natgillin/translations-raw huggingface dataset:
• The Committee considers that the benefit of cilostazol is modest but that a statistically significant increase in walking distance compared with placebo has been shown in patients with intermittent claudication;
• Odbor meni, da so koristi cilostazola majhne, vendar pa so pri bolnikih z intermitentno klavdikacijo opazili statistično pomembno izboljšanje prehojene razdalje v primerjavi s placebom;
The concerns relating to interactions with other medications (in particular CYP3A4 and CYP2C19 inhibitors) and the possibility of an increased risk for adverse effects have been addressed by the recommendation of a dose reduction to 50mg bid in patients taking concomitant medicines that inhibit these enzymes.
Zaradi skrbi glede medsebojnega delovanja z drugimi zdravili (zlasti z zaviralci CYP3A4 in CYP2C19) in možnosti povečanega tveganja za neželene učinke je Odbor pri bolnikih, ki uporabljajo zdravila, ki zavirajo omenjena encima, predlagal zmanjšanje odmerka na 50 mg dvakrat na dan.
The first DUS' will obtain baseline data with the objective to describe the characteristics of new users of cilostazol and the duration of the use of cilostazol and discontinuation patterns.
V prvi študiji bodo pridobili osnovne podatke za opredelitev značilnosti novih uporabnikov cilostazola in trajanja uporabe ter vzorcev prekinitve zdravljenja.
Cilostazol is associated with a modest but statistically significant increase in walking distance compared with placebo in patients with IC, and this has also been demonstrated using quality of life measurements.
Cilostazol je zmerno, vendar statistično pomembno podaljšal prehojeno razdaljo v primerjavi s placebom pri bolnikih z IK, kar so potrdile tudi ocene kakovosti življenja.
In addition, considering its anti-platelet activity, cilostazol is expected to increase the risk of bleeding.
Poleg tega je mogoče pričakovati, da bi cilostazol s svojim antiagregacijskim delovanjem povečal tveganje za krvavitve.
Other adverse events of interest such as myocardial ischemia (myocardial infarction, angina pectoris, coronary artery disease), congestive heart failure and hypotension, were also identified during the mid-term efficacy clinical trials, with a higher incidence in the cilostazol group compared to placebo.
Med srednjeročnimi kliničnimi preskušanji učinkovitosti so se pojavili tudi drugi pomembni neželeni učinki, na primer ishemična bolezen srca (srčni infarkt, angina pektoris, koronarna arterijska bolezen), kongestivno srčno popuščanje in hipotenzija, pri čemer je bila njihova pogostnost večja v skupini s cilostazolom kot v skupini s placebom.
• The Committee is of the opinion that some patients may benefit from cilostazol treatment to a clinically relevant degree; however, in view of the existing safety concerns, the Committee considered it appropriate to restrict use to those who have not responded to lifestyle treatment and to recommend that treatment is only continued in those who have shown a meaningful response within the first 3 months;
• Odbor meni, da bi cilostazol pri nekaterih bolnikih lahko izkazal klinično pomembne koristi; vendar pa je zaradi obstoječih zadržkov glede varnosti Odbor presodil, da je treba uporabo omejiti na tiste bolnike, ki se ne odzovejo na zdravljenje s spremembami življenjskega sloga,
Cilostazol's effect on absolute walking distances on the treadmill, expressed as an absolute increase over baseline walking distance ranged from +23m to +109m, compared with -2m to +65m for placebo.
Učinek cilostazola na absolutno prehojeno razdaljo na tekočem traku, izražen kot absolutno podaljšanje prehojene razdalje glede na izhodišče, je znašal od +23 m do +109 m, učinek placeba pa od -2 m do +65 m. Metaanaliza tehtane srednje razlike (weighted mean difference - WMD) iz devetih preskušanj je prav tako pokazala dosledno učinkovitost cilostazola.
The second DUS will have the objective to evaluate the effectiveness of the proposed SmPC changes, educational initiatives and other implemented risk minimisation measures in terms of the mitigation of off-label use and adherence of prescribers to the SmPC, in comparison with baseline data.
Cilj druge študije bo na podlagi primerjave z osnovnimi podatki oceniti, ali so predlagane spremembe povzetka glavnih značilnosti zdravila, izobraževalne pobude in drugi sprejeti ukrepi za zmanjšanje tveganja učinkoviti v smislu zmanjšanja uporabe, ki ni skladna z odobrenimi indikacijami, in upoštevanja povzetka glavnih značilnosti pri predpisovanju zdravila.
In order to minimise the risk of drug metabolism interaction, warnings have been introduced in the SmPC and it is now recommended to reduce the dose to 50mg bid in patients taking medicines that inhibit CYP3A4 or 2C19.
Za zmanjšanje tveganja za vpliv drugih zdravil na presnovo cilostazola so bila v povzetek glavnih značilnosti zdravila vključena dodatna opozorila, poleg tega pa je sedaj pri bolnikih, ki jemljejo zaviralce CYP3A4 ali 2C19, priporočeno zmanjšanje odmerka na 50 mg dvakrat na dan.
This reduced dose has been shown to be clinically effective in clinical trials in patients using CYP3A4 or CYP2C19 inhibitors.
Poleg tega je CHMP priporočil, naj se pri sočasni uporabi z omenjenimi zdravili odmerek cilostazola zmanjša na 50 mg dvakrat na dan. Klinično učinkovitost tega odmerka so potrdili v kliničnih študijah pri bolnikih, ki so uporabljali zaviralce CYP3A4 ali CYP2C19.
The Committee concluded that the benefit-risk balance of cilostazol products for the improvement of the maximal walking distance and maximal pain-free walking distances in patients with intermittent claudication (IC), who do not have rest pain and who do not have evidence of peripheral tissue necrosis (peripheral arterial disease Fontaine stage II) remains positive under normal conditions of use, subject to restrictions, warning, changes to the product information and risk minimisation measures agreed.
Odbor je zaključil, da razmerje med tveganji in koristmi za zdravila, ki vsebujejo cilostazol in se uporabljajo za izboljšanje najdaljše prehojene razdalje in najdaljše razdalje, prehojene brez bolečin, pri bolnikih z intermitentno klavdikacijo (IK), ki nimajo bolečin med mirovanjem in ne kažejo znakov odmiranja perifernih tkiv (periferne arterijske bolezni (PAB) v II.
The vasodilatory effects of cilostazol may also be mediated through an increase in cAMP.
Zaradi zvišanja ravni cAMP ima lahko cilostazol tudi vazodilatacijske učinke.
Overall, the group was of the view that for a small group of patients with low risk of cardiovascular co-morbidities, limiting intermittent claudication who cannot manage initial exercise rehabilitation, or who are unsuitable for revascularisation, this drug may have a role.
Skupina je podprla predlog imetnikov dovoljenj za promet z zdravili, naj se pri nekaterih podskupinah bolnikov priporoči zmanjšanje odmerka na 50 mg dvakrat na dan. Na splošno je skupina menila, da bi zdravilo lahko imelo koristi pri majhni skupini bolnikov z nizkim tveganjem za sočasne kardiovaskularne bolezni ali intermitentno klavdikacijo, ki jim preprečuje, da bi začeli telesno dejavnost, in pri bolnikih, ki niso primerni za revaskularizacijo.
The anti-platelet activity of cilostazol also raised a concern for haemorrhagic events.
Zaradi antiagregacijskega delovanja cilostazola so se pojavile tudi skrbi zaradi morebitnih krvavitev.
5 x 1 bottle (unit pack)
5 x 1 steklenica (posamično pakiranje)
EU Number
Številka eu
Packaging Content
Ovojnina Vsebina
The study will therefore be repeated, with the final results expected to be ready by the end of June 2013.
Študija bo zato ponovljena, končni rezultati pa se pričakujejo konec junija 2013.
In all three media, both products released more than 85% or close to 85% of the drug substance within 15 minutes and more than 95% in 20 minutes.
V vseh treh sredstvih je zdravilo sprostilo več kot 85 % ali skoraj 85 % zdravilne učinkovine v 15 minutah ter več kot 95 % v 20 minutah.
Overall summary of the scientific evaluation of Cilazapril Teva and associated names (see Annex I)
Splošni povzetek znanstvenega vrednotenja zdravila Cilazapril Teva in povezanih imen (glejte Prilogo I)
• The Committee considered the procedure under Article 31 of Directive 2001/83/EC for Cilazapril Teva and associated names.
• Odbor je obravnaval postopek v skladu s členom 31 Direktive 2001/83/ES za zdravilo Cilazapril Teva in povezana imena.
The report covers the period 1st January 2009 to 31st December 2011 and identified two case reports, both of which were medically confirmed reports describing non-serious adverse reactions.
V poročilu, ki zajema obdobje od 1. januarja 2009 do 31. decembra 2011, sta bili obravnavani dve zdravstveno potrjeni poročili o primeru, v katerih so opisani neresni neželeni učinki.
Cilazapril Teva is available as 0.5 mg, 1 mg and 2.5 mg and 5 mg tablets.
Zdravilo Cilazapril Teva je na voljo v obliki 0,5-, 1-, 2,5- in 5-miligramskih tablet.
Cilazapril Teva contains cilazapril, a pyridazine angiotensin-converting enzyme inhibitor (ACE inhibitor) used for the treatment of hypertension and congestive heart failure.
Zdravilo Cilazapril Teva vsebuje cilazapril, piridazinski zaviralec angiotenzin-konvertaze (zaviralec ACE), ki se uporablja za zdravljenje hipertenzije in kongestivnega srčnega popuščanja.
Finally the MAH noted that the periodic safety update report (PSUR) no. 383/01/12, dated February 13th 2012, reported no increased number of safety concerns with cilazapril.
Na koncu je imetnik dovoljenja za promet z zdravilom omenil, da v rednem posodobljenem poročilu o varnosti zdravila (PSUR) št. 383/01/12 z dne 13. februarja 2012 ni navedbe o povečanem številu varnostnih težav s cilazaprilom.
Only minor deficiencies were identified, which were not considered to influence the outcome of the clinical bioequivalence (e.g. exact EDTA matrix not specified, validated batch size not given, no influence of haemolytic or lipidaemic plasma shown, matrix effect in 4 different plasma batches shown).
Ugotovili so samo majhne razlike, za katere so menili, da ne bodo vplivale na izid klinične biološke enakovrednosti (npr. natančen matriks EDTA ni opredeljen, velikost validirane serije ni navedena, vpliv na hemolitično ali lipidemično plazmo ni prikazan, učinek matriksa prikazan pri 4 različnih serijah plazme).
The quality of the bio-analytical report was checked internally by the MAH and was considered to be of good quality, based on the guideline applicable at that time (“Guideline for Industry - Bioanalytical Method Validation”, May 2001).
Kakovost bioanalitičnega poročila je imetnik dovoljenja za promet z zdravilom preveril interno in je menil, da je dobra, kar je temeljilo na smernici, ki je veljala v tistem času („Guideline for Industry - Bioanalytical Method Validation“ - Smernica za stroko - validacija bioanalitične metode, maj 2001).
The Committee, as a consequence, recommended the suspension of the marketing authorisations for Cilazapril Teva and associated names, pursuant to Article 116 of Directive 2001/83/EC; as a. the risk-benefit balance cannot be considered favourable and b. the particulars supporting the application as provided in Article 10 of Directive 2001/83/EC cannot be considered correct
je odbor priporočil začasen umik dovoljenj za promet z zdravilom Cilazapril Teva in povezanimi imeni v skladu s členom 116 Direktive 2001/83/ES, ker a. razmerje med tveganji in koristmi ni pozitivno ter b. podatki, ki naj bi podprli vlogo v skladu s členom 10 Direktive 2001/83/ES, niso pravilni.
The MAH stated that the calculated f2 values indicated dissolution similarity between the drug products in all three media, and therefore considered the probability of the drug being released in the stomach to be high.
Imetnik dovoljenja za promet z zdravilom je navedel, da so izračunane vrednosti f2 pokazale podobno raztapljanje med zdraviloma v vseh treh sredstvih, zato je verjetnost, da se bo zdravilo sprostilo v želodcu, velika.
The CHMP was of the opinion that the previous conclusions regarding bioequivalence will need to be confirmed by repeating the bioequivalence study.
Odbor CHMP je menil, da bo treba prejšnje zaključke glede biološke enakovrednosti potrditi s ponovno izvedbo študije biološke enakovrednosti.
The resulting solution is not expected to precipitate at higher pH values later in the intestine, due to the good aqueous solubility of the compound.
Ni pričakovati, da se bo nastala raztopina oborila pozneje v črevesu pri večjih vrednostih pH, saj je spojina dobro topna v vodi.
The CHMP therefore recommended the suspension of the marketing authorisations until adequate bioequivalence data is made available.
Odbor CHMP je zato predlagal začasni umik dovoljenj za promet z zdravilom, dokler ustrezni podatki o biološki enakovrednosti ne bodo na voljo.
The CHMP considered that these results could not be extrapolated to confirm the reliability of the pivotal bioequivalence study 2005-980.
Odbor CHMP je menil, da teh podatkov ni mogoče ekstrapolirati, s čimer bi se lahko potrdila zanesljivost ključne študije biološke enakovrednosti 2005-980.
The CHMP also noted the PSUR data, which did not indicate any safety concerns; however this is insufficient to confirm the bioequivalence of the product.
Odbor CHMP je pregledal tudi podatke v poročilu PSUR, v katerih ni izpostavljenih nobenih varnostnih težav, vendar to ni bilo zadostno za potrditev biološke enakovrednosti zdravila.
The initial marketing authorisations applications for the Cilazapril Teva tablets were supported by a single pivotal bioequivalence study (Study 2005-980), comparing Cilazapril Teva with the EU reference product Vascace, for which samples were analysed by BA Research International (now Cetero Research) between May 26th 2005 and December 20th 2005.
Prvotne vloge za dovoljenje za promet z zdravilom Cilazapril Teva tablete so bile podprte z eno ključno študijo biološke enakovrednosti (študijo 2005-980), v kateri so zdravilo Cilazapril Teva primerjali z referenčnim zdravilom v EU Vascace, pri čemer je vzorce analizirala družba BA Research International (zdaj Cetero Research) med 26. majem 2005 in 20. decembrom 2005.
The CHMP was requested to assess whether the deficiencies in conduct of bio-analytical studies performed by the Cetero Research facilities in Houston (Texas, USA) have impact on the benefit/risk of the concerned medicinal products and to give its opinion on whether the marketing authorisations for authorised medicinal products for which studies have been carried out or samples analysed by Cetero Research, during the identified time period, should be maintained, varied, suspended or withdrawn.
Odbor CHMP so zaprosili za oceno o tem, ali pomanjkljivosti v izvedbi bioanalitičnih študij, opravljenih v ustanovi Cetero Research v Houstonu (Teksas, ZDA), vplivajo na razmerje med tveganji in koristmi pri uporabi zadevnih zdravil, ter za mnenje o tem, ali je treba dovoljenja za promet z odobrenimi zdravili, za katera so bile v ustanovi Cetero Research v navedenem časovnem obdobju opravljene študije ali analizirani vzorci, ohraniti, spremeniti, začasno umakniti ali ukiniti.
The MAH also referred to comparative dissolution data for the Cilazapril Teva tablets and the reference product, using three different dissolution media (0.1 N HCl, pH 4.5 acetate buffer and pH 6.8 phosphate buffer).
Imetnik dovoljenja za promet z zdravilom je predložil tudi primerjalne podatke o raztapljanju zdravila Cilazapril Teva tablete in referenčnega zdravila, pri čemer so bila uporabljena tri različna sredstva za raztapljanje (0,1 N HCl, pH 4,5 acetatni pufer in pH 6,8 fosfatni pufer).
Therefore, given the serious doubts regarding the reliability and the correctness of the data from the critical pivotal bioequivalence study 2005-980, submitted in support of the marketing authorisation, and in the absence of a reliable bioequivalence study specifically designed to establish the bioequivalence of Cilazapril Teva to its EU reference product, the CHMP was unable to conclude on the bioequivalence of Cilazapril Teva.
Zaradi resnih pomislekov glede zanesljivosti in pravilnosti podatkov iz kritične, ključne študije biološke enakovrednosti 2005-980, predložene kot podpora za dovoljenje za promet z zdravilom, in zaradi odsotnosti zanesljive študije biološke enakovrednosti, posebej zasnovane za ugotavljanje biološke enakovrednosti zdravila Cilazapril Teva in referenčnega zdravila v EU, odbor CHMP ni mogel sklepati o biološki enakovrednosti zdravila Cilazapril Teva.
The MAH was therefore of the view that the formulation of this immediate-release product will have only little influence on the bioavailability, which is supported by good point estimates for AUC and Cmax in study 2005-980.
Imetnik dovoljenja za promet z zdravilom je zato menil, da bo imela formulacija tega zdravila s takojšnjim sproščanjem samo majhen vpliv na biološko uporabnost, kar podpirajo dobre točkovne ocene za AUC in Cmax v študiji 2005-980.
The CHMP also noted the MAH review of study 2005-980 and the quality of the bio-analytical report and the reported similarity between the results generated by Cetero Research and those found from repeated studies/analysis for other drug products.
Prav tako je upošteval pregled študije 2005-980, ki ga je predložil imetnik dovoljenja za promet z zdravilom, ter kakovost bioanalitičnega poročila in poročano podobnost med rezultati, ki jih je pridobila ustanova Cetero Research, in rezultati, ki so jih ugotovili pri ponovljenih študijah/analizah za druga zdravila.
However, for Cilazapril Teva, the MAH stated that no study samples were available for study 2005-980 and that there is therefore no possibility to reanalyse the data.
Vendar je imetnik dovoljenja za promet z zdravilom navedel, da za zdravilo Cilazapril Teva v študiji 2005-980 niso bili na voljo nobeni vzorci in da zaradi tega ni bilo možnosti za ponovno analizo podatkov.
In response to the CHMP list of questions, the MAH stated that the pivotal bioequivalence study 2005980 conducted for Cilazapril Teva met the bioequivalence criteria (point estimates of 93.4% and 100% for AUC0-4h and Cmax, respectively) with respect to the Guideline on the Investigation of Bioequivalence.
Kot odgovor na seznam vprašanj odbora CHMP je imetnik dovoljenja za promet z zdravilom navedel, da je ključna študija biološke enakovrednosti 2005-980, izvedena za zdravilo Cilazapril Teva, izpolnila merila (točkovni oceni 93,4 % za AUC-4h in 100 % za Cmax) glede smernice za proučevanje biološke enakovrednosti.
The CHMP assessed the MAH responses and noted that the MAH had repeated a number of studies, producing data in line with that obtained by Cetero Research, although no details of these studies were included in the response documentation to support this.
Odbor CHMP je ocenil odgovore imetnika dovoljenja za promet z zdravilom in ugotovil, da je imetnik dovoljenja za promet z zdravilom ponovil številne študije, ki so podale podatke, skladne s podatki, ki so bili pridobljeni v ustanovi Cetero Research, čeprav v dokumentacijo z odgovori niso bile vključene podrobnosti teh študij, ki bi to podprle.
• The Committee considered that the available data gave rise to serious doubts as to the evidence of the bioequivalence of Cilazapril Teva and associated names with the EU reference product in view of concerns on the reliability of the data, due to the findings of the inspection of the Cetero Research facilities.
• Odbor je menil, da so razpoložljivi podatki povzročili resne dvome glede dokazov o biološki enakovrednosti zdravila Cilazapril Teva in povezanih imen ter referenčnega zdravila v EU zaradi pomislekov glede zanesljivosti podatkov, ki so bili izpostavljeni v ugotovitvah inšpekcijskega pregleda ustanove Cetero Research.
Having assessed the available data, the CHMP retained serious doubts due to the findings of the inspection of the Cetero Research facilities in Houston (Texas, USA), regarding the reliability and the correctness of the data from the critical pivotal bioequivalence study submitted in support of the marketing authorisation.
Na podlagi ocene razpoložljivih podatkov ima odbor CHMP še vedno resne dvome zaradi ugotovitev inšpekcijskega pregleda prostorov ustanove Cetero Research v Houstonu (Teksas, ZDA) glede zanesljivosti in pravilnosti podatkov iz kritične, ključne študije biološke enakovrednosti, predložene kot podpora za dovoljenje za promet z zdravilom.
Therefore, and in the absence of a reliable bioequivalence study specifically designed to establish the bioequivalence of Cilazapril Teva to its EU reference product, the benefit-risk balance of Cilazapril Teva cannot be considered to be favourable.
Zaradi odsotnosti zanesljive študije biološke enakovrednosti, posebej zasnovane za ugotavljanje biološke enakovrednosti zdravila Cilazapril Teva in referenčnega zdravila v EU, razmerja med tveganji in koristmi ni mogoče obravnavati kot pozitivnega.
• The Committee is of the opinion that considering the serious doubts in respect of the evidence of bioequivalence, the benefit-risk of Cilazapril Teva and associated names cannot be confirmed.
• Odbor je mnenja, da zaradi resnih dvomov glede dokazov o biološki enakovrednosti ni mogoče potrditi razmerja med tveganji in koristmi zdravila Cilazapril Teva in povezanih imen.
The highly soluble nature of the drug substance over the physiological pH range and the dissolution similarity between Cilazapril Teva and the reference product was also acknowledged.
Upoštevali so tudi veliko topnost zdravilne učinkovine v fiziološkem razponu pH ter raztapljanje, ki je bilo podobno med zdravilom Cilazapril Teva in referenčnim zdravilom.
The MAH considered that the data described in this PSUR did not impact the benefit-risk balance of Cilazapril Teva.
Imetnik dovoljenja za promet z zdravilom je menil, da podatki v tem poročilu PSUR niso vplivali na razmerje med tveganji in koristmi pri zdravilu Cilazapril Teva.
The CHMP also noted that due to the lack of availability of samples, it was not possible to reanalyse the samples from the clinical study in order to check the validity of the original findings, but the CHMP acknowledged the MAH intention to repeat the study, with final results expected to be available by the end of June 2013.
Odbor CHMP je prav tako ugotovil, da zaradi pomanjkljive razpoložljivosti vzorcev ni bilo mogoče ponovno analizirati vzorcev iz klinične študije, da bi se preverila veljavnost izvirnih ugotovitev.
On 01 August 2012, the United Kingdom triggered a referral under Article 31 of Directive 2001/83/EC for the identified nationally authorised products.
Direktive 2001/83/ES za ugotovljena nacionalno odobrena zdravila.
The MAH considered that the satisfactory results of these re-analyses suggest that the final outcome of the Cilazapril Teva study was not influenced by the bioanalytical analyses carried out at Cetero Research, Houston.
Imetnik dovoljenja za promet z zdravilom je menil, da zadovoljivi rezultati ponovnih analiz kažejo, da bioanalitične analize, ki jih je opravila ustanova Cetero Research v Houstonu, niso vplivale na končni izid študije z zdravilom Cilazapril Teva.
• The Committee considered that the responses of the MAH are not adequate to refute the serious doubts as to the evidence of the bioequivalence of Cilazapril Teva and associated names with the EU reference product.
• Odbor je menil, da odgovori imetnika dovoljenja za promet z zdravilom niso zadostni, da bi zavrnili resne dvome glede dokazov o biološki enakovrednosti zdravila Cilazapril Teva in povezanih imen ter referenčnega zdravila v EU.
In addition, the MAH stated that it had already carried out a number of repeats or re-assays of bioanalytical studies potentially affected by the Cetero Research findings for other Teva products in response to the concerns raised by the FDA.
Poleg tega je imetnik dovoljenja za promet z zdravilom kot odziv na pomisleke urada FDA navedel, da je že izvedel številne ponovitve ali ponovne teste za bioanalitične študije, na katere so morebitno vplivale ugotovitve ustanove Cetero Research za druga zdravila Teva.
However, the CHMP did not consider these general data to be sufficient to provide re-assurances specifically regarding the bioequivalence of Cilazapril Teva to its EU reference product.
Odbor CHMP je menil, da ti splošni podatki niso zadostni za ponovno zagotovitev biološke enakovrednosti zdravila Cilazapril Teva in referenčnega zdravila v EU.