natgillin/translations-raw huggingface dataset:
Flolan has been included in the list of products for Summary of Product Characteristics (SmPC) harmonisation in accordance with Article 30(2) of Directive 2001/83/EC.
Zdravilo Flolan je bilo vključeno na seznam za uskladitev povzetkov glavnih značilnosti zdravila v skladu s členom 30(2) Direktive 2001/83/ES.
There are differences in wording of the contraindications across Member States and detail given with respect to these contraindications.
Besedila kontraindikacij v državah članicah se med seboj razlikujejo, prav tako kot podrobnosti za te kontraindikacije.
The CHMP agreed on the rearrangement of this section and the addition of the warning on patients with coronary artery disease.
CHMP se je strinjal s preureditvijo tega poglavja in z dodanim opozorilom za bolnike z boleznijo srčnih arterij.
Section 4.8 - Adverse events
• Poglavje 4.8 - Neželeni dogodki
The effect of the overdose on the blood pressure was added in this section.
• V tem poglavju je bil dodan učinek prevelikega odmerjanja na krvni tlak.
The primary efficacy endpoint for the study was improvement in the 6MWT.
Primarna končna točka učinkovitosti študije je bilo izboljšanje 6minutnega testa hoje.
Eight of 40 (20%) patients receiving conventional therapy alone died, whereas none of the 41 patients receiving epoprostenol died (p=0.003).
Osem od 40 (20 %) bolnikov, ki so prejemali le konvencionalno zdravljenje, je umrlo, od 41 bolnikov, ki so prejemali epoprostenol, pa ni umrl noben (p = 0,003).
Of the patients who continued to bleed, severity generally improved more often and worsened less often in patients receiving heparin in major controlled studies.
Pri bolnikih, ki so še naprej krvaveli, se je resnost krvavitve na splošno pogosteje izboljšala in manj pogosto poslabšala pri bolnikih, ki so v glavnih nadzorovanih študijah prejemali heparin.
Based on the above, the CHMP considers the benefit/risk ratio of Flolan and associated names to be favourable and the harmonised Product Information documents to be approvable.
Na podlagi zgoraj navedenega CHMP meni, da je razmerje med koristmi in tveganji za zdravilo Flolan in povezana imena ugodno ter da je treba usklajene dokumente z informacijami o zdravilu odobriti.
In particular, the indications and their associated posology recommendations, the warnings and the information of fertility, pregnancy and lactation were harmonised.
Usklajene so bile zlasti indikacije in povezana priporočila za odmerjanje, opozorila in informacije o plodnosti, nosečnosti in dojenju.
The indications authorised in various Member States are: Pulmonary Arterial Hypertension and Renal dialysis.
Indikaciji, odobreni v različnih državah članicah, sta: pljučna arterijska hipertenzija in ledvična dializa.
• The committee considered the identified divergences for Flolan and associated names regarding the therapeutic indications, posology, the contraindications and warnings.
• Odbor je obravnaval opredeljene razlike za zdravilo Flolan in povezana imena glede terapevtskih indikacij, odmerjanja, kontraindikacij in opozoril.
Finally as there are no data on the effects of epoprostenol on fertility in humans this information was introduced in the SmPC together with the information on reproductive studies in animals which have shown no effects on fertility.
Ker torej ni podatkov o učinku epoprostenola na plodnost pri ljudeh, je bil ta podatek dodan v povzetek glavnih značilnosti zdravila skupaj s podatki o študijah razmnoževanja pri živalih, ki ne kažejo učinka na sposobnost razmnoževanja.
At week 12, NYHA functional class improved in 21 of 51 (41%) patients treated with epoprostenol compared to none of the 48 patients treated with conventional therapy alone.
V 12. tednu se je funkcionalni razred NYHA izboljšal pri 21 od 51 (41 %) bolnikih, zdravljenih z epoprostenolom, v primerjavi z nobenim od 48 konvencionalno zdravljenih bolnikov.
These haemodynamic improvements appeared to persist when epoprostenol was administered for at least 36 months in an open, nonrandomized study.
Kot kaže, so se hemodinamični kazalci vztrajno izboljševali pri vsaj 36-mesečni uporabi epoprostenola v odprti, nenaključni študiji.
At the end of the treatment period in the 12 weeks study, survival was improved in NYHA functional Class III and Class IV patients.
Ob koncu obdobja zdravljenja v 12-tedenski študiji se je preživetje izboljšalo za bolnike III. in IV. funkcionalnega razreda po razvrstitvi NYHA.
It is a potent inhibitor of platelet aggregation and also a potent vasodilator.
Je močan zaviralec agregacije trombocitov in tudi močan vazodilatator.
Flolan is indicated for use in haemodialysis in emergency situations when use of heparin carries a high risk of causing or exacerbating bleeding or when heparin is otherwise contraindicated (see section 5.1).
Zdravilo Flolan je indicirano za uporabo pri hemodializi v nujnih primerih, ko predstavlja uporaba heparina visoko tveganje za povzročitev ali poslabšanja krvavitev, ali ko je heparin kako drugače kontraindiciran (glejte poglavje 5.1).“
However, more patients in both treatment groups (28/51 [55%] with epoprostenol and 35/48 [73%] with conventional therapy alone) showed no change in functional class, and 2/51 (4%) with epoprostenol and 13/48 (27%) with conventional therapy alone worsened.
Vendar pa se pri več bolnikih v obeh skupinah zdravljenja (28/51 [55 %] z epoprostenolom in 35/48 [73 %] samo konvencionalno zdravljenih bolnikov) ni pokazala sprememba funkcionalnega razreda, stanje pri 2/51 (4 %) bolnikih, zdravljenih z epoprostenolom, in 13/48 (27 %) le konvencionalno zdravljenih bolnikih pa se je poslabšalo.
In major controlled studies and emergency studies, major clotting occurred in approximately 9% (n=56) of all epoprostenol dialyses and in <1% (n=1) of heparin dialyses.
• V glavnih nadzorovanih študijah in študijah razširjenega dostopa se je pomembna koagulacija pojavila pri približno 9 % (n = 56) vseh dializ z epoprostenolom in < 1 % (n = 1) dializ s heparinom.
More patients stopped bleeding with epoprostenol and of those that continued to bleed, bleeding severity improved more often than in patients dialysed with heparin.
Več bolnikov je prenehalo krvaveti z epoprostenolom, med tistimi, ki so še naprej krvaveli, pa se je resnost krvavitve pogosteje izboljšala kot pri bolnikih z dializo s heparinom.
The CHMP assessed the submitted data and recommended the re-arrangement of this section by separating the posology in the administration of epoprostenol for PAH during short-term (acute) dose ranging versus long-term continuous infusion.
CHMP je ocenil predložene podatke in priporočil prerazvrstitev tega poglavja z ločitvijo odmerjanja in načina uporabe epoprostenola za PAH med razponom kratkotrajnega (akutnega) odmerka v primerjavi z dolgo trajajočim stalnim infundiranjem.
Two studies (30 and 31) addressed the possibility that patients' platelets may become refractory to repeated use of epoprostenol and thereby compromise dialysis efficiency with prolonged use.
• Dve študiji (30 in 31) sta obravnavali možnost razvoja odpornosti bolnikovih trombocitov na ponavljajočo se uporabo epoprostenola, kar lahko pri dalj časa trajajoči uporabi ogrozi učinkovitost dialize.
Section 4.3 - Contraindications
• Poglavje 4.3 - Kontraindikacije
The MAH submitted a proposal for harmonisation of the Quality module.
Imetnik dovoljenja za promet z zdravilom je predlagal uskladitev modula „Kakovost“.
Overall, these results indicate that renal dialysis with epoprostenol was consistently beneficial in patients at very high risk of hemorrhage.
• Na splošno rezultati kažejo, da je ledvična dializa z epoprostenolom dosledno koristila bolnikom z zelo velikim tveganjem za krvavitev.
Increases in exercise capacity were accompanied by statistically significant improvements in dyspnoea, as measured by the Borg Dyspnoea Index.
Povečanje fizične zmogljivosti so spremljala statistično značilna izboljšanja dispneje, izmerjena z Borggovo lestvico za dispnejo.
Patients at Very High Risk of Haemorrhage were assessed in major controlled studies; 12 patients at very high risk of haemorrhage received 35 epoprostenol dialyses and 11 patients received 28 heparin dialyses.
• Bolnike, pri katerih je bilo tveganje za krvavitev zelo veliko, so ocenili v glavnih nadzorovanih študijah; 12 bolnikov z zelo velikim tveganjem za krvavitev je prejelo 35 dializ z epoprostenolom, 11 bolnikov pa je prejelo 28 dializ s heparinom.
Following the discussion on the efficacy and safety data the CHMP agreed in the final indications for Flolan for pulmonary arterial hypertension and renal dialysis as per the wording below:
Po razpravi o podatkih o učinkovitosti in varnosti se je CHMP strinjal z naslednjim besedilom za končne indikacije za zdravilo Flolan za pljučno arterijsko hipertenzijo in ledvično dializo:
For renal dialysis the MAH presented an overview of 14 clinical studies investigating the use of epoprostenol in renal dialysis: three cross over studies, six major controlled studies and five emergency also known and as expanded access studies.
• Imetnik dovoljenja za promet z zdravilom je za ledvično dializo predstavil pregled 14 kliničnih študij, v katerih so raziskali uporabo epoprostenola pri ledvični dializi: tri navzkrižne študije, šest glavnih nadzorovanih študij in pet študij nujnih primerov, znanih tudi kot študije razširjenega dostopa.
There was no indication that efficiency was reduced with repeated use of epoprostenol or heparin as shown by the intradialytic removal of BUN, creatinine, potassium and changes in body weight.
Znakov za zmanjšanje učinkovitosti s ponavljajočo se uporabo epoprostenola ali heparina pri odstranjevanju dušika sečnine v krvi med dializo, kreatininu, kaliju ali spremembi telesne mase ni bilo.
The CHMP assessed the harmonised Product Information proposed by the marketing Authorisation Holder (MAH) of the product taking into account the current national ones and the existing scientific data and discussed the indications for each individual medical condition.
CHMP je ocenil usklajene informacije o zdravilu, ki jih je predlagal imetnik dovoljenja za promet z zdravilom za omenjeno zdravilo, ob upoštevanju sedanjih nacionalnih in obstoječih znanstvenih podatkov, ter razpravljal o indikacijah za vsako posamezno zdravstveno stanje.
In emergency studies, compared to each pre-dialysis assessment, incidence of bleeding was generally reduced with each epoprostenol dialysis.
• V študijah nujnih primerov je bila pogostnost krvavitev v primerjavi z vsako oceno pred dializo na splošno zmanjšana pri vsaki dializi z epoprostenolom.
• The committee reviewed the data submitted by the MAH from the existing clinical studies, the pharmacovigilance data and the published literature justifying the proposed harmonisation of the Product Information.
• Odbor je pregledal podatke, ki jih je predložil imetnik dovoljenja za promet z zdravilom, iz obstoječih kliničnih študij, farmakovigilančnih podatkov in objavljene literature, ki utemeljujejo predlagano uskladitev informacij o zdravilu.
When all dialyses were combined for each treatment (heparin or epoprostenol), more heparin patients bled during the day prior to dialysis (-24-0 hours), dialysis day (0-24 hours) and the day following dialysis (24-48 hours) than epoprostenol patients during the same time periods.
Pri združitvi vseh dializ za vsako obliko zdravljenja (heparin ali epoprostenol) je več bolnikov v skupini s heparinom krvavelo dan pred dializo (-24-0 ur), na dan dialize (0-24 ur) in na dan po dializi (24-48 ur), kot bolnikov z epoprostenolom v enakem časovnem obdobju.
For renal dialysis the CHMP recommended the addition to the PI that Flolan is suitable for continuous infusion only, either intravascularly or into the blood supplying the dialyser.
Za ledvično dializo je CHMP priporočil, da se v informacije o zdravilu doda, da je zdravilo Flolan primerno le za stalno infundiranje, bodisi intravaskularno ali v kri, ki oskrbuje dializno napravo.
Section 4.6 - Fertility, Pregnancy and lactation The CHMP agreed that there is limited amount of data from the use of epoprostenol in pregnant women (Schaefer 2007, Reprotox 2010).
• CHMP se je strinjal, da so podatki o uporabi epoprostenola pri nosečnicah omejeni (Schaefer 2007, Reprotox 2010).
Two major prospectively controlled studies (19 and 27), and 5 emergency studies were conducted to investigate bleeding during dialysis.
• V dveh glavnih prospektivnih nadzorovanih študijah (19 in 27) in petih študijah razširjenega dostopa so raziskali pojav krvavitev med dializo.
Grounds for the variation to the terms of the marketing authorisations
Podlaga za spremembo pogojev dovoljenja za promet z zdravilom
Epoprostenol sodium is indicated for use in renal dialysis when use of heparin carries a high risk of causing or exacerbating bleeding.
• Natrijev epoprostenol je indiciran za uporabo pri ledvični dializi, kadar predstavlja uporaba heparina visoko tveganje za nastanek ali poslabšanje krvavitev.
The enhanced hypotensive effects of epoprostenol due to the acetate buffer used during renal dialysis was also emphasised in this section.
V tem poglavju so bili poudarjeni tudi okrepljeni hipotenzivni učinki epoprostenola zaradi acetatnega pufra, ki se uporablja med ledvično dializo.
In emergency studies, 16 patients received 24 epoprostenol dialyses.
V študijah nujnih primerov je 16 bolnikov prejelo 24 dializ z epoprostenolom.
Epoprostenol sodium is also indicated for the treatment of pulmonary arterial hypertension (PAH).
Natrijev epoprostenol je indiciran tudi za zdravljenje pljučne arterijske hipertenzije (PAH).
Annex II Scientific conclusions and grounds for the variation to the terms of the Marketing Authorisations
• Znanstveni zaključki in podlaga za spremembo pogojev dovoljenja za promet z zdravilom
The main divergences were the following SmPC sections:
Glavna razhajanja so bila v naslednjih poglavjih povzetka glavnih značilnosti zdravila:
The CHMP has agreed that taking into account the latest SmPC guidelines the long known information from the clinical studies justifying the indications needed to be added in this section.
CHMP se je strinjal, da je treba ob upoštevanju najnovejših smernic za povzetek glavnih značilnosti zdravila v to poglavje dodati tudi znane informacije iz kliničnih študij, ki utemeljujejo indikacije.
The CHMP assessed the data from the available clinical studies, post-marketing data and published literature and agreed with the following contraindications:
• CHMP je ocenil podatke razpoložljivih kliničnih študij, podatke iz obdobja trženja in objavljene literature ter se strinjal z naslednjimi kontraindikacijami:
Differences identified include, events occurring during infusion, ischemia in patients with severe angina.
Opredeljene so bile razlike v dogodkih, ki se pojavijo med infundiranjem in ishemijo pri bolnikih s hudo obliko angine pektoris.
Flolan is contraindicated in patients with known hypersensitivity to the active substance or to any of the excipients, in patients with congestive heart failure arising from severe left ventricular dysfunction.
• „Zdravilo Flolan je kontraindicirano pri bolnikih z znano preobčutljivostjo na zdravilno učinkovino ali katero koli pomožno snov, pri bolnikih s kongestivnim srčnim popuščanjem zaradi hude disfunkcije levega prekata.
Each patient was randomly assigned to a sequence of heparin or epoprostenol dialyses and received up to 6 dialyses per entry in study 19 and up to 3 dialyses per entry in study 27.
Vsakemu bolniku je bilo naključno dodeljeno zaporedje dializ s heparinom ali epoprostenolom, vsak bolnik v študiji 19 pa je na začetku opravil do šest dializ in v študiji 27 do tri dialize.
• The committee agreed the harmonisation of the summary of product characteristic, labelling and package leaflet proposed by the marketing authorisation holders.
• Odbor se je strinjal z uskladitvijo povzetka glavnih značilnosti zdravila, označevanja in navodila za uporabo, ki jih je predlagal imetnik dovoljenja za promet z zdravilom
Flolan contains epoprostenol sodium which is the monosodium salt of epoprostenol, a naturally occurring prostaglandin produced by the blood vessels.
• Zdravilo Flolan vsebuje natrijev epoprostenol, ki je mononatrijeva sol epoprostenola, tj. naravnega prostaglandina, ki nastaja v žilah.
Patients at high risk of haemorrhage just prior to their first study dialysis, but who bled within 3 days prior were classified at high risk of haemorrhage.
• Bolniki z velikim tveganjem za krvavitev tik pred prvo dializo v okviru študije, ki so krvaveli v treh dneh pred razvrstitvijo, so bili razvrščeni kot bolniki z velikim tveganjem za krvavitev.
In conclusion, based on the assessment of the MAH proposal and responses and following the discussions of the committee, the CHMP adopted the harmonised product information for Flolan and associated names.
• V zaključku je CHMP na podlagi ocene predloga in odgovorov imetnika dovoljenja za promet z zdravilom in po razpravi odbora potrdil usklajene informacije za zdravilo Flolan in povezana imena.
The median baseline value for the conventional therapy group and epoprostenol plus conventional therapy group was 240 meters and 270 meters, respectively.
Mediana izhodiščna vrednost za konvencionalno zdravljeno skupino je bila 240 metrov in za skupino, zdravljeno z epoprostenolom in konvencionalno, 270 metrov.
Section 4.2 - Posology and method of administration There were differences in Section 4.2 of the SmPCs across Member States.
• Poglavje 4.2 - Odmerjanje in način uporabe Poglavje 4.2 povzetka glavnih značilnosti zdravila se je v državah članicah razlikovalo.
The available clinical studies on both these indications were presented by the MAH together with post-marketing data and published literature and discussed by the CHMP both regarding the efficacy and safety aspects.
Imetnik dovoljenja za promet z zdravilom je predstavil razpoložljive klinične študije za obe indikaciji skupaj s podatki iz obdobja trženja in objavljeno literaturo ter s CHMP razpravljal o vidikih njune učinkovitosti in varnosti.
Eight patients received 21 epoprostenol dialyses in emergency studies.
Osem bolnikov je prejelo 21 dializ z epoprostenolom v študijah razširjenega dostopa.
Flolan must not be used chronically in patients who develop pulmonary oedema during dose-ranging.
Kronična uporaba zdravila Flolan ni dovoljena pri bolnikih, pri katerih se med določanjem odmerka razvije pljučni edem.“
Conventional therapy varied among patients and included some or all of the following: anticoagulants in essentially all patients; oral vasodilators, diuretics, and digoxin in one half to two thirds of patients; and supplemental oxygen in about half the patients.
Konvencionalno zdravljenje se je med bolniki razlikovalo in vključevalo nekaj ali vse od naslednjega: antikoagulante pri skoraj vseh bolnikih; peroralne vazodilatatorje, diuretike in digoksin pri polovici do dveh tretjinah bolnikov; nadomestni kisik pri približno polovici bolnikov.
Conventional therapy varied among patients and included some or all of the following: anticoagulants in essentially all patients, supplemental oxygen and diuretics in two thirds of the patients, oral vasodilators in 40% of the patients, and digoxin in a third of the patients.
Konvencionalno zdravljenje se je med bolniki razlikovalo in vključevalo nekaj ali vse od naslednjega: antikoagulante pri skoraj vseh bolnikih; nadomestni kisik in diuretike pri približno dveh tretjinah bolnikov, peroralne vazodilatatorje pri 40 % bolnikov in digoksin pri tretjini bolnikov.
The final Package Leaflet wording was adopted by the CHMP.
CHMP je sprejel končno besedilo navodila za uporabo.
1.45 mm Hg), mean right atrial pressure (-2.26 vs. 0.59 mm Hg), total pulmonary resistance (-4.52 vs. 1.41 Wood U), pulmonary vascular resistance (-3.60 vs. 1.27 Wood U), and systemic vascular resistance (-4.31 vs. 0.18 Wood U) were statistically different between patients who received epoprostenol chronically and those who did not.
v primerjavi z 0,59 mm Hg), skupni pljučni upor (-4,52 v primerjavi z 1,41 enot Wood), pljučni žilni upor (-3,60 v primerjavi z 1,27 enot Wood) in sistemski žilni upor (-4,31 v primerjavi z 0,18 enot Wood) se je med bolniki, ki so kronično prejemali epoprostenol, in med tistimi, ki ga niso, statistično razlikovalo.
The CHMP was requested to assess the available data on the indications and confirm the wording proposed by the MAH.
CHMP je bil naprošen za ocenitev razpoložljivih podatkov za ti indikaciji in za potrditev besedila, ki ga je predlagal imetnik dovoljenja za promet z zdravilom.
the CHMP has recommended the variation to the terms of the marketing authorisations for which the summary of product characteristics and package leaflet are set out in Annex III for Flolan and associated names (see Annex I).
• je odbor CHMP priporočil spremembo pogojev dovoljenj za promet z zdravilom Flolan in povezanih imen (glejte Prilogo I), katerih povzetek glavnih značilnosti zdravila in navodilo za uporabo sta določena v Prilogi III.
The combined baseline 6-minute walk test median values for the conventional therapy group and epoprostenol plus conventional therapy group was 266 meters and 301 meters, respectively.
Kombinirana izhodiščna vrednost za 6minutni test hoje za konvencionalno zdravljeno skupino je bila 266 metrov, za skupino, zdravljeno z epoprostenolom in konvencionalno, pa 301 meter.
Epoprostenol or heparin were used during each dialysis for one month in study 30 and for two months in study 31.
Med vsako dializo so en mesec v študiji 30 in dva meseca v študiji 31 uporabljali bodisi epoprostenol ali heparin.
Statistically significant improvement was observed in exercise capacity (p=0.001), as measured by the 6 minutes walking test (6MWT) in patients receiving continuous intravenous epoprostenol plus conventional therapy (N=52) for 8 or 12 weeks compared to those receiving conventional therapy alone (N=54) (combined week 8 and 12 change from baseline - median: 49 vs. -4 meters; mean: 55 vs. -4 meters).
• Statistično značilna izboljšanja so opazili v fizični zmogljivosti (p = 0,001), izmerjeni s 6-minutnim testom hoje pri bolnikih, ki so prejemali stalno intravenske zdravljenje z epoprostenolom in konvencionalno zdravljenje (n = 52) osem ali 12 tednov, v primerjavi z bolniki, ki so prejemali le konvencionalno zdravljenje (n = 54) (kombinirana mediana sprememba v 8. in 12. tednu od izhodišča: 49 v primerjavi s -4 metri; sredina: 55 v primerjavi s -4 metri).
The following data from clinical studies have been presented by the MAH and discuss during the assessment of these procedure.
• Imetnik dovoljenja za promet z zdravilom je predstavil naslednje podatke iz kliničnih študij in med ocenjevanjem teh postopkov o njih razpravljal.
Chronic continuous infusions of epoprostenol in patients with pulmonary arterial hypertention/scleroderma spectrum of diseases (PAH/SSD) were studied in a prospective, open, randomised trial of 12 weeks' duration comparing epoprostenol plus conventional therapy (N = 56) to conventional therapy alone (N = 55).
Kronično stalno infundiranje epoprostenola pri bolnikih s pljučno arterijsko hipertenzijo/sklerodermalnim spektrom bolezni so proučili v enem prospektivnem, odprtem, naključnem 12-tedenskem preskušanju, v katerem so primerjali epoprostenol in konvencionalno zdravljenje (n = 56) s konvencionalnim zdravljenjem samim (n = 55).
In major controlled studies, when all dialyses were combined, slightly more epoprostenol patients appeared to bleed during the pre-dialysis, dialysis and post-dialysis days compared to heparin patients during the same periods.
• V glavnih nadzorovanih študijah je pri združitvi vseh dializ kazalo, da je v dneh pred dializo, med dializo in po dializi krvavelo nekoliko več bolnikov z epoprostenolom kot bolnikov s heparinom v enakih obdobjih.