natgillin/translations-raw huggingface dataset:
No clinically significant abnormalities were observed and the results confirmed the absence of significant changes in the subjects' state of health.
Klinično pomembnih nepravilnosti niso opazili, rezultati pa so potrdili odsotnost pomembnih sprememb v zdravstvenem stanju oseb.
The National Competent Authorities, coordinated by the Reference Member State, shall ensure that the following conditions are fulfilled by the Marketing Authorisation Holder(s):
Pristojni nacionalni organi, ki jih usklajuje referenčna država članica, zagotovijo, da imetnik(-i) dovoljenja za promet z zdravilom izpolnjujejo sledeče pogoje:
A total of 30 post-dose adverse events were reported, with 6 adverse events probably related to the study treatment, 11 possibly related, 2 remotely related, and 11 unrelated.
Poročali so o skupno 30 neželenih učinkih, opaženih po zaužitju odmerka, od česar je bilo verjetno 6 neželenih učinkov povezanih z obdelavo študije, 11 morda povezanih, 2 šibko povezana in 11 nepovezanih.
The Applicant assumption that the parent compound is inactive was not accepted, as the absolute activity should be taken into account, rather than the ratio of activity compared to the metabolite.
Predlagateljeva domneva, da matična spojina ni aktivna, ni bila sprejeta, saj je treba upoštevati absolutno aktivnost in ne delež aktivnosti v primerjavi z metabolitom.
It was concluded that any arguments for the widening of the acceptance range must be discussed prospectively, and reflected in the protocol.
Zaključili so, da je treba o vseh vprašanjih glede širjenja razpona sprejemljivosti razpravljati vnaprej, in to se mora odražati tudi v protokolu.
The majority of adverse event were considered mild and the most commonly reported was headache (8.8% of subjects).
Večina neželenih učinkov je bila označena kot blagih, najpogosteje opažen pa je bil glavobol (pri 8,8 % oseb).
The statistic analysis was described adequately, and the methods for statistical assessment of this bioequivalence study were acceptable.
Statistična analiza je bila zadostno opisana, metode za statistično oceno te bioekvivalenčne študije pa so bile sprejemljive.
OVERALL SUMMARY OF THE SCIENTIFIC EVALUATION OF LORATADINE SANDOZ 10 AND ASSOCIATED NAMES (SEE ANNEX I)
SPLOŠNI POVZETEK ZNANSTVENEGA VREDNOTENJA ZDRAVILA LORATADINE SANDOZ 10 IN Z NJIM POVEZANIH IMEN (GLEJTE DODATEK I)
According to the guideline, a wider interval may be acceptable, but only if prospectively defined and justified, addressing in particular any safety or efficacy concerns for patients switched between formulations.
Skladno s smernicami je širši interval lahko sprejemljiv, vendar le, če je vnaprej opredeljen in utemeljen ter obravnava zlasti kakršnekoli zadržke glede varnosti ali učinkovitosti za bolnike, ki bi jim zamenjali formulacijo.
The Applicant emphasised that bioequivalence was shown for the metabolite, which is responsible for the main effect.
Predlagatelj je poudaril, da je bioekvivalenca dokazana za metabolit, ki je odgovoren za glavni učinek.
The guidelines state that “In principle, evaluation of bioequivalence should be based upon measured concentrations of the parent compound.
Smernice navajajo, da mora „načeloma ocena bioekvivalence temeljiti na izmerjenih koncentracijah matične spojine.
ANNEX I LIST OF THE NAMES, PHARMACEUTICAL FORM, STRENGTHS OF THE MEDICINAL PRODUCTS, ROUTE OF ADMINISTRATION, APPLICANTS / MARKETING AUTHORISATION HOLDERS IN THE MEMBER STATES
DODATEK I SEZNAM IMEN, FARMACEVTSKIH OBLIK, JAKOSTI ZDRAVIL, POTI UPORABE, PREDLAGATELJEV / IMETNIKOV DOVOLJENJA ZA PROMET V DRŽAVAH ČLANICAH
The data available shows that the parent compound is measurable, and therefore must be measured, in order to assess bioequivalence.
Razpoložljivi podatki kažejo, da je matična spojina merljiva in zato mora biti izmerjena, da se oceni bioekvivalenca.
Because major objections on bioequivalence remained unresolved, an Article 29(4) referral was triggered and the procedure was referred to the CHMP.
Ker so pomembni pomisleki o bioekvivalenci ostali nerazrešeni, je bil sprožen napotitveni postopek v skladu s členom 29(4) in zadeva je bila napotena na CHMP.
The Applicant was requested to provide the CHMP with the parent compound data from the submitted bioequivalence study or to provide satisfactory justifications for the absence of these data.
Predlagatelj je bil pozvan, naj odboru CHMP iz predložene študije bioekvivalence predloži podatke o matičnih spojinah ali pa naj pridobi zadovoljive utemeljitve za pomanjkanje teh podatkov.
The validation process was described in detail and the study and the analyses were made in accordance with GLP principles as well as international regulatory recommendations and guidelines.
Validacijski postopek je podrobno opisan v študiji, analize pa so bile narejene v skladu z načeli dobre laboratorijske prakse ter z mednarodnimi regulativnimi priporočili in smernicami.
In addition, the widening of the Confidence Intervals should be agreed prospectively in the study design.
Poleg tega mora biti razširitev intervala zaupanja sprejeta vnaprej že pri oblikovanju načrta študije.
The CHMP also considered that the choice of pharmacokinetic variables was adequate for this study and that the pharmacokinetic calculation was presented correctly.
CHMP je bil prav tako mnenja, da je bila izbira farmakokinetičnih spremenljivk zadostna za to študijo in da je bil farmakokinetični izračun pravilno prikazan.
The metabolite can be used as a surrogate only if the Applicant presents convincing arguments demonstrating that it is not possible to reliably measure the parent compound after a single administration, which is not the case for loratadine.
Metabolit lahko uporabimo kot nadomestek le, če predlagatelj predloži prepričljive dokaze, da zanesljivo merjenje matične spojine po enkratnem odmerku ni možno, kar pa ne velja za loratadin.
The following pharmacokinetic parameters were determined: AUC0-t, Cmax (primary) and AUC residual area, tmax, Ke;, t1/2 (secondary).
Določili so sledeče farmakokinetične parametre: AUC0-t, Cmax (primarni) in AUC območja preostanka, tmax, Ke;, t1/2 (sekundarni).
Regarding the basic statistical parameter analysis of AUC∞, AUCt and Cmax, both AUCs and Cmax values were subjected to analysis of variance (ANOVA), following the logarithmic transformation.
Glede osnovnih statističnih parametrov pri analizi AUC∞, AUCt in Cmax, so bile vrednosti obeh AUC in Cmax podvržene analizi variance (ANOVA), ki je sledila logaritemski transformaciji.
Treatment with H1 - antagonists for the sought indication requires sufficient therapeutic drug levels for a period superior to 24 hours in order to provide relief from symptoms and the Applicant therefore argued that the therapeutic effect is best represented by the AUC of the unchanged loratadine and the metabolite rather than the peak concentration of parent compound alone.
Zdravljenje te indikacije z zaviralci H1 zahteva zadostne terapevtske ravni zdravila v obdobju, daljšem od 24 ur, da se zagotovi olajšanje simptomov, predlagatelj pa se je glede tega zagovarjal, da terapevtski učinek najbolje predstavlja AUC nespremenjenega loratadina in metabolita, in ne le najvišja koncentracija matične spojine same.
Regarding the results, the Applicant provided the pharmacokinetic parameters for loratadine and for descarboethoxyloratadine as well as all the individual plasma concentrations, pharmacokinetic variables and individual graphs.
Glede rezultatov je predlagatelj predložil farmakokinetične parametre za loratadin in za deskarboetoksiloratadin, pa tudi vse posamezne koncentracije v plazmi, farmakokinetične spremenljivke in posamezne grafe.
The CHMP noted the presented data and stated that according to the current guideline (Questions & Answers on the Bioavailability and Bioequivalence Guideline CHMP/EWP/40326/06), bioequivalence should preferably be based on data for the parent drug, loratadine, as confirmed in the most recent draft guideline on bioequivalence (CPMP/EWP/QWP/1401/98 Rev. 1).
CHMP je upošteval predložene podatke in izjavil, da naj, v skladu s trenutnimi smernicami (Vprašanja in odgovori na smernico o biološki razpoložljivosti in bioekvivalenci CHMP/EWP/40326/06), bioekvivalenca temelji na podatkih o matičnem zdravilu loratadin, kot je bilo potrjeno v najnovejšem osnutku smernice o bioekvivalenci (CPMP/EWP/QWP/1401/98 Rev. 1).
The Applicant considered that due to the large intra-subject variability of loratadine, the use of a wider CI (0,75 - 1,33) was justified, and that differences in Cmax do not have a major clinical effect on the use of this product in humans.
Predlagatelj je bil mnenja, da je zaradi velike variabilnosti loratadina v osebah uporaba širšega intervala zaupanja (0,75-1,33) utemeljena in da razlike v Cmax nimajo velikega kliničnega učinka na uporabo tega zdravila pri ljudeh.
The Applicant, taking into account the lack of serious safety or efficacy concerns, therefore concluded that Loratadine Sandoz 10 can be considered to be efficacious and safe.
Predlagatelj je, ob upoštevanju odsotnosti resnih zadržkov glede varnosti ali učinkovitosti, zaključil, da zdravilo Loratadine Sandoz 10 lahko velja kot učinkovito in varno.
In addition, Sandoz pharmacovigilance database indicates that there are no unaddressed safety or efficacy concerns for Loratadine Sandoz 10.
Poleg tega podatkovna baza farmakovigilance družbe Sandoz nakazuje, da ni nikakršnih nerešenih zadržkov glede varnosti ali učinkovitosti za zdravilo Loratadine Sandoz 10.
The data showed that for loratadine, the 90% confidence interval for Cmax is outside the predefined acceptance range of 80-125% (although the 90% confidence intervals for AUC0-t, AUC0-∞ were respected).
Podatki so pokazali, da je za loratadin 90 % interval zaupanja za Cmax izven vnaprej določenega razpona sprejemljivosti 80-125 % (čeprav so bili upoštevani 90 % intervali zaupanja za AUC0-t in AUC0-∞).
Additionally, the results for AUC0-t, AUC0-∞ and Cmax of descarboethoxyloratadine demonstrated bioequivalence.
Poleg tega so rezultati AUC0-t, AUC0-∞ in Cmax za deskarboetoksiloratadin dokazali bioekvivalenco.
Loratadine is a potent, long acting antihistaminic which has a high selectivity for peripheral histamine H1-receptors and low affinity for H1-receptors in the central nervous system (CNS) in vitro or in vivo.
Loratadin je močan, dolgo delujoči antihistaminik, ki je visoko selektiven za periferne histaminske receptorje H1 in ima nizko afiniteto za receptorje H1 v osrednjem živčnem sistemu in vitro ali in vivo.
The CHMP also noted the statement on GLP compliance in bio-analysis and considered that the analytical methods are acceptable and validated appropriately and seem adequate to accurately determine the concentration of loratadine and descarboethoxyloratadine in plasma.
CHMP je prav tako upošteval izjavo o skladnosti dobre laboratorijske prakse v bioanalizi in je bil mnenja, da so analitične metode sprejemljive in primerno validirane ter se zdijo zadostne za natančno določanje koncentracije loratadina in deskarboetoksiloratadina v plazmi.
- retrospective widening of the confidence interval is not accepted according to the current guidelines,
- v skladu s trenutnimi smernicami retrospektivno širjenje intervala zaupanja ni sprejemljivo,
The Applicant submitted an application for a repeat use procedure of Loratadine Sandoz 10 and associated names, 10 mg tablets on the basis of the marketing authorisation granted by The Netherlands on 12 July 2001.
Predlagatelj je predložil vlogo za postopek ponovne uporabe zdravila Loratadine Sandoz 10 in z njim povezanih imen, 10 mg tablete, na podlagi dovoljenja za promet z zdravilom, ki ga je odobrila Nizozemska 12. julija 2001.
The arguments used by the Applicant that the increase of about 5% in the intra-individual variability of Cmax in the second study (CV of 46.4%) justifies the post-hoc widening of the acceptance criteria cannot be accepted.
Predlagateljeve trditve, da povečana intraindividualna variabilnost Cmax za približno 5 % v drugi študiji (s koeficientom variacije 46,4 %) utemeljuje post hoc širjenje kriterijev sprejemljivosti, ne morejo biti sprejete.
The Applicant should submit the results of a correctly planned study that demonstrates the bioequivalence between Loratadine Sandoz 10 and the reference product in accordance with the current guidelines.
Predlagatelj mora predložiti rezultate pravilno načrtovane študije, ki dokazuje bioekvivalenco med zdravilom Loratadine Sandoz 10 in referenčnim zdravilom, v skladu s trenutnimi smernicami.
The CHMP confirmed that the Guideline and the Q&A document (which were valid and available on the EMEA website at the time when the protocol for the bioequivalence study was finalized) state that a retrospective widening of the acceptance criteria for Cmax results is not allowed.
CHMP je potrdil, da smernica in dokument z vprašanji in odgovori (ki so bili v času, ko je bil protokol za bioekvivalenčno študijo končan, veljavni in na voljo na spletni strani EMEA) navajajo, da retrospektivno širjenje kriterijev sprejemljivosti za rezultate Cmax ni dovoljeno.
Therefore, in view of the results obtained from the original study, demonstrating an intra-individual CV of 41.2% for Cmax, a widening of the confidence interval should have been predefined in the study protocol of the second study (justifying any safety or efficacy concerns for patients switched between formulations).
Zato bi moralo biti glede na rezultate, dobljene iz izvorne študije, ki dokazujejo intraindividualni koeficient variacije za Cmax 41,2 %, širjenje intervala zaupanja v protokolu druge študije vnaprej določeno (z utemeljitvijo morebitnih zadržkov glede varnosti ali učinkovitosti za bolnike, ki bi jim zamenjali formulacijo).
The reason for this is that Cmax of a parent compound is usually more sensitive to detect differences between formulations in absorption rate than Cmax of a metabolite”.
Razlog za to je, da je, za razliko od Cmax metabolita, Cmax matične spojine navadno bolj občutljiv za zaznavo razlik v hitrosti absorpcije med posameznimi formulacijami“.
Detailed explanations of the statistical calculations and the improved bio-analytical methods used were provided and in addition, the Applicant explained that the pharmacokinetics of loratadine increased its intra-individual variability.
Predlagatelj je predložil podrobno razlago statističnih izračunov in uporabljenih izboljšanih bioanalitičnih metod, poleg tega pa je razložil, da farmakokinetika loratadina poveča njegovo variabilnost v osebah.
In conclusion, the submitted study demonstrates the bioequivalence of Loratadine Sandoz 10mg tablets to the reference product for AUC0-t and AUC0-∞ of loratadine, but not for the Cmax parameter.
V zaključku je predložena študija dokazala bioekvivalenco zdravila Loratadine Sandoz 10 mg tablete z referenčnim zdravilom za AUC0-t in AUC0-∞ za loratadin, vendar ne za parameter Cmax.
The CHMP noted that the study site had been satisfactorily inspected and that the study was performed according to GCP guidelines.
CHMP je ugotovil, da je bilo mesto študije zadovoljivo pregledano in da je bila študija izpeljana v skladu s smernicami dobre klinične prakse.
Treatment phases were separated by a washout period of 21 days and subjects were administered a single oral dose as a 1 x 10 mg tablet and blood sampling was carried out prior to dosing (0) and at regular intervals post-dose.
Faze zdravljenja so bile prekinjene z obdobji izpiranja po 21 dni, osebe pa so prejele enojni peroralni odmerek v obliki 1 x 10 mg tablete, pred dajanjem odmerka (0) in ob rednih intervalih po odmerku pa so jim odvzeli vzorec krvi.
Loratadine and descarboethoxyloratadine concentrations in plasma were determined by s liquid chromatography assay with MS-MS detection.
Koncentracije loratadina in deskarboetoksiloratadina v plazmi so določili s tekočinsko kromatografijo z MS/MS detekcijo.
The samples were handled adequately and plausible reasons were presented for analysis repetition.
Z vzorci se je primerno ravnalo, za ponovitev analize pa so bili predstavljeni utemeljeni razlogi.
In the clinical setting, loratadine has been used for over 10 years in the treatment of allergic disorders such as conjunctivitis, atopic dermatitis, urticaria, asthma, and anaphylaxis.
Klinično se loratadin uporablja že več kot 10 let pri zdravljenju alergijskih obolenj, kot so konjunktivitis, atopični dermatitis, urtikarija, astma in anafilaksa.
The Applicant decided to perform a new BE study and submitted the full details of a single centre, randomised, single-dose, open-label, laboratory blinded 2-way crossover bioequivalence study comparing the rate and extent of absorption of Loratadine Sandoz 10 mg tablets versus the reference loratadine (Clarityne by ScheringPlough) under fasting conditions (Study SZ190/08).
Predlagatelj je sklenil izvesti novo študijo bioekvivalence in je predložil vse podrobnosti enocentrične, randomizirane, laboratorijske, slepe, dvosmerne, navzkrižne bioekvivalenčne študije enega odmerka in odprtega zdravljenja, v kateri so primerjali hitrost in obseg absorpcije zdravila Loratadine Sandoz 10 mg tablete z referenčnim loratadinom (zdravilom Clarityne družbe Schering-Plough) v teščem stanju (študija SZ190/08).
According to the current applicable guidelines, bioequivalence must be demonstrated for the parent compound for generic products.
V skladu s trenutno veljavnimi smernicami mora biti za generična zdravila bioekvivalenca dokazana za matično spojino.
Therefore, the products cannot be considered bioequivalent and the CHMP concluded that the benefit-risk of Loratadine Sandoz 10 is negative.
Zato zdravili ne moreta veljati kot bioekvivaletni, CHMP pa je zaključil, da je razmerje med koristmi in tveganji za zdravilo Loratadine Sandoz 10 negativno.
The CHMP concluded that the bioequivalence between Loratadine Sandoz 10 and the reference product was not sufficiently demonstrated and adopted a List of Outstanding Issues, requesting the Applicant to further substantiate bioequivalence.
CHMP je zaključil, da bioekvivalenca med zdravili Loratadine Sandoz 10 in referenčnim zdravilom ni bila zadostno dokazana in je sprejel seznam nerešenih vprašanj, v katerem poziva predlagatelja, naj dodatno podkrepi bioekvivalenco.
Loratadine is an antagonist of histamine at H1 receptor sites (competitive, reversible) leading to the relief of allergic symptoms.
Loratadin je (kompetitivni, reverzibilni) zaviralec histamina na mestih receptorjev H1, kar vodi v olajšanje simptomov alergije.
The study was considered acceptable for the estimation of PK parameters and properly designed in terms of wash-out, sampling periods and drug intake procedures.
Študija velja kot sprejemljiva za oceno farmakokinetičnih parametrov in primerno zasnovana v smislu obdobja izpiranja in vzorčenja ter postopkov vnosa zdravila.
the benefit-risk of the generic Loratadine Sandoz 10 is therefore considered to be negative,
razmerje med koristmi in tveganji za generično zdravilo Loratadine Sandoz 10 je zato negativno,
Loratadine Sandoz 10 is used for the long term treatment of allergies and both parent compound and metabolite contribute to the clinical efficacy.
Zdravilo Loratadine Sandoz 10 se uporablja za dolgotrajno zdravljenje alergij, h klinični učinkovitosti pa pripomoreta tako matična spojina kot tudi metabolit.
The sought indications for Loratadine Sandoz 10 were the relief of symptoms associated with seasonal and perennial allergic rhinitis and the treatment of the symptoms of chronic urticaria.
Indikacije za zdravilo Loratadine Sandoz 10, za katere je bila predložena vloga, so bile olajšanje simptomov, povezanih s sezonskim in celoletnim alergijskim rinitisom in zdravljenje simptomov kronične urtikarije.
While bioequivalence between Loratadine Sandoz 10 and the reference product was shown for the active metabolite, bioequivalence with regards to the parent compound was not demonstrated.
Medtem ko je bila bioekvivalenca med zdravilom Loratadine Sandoz 10 in referenčnim zdravilom dokazana za aktivni metabolit, pa bioekvivalenca z ozirom na matično spojino ni bila dokazana.
- bioequivalence between Loratadine Sandoz 10 and the reference product was not demonstrated for the parent compound,
- bioekvivalenca med zdravilom Loratadine Sandoz 10 in referenčnim zdravilom ni bila dokazana za matično spojino,
the CHMP has recommended the refusal of the granting of the Marketing Authorisations in the Concerned Member States and the suspension of the Marketing Authorisation in the Member States where the product is currently authorised, for Loratadine Sandoz 10 and associated names (see Annex I).
CHMP je za zdravilo Loratadine Sandoz 10 in z njim povezana imena (glejte Dodatek I) priporočil zavrnitev odobritve dovoljenja za promet z zdravilom v zadevnih državah članicah ter umik dovoljenja za promet z zdravilom v državah članicah, v katerih je zdravilo trenutno odobreno.
The calculated 90% CI for AUC0-t, AUCinf and Cmax for the metabolite descarboethoxyloratadine were within the 0.80- 1.25 acceptance range, but bioequivalence for loratadine tablets should also be based on parent compound data and because the 90% CI for Cmax and AUC of the parent compound were outside the standard 0.80 - 1.25 acceptance criterion, the objecting concerned member states considered that bioequivalence between Loratadine Sandoz 10 and the reference product could not be established.
Izračunani 90 % interval zaupanja za AUC0-t, AUCinf in Cmax za metabolit deskarboetoksiloratadin so bili znotraj razpona sprejemljivosti 0,80-1,25, vendar bi morala bioekvivalenca za tablete loratadina prav tako temeljiti na podatkih matičnih spojin.
LORATADINE 10 MG TABLETS10 mg Tablet
LORATADINE 10 mg TABLETS 10 mg Tableta
United Kingdom Sandoz Limited Woolmer way
Sandoz Limited Woolmer way Bordon, Hants, GU35 9 QE Velika Britanija
LORATADIN SANDOZ 10 MG 10 mg Tablet
LORATADIN SANDOZ 10 mg 10 mg Tableta
Prevalence %
Prevalenca %
African/Ethiopian African American
Afriška/Etiopska Afroameriška
Hungarian Northern European
Madžarska Severnoevropska
It allows continued monitoring of the benefit/risk balance of the medicinal product.
To omogoča neprestano spremljanje razmerja koristi/tveganja zdravila.
“Children with compromised respiratory function
" Otroci z ogroženo respiratorno funkcijo
Estimates indicate that up to 7% of the Caucasian population may have this deficiency.
Ocenjujejo, da ima do 7 % kavkazijske populacije pomanjaknje omenjenega encima.
The product information may be subsequently updated by the Member State competent authorities, in liaison with the Reference Member State, as appropriate, in accordance with the procedures laid down in Chapter 4 of Title III of Directive 2001/83/EC.
Informacije o zdravilu se lahko naknadno posodobijo s strani pristojnih organov držav članic, v povezavi z referenčno državo članico, kot je ustrezno, in v skladu s postopki določenimi v Poglavju 4 Naslova III Direktive 2001/83/ES .
By reporting side effects you can help provide more information on the safety of this medicine.
S poročanjem neželenih učinkov pomagate zagotoviti več informacij o varnosti tega zdravila.
These factors may worsen symptoms of morphine toxicity.”
Vsi ti dejavniki lahko poslabšajo simptome morfinske toksičnosti. "
“Paediatric population:
"Pediatrična populacija:
Some people have a variation of this enzyme and this can affect people in different ways.
Nekateri ljudje imajo spremenjen encim, kar lahko vpliva na ljudi na različne načine.
Estimates of prevalence of ultra-rapid metabolisers in different populations are summarized below:
Ocene prevalenc zelo hitrih presnavljalcev različnih populacij so povzete spodaj:
“CYP2D6 metabolism
CYP2D6 metabolizem
If you get any side effects, talk to your <doctor> <or> <,> <pharmacist> <or nurse>.
Če opazite kateri koli neželeni učinek, se posvetujte s svojim <zdravnikom> <ali> <,> <farmacevtom> <ali medicinsko sestro>.
Annex III Amendments to relevant sections of the product information
Priloga III Dopolnitve ustreznih poglavij informacij o zdravilu
Reporting suspected adverse reactions after authorisation of the medicinal product is important.
Poročanje o domnevnih neželenih učinkih po registraciji zdravila je pomembno.
Codeine and morphine passes into breast milk.”
Kodein in morfin prehajata v materino mleko . "
Section 4.8 Undesirable effects
Poglavje 4.8 - Neželeni učinki