FrancophonIA/ELRC3.0 huggingface dataset:
English: The injection must not be administered in areas of the skin where there are signs of infection or inflammation.
Croatian: Injekcija se ne smije primijeniti u područjima kože na kojima postoje znakovi infekcije ili upale.
English: Presence of nusinersen was also demonstrated in neurons and other cell types in the spinal cord and brain, and peripheral tissues such as skeletal muscle, liver, and kidney.
Croatian: Prisutnost nusinersena bila je dokazana i u neuronima i u drugim vrstama stanica u kralježničnoj moždini i mozgu te perifernim tkivima, kao što su skeletni mišići, jetra i bubreg.
English: In Part 1 of the study, patients were followed for a median of 302 days.
Croatian: U 1. dijelu ispitivanja bolesnici su praćeni tijekom razdoblja čiji je medijan iznosio 302 dana.
English: If particles are observed and/or the liquid in the vial is not clear and colourless, the vial must not be used.
Croatian: Ako se opaze čestice i/ili ako tekućina u bočici nije bistra i bezbojna, bočicu se ne smije upotrijebiti.
English: This results in the loss of nerve cells in the spine, leading to weakness of the muscles in the shoulders, hips, thighs and upper back.
Croatian: Rezultat toga je gubitak živčanih stanica u kralježničnoj moždini, što dovodi do slabosti mišića ramena, kukova, natkoljenica i gornjeg dijela leđa.
English: Pharmacotherapeutic group: Other drugs for disorders of the musculo-skeletal system, ATC code: M09AX07
Croatian: Farmakoterapijska skupina: Ostali pripravci za liječenje bolesti mišićno-koštanog sustava, ATK oznaka: M09AX07.
English: Do not use this medicine after the expiry date which is stated on the carton after “EXP”.
Croatian: Ovaj lijek se ne smije upotrijebiti nakon isteka roka valjanosti navedenog na kutiji iza oznake “EXP”.
English: Aseptic technique should be used when preparing and administering Spinraza; see instructions for use in section 6.6.
Croatian: Priprema i primjena lijeka Spinraza mora se izvoditi aseptičkom tehnikom; vidjeti upute za primjenu u dijelu 6.6.
English: Each vial is for single use.
Croatian: Svaka bočica je za jednokratnu upotrebu.
English: Mean plasma Cmax and AUC values increased approximately dose proportionally over the evaluated dose range.
Croatian: Srednje vrijednosti Cmax i AUC u plazmi povećavale su se približno proporcionalno dozi u procijenjenom rasponu doza.
English: The impact of immunogenicity on safety was not formally analysed as the number of patients with ADAs was low.
Croatian: Utjecaj imunogenosti na sigurnost službeno nije analiziran jer je broj bolesnika s protutijelima na lijek bio malen.
English: The remaining 2 events (rash and eosinophil count increased, both nonserious) were possibly related to nusinersen.
Croatian: Za preostala 2 slučaja (osip i povišen broj eozinofila, nijedan od njih ozbiljan) moguće je da su bili povezani s nusinersenom.
English: • Serious infection related to lumbar puncture (e.g. meningitis)
Croatian: • ozbiljna infekcija povezana s lumbalnom punkcijom (npr. meningitis)
English: At the time of interim analysis, 22 out of 24 patients (92%) were alive.
Croatian: U trenutku interim analize živa su bila 22 od 24 bolesnika (92 %).
English: The vial should be taken out of the refrigerator and allowed to warm to room temperature (25°C) without using external heat sources, prior to administration.
Croatian: Prije primjene, bočicu se mora izvaditi iz hladnjaka i ostaviti da se zagrije na sobnu temperaturu (25°C) bez upotrebe vanjskih izvora topline.
English: Displacement of these factors leads to retention of exon 7 in the SMN2 mRNA and hence when SMN2 mRNA is produced, it can be translated into the functional full length SMN protein.
Croatian: Istiskivanje ovih čimbenika dovodi do zadržavanja egzona 7 u genu SMN2 mRNK pa tako, kad se stvara SMN2 mRNK, može se translatirati u funkcionalni protein SMN pune duljine.
English: Taking into account the PRAC Assessment Report on the PSUR(s) for nusinersen, the scientific conclusions of CHMP are as follows:
Croatian: Uzimajući u obzir PRAC-ovo izvješće o ocjeni periodičkog(ih) izvješća o neškodljivosti lijeka (PSUR) za nusinersen, znanstveni zaključci CHMP-a su sljedeći:
English: Two previously non-independent ambulatory patients (Type III) achieved independent walking, and one non-ambulatory patient (Type II) achieved independent walking.
Croatian: Dva bolesnika koja prije nisu mogla samostalno hodati (tip III) počela su samostalno hodati i jedan je bolesnik koji prije nije mogao hodati (tip II) počeo samostalno hodati.
English: Proportion achieving a 4-point worsening
Croatian: Udio koji je postigao pogoršanje za 4 boda
English: Some adverse events commonly associated with lumbar puncture (e.g. headache and back pain) could not be assessed in the infant population exposed to Spinraza due to the limited communication appropriate for that age group.
Croatian: Neki štetni događaji često povezani s lumbalnom punkcijom (npr. glavobolja i bol u leđima), nisu mogli biti ocijenjeni u dojenačkoj populaciji izloženoj lijeku Spinraza zbog ograničenosti komunikacije primjerene toj dobnoj skupini.
English: The exception was an acute, transient deficit in lower spinal reflexes which occurred at the highest dose levels in each study (3 or 4 mg per dose; equivalent to 30 or 40 mg per intrathecal dose in patients).
Croatian: Iznimka je bio akutni, prolazni deficit u spinalnim refleksima donjeg dijela kralježnične moždine, koji je u oba ispitivanja nastao pri najvišoj razini doze (3 ili 4 mg po dozi; što odgovara 30 ili 40 mg po intratekalnoj dozi u bolesnika).
English: The extent of improvement in CHOP INTEND is shown in Figure 1 (change from baseline score for each subject).
Croatian: Opseg poboljšanja rezultata testa CHOP INTEND prikazan je u slici 1 (promjena od početnog rezultata za svakog ispitanika).
English: No impact on male or female fertility, or embryo-foetal development, or pre/post-natal development was observed.
Croatian: Nije bio opažen utjecaj na plodnost mužjaka i ženki ili embriofetalni razvoj ili prenatalni ili postnatalni razvoj.
English: Spinraza is not metabolised via the cytochrome P450 enzyme system in the liver, therefore dose adjustment is unlikely to be required in patients with hepatic impairment (see sections 4.5 and 5.2).
Croatian: Spinraza se ne metabolizira putem sustava enzima citokroma P450 u jetri pa je, stoga, malo vjerojatno da će biti potrebna prilagodba doze u bolesnika s oštećenjem funkcije jetre (vidjeti dijelove 4.5 i 5.2).
English: In the 53-week intrathecal dosing study in cynomolgus monkeys no toxicity effects were seen at levels up to 14-fold the recommended annual clinical maintenance dose.
Croatian: 53-tjednom ispitivanju intratekalne primjene doza u makaki majmuna nisu bili opaženi toksični učinci pri razinama koje su bile do 14 puta više od preporučene godišnje kliničke doze održavanja.
English: All patients who received Spinraza were alive as of the early termination of Part 1, however, one patient in the control arm died at Study Day 289.
Croatian: Svi bolesnici koji su primali lijek Spinrazu bili su živi u trenutku ranog prekida 1. dijela, no jedan je bolesnik u kontrolnoj skupini umro 289. dana ispitivanja.
English: Among patients older than the WHO defined window for expected age of achievement (95th percentile), 17 of 22 (77%) had achieved walking alone.
Croatian: Među bolesnicima starijim od raspona koji je SZO definirao za očekivanu dob postignuća (95. percentil), 17 od 22 (77 %) hodalo je samostalno.
English: Upon completion of Study CS4 (CHERISH) 125 patients enrolled in Study CS11 (SHINE), where all patients received Spinraza.
Croatian: Nakon završetka ispitivanja CS4 (CHERISH) 125 bolesnika uključeno je u ispitivanje CS11 (SHINE), u kojem su svi bolesnici primali lijek Spinraza.
English: Sedation may be required to administer Spinraza, as indicated by the clinical condition of the patient.
Croatian: Možda će biti potrebna sedacija da bi se primijenila Spinraza, na što će ukazati kliničko stanje bolesnika.
English: This injection, called a lumbar puncture, is done by inserting a needle into the space around the spinal cord.
Croatian: Ta injekcija, koja se naziva lumbalna punkcija, daje se uvođenjem igle u prostor oko kralježnične moždine.
English: These results are supported by 2 open label studies (study CS2 and study CS12).
Croatian: Ove su rezultate potkrijepila 2 otvorena ispitivanja (ispitivanje CS2 i ispitivanje CS12).
English: Instructions for preparation of the medicinal product before administration
Croatian: Upute za pripremu lijeka prije primjene
English: If you or your child miss a dose of Spinraza, speak with your doctor so that Spinraza can be given as soon as possible.
Croatian: Ako Vi ili Vaše dijete propustite dozu lijeka Spinraza, obratite se liječniku kako biste lijek Spinraza primili što je prije moguće.
English: • Meningitis not caused by an infection (inflammation of the membrane around the spinal cord and brain, which may present as neck stiffness, headache, fever, nausea and vomiting)
Croatian: • meningitis koji nije uzrokovan infekcijom (upala ovojnice oko leđne moždine i mozga, koja se može očitovati kao ukočenost vrata, glavobolja, vrućica, mučnina i povraćanje)
English: However, individual safety data for the treatment-emergent ADA-positive cases were reviewed, and no AEs of interest were identified.
Croatian: Međutim, pregledani su pojedinačni podaci o sigurnosti za slučajeve pozitivne na protutijela na lijek koji su se pojavili tijekom liječenja, te nisu zabilježni nikakvi značajni štetni događaji.
English: The analysis included 28 patients who received their first dose in study CS2, and then transferred to the extension phase, study CS12.
Croatian: Analiza je uključila 28 bolesnika koji su primili prvu dozu u ispitivanju CS2, a zatim su bili prebačeni u nastavak ispitivanja, tj. ispitivanje CS12.
English: If clinically indicated, urine protein testing (preferably using a first morning urine specimen) is recommended.
Croatian: Ako je klinički indicirano, preporučuje se određivanje proteina u mokraći (po mogućnosti iz uzorka prve jutarnje mokraće).
English: Overall, the incidence of ADAs was low, with 15 (4%) patients classified as ADA positive overall, of which 4 had a transient response, 5 had a persistent response, and 6 patients had responses which could not be classified as transient or persistent at the time of data cut off.
Croatian: Sveukupna incidencija protutijela na lijek bila je niska, s ukupno 15 bolesnika (4 %) ocijenjenih pozitivnim na protutijela na lijek, od kojih su 4 imala privremen odgovor, 5 stalan, a 6 bolesnika imalo je odgovore koji se u trenutku prestanka prikupljanja podataka nisu mogli klasificirati ni kao privremeni ni kao trajni.
English: Twelve out of 20 patients (60%) in the study met the primary endpoint with improvement in mean motor milestone achievement over time.
Croatian: Dvanaest od 20 bolesnika (60%) u ispitivanju postiglo je primarni ishod uz poboljšanje srednje vrijednosti postignutog motoričkog razvoja tijekom vremena.
English: The need for continuation of therapy should be reviewed regularly and considered on an individual basis depending on the patient's clinical presentation and response to the therapy.
Croatian: Potrebu za nastavkom terapije potrebno je redovito provjeravati i razmatrati za pojedinog bolesnika, ovisno o njegovoj kliničkoj slici i odgovoru na terapiju.
English: 5 Based on logistic regression with treatment effect and adjustment for each subject's age at screening and HFMSE score at baseline
Croatian: 5Na temelju logističke regresije s učinkom liječenja i prilagodbom za dob ispitanika na probiru i rezultat HFMSE na početku.
English: CS3B was designed to assess the effect of Spinraza on motor function and survival.
Croatian: Ispitivanje CS3B bilo je ustrojeno tako da se ocijeni učinak lijeka Spinraza na motoričku funkciju i preživljenje.
English: Potential difficulties with this route of administration may be seen in very young patients and those with scoliosis.
Croatian: Potencijalne teškoće povezane s ovim putem primjene mogu se opaziti u vrlo mladih bolesnika i onih sa skoliozom.
English: There may also be difficulties with giving a medicine by this method in very young patients and those with scoliosis (twisted and curved spine).
Croatian: Može biti i poteškoća povezanih s davanjem lijeka na taj način u vrlo mladih bolesnika i onih sa skoliozom (iskrivljenje kralježnice).
English: In Study CS11 all patients received Spinraza, with the length of treatment ranging from 65 to 592 days (median 289 days) at the time of interim analysis.
Croatian: U ispitivanju CS11 svi su bolesnici primali Spinrazu, a duljina liječenja u trenutku interim analize kretala se od 65 do 592 dana (medijan je bio 289 dana).
English: Patients with profound hypotonia and respiratory failure at birth, where Spinraza has not been studied, may not experience a clinically meaningful benefit due to severe SMN protein deficiency.
Croatian: Bolesnici s izrazitom hipotonijom i respiratornim zatajenjem pri rođenju, u kojih lijek Spinraza nije ispitan, možda neće imati klinički značajnu korist zbog teškog nedostatka proteina SMN (engl.
English: As a precautionary measure, it is preferable to avoid the use of Spinraza during pregnancy.
Croatian: Kao mjera opreza, preporučuje se izbjegavati primjenu lijeka Spinraza tijekom trudnoće.
English: Spinraza contains the active substance nusinersen which belongs to a group of medicines known as antisense oligonucleotides.
Croatian: Spinraza sadrži djelatnu tvar nusinersen koja pripada skupini lijekova poznatih pod nazivom protusmjerni oligonukleotidi.
English: Communicating hydrocephalus, aseptic meningitis and hypersensitivity (e.g. angioedema, urticaria and rash) have also been reported.
Croatian: Zabilježeni su i neopstruktivni hidrocefalus, aseptični meningitis i preosjetljivost (npr. angioedem, urtikarija i osip).
English: In vitro studies indicate that the likelihood for interactions with nusinersen due to competition for plasma protein binding, or competition with or inhibition of transporters is low.
Croatian: In vitro ispitivanja pokazuju da je mala vjerojatnost interakcija s nusinersenom prouzročenih kompetitivnim vezanjem za proteine plazme ili kompeticijom s prijenosnicima ili njihovom inhibicijom.
English: It is unknown whether nusinersen/metabolites are excreted in human milk.
Croatian: Nije poznato izlučuju li se nusinersen/metaboliti u majčino mlijeko.
English: The mean terminal elimination half-life in CSF is estimated at 135 to 177 days.
Croatian: Procjenjuje se da je srednja vrijednost terminalnog poluvijeka eliminacije iz cerebrospinalnog likvora 135 do 177 dana.
English: The benefits-and risks of nusinersen treatment in patients with a ventriculoperitoneal shunt are unknown at present and the maintenance of treatment needs to be carefully considered.
Croatian: Koristi i rizici liječenja nusinersenom u bolesnika s ventrikuloperitonealnim drenažnim sustavom za sada nisu poznati pa je potrebno pažljivo razmotriti nastavak liječenja.
English: The median age at screening was 3 years, and the median age of onset of clinical signs and symptoms of SMA was 11 months.
Croatian: Medijan dobi na probiru iznosio je 3 godine, a medijan dobi u kojoj su počeli klinički znakovi i simptomi SMA iznosio je 11 mjeseci.
English: The length of treatment ranged from 74 to 474 days (median 250 days) at the time of the interim analysis.
Croatian: Duljina liječenja u trenutku interim analize kretala se od 74 do 474 dana (medijan je bio 250 dana).
English: If removed from the original carton, the total combined time out of refrigeration should not exceed 30 hours, at a temperature that does not exceed 25°C.
Croatian: Ako se izvadi iz originalnog pakiranja, ukupno vrijeme koje je lijek proveo izvan hladnjaka ne smije biti dulje od 30 sati, na temperaturi koja ne prelazi 25°C.
English: Initiation of treatment sooner after symptom onset resulted in earlier and greater improvement in motor function than those with delayed treatment initiation; however, both groups experienced benefit compared to sham-control.
Croatian: Raniji početak liječenja nakon pojave simptoma doveo je do ranijeg i većeg poboljšanja motoričkih funkcija nego u onih s kasnijim početkom liječenja; međutim, obje su skupine imale korist od liječenja u usporedbi s kontrolnim placebo postupkom.
English: All patients had the ability to suck and swallow at last assessment, with 22 (88%) infants achieving a maximal score on the HINE Section 1.
Croatian: Svi su bolesnici na zadnjoj procjeni imali sposobnost sisanja i gutanja, a 22 (88 %) dojenčadi postiglo je maksimalni rezultat za HINE - 1. dio.
English: In repeat-dose toxicity studies (14-weeks and 53-weeks) of intrathecal administration to juvenile cynomolgus monkeys, nusinersen was well tolerated.
Croatian: U ispitivanjima toksičnosti ponovljenih doza (u trajanju od 14 tjedana i 53 tjedna) primijenjenih intratekalno mladim makaki majmunima, nusinersen se dobro podnosio.
English: The majority of these are reported within 72 hours of the procedure.
Croatian: Većina tih nuspojava zabilježena je unutar 72 sata od postupka.
English: *Adverse events considered related to the lumbar puncture procedure.
Croatian: *Štetni događaji za koje se smatra da su povezani s lumbalnom punkcijom.
English: Reproductive toxicology studies were conducted using subcutaneous administration of nusinersen in mice and rabbits.
Croatian: Ispitivanja reproduktivne toksičnosti provedena su pomoću supkutane primjene nusinersena u miševa i kunića.
English: Of the 20 subjects enrolled, 11 (55%) were alive and free of permanent ventilation at the last visit.
Croatian: Od 20 ispitanika njih 11 (55 %) bilo je živo te tijekom zadnjeg posjeta nije bilo na trajnoj ventilaciji.
English: Study CS11 enrolled infantile and later-onset patients including those who had completed studies CS3B, CS4 and CS12.
Croatian: Ispitivanjem CS11 obuhvaćena su dojenčad i bolesnici s kasnijim početkom bolesti, uključujući one koji su dovršili ispitivanja CS3B, CS4 i CS12.
English: An interim analysis was conducted when patients had been on study for median of 27.1 months (15.135.5 months) and were of a median age at last visit of 26.0 months (14.0 -34.3 months).
Croatian: Interim analiza provedena je kada je medijan razdoblja koje su bolesnici proveli u ispitivanju bio 27,1 mjesec (15,1 do 35,5 mjeseci), a medijan dobi tijekom zadnjeg posjeta bio je 26,0 mjeseci (14,0 do 34,3 mjeseca).
English: MedDRA System Organ Class
Croatian: MedDRA - klasifikacija organskih sustava
English: Proportion of patients who achieved new motor milestones at 15 months4
Croatian: Udio bolesnika koji su postigli nove ključne točke motoričkog razvoja u 15. mjesecu4
English: Very common
Croatian: vrlo često
English: MedDRA preferred term Spinraza frequency category, n=84
Croatian: MedDRA preporučeni izraz Kategorija učestalosti za lijek Spinraza, n=84
English: To allow for long term follow up of these patients, at the end of Study CS3B, 89 patients (Spinraza: n=65; sham-control: n=24) enrolled in Study CS11 (SHINE).
Croatian: Da bi se omogućilo dugoročno praćenje tih bolesnika, krajem ispitivanja CS3B, 89 bolesnika (Spinraza: n = 65; kontrola placebom: n = 24) uključeno je u ispitivanje CS11 (SHINE).
English: The effect of hepatic or renal insufficiency as covariates could not be thoroughly evaluated in the population PK model given the rarity of patients displaying clinically relevant liver or kidney insufficiencies.
Croatian: Učinak zatajivanja jetre ili bubrega kao kovarijati nije se mogao u potpunosti procijeniti u populacijskom farmakokinetičkom modelu s obzirom na to da su bolesnici s klinički značajnim zatajivanjem jetre ili bubrega rijetki.
English: On the basis of the scientific conclusions for nusinersen the CHMP is of the opinion that the benefitrisk balance of the medicinal product(s) containing nusinersen is unchanged subject to the proposed changes to the product information
Croatian: Na temelju znanstvenih zaključaka za nusinersen, CHMP smatra da je omjer koristi i rizika lijeka(ova) koji sadrži(e) nusinersen nepromijenjen, uz predložene izmjene informacija o lijeku.
English: Following intrathecal administration trough plasma concentrations of nusinersen were relatively low compared to the trough CSF concentration.
Croatian: Nakon intratekalne primjene, najniže koncentracije nusinersena u plazmi bile su relativno niske u usporedbi s najnižim koncentracijama u cerebrospinalnom likvoru.
English: Secondary endpoints including functional measures and WHO motor milestone achievement were formally statistically tested and are described in Table 3.
Croatian: Sekundarne mjere ishoda, uključujući funkcionalna mjerenja i postignute ključne točke motoričkog razvoja prema Svjetskoj zdravstvenoj organizaciji (SZO), formalno su statistički testirane i opisane su u tablici 3.
English: Spinraza works by helping the body to produce more of the SMN protein that people with SMA are lacking.
Croatian: Spinraza djeluje tako što pomaže tijelu da proizvede više proteina SMN koji nedostaje osobama sa spinalnom mišićnom atrofijom.
English: At the interim analysis, all 25 patients (2 SMN2 gene copies, n=15; 3 SMN2 gene copies, n=10) were alive without permanent ventilation..
Croatian: U trenutku interim analize svih 25 bolesnika (2 kopije gena SMN2, n = 15; 3 kopije gena SMN2, n = 10) bilo je živo i bez trajne ventilacije.
English: The 6MWT (six-minute walk test) was conducted for ambulatory patients only.
Croatian: 6-Minute Walk Test, 6MWT) proveden je samo u bolesnika koji su mogli hodati.
English: Two events, angioedema and serum sickness, were considered serious and related.
Croatian: Dva su se događaja smatrala ozbiljnima i povezanima: angioedem i serumska bolest.
English: If the vial remains unopened and the solution is not used, it should be returned back to the refrigerator.
Croatian: Ako bočica ostane neotvorena i otopina nije upotrijebljena, potrebno ju je vratiti u hladnjak.
English: Nusinersen demonstrated no evidence of genotoxicity.
Croatian: Nema dokaza da je nusinersen genotoksičan.
English: Survival Event-free survival2
Croatian: Preživljenje Preživljenje bez događaja2
English: Spinraza contains a small amount of sodium
Croatian: Spinraza sadrži male količine natrija
English: This will be done by a doctor experienced in doing lumbar punctures.
Croatian: To će učiniti liječnik s iskustvom u izvođenju lumbalnih punkcija.
English: SMA is a clinical spectrum of disease with disease severity linked to fewer numbers of SMN2 gene copies and younger age of symptom onset.
Croatian: SMA je klinički spektar bolesti s težinom bolesti povezanom s manjim brojem kopija gena SMN2 i mlađom dobi pri pojavi simptoma.
English: Nusinersen is an antisense oligonucleotide (ASO) which increases the proportion of exon 7 inclusion in survival motor neuron 2 (SMN2) messenger ribonucleic acid (mRNA) transcripts by binding to an intronic splice silencing site (ISS-N1) found in intron 7 of the SMN2 pre-messenger ribonucleic acid (pre-mRNA).
Croatian: Nusinersen je protusmjerni oligonukleotid (engl. antisense oligonucleotide, ASO) koji povećava udio uključenih egzona 7 u transkripte glasničke ribonukleinske kiseline (mRNK) gena za preživljenje motoričkih neurona 2 (engl. survival motor neuron 2, SMN2) tako što se veže na intronsko mjesto prigušivanja prekrajanja (engl. intronic splice silencing site, ISS-N1) koje se nalazi na intronu 7 SMN2 predglasničke ribonukleinske kiseline (pre-mRNK).
English: - The active substance is nusinersen.
Croatian: - Djelatna tvar je nusinersen.
English: Among patients treated with Spinraza by lumbar puncture, serious infection, such as meningitis, has been observed.
Croatian: Među bolesnicima liječenim lijekom Spinraza primijenjenim putem lumbalne punkcije opažena je ozbiljna infekcija kao što je meningitis.
English: These results are supported by an open-label Phase 2 study in symptomatic patients diagnosed with SMA (CS3A).
Croatian: Ove je rezultate potkrijepilo otvoreno ispitivanje faze 2 u simptomatskih bolesnika kojima je dijagnosticirana SMA (CS3A).