natgillin/translations-raw huggingface dataset:
Swallow the whole tablet, with a glass of water, do not chew or break the tablet. 
Priporočeni odmerek zdravila Opsumit je ena 10 mg tableta enkrat na dan. Tableto zaužijte celo s kozarcem vode in je ne žvečite ali lomite.
MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS BLISTERS 
PODATKI, KI MORAJO BITI NAJMANJ NAVEDENI NA PRETISNEM OMOTU ALI NA TRAKU
Do not use Opsumit after the expiry date which is stated on the carton, bottle and blister after “EXP”. 
Zdravila Opsumit ne smete uporabljati po datumu izteka roka uporabnosti, ki je naveden na škatli,
However, undesirable effects may occur (e.g., headache, hypotension) that may influence the ability to drive and use machines (see section 
hipotenzija), ki lahko vplivajo na sposobnost vožnje in upravljanja strojev (glejte poglavje 4.8).
QUALITATIVE AND QUANTITATIVE COMPOSITION Each film-coated tablet contains 10 mg macitentan. 
Ena filmsko obložena tableta vsebuje 10 mg macitentana.
NAME OF THE MEDICINAL PRODUCT Opsumit 10 mg tablets macitentan 
IME ZDRAVILA Opsumit 10 mg tablete macitentan
• carbamazepine (used to treat depression and epilepsy), 
• fenitoin (zdravilo, ki se uporablja za zdravljenje epileptičnih napadov), • karbamazepin (zdravilo, ki se uporablja za zdravljenje depresije in epilepsije),
• Influenza (flu) 
• faringitis (vnetje žrela) • influenca (gripa)
At clinically relevant concentrations, macitentan and its active metabolite do not interact with proteins involved in hepatic bile salt transport, i.e., the bile salt export pump (BSEP) and the sodium-dependent taurocholate co-transporting polypeptide (NTCP). 
Macitentan in njegov aktivni presnovek v klinično koncentracijah ne delujejo medsebojno z beljakovinami, ki sodelujejo pri jetrnem prenosu žolčne soli, tj. z eksportno črpalko žolčne soli
Symptomatic endpoints 
Simptomatski opazovani dogodki
Opsumit contains the active substance macitentan, which belongs to the class of medicines called “endothelin receptor antagonists”. 
Zdravilo Opsumit vsebuje zdravilno učinkovino macitentan, ki sodi v razred zdravil, imenovanih
PARTICULARS TO APPEAR ON THE OUTER PACKAGING AND THE IMMEDIATE PACKAGING 
Izgled zdravila Opsumit in vsebina pakiranja
What you need to know before you take Opsumit 
Kaj morate vedeti, preden boste vzeli zdravilo Opsumit Ne jemljite zdravila Opsumit:
Opsumit contains soya bean lecithin. 
Tablete zdravila Opsumit vsebujejo sojin lecitin.
Testicular tubular atrophy, and minimal effects on reproductive variables and sperm morphology were recorded at exposures 3.8-fold the human exposure. 
Pri izpostavljenosti, ki je bila 3,8-krat večja kot izpostavljenost pri ljudeh, so opazili testikularno tubularno atrofijo in minimalni učinek na spremenljivke reprodukcije in morfologijo sperme.
NAME OF THE MEDICINAL PRODUCT Opsumit 10 mg film-coated tablets 
IME ZDRAVILA Opsumit 10 mg filmsko obložene tablete
Thrombocytopenia7 
pogosti trombocitopenija7
The pharmacokinetics of macitentan and its active metabolite were not affected by warfarin. 
Varfarin ni vplival na farmakokinetiko macitentana in njegovega aktivnega presnovka.
In a longterm double-blind study in patients with PAH, the incidence of oedema AEs in the macitentan 10 mg and placebo treatment groups was 21.9% and 20.5%, respectively. 
dvojno slepi študiji z bolniki s PAH je bila incidenca neželenega učinka edema 21,9 % v skupini, ki je prejemala macitentan 10 mg, in 20,5 % v skupini, ki je prejemala placebo.
©2013 Actelion Pharmaceuticals Ltd 
Če imate dodatna vprašanja o zdravljenju, se posvetujte z zdravnikom ali farmacevtom.©2013 Actelion Pharmaceuticals Ltd
Respiratory, thoracic and mediastinal disorders 
Bolezni dihal, prsnega koša in mediastinalnega prostora pogosti kongestija nosu1
• St. John's Wort (an herbal preparation used to treat depression), 
• šentjanževko (zeliščni pripravek, ki se uporablja za zdravljenje depresije),
• If it is possible you could become pregnant, use a reliable form of birth control (contraception) 
• Če lahko zanosite, morate med zdravljenjem z zdravilom Opsumit uporabljati učinkovit način preprečevanja nosečnosti (kontracepcijo).
Do not breastfeed while you are taking Opsumit. 
Med uporabo zdravila Opsumit ne smete dojiti.
NAME OF THE MEDICINAL PRODUCT Opsumit 10 mg film-coated tablets macitentan 
IME ZDRAVILA Opsumit 10 mg filmsko obložene tablete macitentan
• dark-coloured urine 
• temno obarvan urin • srbenje kože
Sildenafil: At steady-state, the exposure to sildenafil 20 mg three times a day was increased by 15% during concomitant administration of macitentan 10 mg once daily. 
Sildenafil: V stanju dinamičnega ravnovesja se je izpostavljenost sildenafilu 20 mg trikrat na dan zvečala za 15 % med sočasno uporabo macitentana 10 mg enkrat na dan. Sildenafil, ki je substrat CYP3A4, ni vplival na farmakokinetiko macitentana, medtem ko se je izpostavljenost aktivnemu presnovku macitentana zmanjšala za 15 %.
C. 
HRa
Nasopharyngitis 
Kaplan-Meierju
Hypotension2 
Žilne bolezni pogosti hipotenzija2
Macitentan and its active metabolite are not inhibitors of hepatic or renal uptake transporters at clinically relevant concentrations, including the organic anion transporting polypeptides (OATP1B1 and OATP1B3). 
Macitentan in njegov aktivni presnovek v klinično pomembnih koncentracijah nista zaviralca jetrnih ali ledvičnih privzemnih prenašalcev, vključno z organskimi anionskimi prenašalskimi polipeptidi
Outcome endpoints 
Izidi opazovanega dogodka
Macitentan has been administered as a single dose of up to 600 mg to healthy subjects. 
Macitentan so dajali zdravim osebam v enkratnem odmerku do 600 mg. Od neželenih učinkov so opazili glavobol, navzeo in bruhanje.
Bronchitis 
Hemoglobin
In a double-blind study in patients with PAH, macitentan 10 mg was associated with a decrease in mean leucocyte count from baseline of 0.7 × 109/L versus no change in placebo-treated patients. 
V dvojno slepi študiji pri bolnikih s PAH je bil macitentan 10 mg povezan z zmanjšanjem povprečnega števila levkocitov glede na izhodišče za 0,7 × 10
• rifampicin, clarithromycin, telithromycin (antibiotics used to treat infections), 
Če jemljete katerega koli od spodaj navedenih zdravil, se posvetujte z zdravnikom ali farmacevtom: • rifampicin, klaritromicin, telitromicin (antibiotiki, ki se uporabljajo za zdravljenje okužb),
Film coating 
ZA SPROŠČANJE SERIJ
• if you are breastfeeding. 
• če dojite.
Immune system disorders 
Bolezni imunskega sistema občasni preobčutljivostne reakcije
Hepatobiliary disorders 
Hemodinamski opazovani dogodki
Blood and lymphatic system disorders 
Bolezni krvi in limfatičnega sistema zelo pogosti anemija, zmanjšana raven hemoglobina5
• Thrombocytopenia (decreased blood platelet counts) 
• trombocitopenija (zmanjšane ravni trombocitov)
Poly(vinyl-alcohol) (E1203) 
Filmska obloga poli(vinilalkohol) (E1203) titanov dioksid (E171) smukec (E553b) sojin lecitin (E322) ksantanski gumi (E415)
The application for Dexamethasone Alapis has therefore been made in accordance with Article 10a of Directive 2001/83/EC, as amended. 
Vloga za zdravilo Dexamethasone Alapis je bila zato predložena v skladu s členom 10(a) Direktive 2001/83/ES, kakor je bila spremenjena.
This corresponds to over 180 literature reports (Randomized Clinical Trials (RCTs); Reviews, Monographs (Martindale etc.). 
To ustreza več kot 180 poročilom iz literature (randomizirana klinična preskušanja, pregledi, monografije (Martindale itd.)).
Overall summary of the scientific evaluation of Dexamethasone Alapis 
Splošni povzetek znanstvenega vrednotenja zdravila Dexamethasone Alapis
It is used principally as an anti-inflammatory or immunosuppressant agent. 
Uporablja se predvsem kot protivnetno ali imunosupresivno zdravilo.
Elixirs are sweetened hydro-alcoholic oral solutions that are specially formulated for oral use in infants and children (Strickley, 2004). 
Eliksirji so sladkane vodno-alkoholne peroralne raztopine, ki so namenjene posebej za peroralno uporabo pri dojenčkih in otrocih (Strickley, 2004).
SCIENTIFIC CONCLUSIONS AND GROUNDS FOR POSITIVE OPINION 
ZNANSTVENI ZAKLJUČKI IN PODLAGA ZA POZITIVNO MNENJE
• Prevention of nausea and vomiting and treatment of cancer with oncolytics that have a serious emetic effect. 
• preprečevanje slabosti in bruhanja ter zdravljenje raka z onkolitičnimi zdravili z močnim emetičnim učinkom.
It also showed that dexamethasone had a broad therapeutic index. 
Pokazala je tudi, da ima deksametazon širok terapevtski indeks.
• Treatment of non-endocrine corticosteroid responsive conditions 
• zdravljenje neendokrinih bolezni, ki se odzivajo na zdravljenje s kortikosteroidi
The Summary of Product Characteristics achieved during the Coordination group procedure was considered to address adequately the safety concerns of this medicinal product. 
Povzetek glavnih značilnosti zdravila, ki je bil pripravljen v postopku usklajevalne skupine, je ustrezno obravnaval varnostne zadržke za to zdravilo.
This active substance is considered to have a ‘well-established use' within the European Community for at least 10 years, with recognised efficacy and an acceptable level of safety in the use in certain endocrine and non-endocrine disorders, in certain cases of cerebral oedema and for diagnostic testing of adrenocortical hyperfunction. 
Za zdravilno učinkovino velja, da ima v Evropski skupnosti „dobro uveljavljeno uporabo“ že vsaj 10 let s priznano učinkovitostjo in sprejemljivo ravnjo varnosti pri uporabi pri nekaterih boleznih endokrinega in neendokrinega sistema, v nekaterih primerih cerebralnega edema in za diagnostično testiranje adrenokortikalne hiperfunkcije.
Dexamethasone has a biological half life of 36 - 54 hours and therefore is suitable in conditions where continuous glucocorticoid action is required. 
Deksametazon ima biološko razpolovno dobo 36-54 ur, zato je primeren za zdravljenje stanj, pri katerih je zahtevano stalno glukokortikoidno delovanje.
The mechanism of action is mediated via activation of glucorticoid receptors that leads to increased or decreased transcription of a number of genes involved in the inflammatory process, particularly the repression of cytokine gene transcription and the direct interaction between the glucocorticoid receptor and other transcription factors activated in chronic inflammation. 
Mehanizem delovanja izhaja iz aktiviranja glukokortikoidnih receptorjev, ki privede do povečane ali zmanjšane transkripcije številnih genov, ki sodelujejo v vnetnem procesu, zlasti do zmanjšane transkripcije gena citokina ter neposrednega medsebojnega delovanja glukokortikoidnega receptorja in drugih faktorjev transkripcije, ki se aktivirajo pri kroničnem vnetju.
Therefore, from a pharmaceutical perspective, elixirs are a type of oral solutions and are expected to behave in vivo as such. 
S farmacevtskega vidika so eliksirji torej vrsta peroralnih raztopin in naj bi tako učinkovali tudi in vivo.
From the literature submitted during the decentralised procedure, it was shown that dexamethasone has been widely used in clinical practice for a number of indications for more than 40 years. 
Iz literature, predložene med decentraliziranim postopkom, je razvidno, da se deksametazon v klinični praksi pri številnih indikacijah množično uporablja že več kot 40 let.
The strength and quality of evidence gathered from the above information was considered adequate for a medicinal product with a well established and broad therapeutic index as dexamethasone. 
Pomen in kakovost dokazov, zbranih iz zgoraj navedenih informacij, sta veljala za ustrezna za zdravilo z dobro uveljavljenim in širokim terapevtskim indeksom, kot je deksametazon.
The Applicant specifically focussed its response on the concerns raised about bridging data. 
Predlagatelj je v svojem odgovoru obravnaval predvsem vprašanja glede premostitvenih podatkov.
The CHMP assessed the dossier and the available data, including the issues raised by the objecting CMS. 
Ta je ocenil dokumentacijo in razpoložljive podatke, vključno z vprašanji, ki jih je izpostavila ugovarjajoča zadevna država članica.
At Day 60 of the CMD(h) procedure, since no agreement could be reached, the procedure was referred to the CHMP. 
Ker sporazum ni bil dosežen, j e bil na 60. dan postopka CMD(h) postopek napoten na CHMP.
In vivo bioequivalence studies may be exempted if an assumption of equivalence in in vivo performance can be justified by satisfactory in vitro data. 
Študije biološke enakovrednosti in vivo je mogoče izvzeti, če je domnevo enakovrednosti pri delovanju in vivo mogoče zadostno utemeljiti s podatki in vitro.
Literature data available on the various routes of administration for the same treatment show that dexamethasone is equally effective via any administration route. 
Podatki iz literature, ki so na voljo za različne poti uporabe pri istem zdravljenju, kažejo, da je deksametazon pri vseh poteh uporabe enako učinkovit.
The BCS-based biowaiver approach is meant to reduce in vivo bioequivalence studies. 
Pristop bio-opustitve na podlagi biofarmacevtskega sistema klasifikacije je namenjen zmanjšanju študij biološke enakovrednosti in vivo.
In addition, the limited number of published studies that used a solution formulation used a similar posology to the tablet formulation. 
Poleg tega je bilo v omejenem številu objavljenih študij, v katerih so uporabili formulacijo v obliki raztopine, odmerjanje podobno kot pri formulaciji v obliki tablet.
The objecting Concerned Member State raised a potential serious risk to public health as it considered that the literature data on dexamethasone tablets that had been submitted could not be extrapolated to dexamethasone oral solution without adequate bridging data and therefore the efficacy and safety of Dexamethasone Alapis could not be demonstrated in the application. 
Ugovarjajoča zadevna država članica je izpostavila morebitna resna tveganja za javno zdravje, saj je menila, da predloženih podatkov iz literature o tabletah deksametazona ni mogoče prenesti na peroralno raztopino deksametazona brez ustreznih premostitvenih podatkov ter da zato učinkovitosti in varnosti zdravila Dexamethasone Alapis v vlogi ni mogoče dokazati.
The CHMP therefore agreed that the bibliographic data provided in support of the application demonstrates the well-established use of dexamethasone sodium phosphate used in the oral solution and that a bioequivalence study was not necessary to show the relevance of the literature used in support of the pharmaceutical form concerned. 
CHMP se je zato strinjal, da bibliografski podatki, predloženi v podporo vlogi, dokazujejo dobro uveljavljeno uporabo deksametazon natrijevega fosfata, uporabljenega v peroralni raztopini, in da študija biološke enakovrednosti ni nujno potrebna za dokaz ustreznosti literature, uporabljene v podporo zadevni farmacevtski obliki.
Most of the literature provided by the Applicant concerned the administration of an oral solid dosage form, i.e. tablet. 
Večina literature, ki jo je predložil predlagatelj, je obravnavala dajanje trdne peroralne oblike odmerjanja, tj. tablete.
Because it has only minimal mineral corticoid properties, the drug is inadequate as a monotherapy for the management of adrenocortical insufficiency. 
Zdravilo ima le minimalne lastnosti mineralnih kortikoidov, zato ni primerno za samostojno zdravljenje pri adrenokortikalni insuficienci.
Dexamethasone is a highly potent and long-acting glucocorticoid with negligible sodium retaining properties. 
Deksametazon je zelo močan in dolgo delujoči glukokortikoid, ki v zanemarljivi količini zadržuje natrij.
According to the Appendix II of the “Guideline on the investigation of bioequivalence (CPMP/PWP/EWP/1401/98 Rev 1/Corr)”, applying for a BCS-based biowaiver is restricted to highly soluble drug substances with known human absorption and considered not to have a narrow therapeutic index. 
V skladu z Dodatkom II „Smernic o raziskavah biološke enakovrednosti (CPMP/PWP/EWP/1401/98 Rev 1/Corr)“ je za bio-opustitev na podlagi biofarmacevtskega sistema klasifikacije mogoče zaprositi le pri visoko topnih zdravilnih učinkovinah, ki imajo znano absorpcijo pri ljudeh in nimajo ozkega terapevtskega indeksa.
From the literature data provided by the Applicant, it was shown that there were no significant differences between the bioavailabilities of immediate release tablet formulations and elixir formulations of dexamethasone (irrespective of the elixir formulation used). 
Iz podatkov iz literature, ki jih je predložil predlagatelj, je bilo razvidno, da ni pomembnih razlik med biološko razpoložljivostjo formulacij v obliki tablet s takojšnjim sproščanjem in formulacij deksametazona v obliki eliksirja (ne glede na vrsto uporabljene formulacije v obliki eliksirja).
However, as information on the composition of the dexamethasone syrup, elixir or oral solution investigated in the provided studies was missing in all articles, some concerns were raised on whether those data could be considered as sufficient to allow bridging of the data between the tablets and the oral formulation applied for. 
Vendar v nobenem članku ni bilo informacij o sestavi sirupa, eliksirja ali peroralne raztopine deksametazona, ki so jih preučevali v predloženih študijah, poleg tega so bili izraženi nekateri pomisleki, ali so ti podatki zadostni, da omogočajo premostitev podatkov med tabletami in peroralno formulacijo, za katero je bila predložena vloga.
Data on the solubility and on the absorption and permeability of dexamethasone were provided by the Applicant during the decentralised and the CMD(h) referral procedure to show that Dexamethasone Alapis met all criteria for a BCS-based biowaiver. 
Podatke o topnosti ter absorpciji in propustnosti deksametazona je predlagatelj predložil med decentraliziranim postopkom in napotitvenim postopkom na CMD(h), da bi dokazal, da zdravilo Dexamethasone Alapis izpolnjuje vse pogoje za bio-opustitev na podlagi biofarmacevtskega sistema klasifikacije.
The majority of data submitted supporting efficacy and safety with dexamethasone in the indications being sought have been obtained with tablet formulations. 
Večina podatkov, predloženih v podporo učinkovitosti in varnosti deksametazona pri indikacijah, za katere je bila predložena vloga, je bila pridobljena s formulacijami v obliki tablet.
A referral was thus triggered at the CMD(h) and the Applicant was asked to provide detailed literature and critical assessment of the efficacy and safety of dexamethasone oral solution in the indications applied for. 
Pri CMD(h) je bil zato sprožen napotitveni postopek, predlagatelj pa je bil pozvan k predložitvi natančne literature ter kritične ocene učinkovitosti in varnosti peroralne raztopine deksametazona pri indikacijah, za katere je bila predložena vloga.
Although the “Guideline on the investigation of bioequivalence (CPMP/PWP/EWP/1401/98 Rev 1/Corr)” states: “In those cases where the test product is an oral solution which is intended to be bioequivalent to another immediate release oral dosage form, bioequivalence studies are required”, the application of a BCS-based biowaiver to bridge data from different pharmaceutical forms was considered to have been adequately justified from a scientific point of view, by provision of parallel artificial membrane permeability assay (PAMPA) data, literature and dissolution data, demonstrating that Dexamethasone drug substance has biopharmaceutical characteristics of BCS Class I/III, and that the excipients have no adverse affects on bioavailability. 
Čeprav je v „Smernicah o raziskavah biološke enakovrednosti (CPMP/PWP/EWP/1401/98 Rev 1/Corr)“ navedeno: „Kadar je preskušano zdravilo peroralna raztopina, ki naj bi se uporabljala kot biološko enakovredno zdravilo drugemu zdravilu s peroralnim načinom odmerjanja s takojšnjim sproščanjem, so potrebne študije biološke enakovrednosti“, je veljalo, da je bilo izvajanje bio opustitve na podlagi biofarmacevtskega sistema klasifikacije za premostitev podatkov iz različnihfarmacevtskih oblik znanstveno zadostno utemeljeno s predložitvijo vzporednih podatkov o testiranju prepustnosti umetne membrane, literature in podatkov o raztapljanju, s čimer je bilo dokazano, da ima zdravilna učinkovina deksametazon biofarmacevtske značilnosti razreda I/III iz biofarmacevtskega sistema klasifikacije ter da pomožne snovi nimajo neželenih učinkov na biološko razpoložljivost.
The bibliography provided was considered sufficient to support the well established use of dexamethasone substance in different tablet formulations. 
Predloženi bibliografski podatki so zadoščali za podporo dobro uveljavljeni uporabi deksametazona v različnih formulacijah v obliki tablet.
It was therefore concluded by the CHMP that efficacy and safety of dexamethasone active substance in the therapeutic indications applied for had been sufficiently demonstrated by the provided literature. 
CHMP je zato zaključil, da sta učinkovitost in varnost zdravilne učinkovine deksametazon pri terapevtskih indikacijah, za katere je bila predložena vloga, zadostno dokazani s predloženo literaturo.
In order to extrapolate efficacy and safety data from these studies to the oral solution formulation applied for, the Applicant provided data that showed that irrespective of immediate release oral dosage formulation (tablet or solution), the bioavailability of dexamethasone in terms of extent and rate of absorption, was similar. 
Da bi bilo mogoče podatke o učinkovitosti in varnosti iz teh študij prenesti na formulacijo v obliki peroralne raztopine, za katero je bila predložena vloga, je predlagatelj predložil podatke, iz katerih je razvidno, da je pri formulacijah s peroralno obliko odmerjanja s takojšnjim sproščanjem (tableta ali raztopina) biološka razpoložljivost deksametazona glede obsega in hitrosti absorpcije podobna.
As a justification for not providing bioequivalence study to bridge the data submitted on the tablet formulation and the oral solution formulation applied for, the Applicant applied for a BCS (Biopharmaceutics Classification System)-based biowaiver. 
Kot utemeljitev, zakaj ni bila predložena študija biološke enakovrednosti za premostitev predloženih podatkov o formulaciji v obliki tablet in formulaciji v obliki peroralne raztopine, za katero je bila predložena vloga, je predlagatelj zaprosil za bio-opustitev na podlagi biofarmacevtskega sistema klasifikacije.
In addition, a few literature reports (CTs) on the efficacy and safety of dexamethasone in oral solution/syrup have been submitted in the following indications applied for: 
Poleg tega je bilo za naslednje indikacije, za katere je bila predložena vloga, predloženih nekaj poročil iz literature (CT) o učinkovitosti in varnosti deksametazona v obliki peroralne raztopine/sirupa:
Therefore, a huge volume of efficacy and safety data exists for the dexamethasone pharmaceutical substance. 
Za farmacevtsko učinkovino deksametazon torej obstaja veliko podatkov o učinkovitosti in varnosti.
Additional bridging data (or its absence fully justified) between the bibliographic data and the proposed pharmaceutical product were therefore requested to the Applicant during the decentralised and the CMD(h) referral procedures. 
Med decentraliziranim postopkom in napotitvenim postopkom na CMD(h) so se zato od predlagatelja zahtevali dodatni premostitveni podatki (ali podrobna utemeljitev njihove odsotnosti) med bibliografskimi podatki in predlaganim zdravilom.
Whereas, - the Applicant has provided sufficient literature data to demonstrate well-established use of dexamethasone, - efficacy and safety of dexamethasone has been adequately shown in the indications applied for - adequate bridging data between the tablet formulation and the oral solution formulation have been provided by the Applicant, the CHMP has recommended the granting of the marketing authorisation(s) for which the summary of product characteristics, labelling and package leaflet remain as per the final versions achieved during the Coordination group procedure as mentioned in Annex III of this Opinion. 
CHMP je priporočil odobritev dovoljenj za promet z zdravilom, katerih povzetek glavnih značilnosti zdravila, označevanje in navodilo za uporabo ostanejo enaki zadnjim različicam, pripravljenim v postopku usklajevalne skupine in navedenim v Prilogi III tega mnenja.