natgillin/translations-raw huggingface dataset:
The estimated volume of distribution of cerliponase alfa following intracerebroventricular infusion of 300 mg (Vz = 435 ml) exceeds the typical CSF volume (100 ml), suggesting distribution to tissues outside the CSF.
Ocenjeni volumen distribucije cerliponaze alfa po intracerebroventrikularnem infundiranju 300 mg (Vz = 435 ml) presega običajni volumen CSL (100 ml), kar kaže na porazdelitev v tkiva zunaj CSL.
• Do not return CSF to the intracerebroventricular access device.
• CSL ne vračajte v pripomoček za intracerebroventrikularni dostop.
An ongoing study provides experience with two patients aged 2 years of age treated with Brineura at 300 mg every other week (see section 5.1).
Iz potekajoče študije obstajajo izkušnje z dvema bolnikoma, starima 2 leti, zdravljena z zdravilom Brineura 300 mg vsak drugi teden (glejte poglavje 5.1).
Intracerebroventricular administration of cerliponase alfa is not expected to result in therapeutic concentrations in the eye due to the limited access from the CSF to the affected cells of the retina and the presence of the blood-retinal barrier.
Ne pričakuje se, da bi intracerebroventrikularno dajanje cerliponaze alfa povzročilo terapevtske koncentracije v očesu zaradi omejenega dostopa iz CSL do zadevnih celic mrežnice in prisotnosti krvno-mrežnične pregrade.
Thus, the non-clinical development is inconclusive with respect to the clinical safety of cerliponase alfa.
Zato predklinični razvoj ne dopušča sklepanja glede klinične varnosti cerliponaze alfa.
Anti-drug antibodies (ADAs) were detected in both serum and CSF in 79% and 21%, respectively, of patients treated with cerliponase alfa for up to 107 weeks.
Protitelesa proti zdravilu (ADA, anti-drug antibodies) so odkrili v serumu pri 79 % in v cerebrospinalnem likvorju (CSL) pri 21 % bolnikov, zdravljenih s cerliponazo alfa do 107 tednov.
The medicine is slowly pumped through the implanted device.
Zdravilo se počasi črpa skozi vsajeni pripomoček.
Brineura has not been given to patients younger than 2 years of age or older than 8 years of age (at the start of the clinical trial).
Zdravila Brineura niso dajali bolnikom, mlajšim od 2 let ali starejšim od 8 let (ob začetku kliničnega preskušanja).
There are no data on the use of Brineura in pregnant women.
Podatkov o uporabi zdravila Brineura pri nosečnicah ni.
Brineura contains the active substance cerliponase alfa, which belongs to a group of medicines known as enzyme replacement therapies.
Zdravilo Brineura vsebuje učinkovino cerliponazo alfa, ki sodi v skupino zdravil, znanih kot encimsko nadomestno zdravljenje.
Transport and distribute frozen (-85°C to -15°C).
Prevažajte in distribuirajte zamrznjeno (-85 °C do -15 °C).
Contents of the pack and other information What Brineura contains
Vsebina pakiranja in dodatne informacije Kaj vsebuje zdravilo Brineura
• A programmable syringe pump with appropriate delivery range, delivery rate accuracy, and alarms for incorrect delivery or occlusion.
• Črpalka za injekcijsko brizgo, ki jo je mogoče programirati in ima ustrezen razpon dovajanja, natančno hitrost dovajanja in alarm za nepravilno dovajanje ali zamašitev.
This medicine replaces the missing enzyme, TPP1, which minimises the build-up of the lysosomal storage materials.
To zdravilo nadomesti manjkajoči encim, TPP1, kar zmanjša lizosomsko kopičenje nerazgrajenih snovi.
The large CSF to plasma ratios in Cmax and AUC0-t (approximately 1000 and 400, respectively) suggest that the majority of administered cerliponase alfa remains localized within the CNS.
Visoki razmerji CSL glede na plazmo pri Cmax in AUC0-t (približno 1000 oz. 400) kažeta, da ostane večina uporabljene cerliponaze alfa v CŽS.
These particles are removed via the 0.2 μm inline filter without having a detectable effect on the purity or strength of Brineura.
Ti delci se odstranijo s filtrom velikosti 0,2 μm v liniji brez zaznavnega učinka na čistost ali jakost zdravila Brineura.
Genotoxicity, carcinogenicity and reproductive toxicity investigations have not been performed.
Preiskav genotoksičnosti, kancerogenosti ali vpliva na sposobnost razmnoževanja niso opravili.
Access device replacement should be considered prior to 4 years of regular administration of Brineura, however it must always be ensured, that the intracerebroventricular access device is used in accordance with the provisions of the respective medical device manufacturer.
Zamenjavo pripomočka za dostop je treba izvesti, preden potečejo 4 leta rednega dajanja zdravila Brineura, pri čemer je vedno treba zagotavljati, da se pripomoček za intracerebroventrikularni dostop uporablja v skladu z določbami izdelovalca ustreznega medicinskega pripomočka.
- The active substance is cerliponase alfa.
- Učinkovina je cerliponaza alfa.
The complete infusion time, including Brineura and the required flushing solution, is approximately 2 to 4.5 hours, depending on the dose and volume administered.
Celotni čas infundiranja zdravila Brineura in potrebne raztopine za izpiranje je približno 2 do 4,5 ure, odvisno od uporabljenega odmerka in količine.
These studies used the aggregate of the motor and language domains of a disease-specific clinical rating scale (see Table 3) to assess disease progression.
V teh študijah so za ocenitev napredovanja bolezni uporabili združek motoričnih in govornih domen z lestvice klinične ocene, specifične za bolezen (glejte preglednico 3).
Thawing the vials outside the carton is recommended.
Priporoča se, da se viale odtajajo zunaj škatle.
The infusion should be interrupted and/or the rate slowed in patients who in the judgement of the treating physician have a possible increase in intracranial pressure during the infusion as suggested by symptoms such as headache, nausea, vomiting, or decreased mental state.
Infundiranje je treba prekiniti in/ali hitrost zmanjšati pri bolnikih, ki imajo po presoji lečečega zdravnika verjetno povečanje intrakranialnega tlaka med infundiranjem, na kar kažejo simptomi, kot so glavobol, siljenje na bruhanje, bruhanje ali zmanjšana duševna sposobnost.
Cerliponase alfa is a protein and is expected to be metabolically degraded through peptide hydrolysis.
Cerliponaza alfa je beljakovina, zato se pričakuje, da bo presnovno razgrajena s hidrolizo peptidov.
The mean baseline CLN2 score was 3.5 (standard deviation (SD) 1.20) with a range from 1 to 6; no patients with advanced disease progression were studied (inclusion criteria: mild to moderate progression of CLN2 disease).
Povprečna izhodiščna ocena za CLN2 je bila 3,5 (standardna deviacija (SD) 1,20) z razponom od 1 do 6; proučevan ni bil noben bolnik z napredovalo obliko bolezni (vključitveni kriteriji: blago do zmerno napredovanje CLN2).
Thaw Brineura vials and flushing solution vial at room temperature for approximately 60 minutes.
Viale zdravila Brineura in raztopine za izpiranje odtajajte pri sobni temperaturi približno 60 minut.
Consequently, impaired liver function is not expected to affect the pharmacokinetics of cerliponase alfa.
Posledično ni za pričakovati, da bi okvarjeno delovanje jeter vplivalo na farmakokinetiko cerliponaze alfa.
What you need to know before you or your child is given Brineura 3.
Kaj morate vedeti, preden boste vi ali vaš otrok prejeli zdravilo Brineura 3.
In case of intracerebroventricular access device-related complications, refer to the manufacturer's labelling for further instruction.
V primeru zapletov, povezanih s pripomočkom za intracerebroventrikularni dostop, glejte izdelovalčev oznake za nadaljnja navodila.
• One single-use infusion set.
• En infuzijski set za enkratno uporabo.
Product should only be withdrawn from the unopened vials immediately prior to use.
Zdravilo je treba izvleči iz neodprtih vial šele tik pred uporabo.
In study 190-201, 20 out of 23 (87%) patients receiving Brineura for 48 weeks did not have an unreversed 2 point decline in the untreated patient population (p=0.0002, binomial test assuming p0= 0.50).
V študiji 190-201 20 od 23 bolnikov (87 %), ki so prejemali zdravilo Brineura 48 tednov, ni imelo nepopravljenega upada za 2 točki kot pri nezdravljeni populaciji bolnikov (p = 0,0002, binomni test s predvidenim p0 = 0,50).
Precautions to be taken before handling or administering the medicinal product Aseptic technique must be strictly observed during preparation and administration.
Previdnostni ukrepi, potrebni pred ravnanjem z zdravilom ali dajanjem zdravila Med pripravo in dajanjem morate striktno upoštevati pravila aseptične tehnike.
The adverse reactions described in this section were evaluated in 24 patients with CLN2 disease who received at least one dose of Brineura in clinical studies of up to 141 weeks.
Neželene učinke, opisane v tem poglavju, so ocenili pri 24 bolnikih s CLN2, ki so prejeli vsaj en odmerek zdravila Brineura v kliničnih študijah, ki so trajale do 141 tednov.
All 23 patients completed study 190-201 and continued to the ongoing extension study 190-202 treated with Brineura at 300 mg every other week to a maximum of 124 weeks.
23 bolnikov je študijo 190-201 zaključilo in v podaljšku študije 190-202 nadaljevalo zdravljenje z zdravilom Brineura 300 mg vsak drugi teden do največ 124 tednov.
In order to evaluate the long-term safety of cerliponase alfa, including the occurrence of serious hypersensitivity reactions and anaphylaxis, the MAH should submit the results of a study based on adequate source of data deriving from a registry of patients with neuronal ceroid lipfuscinosis Type 2 (CLN2).
Da bi ocenili dolgoročno varnost cerliponaze alfa, vključno s pojavom resnih preobčutljivostnih reakcij in anafilakse, mora imetnik dovoljenja za promet z zdravilom predložiti rezultate študije na podlagi ustreznega vira podatkov, izpeljanega iz registra bolnikov z nevronsko ceroidno lipofuscinozo tipa 2 (CLN2).
Your doctor may send samples of brain fluid to check for signs of infection.
Zdravnik lahko vzorce možganskega likvorja pošlje v pregled glede znakov okužbe.
• One empty sterile single-use syringe (for collection of CSF to check patency).
• Ena prazna sterilna injekcijska brizga za enkratno uporabo (za odvzem CSL za preverjanje prehodnosti).
What Brineura is and what it is used for 2.
Kaj je zdravilo Brineura in za kaj ga uporabljamo 2.
What Brineura is and what it is used for
Kaj je zdravilo Brineura in za kaj ga uporabljamo
• Port needle: Deltec GRIPPER Needles
• igla za pristopno odprtino: igle Deltec GRIPPER
Consideration of dose adjustments may be necessary for patients who may not tolerate the infusion.
Morda bo treba pri bolnikih, ki infuzije ne bi prenašali, razmisliti o prilagoditvi odmerka.
Severe (Common Terminology Criteria for Adverse Events (CTCAE) grade 3) hypersensitivity reactions occurred in three patients and no patients discontinued treatment.
Common Terminology Criteria for Adverse Events)) preobčutljivostne reakcije so se pojavile pri treh bolnikih, do prekinitve zdravljenja pa ni prišlo pri nobenem bolniku.
Vision and seizure scores when combined with CLN2 score (motor and language domains) remain stable.
Rezultata za vid in epileptične napade ostaneta stabilna, ko ju združimo z rezultatom CLN2 (motorična in govorna domena).
The intracerebroventricular access device must be implanted prior to the first infusion.
Pripomoček za intracerebroventrikularni dostop je treba vsaditi pred prvim infundiranjem.
In study 190-201, the mean rate of decline in patients treated with Brineura at 300 mg every other week was 0.40 points per 48 weeks.
V študiji 190-201 je bila povprečna stopnja upada pri bolnikih, zdravljenih z zdravilom Brineura 300 mg vsak drugi teden, 0,40 točke v 48 tednih.
People with CLN2 disease do not have any enzyme called TPP1 or they have too little of it and this causes a build-up of substances called lysosomal storage materials.
Ljudje s CLN2 nimajo encima, imenovanega TPP1, ali pa ga imajo premalo, kar povzroči tako imenovano lizosomsko kopičenje nerazgrajenih snovi.
- If you or your child has a device implanted to drain extra fluid from the brain.
- Če imate vi ali vaš otrok vsajen pripomoček za odvajanje odvečne tekočine iz možganov.
Treatment of Brineura was initiated in children 2 to 8 years of age in clinical studies.
Zdravljenje z zdravilom Brineura je bilo v kliničnih študijah uvedeno pri otrocih, starih od 2 do 8 let.
The posology selected for patients is based on age at time of treatment and should be adjusted accordingly (see Table 1).
Odmerjenje, izbrano za bolnike, temelji na starosti v času zdravljenja in ga je treba ustrezno prilagoditi
Intracerebroventricular access devices shown to be compatible with Brineura and flushing solution and used in Brineura clinical studies include CodmanHOLTER RICKHAM and HOLTER SALMON-RICKHAM Reservoirs, Codman Ventricular Catheter, and Medtronic CSF-Ventricular Reservoir (with catheter).
Pripomočki za intracerebroventrikularni dostop, ki so dokazano združljivi z zdravilom Brineura in raztopino za izpiranje in so bili uporabljeni v kliničnih študijah z zdravilom Brineura, vključujejo zbiralnike Codman HOLTER RICKHAM in HOLTER SALMON-RICKHAM, ventrikularni kateter Codman in ventrikularni zbiralnik za CSL (s katetrom) družbe Medtronic.
Label the infusion line for “Intracerebroventricular infusion only”.
Infuzijsko linijo označite kot "Samo za intracerebroventrikularno infundiranje".
You should not receive Brineura treatment during pregnancy unless clearly necessary.
Zdravila Brineura ne smete prejemati med nosečnostjo, razen kadar je nujno potrebno.
Limited data are available for children aged 2 years and no clinical data is available in children below 2 years of age (see section 5.1).
Za otroke, stare 2 leti, je na voljo malo podatkov, za otroke, stare manj kot 2 leti, pa podatki niso na voljo (glejte poglavje 5.1).
As a precautionary measure, appropriate medical support should be readily available when Brineura is administered.
Kot previdnostni ukrep mora biti pri dajanju zdravila Brineura na voljo ustrezna medicinska podpora.
Calculate the flush volume by adding the priming volume of all infusion components, including the intracerebroventricular access device.
Volumen za izpiranje izračunajte tako, da seštejete volumen za polnjenje vseh infuzijskih komponent, vključno s pripomočkom za intracerebroventrikularni dostop.
Limited preclinical safety data of cerliponase alfa were generated from single dose toxicity studies in monkeys and repeated-dose studies in a dachshund dog model of classic late infantile neuronal ceroid lipofuscinosis type 2.
Omejeni predklinični podatki o varnosti cerliponaze alfa so pridobljeni iz študij toksičnosti enega odmerka pri opicah in iz študij ponavljajočega odmerka v modelu klasične pozne infantilne nevronske ceroidne lipofuscinoze tipa 2 na psu jazbečarju.
Attach the syringe containing the calculated volume of flushing solution to the infusion components (see section 6.6).
Priključite injekcijsko brizgo, ki vsebuje preračunano količino raztopine za izpiranje, na komponente za infundiranje (glejte poglavje 6.6).
Caution should be taken in patients prone to complications from intracerebroventricular medicinal product administration, including patients with obstructive hydrocephalus.
Previdnost je potrebna pri bolnikih, nagnjenih k zapletom zaradi intracerebroventrikularnega dajanja zdravil, vključno z bolniki z obstruktivnim hidrocefalusom.
Brineura should be administered with infusion components shown to be chemically and physically compatible with administration of Brineura and flushing solution.
Zdravilo Brineura je treba dajati s komponentami za infundiranje, ki so dokazano kemijsko in fizično združljivi z dajanjem zdravila Brineura in raztopine za izpiranje.
Brineura and flushing solution are supplied and stored frozen (see section 6.4).
Zdravilo Brineura in raztopina za izpiranje sta dobavljena in shranjena zamrznjena (glejte poglavje 6.4).
MedDRA System organ class
MedDRA Organski sistem
See leaflet for further information
Glejte navodilo za uporabo za več informacij
Brineura and flushing solution must be completely thawed and used immediately (see section 6.3).
Zdravilo Brineura in raztopino za izpiranje je treba povsem odtajati in takoj porabiti (glejte poglavje 6.3).
The pharmacokinetics of cerliponase alfa were evaluated in patients with CLN2 disease who received intracerebroventricular infusions of 300 mg over approximately 4.5 hours once every other week.
Farmakokinetiko cerliponaze alfa so ocenili pri bolnikih s CLN2, ki so prejemali intracerebroventrikularne infuzije 300 mg v trajanju približno 4,5 ur, enkrat vsak drugi teden.
In two clinical cases, the ICV access devices did not show signs of failure at the time of infusion; however, after removal, material degradation of the devices were apparent and consistent with data from benchtop testing of ICV access devices.
V dveh primerih kliničnega zdravljenja pripomoček za intracerebroventrikularni dostop med infundiranjem ni kazal napak; vendar je bila po odstranitvi pripomočka degradacija materiala jasno opazna in skladna s podatki laboratorijskega testiranja pripomočka za intracerebroventrikularni dostop.
In the ongoing study 190-202 (as of 03 June 2016), the rate of decline in patients treated with Brineura compared to the natural history control group (N=42 patients) continues to show durability of the treatment effect (see Figure 2).
V potekajoči študiji 190-202 (na 3. junij 2016) stopnja upada pri bolnikih, zdravljenih z zdravilom Brineura, v primerjavi s kontrolno skupino z naravnim potekom bolezni (N = 42 bolnikov) še naprej kaže trajnost učinka zdravljenja (glejte sliko 2).
The recommended dose is 300 mg cerliponase alfa administered once every other week by intracerebroventricular infusion.
Priporočeni odmerek je 300 mg cerliponaze alfa, ki se daje enkrat vsak drugi teden v obliki intracerebroventrikularne infuzije.
Table 1: Dose and volume of Brineura
Preglednica 1: Odmerek in količina zdravila Brineura
Total convulsion events with a temporal relationship to cerliponase alfa administration was 17% and were mild to moderate, grade 1 to 2 in severity.
Skupno je bilo dogodkov konvulzije s časovnim razmerjem do apliciranja cerliponaze alfa 17 %, pri čemer so bili blagi do zmerni, stopnje 1 do 2 po resnosti.
It is not known whether Brineura can cause foetal harm when administered to a pregnant woman or can affect reproductive capacity.
Ni znano, ali lahko zdravilo Brineura škoduje zarodku, če se uporabi pri nosečnici, in ali vpliva na sposobnost razmnoževanja.
In clinical studies, antibiotics were administered, the intracerebroventricular access device was replaced, and Brineura treatment was continued.
V kliničnih študijah so uporabili antibiotike, zamenjali pripomoček za intracerebroventrikularni dostop in nadaljevali zdravljenje z zdravilom Brineura.
The safety and efficacy of Brineura in children less than 3 years of age has not yet been established.
Pediatrična populacija Varnost in učinkovitost zdravila Brineura pri otrocih, starih manj kot 3 leta, še nista bili dokazani.
What you need to know before you or your child is given Brineura You must not receive Brineura:
Kaj morate vedeti, preden boste vi ali vaš otrok prejeli zdravilo Brineura Zdravila Brineura ne smete prejeti:
These adverse reactions were observed during or within 24 hours after completion of the Brineura infusion and did not interfere with treatment.
Te neželene učinke so opazili med infundiranjem ali v 24 urah po infundiranju zdravila Brineura, vendar pa niso motili zdravljenja.
It is not known whether Brineura is excreted in human breast milk.
Ni znano, ali se zdravilo Brineura izloča v materino mleko.
Very common side effects: headache increased or decreased protein in the brain fluid abnormal results of heart electrical activity (ECG) increased cells in the spinal fluid detected by laboratory monitoring infection of your nose or throat (cold) needle issue (infusion needle falls out of implanted device)
Zelo pogosti neželeni učinki: glavobol zvišanje ali znižanje ravni beljakovin v možganskem likvorju nenormalni rezultati električne aktivnosti srca (EKG) povečano število celic v spinalni tekočini, kar se odkrije z laboratorijskim spremljanjem okužba nosu ali žrela (prehlad)
• Extension Set: Fresenius Injectomat® line, Alaris CC Extension set, Vygon Lectro-Cath Extension tube
• podaljševalni set: linija Fresenius Injectomat®, podaljšek Alaris CC, podaljševalna cevka Vygon
Currently no clinical experience of Brineura in children below 2 years of age is available (see section 4.8).
Trenutno ni na voljo kliničnih izkušenj z zdravilom Brineura pri otrocih, starih manj kot 2 leti (glejte poglavje 4.8).
The infusion set must be equipped with a 0.2 µm inline filter.
Infuzijski set mora biti opremljen s filtrom velikosti 0,2 µm v liniji.
Connect a separate empty sterile syringe (no larger than 3 ml) to the port needle.
Povežite posebno prazno sterilno injekcijsko brizgo (naj ne bo večja kot 3 ml) z iglo za pristopno odprtino.
The glycosylation profile of cerliponase alfa results in consistent cellular uptake and lysosomal targeting for activation.
Profil glikozilacije cerliponaze alfa ima za posledico dosledni celični privzem in prispetje v lizosome za aktivacijo.
Using aseptic technique, withdraw the volume of Brineura solution per required dose (see Table 1 in section 4.2) into the sterile syringe labelled “Brineura”.
Z aseptično tehniko izvlecite količino raztopine zdravila Brineura za potreben odmerek (glejte preglednico 1 v poglavju 4.2) v sterilno injekcijsko brizgo z napisom "Brineura".
See Figure 1.
Glejte sliko 1. 3.
This should be taken into consideration for patients on a controlled sodium diet.
To je treba upoštevati pri bolnikih, ki so na dieti z nadzorovanim vnosom natrija.
• Secure the components per institution standard of care.
• Komponente pritrdite v skladu s standardom nege, uveljavljenim v ustanovi.
Brineura treatment should be interrupted in cases of device failure and may require replacement of the access device prior to subsequent infusions.
Zdravljenje z zdravilom Brineura je treba v primeru okvare pripomočka prekiniti in morda bo treba pripomoček za dostop pred naslednjim infundiranjem zamenjati.
The implanted intracerebroventricular access device should be appropriate for accessing the cerebral ventricles for therapeutic administration.
Vsajeni pripomoček za intracerebroventrikularni dostop mora biti ustrezen za dostopanje do možganskih prekatov za terapevtsko apliciranje.
Treatment effect in patients receiving Brineura was assessed using the CLN2 clinical rating scale, and results were compared to the 2 points per 48 weeks predicted decline in the natural history control group.
Učinek zdravljenja pri bolnikih, ki so prejemali zdravilo Brineura, so ocenili z lestvico za klinično oceno CLN2, rezultate pa so primerjali s predvidenim upadom 2 točk na 48 tednov v kontrolni skupini z naravnim potekom.
1 year to < 2 years: 200 mg (first 4 doses), 300 mg (all other doses) ≥ 2 years: 300 mg
od rojstva do < 6 mesecev: 100 mg od 6 mesecev do < 1 leto: 150 mg od 1 leta do < 2 leti: 200 mg (prvi 4 odmerki), 300 mg (vsi naslednji odmerki) ≥ 2 leti: 300 mg
After the medicine has been given, a shorter infusion of a solution is given to flush Brineura out of the infusion equipment so that the full dose reaches the brain.
Po dajanju zdravila se s krajšo infuzijo raztopine za izpiranje zdravilo Brineura izpere iz opreme za infundiranje, tako da možgane doseže polni odmerek.
For instructions on preparation of Brineura and flushing solution before administration, see section 6.6.
Za navodila glede priprave zdravila Brineura in raztopine za izpiranje pred dajanjem glejte poglavje 6.6.
It is used to treat patients with neuronal ceroid lipofuscinosis type 2 (CLN2) disease, also known as tripeptidyl peptidase-1 (TPP1) deficiency.
Uporablja se za zdravljenje bolnikov z nevronsko ceroidno lipofuscinozo tipa 2 (CLN2), ki je znana tudi kot pomanjkanje tripeptidil-peptidaze-1 (TPP1).
No prominent ataxia, no pathologic falls.
Ni izrazite ataksije, ni patoloških padcev.
Pack size: 3 vials (two vials of Brineura and one vial of flushing solution), each containing 5 ml of solution
Velikost pakiranja: 3 viale (dve viali zdravila Brineura in ena viala raztopine za izpiranje), od katerih vsaka vsebuje 5 ml raztopine
Attach the infusion set to the port needle (see Figure 1).
Infuzijski set priključite na iglo za pristopno odprtino (glejte sliko 1).