FrancophonIA/ELRC3.0 huggingface dataset:
English: Breastfeeding (see section 4.6).
Slovenian: Dojenje (glejte poglavje 4.6).
English: Pitolisant blocked hERG channel with an IC50 exceeding therapeutic concentrations and induced a slight QTc prolongation in dogs.
Slovenian: Pri psih je pitolizant zaviral kanalčke hERG, pri čemer je IC50 presegel terapevtske koncentracije, in sprožil rahlo podaljšanje intervala QTc.
English: At high doses, pitolisant induced sperm morphology abnormalities and decreased motility without any significant effect on fertility indexes in male rats and it decreased the percentage of live conceptuses and increased post-implantation loss in female rats (safety margin of 1).
Slovenian: V velikih odmerkih je pitolizant sprožil abnormalnosti morfologije sperme in zmanjšal gibljivost brez kakršnega koli pomembnega učinka na indekse plodnosti pri podganjih samcih ter zmanjšal odstotek živih zanositev in povečal izgubo po nidaciji pri podganjih samicah (varnostni indeks 1).
English: In clinical trials, no specific cardiac safety signal was identified at therapeutic doses of pitolisant.
Slovenian: V kliničnih preskušanjih pri uporabi terapevtskih odmerkov pitolizanta niso opazili nobenih posebnih varnostnih signalov, povezanih s srcem.
English: You should continue to take Wakix for as long as instructed by your doctor.
Slovenian: Zdravilo Wakix jemljite toliko časa, kot vam je naročil zdravnik.
English: The effect on Epworth was supported in two laboratory tests of vigilance and attention (Maintenance of Wakefulness Test (MWT) (p=0.044) and Sustained Attention to Response (SART) (p=0.053, almost but not significant)).
Slovenian: Učinek, izmerjen po Epworthovi lestvici, so podprli v dveh laboratorijskih testih budnosti in pozornosti (testu srednjega trajanja budnosti (TSTB) (p = 0,044) in testu ohranjanja pozornosti na nalogo odzivanja (Sustained Attention to Response Task - SART) (p = 0,053, statistična značilnost skoraj dosežena).
English: Pitolisant is not a substrate of OATP1B1, OATP1B3.
Slovenian: Pitolizant ni substrat OATP1B1 in OATP1B3.
English: In patients with mild hepatic impairment (Child-Pugh A), there was no significant changes in pharmacokinetics compared with normal healthy volunteers.
Slovenian: Pri bolnikih z blago okvaro jeter (stopnje A po Child-Pughovi lestvici) farmakokinetika ni bila bistveno drugačna kot pri normalnih zdravih prostovoljcih.
English: Wakix may reduce the effectiveness of hormonal contraceptives, an alternative method of effective contraception has to be used (see section “Pregnancy).
Slovenian: Zdravilo Wakix lahko zmanjša učinkovitost hormonske kontracepcije, zato je treba uporabljati dodatno metodo učinkovite kontracepcije (glejte poglavje „Nosečnost“).
English: OUTER CARTON WITH BLUE BOX
Slovenian: ZUNANJI ŠKATLA - S PODATKI ZA 'MODRO OKENCE'
English: Renal impairment In patients with renal impairment, the maximum daily dose should be 18 mg.
Slovenian: Okvara ledvic Pri bolnikih z okvaro ledvic je največji dnevni odmerek 18 mg.
English: Harmony CTP, a supportive double blind, randomized, parallel group study of pitolisant versus placebo, was designed to establish pitolisant efficacy in patients with high frequency cataplexy in narcolepsy.
Slovenian: Harmony CTP, podporna dvojno slepa randomizirana študija z vzporednimi skupinami, v kateri so primerjali pitolizant in placebo, je bila zasnovana za dokazovanje učinkovitosti pitolizanta pri bolnikih, ki imajo narkolepsijo s pogosto katapleksijo.
English: Wakix should not be taken by children or adolescents.
Slovenian: Otroci in mladostniki zdravila Wakix ne smejo jemati.
English: Renal impairment In patients with impaired renal function (stages 2 to 4 according to the international classification of chronic kidney disease, i.e. creatinine clearance between 15 and 89 ml/min), Cmax and AUC tended to be increased by a factor of 2.5 without any impact on half-life (see section 4.2).
Slovenian: Okvara ledvic Pri bolnikih z okvarjenim delovanjem ledvic (stadij 2 do 4 po mednarodni klasifikaciji kronične bolezni ledvic, tj. očistek kreatinina med 15 in 89 ml/min) sta bili Cmaks in AUC povečani za 2,5-krat, kar pa ni vplivalo na razpolovni čas (glejte poglavje 4.2).
English: Women of childbearing potential have to use effective contraception during treatment and at least up to 21 days after treatment discontinuation (based on pitolisant/metabolites half-life).
Slovenian: Ženske v rodni dobi morajo med zdravljenjem in še vsaj 21 dni po prekinitvi zdravljenja (glede na razpolovni čas pitolizanta/presnovkov) uporabljati učinkovito kontracepcijo.
English: The most frequent adverse drug reactions (ADRs) reported with pitolisant were insomnia (8.4%), headache (7.7%), nausea (4.8%), anxiety (2.1%), irritability (1.8%), dizziness (1.4%), depression (1.3%), tremor (1.2%), sleep disorders (1.1%), fatigue (1.1%), vomiting (1.0%), vertigo (1.0%), dyspepsia (1.0%), weight increase (0.9%), abdominal pain upper (0.9%).
Slovenian: Najpogostejši neželeni učinki, o katerih so poročali pri uporabi pitolizanta, so bili nespečnost (8,4 %), glavobol (7,7 %), navzea (4,8 %), tesnoba (2,1 %), razdražljivost (1,8 %), omotica (1,4 %), depresija (1,3 %), tremor (1,2 %), motnje spanja (1,1 %), utrujenost (1,1 %), bruhanje (1,0 %), vrtoglavica (1,0 %), dispepsija (1,0 %), povečanje telesne mase (0,9 %) in bolečina v zgornjem delu trebuha (0,9 %).
English: Severe hepatic impairment (Child-Pugh C).
Slovenian: Huda okvara jeter (stopnje C po Child-Pughovi lestvici).
English: The pivotal study (Harmony 1), double-blind, randomized, vs placebo and modafinil (400 mg/day), parallel group studies with flexible dose adaptation, included 94 patients (31 patients treated with pitolisant, 30 with placebo and 33 with modafinil).
Slovenian: Ključna študija (Harmony 1), dvojno slepa randomizirana študija primerjave s placebom in modafinilom (400 mg/dan) z vzporednimi skupinami in prilagodljivimi odmerki je vključevala 94 bolnikov (31 bolnikov, zdravljenih s pitolizantom, 30 s placebom in 33 z modafinilom).
English: Nevertheless, patients with cardiac disease, co-medicated with other QT-prolonging medicinal products or known to increase the risk of repolarization disorders, or co-medicated with medicinal products that significantly increase pitolisant Cmax and AUC ratio (see section 4.5) or patients with severe renal or moderate hepatic impairment (see section 4.4) should be carefully monitored (see section 4.5).
Slovenian: Kljub temu pa je treba bolnike s srčno boleznijo, ki se sočasno zdravijo z drugimi zdravili, ki podaljšajo interval QT ali za katere je znano, da povečajo tveganje za motnje repolarizacije, ali ki sočasno jemljejo zdravila, ki pomembno povečajo Cmax in razmerje AUC pitolizanta (glejte poglavje 4.5), ali bolnike s hudo ledvično ali zmerno jetrno okvaro (glejte poglavje 4.4) pozorno spremljati (glejte poglavje 4.5).
English: 4.6 Fertility, pregnancy and lactation
Slovenian: 4.6 Plodnost, nosečnost in dojenje Ženske v rodni dobi
English: Tri or tetracyclic antidepressants (e.g. imipramine, clomipramine, mirtazapine) may impair the efficacy of pitolisant because they display histamine H1-receptor antagonist activity and possibly cancel the effect of endogenous histamine released in brain by the treatment.
Slovenian: Triciklični ali tetraciklični antidepresivi (npr. imipramin, klomipramin, mirtazapin) lahko zmanjšajo učinkovitost pitolizanta, saj antagonistično delujejo na histaminski receptor H1 in lahko izničijo učinek endogenega histamina, ki se ob zdravljenju sprošča v možganih.
English: Animal study has shown excretion of pitolisant/metabolites in milk.
Slovenian: V študiji na živalih so ugotovili izločanje pitolizanta/presnovkov v mleko.
English: Convulsions were reported at high doses in animal models (see section 5.3).
Slovenian: Pri velikih odmerkih na živalskih modelih so poročali o konvulzijah (glejte poglavje 5.3).
English: Pitolisant should be administered with caution in patients with severe obesity or severe anorexia (see section 4.8).
Slovenian: Pitolizant je treba previdno uporabljati pri bolnikih s hudo debelostjo ali hudo anoreksijo (glejte poglavje 4.8).
English: In rats, transient reversible convulsive episodes occurred at Tmax , that may be attributable to a metabolite abundant in this species but not in humans.
Slovenian: Pri podganah so se pri Tmaks pojavile prehodne reverzibilne konvulzivne epizode, ki so lahko posledica velike količine presnovka pri tej vrsti, kar pa ne velja za človeka.
English: The primary efficacy endpoint was the change in the average number of cataplexy attacks per week between the 2 weeks of baseline and the 4 weeks of stable treatment period at the end of study.
Slovenian: Primarni opazovani dogodek za oceno učinkovitosti je bil sprememba povprečnega števila tedenskih napadov katapleksije med dvotedenskim izhodiščnim zdravljenjem in štiritedenskim ustaljenim zdravljenjem ob koncu študije.
English: Study in animals has shown effects on semen parameters, without a significant impact on reproductive performance in males and reduction on the percentage of live foetuses in treated females (see section
Slovenian: V študijah na živalih so ugotovili učinke na parametre sperme, brez pomembnega vpliva na sposobnost razmnoževanja pri samcih, in zmanjšanje odstotka živih plodov pri samicah, ki so jim dajali zdravilo (glejte poglavje 5.3).
English: Pitolisant is a potent, orally active histamine H3-receptor antagonist/inverse agonist which, via its blockade of histamine auto-receptors enhances the activity of brain histaminergic neurons, a major arousal system with widespread projections to the whole brain.
Slovenian: Pitolizant je močan, peroralno aktiven antagonist/inverzni agonist histaminskih receptorjev H3, ki z zaviranjem histaminskih avtoreceptorjev spodbuja aktivnost histaminergičnih nevronov v možganih, pomembnega sistema, ki skrbi za budnost in katerega projekcije segajo v vse predele možganov.
English: Pitolisant is an inhibitor of CYP2D6 with moderate potency (IC50 = 2.6 µM).
Slovenian: Pitolizant je zmerno močan zaviralec CYP2D6 (IC50 = 2,6 µM).
English: Pitolisant/metabolites may reduce the effectiveness of hormonal contraceptives.
Slovenian: Pitolizant/presnovki lahko zmanjšajo učinkovitost hormonskih kontracepcijskih sredstev.
English: Do not stop taking Wakix suddenly on your own.
Slovenian: Zdravila Wakix ne smete nenadoma prenehati jemati po lastni presoji.
English: The results with pitolisant were significantly superior to those in the placebo group (mean difference: -3.33; 95%CI [-5.83 to -0.83]; p < 0.05) but did not differ significantly from the results in the modafinil group (mean difference: 0.12; 95%CI [-2.5 to 2.7]).
Slovenian: Rezultati v skupini s pitolizantom so bili znatno boljši kot v skupini s placebom (povprečna razlika: -3,33; 95-odstotni IZ [-5,83 do -0,83]; p < 0,05), niso pa se bistveno razlikovali od rezultatov v skupini z modafinilom (povprečna razlika: 0,12; 95-% IZ [-2,5 do 2,7]).
English: As Wakix may reduce the effectiveness of hormonal contraceptive, an alternative method of effective contraception has to be used.
Slovenian: Ker lahko zdravilo Wakix zmanjša učinkovitost hormonske kontracepcije, je treba uporabljati dodatno metodo učinkovite kontracepcije.
English: If any of these apply to you, talk to your doctor or pharmacist before taking Wakix.
Slovenian: Če karkoli od naštetega velja za vas, se pred uporabo zdravila Wakix posvetujte z zdravnikom ali farmacevtom.
English: In patients with moderate hepatic impairment (Child-Pugh B) two weeks after initiation of treatment, the daily dose can be increased without exceeding a maximal dose of 18 mg (see section 5.2).
Slovenian: Okvara jeter Pri bolnikih z zmerno okvaro jeter (stopnje B po Child-Pughovi lestvici) se lahko dnevni odmerek dva tedna po začetku zdravljenja poveča, vendar ne sme preseči največjega odmerka 18 mg (glejte poglavje 5.2).
English: 105 narcoleptic patients with high frequency weekly cataplexy rates at baseline were included (54 patients treated with pitolisant and 51 with placebo).
Slovenian: Sodelovalo je 105 narkoleptičnih bolnikov, ki so ob izhodišču imeli pogoste tedenske napade katapleksije (54 bolnikov, zdravljenih s pitolizantom, in 51 bolnikov, zdravljenih s placebom).
English: This medicine does not require any special storage conditions
Slovenian: Za shranjevanje zdravila niso potrebna posebna navodila
English: Juvenile toxicity studies in rats revealed that the administration of pitolisant at high doses induced a dose related mortality and convulsive episode that may be attributable to a metabolite abundant in rats but not in humans.
Slovenian: Študije toksičnosti pri podganjih mladičih so pokazale, da je dajanje pitolizanta v velikih odmerkih povzročilo z odmerkom povezano smrt in konvulzivne epizode, ki jih je mogoče pripisati obilici presnovkov, ki se pojavljajo pri tej živalski vrsti, ne pa tudi pri ljudeh.
English: With other CYP3A4, CYP2B6 (e.g. efavirenz, bupropion), CYP2C (e.g. repaglinide, phenytoin, warfarin), P-gp (e.g. dabigatran, digoxin) and UGT (e.g. morphine, paracetamol, irinotecan) susbtrates, caution should be made with a clinical monitoring of their efficacy.
Slovenian: Pri drugih substratih CYP3A4, CYP2B6 (npr. efavirenz, bupropion), CYP2C (npr. repaglinid, fenitoin, varfarin), P-gp (npr. dabigatran, digoksin) in UGT (npr. morfin, paracetamol, irinotekan) je treba biti previden in klinično spremljati njihovo učinkovitost.
English: Therefore, breastfeeding is contraindicated during treatment with pitolisant (see section 4.3).
Slovenian: Dojenje je zato med zdravljenjem s pitolizantom kontraindicirano (glejte poglavje 4.3).
English: Several conjugated metabolites were identified, the major ones (inactive) being two glycine conjugates of the acid metabolite of pitolisant and a glucuronide of a ketone metabolite of monohydroxy desaturated pitolisant.
Slovenian: Opazili so več konjugiranih presnovkov, med katerimi sta glavna (neaktivna) dva glicinska konjugata kislinskega presnovka pitolizanta in glukuronid ketonskega presnovka monohidroksi desaturiranega pitolizanta.
English: In monkeys, at the highest doses, transient CNS related clinical signs including emesis, tremors and convulsions were reported.
Slovenian: Pri opicah so pri največjih odmerkih poročali o prehodnih kliničnih znakih, povezanih z osrednjim živčevjem, ki so vključevali bruhanje, tremor in konvulzije.
English: Improvement of the two objective tests of wakefulness and attention, MWT and SART, with pitolisant was significant versus placebo (p=0.009 and p=0.002 respectively) and non-significant versus modafinil (p=0.713 and p=0.294 respectively).
Slovenian: Izboljšanje dveh objektivnih preiskav budnosti in pozornosti, MWT in SART, pri pitolizantu je bilo statistično značilno v primerjavi s placebom (p = 0,009 oziroma p = 0,002) in statistično neznačilno v primerjavi modafinilom (p = 0,713 oziroma p = 0,294).
English: On the primary efficacy endpoint, Weekly Rate of Cataplexy episodes (WRC), the results with pitolisant were significantly superior to those in the placebo group (p < 0.0001), with a progressive 64% decrease from baseline to end of treatment (Figure 2).
Slovenian: Pri primarnem opazovanem dogodku za oceno učinkovitosti, tedenski stopnji epizod katapleksije (Weekly Rate of Cataplexy - WRC), so bili rezultati v skupini s pitolizantom znatno boljši kot v skupini s placebom (p < 0,0001), pri čemer so zabeležili progresivno 64-odstotno znižanje od izhodišča do konca zdravljenja (slika 2).
English: Cataplexy attacks frequency in patients displaying this symptom was decreased significantly (p=0.034) with pitolisant (-65%) compared to placebo (-10%).
Slovenian: Pogostnost napadov katapleksije pri bolnikih z zadevnimi simptomi se je pri pitolizantu pomembno zmanjšala (-65 %) v primerjavi s placebom (-10 %) (p = 0,034).
English: The geometric mean of the ratios (MWTFinal/MWTBaseline) was 1.8 (95%CI 1.19; 2.71, p=0.005).
Slovenian: Geometrijska sredina razmerij (TSTB končno/ TSTB izhodiščno) je bilo 1,8 (95-% IZ 1,19; 2,71, p = 0,005).
English: Anti-histamines
Slovenian: Antihistaminiki
English: In patients with moderate hepatic impairment (Child-Pugh B), AUC increased by a factor 2.4, while half-life doubled (see section 4.2).
Slovenian: Pri bolnikih z zmerno okvaro jeter (stopnje B po Child-Pughovi lestvici) se je AUC povečala za 2,4-krat, podvojil pa se je tudi razpolovni čas (glejte poglavje 4.2).
English: There are no or limited amount of data from the use of pitolisant in pregnant women.
Slovenian: Podatkov o uporabi pitolizanta pri nosečnicah ni ali pa so omejeni.
English: Hypertension Hypotension Hot flush
Slovenian: Žilne bolezni hipertenzija hipotenzija vročinski oblivi
English: What Wakix looks like and contents of the pack
Slovenian: Izgled zdravila Wakix in vsebina pakiranja
English: In rats, pitolisant/metabolites were shown to cross the placenta (see section 5.3).
Slovenian: Pri podganah so pokazali, da pitolizant/presnovki prehajajo skozi placento (glejte poglavje 5.3).
English: Do not change doses of Wakix on your own.
Slovenian: Odmerkov zdravila Wakix ne smete spreminjati sami.
English: Pitolisant should be administered with caution in patients with either renal impairment or moderate hepatic impairment (Child-Pugh B) and dosing regimen should be adapted according to section 4.2.
Slovenian: Pitolizant je treba previdno uporabljati pri bolnikih z okvaro ledvic ali zmerno okvaro jeter (stopnje B po Child-Pughovi lestvici) in režim odmerjanja prilagoditi v skladu s poglavjem 4.2.
English: However, treatment discontinuation should be monitored.
Slovenian: Vendar je treba kljub temu bolnika spremljati po prekinitvi zdravljenja.
English: If you are a woman, you have to take a contraceptive during your treatment with Wakix and at least up to 21 days after treatment discontinuation.
Slovenian: Če ste ženska, morate med zdravljenjem z zdravilom Wakix in še vsaj
English: Wakix is available in a bottle of 30 tablets or 90 tablets.
Slovenian: Zdravilo Wakix je na voljo v plastenki s 30 ali 90 tabletami.
English: The observed WRC in pitolisant group was about half of WRC in the placebo group: the effect size of pitolisant compared with placebo was summarized by the ratio rate rR(Pt/Pb), rR=0.512; 95%CI [0.435 to 0.603]; p < 0.0001).
Slovenian: Opaženi WRC v skupini s pitolizantom je bil približno polovica WRC v skupini s placebom: velikost učinka pitolizanta v primerjavi s placebom je povzeta glede na razmerje incidence rR (Pt/Pb), rR = 0,512; 95-% IZ (0,435 do 0,603); p < 0,0001).
English: Pitolisant may reduce the effectiveness of hormonal contraceptives.
Slovenian: Pitolizant lahko zmanjša učinkovitost hormonskih kontracepcijskih sredstev.
English: In the up-titration scheme, dose increment should take into account this higher exposure.
Slovenian: To višjo izpostavljenost je treba upoštevati v režimu postopnega zviševanja odmerkov (titracije) pri zvišanju odmerka.
English: After 1 month in mice, 6 months in rats and 9 months in monkeys, no adverse effect level (NOAEL) were 75, 30 and 12 mg/kg/day, p.o., respectively, providing safety margins of 9, 1 and 0.4, respectively when compared to the drug exposure at therapeutic dose in human.
Slovenian: Odmerek, pri katerem ni mogoče opaziti neželenih učinkov (NOAEL), je pri miših po 1 mesecu, pri podganah po 6 mesecih in pri opicah po 9 mesecih znašal 75, 30 oziroma 12 mg/kg/dan peroralno, kar pomeni varnostni faktor 9, 1 oziroma 0,4, če to primerjamo z izpostavljenostjo človeka zdravilu pri terapevtskem odmerku.
English: Based on in vitro data, pitolisant and its main metabolites may induce CYP3A4 and CYP2B6 at therapeutic concentrations and by extrapolation, CYP2C, UGTs and P-gp.
Slovenian: Na podlagi podatkov in vitro lahko pitolizant in njegovi glavni presnovki v terapevtskih koncentracijah inducirajo CYP3A4 in CYP2B6, z ekstrapolacijo pa CYP2C, UGT in P-gp.
English: Gastric disorders reactions have been reported with pitolisant, therefore it should be administered with caution in patients with acid related gastric disorders (see section 4.8) or when co-administered with gastric irritants such as corticosteroids or NSAID.
Slovenian: Pri uporabi pitolizanta so poročali o želodčnih reakcijah, zato ga je treba previdno uporabljati pri bolnikih, ki imajo želodčne bolezni, povezane s kislino (glejte poglavje 4.8), ali kadar se daje sočasno s snovmi, ki dražijo želodec, kot so kortikosteroidi ali nesteroidni antirevmatiki.
English: The combination of pitolisant with substrates of CYP3A4 and having a narrow therapeutic margin should be avoided (see section 4.5).
Slovenian: Kombinaciji pitolizanta in substratov CYP3A4 z ozkim terapevtskim razponom se je treba izogibati (glejte poglavje 4.5).
English: Gastric disorders Gastric disorders caused by hyperacidity have been reported during clinical studies in 3.5% of the patients receiving pitolisant.
Slovenian: Želodčne motnje Med kliničnimi študijami so pri 3,5 % bolnikov, ki so prejemali pitolizant, poročali o želodčnih motnjah, ki so bile posledica hiperacidnosti.
English: Clinically relevant interactions are expected with CYP3A4 and CYP2B6 substrates and by extrapolation, UGTs, CYP2C and P-gp substrates (see section 4.5).
Slovenian: Klinično pomembne interakcije so pričakovane pri substratih CYP3A4 in CYP2B6 ter z ekstrapolacijo pri substratih UGT, CYP2C in P-gp (glejte poglavje 4.5).
English: The metabolisation of pitolisant in humans is fully characterized.
Slovenian: Značilnosti presnove pitolizanta pri človeku so v celoti znane.
English: Nutrition disorders
Slovenian: Prehranske motnje
English: If you forget to take Wakix
Slovenian: Če ste pozabili vzeti zdravilo Wakix
English: The effect size of pitolisant compared with placebo based on a model for WRC based on BOCF with centre as a fixed effect was 0.581, 95%CI [0.493 to 0.686]; p<0.0001.
Slovenian: Velikost učinka pitolizanta v primerjavi s placebom na podlagi modela za WRC, ki temelji na BOCF s središčem kot fiksnim učinkom, je bila 0,581, 95-% IZ (0,493 do 0,686); p < 0,0001.
English: Co-administration of pitolisant with paroxetine significantly increases pitolisant mean Cmax and AUC0-72h ratio about 47% and 105%, respectively.
Slovenian: Sočasna uporaba pitolizanta s paroksetinom znatno poveča povprečno Cmaks in razmerje AUC0-72 ur pitolizanta, in sicer za približno 47 % oziroma 105 %.
English: No clinically relevant pharmacokinetic drug-drug interaction was evidenced either with modafinil or with sodium oxybate.
Slovenian: Opazili niso nobene klinično pomembne interakcije med zdravili z modafinilom ali z natrijevim oksibatom.