FrancophonIA/ELRC3.0 huggingface dataset:
English: In repeat-dose toxicity studies in mice, rats and monkeys, siponimod markedly affected the lymphoid system (lymphopenia, lymphoid atrophy and reduced antibody response), which is consistent with its primary pharmacological activity at S1P1 receptors (see section 5.1).
Croatian: U ispitivanjima toksičnosti ponovljenih doza u miševa, štakora i majmuna, siponimod je izrazito utjecao na limfoidni sustav (limfopenija, limfoidna atrofija i smanjeni odgovor protutijela), što je u skladu s njegovom primarnom farmakološkom aktivnošću na S1P1 receptorima (vidjeti dio 5.1).
English: • Patients should be informed about the risk of skin malignancies while on treatment with siponimod and should be cautioned against exposure to sunlight without protection.
Croatian: • Bolesnici trebaju biti obaviješteni o riziku od kožne zloćudne bolesti za vrijeme liječenja siponimodom i upozoreni da se ne izlažu sunčevoj svjetlosti bez zaštite.
English: The receptor affected by siponimod (sphinosine-1-phosphate receptor) is known to be involved in vascular formation during embryogenesis.
Croatian: Za receptor na koji siponimod (sfinozin 1-fosfat receptor) utječe poznato je da je uključen u stvaranje žila tijekom embriogeneze.
English: Tell your doctor straight away if you think your MS worsens after you have stopped treatment with Mayzent.
Croatian: Odmah obavijestite svog liječnika ako mislite da se Vaša MS pogoršava nakon što prekinete liječenje Mayzentom.
English: With continued dosing heart rate starts increasing after day 6 and reaches placebo levels within 10 days after treatment initiation.
Croatian: Uz kontinuirano doziranje srčana se frekvencija počinje povećavati nakon 6. dana i postiže razine kao uz placebo unutar 10 dana nakon početka liječenja.
English: Animal studies have demonstrated siponimod-induced embryotoxicity and foetotoxicity in rats and rabbits and teratogenicity in rats, including embryo-foetal deaths and skeletal or visceral malformations at exposure levels comparable to the human exposure at the daily dose of 2 mg (see section 5.3).
Croatian: Ispitivanja na životinjama pokazala su embriotoksičnost i fetotoksičnost uzrokovanu siponimodom u štakora i kunića te teratogenost u štakora, uključujući embriofetalne smrti i koštane ili visceralne malformacije pri razinama izloženosti koje su usporedive izloženosti u ljudi pri dnevnoj dozi od 2 mg (vidjeti dio 5.3).
English: If CM is diagnosed, appropriate treatment should be initiated.
Croatian: Ako se dijagnosticira KM, potrebno je započeti odgovarajuće liječenje.
English: • Before starting siponimod, test for antibodies to varicella zoster virus (VZV) in patients without a physician-confirmed history of varicella or without documentation of a full course of vaccination against VZV.
Croatian: • Prije započinjanja liječenja siponimodom, test na protutijela na varicella zoster virus (VZV) u bolesnika bez liječnički potvrđene varcielle u anamnezi ili bez dokumentacije o punom ciklusu cijepljenja protiv VZV-a.
English: The maximum decline in heart rate is seen in the first 6 hours post-dose.
Croatian: Maksimalno smanjenje srčane frekvencije opaža se u prvih 6 sati nakon doze.
English: Median age was 49 years, median disease duration was 16 years and median EDSS score was 6.0 at baseline.
Croatian: Medijan dobi bio je 49 godina, medijan trajanja bolesti bio je 16 godina, a medijan rezultata na EDSS-u bio je 6,0 na početku.
English: Siponimod induces a dose-dependent reduction of the peripheral blood lymphocyte count within 6 hours of the first dose, due to the reversible sequestration of lymphocytes in lymphoid tissues.
Croatian: Siponimod uzrokuje o dozi ovisno smanjenje broja limfocita u perifernoj krvi unutar 6 sati od prve doze, zbog reverzibilne sekvestracije limfocita u limfoidnim tkivima.
English: The study involved randomisation of 1,651 patients to either siponimod 2 mg (N=1,105) or placebo (N=546); 82% of patients treated with siponimod and 78% of placebo-treated patients completed the study.
Croatian: Ispitivanje je uključivalo randomizaciju 1651 bolesnika na primanje ili siponimoda 2 mg (N=1105) ili placeba (N=546); 82% bolesnika liječenih siponimodom te 78% bolesnika liječenih placebom dovršilo je ispitivanje.
English: • Cryptococcal infections (a type of fungal infection), including cryptococcal meningitis with symptoms such as headache together with stiff neck, sensitivity to light, feeling sick (nausea) or confusion.
Croatian: • Kriptokokne infekcije (vrsta gljivične infekcije), uključujući kriptokokni meningitis sa simptomima poput glavobolje s ukočenim vratom, osjetljivošću na svjetlo, mučninom ili smetenošću.
English: Before initiation of treatment, women of childbearing potential must be informed of this risk to the foetus, must have a negative pregnancy test and must use effective contraception during treatment and for at least 10 days after treatment discontinuation (see sections 4.3 and 4.6).
Croatian: Prije početka liječenja žene reproduktivne dobi potrebno je informirati o riziku za fetus, moraju imati negativan test na trudnoću i moraju upotrebljavati učinkovitu kontracepciju tijekom liječenja te još najmanje 10 dana nakon prekida liječenja (vidjeti dijelove 4.3 i 4.6).
English: It is unknown whether siponimod or its major metabolites are excreted in human milk.
Croatian: Nije poznato izlučuje li se siponimod ili njegovi glavni metaboliti u majčino mlijeko.
English: For patients receiving a stable dose of beta blocker, the resting heart rate should be considered before introducing treatment.
Croatian: Za bolesnike koji primaju stabilnu dozu beta blokatora potrebno je provjeriti srčanu frekvenciju u mirovanju prije početka liječenja.
English: A decision on whether or not siponimod should be re-initiated after resolution needs to take into account the potential benefits and risks for the individual patient.
Croatian: Kod donošenja odluke o ponovnom uvođenju siponimoda nakon povlačenja makularnog edema treba uzeti u obzir potencijalne koristi i rizike za pojedinog bolesnika.
English: The primary endpoint of the study was the time to 3-month confirmed disability progression (CDP) determined as at least a 1-point increase from baseline in EDSS (0.5 point increase for patients with baseline EDSS of 5.5 or more) sustained for 3 months.
Croatian: Mjera primarnog ishoda ispitivanja bila je vrijeme do 3-mjesečne potvrđene progresije onesposobljenosti (engl. confirmed disability progression, CDP) određene kao povećanje EDSS-a od najmanje 1 boda u odnosu na početni (povećanje od 0,5 bodova za bolesnike s početnim EDSS-om od 5.5 ili više) koje se održalo 3 mjeseca.
English: In such patients, treatment with siponimod should be considered only if the anticipated benefits outweigh the potential risks.
Croatian: U tih se bolesnika liječenje siponimodom smije razmotriti samo ako su predviđene koristi veće od mogućih rizika.
English: At months 3 and 6 of treatment in the phase III clinical study in patients with SPMS, mean changes from baseline in FEV1 in the siponimod group were -0.1 L at each time point, with no change in the placebo group.
Croatian: Nakon 3. i 6. mjeseca liječenja u kliničkom ispitivanju faze III u bolesnika s SPMS-om, srednje promjene u odnosu na početne vrijednosti FEV1 u siponimod skupini bile su -0,1 L u svakoj vremenskoj točki, bez promjena u placebo skupini.
English: Siponimod binds selectively to two out of five G-protein-coupled receptors (GPCRs) for S1P, namely S1P1 and S1P5.
Croatian: Siponimod se selektivno veže za dva od pet G-protein vezanih receptora (GPCR) za S1P, točnije S1P1 i S1P5.
English: - if you have certain types of irregular or abnormal heartbeat (arrhythmia) and you do not have a pacemaker.
Croatian: - ako imate određene vrste nepravilnih ili poremećenih otkucaja srca (aritmija) a nemate elektrostimulator srca.
English: Because residual pharmacodynamic effects, such as lowering effects on peripheral lymphocyte count, may persist for up to 3 to 4 weeks after discontinuation, vigilance for infection should be continued throughout this period (see below section “Stopping siponimod therapy”).
Croatian: Budući da rezidualni farmakodinamički učinci, kao što su učinci na snižavanje broja perifernih limfocita, mogu trajati i do 3 do 4 tjedna nakon prekida primjene, potrebno je nastaviti paziti na infekcije tijekom tog razdoblja (vidjeti u nastavku dio „Prekid terapije siponimodom“).
English: • if you have fever, feel like you have flu or have a headache together with a stiff neck, sensitivity to light, nausea or confusion.
Croatian: • ako imate vrućicu, osjećate se kao da imate gripu ili imate glavobolju s ukočenim vratom, osjetljivošću na svjetlost, mučninom ili smetenošću.
English: Siponimod concentration increases in an apparent dose proportional manner after multiple once-daily doses of siponimod 0.3 mg to 20 mg.
Croatian: Koncentracija siponimoda povećava se prividno proporcionalno dozi nakon višekratnog doziranja siponimoda jedanput dnevno od 0,3 mg do 20 mg.
English: • Before starting treatment, a DNA sample via blood or saliva (buccal swab) is taken to determine the CYP2C9 genotype to help determine appropriate dosing of siponimod.
Croatian: • Prije započinjanja liječenja, uzima se uzorak DNK iz krvi ili sline (bukalni bris) kako bi se utvrdio CYP2C9 genotip da se odredi odgovarajuća doza siponimoda.
English: Multiple doses of siponimod were associated with mild to moderate changes in FEV1 and FEF25-75% which were not dose- and daytime-dependent and were not associated with any clinical signs of increased airway resistance.
Croatian: Višestruke doze siponimoda bile su povezane s blagim do umjerenim promjenama u FEV1 i FEF25-75% koje nisu bile ovisne o dozi i dobu dana te nisu bile povezane ni s kakvim kliničkim znakovima povećanog otpora dišnih puteva.
English: • Do not initiate siponimod treatment in patients with severe active infection until infection is resolved.
Croatian: • Nemojte započeti liječenje siponimodom u bolesnika s teškom aktivnom infekcijom dok se infekcija ne povuče.
English: These may be symptoms of macular oedema.
Croatian: To mogu biti simptomi makularnog edema.
English: Siponimod increased the placebo-corrected baseline-adjusted mean QTcF (ΔΔQTcF) by more than 5 ms, with a maximum mean effect of 7.8 ms (2 mg) and 7.2 ms (10 mg), respectively, at 3 h post-dose.
Croatian: Siponimod je povećao srednju vrijednost QTcF-a korigiranu za placebo i prilagođenu prema početnoj vrijednosti (ΔΔQTcF) za više od 5 ms, uz najveći srednji učinak od 7,8 ms (2 mg) odnosno 7,2 ms (10 mg) 3 sata nakon doze.
English: Medical advice should be given regarding the risk of harmful effects to the foetus associated with treatment and ultrasonography examinations should be performed.
Croatian: Potrebno je dati medicinski savjet oko rizika od štetnih učinaka za fetus povezanih s liječenjem te obaviti preglede ultrazvukom.
English: No patients over 61 years of age were enrolled in clinical studies.
Croatian: Nije bilo bolesnika iznad dobi od 61 godine uključenih u klinička ispitivanja.
English: • If siponimod is discontinued, the possibility of recurrence of high disease activity should be considered.
Croatian: • Ako se prekine primjena siponimoda, potrebno je uzeti u obzir mogućnost vraćanja visoke aktivnosti bolesti.
English: These tumour findings were either regarded as mouse-specific or attributable to metabolic liver adaptations in the particularly sensitive rat species and are of questionable human relevance.
Croatian: Ti su se nalazi tumora smatrali ili specifičnima za miševe ili pripisivima metaboličkim prilagodbama jetre u osobito osjetljivih vrsta štakora te je njihova važnost za ljude upitna.
English: Table 3 Clinical and MRI results of study A2304
Croatian: Tablica 3 Klinički rezultati i rezultati MR-a u ispitivanju A2304
English: In the subgroup of patients (n=779) with active disease (defined as patients with relapse in the 2 years prior to the study and/or presence of Gd-enhancing T1 lesions at baseline) the baseline characteristics were similar to the overall population.
Croatian: U podskupini bolesnika (n=779) s aktivnom bolešću (definirano kao bolesnici s relapsom unutar 2 godine prije ispitivanja i/ili prisutnošću Gd-pojačanih T1 lezija na početku) početne karakteristike bile su slične ukupnoj populaciji.
English: In the prenatal and postnatal development study performed in rats, there was in increased number of dead (stillborn or found dead before postnatal day 4) and malformed pups (male pups with urogenital malformations and/or decreased anogenital distance; pups of both sexes with oedema, swollen soft cranium, or flexed hindlimbs).
Croatian: U ispitivanju prenatalnog i postnatalnog razvoja provedenog u štakora, bio je povećani broj mrtve (mrtvorođene ili pronađene uginule prije 4. dana nakon poroda) i malformirane mladunčadi (muška mladunčad s urogenitalnim malformacijama i/ili smanjenom anogenitalnom udaljenošću; mladunčad oba spola s edemom, oteknutom mekom lubanjom ili savinutim stražnjim udovima).
English: In the subgroup of patients (n=827) without signs and symptoms of disease activity (defined as patients without relapse in the 2 years prior to the study and without presence of Gd-enhancing T1 lesions at baseline), effects on 3-month and 6-month CDP were small (risk reductions were 7% and 13%, respectively).
Croatian: U podskupini bolesnika (n=827) bez znakova i simptoma aktivnosti bolesti (definirano kao bolesnici bez relapsa unutar 2 godine prije ispitivanja i bez prisutnosti Gd-pojačanih T1 lezija na početku), učinci na 3-mjesečni i 6-mjesečni CDP bili su mali (smanjenje rizika iznosilo je 7% odnosno 13%).
English: It is recommended that these patients should undergo an ophthalmological evaluation prior to initiating therapy and regularly while receiving siponimod therapy to detect macular oedema.
Croatian: Preporučuje se u tih bolesnika obaviti oftalmološki pregled prije početka terapije te redovito za vrijeme primanja terapije siponimodom radi otkrivanja makularnog edema.
English: • if you have symptoms such as sudden onset of severe headache, confusion, seizures and vision changes.
Croatian: • ako imate simptome poput iznenadnog nastupa teške glavobolje, smetenosti, napadaja i promjena vida.
English: CYP2C9 is polymorphic and the genotype influences the fractional contributions of the two oxidative metabolism pathways to overall elimination.
Croatian: CYP2C9 je polimorfan i genotip utječe na frakcijske doprinose dvaju puteva oksidativnog metabolizma za cjelokupnu eliminaciju.
English: A thorough QT study demonstrated no significant direct QT-prolonging effect and siponimod is not associated with an arrhythmogenic potential related to QT prolongation.
Croatian: Temeljito ispitivanje QT-a pokazalo je da nema značajnog izravnog učinka na produljenje QT intervala i da siponimod nije povezan s aritmogenim potencijalom povezanim s produljenjem QT-a.
English: Contains lactose and soya lecithin.
Croatian: Sadrži laktozu i sojin lecitin.
English: Patients should be observed for relevant signs of possible severe exacerbation or return of high disease activity upon siponimod discontinuation and appropriate treatment should be instituted as required.
Croatian: Bolesnike treba pratiti zbog uočavanja relevantnih znakova moguće teške egzacerbacije ili povrata visoke aktivnosti bolesti nakon prekida siponimoda te započeti odgovarajuće liječenje prema potrebi.
English: Median age was 47 years, median disease duration was 15 years and median EDSS score at baseline was 6.0.
Croatian: Medijan dobi bio je 47 godina, medijan trajanja bolesti bio je 15 godina i medijan EDSS rezultata na početku je bio 6,0.
English: The results did not suggest an arrhythmogenic potential related to QT prolongation with siponimod.
Croatian: Rezultati nisu ukazivali na aritmogeni potencijal povezan s produljenjem QT-a uz siponimod.
English: If you have to restart Mayzent more than 4 days after you stopped taking it, your doctor will prescribe a new titration pack and you will have to restart treatment at day 1 again.
Croatian: Ako morate ponovno početi uzimati Mayzent nakon što ga niste uzimali 4 ili više dana, liječnik će Vam propisati novo pakiranje za titraciju i morat ćete ponovno započeti liječenje od 1. dana.
English: Initiation of siponimod treatment has been associated with transient atrioventricular conduction delays that follow a similar temporal pattern to the observed decrease in heart rate during dose titration.
Croatian: Početak liječenja siponimodom povezan je s prolaznim odgodama u atrioventrikularnom provođenju koje slijede sličan vremenski obrazac kao i opaženo smanjenje srčane frekvencije tijekom titracije doze.
English: Blood pressure effects
Croatian: Učinci na krvni tlak
English: • medicines that affect the immune system, such as chemotherapy, immunosuppressants or other medicines to treat MS.
Croatian: • lijekove koji utječu na imunološki sustav, kao što su kemoterapija, imunosupresivi ili drugi lijekovi za liječenje multiple skleroze.
English: A peripheral lymphocyte count (CBC) is recommended prior to initiating siponimod to ensure that immune effects of the previous therapy (i.e. cytopenia) have resolved.
Croatian: Preporučuje se provjeriti broj perifernih limfocita (KKS) prije početka liječenja siponimodom kako bi se osiguralo da su se povukli imunološki učinci prethodne terapije (tj. citopenija).
English: Patients homozygous for CYP2C9*3 (CYP2C9*3*3 genotype: approximately 0.3 to 0.4% of the population) should not be treated with siponimod.
Croatian: Bolesnici homozigotni za CYP2C9*3 (CYP2C9*3*3 genotip: otprilike 0,3 do 0,4% populacije) ne smiju se liječiti siponimodom.
English: Your doctor may want you to have eye examinations before you start treatment and regularly while you are on treatment.
Croatian: Vaš liječnik će možda zatražiti da obavite pregled očiju prije nego započnete liječenje te da ih redovito obavljate za vrijeme liječenja.
English: Siponimod is contraindicated in patients with active malignancies.
Croatian: Siponimod je kontraindiciran u bolesnika s aktivnim zloćudnim bolestima.
English: Compared to CYP2C9*1*1 subjects, individuals with the CYP2C9*2*2, *1*3, *2*3 and *3*3 genotypes have 20%, 35-38%, 45-48% and 74% smaller CL/F values, respectively.
Croatian: U usporedbi s ispitanicima CYP2C9*1*1, pojedinci s genotipovima CYP2C9*2*2, *1*3, *2*3 odnosno *3*3 imaju redom 20%, 35-38%, 45-48% odnosno 74% manje vrijednosti CL/F.
English: Due to the characteristics and duration of alemtuzumab immune suppressive effects described in its product information, initiating treatment with siponimod after alemtuzmab is not recommended unless the benefits of treatment clearly outweigh the risks for the individual patient (see section 4.4).
Croatian: Zbog karakteristika i trajanja imunosupresivnih učinaka alemtuzumaba opisanih u njegovim informacijama o lijeku, ne preporučuje se započeti liječenje siponimodom nakon alemtuzmaba osim ako je jasno da su koristi liječenja veće od rizika za pojedinačnog bolesnika (vidjeti dio 4.4).
English: Treatment starts with 0.25 mg once daily on days 1 and 2, followed by once-daily doses of 0.5 mg on day 3, 0.75 mg on day 4, and 1.25 mg on day 5, to reach the patient's prescribed maintenance dose of siponimod starting on day 6 (see Table 1).
Croatian: Liječenje započinje s 0,25 mg jedanput dnevno 1. i 2. dana, nakon čega slijede doze koje se uzimaju jedanput dnevno od 0,5 mg 3. dana, 0,75 mg 4. dana i 1,25 mg 5. dana, kako bi se postigla bolesnikova propisana doza održavanja siponimoda počevši od 6. dana (vidjeti Tablicu 1).
English: A full course of vaccination with varicella vaccine is recommended for antibody-negative patients prior to commencing treatment with siponimod, following which initiation of treatment should be postponed for 1 month to allow the full effect of vaccination to occur (see section 4.8).
Croatian: Preporučuje se cjelokupni ciklus cijepljenja cjepivom za varicellu u bolesnika negativnih na protutijela prije početka liječenja siponimodom, nakon kojeg se početak liječenja treba odgoditi za 1 mjesec kako bi se omogućio puni učinak cijepljenja (vidjeti dio 4.8).
English: In certain cases the patient may not receive treatment with siponimod due to specific CYP2C9 genotype status.
Croatian: U određenim slučajevima bolesnik možda neće dobiti terapiju siponimodom zbog specifičnog CYP2C9 genotipa.
English: - Severe liver impairment (Child-Pugh class C).
Croatian: - Teško oštećenje funkcije jetre (Child-Pugh stadij C).
English: • modafinil and certain other medicines can lower the levels of Mayzent in the blood of certain patients and can therefore stop it from working properly.
Croatian: • modafinil i neki drugi lijekovi mogu smanjiti razine Mayzenta u krvi nekih bolesnika i mogu stoga spriječiti ispravno djelovanje lijeka.
English: Treatment with siponimod resulted in an increase of systolic and diastolic blood pressure starting early after treatment initiation, reaching maximum effect after approximately 6 months of treatment (systolic 3 mmHg, diastolic 1.2 mmHg) and staying stable thereafter.
Croatian: Liječenje siponimodom imalo je za posljedicu povećanje sistoličkog i dijastoličkog krvnog tlaka koje je počelo rano nakon početka liječenja, postiglo maksimalan učinak nakon otprilike 6 mjeseci liječenja (sistolički 3 mmHg, dijastolički 1,2 mmHg) i ostalo stabilno nakon toga.
English: Dose-limiting toxicities in animal species were nephrotoxicity in mice, body weight development in rats and adverse CNS and gastrointestinal effects in monkeys.
Croatian: Toksičnosti koje su ograničavale dozu u životinjskih vrsta bile su nefrotoksičnost u miševa, povećanje tjelesne težine u štakora te nuspojave SŽS-a i gastrointestinalne nuspojave u majmuna.
English: The risk of recurrence after re-challenge has not been evaluated.
Croatian: Nije se ocjenjivao rizik od povrata nakon ponovnog uvođenja lijeka.
English: Before the start of treatment your blood will also be tested to check how well your liver is working.
Croatian: Vaša će se krv također testirati da bi se provjerilo koliko dobro radi
English: Siponimod exposure is therefore approximately 25%, 61%, 91% and 284% higher in CYP2C9*2*2, *1*3, *2*3 and *3*3 subjects, respectively, as compared to *1*1 subjects (see Table 4) (see sections 4.2 and 4.4).
Croatian: Izloženost siponimodu stoga je otprilike 25%, 61%, 91% odnosno 284% veća u redom, CYP2C9*2*2, *1*3, *2*3 i *3*3 ispitanika, u usporedbi s ispitanicima *1*1 (vidjeti Tablicu 4) (vidjeti dijelove 4.2 i 4.4).
English: Severe exacerbation of disease, including disease rebound, has been rarely reported after discontinuation of another S1P receptor modulator.
Croatian: Teška egzacerbacija bolesti, uključujući povrat bolesti, rijetko je bila prijavljena nakon prekida terapije drugim modulatorom S1P receptora.
English: If pharmacological treatment is required, monitoring should be continued overnight and 6-hour monitoring should be repeated after the second dose.
Croatian: Ako je potrebna farmakološka terapija, potrebno je nastaviti praćenje preko noći te je potrebno ponoviti 6-satno praćenje nakon druge doze.
English: The median EDSS was 6.0 at baseline.
Croatian: Medijan početne vrijednosti EDSS-a bio je 6.0.
English: • new moles
Croatian: • novi madeži
English: Start treatment with 0.25 mg on day 1, up-titrated to the maintenance dose of 2 mg or 1 mg on day 6 based on the CYP2C9 metaboliser status.
Croatian: Započnite liječenje s 0,25 mg 1. dana te titracijom povećajte do doze održavanja od 2 mg ili 1 mg 6. dana na temelju CYP2C9 metabolizatorskog statusa.
English: • Siponimod is contraindicated in patients with history of progressive multifocal leukoencephalopathy or cryptococcal meningitis.
Croatian: • Siponimod je kontraindiciran u bolesnika s progresivnom multifokalnom leukoencefalopatijom ili kriptokoknim meningitisom.