natgillin/translations-raw huggingface dataset:
The CHMP was then asked by the European Commission to determine whether there is a need to take specific measures to deal with the consequences of the interaction between strong-opioid modified-release oral products and alcohol.
Evropska komisija je CHMP zaprosila, naj ugotovi, ali je treba sprejeti specifične ukrepe za obravnavanje posledic interakcij med močnimi opioidnimi peroralnimi zdravili s prirejenim sproščanjem in alkoholom.
The assessment within this procedure provided an overview of the modified-release systems used in the European Union in oral opioid products.
Ocena iz tega postopka je omogočila pregled sistemov za prirejeno sproščanje, ki se uporabljajo za peroralna opioidna zdravila v Evropski Uniji.
The Committee is also of the opinion that further minimisations measures would not adequately address the concern.
Odbor tudi meni, da nadaljnji ukrepi za zmanjševanje tveganja ne bi ustrezno obravnavali tega zadržka.
Level III of the WHO scale includes fentanyl, hydromorphone, morphine and oxycodone, however no oral modified-release products containing fentanyl are currently authorised in the EU, as due to a marked first pass effect, oral administration of fentanyl is not feasible.
III. stopnja lestvice SZO vključuje fentanil, hidromorfon, morfin in oksikodon, vendar v EU trenutno ni odobrenih peroralnih zdravil s prirejenim sproščanjem, ki vsebujejo fentanil, saj zaradi učinka prvega prehoda peroralna uporaba fentanila ni možna.
In this respect, it was noted that the in vitro - in vivo correlation is unclear in most cases, and therefore it would be inappropriate to assume a pharmacokinetic interaction.
V zvezi s tem je bilo navedeno, da je v večini primerov korelacija in vitro - in vivo nejasna, zato bi bilo sklepanje o farmakokinetični interakciji neprimerno.
• The Committee is also of the opinion that further risk minimisation measures would not adequately address the concern,
• Odbor tudi meni, da nadaljnji ukrepi za zmanjševanje tveganja ne bi ustrezno obravnavali tega vprašanja.
The Opinion does not provide information on the acceptance criteria to be applied in relation to the clinical significance of pharmacokinetic interactions because there are currently no standard acceptance criteria to be applied in this context.
Mnenje ne daje podatkov o merilih sprejemljivosti, ki bi se morali uporabljati v zvezi s kliničnim pomenom farmakokinetičnih interakcij, saj trenutno ni standardnih meril sprejemljivosti, ki bi se uporabljala v zvezi s tem.
Patients being treated with opioids tend to drink less alcohol than patients who do not use opioids at all.
Bolniki, zdravljeni z opioidi, običajno pijejo manj alkohola kot bolniki, ki opioidov sploh ne uporabljajo.
A similar dissolution study from 2007 however, showed that at 60 minutes the dissolution rate of the reference product (considered by the MAH to be a safe product) in the absence of alcohol was actually higher that the dissolution rate of the competing product presented when exposed to 20% alcohol.
Podobna študija raztapljanja iz leta 2007 pa je pokazala, da je stopnja raztapljanja referenčnega zdravila (imetnik dovoljenja za promet z zdravilom je menil, da je to zdravilo varno) pri 60 minutah v odsotnosti alkohola dejansko višja kot stopnja raztapljanja predstavljenega konkurenčnega zdravila pri izpostavljenosti 20-odstotnemu alkoholu.
For alcohol, the majority of the data available relates to in vitro testing only, and therefore cannot be assumed, for the reasons previously explained, to be directly reproduced in vivo.
Večina razpoložljivih podatkov za alkohol izhaja le iz in vitro testiranja, kar pomeni, da zaradi prej navedenih razlogov ne morejo biti neposredno ponovljeni in vivo.
Therefore, the European Commission requested the CHMP to give its opinion on whether the marketing authorisations for authorised modified-release oral medicinal products of the WHO level III scale for the management of pain (intense sustained pain resistant to previous medications) (containing morphine, oxycodone, fentanyl and hydromorphone) should be maintained, varied, suspended or withdrawn.
Evropska komisija je tako CHMP zaprosila, naj poda mnenje, ali naj se dovoljenja za promet z odobrenimi peroralnimi zdravili s prirejenim sproščanjem III stopnje po lestvici SZO za lajšanje bolečin (močne dolgotrajne bolečine, odporne na predhodna zdravljenja) (ki vsebujejo morfin, oksikodon, fentanil in hidromorfon) ohranijo, spremenijo, začasno prekličejo ali umaknejo.
The advice of the EWP was to consider the worst case scenario, including gastric residence times of 1-2 to hours and potential exposure to high concentrations of alcohol.
Priporočilo delovne skupine za učinkovitost je bilo, da se upošteva najslabši možni scenarij, vključno s časom prisotnosti v želodcu od ene do dveh ur ter možno izpostavljenostjo visokim koncentracijam alkohola.
However, for all of these products, a pharmacodynamic interaction may occur and should be mentioned in the Product information of all products in a consistent manner.
Kljub temu pa se pri vseh teh zdravilih lahko pojavi farmakodinamična interakcija, kar je potrebno na usklajen način omeniti v informacijah o vseh zdravilih.
As not all medicinal products concerned by this review submitted data, the National Competent Authorities should ensure, based on the modified-release mechanism of the products approved in each Member State, that the appropriate actions are taken for individual products.
Ker predloženi podatki za ta pregled ne zadevajo vseh zdravil, morajo pristojni nacionalni organi na podlagi mehanizmov za prirejeno sproščanje zdravil, odobrenih v posamezni državi članici, zagotoviti sprejem ustreznih ukrepov za posamezna zdravila.
While a pharmacodynamic interaction with alcohol may occur irrespective of the formulation, in most cases a pharmacokinetic interaction will not be clinically significant so as to warrant measures beyond the proposed wording for the product information.
Farmakodinamične interakcije z alkoholom se sicer lahko pojavljajo ne glede na formulacijo, v večini primerov pa farmakokinetične interakcije niso klinično pomembne v tej meri, da bi bili potrebni dodatni ukrepi, ki jih predlagano besedilo za informacije o zdravilu ne vključuje.
More than confirming that the generic and originator are bioequivalent, in this review it is important to consider whether the observed in vitro effect constitutes an unacceptable risk for patients.
V tem pregledu je od potrditve biološke enakovrednosti generičnega in originatorskega zdravila pomembneje ugotoviti, ali opaženi in vitro učinek predstavlja nesprejemljivo tveganje za bolnike.
Having considered all the data submitted, it can be concluded that the large majority of modifiedrelease oral opioid products in the European Union do not exhibit a clinically significant interaction with alcohol.
Ob upoštevanju predloženih podatkov se lahko potrdi, da velika večina peroralnih opioidnih zdravil s prirejenim sproščanjem v Evropski uniji ne kaže klinično pomembne interakcije z alkoholom.
In addition, as the medicinal product based on this release-mechanism is intended for once a day dosing, the content of morphine is high and therefore the risk of adverse events following dose-dumping is also higher.
Poleg tega so zdravila, osnovana na takšnem mehanizmu sproščanja, namenjena za uporabo enkrat na dan, vsebnost morfina pa je visoka in zato je nevarnost pojavljanja neželenih učinkov zaradi prekomernega sproščanja prav tako večja.
The issue of additional risk to patients was addressed by CHMP in its initial opinion, and as a consequence a recommendation was adopted to suspend and reformulate the formulations where the interaction was of such magnitude that the products essentially resemble an immediate release formulation (while containing the opioid dose appropriate for a modified release formulation).
Vprašanje dodatnega tveganja za bolnike je CHMP obravnaval v svojem prvotnem mnenju in posledično sprejel priporočilo, da je treba začasno umakniti in spremeniti vse formulacije, pri katerih so bile interakcije tako velike, da je bilo zdravilo v osnovi podobno formulaciji s takojšnjim sproščanjem (vsebovalo pa je odmerek opioida, primeren za formulacijo s prirejenim sproščanjem).
Secondly, because unlike alcohol, SPC information on food interactions will reflect in vivo studies and therefore have clear added value for the prescriber and the patient.
In drugič, ker v nasprotju z alkoholom, podatki v povzetku glavnih značilnosti zdravila o interakcijah s hrano odražajo rezultate in vivo študij in imajo zato jasno dodano vrednost za predpisovalce in bolnike.
Where not possible, the QWP recommended the inclusion of differential wording in the Product Information.
Če to ne bi bilo možno, pa je delovna skupina za kakovost priporočila, da se v informacije o zdravilu vključi drugačno besedilo.
It should be noted that, while the authors of the above mentioned paper go on to conclude that ‘in vitro dissolution may provide evidence regarding the ruggedness of formulations to ingested alcohol', no recommendations are issued to specific products given that ‘…further research is needed to understand the relationship between dosage form, product formulation and configuration and drug release in the presence of ethanol.'
Pri tem pa je treba omeniti, da avtorji prej navedenega dela menijo, da „in vitro raztopine sicer lahko zagotovijo dokaz o odpornosti formulacije na zaužiti alkohol“, vendar pa niso dali nobenih priporočil glede posameznih zdravil, saj so „... potrebne dodatne raziskave, ki bi pojasnile razmerje med obliko odmerjanja, formulacijo zdravila, konfiguracijo in sproščanjem zdravila v prisotnosti etanola“.
This may be further aggravated by the fact that many patients with chronic pain will also suffer from depression.
Dejstvo, da se pri velikem številu bolnikov s kronično bolečino pojavlja tudi depresija, vse le še poslabšuje.
Firstly, the Opinion does not provide any information regarding the acceptance criteria to be applied in relation to the clinical significance of pharmacokinetic interactions with alcohol.
Prvič, mnenje ne vsebuje podatkov o merilih sprejemljivosti, ki jih je treba upoštevati v zvezi s kliničnim pomenom farmakokinetičnih interakcij z alkoholom.
In a limited number of cases, the MAH has also presented the results of in vivo studies and/or a review of adverse event reports which may have been related to the concomitant use of alcohol.
Le v manjšem številu primerov so imetniki dovoljenja za promet z zdravilom predstavili tudi rezultate in vivo študij in/ali pregled poročil o neželenih učinkih, ki bi lahko bili povezani s sočasno uporabo alkohola.
If, however, the modified-release system is influenced by an external factor or substance (such as alcohol), it is possible that a large quantity of the active substance is released in a short timeframe so that it resembles an immediate-release dosage form.
Če pa na sistem s prirejenim sproščanjem vplivajo zunanji dejavniki ali snovi (na primer alkohol), obstaja možnost, da se večja količina zdravilne učinkovine sprosti v krajšem časovnem obdobju, kar bi bilo podobno farmacevtski obliki s takojšnjim sproščanjem.
The anticipated increase in dissolution rate observed for modified-release products is a result of the modified release system being rendered unstable in the presence of alcohol.
Pričakovano povečanje stopnje raztapljanja, opaženo pri zdravilih s prirejenim sproščanjem, je posledica dejstva, da sistemi za prirejeno sproščanje v prisotnosti alkohola postanejo nestabilni.
Fifty-percent of the formulations assessed are affected by alcohol solutions in vitro, but in most cases, the effect of alcohol on the dissolution rate is mild.
Na petdeset odstotkov ovrednotenih formulacij so vplivale alkoholne raztopine in vitro, vendar pa je bil v večini primerov vpliv alkohola na stopnjo raztapljanja blag.
In the context of marketing authorisation procedures for oxycodone-containing products, possible differences in the safety profile of the originator and generic products had been raised concerning the interaction with alcohol.
V kontekstu postopkov za pridobitev dovoljenja za promet z zdravili, ki vsebujejo oksikodon, so bili podani zadržki zaradi možnih razlik v varnostnem profilu med originatorskim in generičnimi zdravili glede interakcije z alkoholom.
The MAH mentioned in his grounds for re-examination a paper by Smith at al (In vitro dissolution of oral modified-release tablets and capsules in ethanolic media, International Journal of Pharmaceutics 398 (2010) 93-96) to illustrate that formulations should not be assumed to be unaffected by alcohol without data being evaluated.
Imetnik dovoljenja za promet z zdravilom je v utemeljitvi zahtevka za ponovni pregled navedel tudi poročilo Smitha et al (In vitro dissolution of oral modified-release tablets and capsules in ethanolic media (In vitro raztapljanje peroralnih tablet in kapsul s prirejenim sproščanjem v etanolnem mediju), International Journal of Pharmaceutics 398 (2010) 93-96), s katerim je želel prikazati, da se brez vrednotenja podatkov ne more sklepati, da alkohol ne učinkuje na formulacije.
According to the data on a competitor product presented by the MAH requesting re-examination, this product starts to exhibit accelerated release of the active substance after approximately 30 min of exposition to alcohol, and is claimed to release 76.5% of the oxycodone dose within one hour of exposure to concentrations of alcohol around 24%.
Podatki o konkurenčnem zdravilu, ki jih je predstavil imetnik dovoljenja za promet z zdravilom, ki je zahteval ponovni pregled, so pokazali, da je pri tem zdravilu prišlo do pospešenega sproščanja zdravilne učinkovine približno 30 minut po izpostavljenosti alkoholu, 76,5 odstotka odmerka oksikodona pa naj bi se sprostilo v eni uri po izpostavljenosti alkoholu s koncentracijo okoli 24 odstotkov.
For all other strong-opioid modified release oral products in the European market (formulations not containing polymethacrylate-triethylcitrate), no significant risk of dose-dumping due to alcohol use was identified.
Pri nobenem drugem močnem opioidnem peroralnem zdravilu s prirejenim sproščanjem na evropskem trgu (formulacije, ki ne vsebujejo polimetakrilata-trietilcitrata) ni bilo ugotovljeno pomembnejše tveganje prekomernega sproščanja zaradi uporabe alkohola.
This is clearly demonstrated by the existing data for one specific product for which the in vitro interaction is significant but where the pharmacokinetic parameters did not differ significantly among subjects taking the product with water or with alcohol (ethylcellulose N-50, methacrylic acid copolymer type C, polyethylene glycol 6000 and diethyl phthalate product).
To je jasno razvidno tudi iz obstoječih podatkov za določeno zdravilo, pri katerem je in vitro interakcija pomembna, farmakokinetični parametri pa se med preiskovanci, ki so zdravilo jemali z vodo ali alkoholom (zdravilo z etilcelulozo N50, kopolimerom metakrilne kisline tipa C, polietilen glikolom 6000 in dietil ftalatom), niso bistveno razlikovali.
• In addition, the Committee considered that the dissolution profile of products containing a polymethacrylate-triethylcitrate coating as modified-release mechanism is significantly affected in the presence of alcohol, leading to an uncontrolled rapid release of the majority of the active substance, and therefore the product exhibits a significant interaction with alcohol with potentially significant clinical effects (e.g. respiratory depression and death),
• Odbor je prav tako ugotovil, da je profil raztapljanja zdravil, ki vsebujejo premaz iz polimetakrilat-trietilcitrata kot mehanizem za prirejeno sproščanje, ob prisotnosti alkohola pomembno spremenjen, kar lahko povzroči nenadzorovano hitro sproščanje večine zdravilne učinkovine, kar pomeni, da zdravilo kaže pomembno interakcijo z alkoholom, pri čemer se lahko pojavijo pomembni klinični učinki (na primer depresija dihanja in smrt).
As a consequence, where accelerated drug release is seen, the EWP's recommendation was for label warnings and risk management strategies to be considered.
Kadar je bilo opaženo pospešeno sproščanje zdravila, je tako delovna skupina za učinkovitost priporočila izdelavo opozoril na ovojnini in strategij za obvladovanje tveganja.
The results of the only study with a morphine product (ethylcellulose N-50, methacrylic acid copolymer type C, polyethylene glycol 6000 and diethyl phthalate formulation) indicate that a relatively high quantity of alcohol has almost no effect in vivo.
Rezultati edine izvedene študije z morfinskim zdravilom (etilceluloza N-50, kopolimer metakrilne kisline tipa C, polietilen glikol 6000 in formulacija dietil ftalata) kažejo, da relativno velika količina alkohola nima skorajda nikakršnega učinka in vivo.
The Committee therefore recommended the amendment of the Marketing Authorisation for which the relevant sections of the Summary of Product Characteristics and Package Leaflet are set out in Annex III.
Odbor je tako priporočil spremembe dovoljenja za promet z zdravilom, za katero so ustrezna poglavja povzetka glavnih značilnosti zdravila in navodila za uporabo navedena v Prilogi III.
It is of note that, in the data presented by the MAH for this competitor product, the most pronounced effect of alcohol is not at the highest alcohol concentrations tested (40%), but between 28%-32%.
Omeniti je treba, da so predstavljeni podatki imetnika dovoljenja za promet z zdravilom o tem konkurenčnem zdravilu pokazali, da je najizrazitejši učinek alkohola pri koncentraciji alkohola med 28 in 32 odstotkov in ne pri največji testirani koncentraciji (40 odstotkov).
It follows from the above that data presented on the in vitro effects of alcohol on the dissolution profile of these products are not necessarily a reliable predictor of in vivo behaviour and therefore recommendations such as suspension and reformulation of products should only be adopted for products for which the in vitro interaction is of such magnitude that the products are considered to pose serious risks to the patients.
Iz zgoraj navedenega izhaja, da predloženi podatki o in vitro učinkih alkohola na profil raztapljanja teh zdravil niso nujno zanesljiv napovednik in vivo delovanja, zato je treba priporočila o začasnem umiku in spremembi zdravil sprejeti samo za tista zdravila, pri katerih se pojavi tako velika in vitro interakcija, da za ta zdravila velja, da predstavljajo resno tveganje za bolnike.
The polymethacrylatetriethylcitrate based formulation is highly sensitive to alcohol with its modified release properties being destroyed shortly after exposure, making it resemble an immediate release formulation.
Formulacija na osnovi polimetakrilat-trietilcitrata je zelo občutljiva za alkohol, njene lastnosti prirejenega sproščanja pa so bile uničene kmalu po njihovi izpostavitvi, zaradi česar je postala podobna formulaciji s takojšnjim sproščanjem.
• The Committee considered all the available data submitted by the MAHs,
• Odbor je upošteval vse razpoložljive podatke, ki so jih predložili imetniki dovoljenja za promet z zdravilom.
• The Committee considered, however, that as a pharmacodynamic interaction with alcohol may occur, the product information of the above mentioned products should describe in a clear and harmonised manner the pharmacodynamic interaction between opioid products and alcohol,
• Odbor je menil, da se farmakodinamična interakcija z alkoholom lahko pojavi, zato mora biti v informacijah o prej navedenih zdravilih na jasen in usklajen način opisana farmakodinamična interakcija med opioidnimi zdravili in alkoholom.
Another study conducted with a hydromorphone formulation based on cellulose acetate 398-10 and Macrogol 3350 formulation confirmed the conclusions of the in vitro studies that the effect of coadministered alcohol on PK parameters is rather limited.
Druga študija, izvedena s formulacijo hidromorfona na osnovi celuloznega acetata 398-10 in formulacijo makrogol 3350, je potrdila ugotovitve in vitro študij, da je vpliv sočasne uporabe alkohola na farmakokinetične dejavnike precej omejen.
An important interaction following alcohol consumption becomes progressively less likely with time due to dilution effect by gastric secretions and saliva, and gastric emptying.
Pomembna interakcija po zaužitju alkohola je po določenem času postopoma manj verjetna zaradi razredčevanja z želodčno kislino in slino ter praznjenjem želodca.
From all the above mentioned considerations, including the limitations of the existing data and the current status of scientific knowledge, it follows that general recommendations for acceptance criteria to be applied in relation to the clinical significance of pharmacokinetic interactions with alcohol can not be determined by the Committee at this time.
Na podlagi zgoraj navedenih zadržkov, vključno z omejitvami obstoječih podatkov in trenutnim stanjem znanstvenega znanja, Odbor trenutno še ne more določiti splošnih priporočil za merila sprejemljivosti, ki naj bi se uporabljala v zvezi s klinično pomembnostjo farmakokinetičnih interakcij z alkoholom.
• The Committee therefore considered that patients exposed to the above mentioned products and concomitant intake of alcohol are at significantly greater risk of developing serious adverse reactions such as respiratory depression and death,
• Odbor je tako ugotovil, da so bolniki, ki so izpostavljeni zgoraj navedenim zdravilom in sočasnemu vnosu alkohola, izpostavljeni bistveno večjemu tveganju, da se pri njih pojavijo hudi neželeni učinki, kot sta depresija dihanja in smrt.
In light of the existing data, including published data on the use of alcohol in patients treated with opioids, the Committee is of the opinion that the current warnings and contraindications are not sufficient to protect patients from the significant alcohol interaction observed with the polymethacrylate- triethylcitrate formulation.
Na podlagi obstoječih podatkov, vključno z objavljenimi podatki o uporabi alkohola pri bolnikih, zdravljenimi z opioidi, Odbor meni, da obstoječa opozorila in kontraindikacije ne zadostujejo za zaščito bolnikov pred pomembno interakcijo z alkoholom, opaženo pri formulaciji s polimetakrilattrietilcitratom.
• The Committee considered that products without a polymethacrylate-triethylcitrate coating as modified-release mechanism do not suggest a significant interaction with alcohol considered to be harmful under normal conditions of use,
• Odbor je menil, da zdravila brez premaza iz polimetakrilat-trietilcitrata kot mehanizma za prirejeno sproščanje ne kažejo pomembne interakcije z alkoholom, ki bi bila pod normalnimi pogoji uporabe škodljiva.
While most products already contain warnings and references to this interaction in the SPC, the wording should be harmonised to ensure the same level of awareness.
V povzetkih glavnih značilnosti večine teh zdravil so že navedena opozorila in navodila v zvezi s to interakcijo, vendar je besedilo potrebno uskladiti in tako zagotoviti enako raven osveščenosti.
The in vitro data showed a release of 80% of the drug within 15 minutes in 20% of alcohol solution.
Podatki in vitro preiskave so pokazali, da se je 80 odstotkov zdravila sprostilo v manj kot 15 minutah v 20 odstotkih alkoholne raztopine.
Having assessed the detailed grounds for re-examination provided by the MAH, the rapporteurs assessment reports, the conclusions from the ad hoc expert meeting together with the MAH's expressed concerns on the conclusions of the ad hoc expert meeting and all the information submitted during the referral procedure, the CHMP discussed each one of the grounds submitted:
Po oceni podrobne utemeljitve zahtevka za ponovni pregled, ki jo predložil imetnik dovoljenja za promet z zdravilom, poročila o oceni poročevalcev, sklepov z ad hoc zasedanja strokovnjakov in izraženih zadržkov imetnika dovoljenja za promet z zdravilom glede sklepov ad hoc zasedanja strokovnjakov ter vseh podatkov, predloženih v napotitvenem postopku, je CHMP odgovoril na vsako točko predložene utemeljitve:
Grounds for amendment of the summaries of product characteristics, package leaflets and labelling
Podlaga za dopolnilo povzetkov glavnih značilnosti zdravila,navodil za uporabo in označevanja