FrancophonIA/ELRC3.0 huggingface dataset:
English: Having considered the abovementioned results from SIPPET, the published literature and all the information submitted by the MAHs, as well as the views expressed by experts expressed at the ad-hoc expert meeting, the PRAC concluded that:
Slovenian: Ob upoštevanju zgoraj omenjenih rezultatov študije SIPPET, objavljene literature, vseh informacij, ki so jih predložili imetniki dovoljenj za promet z zdravilom, in mnenj strokovnjakov, izraženih na ad-hoc strokovnem sestanku, je odbor PRAC sklenil, da:
English: Medical devices for reconstitution and administration are provided with each package of this medicine.
Slovenian: Pribor za rekonstitucijo in uporabo je priložen v vsakem pakiranju tega zdravila.
English: After reconstitution, from a microbiological point of view, the product should be used immediately.
Slovenian: Z mikrobiološkega vidika je treba zdravilo uporabiti takoj po rekonstituciji.
English: Warm the unopened powder vial and the solvent syringe in your hands until they feel as warm as your hands.
Slovenian: Z rokami ogrejte neodprto vialo s praškom in injekcijsko brizgo z vehiklom dokler nista tako topli kot vaše roke.
English: These treatments should be prescribed by doctors with experience in the care of patients with haemophilia A. Speak to your doctor if you would like further information on this.
Slovenian: Dodatno zdravljenje vam mora predpisati zdravnik, ki ima izkušnje z zdravljenjem bolnikov s hemofilijo A. Posvetujte se z zdravnikom, če v zvezi s tem potrebujete še kakršne koli dodatne informacije.
English: The expert group suggested that further data are needed to establish if there are clinically relevant differences in frequency of inhibitor development between different factor VIII products and that, in principle, such data should be collected separately for individual products, as degree of immunogenicity will be difficult to generalise across the classes of products (i.e. recombinant vs. plasma-derived).
Slovenian: Strokovna skupina je predlagala, da so potrebni dodatni podatki za ugotavljanje, ali obstajajo klinično pomembne razlike v pogostnosti pojava zaviralcev med različnimi zdravili s faktorjem VIII in da bi bilo treba takšne podatke načeloma zbirati ločeno za posamezna zdravila, ker bo stopnjo imunogenosti težko posplošiti po razredih zdravil (npr. rekombinantni faktor in faktor, pridobljen iz plazme).
English: Importantly, the EU SmPCs do not include modified prophylaxis (as defined in the SIPPET study) as an authorised posology, and the impact of the apparent imbalance in the unspecified other combinations of treatment modality on the SIPPET findings is unclear.
Slovenian: Pomembno je, da povzetki glavnih značilnosti zdravila v EU ne vključujejo modificirane profilakse (kot je opredeljena v študiji SIPPET) kot dovoljene sheme odmerjanja, zato učinek očitnega neravnovesja v neopredeljenih drugih kombinacijah načina zdravljenja na ugotovitve študije SIPPET ni jasen.
English: The following table provides a guide for factor VIII minimum blood levels.
Slovenian: V naslednji preglednici so navodila glede minimalnih ravni faktorja VIII v krvi.
English: Therefore, it remains uncertain whether the same differential risk of inhibitor development observed in the SIPPET study would be apparent in patient populations treated in routine care in other countries where the modality of treatment (i.e. primary prophylaxis) is different from that in the study.
Slovenian: Posledično še vedno obstaja negotovost, ali bi bila razlika v tveganju za pojav zaviralcev, ugotovljenem v študiji SIPPET, razvidna pri bolnikih, zdravljenih z rutinsko oskrbo, v drugih državah, kjer je način zdravljenja (tj. primarna profilaksa) drugačen od tistega v študiji.
English: Thrombin then converts fibrinogen into fibrin and a clot can be formed.
Slovenian: Nato trombin pretvori fibrinogen v fibrin, ki omogoča nastanek krvnega strdka.
English: • The FVIII products are heterogenous, and the plausibility of different rates of inhibitor development between individual products cannot be excluded.
Slovenian: • zdravila s FVIII so heterogena in verjetnosti različnih stopenj pojavljanja zaviralcev med posameznimi zdravili ni mogoče izključiti;
English: The degree and duration of aPTT normalisation observed after administration of KOGENATE Bayer is similar to that achieved with plasma-derived factor VIII.
Slovenian: Stopnja in trajanje normalizacije APTČ sta po uporabi zdravila KOGENATE Bayer podobna kot pri faktorju VIII, pridobljenim iz plazme.
English: Inhibitors developed in 76 patients, 50 of whom had high-titre inhibitors (≥5 BU).
Slovenian: Zaviralci so se pojavili pri 76 bolnikih, od katerih jih je 50 imelo visoke titre zaviralcev (≥ 5 BU).
English: This result is similar to the reported values for factor VIII derived from human plasma.
Slovenian: Rezultati so podobni kot pri faktorju VIII, pridobljenim iz humane plazme.
English: What KOGENATE Bayer is and what it is used for What you need to know before you use KOGENATE Bayer How to use KOGENATE Bayer Possible side effects
Slovenian: Kaj je zdravilo KOGENATE Bayer in za kaj ga uporabljamo Kaj morate vedeti, preden boste uporabili zdravilo KOGENATE Bayer Kako uporabljati zdravilo KOGENATE Bayer Možni neželeni učinki
English: 2 alcohol swabs for single use
Slovenian: 2 alkoholna tampona za enkratno uporabo
English: If you want to stop using KOGENATE Bayer Do not stop using KOGENATE Bayer without consulting your doctor.
Slovenian: Če želite prenehati uporabljati zdravilo KOGENATE Bayer Ne prenehajte uporabljati zdravila KOGENATE Bayer, ne da bi se prej posvetovali z zdravnikom.
English: The most serious side effects are hypersensitivity reactions or anaphylactic shock (rare side effect).
Slovenian: Najbolj resni neželeni učinki so preobčutljivostne reakcije ali anafilaktični šok (redek neželeni učinek).
English: Given the detailed grounds provided by the MAH, the PRAC carried out a new assessment of the available data in the context of the re-examination.
Slovenian: Glede na podrobno opisane razloge imetnika dovoljenja za promet je odbor PRAC v okviru ponovne proučitve znova ocenil razpoložljive podatke.
English: • Treatment-related factors include intensity of exposure, number of exposure days (EDs), on demand treatment posing a greater risk than prophylaxis, particularly in the context of danger signals such as trauma or surgery, and young age at first treatment poses a higher risk.
Slovenian: • dejavniki, povezani z zdravljenjem, vključujejo intenzivnost izpostavljenosti, število dni izpostavljenosti, nižjo starost pri prvem zdravljenju in zdravljenje na zahtevo ter predstavljajo večje tveganje kot profilaksa, zlasti v zvezi z opozorilnimi signali, kot so travma ali kirurški poseg.
English: • The PRAC considered the procedure under Article 31 of Directive 2001/83/EC resulting from pharmacovigilance data, for human plasma derived and recombinant coagulation factor VIII containing medicinal products (see Annex I and Annex A).
Slovenian: • odbor PRAC je upošteval napotitev v skladu s členom 31 Direktive 2001/83/ES, ki je bila na podlagi farmakovigilančnih podatkov predložena za zdravila, ki vsebujejo rekombinantni koagulacijski faktor VIII (glejte prilogo I in prilogo A);
English: Clinical discussion
Slovenian: Klinična razprava
English: Factor VIII activity in plasma is expressed either as a percentage (relative to normal human plasma) or in International Units (relative to the International Standard for factor VIII in plasma).
Slovenian: Aktivnost faktorja VIII v plazmi je izražena v odstotkih (glede na aktivnost v normalni humani plazmi) ali v mednarodnih enotah (glede na mednarodni standard za faktor VIII v plazmi).
English: If a further dose needs to be administered, use a new syringe with product reconstituted as described above.
Slovenian: Če je potreben dodaten odmerek zdravila, uporabite novo injekcijsko brizgo z zdravilom, rekonstituiranim po postopku, ki je opisan zgoraj.
English: * Frequency is based on studies with all FVIII products which included patients with severe haemophilia A. PTPs = previously-treated patients, PUPs = previously untreated patients
Slovenian: * Pogostnost temelji na študijah z vsemi zdravili s FVIII, ki so vključevale bolnike s hudo hemofilijo A. PZB = predhodno zdravljeni bolniki, PNB = predhodno nezdravljeni bolniki
English: Life threatening haemorrhages (such as intracranial bleed, throat bleed, severe abdominal bleed)
Slovenian: življenjsko ogrožajoče krvavitve (npr. intrakranialna krvavitev, krvavitev v grlo, huda abdominalna krvavitev)
English: Additional pharmacokinetic parameters for KOGENATE Bayer for bolus injection are: mean residence time [MRT (0-48)] of about 22 hours and clearance of about 160 mL/h.
Slovenian: Dodatni farmakokinetični parametri za bolusno injekcijo zdravila KOGENATE Bayer so: povprečni čas zadrževanja [PČZ (0 - 48)] približno 22 ur in očistek približno 160 ml/h.
English: One International Unit (IU) of factor VIII activity is equivalent to that quantity of factor VIII in one mL of normal human plasma.
Slovenian: Ena mednarodna enota (i.e.) aktivnosti faktorja VIII ustreza količini faktorja VIII v enem mililitru normalne humane plazme.
English: Further to the assessment of the totality of the responses submitted by the MAH for susoctocog alfa (Obizur), the PRAC is of the opinion that the outcome of this article 31 referral procedure does not apply to this product in view of the indication of Obizur (acquired haemophilia A due to inhibitory antibodies to endogenous FVIII) and the different target population.
Slovenian: Poleg ocene vseh odgovorov, ki jih je predložil imetnik dovoljenja za promet s susoktokogom alfa (Obizur), je odbor PRAC menil, da izid tega napotitvenega postopka v skladu s členom 31 ne velja za omenjeno zdravilo zaradi indikacije za zdravilo Obizur (pridobljena hemofilija A zaradi inhibitornih protiteles proti endogenemu FVIII) in drugačne ciljne populacije.
English: This trial, known as the SIPPET study (“Survey of Inhibitors in PlasmaProduct Exposed Toddlers”) was conducted to evaluate the relative risk of inhibitors in patients treated with pdFVIII compared to rFVIII.
Slovenian: To preskušanje, imenovano študija SIPPET („Študija zaviralcev pri malih otrocih, izpostavljenih zdravilom iz plazme“), je bilo opravljeno za ocenitev relativnega tveganja za zaviralce pri bolnikih, zdravljenih s pdFVIII, v primerjavi z rFVIII.
English: Although this could not have been prevented, an early termination of an open label trial raises the possibility of investigator bias and inflation of the probability of detecting an effect that is not present.
Slovenian: Čeprav tega ni bilo mogoče preprečiti, pri predčasni prekinitvi neslepih preskušanj obstaja možnost napake raziskovalca in povečanja verjetnosti zaznave neobstoječega učinka;
English: The dose, frequency and duration of the substitution therapy must be individualised according to the patient's needs (weight, severity of disorder of the haemostatic function, the site and extent of the bleeding, the presence of inhibitors, and the factor VIII level desired).
Slovenian: Odmerek, pogostnost in trajanje nadomestnega zdravljenja je treba prilagoditi potrebam posameznega bolnika (odvisno od telesne mase, stopnje motnje strjevanja krvi, mesta in obsega krvavitve, prisotnosti zaviralcev in od želene ravni faktorja VIII).
English: Reconstitute the desired amount of product, repeating steps 2 - 9, using a new syringe and connect it to the venipuncture set.
Slovenian: Za rekonstitucijo želene količine zdravila ponovite korake od 2 do 9, vzemite novo injekcijsko brizgo in jo privijte na pribor za vensko punkcijo.
English: The formation of inhibitors (antibodies) is a known complication that can occur during treatment with all Factor VIII medicines.
Slovenian: Nastanek zaviralcev (protiteles) je znan zaplet, ki se lahko pojavi med zdravljenjem z vsemi zdravili s faktorjem VIII.
English: Documentation
Slovenian: Dokumentiranje
English: Benefit -risk balance
Slovenian: Razmerje med koristmi in tveganji
English: In relation to section 5.1, any reference to inhibitor development studies in PUPs and PTPs should be deleted unless the studies were conducted in compliance with a Paediatric Investigation Plan or the studies provide robust evidence of a frequency of inhibitors in PUP which is less than ‘very common' or for PTPs which is different from ‘uncommon' (as laid down in the attachments of the PRAC AR).
Slovenian: V zvezi s poglavjem 5.1 je treba vse sklice na študije pojava zaviralcev pri predhodno nezdravljenih in predhodno zdravljenih bolnikih izbrisati, razen če so bile študije izvedene v skladu z načrtom študij za pediatrično populacijo ali študije zagotavljajo zanesljive dokaze o pogostnosti pojava zaviralcev pri predhodno nezdravljenih bolnikih, ki je manjša kot „zelo pogosti“ ali pri predhodno zdravljenih bolnikih, ki se razlikuje od „občasni“ (kot je določeno v prilogah PRAC AR).
English: Be sure that the powder is completely dissolved.
Slovenian: Preverite, če je prašek popolnoma raztopljen.
English: In the case of the haemorrhagic events listed, the factor VIII activity should not fall below the given level (in % of normal) in the corresponding period:
Slovenian: V primeru pojava navedenih krvavitev, aktivnost faktorja VIII v določenem obdobju ne sme pasti pod dano raven (% normalne vrednosti):
English: No additional communication, on risk factors for inhibitor development beyond the product information or any additional risk minimisation measures was recommended.
Slovenian: Dodatna sporočila o dejavnikih tveganja za pojav zaviralcev, ki presegajo informacije o zdravilu, ali dodatni ukrepe za zmanjšanje tveganja niso bili priporočeni.
English: Pharmacotherapeutic group: antihemorrhagics: blood coagulation factor VIII, ATC code B02BD02.
Slovenian: Farmakoterapevtska skupina: antihemoragiki, koagulacijski faktor VIII, oznaka ATC: B02BD02
English: The primary and secondary outcomes assessed in the study were the incidence of all inhibitors (≥0.4 BU/ml) and the incidence of high-titre inhibitors (≥5 BU/ml), respectively.
Slovenian: V študiji ocenjeni primarni in sekundarni izidi so bili pojavnost vseh zaviralcev (≥ 0,4 BU/ml) in pojavnost visokega titra zaviralcev (≥ 5 BU/ml).
English: The group also agreed that specific data about frequency of inhibitors for each product should not be included in the SmPC as the available studies are not adequately powered to draw precise conclusions on the absolute frequency for each product or on the relative frequency of inhibitors between products.
Slovenian: Skupina se je strinjala tudi, da se specifični podatki o pogostnosti zaviralcev za vsako zdravilo ne smejo vključiti v povzetek glavnih značilnosti zdravila, ker razpoložljive študije nimajo zadostne moči za natančne sklepe o absolutni pogostnosti za vsako zdravilo ali za relativne pogostnosti pojava zaviralcev med zdravili.
English: Treatment of patients who have developed inhibitors requires careful individual management and can be resistant to therapy.
Slovenian: Zdravljenje bolnikov, pri katerih so se pojavili zaviralci, zahteva skrbno individualno obravnavo in je lahko brez odziva.
English: In patients with inhibitor titres above 10 BU or with high anamnestic response, the use of (activated) prothrombin complex concentrate (PCC) or recombinant activated factor VII (rFVIIa) preparations has to be considered.
Slovenian: Pri bolnikih s titrom zaviralca nad 10 BE ali pozitivno anamnezo je treba razmisliti o uporabi (aktiviranega) koncentrata protrombinskega kompleksa (PCC) ali zdravili z aktiviranim rekombinantnim faktorjem VII (rFVIIa).
English: If these components cannot be used, please contact your doctor.
Slovenian: Če teh sestavnih delov ne morete uporabiti, se posvetujte z zdravnikom.
English: If your or your child's bleeding is not being controlled with KOGENATE Bayer, tell your doctor immediately.
Slovenian: Če krvavitev pri vas ali vašem otroku z zdravilom KOGENATE Bayer ni obvladana, morate to nemudoma povedati zdravniku.
English: Due to very different study methods and patient populations that have been studied over time, and inconsistent findings across studies, the PRAC found that the totality of evidence does not support a conclusion that recombinant factor VIII medicines, as a class, poses a greater risk of inhibitor development than the class derived from plasma.
Slovenian: Zaradi zelo različnih študijskih metod in populacij bolnikov, ki so bili proučeni v različnih obdobjih, ter nedoslednih ugotovitev med študijami, je odbor PRAC ugotovil, da dokazi v celovitosti ne podpirajo sklepa, da zdravila z rekombinantnim faktorjem VIII kot razred predstavljajo večje tveganje za pojav zaviralcev kot razred zdravil, pridobljenih iz plazme.
English: The pdFVIII class consists of products with or without Von Willebrand Factor (VWF), and those with VWF contain a range of VWF levels.
Slovenian: Razred pdFVIII sestavljajo zdravila z Von Willebrandovim faktorjem (VWF) ali brez njega, pri čemer zdravila z VWF vsebujejo različne odmerke VWF.
English: Specific studies with repeated administration such as reproduction toxicity, chronic toxicity, and carcinogenicity were not performed with octocog alfa due to the immune response to heterologous proteins in all non-human mammalian species.
Slovenian: Specifične študije s ponavljajočimi odmerki oktokoga alfa na sposobnost razmnoževanja, kronično toksičnost in kancerogeni potencial niso bile narejene zaradi pričakovanega imunskega odgovora na heterologne beljakovine pri vseh ne-humanih sesalcev.
English: PRAC discussion on grounds for re-examination
Slovenian: Razprava odbora PRAC v zvezi z razlogi za ponovno proučitev
English: Many of these studies were small and not specifically designed to evaluate the inhibitor risk in PUPs with severe haemophilia A. The studies were mostly single arm and do not provide data to perform comparative analysis (either between pdFVIII and rFVIII as a class comparison, or within the rFVIII class).
Slovenian: Mnoge od teh študij so bile majhne in niso bile posebej oblikovane za oceno tveganja za pojav zaviralcev pri predhodno nezdravljenih bolnikih s hudo hemofilijo A. Študije so večinoma imele eno vejo in niso zbirale podatkov za izvedbo primerjalne analize (samo primerjava pdFVIII in rFVIII ali znotraj razreda rFVIII).
English: The occurrence of inhibitor development in haemophilia A patients receiving FVIII products mostly occurs in previously-untreated patients (PUPs) or minimally treated patients (MTPs) who are still within the first 50 days of exposure (EDs) to the treatment.
Slovenian: Pojav zaviralcev pri bolnikih s hemofilijo A, ki so prejemali zdravila s FVIII, se večinoma pojavlja pri predhodno nezdravljenih bolnikih (PUP; previously-untreated patients) ali pri minimalno zdravljenih bolnikih (MTP; minimally treated patients), ki so še vedno v prvih 50 dneh izpostavljenosti zdravljenju.
English: Expert consultation
Slovenian: Posvetovanje s strokovnjaki
English: A major complication of FVIII therapy is the occurrence of IgG alloantibodies (inhibitors) that neutralise FVIII activity, causing loss of bleeding control.
Slovenian: Glavni zaplet zdravljenja s FVIII je pojav aloprotiteles IgG (zaviralcev), ki nevtralizirajo aktivnost FVIII, kar onemogoči obvladovanje krvavitev.
English: What KOGENATE Bayer is and what it is used for
Slovenian: Kaj je zdravilo KOGENATE Bayer in za kaj ga uporabljamo
English: KOGENATE Bayer is used for treatment and prophylaxis of bleeding in adults, adolescents and children of all ages with haemophilia A (congenital factor VIII deficiency).
Slovenian: Zdravilo KOGENATE Bayer se uporablja za zdravljenje in preprečevanje krvavitev pri odraslih, mladostnikih in otrocih vseh starosti s hemofilijo A (prirojeno pomanjkanje faktorja VIII).
English: For long term prophylaxis against bleeding in patients with severe haemophilia A, the usual doses are 20 to 40 IU of KOGENATE Bayer per kg body weight at intervals of 2 to 3 days.
Slovenian: Za dolgotrajno preprečevanje krvavitev pri bolnikih s hudo hemofilijo A so običajni odmerki od 20 do 40 i.e. zdravila KOGENATE Bayer na kg telesne mase vsake 2 do 3 dni.
English: For most rFVIII products, newer and more relevant information from clinical trials in PUPs is available.
Slovenian: Za večino zdravil z rFVIII so na voljo novejši in ustreznejši podatki iz kliničnih preskušanj pri predhodno nezdravljenih bolnikih.
English: Higher infusion rates may be required in conditions with accelerated clearance during major bleedings or extensive tissue damage during surgical interventions.
Slovenian: Večje hitrosti infundiranja so lahko potrebne pri večjih krvavitvah ali obsežni poškodbi tkiva med kirurškimi posegi, kadar je očistek povečan.
English: For the calculation of the initial infusion rate, clearance can be obtained by performing a pre-surgery decay curve, or by starting from an average population value (3.0-3.5 mL/h/kg) and then adjust accordingly.
Slovenian: Za izračun začetne hitrosti infundiranja se lahko očistek določi iz krivulje razpada pred kirurškim posegom ali pa tako, da se izhaja iz povprečne populacijske vrednosti (3 - 3,5 ml/h/kg) in se jo nato ustrezno prilagodi.
English: The safety and efficacy of KOGENATE Bayer in children of all ages have been established.
Slovenian: Varnost in učinkovitost zdravila KOGENATE Bayer pri otrocih vseh starosti sta bili dokazani.
English: Repeat infusion every 8 to 24 hours until threat is resolved
Slovenian: Ponavljajte vsakih 8 - 24 ur, dokler nevarnost za bolnika ni odpravljena.
English: b) By continuous infusion Raise factor VIII activity presurgery with an initial bolus infusion and immediately follow with continuous infusion (in IU/kg/h) adjusting according to patient's daily clearance and desired factor VIII levels for at least 7 days.
Slovenian: b) s kontinuirano infuzijo Pred kirurškim posegom je treba povečati aktivnost faktorja VIII z začetno bolusno infuzijo ter takoj nadaljujte s kontinuirano infuzijo (i.e./kg/h), ki je prilagojena glede na bolnikov dnevni očistek in želene ravni faktorja VIII (vsaj 7 dni).
English: Infusion rate (in IU/kg/h) = Clearance (in mL/h/kg) × desired factor VIII level (in IU/mL)
Slovenian: Hitrost infundiranja (v i.e./kg/h) = očistek (v ml/h/kg) × želena raven faktorja VIII (v i.e./ml)
English: Experience regarding fertility or the use of KOGENATE Bayer during pregnancy and breast-feeding is not available.
Slovenian: Izkušenj glede plodnosti ali uporabi zdravila KOGENATE Bayer med nosečnostjo in dojenjem ni.
English: If you have been told by your doctor that you have developed factor VIII inhibitors you may need to use a larger amount of this medicine to control bleeding.
Slovenian: Če vam je zdravnik povedal, da so pri vas nastali zaviralci faktorja VIII, boste morda za nadzor krvavitev potrebovali večji odmerek tega zdravila kot doslej.
English: The experts also agreed that the degree of immunogenicity of different products was adequately described overall with the amendments to the SmPC proposed by the PRAC highlighting the clinical relevance of inhibitor development (in particular low compared to high titre inhibitors), as well as the frequency of ‘very common' in PUPs and ‘uncommon' in PTPs.
Slovenian: Strokovnjaki so se tudi strinjali, da je bila stopnja imunogenosti različnih zdravil na splošno zadostno opisana s spremembami povzetka glavnih značilnosti zdravila, ki jih je predlagal odbor PRAC, pri čemer so poudarili klinični pomen pojava zaviralcev (zlasti nizkih titrov v primerjavi z visokimi titri) in pogostnosti „zelo pogosti“ pri predhodno nezdravljenih bolnikih in „občasni“ pri predhodno zdravljenih bolnikih.
English: However, in the presence of an inhibitor the doses required are variable and must be adjusted according to clinical response and monitoring of plasma factor VIII activity.
Slovenian: Ob prisotnosti zaviralca so potrebni odmerki različni in jih je treba prilagajati glede na klinični odgovor in spremljati aktivnost faktorja VIII v plazmi.
English: Usually, the substitution therapy with KOGENATE Bayer is a life-time treatment.
Slovenian: Običajno je nadomestno zdravljenje z zdravilom KOGENATE Bayer potrebno celo življenje.