natgillin/translations-raw huggingface dataset:
Taking into account that the MAH had submitted data which showed that tolperisone is a highly soluble and highly permeable active substance, neither solubility nor dissolution was considered to be a limiting factor in terms of in vivo absorption. 
Glede na to, da so podatki, ki jih je predložil imetnik dovoljenja za promet z zdravilom, pokazali, da je tolperizon lahko topna in zelo permeabilna zdravilna učinkovina, se niti topnost niti raztapljanje ne štejeta za omejitveni dejavnik v smislu absorpcije in vivo.
• Therefore, the Committee concluded by majority that the bioequivalence studies conducted in the fasting state give sufficient evidence to conclude on the bioequivalence also in the fed state since Merisone contains a highly soluble and highly permeable active substance, and pharmacokinetic principles and convincing experimental evidence suggest that the food effect of this active substance is formulation independent. 
• odbor je zato z večino zaključil, da sta bioekvivalenčni študiji, izvedeni v pogojih na tešče, zagotovili zadostne dokaze, da je mogoče sklepati o biološki enakovrednosti tudi v pogojih na poln želodec, saj zdravilo Merisone vsebuje lahko topno in zelo permeabilno zdravilno učinkovino, načela farmakokinetike in prepričljivi eksperimentalni dokazi pa kažejo, da vpliv hrane na to zdravilno učinkovino ni odvisen od formulacije;
The objecting concerned member state (CMS) was of the view that a similar extent of the food effect that was shown for the two different products referred to above, does not have to hold true for this generic formulation since it has not been proven that the food effect is a characteristic of the active substance and not a formulation related factor. 
Zadevna država članica, ki je izrazila pomisleke, je menila, da ni nujno, da podoben obseg vpliva hrane, ki so ga opazili pri dveh različnih zdravilih, omenjenih zgoraj, velja tudi za to generično formulacijo, saj ni bilo dokazano, da je vpliv hrane značilen za zdravilno učinkovino, in ni zgolj dejavnik, povezan s formulacijo.
The majority of the CHMP members agreed that in vivo dissolution differences between formulations are likely to be less apparent and more difficult to observe in fed conditions since gastric emptying time is longer in the fed state than in the fasting state. 
Večina članov odbora CHMP se je strinjala, da so razlike v raztapljanju in vivo med formulacijama v pogojih na poln želodec verjetno manj očitne in jih je težje opaziti, saj je čas prehajanja skozi želodec v pogojih na poln želodec daljši kot v pogojih na tešče.
As there is no evidence that the food-effect is formulation dependent and the formulation is a conventional one, some of the PKWP members considered that a bioequivalence study in the fasting state was acceptable in this case. 
Ker ni na voljo nobenih dokazov o tem, da je vpliv hrane odvisen od formulacije, in ker gre za običajno formulacijo, so nekateri člani delovne skupine za farmakokinetiko menili, da je bioekvivalenčna študija v pogojih na tešče v tem primeru sprejemljiva.
As there is no evidence that the food-effect is formulation dependent, the majority of the CHMP concluded that the bioequivalence studies conducted in the fasting state, which is considered to be the most sensitive condition, would give sufficient evidence to conclude on the bioequivalence in both the fasting and fed states in this particular case. 
Glede na to, da ni dokazov o tem, da je vpliv hrane odvisen od formulacije, je večina članov odbora CHMP zaključila, da sta bioekvivalenčni študiji, izvedeni v pogojih na tešče, ki veljajo za najobčutljivejše, zagotovili zadostne dokaze, da je mogoče zaključiti, da je v tem primeru zdravilo biološko enakovredno tako v pogojih na tešče kot na poln želodec.
Since the summary of product characteristics (SmPC) of the reference medicinal product did not make any recommendations regarding food and did not mention a food effect, the MAA that was submitted for Merisone included two bioequivalence studies with 50 and 150 mg tolperisone film-coated tablets conducted under fasting conditions with 52 volunteers each. 
Povzetek glavnih značilnosti zdravila za referenčno zdravilo ni vseboval nobenih priporočil glede hrane niti navedbe o vplivu hrane, zato sta bili k vlogi za pridobitev dovoljenja za promet z zdravilom, ki je bila predložena za Merisone, priloženi dve bioekvivalenčni študiji s 50- in 150-miligramskimi filmsko obloženimi tabletami tolperizona, ki so ju izvedli v pogojih na tešče, v vsaki pa je sodelovalo 52 prostovoljcev.
Taking into account all the evidence and arguments presented, the majority of the CHMP noted that that bioequivalence had been demonstrated in the fasting state for tolperisone, which is highly soluble and highly permeable active substance, demonstrating high within-subject variability. 
Ob upoštevanju vseh predstavljenih dokazov in argumentov je večina članov odbora CHMP izpostavila, da je bila biološka enakovrednost tolperizona dokazana v pogojih na tešče, pri čemer je tolperizon lahko topna in zelo permeabilna zdravilna učinkovina z dokazano veliko spremenljivostjo pri posamezniku.
The Pharmacokinetics Working Party (PKWP) was also consulted to seek their view on whether there is any scientific reasoning that tolperisone (classified as a highly variable drug as the within-subject variability of the Cmax of the reference medicinal product was 46.99%) may have the option of showing bioequivalence in either the fasted or fed state. 
Posvetovali so se tudi z delovno skupino za farmakokinetiko in jo zaprosili za mnenje o tem, ali obstajajo kakršni koli znanstveni argumenti, ki podpirajo sklep, da se lahko biološka enakovrednost tolperizona (ki je zelo spremenljivo zdravilo, saj je bila spremenljivost Cmaks referenčnega zdravila pri posamezniku 46,99-odstotna) dokaže v pogojih na tešče ali na poln želodec.
Other PKWP members were of the view that a fed study would not have been required only if the effects of food were known to be solely hepatic, which however was considered to be insufficiently supported, and since the food effect for tolperisone was considered to be significantly high, a study in a fed state should have been performed. 
Preostali člani delovne skupine za farmakokinetiko pa so menili, da študija v pogojih na poln želodec ne bi bila potrebna samo, če bi bilo dokazano, da je vpliv hrane povezan izključno z jetri, za kar pa ni zadostnih dokazov, in da bi bilo glede na to, da je bil vpliv hrane na tolperizon ocenjen kot precejšen, treba izvesti študijo v pogojih na poln želodec.
The information that was introduced in the SmPC of tolperisone was based on two well-designed studies conducted with different formulations of tablets, which showed that compared to the fasting state, fat-rich food increases the bioavailability of tolperisone by about 
Informacije, ki so bile vključene v povzetek glavnih značilnosti zdravila za tolperizon, so temeljile na dveh dobro zasnovanih študijah, izvedenih z različnimi formulacijami tablet, ki sta pokazali, da hrana, bogata z maščobami, poveča biološko uporabnost tolperizona za približno 100 % v primerjavi z zaužitjem na tešče.
Although the results of the bioequivalence studies were considered to be borderline by the objecting CMS, the applicant argued that the second bioequivalence study was a replicate design study where it was shown that tolperisone is a highly variable drug - the within-subject variability of the reference medicinal product Cmax was 46.99%. 
Zadevna država članica, ki je izrazila pomisleke, je menila, da so rezultati bioekvivalenčnih študij na meji, vendar je predlagatelj ugovarjal, da je bila druga bioekvivalenčna študija izvedena kot študija s ponovitvami, ki je pokazala, da je tolperizon zelo spremenljivo zdravilo - spremenljivost Cmaks referenčnega zdravila pri posamezniku je bila 46,99-odstotna.
Therefore the objecting member state was of the view that the two bioequivalence submitted with the 50 and 150mg tolperisone tablets under fasting conditions were not sufficient, and that bioequivalence should be demonstrated under fed conditions. 
Država članica, ki je izrazila pomisleke, je zato menila, da bioekvivalenčni študiji v pogojih na tešče, predloženi za 50- in 150-miligramske tablete tolperizona, ne zadostujeta in da je treba biološko enakovrednost dokazati v pogojih na poln želodec.
The CHMP also noted that the excipients mannitol and betaine found in the product subject to the referral but not in the reference medicinal product, had no effect on the bioequivalence of these products in fasting state. 
Odbor CHMP je upošteval tudi, da pomožni snovi manitol in betain, ki ju vsebuje zdravilo, ki je predmet napotitve, ne pa tudi referenčno zdravilo, nista vplivali na biološko enakovrednost teh zdravil v pogojih na tešče.
In the study with the 50 mg tablet, bioequivalence was not demonstrated as the upper limit of the Cmax was outside the upper band, i.e. 
V študiji s 50-miligramsko tableto biološke enakovrednosti niso dokazali, saj je bila zgornja meja Cmaks zunaj zgornje meje razpona, tj. 125,49 %.
• The Committee was of the view that results of the submitted bioequivalence studies showed that Merisone 50 and 150 mg tablets was bioequivalent to the reference medicinal product Mydeton 50 and 150-mg tablets under fasting conditions; 
• odbor CHMP je menil, da so rezultati predloženih bioekvivalenčnih študij pokazali, da so 50- in 150-miligramske tablete zdravila Merisone biološko enakovredne 50- in 150-miligramskim tabletam referenčnega zdravila Mydeton v pogojih na tešče;
The CHMP noted that the excipients mannitol and betaine found in the product subject to the referral but not in the reference medicinal product, had no effect on the bioequivalence of these products in fasting state. 
Odbor CHMP je upošteval, da pomožni snovi manitol in betain, ki ju vsebuje zdravilo, ki je predmet napotitve, ne pa tudi referenčno zdravilo, nista vplivali na biološko enakovrednost teh zdravil v pogojih na tešče.
Therefore based on the results of the submitted bioequivalence studies, the CHMP members agreed that Merisone 50 and 150 mg tablets are bioequivalent to the reference medicinal product Mydeton 50 and 150-mg tablets (Gedeon Richter Plc) under fasting conditions. 
Člani odbora CHMP so se na podlagi rezultatov predloženih bioekvivalenčnih študij strinjali, da so 50- in 150-miligramske tablete zdravila Merisone biološko enakovredne 50- in 150-miligramskim tabletam referenčnega zdravila Mydeton (Gedeon Richter Plc) v pogojih na tešče.
However more recently the effect of food on the bioavailability of tolperisone has been established to be significant and was reflected accordingly in the SmPC of the reference medicinal product at the time of submission of the MAA subject to this referral1. 
Vendar so kasneje ugotovili, da hrana pomembno vpliva na biološko uporabnost tolperizona, zato je bila ta ugotovitev ob predložitvi vloge za pridobitev dovoljenja za promet z zdravilom, ki je predmet te napotitve1, ustrezno vključena v povzetek glavnih značilnosti zdravila za referenčno zdravilo.
Because the within-subject coefficient of variation is higher than 30%, the applicant was of the view that according to the current bioequivalence guideline extended limits could have been used to show bioequivalence, which would have been in this case 71.25% 
Ker je bil koeficient spremenljivosti pri posamezniku višji od 30 %, je predlagatelj menil, da bi lahko v skladu z veljavnimi smernicami o
2 Co-ordination group for mutual recognition and decentralised procedures - human 
Usklajevalna skupina za postopek z medsebojnim priznavanjem in decentralizirani postopek - zdravila za uporabo v humani medicini bioekvivalenci za dokaz bioekvivalence uporabili širši razpon mejnih vrednosti, v tem primeru
A positive change indicates improvement. 
Pozitivna sprememba je znak izboljšanja.
Diagnosis should be made according to current guidelines. 
Diagnozo je treba postaviti skladno z veljavnimi smernicami.
Last Observation Carried Forward 
Zadnje opažanje preneseno naprej
In addition, a post-hoc definition of response is provided in the same table. 
V isti tabeli je navedena tudi naknadna opredelitev odziva.
Treatment usually starts with a low dose. 
• Zdravljenje se običajno začne z nizkim odmerkom.
CIBIC-Plus: improvement 
CIBIC-Plus: izboljšanje
The in vivo micronucleus test was negative. 
Test mikronukleusa in vivo je bil negativen.
Use of scopolamine as an antidote is not recommended. 
Uporaba skopolamina kot antidota ni priporočena.
Individual response to rivastigmine cannot be predicted. 
Odziva posameznika na rivastigmin ni mogoče predvideti.
To benefit from your medicine, take it every day. 
• Da vam bo zdravilo pomagalo, ga morate jemati vsak dan.
Dose titration should then be carried out as described above. 
Takrat je treba odmerek titrirati enako, kot je opisano zgoraj.
The use of Rivastigmine Teva in children and adolescents (age below 18 years) is not recommended. 
Uporaba zdravila Rivastigmine Teva pri otrocih in mladostnikih (mlajših od 18 let) ni priporočena.
No target organ toxicity was observed. 
Ciljnih organov za toksičnost niso opazili.
No safety margins to human exposure were achieved in the animal studies due to the sensitivity of the animal models used. 
V študijah pri živalih varnostnih meja za izpostavljenost pri človeku niso dosegli zaradi občutljivosti živalskega modela, ki so ga uporabili.
Rivastigmine is rapidly and completely absorbed. 
Absorpcija Rivastigmin se hitro in popolnoma absorbira.
Patients with Alzheimer's disease may lose weight. 
Bolniki z Alzheimerjevo boleznijo lahko shujšajo.
Táncsics Mihály út 82 
Táncsics Mihály út 82 Madžarska
If you have not taken Rivastigmine Teva for several days, do not take the next dose until you have talked to your doctor. 
Če zdravila Rivastigmine Teva niste jemali že nekaj dni, ne vzemite naslednjega odmerka, dokler se ne pogovorite s svojim zdravnikom.
Most cases of accidental overdose have not been associated with any clinical signs or symptoms and almost all of the patients concerned continued rivastigmine treatment. 
Večina primerov naključnega prevelikega odmerjanja ni bila povezana s kakršnimi koli kliničnimi znaki ali simptomi, skoraj vsi bolniki pa so nadaljevali zdravljenje z rivastigminom.
If you find you have forgotten to take your dose of Rivastigmine Teva, wait and take the next dose at the usual time. 
Če ugotovite, da ste pozabili vzeti odmerek zdravila Rivastigmine Teva, počakajte in vzemite naslednji odmerek ob običajnem času.
Peak plasma concentrations are reached in approximately 1 hour. 
Najvišje koncentracije v plazmi so dosežene v približno 1 uri.
ADAS-Cog: improvement of at least 4 points 
ADAS-Cog: izboljšanje za vsaj 4
Clinical monitoring is recommended for these adverse reactions. 
Priporočen je klinični nadzor teh neželenih reakcij.
Patients without visual hallucinations 
Bolniki brez vizualnih halucinacij
The MAH must ensure that the system of pharmacovigilance presented in Module 1.8.1. of the Marketing Authorisation Application, is in place and functioning before and whilst the product is on the market. 
Imetnik dovoljenja za promet z zdravilom mora zagotoviti, da je sistem farmakovigilance, predložen v modulu 1.8.1 dovoljenja za promet z zdravilom, vzpostavljen in deluje, preden da zdravilo v promet in ves čas trženja zdravila.
Motor dysfunction 
Motorična disfunkcija
In massive overdose, atropine can be used. 
Pri izjemnem prevelikem odmerjanju se lahko uporabi atropin.
While bioavailability of rivastigmine is greater in elderly than in young healthy volunteers, studies in Alzheimer patients aged between 50 and 92 years showed no change in bioavailability with age. 
Biološka uporabnost rivastigmina je pri starejših večja kot pri mladih zdravih prostovoljcih, vendar študije pri bolnikih z Alzheimerjevo boleznijo, starih od 50 do 92 let, niso pokazale spremembe biološke uporabnosti glede na starost.
Your doctor will tell you what dose of Rivastigmine Teva to take. 
Zdravnik vam bo povedal, kakšen odmerek zdravila Rivastigmine Teva morate jemati.
TEVA UK Ltd Brampton Road, Hampden Park, Eastbourne, East Sussex, BN22 9AG United Kingdom 
TEVA UK Ltd Brampton Road, Hampden Park, Eastbourne, East Sussex, BN22 9AG Velika Britanija
Table 1 * 
Tabela 1 *
Shellac glaze-45% 
glazura iz šelaka - 45 %
Maintenance treatment can be continued for as long as a therapeutic benefit for the patient exists. 
Vzdrževalno zdravljenje se lahko nadaljuje, dokler pri bolniku obstaja koristen terapevtski učinek.
However, Rivastigmine Teva may be used in this patient population and close monitoring is necessary. 
Vendar se zdravilo Rivastigmine Teva v tej populaciji bolnikov lahko uporabi in potrebno je natančno spremljanje.
ITT: Intent-To-Treat; RDO: Retrieved Drop Outs 
ITT: Intent-To-Treat (namera zdravljenja); RDO: Retrieved Drop Outs (nadomeščeni izpadli).
In vitro, this metabolite shows minimal inhibition of acetylcholinesterase (<10 %). 
In vitro ta presnovek kaže minimalno zaviranje acetilholinesteraze (< 10 %).
Ingestion of 46 mg occurred in one case; following conservative management the patient fully recovered within 24 hours. 
V enem primeru je bolnik zaužil 46 mg; po konservativnem zdravljenju je v 24 urah popolnoma okreval.
Your doctor will slowly increase your dose depending on how you respond to the treatment. 
• Zdravnik vam bo odmerek počasi zviševal glede na vaš odziv na zdravljenje.
Rivastigmine should not be used during pregnancy unless clearly necessary. 
Rivastigmin se ne sme uporabljati med nosečnostjo, razen če je to nujno potrebno.
Adverse reactions in Table 1 are listed according to MedDRA system organ class and frequency category. 
Neželeni učinki v Tabeli 1 so v skladu z MeDRA razvrščeni po organskih sistemih in pogostnosti.
It readily crosses the blood brain barrier and has an apparent volume of distribution in the range of 1.8 - 2.7 l/kg. 
Rivastigmin hitro prehaja skozi krvno možgansko pregrado, navidezni volumen porazdelitve pa je v območju 1,8 - 2,7 l/kg.
In case of severe vomiting associated with rivastigmine treatment, appropriate dose adjustments as recommended in section 4.2 must be made. 
Pri hudem bruhanju, povezanim z zdravljenjem z rivastigminom, je treba odmerek ustrezno prilagoditi, kot je priporočeno v poglavju 4.2.
Therapy with rivastigmine should only be started if a caregiver is available who will regularly monitor intake of the medicinal product by the patient. 
Zdravljenje z rivastigminom se lahko začne samo, če je na voljo skrbnik, ki bo redno nadzoroval, ali bolnik pravilno jemlje zdravilo.
The most commonly reported adverse reactions are gastrointestinal, including nausea (38 %) and vomiting (23 %), especially during titration. 
Najpogostejše neželene reakcije, o katerih so poročali, so gastrointestinalne, vključno z navzeo (38 %) in bruhanjem (23 %), posebej med titriranjem odmerka.
Usually, the side effects slowly go away as your body gets used to the medicine. 
Običajno neželeni učinki počasi izzvenijo, ko se telo zdravila navadi.
- if you have a low body weight. 
- če imate majhno telesno maso,
Response Measure 
Meritev odziva
Rivastigmine Teva is used for the treatment of memory disorders in patients with Alzheimer's disease. 
Zdravilo Rivastigmine Teva se uporablja za zdravljenje spominskih motenj pri bolnikih z Alzheimerjevo boleznijo.
Due to the known vagotonic effect of cholinesterase inhibitors on heart rate, bradycardia and/or syncope may also occur. 
Glede na znan vagotonični učinek zaviralcev holinesteraze na hitrost srčnega utripa, se lahko pojavita tudi bradikardija in/ali sinkopa.
If any of these apply to you, your doctor may need to monitor you more closely while you are on this medicine. 
Če karkoli od navedenega velja za vas, vas bo morda moral zdravnik med jemanjem zdravila spremljati bolj pozorno.
As a consequence of rivastigmine's interaction with its target enzyme, the increase in bioavailability is about 1.5-fold greater than that expected from the increase in dose. 
Zaradi interakcije rivastigmina s svojim ciljnim encimom, je povečanje biološke uporabnosti približno 1,5krat večje, kot bi bilo pričakovati zaradi povečanja odmerka.
• The signs of Parkinson's disease get worse or getting similar signs - such as stiff muscles, 
• poslabšanje znakov Parkinsonove bolezni ali pojav podobnih znakov - na primer togih mišic ali težav
If after 3 months of maintenance dose treatment the patient's rate of decline in dementia symptoms is not altered favourably, the treatment should be discontinued. 
Če se po 3 mesecih zdravljenja z vzdrževalnim odmerkom stopnja simptomov demence ne spremeni v bolnikovo korist, je treba zdravljenje prekiniti.
Not all pack sizes may be marketed. 
Na tržišču morda ni vseh navedenih pakiranj.
1 Based on ANCOVA with treatment and country as factors and baseline ADAS-Cog as a covariate. 
1 Na podlagi analize kovariance (ANCOVA), pri kateri sta bila zdravljenje in država dejavnika, izhodiščni rezultat ADAS-Cog pa kovariat.
The incidence and severity of adverse reactions generally increase with higher doses. 
Pogostnost in stopnja neželenih učinkov se pri večjih odmerkih na splošno povečata.
Less than 1 % of the administered dose is excreted in the faeces. 
Manj kot 1 % uporabljenega odmerka se izloča z blatom.
Where symptoms have occurred, they have included nausea, vomiting and diarrhoea, hypertension or hallucinations. 
Kadar so se simptomi pojavili, so vključevali navzeo, bruhanje in diarejo, hipertenzijo ali halucinacije.
Rivastigmine 6-12 mg N=379 
Rivastigmin 6-12 mg N = 379
Possible dose adjustments or temporarily stopping treatment can be considered if needed. 
Po potrebi se lahko prilagodi odmerek ali začasno ustavi zdravljenje.
They may respond to a dose reduction. 
Ti bolniki se lahko odzovejo na zmanjšanje odmerka.
In peri/postnatal studies in rats, an increased gestation time was observed. 
V peri- in postnatalnih študijah pri podganah so opazili povečan čas gestacije.
Absolute bioavailability after a 3 mg dose is about 36 % ± 13 %. 
Absolutna biološka uporabnost po 3miligramskem odmerku je približno 36 % ± 13 %.
Therefore, the clinical benefit of rivastigmine should be reassessed on a regular basis, especially for patients treated at doses less than 3 mg twice a day. 
Zato je treba klinično korist rivastigmina ocenjevati redno, zlasti pri bolnikih, ki prejemajo odmerke, manjše od 3 mg dvakrat na dan.
Tell your caregiver that you are taking Rivastigmine Teva. 
• Povejte svojemu negovalcu, da jemljete zdravilo Rivastigmine Teva.
Take Rivastigmine Teva twice a day, in the morning and evening, with food. 
• Zdravilo Rivastigmine Teva jemljite s hrano dvakrat na dan, zjutraj in zvečer.
Inhibition of butyrylcholinesterase activity in CSF of 14 Alzheimer patients treated by rivastigmine was similar to that of AChE. 
Zaviranje aktivnosti butirilholinesteraze v cerebrospinalni tekočini pri 14 bolnikih z Alzheimerjevo boleznijo, ki so prejemali rivastigmin, je bilo podobno kot pri AChE.
Rivastigmine Teva should not be given at the same time as other medicines with similar effects to Rivastigmine Teva. 
Zdravila Rivastigmine Teva se ne sme jemati sočasno z drugimi zdravili, ki imajo podobne učinke kot zdravilo Rivastigmine Teva.
At least 4 points improvement on ADAS-Cog with no worsening on CIBIC-Plus and PDS *p<0.05, **p<0.01, ***p<0.001 
PDS: izboljšanje za vsaj 10 % 26*** Izboljšanje rezultata ADAS-Cog za vsaj 4 točke brez poslabšanja rezultata CIBIC-Plus in PDS *p<0,05, **p<0,01, ***p<0,001
It is not known if rivastigmine is excreted into human milk. 
Ni znano, ali se rivastigmin izloča v mleko pri človeku.
Furthermore, rivastigmine can induce dizziness and somnolence, mainly when initiating treatment or increasing the dose. 
Poleg tega lahko rivastigmin povzroči omotico in somnolenco, predvsem ob začetku zdravljenja ali povečanju odmerka.
Discontinuation should also be considered when evidence of a therapeutic effect is no longer present. 
Zdravljenje je treba prekiniti tudi, ko znakov terapevtskega učinka ni več.
Computerweg 10, 3542 DR Utrecht The Netherlands 
Computerweg 10, 3542 DR Utrecht Nizozemska
Such events appeared to occur particularly after dose increments or high doses of rivastigmine. 
Takšni primeri so se pojavili zlasti po povečanju odmerka ali pri uporabi velikih odmerkov rivastigmina.