natgillin/translations-raw huggingface dataset:
The Package Leaflet amendments include a note on increasing the dosage of Alvesco up to 640 micrograms/day, delivered as 320 micrograms twice daily, for a short period in patients who experience a worsening of their asthma symptoms.
Spremembe navodil za uporabo vključujejo navodilo glede kratkoročnega povečanja odmerka zdravila Alvesco na 640 mikrogramov/dan v obliki dveh dnevnih odmerkov po 320 mikrogramov pri bolnikih, pri katerih je prišlo do poslabšanja simptomov astme.
The valid Summary of Product Characteristics is the final version achieved during the Coordination group procedure with the following amendments:
Veljavni povzetek glavnih značilnosti zdravila je končna različica pripravljena v skupini za koordiniranje s sledečimi dopolnili:
The recommended dose of Alvesco is 160 micrograms once daily, which leads to asthma control in the majority of patients.
Priporočeni odmerek zdravila Alvesco je 160 mikrogramov enkrat dnevno, kar omogoča nadzor astme pri večini bolnikov.
ANNEX II SCIENTIFIC CONCLUSIONS AND GROUNDS FOR AMENDMENT OF THE SUMMARY(IES) OF PRODUCT CHARACTERISTICS, LABELLING AND PACKAGE LEAFLET PRESENTED BY THE EMEA
DODATEK II ZNANSTVENI ZAKLJUČKI IN PODLAGA ZA DOPOLNILO POVZETKA GLAVNIH ZNAČILNOSTI ZDRAVILA, OZNAČEVANJA IN NAVODILA ZA UPORABO, KI JIH JE PREDSTAVILA EVROPSKA AGENCIJA ZA ZDRAVILA
- The proposed wording for Section 4.2 of the SPC at the end of CMDh procedure has been amended to reflect that in severe asthmatics, a 12 week study has shown that a dose of 640µg/d (given 320µg/d twice daily) has demonstrated a reduction in the frequency of exacerbations but without an improvement in lung function.
- predlagano besedilo poglavja 4.2 povzetka glavnih značilnosti zdravila je bilo ob zaključku postopka v okviru CMDh dopolnjeno tako, da odraža ugotovitev iz 12-tedenske študije, da je pri hudih astmatikih odmerek 640 µg/dan (v obliki dveh odmerkov po 320 µg na dan) vplival na zmanjšanje pogostosti izbruhov, vendar ni izboljšal funkcije pljuč;
The valid package leaflet is the final version achieved during the Coordination group procedure with the following amendments:
Veljavno navodilo za uporabo je končna različica pripravljena v skupini za koordiniranje s sledečimi dopolnili:
A study powered to show a statistically significant difference between all doses, is considered to be the most adequate from a statistical and clinical point of view The trial proposed (referred to as Scenario B) should generate all the information needed by the applicant in order to submit a variation to Section 4.2 of the SPC which would include a recommendation to use higher doses of ciclesonide as proposed by the MAH.
Predlagana študija (imenovana scenarij B) bo predvidoma zagotovila vse informacije, ki jih vlagatelj potrebuje za predložitev spremembe poglavja 4.2 povzetka glavnih značilnosti zdravila, ki bi naj vključevalo priporočilo za uporabo večjih odmerkov ciklesonida, v skladu s predlogom imetnika dovoljenja za promet z zdravilom.
• The recommended dose of Alvesco is 160 micrograms once daily, which leads to asthma control in the majority of patients.
• Priporočen odmerek zdravila Alvesco je 160 mikrogramov enkrat dnevno, kar pri večini bolnikov vodi do obvladovanja astme.
However in severe asthmatics, a 12 week study has shown that a dose of 640 micrograms/day (given 320 micrograms twice daily) has demonstrated a reduction in the frequency of exacerbations but without an improvement in lung function (see section 5.1).
Vendar je pri hudih astmatikih 12 tedenska študija pokazala, da je odmerek 640 mikrogramov/dan (odmerjen dvakrat dnevno po 320 mikrogramov) privedel do znižanja pogostnosti poslabšanj, toda brez izboljšanja pljučne funkcije (glejte poglavje 5.1).
The proposed wording of the Package Leaflet at the end of the CMDh was also modified to be in line with the amendments to the SPC.
Predlagano besedilo navodila za uporabo je bilo ob zaključku postopka v okviru CMDh spremenjeno v skladu z dopolnitvami povzetka glavnih značilnosti zdravila.
HOW TO USE ALVESCO
Kako uporabljati zdravilo Alvesco
Immediate or delayed hypersensitivity reactions such swelling of lips, tongue and throat (angioedema).
Zelo redki neželeni učinki (pojavijo se pri manj kot enem od 10.000 bolnikov): Takojšnje ali zapoznele preobčutljivostne reakcije kot je otekanje ustnic, jezika in grla (angioedem).
GROUNDS FOR AMENDMENT OF THE SUMMARY OF PRODUCT CHARACTERISTICS, LABELLING AND PACKAGE LEAFLET
PODLAGA ZA DOPOLNITEV POVZETKA GLAVNIH ZNAČILNOSTI ZDRAVILA, OZNAČEVANJA IN NAVODILA ZA UPORABO
However in severe asthmatics, a 12 week study has shown that a dose of 640µg/d (given 320µg/d twice daily) has demonstrated a reduction in the frequency of exacerbations but without an improvement in lung function (see section 5.1).
Vendar pa je 12-tedenska študija pokazala, da je pri hudih astmatikih odmerek 640 µg/dan (v obliki dveh dnevnih odmerkov po 320 µg) privedel do zmanjšanja pogostosti izbruhov, vendar ni izboljšal funkcije pljuč (glejte poglavje 5.1).
ANNEX III AMENDMENTS TO THE SUMMARY OF PRODUCT CHARACTERISTICS, LABELLING AND PACKAGE LEAFLET
DODATEK III DOPOLNILA K POVZETKU GLAVNIH ZNAČILNOSTI ZDRAVILA, OZNAČEVANJU IN NAVODILU ZA UPORABO
please tell your doctor or pharmacist.
Če ste negotovi, se posvetujte z zdravnikom ali s farmacevtom.
HOW TO STORE ALVESCO
Shranjevanje zdravila Alvesco
Treatment-related adverse events were seen in 3.8% and 5% of patients treated with 160 or 640 micrograms per day of ciclesonide respectively.
Neželene učinke v povezavi z zdravljenjem so opazili pri 3,8% bolnikov, ki so bili zdravljeni s 160 mikrogrami ciklesonida na dan ter pri 5% bolnikov zdravljenih s 640 mikrogrami ciklesonida na dan. Raziskava, kjer bi primerjali dnevne odmerke 160 mikrogramov, 320 mikrogramov in 640 mikrogramov pri bolnikih s hudo astmo, ni bila izvedena.
Always use this medicine exactly as your doctor has told you.
Pri uporabi tega zdravila natančno upoštevajte zdravnikova navodila.
AMENDMENTS TO BE INCLUDED IN THE RELEVANT SECTIONS OF THE PACKAGE LEAFLET
DOPOLNILA, KI NAJ SE VKLJUČIJO V ODGOVARJAJOČA POGLAVJA NAVODILA ZA UPORABO
Marketing Authorisation Holder
Država članica Imetnik dovoljenja za promet z zdravilom
PACKAGE LEAFLET: INFORMATION FOR THE USER Alvesco 40, 80 and 160 micrograms pressurised inhalation, solution Ciclesonide
Alvesco 40, 80 in 160 µg inhalacijska raztopina pod tlakom Ciklesonid
ANNEX
DODATEK
The monitoring of NO2 formation
• Nadzor nastajanja NO2
Educational material for Healthcare Professionals
• Izobraževalni material za zdravstvene delavce.
The educational material should be a pocket size guide that includes information on the following key elements:
Izobraževalni material naj bo vodič žepne velikosti, ki vključuje informacije o naslednjih ključnih elementih:
The monitoring of Methaemoglobin level
• Nadzor ravni methemoglobina
CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND EFFECTIVE USE OF THE MEDICINAL PRODUCT TO BE IMPLEMENTED BY THE MEMBER STATES
POGOJI ALI OMEJITVE V ZVEZI Z VARNO IN UČINKOVITO UPORABO ZDRAVILA, KI MORAJO BITI IZVEDENI V DRŽAVAH ČLANICAH
The Marketing Authorisation Holder (MAH) should ensure that, at launch of the new indication, all Healthcare Professionals who are expected to use and/or prescribe INOmax as part of the treatment of peri- or post- operative pulmonary hypertension in adults and children in conjunction to heart surgery are provided with an Educational pack.
• Imetnik dovoljenja za promet z zdravilom (MAH) mora zagotoviti, da ob uvedbi nove indikacije vsi zdravstveni delavci, za katere se pričakuje, da bodo uporabljali in/ali predpisovali zdravilo INOmax v okviru zdravljenja pred- ali pooperativne pljučne hipertenzije pri odraslih in otrocih, povezane s srčnim kirurškim posegom, dobijo gradivo za izobraževanje.
The risk of rebound effect and the precautions to take when discontinuing the treatment The risk of abrupt discontinuation of Inomax therapy in the event of critical failure of the delivery system and how to prevent it
• Tveganje nenadne prekinitve zdravljenja z zdravilom INOmax v primeru kritične odpovedi sistema za dovajanje in kako to preprečiti
The potential risk of bleeding and haemostasis disorders The potential risks if used in combination with other vasodilators which act on cGMP or cAMP
• Potencialna tveganja, če se uporablja v kombinaciji z drugimi vazodilatatorji, ki delujejo na cGMP ali cAMP.
The educational pack should contain the following: Summary of Product Characteristics and Patient Information Leaflet for INOmax
Gradivo za izobraževanje naj vsebuje naslednje: • Povzetek glavnih značilnosti zdravila in navodila za uporabo zdravila INOmax
The Member States must ensure that all conditions or restrictions with regard to the safe and effective use of the medicinal product described below are implemented in their national territory: Prior to launch of the new indication of the product in the Member State, the national competent authority shall agree the content and format of the educational material with the Marketing Authorisation Holder
• Pred uvedbo nove indikacije za zdravilo v državi članici naj imetnik dovoljenja promet z zdravilom pridobi soglasje o vsebini in obliki izobraževalnega materiala s pristojnim nacionalnim organom.
The Opinion was not properly reasoned.
Mnenje ni bilo ustrezno utemeljeno.
The CHMP's conclusions were arbitrary.
Sklepi CHMP so bili arbitrarni.
The Committee is therefore of the opinion that its 22 July 2010 opinion should be maintained.
Odbor je tako menil, da je treba mnenje z dne 22. julija 2010 ohraniti.
Re-examination procedure
Postopek ponovnega pregleda
The new formulation must be approved by the National Competent Authorities of the concerned Member States (see Annex IV).
Novo formulacijo morajo odobriti pristojni nacionalni organi zadevnih držav članic (glejte Prilogo IV).
About 20% of the responders reported chronic pain (>6 months).
Okoli 20 odstotkov odzivnih bolnikov je poročalo o kronični bolečini (>6 mesecev).
This aspect is outside the scope of this procedure and it does not provide any relevant information to the issue at stake.
Ta vidik ne sodi v okvir tega postopka in ne ponuja nobenih pomembnih informacij glede obravnavanega vprašanja.
It is well known that food can have an effect on the pharmacokinetic parameters of medicinal products.
Dobro znano je, da lahko hrana vpliva na farmakokinetične parametre zdravil.
In its assessment, the Committee took into consideration data submitted for the different timepoints.
Odbor je pri ocenjevanju upošteval predložene podatke za različne časovne točke.
On 18 September 2009, the European Commission triggered a referral under Article 31 of Directive 2001/83/EC, as amended.
Evropska komisija je 18. septembra 2009 sprožila napotitveni postopek v skladu s členom 31 Direktive 2001/83/ES, kakor je bila spremenjena.
The remaining systems were not significantly affected by alcohol.
Na preostale sisteme alkohol ni pomembneje vplival.
Quality issues
Vprašanja kakovosti
The question under discussion is, however, whether the magnitude of the interaction is such that it can be assumed to have clinical significance and represent a significant risk for the patient.
Obravnavano vprašanje pa je, ali je obseg interakcij takšen, da bi lahko bil klinično pomemben in predstavljal pomembno tveganje za bolnika.
In particular, assumptions were made about the behaviour of some formulations based solely on the excipients; in this respect the CHMP did not take into account the evidence provided in the Oral Hearing on 23 June 2010 that such assumptions are flawed.
Zlasti so bile oblikovane predpostavke o delovanju nekaterih formulacij, ki so bile utemeljene zgolj na pomožnih snoveh; pri tem CHMP ni upošteval dokazov, predloženih na ustni obravnavi dne 23. junija 2010, da so takšne predpostavke napačne.
However, a significant percentage of the patients with chronic pain who uses opioids still reports high alcohol intake (10.8%) and binge drinking at least once a month (22.3%), despite existing warnings.
Kljub temu pa pomemben odstotek bolnikov s kronično bolečino, ki uporabljajo opioide, še vedno poroča o visokem vnosu alkohola (10,8 odstotka) in popivanju vsaj enkrat na mesec (22,3 odstotka) navkljub obstoječim opozorilom.
This product has never been marketed.
To zdravilo ni bilo nikoli trženo.
This further illustrates the limitations of the data presented.
To prav tako kaže na to, da so predstavljeni podatki omejeni.
Source; Brennan et al., Addiction 2005; 100 : 777-86
Vir: Brennan et al., Addiction 2005; 100 : 777-86
Benefit-Risk balance
Razmerje med koristmi in tveganji
Dissolution data was submitted for two different controlled release systems of hydromorphone, four different controlled release systems of oxycodone, and seven different controlled release systems containing morphine.
Podatki o raztapljanju so bili predloženi za dva različna sistema z nadzorovanim sproščanjem hidromorfona, štiri različne sisteme z nadzorovanim sproščanjem oksikodona ter sedem različnih sistemov nadzorovanega sproščanja, ki so vsebovali morfin.
In the scientific literature, drinking alcohol is referred as a coping mechanism to deal with the stress associated with pain.
V znanstveni literaturi se pitje alkohola obravnava kot mehanizem za spoprijemanje s stresom, povezanim z bolečino.
For most of the products assessed, only in vitro data was submitted.
Za večino ocenjevanih zdravil so bili predloženi samo in vitro podatki.
In this study, subjects were interviewed about their number of alcohol consumptions of the last week and frequency of binge drinking in the last month (5292 responders).
V tej študiji so preiskovance spraševali o količini porabljenega alkohola v preteklem tednu in pogostosti popivanja v preteklem mesecu (5292 odzivnih bolnikov).
Secondly, the CHMP's approach to alcohol interaction is inconsistent with its approach to food interactions.
Drugič, pristop CHMP do interakcije z alkoholom ni skladen z njegovim pristopom do interakcije s hrano.
A significant effect was observed also in a hydromorphone once a day formulation which is not marketed in the EU.
Pomemben vpliv so opazili tudi pri formulaciji hidromorfona za uporabo enkrat na dan, ki se v EU ne trži.
The effect of alcohol on the dissolution rate was mild in most cases, except for one morphine formulation (morphine once-daily capsules).
Vpliv alkohola na stopnjo raztapljanja je bil v večini primerov blag, razen pri eni formulaciji morfina (kapsule morfina enkrat na dan).
Both problem drinkers and non-problem drinkers were included.
Vključeni so bili tako problematični kot neproblematični pivci.
It is important to note in this regard that the effects of food related interactions are measured in vivo, and therefore the data on food effect reflects, as accurately as possible, the real extent of the interaction.
V zvezi s tem je pomembno omeniti, da so interakcije, povezane s hrano, merjene in vivo, kar pomeni, da podatki o učinku hrane kar najbolj natančno odražajo resnični obseg interakcije.
This will be related to the specificities of each formulation, namely the physical characteristics of the excipients and the manufacturing process.
Na to vplivajo predvsem posebnosti posameznih formulacij, in sicer fizikalne lastnosti pomožnih snovi in proizvodni postopek.
While it may be argued that patients may use less alcohol as a self-medication strategy if they are sufficiently treated with analgesics like opioids, the results of a recently published Danish Health survey (Ekholm et al. Eur J Pain 2009; 13: 606-12) reveal a different pattern of behavior.
Čeprav nekateri morda zagovarjajo stališče, da bi bolniki uporabljali manj alkohola kot sredstva za samozdravljenje, če bi bili ustrezno zdravljeni z analgetiki kot so opioidi, pa rezultati nedavno objavljene danske zdravstvene raziskave (Ekholm et al.. Eur J Pain 2009; 13: 606-12) kažejo drugačne vzorce vedenja.
Concurrent depression and pain have a much greater impact than either disorder alone and, in patients with pain, depression is associated to more pain sites, greater pain intensity, longer duration of pain, and greater likelihood of poor treatment response (Bair, J et al., Psychosom Med. 2008 October; 70(8): 890-897).
Sočasno pojavljanje depresije in bolečine ima veliko večji vpliv kot vsaka motnja posebej, pri bolnikih z bolečino je depresija povezana z več bolečimi mesti, večjo intenzivnostjo bolečine, daljšim trajanjem bolečine in večjo verjetnostjo, da bo odziv na zdravljenje slab (Bair, J et al., Psychosom Med. 2008 October; 70(8): 890-897).
Clinical issues
Klinična vprašanja
The MAH expressed the view that:
Imetnik dovoljenja za promet z zdravilom je izrazil stališče, da:
Pain at baseline was a significant predictive factor for alcohol use in the 3-years follow-up period.
Bolečina v izhodišču je bila pomemben napovedni dejavnik uporabe alkohola v triletnem nadaljevalnem obdobju.
It is therefore concluded that the approach is not inconsistent, firstly because in the case of alcohol, a recommendation not to take the product with alcohol will always exist regardless of the formulation.
Na podlagi tega se sklepa, da pristop ni neskladen, prvič zato, ker bo v primeru alkohola vedno obstajalo priporočilo, naj se zdravilo ne jemlje z alkoholom, ne glede na formulacijo.
Given the type of products and patient population involved, it is acknowledged that underreporting is considerable.
Ob upoštevanju vrste zdravil in vključene populacije bolnikov se priznava, da je neporočanje o interakcijah precejšnje.
The association between pain and drinking was evaluated by Brennan et al in a cohort of 401 elderly with different drinking behavior (Brennan, Addiction.
Povezavo med bolečino in pitjem so ocenjevali Brennan et al. v skupini 401 starostnika z različnimi vzorci pitja (Brennan, Addiction.
A low number of cases of interaction between alcohol and opioid products have been reported, most reports involved intentional overdose or abuse in conjunction with other products and some were fatal.
V manjšem številu primerov so poročali o interakciji med alkoholom in opioidnimi zdravili, večina poročil pa je vključevala namerno preveliko odmerjanje ali zlorabo skupaj z drugimi zdravili in nekateri primeri so bili smrtni.
In this context, the fact that the product is meant for use once or twice a day may be of importance given the higher dose usually contained in once a day formulations.
Pri tem je lahko pomembno tudi dejstvo, da je zdravilo namenjeno uporabi enkrat ali dvakrat na dan, saj so v formulacijah za uporabo enkrat na dan načeloma večji odmerki.
Grounds for suspension of the marketing authorisation
Podlaga za začasni umik dovoljenja za promet z zdravilom
With food the gastric emptying of alcohol is delayed, but still significant (50-60% in 1 hour, Levitt, 1997, and Cortot et al, Digestive Diseases and Sciences 1986; 31:343-48).
S hrano se praznjenje alkohola iz želodca nekoliko upočasni, vendar je še vedno pomembno (50-60 odstotkov v eni uri; Levitt, 1997, in Cortot et al, Digestive Diseases and Sciences 1986; 31:343-48).
In addition, the CHMP agreed on the inclusion for all other products in the European market of a pharmacodynamic warning.
Poleg tega je CHMP potrdil tudi vključitev farmakodinamičnega opozorila za vse druga zdravila na evropskem trgu.
This effect is known as ‘dose-dumping'.
Ta učinek je znan kot „prekomerno sproščanje“.
In its initial Opinion, the CHMP did not conclude that the formulations analysed were unaffected by alcohol.
V svojem prvotnem mnenju CHMP ni menil, da alkohol ni učinkoval na analizirane formulacije.
Gastric ethanol concentrations dropped rapidly after the consumption of alcohol by 70% in 10 min (Levitt et all, Am J Physiol Gastrointest Liver Physiol 273:951-957, 1997).
Koncentracija etanola v želodcu se je po zaužitju alkohola hitro zmanjšala, in sicer do 70 odstotkov v 10 minutah (Levitt et al, Am J Physiol Gastrointest Liver Physiol 273:951-957, 1997).
When adopting its 22 July 2010 opinion on this procedure, CHMP was fully aware of the positions of the different working parties.
CHMP se je pri sprejemanju mnenja o tem postopku dne 22. julija 2010 popolnoma zavedal stališč različnih delovnih skupin.
The National Competent Authorities should therefore determine, based on the modified-release mechanism of the products approved in their Member State, the appropriate actions to be taken for individual products.
Pristojni nacionalni organi morajo zato na podlagi mehanizmov za prirejeno sproščanje zdravil, odobrenih v njihovi državi članici, določiti ustrezne ukrepe za posamezna zdravila.
Alcohol use is common in patients with chronic pain due to the fact that it reduces pain perception.
Uporaba alkohola je pri bolnikih s kroničnimi bolečinami običajna, saj zmanjšuje zaznavanje bolečine.
A product with this dissolution profile cannot be considered to behave as an immediate release formulation.
Za zdravilo s takim profilom raztapljanja ne more veljati, da deluje kot formulacija s takojšnjim sproščanjem.
The association between chronic pain and alcohol use is summarized in the table below.
Povezava med kronično bolečino in uporabo alkohola je povzeta v spodnji preglednici.
Modified-release products are complex dosage forms designed to release drugs in a controlled manner to achieve desired efficacy and safety profiles.
Zdravila s prirejenim sproščanjem imajo kompleksno farmacevtsko obliko, ki omogoča sproščanje zdravila na nadzorovan način za doseganje želene učinkovitosti in varnostnih profilov.
Both problem drinkers as non-problem drinkers reported to use alcohol to manage pain, although in the latter group to less extent (see figure 1).
Tako problematični kot neproblematični pivci so poročali, da alkohol uporabljajo za obvladovanje bolečine, čeprav neproblematični pivci v manjšem obsegu (glejte sliko 1).
The advice of the QWP was that formulations should, if possible, be developed such that a physicochemical incompatibility with alcohol is avoided.
Priporočilo delovne skupine za kakovost je bilo, da naj se formulacije, kadar je le mogoče, razvijejo na tak način, da ne bo prišlo do fizikalno-kemijske inkompatibilnosti z alkoholom.
Therefore, patients taking this particular formulation are exposed to a significantly greater risk of developing serious adverse reactions such as respiratory depression and death.
Bolniki, ki jemljejo to določeno formulacijo, so tako izpostavljeni bistveno večjemu tveganju, da se pri njih pojavijo hudi neželeni učinki, kot sta depresija dihanja in smrt.
This is demonstrated by measurements of gastric-duodenal ethanol levels after consumption of alcohol in healthy volunteers.
To je prikazano z meritvami ravni etanola v želodcu in dvanajstniku po zaužitju alkohola pri zdravih prostovoljcih.
Scientific conclusions and grounds for suspension/amendment of the summaries of product characteristics, package leaflets and labelling presented by the European Medicines Agency
Znanstveni zaključki in podlaga za začasni umik/dopolnilo povzetkov glavnih značilnosti zdravila, navodil za uporabo in označevanja, ki jih je predstavila Evropska agencija za zdravila
The Committee also discussed the possibility of the introduction of a pharmacokinetic warning in those cases where some degree of additional formulation interaction could be suspected.
Odbor je prav tako razpravljal o možnosti vključitve farmakokinetičnega opozorila v primerih, kadar obstaja možnost dodatnih interakcij formulacije.
For the suspension to be lifted, the Marketing Authorisation Holders need to provide evidence that the product has been reformulated, that it exhibits an acceptable release profile with the same quality, safety and efficacy profile of the currently authorised formulation but without the clinically significant interaction with alcohol.
Za preklic začasnega umika morajo imetniki dovoljenja za promet z zdravilom predložiti dokaze, da je bila formulacija zdravila spremenjena ter da ima ustrezen profil sproščanja z enakim profilom kakovosti, varnosti in učinkovitosti, kot ga ima trenutno odobrena formulacija, vendar brez klinično pomembne interakcije z alkoholom.
Following the CHMP Opinion of 22 July 2010, one MAH submitted detailed grounds for the re-examination of the opinion.
Ob upoštevanju mnenja CHMP z dne 22. julija 2010 je imetnik dovoljenja za promet z zdravilom predložil podrobno utemeljitev zahtevka za ponovni pregled mnenja.