Uporablja se, kadar se bolezen ne odzove na zdravljenje ali se ponovi po vsaj dveh drugih zdravljenjih in kadar se ne pričakuje učinkovitost nobene druge oblike zdravljenja.
This stops the cells making new DNA and slows down the growth of tumour cells.
Zato celice prenehajo izdelovati novo DNK, rast tumorskih celic pa se upočasni.
The change concerned an extension of indication to add the treatment of acute myeloid leukaemia in elderly patients.
Sprememba se je nanašala na razširitev indikacije za zdravljenje akutne mieloidne levkemije pri starejših bolnikih.
There were also some concerns over the medicine's side effects affecting the kidneys.
Nekaj zadržkov je bilo tudi zaradi stranskih učinkov zdravila na ledvica.
There are no consequences on the use of Evoltra in the authorised indication, for which the balance of benefits and risks remains unchanged.
Umik nima nobenih posledic za uporabo zdravila Evoltra za odobreno indikacijo, pri kateri ostaja razmerje med koristmi in tveganji nespremenjeno.
Clofarabine is an analogue of adenine, which is part of the DNA, the fundamental genetic material of cells.
Klofarabin je analog adenina, ki je del DNK, osnovnega genetskega materiala celic.
The company presented results from one main study involving 66 patients aged 65 years or older with AML, who had not been treated before and were considered to be unsuitable for intensive chemotherapy.
Družba je predstavila izide ene glavne študije, v katero je bilo vključenih 66 bolnikov, starih 65 let ali več, z AML, ki pred tem niso bili zdravljeni in pri katerih se je menilo, da intenzivna kemoterapija ne bi bila primerna.
Based on the review of the data and the company's response to the CHMP list of questions, at the time of the withdrawal, the CHMP had some concerns and was of the provisional opinion that Evoltra could not have been approved for the treatment of the treatment of AML in elderly patients.
Na podlagi pregleda podatkov in odgovorov družbe na seznam vprašanj, ki jih je zastavil CHMP v času umika vloge, je imel CHMP zadržke in bil začasnega mnenja, da zdravila Evoltra ni mogoče odobriti za zdravljenje AML pri starejših bolnikih.
The main measure of effectiveness was the number of patients who went into ‘remission' (clearance of leukaemia from the bone marrow and complete or partial recovery of blood cell counts to normal levels).
Glavno merilo učinkovitosti je bilo število bolnikov, pri katerih je bila dosežena remisija (očistek levkemije iz kostnega mozga in popolno ali delno povečanje števila krvnih celic na normalne ravni).
It was to be used in patients who are not suitable for intensive chemotherapy, because they have certain genetic abnormalities in their myeloid cells, ‘secondary' AML (AML following a previous blood disorder) or another disease in addition to AML, or because they are 70 years of age or older.
Uporabljalo naj bi se pri bolnikih, pri katerih intenzivna kemoterapija ni primerna zaradi določenih genetskih nenormalnosti mieloidnih celic, „drugotne“ AML (AML, ki sledi predhodni krvni motnji) ali druge bolezni, ki se pojavi hkrati z AML, oziroma ker so stari sedemdeset let ali več.
What are the consequences of the withdrawal for patients in clinical trials or compassionate use programmes using Evoltra?
Kakšne so posledice umika za bolnike, ki sodelujejo v kliničnih preskušanjih ali programih sočutne uporabe zdravila Evoltra?
What is Evoltra?
Kaj je zdravilo Evoltra?
In the body, clofarabine takes the place of adenine, and interferes with the enzymes involved in making genetic material.
V telesu klofarabin prevzame mesto adenina in ovira encime, ki sodelujejo pri izgradnji genetskega materiala.
The Committee was concerned that the main study included a number of patients who could have been suitable for intensive chemotherapy and this could have made the effectiveness of Evoltra look more promising.
Odbor je izrazil zaskrbljenost, da je glavna študija vključevala številne bolnike, pri katerih bi lahko bilo primerno zdravljenje z intenzivno kemoterapijo, pri čemer bi bila učinkovitost zdravila Evoltra obetavnejša.
It contains the active substance clofarabine.
Vsebuje zdravilno učinkovino klofarabin.
The application was at day 90 when the company withdrew.
Družba je vlogo umaknila na 90. dan postopka.
The company informed the CHMP that this withdrawal has no consequences for patients enrolled in clinical trials or compassionate use programmes with Evoltra.
Družba je obvestila CHMP, da umik nima posledic za bolnike, ki so vključeni v klinična preskušanja ali programe sočutne uporabe za zdravilo Evoltra.
The CHMP was concerned that the main study was not sufficient to establish the benefit of Evoltra in the treatment of AML in elderly patients who were unsuitable for intensive chemotherapy, and that the results of a study comparing Evoltra with standard treatment would be necessary to determine the medicine's effectiveness.
CHMP je imel zadržke, da glavna študija ni zadovoljivo dokazala koristnih učinkov zdravila Evoltra za zdravljenje AML pri starejših bolnikih, pri katerih izvajanje intenzivne kemoterapije ne bi bilo primerno, ter da bi bili za ugotovitev učinkovitosti zdravila potrebni rezultati študije, s katero bi primerjali učinke zdravila Evoltra z učinki pri standardnem zdravljenju.
What was Evoltra expected to be used for?
Za kaj naj bi se zdravilo Evoltra uporabljalo?
In the new indication, Evoltra was also expected to be used to treat patients aged over 65 years who have acute myeloid leukaemia (AML, cancer of the myeloid cells, a type of immature white blood cell).
V novi indikaciji naj bi se zdravilo Evoltra uporabljalo tudi pri bolnikih, starih 65 let ali več, z akutno mieloidno levkemijo (AML, rak mieloidnih celic, vrsta nezrelih belih krvnih celic).
How is Evoltra expected to work?
Kako naj bi zdravilo Evoltra delovalo?
Therefore, at the time of the withdrawal, the CHMP's view was that a benefit of Evoltra had not been sufficiently demonstrated and any benefits did not outweigh the identified risks.
Zato je CHMP v času umika menil, da koristi zdravila Evoltra niso bile zadostno dokazane in ne odtehtajo znanih tveganj.
Evoltra is already used to treat children with acute lymphoblastic leukaemia (ALL, cancer of the lymphocytes, a type of white blood cell).
Zdravilo Evoltra se že uporablja za zdravljenje otrok z akutno limfoblastno levkemijo (ALL, rakom limfocitov, vrsta belih krvnih celic).
Evoltra is a concentrate that is made up into a solution for infusion (drip into a vein).
Zdravilo Evoltra je koncentrat za pripravo raztopine za infundiranje (dajanje v veno).
What is happening for Evoltra for treatment of ALL in children?
Kaj to pomeni za zdravilo Evoltra, indicirano za zdravljenje ALL pri otrocih?
The active substance in Evoltra, clofarabine, is a cytotoxic (a medicine that kills cells that are dividing, such as cancer cells).
Zdravilna učinkovina zdravila Evoltra, klofarabin, je citotoksična (zdravilo, ki ubija deleče se celice, kot so rakaste celice).
Within 3 months of Commission Decision
V 3 mesecih po odločbi Komisije.
This 5 years retrospective (new users) study will also compare the relative risk between dexamfetamine and other stimulants in the patient population.
Ta petletna retrospektivna (novi uporabniki) študija bo primerjala tudi relativno tveganje pri deksamfetaminu in drugih stimulantih pri populaciji bolnikov.
The national competent authorities, coordinated by the reference Member State, shall ensure that the following conditions are fulfilled by the marketing authorisation holders:
Pristojni nacionalni organi, ki jih usklajuje referenčna država članica, morajo zagotoviti, da imetniki dovoljenja za promet z zdravilom izpolnijo naslednje pogoje:
4. part III, pharmacovigilance plan: category 1 should be added for the PASS and the DUS.
4. del III, načrt farmakovigilance: kategorija 1 se mora dodati za študijo PASS in študijo o uporabi zdravila.
The applicant shall conduct a PASS to evaluate the long-term safety profile of dexamfetamine in children with ADHD, specifically targeting key issues such as cardiovascular events, growth and psychiatric related adverse events.
Predlagatelj mora izvesti študijo PASS za ovrednotenje profila dolgoročne varnosti deksamfetamina pri otrocih z ADHD, s posebnim poudarkom na ključnih problemih, kot so srčno-žilni dogodki, rast in psihiatrični neželeni dogodki.
As part of this study the MAH shall actively obtain reports of abuse, misuse, diversion and dependence in children with ADHD from poison centres, drug monitoring centres, other databases, publicly available information in the literature and online.
V okviru te študije mora imetnik dovoljenja za promet z zdravilom aktivno zbirati poročila o zlorabi, napačni uporabi, uporabi za rekreativne namene in odvisnosti pri otrocih z ADHD iz centrov za zastrupitve, centrov za spremljanje drog, drugih podatkovnih zbirk, javno dostopnih informacij iz literature in spleta.
3. annex 7: should include the text of a proposed follow up form to be used for specific adverse event follow-up.
3. priloga 7 mora vsebovati besedilo predlaganega obrazca za spremljanje, ki se bo uporabljal za spremljanje določenih neželenih dogodkov;
The applicant shall undertake a DUS to follow the use of prescribed dexamfetamine in the European Union using multiple data sources.
Predlagatelj mora izvesti študijo o uporabi zdravila, namenjeno spremljanju uporabe predpisanega deksamfetamina v Evropski uniji s pomočjo različnih virov podatkov.
The applicant shall submit an updated RMP taking into consideration the following recommendations: 1. section VI.2.5 Documentation for public summary should include a summary of risk minimisation measures by safety concern.
1. poglavje VI.2.5 Dokumentacija za povzetek za javnost mora vsebovati povzetek ukrepov za zmanjšanje tveganja po varnostnih tveganjih;
2. annex 2 should include the proposed text of the package leaflet in addition to the proposed SmPC.
2. priloga 2 mora poleg predlaganega povzetka glavnih značilnosti zdravila vsebovati tudi predlagano besedilo navodila za uporabo;
This opinion supersedes the opinion on temporary measures adopted on 4 July 2011.
To mnenje nadomesti mnenje o začasnih ukrepih, sprejeto 4. julija 2011.
The mean age was 70.2 and 71.6 years, respectively.
Povprečna starost je bila 70,2 oziroma 71,6 let.
years of age).
stopnje)“.
As a result, a procedure under Article 107 of Directive 2001/83/EC, as amended was automatically initiated.
Samodejno je bil sprožen postopek iz člena 107 Direktive 2001/83/ES, v skladu s spremembami le-te.
The need to consider renal function was also introduced.
Uvedena je bila tudi potreba po upoštevanju ledvične funkcije.
Safety of the injectable formulations of buflomedil
Varnost injekcijskih formulacij buflomedila
The CHMP also noted the two French pharmacovigilance enquiries covering the period 1998 to 2004 and 2006 to 2009.
CHMP je upošteval tudi dve francoski farmakovigilančni poizvedbi, ki pokrivata obdobji od leta 1998 do 2004 in od leta 2006 do 2009.
The procedure started during the February 2011 CHMP meeting.
Postopek se je začel februarja 2011 med sejo Odbora za zdravila za uporabo v humani medicini (CHMP).
Thalès observational drug utilisation study
Thalèsova opazovalna študija o uporabi zdravil
Overall summary of the scientific evaluation of buflomedil-containing medicinal products (see Annex I)
Splošni povzetek znanstvenega vrednotenja zdravil, ki vsebujejo buflomedil (glejte Prilogo I)
Buflomedil-containing medicines are authorised and marketed in 12 EU countries by national procedures and were first authorised in France in 1974.
Zdravila, ki vsebujejo buflomedil, so odobrena z nacionalnimi postopki in prisotna na trgu v 12 državah EU, prvič pa so bila odobrena leta 1974 v Franciji.
Discussion on efficacy
Razprava o učinkovitosti
Overall summary on safety and on risk minimisation measures
Splošni povzetek o varnosti in o ukrepih za zmanjšanje tveganj
Annex II Scientific conclusions and grounds for the suspension of the marketing and use of the products presented by the EMA
Priloga II Znanstveni zaključki in podlaga za začasni preklic prometa z zdravilom in uporabe proizvodov, ki jih kje predstavila agencija EMA
Overall conclusions on safety
Splošni zaključki o varnosti
In addition to these 5 cases, a further two cases related to renal impairment were identified, where the dose was unknown.
Poleg teh 5 primerov so opredelili še dva primera, povezana z okvaro ledvic, pri čemer je bil odmerek neznan.
In addition, 32 cardiological adverse events were retrieved; the most frequent reactions were tachycardia, hypertension, flushing and hypotension.
Poleg tega je bilo opaženih 32 kardioloških neželenih učinkov; najpogostejše reakcije so bile tahikardija, hipertenzija, oblivanje in hipotenzija.
Risk minimisation measures
Ukrepi za zmanjšanje tveganj
Usage of buflomedil according to these conditions is considered to be under normal conditions of use.
Uporaba buflomedila v skladu s temi pogoji velja za uporabo v okviru običajnih pogojev uporabe.
Regarding the proposed additional pharmacovigilance activities, the CHMP was of the opinion that signal detection is no longer a priority, given that the risks associated with buflomedil are now identified and confirmed.
Glede predlaganih dodatnih farmakovigilančnih dejavnosti je CHMP menil, da dodatno zaznavanje signalov ni več prednostna naloga, saj so sedaj tveganja, povezana z buflomedilom, opredeljena in potrjena.
Discussion on safety
Razprava o varnosti
The study compared a reference period of 6 months before the 2006 French evaluation with two 6-months evaluation periods following the implementation of the resulting RMMs and the circulation of a DHPC.
V študiji so primerjali referenčno obdobje 6 mesecev pred francosko ocenitvijo iz leta 2006 z dvema 6-mesečnima ocenitvenima obdobjema po uvedbi posledičnih ukrepov za obvladovanje tveganj in kroženjem neposrednega sporočila med zdravstvenim osebjem.
However, the CHMP noted that the analysis did not demonstrate statistical significance and that the results therefore did not allow to conclude on a statistically significant reduction in the combined primary endpoint compared to placebo.
Vendar pa je CHMP opazil, da analiza ni pokazala statistične značilnosti, zato na podlagi rezultatov ni bilo mogoče sklepati na statistično značilno zmanjšanje kombiniranega primarnega izida v primerjavi s placebom.
In 70% of the cases, the dose of buflomedil received by the patients was inappropriate because of underlying renal failure.
V 70 % primerov je bil odmerek buflomedila, ki so ga bolniki prejeli, neustrezen zaradi osnovne odpovedi ledvic.
Grounds for the suspension of the Marketing Authorisations
Razlog za začasni preklic dovoljenja za promet z zdravilom
The CHMP was of the opinion that despite this reduction, the percentage of patients at risk remained unacceptably high.
CHMP je bil mnenja, da ostaja odstotek bolnikov, izpostavljenih tveganju, kljub temu zmanjšanju nesprejemljivo visok.
Consequently, the CHMP recommended to the European Commission the suspension of the Marketing Authorisations of buflomedil-containing medicinal products listed in Annex I of the Opinion in all concerned EU Member States.
Posledično je CHMP Evropski komisiji predlagal začasni preklic dovoljenja za promet z zdravili, ki vsebujejo buflomedil, naštetimi v Prilogi I tega mnenja, v vseh zadevnih državah članicah EU.
The approved maximum daily dose in patients with normal renal function is 600 mg and 300 mg in patients with renal impairment.
Odobren največji dnevni odmerek pri bolnikih z normalnim delovanjem ledvic je 600 mg, pri bolnikih z okvaro ledvic pa 300 mg.
For the lifting of the suspension, the Marketing Authorisation Holders should provide convincing data to identify a population in which the benefits of buflomedil clearly outweigh its identified risks (see Annex III).
Za odpravo začasnega preklica dovoljenja za promet mora imetnik dovoljenja za promet predložiti prepričljive podatke z opredelitvijo populacije, v kateri koristi zdravljenja z buflomedilom jasno odtehtajo opredeljena tveganja (glejte Prilogo III).
In December 2010, a further French benefit-risk evaluation of buflomedil was carried out, following which the French National Competent Authority suspended all French Marketing Authorisations for buflomedil-containing products.
V decembru leta 2010 so v Franciji opravili dodatno oceno razmerja med koristmi in tveganji uporabe buflomedila, po kateri je pristojni francoski nacionalni organ začasno umaknil vsa francoska dovoljenja za promet z zdravili, ki vsebujejo buflomedil.
In addition, review of all available individual case safety data related to buflomedil identified 28 cases of overdoses in elderly patients (over 65
Poleg tega je pregled vseh razpoložljivih podatkov o varnosti iz posamičnih primerov, povezanih z buflomedilom, opredelil 28 primerov prevelikega odmerjanja pri starejših bolnikih (starih 65 let ali več).
There were 6 cases of cardiovascular and 6 cases of neurological serious adverse events.
6 primerov je navajalo kardiovaskularne in 6 primerov nevrološke resne neželene učinke.
Buflomedil is an α1-, α2-adrenolytic agent with vasoactive and haemorheologic properties, improving the blood flow in the microcirculation as well as tissue oxygenation.
Buflomedil je adrenolitično α1-, α2-sredstvo z vazoaktivnim in hemoreološkim delovanjem, ki izboljšuje krvni pretok na mikrocirkulatorni ravni in oskrbo tkiva s kisikom.
Following an oral explanation held in July 2011, the MAH was requested to propose further risk minimisation measures and asked whether a restricted population could be identified.
Po ustni razlagi v juliju 2011 so imetnika dovoljenja za promet z zdravilom zaprosili za dodatne ukrepe za zmanjšanje tveganj in za opredelitev populacije z omejeno uporabo.
The study showed that about 30% of patients with renal failure still receive an excessive dose, although it was noted that this had decreased from 75% prior to the DHPC.
Študija je pokazala, da je približno 30 % bolnikov z ledvično odpovedjo še vedno prejelo prevelik odmerek, čeprav je bilo zabeleženo, da se je to zmanjšalo s 75 % pred neposrednim sporočilom za zdravstveno osebje.
One patient experienced convulsions after taking two 300 mg tablets at the same time instead of two tablets BID.
Pri enem bolniku so se pojavili krči po sočasnem vnosu dveh 300 mg tablet namesto dveh tablet dvakrat na dan.
The CHMP noted that of the 24 reported cases (about 5% of all adverse drug reactions recorded in the MAH database), a majority (13 out of 24) were cases of accidental overdose.
CHMP je opazil, da je bila od 24 sporočenih primerov (približno 5 % vseh neželenih učinkov na zdravilo, zabeleženih v podatkovni bazi imetnika dovoljenja za promet z zdravilom), večina (13 od 24) primerov nenamernega prevelikega odmerjanja.
Various indications previously registered across the EU were deleted and the indication was restricted to the Symptomatic treatment of chronic peripheral vascular disease (stage 2) (intermittent claudication), bringing it in line with the French SmPC.
Izbrisane so bile različne indikacije, ki so bile pred tem registrirane po vsej EU, indikacija pa je bila omejena na Simptomatsko zdravljenje kronične periferne žilne bolezni (2. stopnje) (intermitentna klavdikacija) v skladu s francoskim povzetkom glavnih značilnosti zdravila.
Buflomedil is currently approved in France in the treatment of ”symptomatic peripheral arterial occlusive disease (PAOD Stage II) symptoms”.
Buflomedil je v Franciji trenutno odobren za zdravljenje „simptomov bolezni sistemske okluzije perifernih arterij (BOPA II.
As the Risk Management Plan (RMP) proposed in the scope of this Article 107 procedure is equivalent to the French RMP implemented in 2006, the CHMP was therefore of the opinion that it is possible to conclude on the effectiveness of the proposed RMMs, despite the lack of implementation in all member states.
Ker je načrt za obvladovanje tveganja, predlagan v okviru postopka iz člena 107, enakovreden francoskemu RMP, ki je bil uveden leta 2006, CHMP meni, da je možno zaključiti o učinkovitosti predlaganih ukrepov za zmanjševanje tveganj, čeprav še niso bili vpeljani v vseh državah članicah.
If dose-adaptation is not done correctly, this leads to serious and lifethreatening toxicity.
Nepravilna prilagoditev odmerka lahko povzroči hudo do življenjsko nevarno toksičnost.
In addition, the CHMP observed with concern that an initial assessment of renal function was only carried out in 20% of patients and that measurements of creatinine clearance were only performed in 17% of patients, despite the SmPC recommendations.
CHMP je z zaskrbljenostjo opazoval tudi, da so začetno ocenitev delovanja ledvic opravili le pri 20 % bolnikov in da so očistek kreatinina izmerili le pri 17 % bolnikov, kljub priporočilom v povzetku glavnih značilnosti zdravila.
The CHMP acknowledged that variations to implement the European harmonisation of the SmPC are still ongoing in some countries but noted that the RMP proposed by Amdipharm in May 2010 was largely equivalent to the RMPs already implemented in France.
CHMP priznava, da so spremembe za uvedbo evropske uskladitve povzetka glavnih značilnosti zdravila v nekaterih državah še vedno v teku, vendar je opazil, da se načrt za obvladovanje tveganja, ki ga je maja 2010 predlagalo podjetje Amdipharm, v veliki meri ujema z načrtom za obvladovanje tveganja, ki se v Franciji že uporablja.
The CHMP also examined a review of all available individual case safety data related to buflomedil, conducted by the MAH, based on post-marketing safety data from Abbott Laboratories' global safety database and Amdipharm's safety database, published medical literature (worldwide) and from a number of other sources, including Toxicology/Poison Control Centres and Regulatory Authorities.
CHMP je proučila tudi pregled vseh razpoložljivih posamičnih poročil o škodljivih neželenih učinkih, povezanih z buflomedilom, ki ga je opravil imetnik dovoljenja za promet z zdravilom na podlagi podatkov o varnosti v obdobju po začetku trženja, iz svetovne baze podatkov o varnosti podjetja Abbott Laboratories in baze podatkov o varnosti podjetja Amdipharm, objavljene medicinske literature (po vsem svetu) in podatke številnih drugih virov, vključno s podatki centrov za toksikologijo/nadzor zastrupitev in regulatornih organov.
Serious cardiovascular and neurological adverse events under normal conditions of use
Resni kardiovaskularni in nevrološki neželeni učinki v običajnih pogojih uporabe
The CHMP also noted the pharmacovigilance and toxicovigilance data which show no improvement of the safety profile of buflomedil despite the implementation of the RMP in France in 2006; instead, a two fold increase of misuse compared to the previous period was observed.
CHMP je opazil tudi, da podatki o farmakovigilanci in toksikovigilanci ne kažejo na izboljšanje varnostnega profila buflomedila kljub uvedbi načrta za obvladovanje tveganja v Franciji leta 2006; nasprotno, opazili so dvakratno povečanje napačne uporabe v primerjavi s prejšnjim obdobjem.
From these cases, a total of 12 cases were identified in which patients were treated within the maximum therapeutic range (i.e. up to 600 mg daily) of buflomedil.
Ugotovljeno je bilo, da so v skupaj 12 od teh primerov bolnike zdravili znotraj največjega terapevtskega razpona (tj. do 600 mg na dan) za uporabo buflomedila.