natgillin/translations-raw huggingface dataset:
It acts to increase the level of a substance called dopamine in the brain, which is involved in the control of movement and is present in reduced amounts in the brain of patients with Parkinson's disease.
Ona djeluje podizanjem razine tvari koji se naziva dopamin u mozgu, koja je uključena u kontrolu pokreta a prisutna je u smanjenim količinama u mozgu bolesnika s Parkinsonovom bolešću.
Substance-related radioactivity was largely excreted in urine (76%) and only to a low extent in faeces (1.5%) after 192 hours.
Radioaktivnost povezana s tvari se velikim dijelom izlučuje urinom (76%), a samo u manjoj mjeri fecesom (1,5%) nakon 192 sata.
Adverse reactions are ranked under headings of frequency using the following conventions: very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1000 to <1/100), rare (≥1/10,000 to <1/1000), very rare (<1/10,000) and not known (cannot be estimated from the available data).
Nuspojave su rangirane prema učestalosti korištenjem sljedećih konvencija: vrlo često (≥1/10) često (≥1/100 i <1/10); manje često (≥1/1000 i <1/100), rijetko (≥1/10 000 i <1/1000), vrlo rijetko (<1/10 000) i nepoznato (ne može se procijeniti iz dostupnih podataka).
The pharmacodynamic effects of safinamide have not been assessed in children and adolescents.
Farmakodinamički učinci safinamida nisu procijenjeni u djece i adolescenata.
Foot fracture
Fraktura stopala
In one patient suspected of consuming more than the daily prescribed dose of 100 mg for one month, symptoms of confusion, sleepiness, forgetfulness and dilated pupils were reported.
U jednog bolesnika za kojeg se sumnja da je konzumirao više od propisane dnevne doze od 100 mg u trajanju od jednog mjeseca, prijavljeni su simptomi konfuzije, pospanosti, zaboravnosti i proširenih zjenica.
There is no known antidote to safinamide or any specific treatment for safinamide overdose.
Nema poznatog antidota za safinamid ili specifičnog liječenja za predoziranje safinamidom.
To what extent the nondopaminergic effects contribute to the overall effect has not been established.
U kojoj mjeri nedopaminergički učinci doprinose ukupnom učinku nije ustanovljeno.
Xadago may be taken with or without food.
Xadago se može uzimati s hranom ili bez nje.
The pharmacokinetics of safinamide are linear after single and repeated doses.
Farmakokinetika safinamida je linearna nakon jedne i ponovljenih doza.
Studies were not stratified for co-medication, and no randomized interaction studies were performed for these medicinal products.
Ispitivanja nisu stratificirana za prateće lijekove i nisu provedena randomizirana ispitivanja interakcije za te lijekove.
The volume of distribution (Vss) is approximately 165 L which is 2.5-fold of body volume indicating extensive extravascular distribution of safinamide.
Volumen distribucije (Vss) je oko 165 l, što je 2,5 puta volumen tijela i ukazuje na opsežnu ekstravaskularnu distribuciju safinamida.
95% CI p-value
95 % CI p-vrijednost
• At the request of the European Medicines Agency; • Whenever the risk management system is modified, especially as the result of new information being received that may lead to a significant change to the benefit/risk profile or as the result of an important (pharmacovigilance or risk minimisation) milestone being reached.
• prilikom svake izmjene sustava za upravljanje rizicima, a naročito kada je ta izmjena rezultat primitka novih informacija koje mogu voditi ka značajnim izmjenama omjera korist/rizik, odnosno kada je izmjena rezultat ostvarenja nekog važnog cilja (u smislu farmakovigilancije ili minimizacije rizika).
If you take more Xadago than you should
Ako uzmete više lijeka Xadago nego što ste trebali
Safinamide does not appear to significantly induce or inhibit enzymes at clinically relevant systemic concentrations.
Izgleda da safinamid značajno ne inducira i ne inhibira enzime u klinički relevantnim sistemskim koncentracijama.
Amidase present in blood, plasma, serum, simulated gastric fluid and simulated intestinal fluid as well as human carboxylesterases hCE-1 and hCE-2 are not responsible for the biotransformation of safinamide to NW-1153.
Amidaza prisutna u krvi, plazmi, serumu, simuliranoj želučanoj tekućini i simuliranoj crijevnoj tekućini, kao i ljudske karboksilesteraze hCE-1 i hCE-2 nisu odgovorne za biotransformaciju safinamida u NW-1153.
Safinamide undergoes almost complete metabolic transformation (<10% of the administered dose was found unchanged in urine).
Safinamid prolazi gotovo potpunu metaboličku transformaciju (<10% primijenjene doze pronađeno je nepromijenjeno u urinu).
What you need to know before you take Xadago
Što morate znati prije nego počnete uzimati Xadago
Dyskinesia occurred early in treatment, was rated “severe”, led to discontinuation in very few patients (approx. 1.5%), and did not require reduction of dose in any patient.
Diskinezija se javila rano u liječenju, ocijenjena je kao „teška“, dovela je do prekida liječenja u vrlo malom broju bolesnika (oko 1,5 %) i nije zahtijevala smanjenje doze kod niti jednog bolesnika.
The primary efficacy parameter was the change from baseline to endpoint in ‘ON Time without troublesome dyskinesia'.
Parametar primarne djelotvornosti bio je promjena od početne vrijednosti do ishoda u „ON razdoblju bez problematične diskinezije“.
The effect on ON Time was maintained at the end of the 24-month double-blind treatment period for both safinamide doses as compared to placebo.
Učinak ON razdoblja održavan je na kraju razdoblja dvostruko slijepog liječenja u trajanju od 24 mjeseca za obje doze safinamida u usporedbi s placebom.
Long-term studies in animals have shown convulsions (1.6 to 12.8 times human clinical exposure, based on plasma AUC).
Dugoročna ispitivanja na životinjama pokazala su konvulzije (pri kliničkoj izloženosti 1,6 do 12,8 puta većoj od one u ljudi, na temelju AUC-a u plazmi).
If an important overdose occurs, safinamide treatment should be discontinued and supportive treatment should be administered as clinically indicated.
Ako se dogodi važno predoziranje, liječenje safinamidom mora se prekinuti i potrebno je primijeniti potporno liječenje kako je klinički indicirano.
The safety and efficacy of safinamide in children and adolescents under 18 years of age have not been established.
Sigurnost i djelotvornost safinamida u djece i adolescenata mlađih od 18 godina nisu još ustanovljene.
The lower dose of 50 mg/day is recommended for patients with moderate hepatic impairment.
Niža doza od 50 mg/dan se preporučuje za bolesnike s umjerenim oštećenjem jetre.
- Uncontrollable jerky movements may occur or worsen when Xadago is used together with levodopa.
- Nevoljni trzajni pokreti mogu se pojaviti ili pogoršati kada se Xadago primjenjuje zajedno s levodopom.
Metabolite structure elucidation revealed three metabolic pathways of safinamide.
Rasvjetljavanje strukture metabolita otkrilo je tri metabolička puta safinamida.
Available pharmacodynamic/toxicological data in animals have shown excretion of safinamide in milk (for details see 5.3).
Dostupni farmakodinamički/toksikološki podaci za životinje pokazali su izlučivanje safinamida u mlijeko (za pojedinosti vidjeti dio 5.3).
Safinamide may be taken with or without food.
Safinamid se može uzeti s hranom ili bez nje.
The relevant plasma concentrations of safinamide are substantially lower, therefore a clinically relevant interaction with co-administered substrates of these transporters is unlikely.
Relevantne koncentracije safinamida u plazmi su znatno manje, stoga su klinički relevantne interakcije s istovremeno primjenjivanim supstratima tih transportera malo vjerojatne.
The amidase FAAH was able to catalyse the formation of NW-1153 at low rates only.
Amidaza FAAH mogla je katalizirati stvaranje NW-1153 samo u niskim stopama.
Safinamide is a highly selective and reversible MAO-B inhibitor causing an increase in extracellular levels of dopamine in the striatum.
Safinamid je visoko selektivni i reverzibilni MAO-B inhibitor koji uzrokuje porast u ekstracelularnim razinama dopamina u striatumu.
Description of selected adverse dreactions
Opis odabranih nuspojava
The expected pattern of events or symptoms following intentional or accidental overdose with Safinamide would be those related to its pharmacodynamic profile: MAO-B inhibition with activity-dependent inhibition of Na channels.
Očekivani slijed događaja ili simptoma nakon namjernog ili slučajnog predoziranja safinamidom bio bi povezan s njegovim farmakodinamičkim profilom: MAO-B inhibicija s inhibicijom ovisnom o aktivnosti Na+ kanala.
Therefore, other amidases are likely to be involved in the conversion to NW-1153.
Stoga, druge amidaze su vjerojatno uključene u pretvorbu u NW-1153.
In human liver microsomes (HLM), the N-dealkylation step appears to be catalysed by CYP3A4, as safinamide clearance in HLM was inhibited by ketoconazole by 90%.
U ljudskim mikrosomima jetre (engl. human liver microsomes, HLM), čini se da je korak N-dealkilacije kataliziran s CYP3A4, jer je klirens safinamida u HLM-u inhibiran ketokonazolom za 90 %.
Pharmacotherapeutic group: Anti-Parkinson-Drugs, monoamine oxidase -B inhibitors, ATC code: N04BD03.
Farmakoterapijska skupina: Antiparkinsonici, inhibitori monoaminooksidaze B, ATK oznaka: N04BD03
Elderly No change in dose is required for elderly patients.
Nije potrebna promjena doze u starijih bolesnika.
Safinamide did not present genotoxic potential in in vivo and in several in vitro systems using bacteria or mammalian cells.
Safinamid nije pokazao genotoksični potencijal ni u in vivo ni u nekoliko in vitro sustava koji koriste bakterije ili stanice sisavaca.
Animal studies indicate that safinamide treatment is associated with adverse reactions on female rat reproductive performance and sperm quality.
Ispitivanja na životinjama ukazuju da je liječenje safinamidom povezano s nuspojavama koje se odnose na reproduktivnu sposobnost ženki štakora i kvalitetu sperme.
Absolute bioavailability is high (95%), showing that safinamide is almost completely absorbed after oral administration and first pass metabolism is negligible.
Apsolutna bioraspoloživost je visoka (95%), što pokazuje da se safinamid gotovo u potpunosti apsorbira nakon peroralne primjene i metabolizam prvog prolaza je zanemariv.
Change LSM (SE)
Promjena LSM (SE) -0,8
Therefore, caution is necessary when safinamide is taken concomitantly with medicinal products that are OCT1 substrates and have a tmax similar to safinamide (2 hours) (e.g. metformin, aciclovir, ganciclovir) as exposure to these substrates might be increased as a consequence.
Stoga je potreban oprez kada se safinamid uzima istodobno s lijekovima koji su supstrati OCT1 i imaju Tmax sličan safinamidu (2 sata) (npr. metformin, aciklovir, ganciklovir) budući da se posljedično može povećati izloženost tim supstratima.
Skip the missed dose and take the next dose at the time you normally take it.
Preskočite propuštenu dozu i uzmite sljedeću dozu po redovitom rasporedu, u vrijeme kada ju uobičajeno uzimate.
Toxic effects on the liver and accompanying symptoms as yellow/orange skin and skull, in pups exposed to safinamide during lactation are mediated mainly via in utero exposure, whereas exposure via the mother's milk had only a minor influence.
Toksični učinci na jetru i prateći simptomi kao žuta/narančasta koža i lubanja, u mladunaca izloženih safinamidu tijekom dojenja posredovani su uglavnom izloženošću in utero, dok je izloženost preko majčinog mlijeka imala samo manji utjecaj.
This potential increase is most likely of no clinical relevance as NW-1153, the first product in the metabolic pathway, is further transformed to secondary and tertiary metabolites.
Taj mogući rast najvjerojatnije nije od kliničke važnosti, jer NW-1153, prvi produkt u metaboličkom putu, dalje se transformira u sekundarne i tercijarne metabolite.
At concentrations of 50µM, safinamide inhibited OATP1A2 and OATP2P1.
Pri koncentracijama od 50μM, safinamid je inhibirao OATP1A2 i OATP2P1.
Impulse control disorders can occur in patients treated with dopamine agonists and/or dopaminergic treatments.
Poremećaji kontrole impulsa mogu se pojaviti u bolesnika liječenih agonistima dopamina i/ili dopaminergičkim lijekovima.
In general, safinamide may be used with selective serotonin re-uptake inhibitors (SSRIs) at the lowest effective dose, with caution for serotoninergic symptoms.
Općenito, safinamid se može primjenjivati sa selektivnim inhibitorima ponovne pohrane serotonina (engl. selective serotonin re-uptake inhibitors, SSRI) u najnižoj učinkovitoj dozi, uz oprez za serotoninergičke simptome.
Safinamide must not be administered along with other MAO inhibitors (including moclobemide) as there may be a risk of non-selective MAO inhibition that may lead to a hypertensive crisis (see section 4.3).
Safinamid se ne smije primjenjivati zajedno s drugim MAO inhibitorima (uključujući moklobemid), jer može postojati rizik od neselektivne MAO inhibicije koja može dovesti do hipertenzivne krize (vidjeti dio 4.3).
Somnolence and dizziness may occur during safinamide treatment, therefore patients should be cautioned about using hazardous machines, including motor vehicles, until they are reasonably certain that safinamide does not affect them adversely.
Tijekom liječenja safinamodom može doći do pojave somnolencije i omaglice, stoga je bolesnike potrebno upozoriti na oprez pri upravljanju opasnim strojevima uključujući motorna vozila, sve dok nisu razumno sigurni da safinamid ne utječe štetno na njih.
This effect was not seen when safinamide was used as an adjunct to dopamine agonists in early stage PD patients.
Taj učinak nije uočen kada je safinamid primijenjen kao dodatna terapija uz agoniste dopamina u bolesnika u ranom stadiju PB-a.
Moderate or severe renal impairment did not alter the exposure to safinamide, compared to healthy subjects (see section 4.2).
Umjereno ili teško oštećenje bubrega nije promijenilo izloženost safinamidu u usporedbi sa zdravim ispitanicima (vidjeti dio 4.2).
Other medicines and Xadago
Drugi lijekovi i Xadago
Transporters
Transporteri
Safinamide absorption is rapid after single and multiple oral dosing, reaching Tmax in the time range 1.82.8 h after dosing under fasting conditions.
Apsorpcija safinamida je brza nakon jednog i više peroralnih doziranja, dostižući Tmax u rasponu vremena od 1,8 - 2,8 h nakon doziranja natašte.
In vitro experiments indicated that inhibition of amidases in human hepatocytes led to complete suppression of the NW-1153 formation.
In vitro eksperimenti pokazuju da je inhibicija amidaza u humanih hepatocita dovela do potpunog potiskivanja stvaranja NW-1153.
Hypersensitivity to the active substance or to any of the excipients (see section 6.1).
Preosjetljivost na djelatnu tvar ili neku od pomoćnih tvari (vidjeti dio 6.1).
The systemic exposure of NW-1153 is low (1/10 of parent safinamide).
Sistemska izloženost NW-1153 je niska (1/10 ishodišnog safinamida).
In view of the selective and reversible MAO-B inhibitory activity of safinamide, antidepressants may be administered but used at the lowest doses necessary.
S obzirom na selektivnu i reverzibilnu MAO-B inhibicijsku aktivnost safinamida, antidepresivi se mogu primijeniti, ali u najnižoj potrebnoj dozi.
NW-1153 is not an inhibitor of OCT2, MATE1, or MATE2-K up to concentrations of 5µM.
NW-1153 nije inhibitor OCT2, MATE1 ili MATE2-K do koncentracije od 5 µM.
Liver hypertrophy and fatty changes were seen only in rodent livers at exposures similar to humans.
Hipertrofija jetre i masne promjene uočene su samo u jetri glodavaca pri izloženosti sličnoj onoj u ljudi.
D- 73614 Schorndorf Germany
D- 73614 Schorndorf, Njemačka
The high absorption classifies safinamide as a highly permeable substance.
Visoka apsorpcija klasificira safinamid kao visoko propusnu tvar.
Both the SETTLE and 016/018 studies indicated significant superiority of safinamide, compared to placebo, at the target doses of 50 and 100 mg/day for the primary, and selected secondary, efficacy variables, as summarized in the table below.
Oba ispitivanja, i SETTLE i 016/018, pokazala su značajnu superiornost safinamida u usporedbi s placebom, u ciljanim dozama od 50 i 100 mg/dan za primarnu i odabranu sekundarnu varijablu djelotvornosti, kako je sažeto u tablici u nastavku.
Safinamide's metabolism is not dependent on Cytochrome P450 (CYP) based enzymes.
Metabolizam safinamida ne ovisi o enzimima citokroma P450 (CYP).
Phospholipidosis was seen mainly in the lungs in rodents (at exposures similar to humans) and monkeys (at exposures greater than 12 fold higher than human).
Fosfolipidi su uglavnom uočeni u plućima glodavaca (pri izloženostima sličnima izloženosti u ljudi) i u majmuna (pri izloženostima 12 puta većima od one u ljudi).
The combination of safinamide with levodopa/carbidopa resulted in additive effects in the embryo-foetal development studies with a higher incidence of foetal skeletal abnormalities than seen with either treatment alone.
Kombinacija safinamida s levodopom/karbidopom rezultirala je aditivnim učincima u ispitivanjima embriofetalnog razvoja s višom incidencijom fetalnih koštanih abnormalnosti nego što je uočeno u samostalnom liječenju.
The tabulation below includes all adverse reactions in clinical trials where adverse reactions were considered related.
Tablični prikaz u nastavku uključuje sve nuspojave u kliničkim ispitivanjima gdje su nuspojave smatrane povezanima.
The ‘N-dealkylated acid' (NW-1689) undergoes conjugation with glucuronic acid yielding its acyl glucuronide.
„N-dealkilirana kiselina“ (NW-1689) podliježe konjugaciji s glukuronskom kiselinom dajući svoj acil glukuronid.
Dedicated drug-drug interaction studies performed with ketoconazole, L-dopa and CYP1A2 and CYP3A4 substrates (caffeine and midazolam), did not detect any clinically significant effects on the pharmacokinetics of safinamide, or L-dopa, caffeine and midazolam.
Namjenska ispitivanja interakcija između lijekova provedena s ketokonazolom, L-dopom i supstratima CYP1A2 i CYP3A4 (kofein i midazolam), nisu otkrila nikakve klinički značajne učinke na farmakokinetiku safinamida ili L-dope, kofeina i midazolama.
Safinamide exposure in patients with mild hepatic disease increased marginally (30% in AUC), while in patients with moderate hepatic impairment exposure increased by approximately 80% (see section
Izloženost safinamidu u bolesnika s blagom bolešću jetre neznatno se povećala (30% u AUC-u), dok je u bolesnika s umjerenim oštećenjem jetre izloženost povećana za oko 80% (vidjeti dio 4.2).
You must wait at least 7 days after stopping Xadago treatment before starting treatment with MAO inhibitors or pethidine.
Morate čekati najmanje 7 dana između prestanka liječenja lijekom Xadago i početka liječenja MAO inhibitorima ili petidinom.
Potential for retinal degeneration in patients with prior history of retinal disease
Moguća degeneracija mrežnice u bolesnika s prethodnom anamnezom bolesti mrežnice
Medicinal products that are inhibitors of OAT3 given concomitantly with safinamide may reduce clearance of NW-1153, i.e., and thus may increase its systemic exposure.
Lijekovi koji su inhibitori OAT3 kada se daju istodobno sa safinamidom mogu smanjiti klirens NW1153, tj., i tako mogu povećati njegovu sistemsku izloženost.
The recommended starting dose of Xadago is one 50 mg tablet that may be increased to one 100 mg tablet, taken once daily preferably in the morning by mouth with water.
Preporučena početna doza lijeka Xadago je jedna tableta od 50 mg koja se uzima jednom dnevno na usta s vodom, po mogućnosti ujutro.
In vitro metabolism studies have indicated that there is no meaningful induction or inhibition of cytochrome P450, CYP2A6, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1 and 3A3/5 at concentrations which are relevant (Cmax of free safinamide 0.4 µM at 100 mg/day) in man.
In vitro ispitavanja metabolizma pokazala su da ne postoji značajna indukcija ili inhibicija citokroma P450, CYP2A6, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1 i 3A3/5 u koncentracijama koje su relevantne (Cmax slobodnog safinamida 0,4 µM kod 100 mg/dan) u ljudi.
14 film-coated tablets 28 film-coated tablets 30 film-coated tablets 90 film-coated tablets 100 film-coated tablets
14 filmom obloženih tableta 28 filmom obloženih tableta 30 filmom obloženih tableta 90 filmom obloženih tableta 100 filmom obloženih tableta
Arterial spasm, arteriosclerosis, hypertensive crisis
Spazam arterija, arterioskleroza, hipertenzivna kriza
If you stop taking Xadago
Ako prestanete uzimati Xadago
Preliminary in vitro studies have shown that safinamide is not a substrate for the transporters P-gp, BCRP, OAT1B1, OAT1B3, OATP1A2 or OAT2P1.
Preliminarna in vitro ispitivanja pokazala su da safinamid nije supstrat za transportere P-gp, BCRP, OAT1B1, OAT1B3, OATP1A2 ili OAT2P1.
In humans, safinamide is almost exclusively eliminated via metabolism (urinary excretion of unchanged safinamide was <10%) mediated principally through high capacity amidases, that have not yet been characterized.
U ljudi, safinamid se gotovo isključivo eliminira metabolizmom (ekskrecija nepromijenjenog safinamida urinom bila je <10%) posredovanim prvenstveno amidazama visokog kapaciteta, koje još uvijek nisu okarakterizirane.
This interaction has the potential to reduce the clearance of NW1153 and increase its exposure; however the systemic exposure of NW-1153 is low (1/10 of parent safinamide), and as it is metabolised to secondary and tertiary metabolites, it is unlikely to be of any clinical relevance.
Ta interakcija ima potencijal smanjivanja klirensa NW-1153 i povećanja njegove izloženosti; međutim, sistemska izloženost NW-1153 je niska (1/10 ishodišnog safinamida), a kako se metabolizira u sekundarne i tercijarne metabolite, malo je vjerojatno da će biti od kliničke važnosti.
No retinal degeneration was noted in monkeys despite higher systemic exposure than in rodents or in patients at the maximum human dose.
Degeneracija mrežnice nije uočena u majmuna usprkos većoj sistemskoj izloženosti nego u glodavaca ili u bolesnika na maksimalnoj ljudskoj dozi.
There are no or limited amount of data from the use of safinamide in pregnant women.
Nema podataka ili su podaci o primjeni safinamida u trudnica ograničeni.
In particular, the concomitant use of safinamide and fluoxetine or fluvoxamine should be avoided, or if concomitant treatment is necessary these medicinal products should be used at low doses (see section 4.5).
Osobito je potrebno izbjegavati istodobnu primjenu safinamida i fluoksetina ili fluvoksamina, a ako je istodobno liječenje neophodno ti se lijekovi moraju koristiti u niskim dozama (vidjeti dio 4.5).
Caution should be exercised when initiating treatment with safinamide in patients with moderate hepatic impairment.
Potreban je oprez prilikom početka liječenja safinamidom u bolesnika s umjerenim oštećenjem jetre.
Safinamide used as an adjunct to levodopa may potentiate the side effects of levodopa, and preexisting dyskinesia may be exacerbated, requiring a decrease of levodopa.
Safinamid primijenjen kao dodatna terapija uz levodopu može pojačati nuspojave levodope, a već postojeća diskinezija može se pogoršati, zahtijevajući smanjenje doze levodope.
Safinamide inhibits OCT1 in vitro at clinically relevant portal vein concentrations.
Safinamid inhibira OCT1 in vitro pri klinički relevantnim koncentracijama u portalnoj veni.
Safinamide is almost exclusively eliminated via metabolism, largely by high capacity amidases that have not yet been characterized.
Safinamid se gotovo isključivo eliminira putem metabolizma, najvećim dijelom amidazama visokog kapaciteta koje još nisu okarakterizirane.
Impulse control disorders; pathological gambling, increased libido, hypersexuality, compulsive spending or buying, binge eating and compulsive eating can occur in patients treated with dopamine agonists and/or other dopaminergic treatments.
Poremećaji kontrole impulsa; patološko kockanje, povećani libido, hiperseksualnost, kompulzivno trošenje ili kupovanje, prejedanje i kompulzivno jedenje mogu se pojaviti u bolesnika liječenih agonistima dopamina i/ili drugim dopaminergičkim lijekovima.
Breast Feeding Xadago is likely to be excreted in breast milk.
Dojenje Xadago se vjerojatno izlučuje u majčino mlijeko.