natgillin/translations-raw huggingface dataset:
Plasma concentrations followed a first order absorption process and reached Cmax in approximately 5 hours. 
Plazemske koncentracije so sledile procesu absorpcije prvega reda in so dosegle Cmax v približno 5 urah.
You can also report side effects directly via the national reporting system listed in Appendix V By reporting side effects, you can help provide more information on the safety of this medicine. 
O neželenih učinkih lahko poročate tudi neposredno na nacionalni center za poročanje, ki je naveden v Prilogi V. S tem, ko poročate o neželenih učinkih, lahko prispevate k zagotovitvi več informacij o varnosti tega zdravila.
It can be taken with or without food. 
Kapsulo je mogoče vzeti s hrano ali brez nje.
After completion of cycle 1, patients had the option to participate in a multiple-cycle extension, receiving the same treatment as assigned in cycle 1. 
Po zaključku 1. cikla so bolniki imeli možnost sodelovanja v podaljšku z več cikli, v katerem bi prejemali enako zdravljenje kot v 1. ciklu.
Overall phase 
Celotna faza
• sleep problems 
• težave s spanjem,
• Take the capsule about 1 hour before you start your chemotherapy cycle. 
• Vzemite kapsulo približno 1 uro pred začetkom cikla kemoterapije.
• lack of energy (feeling weak) 
• izguba energije (občutek slabotnosti),
• you are allergic to netupitant or palonosetron, or any of the other ingredients of this medicine (listed in section 6). 
• če ste alergični na netupitant ali palonosetron ali katero koli sestavino tega zdravila (navedeno v poglavju 6).
Since it may induce dizziness, somnolence or fatigue, patients should be cautioned not to drive or use machines if such symptoms occur. 
Ker lahko povzročijo omotičnost, somnolenco ali utrujenost, je treba bolnike opozoriti, naj ne vozijo in naj ne upravljajo strojev, če se pojavijo tovrstni simptomi.
Approximately 62% of palonosetron is bound to plasma proteins. 
Približno 62 % palonosetrona se veže na beljakovine v plazmi.
The AUC was 30% higher in cancer patients than in healthy subjects. 
AUC je bila 30 % višja pri bolnikih z rakom kot pri zdravih osebah.
Hypokalaemia and hypomagnesaemia should be corrected prior to administration. 
Hipokaliemijo in hipomagneziemijo je treba popraviti pred dajanjem zdravila.
If you are allergic to peanut or soya, see your doctor straight away if you notice any signs of an allergic reaction. 
Če ste alergični na arašide ali sojo, takoj obiščite zdravnika, če opazite kakršen koli znak alergijske reakcije.
Absolute netupitant bioavailability data are not available in humans; based on data from two studies with intravenous netupitant, the bioavailability in humans is estimated to be greater than 60%. 
Podatkov o absolutni biološki uporabnosti netupitanta pri ljudeh ni; na osnovi podatkov iz dveh študij z intravenskim netupitantom ocenjujejo, da je biološka uporabnost pri ljudeh večja od 60 %.
A summary of the key results from this study is shown in Table 3 below. 
Povzetek ključnih rezultatov iz te študije je prikazan v spodnji preglednici 3.
There was no pre-specified limit of the number of repeat consecutive cycles for any patient. 
Za nobenega bolnika ni bilo vnaprej določene omejitve številka ponovljenih zaporednih ciklov.
• You can take Akynzeo with or without food. 
• Zdravilo Akynzeo lahko jemljete s hrano ali brez nje.
The impact of nausea and vomiting on patients' daily lives was assessed using the Functional Living Index-Emesis (FLIE). 
Vpliv navzee in bruhanja na vsakodnevno življenje bolnikov so ocenili z lestvico Functional Living Index-Emesis (FLIE).
It is not excluded that this effect may be more marked, and then clinically relevant, in cancer patients, notably those having abnormal renal function. 
Ni izključeno, da je lahko ta pojav izrazitejši in s tem klinično pomemben pri bolnikih z rakom, še posebej tistih z nenormalnim delovanjem ledvic.
Of these, 1438 patients (98.8%) completed cycle 1 and 1286 patients (88.4%) continued treatment in the multiple-cycle extension. 
Od teh je 1438 bolnikov (98,8 %) dokončalo 1. cikel in 1286 bolnikov (88,4 %) je nadaljevalo zdravljenje v podaljšku z več cikli.
In a population PK study, patients with a reduced creatinine clearance (CLCR) also had a reduced palonosetron clearance, but this reduction would not result in a significant change in palonosetron exposure. 
V populacijski študiji FK so imeli bolniki z zmanjšanim očistkom kreatinina (CLCR) tudi zmanjšan očistek palonosetrona, vendar pa to zmanjšanje ni povzročilo znatne spremembe izpostavljenosti palonosetronu.
If you do not want to take Akynzeo, discuss this with your doctor. 
Če zdravila Akynzeo ne želite jemati, se o tem posvetujte z zdravnikom.
Days 2 to 3 
2. do 3. dan
The clinical relevance of this effect is not established. 
Klinična pomembnost tega učinka ni bila ugotovljena.
One 300 mg/0.5 mg capsule should be administered approximately one hour prior to the start of each chemotherapy cycle. 
Eno 300 mg/0,5 mg kapsulo je treba dati približno eno uro pred začetkom vsakega cikla kemoterapije.
Following oral administration, palonosetron is well absorbed with its absolute bioavailability reaching 97%. 
Po peroralnem dajanju se palonosetron dobro absorbira, pri čemer njegova absolutna biološka uporabnost doseže 97 %.
All patients were additionally treated with either doxorubicin (68.0%) or epirubicin (32.0%). 
Vsi bolniki so bili dodatno zdravljeni z doksorubicinom (68,0 %) ali epirubicinom (32,0 %).
Days 2 to 4 
2. do 4. dan
Effect of ketoconazole and rifampicin 
Učinek ketokonazola in rifampicina
Furthermore, the population PK study showed no correlation between PK parameters of netupitant and markers of renal dysfunction. 
Poleg tega populacijska študija FK ni pokazala korelacije med FK parametri netupitanta in markerji disfunkcije ledvic.
Recent guidance has updated these regimens to highly emetogenic. 
V nedavnih smernicah so bili tovrstni režimi uvrščeni med zelo emetogene.
A summary of the key results from this study is shown in Table below. 
Povzetek ključnih rezultatov iz te študije je prikazan v spodnji preglednici.
The significance of these findings in humans is unknown. 
Pomen teh ugotovitev za ljudi ni znan.
The safety and efficacy of Akynzeo capsules in the paediatric population have not been established. 
Varnost in učinkovitost kapsul zdravila Akynzeo pri pediatrični populaciji nista bili dokazani.
Palonosetron has a volume of distribution of approximately 8.3 ± 2.5 L/kg. 
Palonosetron ima volumen porazdelitve približno 8,3 ± 2,5 l/kg.
The underlying mechanisms are not fully understood, but because of the high doses employed and since the medicinal product is intended for single application in humans, these findings are not considered relevant for clinical use. 
Mehanizmi v ozadju niso povsem razumljeni, vendar pa zaradi velikih odmerkov in dejstva, da je zdravilo namenjeno za enkratno uporabo pri človeku, te ugotovitve ne veljajo za relevantne za klinično uporabo.
If you think you have forgotten to take your dose, tell your doctor straight away. 
Če mislite, da ste pozabili vzeti svoj odmerek, to takoj povejte zdravniku.
Stop taking Akynzeo and tell your doctor straight away if you notice the following serious side effectyou may need urgent medical treatment: 
Nehajte jemati zdravilo Akynzeo in takoj povejte zdravniku, če opazite naslednji resni neželeni učinek, saj boste morda potrebovali nujno medicinsko pomoč:
Do not take Akynzeo if you are pregnant or if you are a woman of childbearing potential not using contraception. 
Ne vzemite zdravila Akynzeo, če ste noseči ali ste ženska v rodni dobi in ne uporabljate kontracepcije.
If you think you may have taken more than you should, tell your doctor straight away. 
Če mislite, da ste morda vzeli večji odmerek, kot bi smeli, to takoj povejte zdravniku.
No common adverse reactions are attributable to netupitant, the new component of the fixed combination. 
Nobenega od pogostih neželenih učinkov ni mogoče pripisati netupitantu, ki je nova sestavina fiksne kombinacije.
The hard capsule is filled with three tablets and one soft capsule. 
Trda kapsula vsebuje tri tablete in eno mehko kapsulo.
Erythromycin and Midazolam 
Eritromicin in midazolam
Patients continued into the Multiple-Cycle extension for up to 7 additional cycles of chemotherapy. 
Bolniki so nadaljevali zdravljenje v podaljšku z več cikli, in sicer do največ 7 dodatnih ciklov kemoterapije.
Akynzeo should not be taken by children and adolescents under 18 years. 
Otroci in mladostniki, mlajši od 18 let, ne smejo jemati zdravila Akynzeo.
A total of 907 patients (62.3%) completed the multiple-cycle extension up to a maximum of eight treatment cycles. 
Skupno 907 bolnikov (62,3 %) je dokončalo podaljšek z več cikli, in sicer z največ osmimi cikli zdravljenja.
Netupitant is a selective antagonist of human substance P/neurokinin 1 (NK1) receptors. 
Netupitant je selektiven antagonist človeških receptorjev snovi P/nevrokinina 1 (NK1).
Caution should be exercised when using this medicinal product in patients over 75 years, due to the long half-life of the active substances and the limited experience in this population. 
Pri uporabi tega zdravila pri bolnikih, starejših od 75 let, je potrebna previdnost zaradi dolgega razpolovnega časa učinkovin in omejenih izkušenj s to populacijo.
• ring in the ear 
• zvonjenje v ušesu,
However, clinical pharmacokinetic parameters are not significantly different between poor and extensive metabolizers of CYP2D6 substrates. 
Vendar pa se klinični farmakokinetični parametri pomembno ne razlikujejo med slabimi in dobrimi presnavljalci substratov CYP2D6.
• ketoconazole - to treat Cushing's syndrome 
• ketokonazol za zdravljenje Cushingovega sindroma;
• erythromycin - to treat bacterial infections 
• eritromicin za zdravljenje bakterijskih okužb;
1 hard capsule 4x1 hard capsules 
1 trda kapsula 4 x1 trda kapsula
If you decide not to take Akynzeo (or another similar medicine), your chemotherapy is likely to make you feel sick and be sick. 
Če se odločite, da zdravila Akynzeo (ali podobnega zdravila) ne boste jemali, bo kemoterapija pri vas verjetno povzročila občutek slabosti in bruhanje.
Women of childbearing potential must use effective contraception during therapy and up to one month after treatment with this medicinal product. 
Ženske v rodni dobi morajo uporabljati učinkovito kontracepcijo med zdravljenjem in še en mesec po njem.
A pregnancy test should be performed on all pre-menopausal women prior to treatment. 
Pred začetkom zdravljenja je treba opraviti test nosečnosti pri vseh ženskah, ki še niso imele menopavze.
Therefore, caution is recommended when netupitant is combined with digoxin or with other P-gp substrates such as dabigatran, or colchicine. 
Zato priporočamo previdnost pri kombiniranju netupitanta z digoksinom ali drugimi substrati P-gp, kot sta dabigatran ali kolhicin.
• high levels of certain enzymes, including blood alkaline phosphatase and liver transaminases 
• visoke ravni določenih encimov, vključno z alkalno fosfatazo in jetrnimi transaminazami v krvi
EU/1/15/1001/001 1 hard capsule EU/1/15/1001/002 4x1 hard capsules 
EU/1/15/1001/001 1 trda kapsula EU/1/15/1001/002 4 x 1 trda kapsula
When netupitant was administered on Day 8 of a 12-day regimen of digoxin, no changes in digoxin pharmacokinetics were observed. 
Pri dajanju netupitanta 8. dan 12-dnevnega režima zdravljenja z digoksinom niso opazili sprememb farmakokinetike digoksina.
• sudden nervous breakdown, change in mood 
• nenaden živčni zlom, sprememba razpoloženja;
The amount of unchanged palonosetron excreted in the urine represented approximately 40% of the administered dose. 
Količina palonosetrona, ki se je nespremenjen izločil v urin, je predstavljala približno 40 % danega odmerka.
Women of childbearing potential should not be pregnant or become pregnant while on treatment with netupitant/palonosetron capsules. 
Ženske v rodni dobi ne smejo biti noseče ali zanositi med zdravljenjem s kapsulami netupitanta in palonosetrona.
Post-marketing data indicates that the adverse reactions profile is generally similar to that seen in clinical trials. 
Podatki v obdobju trženja zdravila kažejo, da je profil neželenih učinkov na splošno podoben tistemu v kliničnih preskušanjih.
Antiemetic activity of Akynzeo was maintained throughout repeat cycles for those patients continuing in each of the multiple cycles. 
Antiemetično delovanje zdravila Akynzeo se je ohranilo skozi ponovljene cikle pri bolnikih, ki so nadaljevali z vsakim od več dodatnih ciklov.
Marketing Authorisation Holder and Manufacturer: 
Imetnik dovoljenja za promet z zdravilom in proizvajalec:
The ratios were time dependent with values decreasing gradually beyond 24 h post-dose, indicating that netupitant is being rapidly metabolized. 
Razmerja so bila odvisna od časa in vrednosti so postopno upadale po 24 urah po odmerku, kar kaže na zelo hitro presnovo netupitanta.
All these reactions were uncommon. 
Vsi ti učinki so bili občasni.
Multiple-cycle safety study in patients receiving either Highly Emetogenic Chemotherapy or Moderately Emetogenic Chemotherapy 
Študija varnosti več ciklov pri bolnikih, ki so prejemali zelo emetogeno kemoterapijo ali zmerno emetogeno kemoterapijo
In single dose oral studies, netupitant was measurable in plasma between 15 minutes and 3 hours after dosing. 
V študijah z enkratnim peroralnim odmerkom je bil netupitant merljiv v plazmi med 15 minutami in 3 urami po odmerjanju.
Chemotherapeutic substances produce nausea and vomiting by stimulating the release of serotonin from the enterochromaffin cells of the small intestine. 
Kemoterapevtske snovi povzročajo navzeo in bruhanje prek stimulacije sproščanja serotonina iz enterokromafinih celic tankega črevesa.
This medicine contains sucrose, sorbitol, sodium and may contain soya - see section 2 for more information. 
To zdravilo vsebuje saharozo, sorbitol, natrij ter lahko vsebuje sojo - za več informacij glejte poglavje 2.
Renal clearance is not a significant elimination route for netupitant-related entities. 
Ledvični očistek ni pomembna pot izločanja za entitete, povezane z netupitantom.
The pharmacokinetics of palonosetron or netupitant has not been studied in subjects with end-stage renal disease requiring hemodialysis and no data on the effectiveness or safety of netupitant/palonosetron capsules in these patients are available. 
Farmakokinetike palonosetrona ali netupitanta niso preučili pri osebah s končnim stadijem bolezni ledvic, ki potrebujejo hemodializo, in podatkov o učinkovitosti ali varnosti kapsul netupitanta in palonosetrona pri teh bolnikih ni na voljo.
Serotonergic medicinal products (e.g. SSRIs and SNRIs) 
Serotonergična zdravila (npr. SSRI in SNRI)
M1, M2 and M3 metabolites were all shown to be pharmacologically active in an animal pharmacodynamic model, where M3 was most potent and M2 least active. 
Za presnovke M1, M2 in M3 so na živalskem farmakodinamičnem modelu dokazali, da so farmakološko aktivni, pri čemer je bil M3 najbolj, M2 pa najmanj aktiven.
As use in patients with severe hepatic impairment may be associated with increased exposure of netupitant, this medicinal product should be used with caution in these patients (see sections 4.4 and 
Ker je uporaba pri bolnikih s hudo okvaro jeter lahko povezana z zvečano izpostavljenostjo netupitantu, je treba to zdravilo pri teh bolnikih uporabljati previdno (glejte poglavji 4.4 in 5.2).
In a study performed in healthy volunteers, netupitant does not affect the exposure of digoxin, a P-gp substrate, whereas it increases its Cmax by 1.09 fold [90%CI 0.9-1.31]. 
V študiji z zdravimi prostovoljci netupitant ni vplival na izpostavljenost digoksinu, ki je substrat P-gp, pri čemer pa je povečal njegovo Cmax za 1,09-krat [90 % IZ 0,9-1,31].
• problems with the muscles in your heart (cardiomyopathy) 
• težave z mišicami v srcu (kardiomiopatija),
Maximum concentrations and total exposure of netupitant were increased in subjects with mild (n=8), moderate (n=8), and severe (n=2) hepatic impairment compared to matching healthy subjects, although there was pronounced individual variability in both hepatically-impaired and healthy subjects. 
Največje koncentracije in celotna izpostavljenost netupitantu so bile večje pri osebah z blago (n = 8), zmerno (n = 8) in hudo (n = 2) okvaro jeter v primerjavi z ujemajočimi se zdravimi osebami, čeprav je bila individualna variabilnost pri osebah z okvaro jeter in zdravih osebah izrazita.
(shown in blood tests) 
(vidne pri krvnih preiskavah);
Appropriate observation of patients for serotonin syndrome-like symptoms is advised (see section 4.8). 
Priporočamo ustrezno opazovanje bolnikov glede simptomov, podobnih kot pri serotoninskem sindromu (glejte poglavje 4.8).
In female subjects (n=18), the mean AUC was 35% higher and the mean Cmax was 26% higher than in male subjects (n=18). 
Pri ženskah (n = 18) je bila povprečna AUC za 35 % višja in povprečna Cmax je bila za 26 % višja kot pri moških (n = 18).
Netupitant is not a substrate for P-gp. 
Netupitant ni substrat za P-gp.
It is unknown whether palonosetron or netupitant are excreted in human milk. 
Ni znano, ali se palonosetron ali netupitant izločata v materino mleko.
Caution should be exercised in patients with severe hepatic impairment since limited data are available in these patients. 
Pri bolnikih s hudo okvaro jeter je potrebna previdnost, saj je za te bolnike na voljo malo podatkov.
In the ADME trial, less than 5% of all netupitant-related material was excreted in urine and less than 1% of the netupitant dose was eliminated unchanged in the urine and therefore any accumulation of netupitant or metabolites after a single dose would be negligible. 
V preskušanju ADME se je manj kot 5 % vsega z netupitantom povezanega materiala izločilo v urin in manj kot 1 % odmerka netupitanta se je nespremenjenega izločilo v urin, kar pomeni, da je akumulacija netupitanta ali presnovkov po enkratnem odmerku zanemarljiva.
• modifications (or disturbances) in heart rhythm 
• spremembe (ali motnje) srčnega ritma,
Palonosetron is a 5-HT3 receptor antagonist with a strong binding affinity for this receptor and little or no affinity for other receptors. 
Palonosetron je antagonist receptorjev 5-HT3 z močno afiniteto k vezavi na ta receptor in malo ali nič afinitete za druge receptorje.
The primary efficacy endpoint was complete response (CR) rate (defined as no emetic episodes, no rescue medication) within 120 hours (overall phase) after the start of the highly emetogenic chemotherapy administration. 
Primarni kriterij učinkovitosti je bila stopnja popolnega odziva (CR; opredeljena kot odsotnost emetičnih epizod in uporabe reševalnih zdravil) v roku 120 ur (celotna faza) po začetku dajanja zelo emetogene kemoterapije.
Hepatic impairment does not significantly affect total body clearance of palonosetron compared to the healthy subjects. 
Okvara jeter nima znatnega vpliva na celoten telesni očistek palonosetrona v primerjavi z zdravimi osebami.
• The active substances are palonosetron and netupitant. 
• Učinkovini sta palonosetron in netupitant.
Palonosetron soft capsule 
Mehka kapsula palonosetrona
Renal excretion for netupitant is negligible. 
Izločanje netupitanta prek ledvic je zanemarljivo.
All patients received a single oral dose of dexamethasone. 
Vsi bolniki so prejeli enkraten peroralni odmerek deksametazona.
Netupitant/palonosetron capsules are contraindicated during pregnancy (see section 4.3). 
Kapsule netupitanta in palonosetrona so kontraindicirane med nosečnostjo (glejte poglavje 4.3).
Pharmacotherapeutic group: Antiemetics and antinauseants, serotonin (5-HT3) antagonists; ATC code: A04AA55 
Farmakoterapevtska skupina: Antiemetiki in zdravila proti slabosti, antagonisti serotonina (5-HT3), oznaka ATC: A04AA55
High doses of palonosetron (each dose causing at least 15 times the human therapeutic exposure) applied daily for two years caused an increased rate of liver tumors, endocrine neoplasms (in thyroid, pituitary, pancreas, adrenal medulla) and skin tumors in rats but not in mice. 
Veliki odmerki palonosetrona (vsak odmerek je povzročil vsaj 15-krat večjo izpostavljenost od terapevtske izpostavljenosti pri človeku), ki so jih dve leti dajali vsak dan, so povzročili povečano stopnjo jetrnih tumorjev, endokrinih neoplazem (v ščitnici, hipofizi, trebušni slinavki ter sredici nadledvične žleze) in kožnih tumorjev pri podganah, ne pa pri miših.
The primary efficacy endpoint was the CR rate in the delayed phase, 25-120 hours after the start of the chemotherapy administration. 
Primarni kriterij učinkovitosti je bila stopnja CR v zakasnjeni fazi, in sicer 25-120 ur po začetku prejemanja kemoterapije.
However, due to the large volume of distribution of palonosetron and netupitant, dialysis is unlikely to be an effective treatment for overdose. 
Vendar pa zaradi velikega volumna porazdelitve palonosetrona in netupitanta ni verjetno, da bi bila dializa učinkovito zdravljenje prevelikega odmerjanja.
There are no data about the use of netupitant in pregnant women. 
Podatkov o uporabi netupitanta pri nosečnicah ni.
• midazolam - a sedative used to treat anxiety 
• midazolam, ki je pomirjevalo, ki se uporablja za zdravljenje anksioznosti;
However, since netupitant/palonosetron capsules contains a 5-HT3 receptor antagonist, caution should be exercised in concomitant use with medicinal products that increase the QT interval or in patients who have or are likely to develop prolongation of the QT interval. 
Ker pa kapsule netupitanta in palonosetrona vsebujejo antagonist receptorjev 5-HT3, je potrebna previdnost pri sočasni uporabi z zdravili, ki podaljšujejo interval QT, ali pri bolnikih, ki so razvili podaljšan interval QT, oziroma je verjetno, da ga bodo.
No dosage adjustment is necessary for elderly patients. 
Prilagoditev odmerka pri starejših bolnikih ni potrebna.
moxifloxacin, haloperidol, chlorpromazine, quetiapine, thioridazine or domperidone 
moksifloksacin, haloperidol, klorpromazin, kvetiapin, tioridazin ali domperidon;
Palonosetron is eliminated by multiple routes with approximately 50% metabolized to form two primary metabolites: N-oxide-palonosetron and 6-S-hydroxy-palonosetron. 
Palonosetron se izloča prek več poti, pri čemer se ga približno 50 % presnovi v dva osnovna presnovka: N-oksid-palonosetron in 6-S-hidroksi-palonosetron.
Also tell your doctor, pharmacist or nurse if you are taking any of the following medicines as your doctor may need to change the dose of these other medicines: 
Zdravniku, farmacevtu ali medicinski sestri povejte tudi, če jemljete katero koli od naslednjih zdravil, saj bo zdravnik morda moral spremeniti odmerek teh zdravil:
The proportion of patients with Overall no impact on daily life was 6.3% higher (p value =0.005) in the Akynzeo group (78.5%) than in the palonosetron group (72.1%). 
Delež bolnikov brez vpliva na vsakodnevno življenje v kategoriji Skupno je bil za 6,3 % večji (vrednost p = 0,005) v skupini z zdravilom Akynzeo (78,5 %) kot v skupini s palonosetronom (72,1 %).
Effect of other medicinal products on the pharmacokinetics of Akynzeo 
Učinek drugih zdravil na farmakokinetiko zdravila Akynzeo
Only limited data from animal studies are available regarding the placental transfer (see section 4.6). 
Iz živalskih študij je na voljo le malo podatkov o prehajanju skozi placento (glejte poglavje 4.6).
Exposure to netupitant (Cmax, AUC0-t and AUC0-∞) compared to matching healthy subjects was 11%, 28% and 19% higher in mild and 70%, 88% and 143% higher in moderate hepaticallyimpaired subjects, respectively. 
Izpostavljenost netupitantu (Cmax, AUC0-t in AUC0-∞) v primerjavi z ujemajočimi se zdravimi osebami je bila za 11 %, 28 % oziroma 19 % večja pri osebah z blago okvaro jeter ter za 70 %, 88 % oziroma 143 % večja pri osebah z zmerno okvaro jeter.