natgillin/translations-raw huggingface dataset:
The Committee for Medicinal Products for Veterinary Use (CVMP) concluded that the benefits of Osurnia exceed the risks for the approved indications and recommended that Osurnia be given a marketing authorisation.
Odbor za veterinarske lijekove (CVMP) zaključio je da koristi proizvoda Osurnia premašuju rizike za odobrene indikacije i preporučio izdavanje odobrenja za stavljanje u promet za lijek Osurnia.
What is Osurnia?
Što je Osurnia?
Florfenicol is an antibiotic which works by blocking protein formation in bacterial cells.
Florfenikol je antibiotik koji djeluje blokadom nastanka proteina u stanicama bakterija.
Osurnia must not be used if the ear drum is perforated or in dogs with generalised demodicosis (mange caused by the mite Demodex canis).
Osurnia se ne smije koristiti ako je bubnjić uha perforiran ili kod pasa s generaliziranom demodikozom (šuga uzrokovana grinjom Demodex canis).
Ear infections in dogs can be caused by bacteria or yeasts/fungi.
Infekcije uha u pasa mogu biti uzrokovane bakterijom ili kvascima/gljivicama.
Terbinafine kills fungi by blocking the formation of ergosterol, an important part of fungal cell walls.
Terbinafin ubija gljivice blokadom nastanka ergosterola, važnog dijela stjenke stanica gljiva.
What is the risk associated with Osurnia?
Koji su rizici povezani s lijekom Osurnia?
Osurnia is a veterinary medicine that contains three active substances: terbinafine, florfenicol and betamethasone acetate.
Osurnia je veterinarsko-medicinski proizvod koji sadrži tri djelatne tvari: terbinafin, florfenikol i betametazon acetat.
The benefit/risk balance may be found in the scientific discussion module of this EPAR.
Omjer koristi/rizika može se naći u modulu ovog EPAR-a koji sadrži znanstvene rasprave.
The US study involved 284 dogs, 190 of which were treated with Osurnia, while 90 dogs received placebo gel (dummy treatment).
Američko ispitivanje uključivalo je 284 psa od kojih je 190 bilo liječeno Osurnijom dok je 90 pasa primilo placebo gel (slijepo liječenje).
Why has Osurnia been approved?
Zašto je lijek Osurnia odobren?
It is available as a gel to be given into the ear.
Dostupan je u obliku gela koji se stavlja u uho.
Two of the active substances in Osurnia terbinafine and florfenicol, act against possible causes of infection.
Dvije djelatne tvari u proizvodu Osurnia, terbinafin i florfenikol djeluju protiv mogućih uzročnika infekcije.
If the veterinary medicine is accidentally swallowed, immediate medical advice should be sought and the package leaflet or label shown to the doctor.
Međutim, ako osoba slučajno proguta veterinarsko-medicinski proizvod, potrebno je odmah potražiti savjet liječnika i pokazati mu naljepnicu proizvoda ili uputu o proizvodu.
Terbinafine, florfenicol and betamethasone
Terbinafin/florfenikol/betametazon acetat
Three field studies were conducted in dogs with otitis externa caused by bacterial or fungal infections, investigating the effect of treatment following cleaning out of the ear with saline solution; treatment with two doses of Osurnia, one week apart, was compared with another comparable ear medicine or with placebo (dummy treatment).
Tri terenska ispitivanja provedena su na psima s otitisom externa koji je uzrokovan bakterijskim ili gljivičnim infekcijama, istražujući učinak terapije nakon čišćenja vanjskog dijela uha fiziološkom otopinom; liječenje s dvije doze Osurnije, u razmaku od tjedan dana uspoređeno je s drugim usporedivim lijekom za uho ili placebom (slijepo liječenje).
In the Japanese study Osurnia was as effective as the other medicine with 78% improvement in otitis externa in both treatment groups.
Osurnia je bila jednako djelotvorna kao i drugi lijekovi sa 78-postotnim poboljšanjem u otitisu externi u obje terapijske skupine.
What is Osurnia used for?
Za što se Osurnia koristi?
Osurnia is used to treat short lived or recurrent ear infections (otitis externa) due to Staphylococcus pseudintermedius (a bacterium) and Malassezia pachydermatitis (a yeast).
Osurnia se koristi za liječenje kratkoročnih ili povratnih infekcija uha (otitis externa) uzrokovanih Staphylococcus pseudintermedius (bakterija) i Malassezia pachydermatitis (kvasac).
In the EU study Osurnia was as effective as the comparator medicine with both treatments resulting in 63% reduction in severity of otitis externa.
Osurnia je bila jednako djelotvorna kao i usporedni lijek s obje terapije koje su rezultirale u 63-postotnoj redukciji težine otitisa externe.
The Japanese study involved 71 dogs; 49 dogs were treated with Osurnia and 22 dogs with another ear medicine containing clotrimazole (for fungal infections), gentamicin (an antibiotic) and betamethasone valerate (corticosteroid).
Japansko ispitivanje uključivalo je 71 psa; 49 pasa liječeno je Osurnijom, a 22 psa liječena su lijekom za uho koji sadrži klotrimazol (za gljivične infekcije), gentamicin (kao antibiotik) i betametazon valerat (kortikosteroid).
The first was an EU study involving 286 dogs in which 148 dogs given Osurnia were compared with 138 dogs treated with another ear medicine containing miconazole (a medicine against fungal infections), gentamicin (an antibiotic) and hydrocortisone aceponate (a corticosteroid) for five consecutive days.
Prvo je bilo europsko ispitivanje koje je uključivalo 286 pasa tretiranih s lijekom za uho koji je sadržavao mikonazol (lijek protiv gljivičnih infekcija), gentamicin (antibiotik) i hidrokortizon aceponat (kortikosteroid) tijekom pet uzastopnih dana.
How does Osurnia work?
Kako djeluje Osurnia?
What benefit has Osurnia shown during the studies?
Osurnia su utvrđene tijekom ispitivanja?
EPAR summary for the public
U europskom ispitivanju
How has Osurnia been studied?
Kako se Osurnia ispitivala?
0.25 mg Capsule, hard
0,25 mg Kapsula, tvrda
1 vial
(Zaštićeno) ime
Abstract 318.
Sažetak 318.
Results of the bioequivalence studies
Rezultati studija bioekvivalencije
Scientific conclusions and grounds for positive opinion presented by the European Medicines Agency
Znanstveni zaključci i razlozi za pozitivno mišljenje koje je prikazala Europska agencija za lijekove
Paper presented at 8th conference on Retrovirus and opportunistic infections.
Papir prikazan na 8. konferenciji o retrovirusima i oportunističkima infekcijama.
• The Committee considered the notification of the referral triggered by the United Kingdom under article 29(4) of Directive 2001/83/EC.
• Povjerenstvo je razmatralo obavijest o procjeni koju je zatražila Ujedinjena Kraljevina u skladu s člankom 29. stavkom 4. Direktive 2001/83/EZ.
the Netherlands and France considered that the granting of the marketing authorisation constitutes a potential serious risk to public health.
Nizozemska i Francuska smatrale su da izdavanje odobrenja za lijek sadrži potencijalni ozbiljan rizik za javno zdravlje.
However, the 90% CI for Cmax was 100.36132.76%.
Međutim, 90 %-tni CI za Cmax iznosio je 100,36 - 132,76 %.
The applicant provided literature references which showed that for the action of Didanosine, AUC is the most important parameter9,10,11,12,13.
Predlagatelj je predao reference za literaturu koje su pokazale da je za djelovanje didanozina AUC najvažniji parametar9,10,11,12,13.
• Dosing recommendations for didanosine
• Preporuke za doziranje didanozina
The reference product in EU is Videx EC (200, 250 and 400 mg) hard capsules, first authorised in the United Kingdom (UK) on 19 September 2000.
Referentni lijek u EU-u su Videx EC (200, 250 i 400 mg) tvrde kapsule, odobrene prvi put u Ujedinjenoj Kraljevini (UK) 19. rujna 2000.
The only difference is the magnitude of the decrease, which is less for the test than for the reference product.
Jedina je razlika u jačini pada, koji je manji za testni nego za referentni lijek.
The application for Didanosine and associated names was considered under Article 10.3 of Directive 2001/83/EC in all Concerned Members States (CMSs).
Primjena didanozina i pridruženih naziva razmatrana je u skladu s člankom 10.3 Direktive 2001/83/EK u svim državama članicama na koje se to odnosi.
Irrespective of whether Didanosine is taken with or without food, the virological response is based on the total drug exposure.
Neovisno o tome uzima li se didanozin s hranom ili bez nje, virološki odgovor temelji se na ukupnoj izloženosti lijeku.
The decentralised procedure was closed on day 210, with most of the CMSs agreeing with the conclusions of the reference Member State (RMS)'s assessment report except France and the Netherlands which raised a potential serious risk to public health (PSRPH).
Decentralizirani postupak zaključen je 210. dana, a većina država članica na koje se to odnosi složila se sa zaključcima iz izvješća referente države članice, osim Francuske i Nizozemske koje su izjavile prigovor u vezi potencijalno ozbiljnih rizika za javno zdravstvo (PSRPH).
A referral was thus triggered at the Co-ordination Group for Mutual Recognition and Decentralised ProceduresHuman (CMD(h)).
Procjena je stoga potaknuta pri grupi za Koordinaciju za međusobno priznavanje i decentralizirane postupke - za humane lijekove (CMD(h)).
However, both formulations are equivalent in terms of extent of absorption (i.e. AUC).
Međutim, obje su formulacije jednake u smislu stupnja apsorpcije (tj. AUC).
It is acknowledged that these results were outside the standard range of 80 - 125%; however these were within the wider acceptance criteria of 70 - 143% which may be used for highly variable drugs.
Potvrđeno je da su ti rezultati bili izvan standardnog raspona od 80-125 %, međutim bili su unutar širih kriterija prihvatljivosti od 70-143 % koji se mogu koristiti za visoko varijabilne lijekove.
Berenguer J et al. Didanosine, Lamivudine, and Efavirenz versus Zidovudine, Lamivudine, and Efavirenz for the Initial Treatment of HIV Type 1 Infection: Final Analysis (48 Weeks) of a Prospective, Randomized, Noninferiority Clinical Trial, GESIDA 3903 HIV/AIDS.
Didanosine, Lamivudine, and Efavirenz versus Zidovudine, Lamivudine, and Efavirenz for the Initial Treatment of HIV Type 1 Infection: Final Analysis (48 Weeks) of a Prospective, Randomized, Noninferiority Clinical Trial, GESIDA 3903 HIV/AIDS.
• Clinical significance of Cmax with Didanosine
• Klinički značaj Cmax-a s didanozinom
The major concern raised by France and the Netherlands could not be solved during the CMD(h) referral and the issue was therefore referred to the Committee for Medicinal Products for Human Use (CHMP).
Glavna bojazan koju su izrazile Francuska i Nizozemska ne mogu se riješiti tijekom procjene CMD(h) te je problem stoga upućen Povjerenstvu za humane lijekove Europske agencije za lijekove (CHMP).
The applicant claimed that differences in plasma concentrations of didanosine are not of clinical relevance as such since it may not result in changes in the intracellular triphosphate concentrations.
Predlagatelj je tvrdio da razlike u plazmatskim koncentracijama didanozina nisu klinički značajne kao takve jer ne mogu rezultirati promjena unutarstaničnih koncentracija trifosfata.
Clinical Infectious Diseases 1993; 16: S26-S31
Clinical Infectious Diseases 1993; 16: S26-S31 6 Drusano GL et al.
1 Note for Guidance on the investigation of bioavailability and bioequivalence (EMA/CPMP/EWP/QWP/1401/98) 2 Guideline on the pharmacokinetic and clinical evaluation of modified release dosage forms
1 Napomena za Upute za ispitivanje bioraspoloživosti i bioekvivalencije (EMA/CPMP/EWP/QWP/1401/98) 2 Smjernice o farmakokinetičkoj i kliničkoj procjeni doziranih oblika s modificiranim otpuštanjem
Considering this, the sample size that may be required to meet the standard bio-equivalence criteria would be as high as 232 subjects to obtain power of at least 80%.
Uzimajući to u obzir, veličina uzorka koja bi se mogla zahtijevati za ispunjavanje kriterija standardne bioekvivalencije trebala biti do 232 ispitanika kako bi se postigla snaga testa od 80 %.
However, the observed effect of food is lower and the Committee is of the opinion that this is not clinically relevant based on considerations relating to the mechanism of action and, in particular, that Didanosine and associated names is to be administrated on an empty stomach.
Međutim, uočeni učinak hrane je niži i Povjerenstvo je smatralo da to nije klinički značajno na temelju razmatranja mehanizma djelovanja i posebice činjenice da se didanozin i lijekovi pridruženih naziva moraju davati natašte.
Background
Podloga
The administration of the reference product with a high fat meal significantly decreases the AUC (19%) and Cmax (46%) of didanosine.
Primjena referentnog lijeka s punomasnim obrokom znatno smanjuje AUC (19 %) i Cmax (46 %) didanozina.
Therefore, it is considered that the fact that both formulations have been used for the same indications and at similar doses suggests that AUC is more relevant for ensuring efficacy of didanosine in antiviral therapy, and the changes in Cmax are unlikely to compromise antiviral efficacy.
Stoga se smatra da činjenica da su obje formulacije korištene za iste indikacije i pri sličnim dozama ukazuje da je AUC važniji za osiguravanje djelotvornosti didanozina u antivirusnoj terapiji te da nije vjerojatno da će promjene u Cmax ugroziti antivirusnu djelotvornost.
Didanosine is intended to be administrated on en empty stomach as stated in the proposed Summary of Product Characteristics (SmPC): “Didanosine absorption is reduced in the presence of food, and hence Didanosine gastro-resistant capsules should be administrated on an empty stomach (at least 2 hours before or 2 hours after a meal)”.
Didanozin je namijenjen za primjenu na prazan želudac kako je to navedeno u predloženom sažetku opisa svojstava lijeka (SmPC): „Apsorpcija didanozina smanjena je u prisutnosti hrane i stoga želučanootporne kapsule didanozina treba primijeniti na prazan želudac (najmanje 2 sata prije ili poslije obroka)”.
Didanosine has to be first converted intracellularly to its active metabolite ddATP (responsible for antiviral activity) which has a significantly longer intracellular half-life (about 43 hours) as compared with plasma half-life of didanosine.
Didanozin treba prvo konvertirati u stanici u njegov aktivni metabolit ddATP (koji je odgovoran za antivirusnu aktivnost) koja ima znatno dulji unutarstanični poluživot (oko 43 sata) u usporedbi plazmatskim poluživotom didanozina.
In addition, the objecting Members States considered that the arguments provided by the applicant did not sufficiently address the consequences of the difference observed in didanosine pharmacokinetics in the fed state between test and reference products.
Osim toga, države članice koje su se protivile smatrale su da argumenti koje je podnio predlagatelj nisu dostatni za objašnjenje posljedica razlika uočenih u farmakokinetici didanozina, u stanju kad su bolesnici bili siti između testnih i referentnih lijekova.
• The Committee reviewed all the data submitted by the applicant in order to support the bioequivalence between Didanosine and associated names and the reference product.
• Povjerenstvo je pregledalo sve predane podatke kako bi poduprlo bioekvivalenciju između didanozina i pridruženih naziva i referentnog lijeka.
The Committee acknowledged that the conventional criterion for bioequivalence for maximum plasma concentration (Cmax) was outside the 80-125% acceptability limits.
Povjerenstvo je priznalo da su standardni kriteriji za bioekvivalenciju za maksimalnu plazmatsku koncentraciju (Cmax) bili izvan granica prihvatljivosti od 80 do 125 %.
Overall summary of the scientific evaluation of didanosine and associated names (see Annex I)
Ukupni sažetak znanstvene procjene didanozina i pridruženih naziva (vidjeti Prilog I.)
This is attributed to the delay in absorption rate of enteric coated formulation which is reflected in the Tmax which is about 2 hours for the enteric coated formulation compared to 0.67 hours for the buffered tablet.
To se pripisuje odgodi u brzini apsorpcije enterički obloženih formulacija što se odražava u Tmax koji iznosi otprilike 2 sata za enterički obloženu formulaciju u usporedbi sa 0,67 sati za puferirane tablete.
Both studies were carried out using open label, randomised, two treatment, two sequence, two period, single dose cross-over design.
Oba su ispitivanja provedena upotrebom otvorenih, nasumičnih, unakrsnih ispitivanja čiji se dizajn temeljio na dvije terapije, dvije sekvence, dva razdoblja i na pojedinačnoj dozi.
didanosine in treatment of HIV infecting were conducted using buffered tablets3,4,5,6,7,8.
Početna klinička ispitivanja koja su dokazala djelotvornost didanozina u liječenju infekcije HIV-om provedena su upotrebom puferiranih tableta3,4,5,6,7,8.
The pharmacokinetics data reveals that the plasma concentration (Cmax) obtained from enteric-coated capsule formulation of didanosine is about 40% lower as compared to the buffered tablet formulation.
Farmakokinetički podaci otkrivaju da su plazmatske koncentracije (Cmax) dobivene iz formulacija enteričko obloženih kapsula didanozina za otprilike 40 % niža u usporedbi s formulacijom puferiranih tableta.
Didanosine (2', 3'-dideoxyinosine) is an inhibitor of the in vitro replication of human immunodeficiency virus (HIV) in cultured human cells and cell lines.
Didanozin (2', 3'-dideoksididanozin) je inhibitor in vitro replikacije virusa humane imunodeficijencije (HIV) u kulturama humanih stanica i linija stanica.
6 Drusano GL et al.
3 Damle BD et al.
the CHMP has recommended the granting of the marketing authorisations for which the summary of product characteristics, labelling and package leaflet remain as per the final versions achieved during the Coordination group procedure as mentioned in Annex III for Didanosine and associated names (see Annex I).
CHMP je preporučio izdavanje odobrenja za stavljanje u promet, uz sažetak svojstava proizvoda, označivanje i upute o lijeku koji ostaju kao kod zadnje verzije utvrđene tijekom postupka Skupine za koordinaciju, kao što je spomenuto u Prilogu III. ovog mišljenja za didanozin i pridružene nazive (vidjeti Prilog 1.).
During the decentralised procedure France and the Netherlands expressed the opinion that bioequivalence had not been demonstrated in the fed conditions as Cmax was outside the 80-125% acceptability limits1.
Tijekom decentraliziranog postupka Francuska i Nizozemska izrazile su mišljenje da bioekvivalencija nije dokazana u uvjetima kad su ispitanici smjeli jesti jer je Cmax bio izvan granica prihvatljivosti od 80-125 %1.
Ann Intern Med 1992: 116:562-566
Ann Intern Med 1992: 116 (562)-566 7 Perry CM, Balfour JA.
The results were satisfactory in terms of extent of absorption (i.e. AUC).
Rezultati su bili zadovoljavajući u smislu apsorpcije (tj. AUC).
Of note, bioequivalence in fasted state is considered to be the most important as this product is intended to be taken on an empty stomach.
Potrebno je zabilježiti da se bioekvivalencija u situaciji kad su bolesnici morali biti natašte smatrala najvažnijom jer je ovaj lijek namijenjen uzimanju na prazan želudac.
Didanosine and associated names is indicated in combination with other antiretroviral drugs for the treatment of HIV-1 infected patients.
Didanozin i pridruženi nazivi indicirani su u kombinaciji s drugim antiretrovirusnim lijekovima za liječenje bolesnika zaraženih virusom HIV-1.
Since the product is to be administrated at least 2 hours before or after food intake, it is unlikely that the product ingested will be exposed to in vivo conditions, prevailing under fed state.
S obzirom da će se lijek primijeniti najmanje 2 sata prije ili nakon uzimanja hrane, nije vjerojatno da će se progutani lijek izložiti pod in-vivo uvjetima, ako ga bolesnici uzimaju na pun želudac.
• The Committee noted that in the fed study, both formulations were subject to a food effect reducing plasma concentrations.
• Povjerenstvo je napomenulo da su u ispitivanju u uvjetima kad su bolesnici smjeli jesti obje formulacije bile podložne utjecaju hrane u smislu smanjivanja plazmatskih koncentracija.
The main purpose of conducting bioequivalence fed study is to exclude food related effects, such as dose-dumping (in particular for gastro-resistant formulations) or failure of protection from acid mediated degradation in the stomach.
Glavna svrha provođenja studija bioekvivalencije kad su bolesnici smjeli jesti je isključivanje učinaka hrane poput naglog i prekomjernog otpuštanja doze lijeka u krv (posebice za želučanootporne formulacije) ili neuspjeh u zaštiti od kiselinom posredovane razgradnje u želucu.
Damle BD et al. Bioequivalence of two formulations of didanosine, encapsulated enteric-coated beads and buffered tablet, in healthy volunteers and HIV-infected subjects.
Bioequivalence of two formulations of didanosine, encapsulated enteric-coated beads and buffered tablet, in healthy volunteers and HIV-infected subjects.
The Applicant claimed that the significant decrease observed under fed conditions for Cmax for the test product (90% CI outside the standard range) may be attributed to high inter-individual variability with respect to Cmax which was 36% in the study conducted under fed conditions.
Predlagatelj je tvrdio da se značajan pad uočen u uvjetima kad su bolesnici smjeli jesti za Cmax za testni lijek (90 % intervala pouzdanosti izvan standardnog raspona) može pripisati visokoj interindividualnoj varijabilnosti s obzirom na Cmax koja je iznosila 36 % u ispitivanju koje je provedeno pod uvjetima kad su ispitanici smjeli jesti.
Pharmacokinetics studies conducted on Didanosine formulations reveal that administration of the product with food or immediately after food results in decreased in vivo availability of the drug.
Farmakokinetička ispitivanja provedena na formulaciji didanozina otkrivaju da primjena lijeka s hranom ili neposredno nakon uzimanja hrane rezultira smanjenom in-vivo raspoloživosti lijeka.
The primary pharmacokinetic parameters (Cmax and AUC) were satisfactory in the fasting study with the 90% confidence interval (CI) falling within the standard criteria of 80.00 - 125.00%.
Primarni farmakokinetički parametri (Cmax i AUC) bili su zadovoljavajući u ispitivanjima natašte s 90 %-tnim intervalom pouzdanosti (CI) koji spada unutar standardnih kriterija od 80,00 - 125,00
• The Committee is of the opinion that bioequivalence has been demonstrated under fasting conditions which is the recommended state for administration of didanosine.
• Povjerenstvo je smatralo da je bioekvivalencija dokazana u uvjetima kad su bolesnici bili natašte što je i preporučeno stanje za primjenu didanozina.
In order to demonstrate the safety and efficacy of Didanosine and associated names in combination with other antiretroviral drugs in the treatment of HIV-1 infected patients, the application dossier was based on two single dose bioequivalence studies, one under fasting state and one under fed state.
Kako bi se dokazala sigurnost i djelotvornost didanozina i pridruženih naziva u kombinaciji s drugim antiretrovirusnim lijekovima u liječenju bolesnika s infekcijom HIV-1, dosje lijeka za potrebe registracije temeljio se na dvije pojedinačne studije bioekvivalencije, jedna u stanju kad su bolesnici morali biti natašte, a druga kad su bolesnici smjeli jesti.
After didanosine enters the cell, it is enzymatically converted to dideoxyadenosine-triphosphate (ddATP), its active metabolite.
Nakon što didanozin uđe u stanicu, enzimatski se konvertira u dideoksiadenozin-trifosfat (ddATP), svoj aktivni metabolit.
In viral nucleic acid replication, incorporation of this 2', 3'-dideoxynucleoside prevents chain extension, and thereby inhibits viral replication.
Kod replikacije nukleinskih kiselina inkorporacija ovog metabolita 2', 3'-dideoksinukleozid sprječava produljenje lanca i tako inhibira replikaciju virusa.
In addition, ddATP inhibits HIV-reverse transcriptase by competing with deoxyadenosine-triphosphate (dATP) for binding to the enzyme's active site, preventing proviral DNA synthesis.
Osim toga, ddATP inhibira HIV reverznu transkriptazu djelujući s deoksiadenozin-trifosfatom (dATP) za vezanje na aktivno mjesto enzima, sprječavajući sintezu proviralne DNK.