FrancophonIA/ELRC3.0 huggingface dataset:
English: Nusinersen is metabolized slowly and predominantly via exonuclease (3'- and 5') -mediated hydrolysis and is not a substrate for, or inhibitor or inducer of CYP450 enzymes.
Danish: Nusinersen metaboliseres langsomt og hovedsageligt ved exonuklease (3' og 5')-medieret hydrolyse, og det er ikke et substrat for eller en hæmmer eller induktor for CYP450-enzymer.
English: Autopsy data from patients (n=3) show that nusinersen administered intrathecally is broadly distributed within the CNS achieving therapeutic levels in the target spinal cord tissues.
Danish: Obduktionsdata fra patienter (n=3) viser, at nusinersen, der administreres intratekalt, fordeles vidt i CNS og opnår terapeutiske niveauer i målvævene i rygmarven.
English: In vitro studies indicated that nusinersen is not an inducer or inhibitor of CYP450-mediated oxidative metabolism and therefore should not interfere with other medicinal products for these metabolic pathways.
Danish: In vitro-studier indikerede, at nusinersen ikke er en induktor eller hæmmer af den CYP450-medierede oxidative metabolisme og derfor ikke skulle påvirke andre lægemidler for disse metaboliske veje.
English: Other products that are in the same group of medicines as Spinraza have been shown to affect the kidneys.
Danish: Andre produkter, der tilhører den samme gruppe af lægemidler som Spinraza, har vist sig at påvirke nyrerne.
English: In patients randomized to Spinraza in Study CS3B and including the experience in Study CS11, the median time to death or permanent ventilation was 73 weeks.
Danish: For patienter, der blev randomiseret til Spinraza i studie CS3B og inklusive erfaringerne fra studie CS11, var mediantiden til død eller permanent ventilering 73 uger.
English: If a loading dose is delayed or missed Spinraza should be administered as soon as possible, with at least 14 days between doses, and continue dosing at the prescribed frequency.
Danish: Hvis en støddosis er forsinket eller glemt, skal Spinraza administreres snarest muligt med mindst 14 dage mellem doserne, og doseringen skal fortsætte med den ordinerede hyppighed.
English: Potential difficulties with this route of administration may be seen in very young patients and those with scoliosis.
Danish: ved denne administrationsvej kan ses hos meget unge patienter og patienter med skoliose.
English: Before you or your child are given Spinraza your doctor may decide to do a blood test to check that your or your child's blood can clot properly.
Danish: Før du eller dit barn får Spinraza, kan din læge beslutte at lave en blodanalyse for at kontrollere, at dit eller dit barns blod kan størkne.
English: If clinically indicated, platelet and coagulation laboratory testing is recommended prior to administration of Spinraza.
Danish: Hvis det er klinisk indiceret, anbefales laboratorieanalyser af trombocytter og koagulation før administration af Spinraza.
English: Of those with observed values at Month 15, a higher proportion of Spinraza treated subjects had improvement (73% vs 41%, respectively) and a lower proportion of Spinraza treated subjects had worsening (23% vs 44%, respectively) in total HFMSE score compared to sham-control.
Danish: Af patienterne med værdier observeret ved måned 15 havde en højere andel af de Spinraza-behandlede forsøgspersoner en forbedring (henholdsvis 73 % vs. 41 %), og en lavere andel af de Spinraza-behandlede forsøgspersoner havde en forværring (henholdsvis 23 % vs. 44 %) i samlet HFMSE-score sammenlignet med sham-kontrol.
English: The safety assessment of Spinraza was based on two Phase 3 clinical studies in infants (CS3B) and children (CS4) with SMA, together with one Phase 2 study in infants and children with SMA (CS7) and open-label studies including pre-symptomatic infants (CS5) genetically diagnosed with SMA and infants and children with SMA.
Danish: Sikkerhedsvurderingen for Spinraza var baseret på to fase 3 kliniske studier hos spædbørn (CS3B) og børn (CS4) med SMA sammen med et fase 2-studie hos spædbørn og børn med SMA (CS7) og åbne studier, der inkluderede præsymptomatiske spædbørn (CS5), der var genetisk diagnosticeret med SMA, og spædbørn og børn med SMA.
English: At the final analysis, a statistically significant improvement in HFMSE score from baseline to Month 15 was seen in the Spinraza group compared to the sham-control group (Table 3, Figure 2).
Danish: Ved den endelige analyse sås en statistisk signifikant forbedring i HFMSE-scoren fra baseline til måned 15 i Spinraza-gruppen sammenlignet med sham-kontrolgruppen (tabel 3, figur 2).
English: Treatment with Spinraza should only be initiated by a physician with experience in the management of spinal muscular atrophy (SMA).
Danish: Behandling med Spinraza bør kun påbegyndes af en læge med erfaring i behandling af spinal muskelatrofi (SMA).
English: Study CS11 enrolled infantile and later-onset patients including those who had completed studies CS3B, CS4 and CS12.
Danish: Studie CS11 inkluderede patienter med debut som spæde og senere, herunder dem, der havde gennemført studie CS3B, CS4 og CS12.
English: Unopened vials of Spinraza can be removed from and returned to the refrigerator if necessary.
Danish: Uåbnede hætteglas med Spinraza kan fjernes fra og sættes tilbage i køleskabet, hvis det er nødvendigt.
English: Later onset
Danish: Senere debut
English: Change from baseline in total HFMSE score at 15 months1,2,3
Danish: Ændring fra baseline i total HFMSEscore efter 15 måneder1,2,3
English: The median age of onset of clinical signs and symptoms of SMA was 6.5 weeks and 8 weeks for Spinraza treated versus sham-control patients respectively, with 99% of patients having 2 copies of the SMN2 gene and therefore deemed most likely to develop Type I SMA.
Danish: Medianalderen for debut af kliniske tegn og symptomer på SMA var hhv. 6,5 uger og 8 uger for Spinraza-behandlede patienter versus sham-kontrolpatienter, hvor 99 % af patienterne havde 2 kopier af SMN2-genet, og derfor var blevet vurderet til at have den største sandsynlighed for at udvikle type 1 SMA.
English: Figure 1: Change in CHOP INTEND from Baseline to Later of Day 183, Day 302, and Day 394 Study Visit - Endear Study /CS3B (Efficacy Set, ES)
Danish: Figur 1: Ændring i CHOP INTEND fra baseline til det senere studiebesøg ved dag 183, dag 302 og dag 394- Endear-studiet /CS3B gruppen for effektevaluering (efficacy set, ES)
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.
Danish: Samlet var forekomsten af ADA'er lav, idet i alt 15 (4 %) patienter blev klassificeret som ADA-positive, heraf havde 4 forbigående respons, 5 vedvarende respons, og 6 patienter havde et respons, der ikke kunne klassificeres som hverken forbigående eller vedvarende på tidspunktet for data cut-off. Immunogenicitets virkning på sikkerheden blev ikke analyseret formelt, eftersom antallet af patienter med ADA'er var lavt.
English: No cases of overdose associated with adverse reactions were reported in clinical studies.
Danish: Der er ikke blevet indberettet tilfælde af overdosering forbundet med bivirkninger i de kliniske studier.
English: The pharmacokinetics of nusinersen in patients with renal or hepatic impairment has not been studied.
Danish: Nusinersens farmakokinetik hos patienter med nedsat nyre- eller leverfunktion er ikke blevet undersøgt.
English: 4 Assessed using the Month 15 Efficacy Set (Spinraza n=66; Sham control n=34); analyses are based on imputed data when there are missing data.
Danish: 4Vurderet ved hjælp af måned 15-gruppen for effektevaluering (Spinraza n=66; Sham-kontrol n=34); analyser baseret på imputerede data, når data mangler.
English: Among patients without permanent ventilation at the baseline of Study CS11, a majority were alive and without permanent ventilation at the time of interim analysis.
Danish: Blandt patienter uden permanent ventilering ved baseline i studie CS11 var de fleste i live og uden permanent ventilering på tidspunktet for interimanalysen.
English: Adverse reactions have been identified during post-approval use of Spinraza.
Danish: Der er blevet identificeret bivirkninger ved brug af Spinraza efter godkendelse.
English: What you need to know before you or your child are given Spinraza Spinraza must not be given:
Danish: Det skal du vide, før du eller dit barn begynder at få Spinraza Spinraza må ikke gives:
English: Of the 8 patients with later-onset SMA, 4 out of 5 patients (80%; 95% CI: 38, 96) in the Spinraza group and 2 out of 3 (67%; 95% CI: 21, 94) in the sham-control group met this definition of response.
Danish: Af de 8 patienter med senere debut af SMA opfyldte 4 ud af 5 patienter (80 %; 95 % CI: 38, 96) i Spinraza-gruppen og 2 ud af 3 (67 %; 95 % CI: 21, 94) i sham-kontrolgruppen denne definition på respons.
English: Mean change from baseline to month 15 in total RULM score2,3
Danish: Gennemsnitlig ændring fra baseline til måned 15 i total RULM-score,2,3
English: out of 20 patients (55%) met the endpoint of an increase in total CHOP INTEND score of ≥4 points as of the last study visit.
Danish: Samlet opfyldte 11 ud af 20 patienter (55 %) endepunktet med en forbedring i samlet CHOP INTEND-score på ≥4 point ved det sidste studiebesøg.
English: If removed from the original carton, the total time out of refrigeration should not exceed 30 hours, at a temperature that does not exceed 25°C.
Danish: Hvis det fjernes fra den originale karton, bør den totale tid ude af køleskabet ikke overskride 30 timer ved en temperatur, der ikke overskrider 25 °C.
English: Package leaflet: Information for the user Spinraza 12 mg solution for injection nusinersen
Danish: Indlægsseddel: Information til brugeren Spinraza 12 mg injektionsvæske, opløsning nusinersen
English: Contents of the pack and other information What Spinraza contains
Danish: Pakningsstørrelser og yderligere oplysninger Spinraza indeholder:
English: Patients who initiated Spinraza treatment in Study CS11 (n=20) had a median age of 4.0 years (range 3 - 8 years).
Danish: De patienter, der startede behandling med Spinraza i studie CS11 (n=20), havde en medianalder på 4,0 år (interval 3-8 år).
English: A majority of Spinraza treated patients experienced stabilization or improvement in motor function, with the greatest benefit observed in those with earlier treatment initiation.
Danish: Størstedelen af de patienter, der blev behandlet med Spinraza, oplevede stabilisering eller forbedring af de motoriske funktioner; den største forbedring blev observeret hos dem, der havde startet behandlingen tidligere.
English: Table 2: Primary and secondary endpoints at final analysis - Study CS3B Efficacy Parameter
Danish: Tabel 2: Primære og sekundære endepunkter ved den endelig analyse - studie CS3B Effekt
English: A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from Spinraza therapy taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman.
Danish: Det skal besluttes, om amning eller behandling med Spinraza skal ophøre, idet der tages højde for fordelene ved amning for barnet i forhold til de terapeutiske fordele for moderen.
English: 3At the final analysis, CHOP INTEND and motor milestone analyses were conducted using the Efficacy Set (Spinraza n=73; Sham-control n=37).
Danish: 3 Ved den endelige analyse blev der udført analyser af CHOP INTEND og motoriske milepæle ved hjælp af gruppen for effektevaluering (Spinraza n=73, sham-kontrol n=37).
English: The use of ultrasound or other imaging techniques to assist with intrathecal administration of Spinraza, can be considered at the physician's discretion.
Danish: Anvendelse af ultralyd eller andre teknikker til billeddannelse til at guide intratekal administration af Spinraza kan overvejes efter lægens vurdering.
English: The primary endpoint, time to death or respiratory intervention (defined as invasive or non-invasive ventilation for ≥6 hours/day continuously for ≥7 consecutive days OR
Danish: Det primære endepunkt, tidsperioden til død eller respirationsintervention (defineret som invasiv eller ikke-invasiv ventilering i ≥6 timer/dag kontinuerligt i ≥7 på hinanden følgende dage ELLER trakeostomi), kunne ikke estimeres, da der var for få tilfælde.
English: Of the twelve patients (50%) who had not met the definition of permanent ventilation in Study CS3B, 7 patients (58%) were alive without permanent ventilation in Study CS11.
Danish: Af de 12 patienter (50 %), der ikke havde opfyldt definitionen på permanent ventilering i studie CS3B, var 7 patienter (58 %) i live uden permanent ventilering i studie CS11.
English: It is preferable to avoid the use of Spinraza during pregnancy and breast-feeding.
Danish: Det anbefales at undgå at bruge Spinraza under graviditet og amning.
English: Baseline disease characteristics were largely similar in the Spinraza treated patients and sham-control patients except that Spinraza treated patients at baseline had a higher percentage compared to sham-control patients of paradoxical breathing (89% vs 66%), pneumonia or respiratory symptoms (35% vs 22%), swallowing or feeding difficulties (51% vs 29%) and requirement for respiratory support (26% vs 15%).
Danish: Sygdomskarakteristika ved baseline var i det store og hele tilsvarende for Spinraza-behandlede patienter og sham-kontrolpatienterne, bortset fra at Spinrazabehandlede patienter havde en større procentdel af paradoks vejrtrækning (89 % vs. 66 %), pneumoni eller vejrtrækningssymptomer (35 % vs. 22 %), synke- eller spisebesvær (51 % vs. 29 %) og behov for hjælp til at trække vejret (26 % vs. 15 %) sammenlignet med sham-kontrolpatienterne.
English: required respiratory intervention >6 hours/day continuously for ≥7 days, all of whom initiated ventilatory support during an acute reversible illness
Danish: 4 patienter (2 SMN2-kopier) krævede respirationsintervention >6 timer/dag kontinuerligt i ≥7 dage, og for dem alle blev der indledt ventilering under en akut reversibel sygdom.
English: Of the 13 patients with infantile-onset SMA, 7 of out 9 patients (78%; 95%CI: 45, 94) in the Spinraza group and 0 out of 4 patients (0%; 95%CI: 0, 60) in the sham group met the criteria for motor milestone response (according to HINE section 2: ≥2 point increase [or maximal score] in ability to kick OR ≥1 point increase in the motor milestones of head control, rolling, sitting, crawling, standing or walking and improvement in more categories of motor milestones than worsening) .
Danish: Af de 13 patienter, der debuterede med SMA i spædbørnsalderen, opfyldte 7 ud af 9 patienter (78 %; 95 % CI: 45, 94) i Spinraza-gruppen og 0 ud af 4 patienter (0 %; 95 % CI: 0, 60) i sham-gruppen kriterierne for motorisk milepæl-respons (i henhold til HINE afsnit 2: ≥2 point forbedring [eller maksimal score] i evne til at sparke ELLER ≥1 point forbedring i de motoriske milepæle hovedkontrol, rulle, sidde, kravle, stå eller gå og forbedring i flere kategorier af motoriske milepæleend forværring).
English: In vitro studies indicated that nusinersen is not an inducer or inhibitor of CYP450 mediated metabolism.
Danish: In vitro-studier indikerede, at nusinersen ikke er en induktor eller hæmmer af CYP450-medieret metabolisme.
English: Spinraza is for intrathecal use by lumbar puncture.
Danish: Spinraza er til intratekal anvendelse ved lumbalpunktur.
English: Prior to administration, unopened vials of Spinraza can be removed from and returned to the refrigerator if necessary.
Danish: Før administration kan uåbnede hætteglas med Spinraza tages ud af og sættes tilbage i køleskabet om nødvendigt.
English: Study CS5 (NURTURE) is an open-label study in pre-symptomatic infants genetically diagnosed with SMA, who were enrolled at 6 weeks of age or younger.
Danish: Studie CS5 (NURTURE) er et åbent studie hos præsymptomatiske spædbørn, der er genetisk diagnosticeret med SMA, som blev inkluderet i 6-ugers-alderen eller tidligere.
English: No serious complications of lumbar puncture, such as serious infections, have been observed in the clinical trials of Spinraza.
Danish: Der er ikke observeret alvorlige komplikationer, såsom alvorlige infektioner, fra lumbalpunkturen i de kliniske studier med Spinraza..
English: Spinraza is used to treat a genetic disease called spinal muscular atrophy (SMA).
Danish: Spinraza anvendes til at behandle en genetisk sygdom, der kaldes spinal muskelatrofi (SMA).
English: Median age of onset of clinical signs and symptoms was 56 days and patients had either 2 SMN2 gene copies (n=17) or 3 SMN2 gene copies (n=2) (SMN2 gene copy number unknown for 1 patient).
Danish: Medianalderen for debut af kliniske tegn og symptomer var 56 dage, og patienterne havde enten 2 SMN2-genkopier (n=17) eller 3 SMN2-genkopier (n=2) (antallet af SMN2-genkopier var ukendt for 1 patient).
English: In toxicity studies in animals no effects on male or female fertility were observed (see section 5.3).
Danish: I toksicitetsstudier med dyr blev der ikke observeret nogen virkning på fertiliteten hos hanner eller hunner (se pkt.
English: Adverse reactions associated with the administration of Spinraza by lumbar puncture have been observed.
Danish: Der er blevet observeret bivirkninger forbundet med administration af Spinraza via lumbalpunktur.
English: The Spinraza vial should be inspected for particles prior to administration.
Danish: Hætteglasset med Spinraza skal inspiceres for partikler før administration.
English: Of the 45 patients who had not met the definition of permanent ventilation in Study CS3B, 38 patients (84%) were alive without permanent ventilation in Study CS11 at the time of interim analysis.
Danish: Af de 45 patienter, der ikke havde opfyldt definitionen på permanent ventilering i studie CS3B, var 38 patienter (84 %) i live uden permanent ventilering i studie CS11 på tidspunktet for interimanalysen.
English: Renal toxicity has been observed after administration of other subcutaneously and intravenously administered antisense oligonucleotides.
Danish: Nyretoksicitet er observeret efter administration af andre subkutant eller intravenøst administrerede antisense-oligonukleotider.
English: If the vial remains unopened and the solution is not used, it should be returned back to the refrigerator.
Danish: Hvis hætteglasset ikke åbnes, og opløsningen ikke bruges, skal det sættes tilbage i køleskabet.
English: Single- and multiple-dose pharmacokinetics (PK) of nusinersen, administered via intrathecal injection, were determined in paediatric patients diagnosed with SMA.
Danish: Farmakokinetikken efter en enkelt og flere doser af nusinersen administreret via intratekal injektion blev bestemt hos pædiatriske patienter diagnosticeret med SMA.
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.
Danish: Virkningen af nedsat lever- eller nyrefunktion som kovariater kunne ikke evalueres grundigt i den populationsfarmakokinetiske model, da patienter med en klinisk relevant nedsat levereller nyrefunktion var sjældne.
English: Post-authorisation efficacy study (PAES): In order to evaluate the long term efficacy and safety of nusinersen in symptomatic patients with spinal muscular atrophy, the MAH should conduct and submit the results of the Phase 3, open-label extension study (SHINE, CS11)
Danish: Virkningsundersøgelse efter tilladelse til markedsføring (PAES): For at evaluere langtidsvirkningen og -sikkerheden af nusinersen hos symptomatiske patienter med spinal muskalatrofi skal indehaveren af markedsføringstilladelsen gennemføre og fremsende resultaterne af det åbne fase 3-forlængelsesstudie (SHINE, CS11)
English: The analysis was conducted in the ITT population (Spinraza: n=84; sham-control: n=42), and post-baseline HFMSE data for patients without a Month 15 visit were imputed using the multiple imputation method.
Danish: Analysen blev udført for ITT-populationen (Spinraza: n=84, sham-kontrol: n=42), og HFMSE-data postbaseline for patienter uden et besøg ved måned 15 blev beregnet ved hjælp af den multiple imputeringsmetode.
English: Proportion with any improvement Proportion with any worsening p<0.0001
Danish: Andel, der opnåede en forbedring på 4 point p<0,0001
English: Spinraza is a clear colourless solution for injection.
Danish: Spinraza er en klar, farveløs injektionsvæske, opløsning.
English: If the vial remains unopened and the solution is not used, it should be returned back to the refrigerator (see section 6.4).
Danish: Hvis hætteglasset ikke åbnes, og opløsningen ikke bruges, skal det sættes tilbage i køleskabet (se pkt.
English: Patients were randomized 2:1 to either Spinraza (dosed with 3 loading doses and maintenance doses every 6 months) or sham-control, with a length of treatment ranging from 324 to 482 days.
Danish: Patienterne blev randomiseret i forholdet 2:1 til enten Spinraza (doseret med 3 støddoser og vedligeholdelsesdoser hver 6. måned) eller sham-kontrol med en behandlingslængde fra 324 til 482 dage.
English: Population PK analyses revealed no apparent correlation between hepatic and renal clinical chemistry markers and inter-subject variability.
Danish: Populationsfarmakokinetiske analyser viste ingen tilsyneladende korrelation mellem kliniske kemimarkører for lever og nyrer og variationen fra forsøgsperson til forsøgsperson.
English: Thrombocytopenia and coagulation abnormalities
Danish: Trombocytopeni og koagulationsanormaliteter
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).
Danish: For at muliggøre langsigtet opfølgning af disse patienter blev 89 patienter (Spinraza: n=65; shamkontrol: n=24) inkluderet i studie CS11 (SHINE) ved slutningen af studie CS3B.
English: Patients were randomized 2:1 to either Spinraza (as per the approved dosing regimen) or sham-control, with a length of treatment ranging from 6 to 442 days.
Danish: Patienterne blev randomiseret i forholdet 2:1 til enten Spinraza (ifølge den godkendte administrationsplan) eller sham-kontrol med en behandlingslængde fra 6 til 442 dage.
English: Aseptic technique should be used when preparing Spinraza solution for intrathecal administration.
Danish: Der bør anvendes aseptisk teknik ved klargøring af Spinraza-opløsning til intratekal administration.
English: It is recommended that the volume of cerebral spinal fluid (CSF), equivalent to the volume of Spinraza to be injected, is removed prior to administration of Spinraza.
Danish: Det anbefales, at et volumen af cerebrospinalvæske (cerebral spinal fluid, CSF), som svarer til det volumen Spinraza, der skal injiceres, fjernes før administration af Spinraza.
English: It is recommended that the volume of CSF, equivalent to the volume of Spinraza to be injected, is removed prior to administration of Spinraza.
Danish: Det anbefales, at et volumen af CSF, der svarer til det volumen Spinraza, der skal injiceres, udtages før administration af Spinraza.
English: How long to use Spinraza
Danish: Hvor længe skal Spinraza bruges
English: In patients with decreased consciousness, an evaluation for hydrocephalus should be considered.
Danish: Det bør overvejes at foretage en udredning for hydrocephalus hos patienter med nedsat bevidsthedsniveau.
English: Once drawn into the syringe, if the solution is not used within 6 hours, it must be discarded.
Danish: Når opløsningen er trukket op i sprøjten, skal den bortskaffes, hvis den ikke anvendes inden for 6 timer.
English: sodium hydroxide, hydrochloric acid, water for injections.
Danish: natriumhydroxid, saltsyre, vand til injektionsvæsker.
English: Pre-symptomatic infants
Danish: Præsymptomatiske spædbørn