natgillin/translations-raw huggingface dataset:
The major concern raised by France and the Netherlands could not be solved during the CMD(h) referral and the issue was therefore referred to the Committee for Medicinal Products for Human Use (CHMP).
Glavnega pomisleka, ki sta ga izpostavili Francija in Nizozemska, med napotitvenim postopkom skupine CMD(h) ni bilo mogoče razrešiti, zato je bila zadeva posredovana Odboru za zdravila za uporabo v humani medicini (CHMP).
It is acknowledged that these results were outside the standard range of 80 - 125%; however these were within the wider acceptance criteria of 70 - 143% which may be used for highly variable drugs.
Upoštevali so, da so bili ti rezultati zunaj standardnega razpona 80-125 %; vendar so bili znotraj širših meril sprejemljivosti 70-143 %, ki se lahko uporabijo za zelo variabilna zdravila.
The decentralised procedure was closed on day 210, with most of the CMSs agreeing with the conclusions of the reference Member State (RMS)'s assessment report except France and the Netherlands which raised a potential serious risk to public health (PSRPH).
Decentralizirani postopek se je končal na 210. dan, ko je večina zadevnih držav članic soglašala z zaključki poročila o oceni referenčne države članice z izjemo Francije in Nizozemske, ki sta izrazili zaskrbljenost zaradi možnega resnega tveganja za javno zdravje (PSRPH).
The applicant provided literature references which showed that for the action of Didanosine, AUC is the most important parameter9,10,11,12,13.
Predlagatelj je predložil reference iz literature, ki so pokazale, da je za delovanje zdravila Didanosine najpomembnejši parameter vrednost AUC9,10,11,12,13.
Considering this, the sample size that may be required to meet the standard bio-equivalence criteria would be as high as 232 subjects to obtain power of at least 80%.
Glede na navedeno bi morala biti velikost vzorca, potrebna za izpolnjevanje standardnih meril biološke enakovrednosti, kar 232 preiskovancev, da bi dobili moč vsaj 80 %.
• Clinical significance of Cmax with Didanosine
• Klinični pomen vrednosti Cmax za zdravilo Didanosine
• The Committee reviewed all the data submitted by the applicant in order to support the bioequivalence between Didanosine and associated names and the reference product.
• Odbor je pregledal vse podatke, ki jih je predlagatelj predložil v podporo biološki enakovrednosti med zdravilom Didanosine in povezanimi imeni ter referenčnim zdravilom;
Irrespective of whether Didanosine is taken with or without food, the virological response is based on the total drug exposure.
Ne glede na to, ali se zdravilo Didanosine zaužije s hrano ali brez, virološki odziv temelji na skupni izpostavljenosti zdravilu.
The application for Didanosine and associated names was considered under Article 10.3 of Directive 2001/83/EC in all Concerned Members States (CMSs).
Vloga za zdravilo Didanosine in povezana imena je bila obravnavana v členu 10.3 Direktive 2001/83/ES v vseh zadevnih državah članicah.
A referral was thus triggered at the Co-ordination Group for Mutual Recognition and Decentralised ProceduresHuman (CMD(h)).
Napotitveni postopek je bil zato sprožen pri usklajevalni skupini za postopek z medsebojnim priznavanjem in decentralizirani postopek - zdravila za uporabo v humani medicini (CMD(h)).
However, the observed effect of food is lower and the Committee is of the opinion that this is not clinically relevant based on considerations relating to the mechanism of action and, in particular, that Didanosine and associated names is to be administrated on an empty stomach.
Vendar pa je zabeleženi vpliv hrane nižji in Odbor meni, da to ni klinično pomembno na podlagi premislekov v zvezi z mehanizmom delovanja, zlasti ker je zdravilo Didanosine in povezana imena namenjeno zaužitju na prazen želodec;
Schrader S et al.
Lopez JC et al.
In addition, the objecting Members States considered that the arguments provided by the applicant did not sufficiently address the consequences of the difference observed in didanosine pharmacokinetics in the fed state between test and reference products.
Poleg tega sta državi članici, ki sta izrazili pomisleke, menili, da argumenti, ki jih je predložil predlagatelj, niso zadostno obravnavali posledic razlik, ki so jih opazili pri farmakokinetiki didanozina pri zaužitju po obroku med testnim in referenčnim zdravilom.
The applicant claimed that differences in plasma concentrations of didanosine are not of clinical relevance as such since it may not result in changes in the intracellular triphosphate concentrations.
Predlagatelj je trdil, da razlike v koncentracijah didanozina v plazmi kot take niso klinično pomembne, saj ne povzročijo nujno sprememb znotrajceličnih koncentracij trifosfata.
The administration of the reference product with a high fat meal significantly decreases the AUC (19%) and Cmax (46%) of didanosine.
Zaužitje referenčnega zdravila z zelo mastnim obrokom močno zmanjša vrednosti AUC (19 %) in Cmax (46 %) didanozina.
the CHMP has recommended the granting of the marketing authorisations 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 for Didanosine and associated names (see Annex I).
je odbor CHMP priporočil odobritev dovoljenja za promet z zdravilom, katerega povzetek glavnih značilnosti zdravila, označevanje in navodilo za uporabo ostanejo enaki kot končne različice, pripravljene med postopkom usklajevalne skupine, kot je navedeno v Prilogi III za zdravilo Didanosine in povezana imena (glejte Prilogo I).
Comparison of HIV RNA suppression produced by triple regimens containing either didanosine enteric-coated or didanosine tablet formulations each administered once daily.
Schrader S et al. Comparison of HIV RNA suppression produced by triple regimens containing either didanosine enteric-coated or didanosine tablet formulations each administered once daily.
This is attributed to the delay in absorption rate of enteric coated formulation which is reflected in the Tmax which is about 2 hours for the enteric coated formulation compared to 0.67 hours for the buffered tablet.
To je posledica zakasnitve stopnje absorpcije enterično obložene formulacije, kar odraža Tmax, ki znaša približno 2 uri za enterično obloženo formulacijo v primerjavi z 0,67 ure za pufrano tableto.
Didanosine and associated names is indicated in combination with other antiretroviral drugs for the treatment of HIV-1 infected patients.
Didanozin in povezana imena je indiciran v kombinaciji z drugimi protiretrovirusnimi zdravili za zdravljenje bolnikov, okuženih z virusom HIV-1.
Therefore, it is considered that the fact that both formulations have been used for the same indications and at similar doses suggests that AUC is more relevant for ensuring efficacy of didanosine in antiviral therapy, and the changes in Cmax are unlikely to compromise antiviral efficacy.
Zato velja, da dejstvo, da sta bili obe formulaciji uporabljeni za enake indikacije in pri podobnih odmerkih, nakazuje, da je vrednost AUC pomembnejša za zagotovitev učinkovitosti didanozina pri protivirusni terapiji, in da spremembe vrednosti Cmax najverjetneje ne bodo poslabšale protivirusne učinkovitosti.
Didanosine and associated names (Gastro-resistant capsules 400 mg) was compared to the reference product Videx EC (Gastro-resistant capsules 400 mg) in 60 healthy adults under fasting conditions.
Zdravilo Didanosine in povezana imena (gastrorezistentne kapsule 400 mg) so primerjali z referenčnim zdravilom Videx EC (gastrorezistentne kapsule 400 mg) pri 60 zdravih odraslih pri zaužitju na tešče.
Since the product is to be administrated at least 2 hours before or after food intake, it is unlikely that the product ingested will be exposed to in vivo conditions, prevailing under fed state.
Ker je treba zdravilo vzeti vsaj 2 uri pred obrokom oz. 2 uri po njem, je malo verjetno, da bo zaužito zdravilo izpostavljeno pogojem in-vivo, ki prevladujejo pri zaužitju po obroku.
Both studies were carried out using open label, randomised, two treatment, two sequence, two period, single dose cross-over design.
Obe študiji sta bili izvedeni z odprto, randomizirano, enoodmerno navzkrižno zasnovo z dvema oblikama zdravljenja, dvema zaporedjema in dvema fazama.
During the decentralised procedure France and the Netherlands expressed the opinion that bioequivalence had not been demonstrated in the fed conditions as Cmax was outside the 80-125% acceptability limits1.
Med decentraliziranim postopkom sta Francija in Nizozemska izrazili mnenje, da biološka enakovrednost ni bila dokazana pri zaužitju po obroku, saj je bila vrednost Cmax zunaj meja sprejemljivosti 80−125 %1.
Didanosine (2', 3'-dideoxyinosine) is an inhibitor of the in vitro replication of human immunodeficiency virus (HIV) in cultured human cells and cell lines.
Didanozin (2', 3'-dideoksinozin) je zaviralec in vitro replikacije virusa humane imunske pomanjkljivosti (HIV) v gojenih človeških celicah in celičnih linijah.
• The Committee noted that in the fed study, both formulations were subject to a food effect reducing plasma concentrations.
• Odbor je zabeležil, da se je v študiji pri zaužitju po obroku pri obeh formulacijah pojavilo zmanjšanje koncentracij v plazmi zaradi hrane.
The Applicant claimed that the significant decrease observed under fed conditions for Cmax for the test product (90% CI outside the standard range) may be attributed to high inter-individual variability with respect to Cmax which was 36% in the study conducted under fed conditions.
Predlagatelj je trdil, da je pomembno zmanjšanje vrednosti Cmax, ki so ga opazili pri zaužitju po obroku za testno zdravilo (90-odstotni interval zaupanja zunaj standardnega razpona), mogoče pripisati visoki interindividualni variabilnosti glede Cmax, ki je bila v študiji, izvedeni pri zaužitju po obroku, 36 %.
This observation is in line with the results presented in the current application where AUC and Cmax of the test product significantly decrease under fed conditions.
Ta ugotovitev je v skladu z rezultati, predstavljenimi v trenutni vlogi, kjer se vrednosti AUC in Cmax testnega zdravila močno zmanjšata pri zaužitju po obroku.
The main purpose of conducting bioequivalence fed study is to exclude food related effects, such as dose-dumping (in particular for gastro-resistant formulations) or failure of protection from acid mediated degradation in the stomach.
Glavni namen izvajanja študije biološke enakovrednosti pri zaužitju po obroku je izločiti vplive, povezane s hrano, kot so sprostitev celotnega odmerka naenkrat (zlasti za gastrorezistentne formulacije) ali odpoved zaščite pred s kislino povzročeno degradacijo v želodcu.
Of note, bioequivalence in fasted state is considered to be the most important as this product is intended to be taken on an empty stomach.
Upoštevati je treba še, da kot najpomembnejša šteje biološka enakovrednost pri zaužitju na tešče, saj je to zdravilo namenjeno zaužitju na prazen želodec.
• Observed food effect for test and reference products As per the current recommendations for modified release formulations1,2, bioequivalence studies in fasted and fed conditions are required.
• Opažen vpliv hrane na testno in referenčno zdravilo V skladu s trenutnimi priporočili za formulacije s prirejenim sproščanjem 1,2 je treba predložiti študije biološke enakovrednosti pri zaužitju na tešče in po obroku.
In order to demonstrate the safety and efficacy of Didanosine and associated names in combination with other antiretroviral drugs in the treatment of HIV-1 infected patients, the application dossier was based on two single dose bioequivalence studies, one under fasting state and one under fed state.
Da bi dokazali varnost in učinkovitost zdravila Didanosine in povezanih imen v kombinaciji z drugimi protiretrovirusnimi zdravili pri zdravljenju bolnikov, okuženih z virusom HIV-1, je dokumentacija vloge temeljila na dveh enoodmernih študijah biološke enakovrednosti, eno pri zaužitju na tešče in drugo pri zaužitju po obroku.
The pharmacokinetics data reveals that the plasma concentration (Cmax) obtained from enteric-coated capsule formulation of didanosine is about 40% lower as compared to the buffered tablet formulation.
Farmakokinetični podatki kažejo, da so koncentracije v plazmi (Cmax), pridobljene iz didanozina v obliki enterično obložene kapsule, približno 40 % nižje v primerjavi z didanozinom v obliki pufrane tablete.
The Committee acknowledged that the conventional criterion for bioequivalence for maximum plasma concentration (Cmax) was outside the 80-125% acceptability limits.
Odbor je upošteval, da je bilo konvencionalno merilo biološke enakovrednosti za največjo koncentracijo v plazmi (Cmax) zunaj meja sprejemljivosti 80−125 %.
• The Committee is of the opinion that bioequivalence has been demonstrated under fasting conditions which is the recommended state for administration of didanosine.
• Odbor meni, da je bila biološka enakovrednost dokazana pri zaužitju na tešče, kar se tudi priporoča za zaužite didanozina;
1 Note for Guidance on the investigation of bioavailability and bioequivalence (EMA/CPMP/EWP/QWP/1401/98) 2 Guideline on the pharmacokinetic and clinical evaluation of modified release dosage forms
1 Navodila o raziskovanju biološke razpoložljivosti in biološke enakovrednosti (EMA/CPMP/EWP/QWP/1401/98) 2 Navodila o farmakokinetičnem in kliničnem vrednotenju formulacij odmerkov s prirejenim sproščanjem (EMA/CPMP/EWP/280/96/Corr1)
Pharmacokinetics studies conducted on Didanosine formulations reveal that administration of the product with food or immediately after food results in decreased in vivo availability of the drug.
V farmakokinetičnih študijah formulacij zdravila Didanosine so ugotovili, da zaužitje zdravila s hrano ali takoj po obroku zmanjša in-vivo razpoložljivost zdravila.
didanosine in treatment of HIV infecting were conducted using buffered tablets3,4,5,6,7,8.
V začetnih kliničnih preskušanjih za dokaz učinkovitosti didanozina pri zdravljenju bolnikov, okuženih z virusom HIV, so uporabljali pufrane tablete3,4,5,6,7,8.
Didanosine has to be first converted intracellularly to its active metabolite ddATP (responsible for antiviral activity) which has a significantly longer intracellular half-life (about 43 hours) as compared with plasma half-life of didanosine.
Didanozin se mora najprej pretvoriti znotrajcelično v aktivni presnovek ddATP (odgovoren za protivirusno aktivnost), ki ima veliko daljši znotrajcelični razpolovni čas (približno 43 ur) od razpolovnega časa didanozina v plazmi.
Didanosine is intended to be administrated on en empty stomach as stated in the proposed Summary of Product Characteristics (SmPC): “Didanosine absorption is reduced in the presence of food, and hence Didanosine gastro-resistant capsules should be administrated on an empty stomach (at least 2 hours before or 2 hours after a meal)”.
• Priporočila za odmerjanje didanozina Didanozin je namenjen zaužitju na prazen želodec, kot je navedeno v predlaganem povzetku glavnih značilnosti zdravila: „Ker se absorpcija didanozina v prisotnosti hrane zmanjša, je treba gastrorezistentne kapsule zdravila Didanosine zaužiti na prazen želodec (vsaj 2 uri pred obrokom oz. 2 uri po njem)“.
Background
Podlaga
In viral nucleic acid replication, incorporation of this 2', 3'-dideoxynucleoside prevents chain extension, and thereby inhibits viral replication.
Med replikacijo virusne nukleinske kisline vgradnja tega 2', 3'-dideoksinukleozida prepreči podaljševanje verige in tako zavre replikacijo virusa.
After didanosine enters the cell, it is enzymatically converted to dideoxyadenosine-triphosphate (ddATP), its active metabolite.
Po vstopu v celico se didanozin encimsko pretvori v dideoksiadenozin-trifosfat (ddATP), ki je njegov aktivni presnovek.
The presented data does not give evidence of in vivo dose-dumping from the formulation under fed conditions.
Predstavljeni podatki ne dokazujejo in-vivo sprostitve celotnega odmerka naenkrat iz formulacij pri zaužitju po obroku.
In addition, ddATP inhibits HIV-reverse transcriptase by competing with deoxyadenosine-triphosphate (dATP) for binding to the enzyme's active site, preventing proviral DNA synthesis.
Poleg tega ddATP zavre reverzno transkriptazo HIV, ker z deoksiadenozin-trifosfatom (dATP) tekmuje za vezavo na aktivno mesto encima, in tako prepreči sintezo provirusne DNK.
In the fed study, the results were satisfactory in terms of extent of absorption (i.e. AUC) with 90% CI within standard range of 80.00 - 125.00%.
V študiji pri zaužitju po obroku so bili rezultati glede obsega absorpcije (tj. AUC) zadovoljivi, z 90odstotnim intervalom zaupanja znotraj standardnega razpona 80,00-125,00 %.
Hence, both test and reference products can be considered as having similar food effect in terms of reduction in Cmax and AUC.
Zato je mogoče za testno in tudi za referenčno zdravilo zaključiti, da obstaja pri obeh podoben vpliv hrane kar zadeva zmanjšanje vrednosti Cmax in AUC.
The bioequivalence studies confirmed that dose dumping did not occur with Didanosine and associated names.
Študije biološke enakovrednosti so potrdile, da pri zdravilu Didanosine in povezanih imenih ni prišlo do sprostitve celotnega odmerka naenkrat.
The fed study was conducted during an extended clock-stop.
Študija pri zaužitju po obroku je bila izvedena med podaljšanim obdobjem od napotitve na zdravljenje do prvega prejetega dokončnega zdravljenja.
The results were satisfactory in terms of extent of absorption (i.e. AUC).
Kar zadeva obseg absorpcije (tj. vrednost AUC) so bili rezultati zadovoljivi.
The primary pharmacokinetic parameters (Cmax and AUC) were satisfactory in the fasting study with the 90% confidence interval (CI) falling within the standard criteria of 80.00 - 125.00%.
Rezultati študij biološke enakovrednosti V študiji pri zaužitju na tešče so bili primarni farmakokinetični parametri (Cmax in AUC) zadovoljivi, z 90-odstotnim intervalom zaupanja znotraj standardnih meril 80,00-125,00 %.
Therefore, for both the test and the reference product in the fed state the absorption of didanosine decreases which indicate that both products possess similar food effect in terms of reduction in Cmax and AUC with no evidence of dose-dumping.
Absorpcija didanozina se zato pri testnem in tudi pri referenčnem zdravilu pri zaužitju po obroku zmanjša, kar označuje, da je vpliv hrane pri obeh zdravilih podoben kar zadeva zmanjšanje vrednosti Cmax in AUC brez dokaza o sprostitvi celotnega odmerka naenkrat.
In the current application, the AUC under both fasted and fed conditions was within the acceptance criteria of 80
V trenutni vlogi je bila vrednost AUC pri zaužitju na tešče in tudi pri zaužitju po obroku znotraj meril sprejemljivosti 80−125 %.
Pharmaceutical Form Route of Administration
Številka EU Izmišljeno ime jakost farmacevtska oblika pot uporabe ovojnina vsebina (koncentracija) velikost pakiranja
This summary was last updated in 10-2007.
Ta povzetek je bil nazadnje posodobljen 10-2007.
The European Commission granted a marketing authorisation valid throughout the EU for Velosulin to Novo Nordisk A/S on 7 October 2002.
Evropska Komisija je dovoljenje za promet z zdravilom Velosulin, veljavno po vsej Evropski uniji, odobrila družbi Novo Nordisk A/S dne 7. oktobra 2002.
Other information about Velosulin:
Druge informacije o zdravilu Velosulin:
EUROPEAN PUBLIC ASSESSMENT REPORT (EPAR) VELOSULIN EPAR summary for the public
EVROPSKO JAVNO POROČILO O OCENI ZDRAVILA (EPAR) VELOSULIN Povzetek EPAR za javnost
By controlling the blood glucose, the symptoms and complications of diabetes are reduced.
Z nadzorovanjem sladkorja v krvi se zmanjšajo simptomi in zapleti, povezani s sladkorno boleznijo.
What benefit has Velosulin shown during the studies?
Kakšne koristi je zdravilo Velosulin izkazalo med raziskavami?
Velosulin was effective for both type 1 and type 2 diabetes.
Zdravilo Velosulin se je izkazalo za učinkovito tako pri sladkorni bolezni tipa 1 kot tudi tipa 2.
The Committee for Medicinal products for Human Use (CHMP) decided that Velosulin's benefits are greater than its risks for the treatment of diabetes.
Odbor za zdravila za uporabo v humani medicini (CHMP) je odločil, da so koristi zdravila Velosulin pri zdravljenju sladkorne bolezni večje od z njim povezanih tveganj.
What is the risk associated with Velosulin?
Kakšna tveganja so povezana z zdravilom Velosulin?
The studies measured the level of fasting blood sugar or a substance in the blood called glycosylated haemoglobin (HbA1c), which gives an indication of how well the blood glucose is controlled.
V raziskavah so merili raven sladkorja v krvi na tešče ali tiste snovi v krvi (glikoziliranega hemoglobina, HbA1c), ki kaže, kako dobro je raven sladkorja v krvi nadzorovana.
Velosulin should not be used in people who may be hypersensitive (allergic) to insulin human (rDNA) or to any of the other ingredients.
Zdravila Velosulin ne smejo uporabljati osebe, ki utegnejo biti preobčutljive za (alergične na) humani insulin (rDNA) ali katerokoli drugo sestavino zdravila.
The studies used to support Velosulin are those that have been used to support Actrapid, another insulin approved in the European Union (EU).
Raziskave, ki so podprle uporabo zdravila Velosulin so iste kot za podporo uporabi zdravila Actrapid, še enega insulina, ki je odobren v EU.
The replacement insulin acts in same way as naturally produced insulin and helps glucose to enter cells from the blood.
Nadomestni insulin deluje na enak način kot naravno proizveden insulin, ter omogoča, da lahko glukoza vstopi iz krvi v celico.
Diabetes is a disease in which the body does not produce enough insulin to control the blood glucose.
Sladkorna bolezen je bolezen, pri kateri telo ne tvori dovolj insulina za uravnavanje sladkorja v krvi.
Velosulin is used to treat patients with diabetes.
Velosulin se uporablja za zdravljenje sladkorne bolezni.
The Committee recommended that Velosulin be given marketing authorisation.
Zato je priporočil, da se za zdravilo Velosulin podeli dovoljenje za promet z zdravilom.
Velosulin has also been studied used in an insulin pump.
Zdravilo Velosulin je bilo raziskano tudi uporabljeno v insulinski črpalki.
Why has Velosulin been approved?
Zakaj je bilo zdravilo Velosulin odobreno?
Velosulin led to a decrease in the level of HbA1c, indicating that blood glucose levels had been controlled to a similar level to that seen with the other human insulin.
Z uporabo zdravila Velosulin se je znižala raven HbA1c, kar kaže na to, da je bila raven sladkorja v krvi vzdrževana na podobnih ravneh kot pri uporabi drugih vrst humanega insulina.
Velosulin is a replacement insulin that is identical to the insulin made by the pancreas.
Velosulin je nadomestni insulin, ki je enak insulinu, ki ga proizvaja trebušna slinavka.
As with all insulins, Velosulin may cause hypoglycaemia (low blood glucose).
Zdravilo Velosulin lahko povzroči hipoglikemijo (nizko raven glukoze v krvi).
Velosulin is intended for continuous subcutaneous infusion (under the skin) using an insulin infusion pump.
Zdravilo Velosulin je namenjeno za stalno subkutano (podkožno) infuzijo z uporabo insulinske infuzijske črpalke.
The solution of insulin in Velosulin is specially prepared to make it stable for the duration of administration in an infusion pump.
Raztopina insulina v zdravilu Velosulin je pripravljena tako, da ostane stabilna ves čas trajanja dajanja v infuzijski črpalki.
Velosulin may also be injected into a vein or given subcutaneously by injection.
Velosulin je mogoče dati tudi v intravenski ali subkutani injekciji.
The full EPAR for Velosulin is available here.
Celotno Evropsko javno poročilo o oceni zdravila (EPAR) za zdravilo Velosulin je na voljo tukaj.
Velosulin is a fast-acting insulin and may be used with longer-acting insulin products.
Velosulin je hitrodelujoč insulin in se lahko uporablja v kombinaciji z insulinom z daljšim delovanjem.
The patient's blood glucose (sugar) should be tested regularly to find the lowest effective dose.
Za določitev najnižjega učinkovitega odmerka je potrebno redno spremljati raven sladkorja v krvi bolnika.
It contains the active substance insulin human (rDNA).
Zdravilo Velosulin vsebuje zdravilno učinkovino humani insulin (rDNA).