natgillin/translations-raw huggingface dataset:
However, the applicant claims there is a very fast distribution of meloxicam from the intramuscular injection site into the general circulation and subsequently a very fast elimination from tissues like liver, kidney and muscle taking into consideration the identical elimination half-life in pigs after intravenous or intramuscular administration, which justifies the claim for waiver of a bioequivalence study in pigs based on results of the residue depletion study in comparison to the Metacam 20 mg/ml product.
Vendar predlagatelj trdi, da je porazdelitev meloksikama z mesta intramuskularnega injiciranja v splošni obtok zelo hitra, kar posledično pomeni zelo hitro izločanje iz tkiv, kot so jetra, ledvice in mišice, če upoštevamo identično razpolovno dobo izločanja pri prašičih po intravenskem ali intramuskularnem injiciranju, ki upravičuje zahtevek za oprostitev bioekvivalenčnih študij pri prašičih na osnovi rezultatov študije izločanja ostankov v primerjavi z zdravilom Metacam 20 mg/ml.
The CVMP does not accept that the comparison of residues from two different products at a single time point allows conclusions to be drawn about the blood concentration-time profile, or that the studies provide an accurate estimate of relative bioavailability.
CVMP meni, da enkratna primerjava ostankov dveh različnih zdravil ne omogoča sklepanja o časovnem profilu krvne koncentracije in da študije ne omogočajo točne ocene relativne biološke uporabnosti.
Both studies showed that meloxicam is rapidly eliminated from the tissues of the pig, falling below MRL in most tissues within a day of administration.
Študiji sta pokazali, da se meloksikam hitro izloča iz tkiva prašičev in v roku enega dneva injiciranja ostane pod mejnimi vrednostmi ostankov v večini tkiv.
This is supported by the evidence from the bioequivalence study between Metacam 5 mg/ml and Metacam 20 mg/ml which showed that Cmax and AUC were higher for the higher concentration formulation, and the findings in residues studies that suggest more rapid absorption from the 40 mg/ml product.
To podpirajo ugotovitve bioekvivalenčne študije zdravila Metacam 5 mg/ml in zdravila Metacam 20 mg/ml, pri kateri sta bili vrednosti Cmax in AUC višji pri večjih koncentracijah zdravila, in ugotovitve študij ostankov, ki navajajo hitrejšo absorpcijo zdravila pri odmerku 40 mg/ml.
Based on the data presented and the responses to questions, the CVMP concluded that the data for Melosolute 40 mg/ml solution for injection for cattle, pigs and horses were not in accordance with the requirements of Directive 2001/82/EC, and that the benefit-risk balance is currently not favourable with respect to its proposed indications in the target species pigs.
Na osnovi predloženih podatkov in odgovorov na vprašanja je CVMP zaključil, da podatki za zdravilo Melosolute 40 mg/ml raztopina za injiciranje za govedo, prašiče in konje niso v skladu z zahtevami Direktive 2001/82/ES in da razmerje med tveganji in koristmi trenutno ni ugodno.
• In horses, the proposed indications are for the alleviation of inflammation and relief of pain in both acute and chronic musculo-skeletal disorders and for the relief of pain associated with equine colic.
• Pri konjih je predlagana indikacija za umirjanje vnetja in lajšanje bolečine pri akutnih ter kroničnih mišično-skeletnih obolenjih in za lajšanje s koliko povezane bolečine pri konjih.
Therefore the CVMP recommends the refusal of the granting of the marketing authorisation for Melosolute 40 mg/ml solution for injection for the target species pigs.
CVMP zato priporoča zavrnitev izdaje dovoljenja za promet za zdravilo Melosolute 40 mg/ml raztopina za injiciranje za ciljne vrste prašičev.
Therefore the applicant has not provided satisfactory data in pigs to enable extrapolation of the safety and efficacy data from the Metacam 20 mg/ml product and to allow this species to be included in the product information.
Predlagatelj torej ni predložil zadovoljivih podatkov za prašiče, ki bi omogočali ekstrapolacijo podatkov o varnosti in učinkovitosti zdravila Metacam 20 mg/ml in vključitev te vrste v podatke o zdravilu.
This is a ‘hybrid' application and the requirements differ from those of a generic product due to the fact that the test formulation contains an increase in concentration of the active substance compared to the reference formulation.
Ker gre za „hibridno“ vlogo, se zahteve razlikujejo od tistih za generična zdravila, saj vsebujejo testni pripravki večjo koncentracijo zdravilne učinkovine kot referenčni pripravki.
These issues remained unsolved and therefore a referral under Article 33(1) of Directive 2001/82/EC to the CMD(v) was started.
Ta vprašanja so ostala nerešena, zato je bil sprožen napotitveni postopek v skladu s členom 33(1) Direktive 2001/82/ES, ki je bil predložen Usklajevalni skupini za postopek medsebojnega priznavanja in decentralizirani postopekzdravila za uporabo v veterinarski medicini (CMD(v)).
• In pigs, the proposed indications are for use in non-infectious locomotor disorders to reduce the symptoms of lameness and inflammation, and for adjunctive therapy in the treatment of puerperal septicaemia and toxaemia (mastitis-metritis-agalactia syndrome) with appropriate antibiotic therapy.
• Pri prašičih je predlagana indikacija za ublažitev ohromelosti in vnetja pri neinfekcijskih lokomotornih motnjah in za pomožno zdravljenje pri zdravljenju puerperalne septikemije ter toksemije (sindroma mastitisa, metritisa in agalaktije) ob ustreznem antibiotičnem zdravljenju.
It is also noted that the Bioequivalence GL does not give an exemption from in vivo studies for solutions intended for parenteral injection where there is a difference in the concentration of the active substance.
Navedeno je tudi, da bioekvivalenčne smernice ne izvzemajo študij in vivo za raztopine za parenteralno injiciranje z razliko v koncentraciji zdravilne učinkovine.
• Residues studies would suffice as a substitute for bioequivalence, considering that as the meloxicam residues in liver and muscle were comparable at the 4 hour sampling point and as the withdrawal times for Melosolute 40 mg/ml and Metacam 20 mg/ml are the same, the pharmacokinetic parameters will be comparable.
• Študije ostankov zadostujejo kot nadomestek za bioekvivalenco, saj bodo farmakokinetični parametri, glede na to, da so bili ostanki meloksikama v jetrih in mišicah primerljivi pri vzorčenju po 4 urah in da je karencaza zdravilo Melosolute 40 mg/ml in zdravilo Metacam 20 mg/ml enaka,
It is noticed that peak plasma concentration was reached 1 hour after the second administration in the residue depletion study using 14C-Meloxicam 20 mg/ml and declined rapidly from a Cmax of 1730 ng equivalent/ml at 1 hour after administration and over the next 95 hours (no sampling time points stated).
V študiji izločanja ostankov so zabeležili, da se največja plazemska koncentracija pojavi 1 uro po drugem injiciranju zdravila 14C-Meloxicam 20 mg/ml in hitro upada s Cmax, ki znaša 1730 ng ekvivalenta/ml, 1 uro po injiciranju in naslednjih 95 ur (časi vzorčenj niso navedeni).
Potential serious risks were identified during the decentralised procedure by Ireland and the United Kingdom as they considered the bioequivalence of Melosolute 40 mg/ml solution for injection with the reference product, Metacam 20 mg/ml solution for injection had not been sufficiently demonstrated for the target species pigs, and no other satisfactory data had been provided to enable extrapolation of safety and efficacy data from the reference product for this species.
Irska in Združeno kraljestvo sta med decentraliziranim postopkom opozorila na potencialno resna tveganja, saj za ciljne vrste prašičev bioekvivalenca zdravila Melosolute 40 mg/ml raztopina za injiciranje in referenčnega zdravila Metacam 20 mg/ml raztopina za injiciranje ni bila zadostno dokazana, predloženi pa niso bili nobeni drugi zadovoljivi podatki, ki bi omogočali ekstrapolacijo podatkov o varnosti in učinkovitosti referenčnega zdravila na te vrste.
For this generic ‘hybrid' application, the benefits are extrapolated from the safety and efficacy data for the reference product, Metacam 20 mg/ml.
Za to generično „hibridno“ vlogo so koristi ekstrapolirane iz podatkov o varnosti in učinkovitosti referenčnega zdravila Metacam 20 mg/ml.
This is a generic ‘hybrid' application in which the applicant is extrapolating pre-clinical and clinical data from the reference product Metacam 20 mg/ml.
Gre za generično „hibridno“ vlogo, pri kateri predlagatelj ekstrapolira predklinične in klinične podatke o referenčnem zdravilu Metacam 20 mg/ml.
This referral under Article 33(4) of Directive 2001/82/EC was made due to concerns that the applicant had not satisfactorily demonstrated the bioequivalence of Melosolute 40 mg/ml solution for injection with the reference product, Metacam 20 mg/ml solution for injection for the target species pigs, or provided other satisfactory justification to extrapolate the data of the reference product.
Ta napotitveni postopek je bil v skladu s členom 33(4) Direktive 2001/82/ES sprožen zaradi pomislekov, da predlagatelj ni zadovoljivo dokazal bioekvivalence zdravila Melosolute 40 mg/ml raztopina za injiciranje z referenčnim zdravilom Metacam 20 mg/ml raztopina za injiciranje za ciljne vrste prašičev ali predložil drugih zadovoljivih obrazložitev za ekstrapolacijo podatkov o referenčnem zdravilu.
• In cattle, the proposed indications are for use in acute respiratory infection with appropriate antibiotic therapy to reduce clinical signs; for use in diarrhoea in combination with oral re hydration therapy to reduce clinical signs in calves of over one week of age and in young, non lactating cattle, and for adjunctive therapy in the treatment of acute mastitis, in combination with antibiotic therapy.
• Pri govedu je predlagana indikacija za zmanjšanje kliničnih znakov pri akutnih okužbah dihal ob ustreznem antibiotičnem zdravljenju, za umirjanje driske v kombinaciji s peroralnim rehidracijskim zdravljenjem pri teletih, starejših od enega tedna, in mladih govedih, ki niso v obdobju laktacije,
In the absence of such a study, the residues depletion data provide no firm evidence that allows quantification of any difference in rate and extent of absorption of meloxicam between Melosolute 40 mg/ml and Metacam 20 mg/ml, and consequently the identification of its impact on clinical safety and efficacy is not possible.
Če taka študija ni bila izvedena, podatki izločanja ostankov ne zagotavljajo trdnih dokazov za kvantifikacijo kakršnihkoli razlik v hitrosti in obsegu absorpcije meloksikama med zdravilom Melosolute 40 mg/ml in zdravilom Metacam 20 mg/ml, zato določanje njegovega vpliva na klinično varnost in učinkovitost ni mogoče.
The current guideline on the conduct of bioequivalence studies (EMA/CVMP/016/00-Rev.2) gives no exemption from the need to conduct in vivo bioequivalence studies for parenterally administered solutions when the strength of the active substance differs from that of the reference product and evidence suggests that this change does have the potential to influence the rate and possibly the extent of absorption;
Trenutne smernice o izvajanju bioekvivalenčnih študij (EMA/CVMP/016/00-Rev.2) ne izvzemajo potrebe po izvajanju bioekvivalenčnih študij in vivo za parenteralno injicirane raztopine, pri katerih je jakost zdravilne učinkovine drugačna od jakosti zdravilne učinkovine referenčnega zdravila, in dokazi navajajo, da ta sprememba lahko potencialno vpliva na hitrost in morda tudi obseg absorpcije.
The applicant submitted an application for a decentralised procedure for Melosolute 40 mg/ml solution for injection for cattle, pigs and horses.
Predlagatelj je predložil vlogo za decentralizirani postopek za zdravilo Melosolute 40 mg/ml raztopina za injiciranje za govedo, prašiče in konje.
The relevant guidance gives no exemption from the need to conduct in vivo bioequivalence studies for parenterally administered solutions when the strength of the active substance differs from that of the reference product and evidence suggests that this change does have the potential to influence the rate and possibly the extent of absorption.
Relevantne smernice ne izvzemajo potrebe po izvajanju bioekvivalenčnih študij in vivo za parenteralno injicirane raztopine, pri katerih je jakost zdravilne učinkovine drugačna od jakosti zdravilne učinkovine referenčnega zdravila, in dokazi navajajo, da ta sprememba lahko potencialno vpliva na stopnjo in morda tudi obseg absorpcije.
The applicant should have provided a blood-level comparative pharmacokinetic study between Melosolute 40 mg/ml and the reference product.
Predlagatelj bi moral predložiti primerjalno farmakokinetično študijo na krvni ravni med zdravilom Melosolute 40 mg/ml in referenčnim zdravilom.
The timing and sparsity of sampling of tissues does not allow tissue residue concentrations to be used as a surrogate for plasma levels that would allow an estimation of blood Cmax and AUC.
Časovna razporeditev in razpršenost vzorčenja tkiva ne omogoča uporabe koncentracij ostankov tkiva kot nadomestka za plazemske koncentracije, s pomočjo katerih bi lahko podali oceno vrednosti C
The benefit-risk balance for pigs remains inconclusive in absence of adequate information on the safety and efficacy of the product.
Vrednotenje razmerja med tveganji in koristmi Zaradi pomanjkanja ustreznih informacij o varnosti in učinkovitosti zdravila razmerje med tveganji in koristmi za prašiče ostaja nedoločeno.
The Committee considered whether the bioequivalence of the test product with the reference product in the target species pigs had been proven, based on the available data.
Na podlagi razpoložljivih podatkov je Odbor preučil, ali je bila za ciljne vrste prašičev dokazana bioekvivalenca testnega zdravila z referenčnim zdravilom.
This is a ‘hybrid' application according to Article 13(3) Directive 2001/82/EC, as amended, referring to the centrally authorised reference product Metacam 20 mg/ml solution for injection for cattle, pigs and horses (EU/2/97/004).
V skladu s členom 13(3) dopolnjene Direktive 2001/82/ES gre za „hibridno“ vlogo, ki se opira na referenčno zdravilo Metacam 20 mg/ml raztopina za injiciranje za govedo, prašiče in konje (EU/2/97/004), odobreno po centraliziranem postopku.
• The pharmaceutical similarity of Melosolute 40 mg/ml and Metacam 20 mg/ml formulations.
• Farmacevtska podobnost zdravila Melosolute 40 mg/ml in zdravila Metacam 20 mg/ml.
It should be noted that for cattle and horses, the applicant is exempt from providing an in vivo bioequivalence study under waiver 7.1.a of the CVMP guideline on the conduct of bioequivalence studies for veterinary medicinal products (EMA/CVMP/016/00-Rev.2)1 (Bioequivalence GL).
Opozoriti je treba, da v skladu z izvzetjem pod točko 7.1.a smernic CVMP o izvajanju bioekvivalenčnih študij za zdravila za uporabo v veterinarski medicini (EMA/CVMP/016/00-Rev.2)1 predlagatelju ni treba predložiti bioekvivalenčne študije in vivo za govedo in konje (bioekvivalenčne smernice).
In order to address the concerns raised by the referral, the applicant presented a justification for the omission of a bioequivalence study for Melosolute 40 mg/ml solution for injection and the reference product, Metacam 20 mg/ml solution for injection.
Da bi odgovoril na pomisleke v napotitvenem postopku, je predlagatelj predložil obrazložitev za izključitev bioekvivalenčne študije za zdravilo Melosolute 40 mg/ml raztopina za injiciranje in referenčno zdravilo Metacam 20 mg/ml raztopina za injiciranje.
Meloxicam is a NSAID of the oxicam class which acts by inhibition of prostaglandin synthesis, thereby exerting anti-inflammatory, anti-exudative, analgesic and antipyretic effects.
Njegovo delovanje temelji na zaviranju sinteze prostaglandinov, zato deluje protivnetno, antieksudativno, analgetično in antipiretično.
The proposed indications in cattle, pigs and horses for Melosolute 40 mg/ml are identical to the approved indications for the reference product, Metacam 20 mg/ml solution for injection for cattle, pigs and horses.
Predlagane indikacije zdravila Melosolute 40 mg/ml za govedo, prašiče in konje so popolnoma enake odobrenim indikacijam za referenčno zdravilo, tj. zdravilo Metacam 20 mg/ml raztopina za injiciranje za govedo, prašiče in konje.
Melosolute differs from the reference product through different strength of the active substance, meloxicam (40 mg/ml versus 20 mg/ml) and a different concentration of one of the excipients.
Zdravilo Melosolute se od referenčnega zdravila razlikuje v jakosti zdravilne učinkovine meloksikam (40 mg/ml namesto 20 mg/ml) in koncentraciji ene od pomožnih snovi.
Any increase in the rate/extent of absorption has not been quantified for Melosolute 40 mg/ml in a comparative pharmacokinetic study with the reference product and it could have implications in terms of target animal safety.
V primerjalni farmakokinetični študiji z referenčnim zdravilom ni bilo kvantificirano nobeno povečanje hitrosti/obsega absorpcije za zdravilo Melosolute 40 mg/ml, kar bi lahko imelo posledice za varnost ciljnih živali.
Melosolute 40 mg/ml solution for injection for cattle, pigs and horses contains meloxicam 40 mg/ml.
Zdravilo Melosolute 40 mg/ml raztopina za injiciranje za govedo, prašiče in konje vsebuje 40 mg/ml meloksikama.
In conclusion, the following points were not adequately addressed by the applicant: (i) the impact of using different studies for comparison of formulation effects, (ii) the choice of time points which are not consistent with the absorption phase, and do not provide evidence of the rate and extent of absorption (iii) the robustness of the data in relation to the precision of the estimates needed to provide accurate comparison between formulations.
Čeprav so stopnje meloksikama v jetrih in mišičnem tkivu pri vzorčenju po 4 urah podobne za oba odmerka zdravila, to odraža eno časovno točko in ne dokazuje, da bodo plazemsk koncentracije podobne v celotnem trajanju časovne krivulje koncen Predlagatelj prav tako ni pravilno pojasnil naslednjih točk: (i) vpliv uporabe različnih študij za primerjavo učinkov različnih odmerkov, (ii) izbira časovnih točk, ki niso skladne s fazo absorpcije in ne dokazujejo stopnje in obsega absorpcije, (iii) stabilnost podatkov glede na natančnost ocen, potrebnih za ustrezno primerjavo med različnima odmerkoma.
Meloxicam appeared to be more rapidly absorbed from the 40 mg/ml compared to the 20 mg/ml injection site, as suggested from the residue depletion data at the first (4 hours) sampling time-point, where the injection site levels were lower and kidney levels higher for the 40 mg/ml formulation.
Podatki izločanja ostankov po prvem vzorčenju (po 4 urah) nakazujejo, da se meloksikam hitreje absorbira pri injiciranju odmerka 40 m kot pri odmerku 20 mg/ml, ker so bile pri odmerku 40 mg/ml stopnje na mestu injiciranja nižje, stopn v ledvicah pa višje.
The presented studies evaluate the depletion of tissue residues following the administration of the products in the target species using the recommended or proposed dose rate and route of administration, with the purpose of determining when these fall below the MRLs.
CVMP meni, da se namen in zasnova biokevivalenčnih študij in študij ostankov močno razlikujejo.Predstavljene študije ocenjujejo izločanje ostankov tkiva po injiciranju zdravila v ciljno vrsto z uporabo priporočene ali predlagane stopnje odmerka in poti uporabe, da bi določili, kdaj so parametri pod mejnimi vrednostmi ostankov.
Metacam 5 mg/ml formulation.
To je Odbor že sprejel za zdravilo Metacam 5 mg/ml.
Melosolute 40 mg/ml solution for injection is administered intramuscularly in pigs, whereas in cattle and horses it is administered intravenously.
Zdravilo Melosolute 40 mg/ml raztopina za injiciranje se pri prašičih injicira intramuskularno, pri govedu in konjih pa intravensko.
The CVMP acknowledged the similarity of the formulations of the Melosolute 40 mg/ml and Metacam 20 mg/ml in terms of their excipients.
CVMP je potrdil podobnost pomožnih snovi v zdravilu Melosolute 40 mg/ml in zdravilu Metacam 20 mg/ml.
The applicant has submitted a residue depletion study conducted with Melosolute 40 mg/ml as evidence of the comparative pharmacokinetic profile between their product and Metacam 20 mg/ml.
Predlagatelj je kot dokaz komparativnega farmakokinetičnega profila med zdravilom Melosolute 40 mg/ml in Metacam 20 mg/ml predložil študijo izločanja ostankov za zdravilo Melosolute 40 mg/ml.
• the residues depletion data provided no firm evidence that allows quantification of any difference in rate and extent of absorption of meloxicam between Melosolute 40 mg/ml and Metacam 20 mg/ml, and therefore to quantify its impact on clinical safety and efficacy; the particulars concerning the target species pigs that were submitted in support of the application do not comply with Article 13 of Directive 2001/82/EC, and consequently do not satisfy the criteria for authorisation in respect of safety and efficacy for the target species pigs.
• Podatki o izločanju ostankov ne zagotavljajo trdnih dokazov, ki bi omogočali kvantifikacijo kakršnekoli razlike v hitrosti in obsegu absorpcije meloksikama med zdravilom Melosolute 40 mg/ml in zdravilom Metacam 20 mg/ml ter s tem kvantifikacijo njegovega vpliva na klinično varnost in učinkovitost.
This is the standard approach that has been applied in the past for intramuscularly or subcutaneously administered injections when the concentration of the active substance is changed, and it would be possible and scientifically valid for the applicant to conduct a comparative pharmacokinetic study to compare the Melosolute 40 mg/ml formulation with the Metacam 20 mg/ml formulation.
Za predlagatelja bi bilo možno in znanstveno veljavno, da izvede komparativno farmakokinetično študijo za primerjavo zdravila Melosolute 40 mg/ml z zdravilom Metacam 20 mg/ml.
After first opening: 5 months
Po prvem odprtju: 5 mesecev
Make sure it is fixed well in place.
Prepričajte se, da je dobro pritrjen.
Instructions for use for patients or carers:
Navodila za uporabo za bolnike ali skrbnike:
* Statistically significant (p-value)
* statistično pomembno (p-vrednost)
- These effects are more likely at the start of the treatment or after a dose increase.
- Ti učinki so verjetnejši ob začetku zdravljenja ali ob povečanju odmerka.
Formal interaction studies have only been performed in adults.
Formalne študije medsebojnega delovanja so izvedli le pri odraslih.
Learning and memory function were not affected.
Učenje in delovanje spomina nista bila prizadeta.
Percent reduction over placebo (%)
Odstotek zmanjšanja v primerjavi s placebom (%)
However, this is not considered to be a clinically relevant difference.
Vendar to ne šteje za klinično pomembno razliko.
- The medicine may be taken with or without food.
- Zdravilo lahko jemljete s hrano ali brez.
After first opening of the bottle, use within 5 months.
Po prvem odprtju steklenice porabite zdravilo v 5 mesecih.
No safety risks were observed.
Varnostnih tveganj niso opazili.
The dose per intake for each patient should be calculated using the following formula:
Odmerek na vnos za vsakega bolnika se izračuna po naslednji formuli:
Belgium (name and address only for outer carton, logo on carton and etiquette)
Belgija (ime in naslov le za zunanjo škatlo, logotip na škatli in nalepki)
See also section 4.8, paediatric data.
Glejte tudi poglavje 4.8, pediatrični podatki.
Juvenile animals studies
Študije pri mladičih živali
Partial seizures are fits that start by only affecting one side of the brain.
- Parcialni napadi so krči, ki na začetku prizadanejo samo eno stran možganov.
None (monohydroxy derivative, MHD)
Nič (monohidroksi derivat, MHD)
The types of adverse reactions reported during the first 7 days of treatment were similar to those reported for the overall treatment period.
Vrste neželenih učinkov, o katerih so poročali med prvimi 7 dnevi zdravljenja, so bili podobni tistim, o katerih so poročali za celotno obdobje zdravljenja.
The terminal plasma half-life (t1/2) is approximately 9 hours.
Končni plazemski razpolovni čas (t1/2) je približno 9 ur.
Across all studies, 81.7 % of the patients who completed randomized studies were enrolled in the long-term open-label extension studies.
V vseh študijah se je 81,7 % bolnikov, ki so zaključili randomizirane študije, vključilo v dolgotrajne odprte študije.