natgillin/translations-raw huggingface dataset:
It is noted that the majority of cases involves the use of high concentration oral liquid formulations, which are currently approved under a number of different formulations (oral drops, oral solution, syrup) with very different concentrations and a range of administration devices.
Ugotovljeno je bilo, da je bila večina primerov povezana z uporabo močno koncentriranih tekočih pripravkov za peroralno uporabo, ki so trenutno odobreni v več različnih oblikah (peroralne kapljice, peroralna raztopina, sirup) z zelo različnimi koncentracijami in vrsto pripomočkov za aplikacijo.
The Committee considered the proposal by one MAH to explicitly restrict intravenous administration to locations where resuscitation equipment is available, but noted that most places where intravenous drugs are administrated will already have such equipment.
Odbor je proučil predlog enega od imetnikov dovoljenj za promet z zdravilom, da bi intravensko uporabo izrecno omejili na zdravstvene ustanove, v katerih je na voljo oprema za oživljanje, vendar je menil, da večina ustanov, v katerih uporabljajo intravenska zdravila, že zdaj ima tovrstno opremo.
Also, the onset of action may be faster with the solution in comparison to that of tablets, as tablets have first to be dissolved in the gastrointestinal tract.
Poleg tega lahko raztopina začne delovati hitreje kot tablete, saj se morajo te najprej raztopiti v prebavilih.
Therefore, in order to minimise the risk of serious neurological adverse reactions such as acute extrapyramidal symptoms and irreversible tardive dyskinesia, the dose should be restricted to the minimum effective dose, which for adults is considered to be 10 mg three times daily.
Zato je treba za zmanjšanje tveganja za resne nevrološke neželene učinke, kot so akutni ekstrapiramidni simptomi in trajna tardivna diskinezija, odmerek omejiti na najmanjši učinkoviti odmerek, ki je pri odraslih 10 mg trikrat na dan.
In conclusion, the Committee considered that oral liquid formulations with concentration 1 mg/ml are suitable for all situations mentioned, and that the availability of higher concentrations carries a risk of overdose in the paediatric population that is unlikely to be resolved by the proposed changes to the product information.
Na koncu je odbor zaključil, da so tekoči pripravki za peroralno uporabo s koncentracijo 1 mg/ml primerni za uporabo v vseh navedenih okoliščinah in da dostopnost večjih koncentracij prinaša tveganje za preveliko odmerjanje pri pediatrični populaciji, ki ga predlagane spremembe informacij o zdravilu verjetno ne bi odpravile.
This raises an issue of dose accuracy and reproducibility, particularly with high concentration formulations, and may explain at least partially the reason behind the reports of accidental overdose in the paediatric population.
To dejstvo sproža vprašanja glede ustreznosti in ponovljivosti odmerka, zlasti pri močno koncentriranih pripravkih, in bi lahko vsaj delno pojasnilo razlog za poročila o nenamernem prevelikem odmerjanju pri pediatrični populaciji.
According to the BNFc, in patients at low risk of emesis, pre-treatment with metoclopramide continued for up to 24 hours after chemotherapy is often effective.
Priročnik BNFc navaja, da je pri bolnikih z majhnim tveganjem za bruhanje pogosto učinkovito predhodno zdravljenje z metoklopramidom, ki se nadaljuje še do 24 ur po kemoterapiji.
Following the adoption of the CHMP opinion in July 2013, a request for re-examination was received from one MAH concerned by the procedure.
Potem ko je odbor CHMP julija 2013 sprejel mnenje, je eden od imetnikov dovoljenj za promet z zdravilom, na katere se je nanašal postopek, zahteval ponoven pregled mnenja.
For the indication acute CINV, while there is some data indicative of efficacy, it requires the intravenous use of high doses of metoclopramide which carry higher risks not only of neurological but also cardiovascular adverse reactions (including cardiac arrest).
Za indikacijo akutna CINV je sicer na voljo nekaj podatkov, ki kažejo na učinkovitost, vendar je potrebna intravenska uporaba velikih odmerkov metoklopramida, s čimer se poveča tveganje ne samo za nevrološke, ampak tudi za srčno-žilne neželene učinke (vključno z zastojem srca).
Based on the data presented, there is little evidence of efficacy of metoclopramide in treatment of gastroesophageal reflux disease or dyspepsia and existing data is not consistent in terms of effect.
Glede na predložene podatke obstaja malo dokazov o učinkovitosti metoklopramida pri zdravljenju gastroezofagealne refluksne bolezni ali dispepsije, obstoječi podatki o učinkovitosti pa niso dosledni.
Both gastroesophageal reflux disease and dyspepsia may be chronic diseases, and therefore existing data cannot be considered sufficient to support the use in these indications.
Gastroezofagealna refluksna bolezen in dispepsija sta lahko kronični bolezni, zato obstoječi podatki ne zadoščajo za utemeljitev uporabe pri teh indikacijah.
The Committee, as a consequence, concluded that the benefit-risk balance of metoclopramidecontaining medicinal products remains positive, taking into account the changes to the product information and risk minimisation measures recommended.
Odbor je posledično zaključil, da je razmerje med tveganji in koristmi zdravil, ki vsebujejo metoklopramid, še naprej pozitivno, če se upoštevajo priporočene spremembe informacij o zdravilu in ukrepi za zmanjšanje tveganja.
• Post-operative nausea and vomiting (PONV)
• slabost in bruhanje po operaciji (PONV);
However, a few cases of extrapyramidal reactions in newborns exposed to metoclopramide before delivery have been identified.
Kljub temu pa so zabeležili nekaj primerov ekstrapiramidnih reakcij pri novorojenčkih, ki so bili pred porodom izpostavljeni metoklopramidu.
The available evidence from small single dose studies suggests that metoclopramide clearance is substantially reduced in patients with hepatic cirrhosis.
Razpoložljivi dokazi iz majhnih študij z enkratnim odmerkom kažejo, da je očistek metoklopramida pomembno manjši pri bolnikih s cirozo jeter.
In this scenario where the unintended misuse is already taking place, to include a contraindication in the product information alongside a statement in the labelling is unlikely to be sufficient to change administration habits.
Ker že prihaja do nenamerne napačne uporabe, je malo verjetno, da bi vključitev kontraindikacije v informacije o zdravilu skupaj z zgoraj navedeno navedbo pri označevanju zadoščala za to, da bi se spremenile navade pri uporabi zdravila.
The elderly appear to be at particular risk of developing tardive dyskinesia following long-term treatment, which in some cases may be irreversible.
Pri starejših pa pri dolgotrajnem zdravljenju obstaja še posebno veliko tveganje za razvoj tardivne diskinezije, ki je v nekaterih primerih lahko trajna.
o Is favourable in adults for ‘symptomatic treatment of nausea and vomiting, including acute migraine induced nausea and vomiting' (parenteral route) and ‘symptomatic treatment of nausea and vomiting, including acute migraine induced nausea and vomiting.
o ugodno pri odraslih za indikacijo „simptomatsko zdravljenje slabosti in bruhanja, vključno s slabostjo in bruhanjem zaradi akutne migrene“ (parenteralna uporaba) in „simptomatsko zdravljenje slabosti in bruhanja, vključno s slabostjo in bruhanjem zaradi akutne migrene.
The lack of placebo-controlled trial data prevents assessment of the absolute efficacy of metoclopramide in these indications.
Zaradi pomanjkanja podatkov iz preskušanj, nadzorovanih s placebom, ni mogoče oceniti absolutne učinkovitosti metoklopramida pri teh indikacijah.
The majority of cases of accidental overdose occurred in children and involve the use of high concentration oral liquid formulations.
Večina primerov nenamernega prevelikega odmerjanja se je zgodila pri otrocih in je bila povezana z uporabo močno koncentriranih tekočih pripravkov za peroralno uporabo.
For therapeutic indications such as delayed CINV, prevention of RINV, prevention of PONV and symptomatic treatment of nausea and vomiting including migraine induced nausea and vomiting, data is indicative of efficacy at low doses (10mg, three times daily) which minimise the risk of serious neurological adverse reactions.
Podatki za terapevtske indikacije, kot so zapoznela CINV, preprečevanje RINV, preprečevanje slabosti in bruhanja po operaciji in simptomatsko zdravljenje slabosti in bruhanja, vključno s slabostjo in bruhanjem zaradi migrene, kažejo na učinkovitost majhnih odmerkov (10 mg, trikrat na dan), ki zmanjšajo tveganje za resne nevrološke neželene učinke.
Considering the newly recommended posology, parenteral formulations with concentration higher than 5mg/ml currently approved in the European Union (mainly for the management of acute CINV) will not be suitable for administration of the 10mg dose, are therefore considered to have a negative benefitrisk balance and should be revoked.
Glede na priporočeno novo odmerjanje parenteralni pripravki s koncentracijo več kot 5 mg/ml, ki so trenutno odobreni v Evropski uniji (predvsem za obvladovanje akutne CINV), ne bodo primerni za dajanje odmerka 10 mg, zato je odbor menil, da je zanje razmerje med tveganji in koristmi negativno in jih je treba ukiniti.
In the absence of an established benefit, and taking into account the safety profile of metoclopramide, the Committee considered that the benefit-risk balance of metoclopramide in this indication is negative.
Zaradi odsotnosti dokazov o koristi in ob upoštevanju varnostnega profila metoklopramida je odbor menil, da je razmerje med tveganji in koristmi metoklopramida pri tej indikaciji negativno.
The Committee also considered that the risk of unintentional overdose and associated adverse events in children can be lowered by limiting the maximum concentration of oral liquid formulations.
Prav tako je menil, da je tveganje za nenamerno preveliko odmerjanje in z njim povezane neželene dogodke pri otrocih mogoče zmanjšati z omejitvijo največje koncentracije tekočih pripravkov za peroralno uporabo;
While considering that the concentration 4 mg/ml is appropriate for adults, the MAH recognised that it is too high for children and therefore proposed the measures to avoid the risk of overdose in children, including contraindication in this patient population.
Medtem ko je imetnik dovoljenja za promet z zdravilom menil, da je koncentracija 4 mg/ml primerna za odrasle, se je strinjal, da je prevelika za otroke, in zato predlagal ukrepe za preprečevanje prevelikega odmerjanja pri otrocih, vključno s kontraindikacijo pri tej populaciji bolnikov.
An oral bioequivalence study of metoclopramide tablets compared to liquid showed that Cmax and Tmax are not significantly different for the two oral formulations.
Študija biološke enakovrednosti, v kateri so primerjali tablete metoklopramida s tekočim pripravkom, je pokazala, da se Cmax in Tmax pri obeh peroralnih oblikah ne razlikujeta veliko.
The CHMP, having considered the data submitted, is of the opinion that in addition to product information amendments which include the use of the minimum effective dose and the limitation of treatment duration, the following risk minimisation activities are necessary for the safe and effective use of the medicinal product:
Potem ko je CHMP pregledal predložene podatke, je menil, da so za zagotovitev varne in učinkovite uporabe zdravila poleg sprememb informacij o zdravilu, ki vključujejo uporabo najmanjšega učinkovitega odmerka in omejitev trajanja zdravljenja, potrebni tudi naslednji ukrepi za zmanjšanje tveganja:
Much of the available data is derived from trials designed to investigate newer agents such as the 5-HT3 receptor antagonists, and therefore do not always allow for a definite conclusion of the effect of metoclopramide due to the absence of a comparison to placebo.
Večino razpoložljivih podatkov so pridobili v preskušanjih, zasnovanih za raziskovanje novejših učinkovin, kot so na primer antagonisti receptorjev 5-HT3, zato zaradi dejstva, da metoklopramida niso primerjali s placebom, včasih ni mogoče podati dokončnih zaključkov o njegovem učinku.
However, for patients with moderate to severe impairment (ClCr 15-60 ml/min), a 50% reduction remains appropriate.
Na drugi strani je za bolnike z zmerno do hudo okvaro (očistek kreatinina 15-60 ml/min) še naprej primerno zmanjšanje za 50 %.
Therefore the Committee considered that it is an important risk minimisation measure to restrict the maximum concentration of oral liquid formulations to 1 mg/ml, to ensure that clear instructions are given in the product information on posology for paediatric patients and that these oral liquid formulations are supplied with an appropriate measuring device such as a graduated oral syringe.
Zato je odbor menil, da je za zmanjšanje tveganja pomembno, da se omeji največja koncentracija tekočih pripravkov za peroralno uporabo na 1 mg/ml ter zagotovijo jasna navodila v informacijah o zdravilu glede odmerjanja za pediatrične bolnike in da se tem tekočim pripravkom priloži primeren odmerni pripomoček, kot je na primer graduirana brizga za peroralno dajanje.
− rectal formulations dosed at 20mg
− pripravke za rektalno uporabo v odmerku 20 mg;
In addition, data is indicative that the burden of adverse reactions is increased with dose.
Poleg tega podatki kažejo, da se z odmerkom povečuje tudi pojavnost neželenih učinkov.
This may be due to an issue of dose accuracy and reproducibility, unclear information on dosing and possibly difficulties measuring and administering the correct dose, particularly with high concentration formulations and poorly validated devices.
Vzroki bi lahko bili vprašljiva ustreznost in ponovljivost odmerka, nejasne informacije o odmerjanju in morda tudi težave pri odmerjanju in dajanju ustreznega odmerka, zlasti ob uporabi močno koncentriranih pripravkov in nezadostno potrjenih pripomočkov.
When administered for moderately emetic chemotherapy, doses ranging from 30 to 60mg appear to be effective.
Po zmerno emetogeni kemoterapiji pa so, kot kaže, učinkoviti odmerki od 30 do 60 mg.
The data presented in relation to the prevention of delayed CINV is predominantly in patients receiving moderately emetogenic chemotherapy, using oral metoclopramide at doses of 10-20 mg three or four times a day.
Podatki, ki so bili predloženi v zvezi s preprečevanjem zapoznele CINV, se pretežno nanašajo na bolnike, ki so prejemali zmerno emetogeno kemoterapijo in so uporabljali metoklopramid v odmerku od 10-20 mg trikrat ali štirikrat na dan.
This body of data is more consistent and indicates similar efficacy for these doses of metoclopramide given orally to the efficacy of 5-HT3 receptor antagonists.
Ta nabor podatkov je doslednejši in kaže, da je učinkovitost teh peroralnih odmerkov metoklopramida primerljiva z učinkovitostjo antagonistov receptorjev 5-HT3.
For this indication, prophylaxis is usually initiated with a 5-HT3 receptor antagonist before chemotherapy and is followed by metoclopramide (usually oral) prescribed for a further 24-48 hours.
Pri tej indikaciji se običajno pred kemoterapijo uvede profilaktično zdravljenje z antagonistom receptorjev 5-HT3, nato pa se za nadaljnjih 24-48 ur predpiše (običajno peroralna) uporaba metoklopramida.
Grounds for the revocation / variation to the terms of the marketing authorisation
Razlogi za razveljavitev/spremembo pogojev dovoljenja za promet z zdravilom
• In view of the available data the Committee also concluded that the benefit-risk balance of metoclopramide-containing products:
• na podlagi razpoložljivih podatkov je odbor zaključil tudi, da razmerje med tveganji in koristmi zdravil, ki vsebujejo metoklopramid:
In order to minimise the risk of overdose in children, the MAH proposed to add the statement ‘for adults' in the label of oral liquid formulations with concentration > 1 mg/ml, and a contraindication in the paediatric population.
Za zmanjšanje tveganja za preveliko odmerjanje pri otrocih je imetnik dovoljenja za promet z zdravilom predlagal, da se doda navedba „za odrasle“ pri označevanju tekočih pripravkov za peroralno uporabo s koncentracijo, ki presega 1 mg/ml, in kontraindikacija pri pediatrični populaciji.
It is possible that there is unintended misuse of the high concentration oral liquid formulations, leading to the inadvertent administration of doses higher than intended.
Mogoče je, da prihaja do nenamerne napačne uporabe močno koncentriranih tekočih pripravkov za peroralno uporabo, ki povzroči nenamerno zaužitje odmerkov, večjih od predvidenih.
The data presented in support of the effect of metoclopramide in post-operative nausea and vomiting indicates that it has similar efficacy to other active substances authorised in this indication.
Predloženi podatki, ki naj bi dokazovali učinkovitost metoklopramida pri slabosti in bruhanju po operaciji, kažejo, da je metoklopramid podobno učinkovit kot druge zdravilne učinkovine, odobrene za to indikacijo.
The CHMP considered that formulations with concentration 1mg/ml are suitable for those patients that may prefer an oral liquid formulation to a solid pharmaceutical form.
CHMP je menil, da so pripravki s koncentracijo 1 mg/ml primerni za tiste bolnike, ki imajo raje tekoče pripravke za peroralno uporabo kot trdne farmacevtske oblike.
No data was submitted by the MAH in support of the above claims.
Imetnik dovoljenja za promet z zdravilom ni predložil nobenih podatkov, ki bi podprli zgornje trditve.
The studies assessed seem to indicate that metoclopramide reduces gastric transit time, but this did not translate into a clinically meaningful outcome (time taken to complete the examination).
Ocenjene študije kažejo, da metoklopramid skrajša čas prehoda skozi želodec, vendar se to ni izkazalo za klinično pomembno (v smislu časa, potrebnega za dokončanje preiskave).
There is sufficient evidence of efficacy of metoclopramide in the treatment of post-operative nausea and vomiting in the paediatric population.
O učinkovitosti metoklopramida pri zdravljenju slabosti in bruhanja po operaciji pri pediatrični populaciji obstaja dovolj dokazov.
Post marketing data is suggestive of unintended misuse of these formulations (oral drops, oral solution, syrup), approved under a range of concentrations and with a range of administration devices potentially leading to the inadvertent administration of doses higher than intended.
Podatki iz obdobja trženja kažejo, da prihaja do nenamerne napačne uporabe teh pripravkov (peroralnih kapljic, peroralne raztopine, sirupa), ki so odobreni v različnih koncentracijah in skupaj z vrsto pripomočkov za aplikacijo, kar lahko povzroči nenamerno zaužitje odmerkov, ki so večji od predvidenih.
The doses, routes of administration and treatment durations of metoclopramide used in these studies are not always consistent, and only one specific dose-finding study was identified (in PONV).
Odmerki, poti uporabe in trajanje zdravljenja z metoklopramidom, ki so jih določili v teh študijah, niso povsem enaki, poleg tega pa so izvedli samo eno posebno študijo za določitev odmerka (za slabost in bruhanje po operaciji).
Based on data from both the Jantunen meta-analysis and the randomised clinical studies assessed, metoclopramide administered intravenously or orally is consistently inferior to 5-HT3 receptor antagonists for prevention of acute CINV for highly or moderately emetogenic chemotherapy.
Podatki iz metaanalize, ki jo je opravil Jantunen, in podatki iz pregledanih randomiziranih kliničnih preskušanj kažejo, da je metoklopramid, ki se daje intravensko ali peroralno, dosledno slabši od antagonistov receptorjev 5-HT3 pri preprečevanju akutne CINV po močno ali zmerno emetogeni kemoterapiji.
The studies assessed seem to indicate that metoclopramide reduces gastric transit time, but this did not affect the time taken to complete the examination.
Ocenjene študije kažejo, da metoklopramid skrajša čas prehoda skozi želodec, vendar to ni vplivalo na čas, potreben za dokončanje preiskave.
In its July 2013 opinion, the CHMP also recommended that oral liquid formulations be supplied with an appropriate measuring device such as a graduated oral syringe.
V okviru mnenja, ki ga je odbor CHMP sprejel julija 2013, je prav tako priporočil, naj se vsem tekočim pripravkom za peroralno uporabo priloži primeren odmerni pripomoček, kot je na primer graduirana brizga za peroralno dajanje.
For this reason, the Committee considered that the benefit-risk balance of metoclopramide in this indication is negative and recommended that it is deleted.
Zato je odbor menil, da je razmerje med tveganji in koristmi metoklopramida pri tej indikaciji negativno, in priporočil, da se indikacija izbriše.
The MAH considered that oral liquid formulations with concentration higher than 1 mg/ml continue to be useful for adult patients, in terms of dosing (less number of drops are necessary to achieve the intended dose with a higher concentration solution) and in terms of easiness of administration vis-à-vis tablets.
Imetnik dovoljenja za promet z zdravilom je menil, da so tekoči pripravki za peroralno uporabo s koncentracijo, večjo od 1 mg/ml, še vedno koristni za odrasle bolnike zaradi odmerjanja (zaradi bolj koncentrirane raztopine je potrebno manjše število kapljic, da se doseže ciljni odmerek) in enostavnejšega dajanja v primerjavi s tabletami.
Gastroesophageal reflux disease and dyspepsia
Gastroezofagealna refluksna bolezen in dispepsija
For the indication adjuvant to surgical and radiological procedures, very limited efficacy data exists, and the existing data is not consistent.
Pri indikaciji dodatek pri kirurških in radioloških posegih so na voljo zelo omejeni podatki o učinkovitosti, ki poleg tega niso dosledni.
For this indication, only the intravenous formulation is of relevance, in line with the outcome of the procedure under Article 45 of Regulation (EC) No
Za to indikacijo so v skladu z izidom postopka iz člena 45 Uredbe (ES) št. 1901/2006 primerni samo intravenski pripravki.
• Nausea and vomiting associated with migraine
• slabost in bruhanje, povezana z migreno;
Data on the use of metoclopramide in the prevention of RINV is limited.
Podatki o uporabi metoklopramida za preprečevanje slabosti in bruhanja zaradi radioterapije (RINV) so omejeni.
The MAH considered in its grounds that for oral liquid solutions a concentration of 4 mg/ml is too high for children and that there is a risk of overdose in this population.
Imetnik dovoljenja za promet z zdravilom je v utemeljitvi navedel, da je koncentracija tekočih pripravkov za peroralno uporabo 4 mg/ml prevelika za otroke in da pri tej populaciji obstaja tveganje za preveliko odmerjanje.
Metoclopramide has long been associated with a risk of serious neurological adverse reactions such as acute extrapyramidal symptoms and irreversible tardive dyskinesia.
Metoklopramid že dolgo povezujejo s tveganjem za resne nevrološke neželene učinke, kot so akutni ekstrapiramidni simptomi in trajna tardivna diskinezija.
Nausea and vomiting associated with migraine
Slabost in bruhanje, povezana z migreno
Adjuvant to surgical and radiological procedures
Dodatek pri kirurških in radioloških posegih
While metoclopramide was found to improve gastric emptying and relieve symptoms in diabetic and idiopathic gastroparesis in short term treatment when compared to placebo, no consistent benefit was observed in the long term.
Ugotovili so, da je metoklopramid, ki so ga primerjali s placebom, pri kratkoročnem zdravljenju izboljšal praznjenje želodca in olajšal simptome diabetične in idiopatske gastropareze, medtem ko pri dolgoročnem zdravljenju niso opazili doslednih koristi.
• The Committee considered that metoclopramide is associated with a risk of serious adverse events, including neurological adverse events such as extrapyramidal symptoms and irreversible tardive dyskinesia.
• odbor je menil, da je metoklopramid povezan s tveganjem za resne neželene dogodke, vključno z nevrološkimi neželenimi dogodki, kot so ekstrapiramidni simptomi in trajna tardivna diskinezija.
− parenteral formulations with concentration higher than 5mg/ml
− parenteralne pripravke s koncentracijo, večjo od 5 mg/ml,