natgillin/translations-raw huggingface dataset:
This leaflet was last approved in 
To navodilo je bilo odobreno
Please tell your doctor or pharmacist if you are taking or have recently taken any other medicines, including medicines obtained without a prescription. 
Prosimo, obvestite svojega zdravnika ali farmacevta, če jemljete, ali ste pred kratkim jemali katerokoli zdravilo, tudi če ste ga dobili brez recepta.
Tell your doctor about medications that you are taking or plan to take whilst you are taking ORACEA . 
Obvestite svojega zdravnika o zdravilih, ki jih jemljete, ali jih nameravate jemati med jemanjem zdravila ORACEA.
A. SUMMARY OF PRODUCT CHARACTERISTICS 
A. POVZETEK GLAVNIH ZNAČILNOSTI ZDRAVILA
As for other tetracyclines, doxycycline forms a stable calcium complex in any boneforming tissue. 
Tako kot drugi tetraciklini tudi doksiciklin tvori stabilen kalcijev kompleks v kateremkoli kostnem tkivu.
The CHMP also considered that the survey referred to by the Applicant, showing that papulopustular lesions are readily recognized and rated by dermatologists providing a qualitative as well as quantitative measurement, was relevant; therefore the currently proposed indication was considered clinically applicable and practical. 
Odbor je tudi menil, da je pomembna raziskava, na katero se sklicuje predlagatelj in ki kaže, da dermatologi enostavno prepoznavajo in ocenjujejo papulopustularne lezije, kar omogoča kvalitativno in kvantitativno merjenje, zato se trenutno predložena indikacija šteje za klinično uporabno in praktično.
ORACEA must not be used to treat infections caused by organisms susceptible (or suspected to be susceptible) to doxycycline. 
Zdravilo ORACEA se ne sme uporabljati za zdravljenje okužb, ki jih povzročajo organizmi, ki so občutljivi (ali za katere sumimo, da so občutljivi) na doksiciklin.
Post-marketing experience has not identified any new safety concerns. 
V obdobju trženja zdravila niso odkrili nobenih novih varnostnih zadržkov.
Very rare: Brown-black microscopic discolouration of thyroid tissue has been reported with long term use of tetracyclines. 
Zelo redki: O rjavo-črnem mikroskopskem obarvanju tkiva ščitnice so poročali po dolgotrajni uporabi tetraciklinov.
If you take more ORACEA capsules than you should, ask your doctor immediately for advice. 
Če vzamete več kapsul zdravila ORACEA, kot bi jih morali, nemudoma poiščite nasvet pri svojem zdravniku.
Treatment should cease if evidence of raised intracranial pressure develops. 
Z zdravljenjem je treba prenehati, če se pojavi povišan intrakranialni tlak.
The following adverse reactions have been observed in patients receiving tetracyclines: 
Naslednje neželene učinke so zaznali pri bolnikih, ki so prejemali tetracikline:
The manufacturer responsible for batch release is: 
Izdelovalec, odgovoren za izdajo serije je:
The procedure was referred to the CHMP, who raised a number of issues through a List of Questions and a subsequent List of Outstanding Issues, which were addressed by the Applicant. 
Postopek je bil napoten na Odbor za zdravila za uporabo v humani medicini (CHMP), ki je sprožil številne zadržke preko seznama vprašanj in naknadnega seznama nerešenih zadržkov, ki jih je naslovil na predlagatelja.
A peri/postnatal toxicity study in rats revealed no significant effects at therapeutically relevant doses. 
Peri/postnatalna študija toksičnosti pri podganah ni pokazala pomembnejših učinkov pri terapevtsko ustreznih odmerkih.
Doxycycline is excreted in the urine and faeces as unchanged active substance. 
Doksiciklin se izloča v urin in blato kot nespremenjena aktivna snov.
In the pivotal placebo-controlled studies with ORACEA in rosacea, 269 patients were treated with ORACEA 40 mg once daily and 268 patients were treated with placebo for 16 weeks. 
V študijah, kontroliranih s placebom, z zdravilom ORACEA pri rozacei, so 269 bolnikov zdravili z zdravilom ORACEA 40 mg enkrat dnevno in 268 bolnikov s placebom 16 tednov.
Mechanism of Action: The pathophysiology of the inflammatory lesions of rosacea is, in part, a manifestation of a neutrophil-mediated process. 
Mehanizem delovanja: Patofiziologija vnetnih lezij pri rozacei, je delno manifestacija nevtrofilno povzročenega postopka.
The Applicant addressed the concern that no comparator study was provided by arguing that a controlled clinical trial using an active comparator such as systemic doxycycline was not required, as the development program was in line with a number of ICH guidelines CPMP/ICH/291/95 and CPMP/ICH/135/95 which do not require an active comparator and with the E10 Guidance for the choice of control group in clinical trials (CPMP/ICH/364/96), which supports the use of a placebo control group as the most appropriate design where ethically and practically feasible. 
Predlagatelj je odgovoril na zadržek, da ni predložil študije s komparatorjem, z argumentom, da nadzorovano klinično preskušanje z aktivnim komparatorjem, kot je sistemski doksiciklin, ni potrebno, saj je bil razvojni program v skladu z več priporočili ICH, CPMP/ICH/291/95 in CPMP/ICH/135/95, ki ne zahtevajo uporabe aktivnega komparatorja, ter s priporočilom E10 za izbiro kontrolnih skupin v kliničnih preskušanjih (CPMP/ICH/364/96), ki podpira uporabo kontrolne skupine s placebom, kot najprimernejšo zasnovo v primerih, ko je to etično in praktično izvedljivo.
Following the administration of the 40 mg modified release formulation of doxycycline, the maximum excreted concentrations of doxycycline will be between 0.03 - 0.16 mg/L for all excretion mechanisms. 
Po uporabi 40 mg oblike doksiciklina z modificiranim sproščanjem so največje izločene koncentracije doksiciklina od 0,03 do 0,16 mg/l za vse mehanizme izločanja.
The CHMP agreed with the ICH guidelines, stating that an active comparator is not required if it is considered ethically and practically feasible to use placebo in the control group. 
Odbor CHMP se je strinjal s priporočili ICH in navedel, da aktivni komparator ni potreben, če je uporaba placeba v kontrolni skupini etična in praktično dostopna.
This reaction was shown to be reversible when the medicinal product was discontinued. 
Izkazalo se je, da je ta reakcija reverzibilna, ob prenehanju zdravljenja.
Finally, the CHMP also acknowledged the difficulty in breaking down the different subgroups of rosacea since symptoms often overlap between the different subtypes and recognised that Oracea is aimed towards the treatment of papules and pustules rather than treatment of rosacea as a whole or treatment of a specific subtype. 
Na koncu je odbor CHMP tudi potrdil težavno razvrščanje rozacee v podskupine, ker se med podtipi bolezni simptomi pogosto prekrivajo, ter ugotovil, da je zdravilo Oracea usmerjeno k zdravljenju papul in pustul in ne zdravljenju rozacee kot celote ali zdravljenju specifičnega podtipa.
The clinical studies showed no treatment-related serious AEs and tolerability seems to be unaffected by gender, age or disease severity. 
V kliničnih študijah niso odkrili resnih neželenih učinkov, povezanih z zdravljenjem, hkrati pa toleranca ni odvisna od spola, starosti ali resnosti bolezni.
Doxycycline has been shown to inhibit neutrophil activity and several pro-inflammatory reactions including those associated with phospholipase A2, endogenous nitric oxide and interleukin-6. 
Doksiciklin zavira nevtrofilno aktivnost in številne predvnetne reakcije, vključno tiste, povezane s fosfolipazo A2, endogenim dušikovim oksidom in interlevkinom-6.
ORACEA should not be used in patients with ocular manifestations of rosacea (such as ocular rosacea and/or blepharitis/meibomianitis) as there are limited efficacy and safety data in this population. 
Zdravila ORACEA se ne sme uporabljati pri bolnikih z očesno manifestacijo rozacee (kot je očesna rozacea in/ali blefaritis/meibomianitis), ker v tej populaciji ni zadostne učinkovitosti in obstaja premalo podatkov o varnostni.
Concomitant use not recommended: 
Sočasna uporaba se odsvetuje:
OTHER SPECIAL WARNING(S), IF NECESSARY Swallow whole, do not crush or chew. 
DRUGA POSEBNA OPOZORILA, ČE SO POTREBNA Pogoltnite celo kapsulo, ne trite ali ne žvečite.
Doxycycline has no or negligible influence on the ability to drive and use machines. 
Doksiciklin nima ali ima zanemarljiv vpliv na sposobnost vožnje in upravljanja s stroji.
If you suspect or learn that you are pregnant whilst taking ORACEA, contact your doctor immediately. 
Če med jemanjem zdravila ORACEA sumite, ali izveste, da ste noseči, se nemudoma posvetujte s svojim zdravnikom.
If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor or pharmacist. 
Če katerikoli neželeni učinek postane resen, ali če opazite katerikoli neželeni učinek, ki ni omenjen v tem navodilu, obvestite svojega zdravnika ali farmacevta.
Mean change from baseline to Week 16 in total inflammatory lesion count: 
Povprečna sprememba od izhodišča do 16. tedna v skupnem številu vnetnih lezij:
The only treatments currently widely authorized in the EU are topical therapies containing metronidazole or azelaic acid, which require twice daily administration and may give rise to local adverse events such as skin irritation or worsening of rosacea. 
Edini terapiji, ki sta trenutno odobreni v EU, sta topični terapiji z metronidazolom ali azelainsko kislino, pri katerih je potrebna uporaba dvakrat dnevno, obstaja pa možnost lokalnih neželenih učinkov, kot sta draženje kože in poslabšanje rozacee.
This may include the discontinuation of doxycycline and the institution of specific antibiotic therapy. 
To lahko vključuje prenehanje zdravljenja z doksiciklinom in uvedba specifičnega antibiotičnega zdravljenja.
At doses greater than 50 mg/kg/day fertility and reproductive performance were adversely affected in rats. 
Pri odmerkih, večjih od 50 mg/kg/dan, je bila fertilnost in reproduktivna učinkovitost pri podganah močno prizadeta.
In vivo microbiological studies using similar exposure to the active substance for 6 to 18 months could not demonstrate any effect on the dominating bacterial flora sampled from the oral cavity, skin, intestinal tract and vagina. 
In vivo mikrobiološke študije z uporabo podobne izpostavljenosti aktivni učinkovini 6 do 18 mesecev niso pokazale učinka na prevladujočo bakterijsko floro, vzeto iz ustne votline, s kože, iz intestinalnega trakta ali vagine.
There is a possibility that ORACEA reduces the effectiveness of oral contraceptives, resulting in pregnancy. 
Obstaja možnost, da zdravilo ORACEA zmanjša učinkovitost oralnih kontraceptivov, kar ima lahko za rezultat nosečnost.
With regard to target site exposure of bacteria to doxycycline, the Applicant referred to several publications stating that the resulting concentrations of antibacterially-active drug will be very low, leading to a very low risk of resistance pressure. 
V zvezi z izpostavljenostjo bakterij doksiciklinu na ciljnem mestu se je predlagatelj skliceval na več objav, kjer je navedeno, da so nastale koncentracije protibakterijsko aktivnega zdravila zelo nizke, kar povzroči zelo majhno tveganje pritiska na odpornost.
ANNEX I LIST OF THE NAME, PHARMACEUTICAL FORM, STRENGTH OF THE MEDICINAL PRODUCT, ROUTE OF ADMINISTRATION, APPLICANT(S) IN THE MEMBER STATES 
DODATEK I SEZNAM IMEN, FARMACEVTSKIH OBLIK, JAKOSTI ZDRAVILA, POTI UPORABE ZDRAVILA, PREDLAGATELJEV, IMETNIKOV DOVOLJENJA ZA PROMET Z ZDRAVILOM V DRŽAVAH ČLANICAH
Doxycycline showed no mutagenic activity and no convincing evidence of clastogenic activity. 
Doksiciklin ni izkazal mutagene aktivnosti in nobene prepričljive prisotnosti klastogene aktivnosti.
- The CHMP considers that Oracea is well tolerated and is satisfied with the safety profile when in conjunction with the commitment to carry out a post-marketing study as set out in Annex IV and the revision of the Summary of Product Characteristics as set out in Annex III, 
- Odbor CHMP meni, da bolniki zdravilo Oracea dobro prenašajo, in je zadovoljen z varnostnim profilom v povezavi z zavezo k izvedbi študije v obdobju trženja, kakor je določeno v Dodatku IV in popravljenem povzetku glavnih značilnosti zdravila, ki je opredeljen v Dodatki III,
• Yeast infection around the anus or genitals 
• Infekcija s kvasovkami okoli anusa ali genitalij
The Applicant also presented data from six placebocontrolled studies conducted in over 400 patients, showing no evidence of increase in resistance of the microbiological flora of the gastrointestinal tract (faeces), vagina, skin, saliva or dental plaque after long-term treatment with doxycycline 40 mg/day for 6 to 18 months, which is in line with pharmacokinetic investigations on target site exposure. 
Predlagatelj je tudi predložil podatke šestih s placebom nadzorovanih študij, opravljenih na več kot 400 bolnikih, kjer ni dokazov po povečani odpornosti mikrobne flore prebavil (blato), nožnice, kože, sline ali zobnih oblog po dolgoročnem zdravljenju z doksiciklinom 40 mg/dan za 6 do 18 mesecev, kar je v skladu s farmakokinetičnimi raziskavami izpostavljenosti na ciljnem mestu.
* Tell your doctor immediately or go to casualty if you suffer side effects such as swollen face, lips, tongue and throat, difficulty in breathing, hives or itchy skin and eyes, or rapid heart beat (palpitations) and feeling faint. 
* Nemudoma obvestite svojega zdravnika ali pojdite na urgenco, če imate neželene učinke, kot so zatekel obraz, ustnice, jezik in grlo, težave z dihanjem, koprivnica ali srbeča koža ali oči, ali vam hitro bije srce (palpitacije) in čutite omedlevico.
ORACEA should not be used at the same time as the medicine isotretinoin because of the risk of increased pressure in the brain. 
Zdravila ORACEA ne smete uporabljati sočasno z zdravilom izotretinoin zaradi tveganja povečanega tlaka v možganih.
Excipient: Each hard capsule contains 102 - 150 mg of sucrose. 
Pomožna snov: Ena trda kapsula vsebuje 102 - 150 mg saharoze.
These effects were seen at exposure levels of 1.5 to 2 times those seen in humans administered ORACEA at the proposed dose. 
Ti učinki so bili opaženi pri stopnjah izpostavljenosti, ki so bile 1,5-krat do 2-krat večje od tistih, opaženih pri ljudeh, kateri so prejemali zdravilo ORACEA po predlaganih odmerkih.
The daily dose is 40 mg (1 capsule). 
Dnevni odmerek je 40 mg (1 kapsula).
If administered in combination with these medicinal products, blood glucose levels should be monitored and, if necessary, the doses of the sulphonylureas should be reduced. 
Če se ga daje v kombinaciji s temi zdravili, je treba spremljati nivo glukoze v krvi in po potrebi odmerke sulfonilsečnine zmanjšati.
Both studies showed significant superiority of Oracea compared with placebo. 
V obeh študijah so dokazali bistveno superiornost zdravila Oracea v primerjavi s placebom.
The Applicant was also requested to reflect information on this issue in sections 4.4 and 5.1 of the SPC. 
Predlagatelj je bil naprošen, da podatke o tem zadržku predstavi v poglavjih 4.4 in 5.1 povzetka glavnih značilnosti zdravila.
However, it can not be excluded that long-term use of Oracea can lead to emergence of resistant intestinal bacteria such as Enterobacteriaceae and enterococci, as well as to enrichment of resistance genes. 
Vendar ni mogoče izključiti, da lahko dolgotrajna uporaba zdravila Oracea privede do pojava odpornosti intestinalnih bakterij, kot so Enterobacteriaceae in enterokoki, in do oplemenitenja rezistentnih genov.
The terminal elimination half-life of doxycycline after administration of ORACEA was approximately 21 h after a single dose and approximately 23 h at steady state. 
Končno eliminiranje razpolovne dobe doksiciklina po prejemu zdravila ORACEA je bilo približno 21 ur po enkratnem odmerku in približno 23 ur pri stabiliziranem stanju.
The recommendations below regarding the potential interactions between doxycycline and other medicinal products are based upon experience with the larger doses generally used in antimicrobial formulations of doxycycline rather than with ORACEA. 
Priporočila, ki so navedena spodaj, glede potencialnega medsebojnega delovanja doksiciklina in drugih zdravil temeljijo na izkušnjah z višjimi odmerki, ki se običajno uporabljajo v antimikrobnih farmacevtskih oblikah doksiciklina, in ne pri zdravilu ORACEA.
The Applicant should complete this study and file a report within a reasonable period of time (e.g. 2 years) from the date of approval. 
Predlagatelj mora opraviti to študijo in vložiti poročilo v primernem obdobju (npr. 2 leti) od datuma odobritve.
If administered in combination with these agents, coagulation parameters including INR should be monitored and, if necessary, the doses of the anticoagulant medicinal products reduced. 
Če se ga daje v kombinaciji s temi zdravili, je treba spremljati koagulacijske parametre, vključno z INR, in po potrebi odmerke antikoagulacijskih zdravil zmanjšati.
In rats, doses of 50 mg/kg/day doxycycline caused a decrease in the straight-line velocity of sperm but did not affect male or female fertility or sperm morphology. 
Pri podganah so odmerki 50 mg/kg/dan doksiciklina povzročili zmanjšano hitrost sperme v ravni črti, vendar niso vplivali na fertilnost samca ali samice ali na morfologijo sperme.
In humans, the use of tetracyclines during tooth development may cause permanent discolouration of the teeth (yellow-grey-brown). 
Pri ljudeh lahko uporaba tetraciklinov pri rasti zob povzroči trajno obarvanje zob (rumeno-sivo-rjavo obarvanje).
However, increased knowledge of the ecological effects of long-term administration of low-dose doxycycline is highly desirable, and the Applicant is requested to commit to submitting a study protocol for a well designed post-marketing clinical study investigating emergence of resistance in relevant bacterial groups in the intestinal and upper respiratory tract for validation and to carry out a study accordingly within 3 months of approval. 
Vendar je večje znanje o ekoloških učinkih dolgoročnega dajanja majhnih odmerkov doksiciklina zelo zaželeno, zato je bil predlagatelj naprošen, da se za validacijo podatkov obveže k predložitvi študijskega protokola dobro zasnovane klinične študije v obdobju trženja zdravila, v kateri bi raziskali pojav odpornosti pri ustreznih bakterijskih skupinah v črevesju in zgornjih dihalih, ter da študijo izvede v 3 mesecih od odobritve.
ORACEA has been evaluated in two pivotal randomised, double-blind, placebo-controlled, 16-week studies in 537 patients with rosacea (10 to 40 papules and pustules, and two or fewer nodules). 
Zdravilo ORACEA so vrednotili v dveh randomiziranih, dvojno slepih, s placebom kontroliranih, 16tedenskih študijah pri 537 bolnikih z rozaceo (10 do 40 papul in pustul, in dva ali manj nodulov).
These conditions disappeared rapidly when the drug was discontinued. 
To stanje je hitro izzvenelo, ko so prenehali z zdravljenjem.
Furthermore, the CHMP was of the opinion that although the efficacy of doxycycline 40mg daily has not been demonstrated in patients with ocular rosacea, the literature data combined with the results from the two placebo-controlled studies submitted indicated no specific safety concerns in this subgroup. 
Poleg tega je Odbor menil, da čeprav učinkovitost doksiciklina 40 mg na dan za bolnike z očesno rozaceo ni dokazana, predloženi podatki iz literature in rezultati dveh s placebom nadzorovanih študij ne kažejo specifičnih varnostnih zadržkov v tej podskupini.
In contrast to higher, antimicrobial doses of doxycycline that may lead to the development of resistance and opportunistic overgrowth, long-term clinical trial experience with doxycycline 40 mg/day confirms the good tolerability of doxycycline at this dose level during prolonged treatment. 
V nasprotju z velikimi, protimikrobnimi odmerki doksiciklina, ki lahko povzročijo razvoj odpornosti in preraščanje oportunističnih povzročiteljev, izkušnje v dolgoročnih kliničnih preskušanjih z doksiciklinom 40 mg/dan potrjujejo dobro toleranco doksiciklina pri tej ravni odmerkov za dolgoročno zdravljenje.
Doxycycline, generally in the dose of 100-200 mg daily, has been widely used in clinical practice for the treatment of various infectious diseases for more than 25 years, with a well documented safety profile. 
Doksiciklin, običajno v odmerku 100-200 mg na dan, se na splošno uporablja v klinični praksi za zdravljenje različnih nalezljivih bolezni že več kot 25 let in ima dobro opisan varnostni profil.
Patients with rare hereditary problems of fructose intolerance, glucose-galactose malabsorption or sucrase-isomaltase insufficiency should not take this medicinal product. 
Bolniki z redkimi dednimi boleznimi, kot so intoleranca na fruktozo, malabsorpcija glukoze-galaktoze ali insuficienca saharaze-izomaltaze, ne smejo jemati tega zdravila.
Treatment: 
Zdravljenje:
Regarding the risk of resistance induction, the Applicant provided data from several studies demonstrating that the 100 mg doxycycline dose leads to marked emergence of resistant strains in the oral and intestinal micro flora. 
V zvezi s tveganjem o indukciji odpornosti je predlagatelj predložil podatke več študij, ki kažejo, da odmerek 100 mg doksiciklina povzroči pomemben pojav odpornih sevov v ustni in črevesni mikroflori.
Doxycycline is greater than 90% bound to plasma proteins and has an apparent volume of distribution of 50 L. Major metabolic pathways of doxycycline have not been identified but enzyme inducers decrease the half-life of doxycycline. 
Več kot 90% doksiciklina se veže na plazemske beljakovine in ima navidezen volumen porazdelitve 50 l. Pomembne metabolične poti doksiciklina niso bile ugotovljene, vendar induktorji encimov zmanjšajo razpolovno dobo doksiciklina.
Treatment with higher doses of tetracyclines is associated with emergence of resistant intestinal bacteria, such as enterococci and enterobacteria. 
Zdravljenje z višjimi odmerki tetraciklinov je povezano z nastankom odpornih intestinalnih bakterij, kot so enterokoki in enterobakterije.
if you have a condition causing absence of acid in the stomach (achlorhydria) or if you have had surgery on the upper part of the gut (called the duodenum). 
če imate bolezen, ki povzroča odsotnost kisline v želodcu (aklorhidrija) ali če ste bili operirani na zgornjem delu črevesja (imenovanem dvanajstnik).
The usual dose of ORACEA is less than half the usual doses of doxycycline used for antimicrobial therapy. 
Običajni odmerek zdravila ORACEA je manj kot polovica običajnega odmerka doksiciklina, ki se uporablja za antimikrobno zdravljenje.
Based on these findings it is scientifically reasonable to conclude that the effect of low dose doxycycline on the normal residential flora including E coli, Enterococci, Staphylococci and Streptococci to be almost non-existent and concluded that the risk of inducing resistance development is negligible. 
Ker je na podlagi teh številk znanstveno utemeljen zaključek, da učinka majhnega odmerka doksiciklina na normalno naseljeno floro, vključno z E. coli, enterokoki, stafilokoki in streptokoki skoraj ni, je Odbor zaključil, da je tveganje indukcije razvoja odpornosti zanemarljivo.
Endocrine disorders: 
Bolezni endokrinega sistema:
Aluminium/PVC/Aclar blister 
Aluminij/PVC/aclar pretisni omot
Medicinal products which increase gastric pH may reduce the absorption of doxycycline, and should be taken at least 2 hours after doxycycline. 
Zdravila, ki zvišujejo pH v želodcu, lahko zmanjšajo absorpcijo doksiciklina, zato jih je treba vzeti vsaj 2 uri po doksiciklinu.
However, at the present time, insufficient data exist for reassurance that the interactions described with higher doses of doxycycline will not occur with ORACEA. 
Trenutno je še premalo podatkov, da bi lahko z gotovostjo trdili, da se opisane interakcije z visokimi odmerki doksiciklina ne bodo pojavile tudi pri zdravilu ORACEA.
Hypersensitivity to the active substance, to other tetracyclines or to any of the excipients. 
Preobčutljivost na zdravilno učinkovino, na ostale tetracikline ali katerokoli pomožno snov.