natgillin/translations-raw huggingface dataset:
Testicular tubular atrophy, which was occasionally associated with aspermia, was observed in oral repeat dose toxicity and fertility studies with male rats and mice without safety margin.
Pri študijah toksičnosti in vplivov na plodnost so pri samcih podgan in miši pri ponavljajočih se peroralnih odmerkih brez varnostne meje poročali o atrofiji testikularnih tubulov, ki je bila občasno povezana z azospermijo.
However no testicular changes were observed in dog studies of up to 39 weeks duration at an exposure 35– fold that seen in humans based on AUC.
Pri študijah na psih, ki so trajale do 39 tednov, pri izpostavljenosti, ki je bila na osnovi vrednosti AUC 35- krat večja od izpostavljenosti pri človeku, sprememb na modih niso opazili.
12 Ambrisentan has been shown to be teratogenic in rats and rabbits.
Pri podganah in kuncih je bilo dokazano, da je ambrisentan teratogen.
Abnormalities of the lower jaw, tongue, and/ or palate were seen at all doses tested.
Pri vseh raziskovanih odmerkih so poročali o nepravilnostih mandibule, jezika in/ ali neba.
In addition, interventricular septal defects, trunk vessel defects, thyroid and thymus abnormalities, ossification of the basisphenoid bone and increased incidence of left umbilical artery were seen in the rat study.
Poleg tega so pri študiji na podganah poročali o okvarah medprekatnega pretina, okvarah glavnih žil, nepravilnostih ščitnice in priželjca, osifikaciji bazisfenoidne kosti in večji pojavnosti leve umbilikalne arterije.
Administration of ambrisentan to female rats from late-pregnancy through lactation caused adverse events on maternal behaviour, reduced pup survival and impairment of the reproductive capability of the offspring (with observation of small testes at necropsy), at exposure 3-fold the AUC at the maximum recommended human dose.
Pri samicah podgan, ki so ambrisentan prejemale od pozne brejosti in v času laktacije so pri izpostavljenosti, ki je bila 3- kratnik AUC pri maksimalnem priporočenem odmerku pri človeku, poročali o neželenih učinkih na vedenje mater, zmanjšanem preživetju mladičev in manjši sposobnosti za razmnoževanje mladičev (pri nekropsiji so poročali o majhnih testisih).
Tablet core Lactose monohydrate Microcrystalline cellulose Croscarmellose sodium Magnesium stearate
Jedro tablete laktoza monohidrat mikrokristalna celuloza premreženi natrijev karmelozat magnezijev stearat
Film coat Polyvinyl alcohol (Partially Hydrolyzed) Talc (E553b) Titanium dioxide (E171) Macrogol / PEG 3350 Lecithin (Soya) (E322) Allura red AC Aluminium Lake (E129)
Filmska obloga polivinilalkohol (delno hidrolizirani) smukec (E553b) titanov dioksid (E171) makrogol / PEG 3350 lecitin (soja) (E322) rdeče AC (E129)
PVC/ PVDC/ aluminium foil blisters.
Pretisni omoti iz PVC/ PVDC/ aluminijske folije.
Pack sizes of 10 or 30 film-coated tablets.
Pakiranje po 10 ali 30 filmsko obloženih tablet.
14 1.
14 Podrobne informacije o zdravilu so objavljene na spletni strani Evropske agencije za zdravila (EMEA) http: // www. emea. europa. eu /.
Each tablet contains lactose monohydrate (approximately 90 mg), Lecithin (Soya) (E322) (approximately 0.25 mg) and Allura red AC Aluminium Lake (E129) (approximately 0.45 mg).
Ena tableta vsebuje laktozo monohidrat (približno 90 mg), lecitin (soja) (E322) (približno 0, 25 mg) in rdeče AC (E129) (približno 0, 45 mg).
Deep-pink, oval, convex, film-coated tablet with “ GS ” debossed on one side and “ KE3” on the other side.
Temnorožnate, ovalne, konveksne, filmsko obložene tablete z oznako "GS" na eni in "KE3" na drugi strani.
15 Volibris is not recommended for use in patients below 18 years of age due to a lack of data on safety and efficacy.
16 Zaradi pomanjkanja podatkov o varnosti in učinkovitosti uporaba zdravila Volibris pri bolnikih, mlajših od 18 let, ni priporočljiva.
16 Liver function abnormalities have been associated with PAH.
17 V povezavi s PAH so poročali o motnjah delovanja jeter.
17 Volibris tablets contain lactose monohydrate.
18 Volibris tablete vsebujejo laktozo monohidrat.
In vitro, ambrisentan has no inhibitory effect on the P-glycoprotein (Pgp)-mediated efflux of digoxin and is a weak substrate for Pgp-mediated efflux.
19 Ambrisentan in vitro ni zaviral s P- glikoproteinom (Pgp- P- glycoprotein) pogojenega efluksa digoksina in je šibek substrat za s Pgp pogojeni efluks.
18 Steady-state administration of ambrisentan in healthy volunteers had no clinically relevant effects on the single-dose pharmacokinetics of digoxin, a substrate for Pgp (see section 5.2).
Pri zdravih prostovoljcih pri uporabi ambrisentana v stanju dinamičnega ravnovesja niso opazili klinično pomembnih učinkov na farmakokinetiko enkratnega odmerka digoksina, substrata za P- gp (glejte poglavje 5. 2).
Safety of Volibris has been evaluated in clinical trials of more than 483 patients with PAH (see section 5.1).
20 Varnost zdravila Volibris so v kliničnih preskušanjih vrednotili pri več kot 483 bolnikih s PAH (glejte poglavje 5. 1).
Anaemia (decreased haemoglobin, decreased haematocrit)
Anemija (znižana vrednost hemoglobina, znižana Pogosti vrednost hematokrita)
3 Peripheral oedema was reported more frequently with 10 mg Volibris.
21 3 O perifernem edemu so pogosteje poročali pri uporabi 10 mg odmerka zdravila Volibris.
20 In addition to adverse reactions identified from clinical studies, the following adverse reactions were identified during post-approval use of Volibris.
Poleg neželenih učinkov, ki so jih ugotovili med kliničnimi študijami, so med uporabo zdravila Volibris po njegovi odobritvi zabeležili naslednje neželene učinke.
Ambrisentan is an orally active, propanoic acid-class, ERA selective for the endothelin A (ETA) receptor.
22 Ambrisentan je peroralno delujoč antagonist endotelinskih receptorjev (ERA) iz razreda propionske kisline, selektiven za receptorje endotelin A (ETA).
21 Two randomised, double-blind, multi-centre, placebo controlled, Phase 3 pivotal studies were conducted (ARIES-1 and 2).
Izvedeni sta bili dve randomizirani, dvojno slepi, multicentrični s placebom nadzorovani ključni študiji 3. faze (ARIES- 1 in 2).
Long term data
23 Dolgoročni podatki
22 An improvement in haemodynamic parameters was observed in patients with PAH after 12 weeks (n=29) in a Phase 2 study (AMB220).
Pri bolnikih s PAH je bilo po 12 tednih (n = 29) v študiji 2. faze (AMB220) opaženo izboljšanje hemodinamskih parametrov.
23 The effects of steady-state ambrisentan (10 mg once daily) on the pharmacokinetics and pharmacodynamics of a single dose of warfarin (25 mg), as measured by PT and INR, were investigated in 20 healthy volunteers.
Učinek ambrisentana v stanju dinamičnega ravnovesja (10 mg enkrat na dan) na farmakokinetiko in farmakodinamiko enkratnega odmerka varfarina (25 mg), vrednoteno s PT in INR, so raziskovali pri 20 zdravih prostovoljcih.
The effects of 12 days dosing with ambrisentan (10 mg once daily) on the pharmacokinetics of a single dose of oral contraceptive containing ethinyl estradiol (35 μ g) and norethindrone (1 mg) were studied in healthy female volunteers.
25 Pri zdravih prostovoljkah so raziskali učinke 12- dnevne uporabe ambrisentana (10 mg enkrat na dan) na farmakokinetiko enkratnega odmerka peroralnega kontraceptiva z etinilestradiolom (35 μg) in noretindronom (1 mg).
24 Ambrisentan does not undergo significant renal metabolism or renal clearance (excretion).
Ambrisentan ni podvržen pomembni ledvični presnovi ali ledvičnemu očistku (izločanju).
Nasal bone hyperplasia of the ethmoid turbinates has been observed in the nasal cavity of rats treated with ambrisentan, at exposure levels 3-fold the clinical AUC.
26 Pri podganah, ki so prejemale ambrisentan, so pri izpostavljenosti, ki je ustrezala 3- kratni vrednosti AUC pri klinični uporabi, poročali o hiperplaziji nosne kosti etmoidnega labirinta.
25 Ambrisentan has been shown to be teratogenic in rats and rabbits.
Pri podganah in kuncih je bilo dokazano, da je ambrisentan teratogen.
Film coat Polyvinyl alcohol (Partially Hydrolyzed) Talc (E553b) Titanium dioxide (E171) Macrogol / PEG 3350 Allura red AC Aluminium Lake (E129) Lecithin (Soya) (E322)
Filmska obloga polivinilalkohol (delno hidrolizirani) smukec (E553b) titanov dioksid (E171) makrogol / PEG 3350 rdeče AC (E129) lecitin (soja) (E322)
Detailed information on this medicinal product is available on the website of the European Medicines Agency (EMEA) http: / /www. emea. europa. eu/.
28 Podrobne informacije o zdravilu so objavljene na spletni strani Evropske agencije za zdravila (EMEA) http: // www. emea. europa. eu /.
27 ANNEX II
29 DODATEK II
KG Industriestrasse 32-36 D-23843 Bad Oldesloe Germany
KG Industriestrasse 32- 36 D- 23843 Bad Oldesloe Nemčija
The MAH shall set up a post-marketing surveillance study as per the synopsis in the EU-Risk Management Plan.
Imetnik dovoljenja za promet z zdravilom mora pripraviti študijo postmarketinškega nadzora v skladu s povzetkom Načrta obvladovanja tveganja v EU.
Details of the implementation of the post-marketing surveillance study should be agreed with the National Competent Authorities in each member state and put in place prior to marketing of the product.
O podrobnostih za izvedbo študije postmarketinškega nadzora se mora dogovoriti s pristojnimi nacionalnimi organi v vsaki državi članici in zagotoviti njeno izvajanje pred začetkom trženja zdravila.
The MAH must agree the details of a controlled distribution system with the National Competent Authorities and must implement such programme nationally to ensure that prior to prescribing (and where appropriate and in agreement with the National Competent Authority, dispensing) all health care professionals who intend to prescribe (and where appropriate, dispense) Volibris have been provided with the following:
Imetnik dovoljenja za promet z zdravilom se mora s pristojnimi nacionalnimi organi dogovoriti o podrobnostih sistema nadzorovane distribucije in takšen program uvesti na nacionalni ravni tako, da zagotovi, da imajo pred začetkom predpisovanja zdravila (in kjer je primerno ter v dogovoru s pristojnimi nacionalnimi organi, izdajanjem zdravila) vsi zdravstveni delavci, ki bodo predpisovali (in kjer je primerno, izdajali) zdravilo Volibris na voljo naslednje:
• Product information (Summary of Product Characteristics (SPC) and Package Leaflet) • Healthcare professional information regarding Volibris • Pre-prescription checklist for physicians • Information about the post marketing surveillance study • Information booklets for patients • Information booklets for male partners of female patients with child-bearing potential • Patient reminder cards • Pregnancy reporting forms • Adverse drug reaction reporting forms
• podatke o zdravilu (Povzetek glavnih značilnosti zdravila (SmPC) in Navodilo za uporabo) • - podatke o zdravilu Volibris za zdravstvene delavce • - kontrolni seznam za zdravnika • - podatke o študiji postmarketinškega nadzora • - informacijske brošure za bolnike • - informacijske brošure za moške partnerje bolnic v rodni dobi • - opozorilne kartončke za bolnika • - obrazce za poročanje o nosečnosti • -- obrazce za poročanje o neželenih učinkih zdravila
The healthcare professional information regarding Volibris should contain the following key elements:
- Podatki o zdravilu Volibris za zdravstvene delavce morajo vključevati naslednje bistvene elemente:
Obligations of health care professionals in relation to the prescribing of Volibris:
Obveznosti zdravstvenih delavcev pri predpisovanju zdravila Volibris:
29 • That patients should be capable of complying with the requirements for the safe use of Volibris. • The need to provide comprehensive advice and counselling to patients. • The need to provide patients with the appropriate information booklet(s) and patient reminder card. • Should consider monthly prescription of 30 day supply to ensure that patients and key test results are reviewed prior to further prescription. • That the safety database of Volibris is limited and physicians are encouraged to enrol patients in a post marketing surveillance study. • To report suspected adverse reactions and pregnancy.
31 • - presoditi morajo, da so bolniki sposobni izpolnejvati zahteve glede varne uporabe zdravila Volibris. • - bolnikom morajo zagotoviti razumljiv in izčrpen nasvet ter svetovanje. • - bolnikom morajo zagotoviti ustrezno informacijsko brošuro (brošure) in opozorilni kartonček za bolnika. • - presoditi morajo o mesečnem predpisovanju zdravila za 30- dnevno zalogo, da lahko pred nadaljnjim predpisovanjem pregledajo tako bolnika kot rezultate ključnih testov. • - seznaniti se morajo s celotno podatkovno bazo o varnosti zdravila Volibris in možnostjo vključitve bolnikov v študijo postmarketinškega nadzora. • - poročati morajo o vseh sumih na neželene učinke in o primerih nosečnosti.
• Volibris is contraindicated in pregnancy and in women of child-bearing potential who are not using reliable contraception. • That women receiving Volibris should be advised of the risk of foetal harm. • Guidance for identifying women of child-bearing potential and the actions the physician should take if unsure.
• - Uporaba zdravila Volibris je kontraindicirana med nosečnostjo in pri ženskah v rodni dobi, ki ne uporabljajo zanesljive metode kontracepcije. • - Ženske, ki se zdravijo z zdravilom Volibris, je treba seznaniti s tveganjem za okvaro plodu. • - Smernice za ugotovitev rodne dobe pri ženskah in ukrepe, ki jih morajo v primeru negotovosti izvesti zdravniki.
• Exclusion of pregnancy prior to treatment initiation and monthly pregnancy testing during treatment. • The need to advise women (even if a woman has amenorrhoea) on the use of reliable contraception during treatment and for one month following permanent discontinuation of treatment. • Definition of reliable contraception and the need to seek expert advice if unsure what is suitable for an individual patient. • That if a woman of child-bearing potential needs to change or stop her method of contraception she should inform the physician prescribing her contraception that she is taking Volibris. • That if a women of child-bearing potential needs to change or stop her method of contraception she should inform the physician prescribing Volibris. • That the patient should contact her doctor immediately if pregnancy is suspected and that alternative therapy should be initiated if pregnancy confirmed. • The need to refer patients who become pregnant to a physician specialised or experienced in teratology and its diagnosis for evaluation and advice. • To report all cases of pregnancy occurring during therapy.
Če se nosečnost potrdi, je treba uvesti alternativno obliko zdravljenja. • - Bolnico, ki je zanosila, je treba napotiti k specialistu ali zdravniku z izkušnjami v teratologiji, ki mora izvesti diagnostične preiskave in podati svoje mnenje. • -- Poročati je treba o vseh primerih nosečnosti, do katerih je prišlo med zdravljenjem.
• Contraindication in patients with severe hepatic impairment (with or without cirrhosis) and in patients with baseline values of hepatic aminotransferases (AST and/ or ALT) > 3X ULN. • Hepatic aminotransferases (ALT and/ or AST) should be evaluated prior to initiation of ambrisentan. • During therapy, monthly monitoring of ALT and AST is recommended. • Discontinuation of ambrisentan therapy if patients develop sustained, unexplained clinically significant ALT and/ or AST elevation or if ALT and/ or AST elevation is accompanied by signs or symptoms of hepatic injury (e. g. jaundice). • In subjects without clinical symptoms of hepatic injury or jaundice, reinitiation of ambrisentan may be considered following resolution of hepatic enzyme abnormalities.
• - Kontraindikacija pri bolnikih s hudo okvaro jeter (s cirozo ali brez) in pri bolnikih z izhodiščnimi vrednostmi jetrnih aminotransferaz (AST in/ ali ALT) > 3X ZNV. • - Pred uvedbo zdravljenja z ambrisentanom je treba ovrednotiti vrednost jetrnih aminotransferaz (ALT in/ ali AST). • - Med zdravljenjem je priporočljivo mesečno nadzirati vrednosti ALT in AST. • - Če se pri bolniku pojavi trdovratno, nepojasnjeno klinično pomembno zvišanje vrednosti ALT in/ ali AST, ali če zvišanje vrednosti ALT in/ ali AST spremljajo znaki ali simptomi okvare jeter (npr. zlatenica), je treba zdravljenje z ambrisentanom prekiniti. • - Pri osebah brez kliničnih simptomov okvare jeter ali zlatenice se o ponovni uvedbi zdravljenja z ambrisentanom lahko razmisli, ko nenormalnosti jetrnih encimov minejo.
That treatment with Volibris often causes a decrease in haemoglobin and haematocrit
Da je zdravljenje z zdravilom Volibris pogosto povezano z znižanjem vrednosti hemoglobina in hematokrita
30 • Initiation of Volibris is not recommended for patients with clinically significant anaemia. • Patients taking Volibris should have their haemoglobin and/ or haematocrit levels measured regularly. • If tests show a clinically significant decrease in haemoglobin or haematocrit, and other causes have been excluded, consider reducing the dose of Volibris, or stopping treatment.
32 • - Pri bolnikih s klinično pomembno anemijo uvedba zdravljenja z zdravilom Volibris ni priporočljiva. • - Pri bolnikih, ki jemljejo zdravilo Volibris, je treba redno nadzirati vrednosti hemoglobina in/ ali hematokrita. • - Če preiskave pokažejo klinično pomembno znižanje vrednosti hemoglobina ali hematokrita in so drugi vzroki izključeni, je treba razmisliti o zmanjšanju odmerka zdravila Volibris ali o prekinitvi zdravljenja.
That treatment with Volibris causes peripheral oedema and fluid retention
Da je zdravljenje z zdravilom Volibris povezano s perifernim edemom in kopičenjem tekočin
• If a patient develops clinically significant peripheral oedema, with or without associated weight gain, carry out further evaluation to determine the cause and if appropriate consider discontinuation of Volibris.
• - Če se pri bolniku pojavi klinično pomemben periferni edem, s pridruženim povečanjem telesne mase ali brez, je za ugotovitev vzroka treba izvesti dodatne diagnostične postopke in po potrebi razmisliti o prekinitvi zdravljenja z zdravilom Volibris.
That Volibris should be initiated with caution in patients with severe renal impairment.
Da je treba zdravljenje z zdravilom Volibris pri bolnikih s hudo okvaro ledvic uvesti previdno.
That hypersensitivity reactions, although uncommon, have been reported with Volibris.
Da so pri uporabi zdravila Volibris občasno poročali o pojavu preobčutljivostnih reakcij.
The physician pre-prescription checklist will highlight the contraindications to the use of ambrisentan and important pre-prescription assessments including:
V kontrolnem seznamu za zdravnike morajo biti posebej poudarjene kontraindikacije za uporabo ambrisentana in pomembna dejstva/ preiskave, ki jih je treba poznati/ izvesti pred začetkom zdravljenja, vključno s/ z:
• Liver function tests. • Determination of child-bearing potential in female patients. • Pregnancy test if female patient with child-bearing potential. • That women of child-bearing potential are on reliable contraception.
• - preiskavami delovanja jeter. • - določitvijo rodne dobe pri bolnicah. • - testom za ugotavljanje nosečnosti pri bolnicah v rodni dobi. • -- preverjanjem, če ženska v rodni dobi uporablja zanesljivo metodo kontracepcije.
Patient information
Podatki za bolnike
The information for patients should include the following information:
Podatki za bolnike morajo vključevati naslednje podatke:
• That Volibris may cause serious birth defects in unborn babies conceived before, during, or within a month after stopping treatment. • That Volibris cannot be initiated if patient is pregnant. • Women with child-bearing potential must have a pregnancy test immediately prior to the first prescription and at monthly intervals whilst taking Volibris. • The need to ensure that women of child-bearing potential are using reliable contraception and that patients should inform their doctors of any possibility of pregnancy before a new prescription is issued. • That if a women of child-bearing potential needs to change or stop her method of contraception she should inform the physician prescribing her contraception that she is taking Volibris. • That if a women of child-bearing potential needs to change or stop her method of contraception she should inform the physician prescribing Volibris. • The need for female patients to contact their treating doctor immediately if they suspect that they might be pregnant. • The need for the patient to discuss with her doctor if she is planning to become pregnant. • That Volibris may cause liver injury. • That because of the potential for liver injury and anaemia, patients should have regular blood tests and also tell their doctor if experiencing any symptoms of liver injury. • That the patient should not give Volibris to any other person. • That the patient should tell their doctor about any adverse event.
33 • -- da lahko zdravilo Volibris povzroči resne okvare ploda, če ženska zanosi pred, med ali v enem mesecu po prekinitvi zdravljenja. • - da se zdravljenje z zdravilom Volibris ne sme uvesti, če je bolnica noseča. • - da morajo ženske v rodni dobi neposredno pred začetkom zdravljenja z zdravilom Volibris opraviti test za ugotavljanje nosečnosti in ga nato med zdravljenjem opravljati v mesečnih intervalih. • - da morajo ženske v rodni dobi uporabljati zanesljivo metodo kontracepcije in da morajo bolnice pred izdajo novega recepta svojega zdravnika obvestiti o vsaki možnosti zanositve. • -- da mora ženska v rodni dobi, ki mora spremeniti ali prenehati uporabljati dosedanjo metodo kontracepcije zdravnika, ki ji je predpisal kontracepcijo obvestiti, da jemlje zdravilo Volibris. • --- da mora ženska v rodni dobi, ki mora spremeniti ali prenehati uporabljati dosedanjo metodo kontracepcije, o tem obvestiti zdravnika, ki ji je predpisal zdravilo Volibris. • - da mora bolnica o vsaki možnosti zanositve nemudoma obvestiti svojega lečečega zdravnika. • - da se mora bolnica posvetovati s svojim zdravnikom, če namerava zanositi. • - da lahko zdravilo Volibris povzroči okvaro jeter. • - da je zaradi možne okvare jeter in anemije treba redno izvajati krvne preiskave in da mora bolnik obvestiti svojega zdravnika, če se pojavi kakršenkoli simptom okvare jeter. • - da bolnik zdravila Volibris ne sme dajati drugi osebi. • -- da mora bolnik svojega zdravnika obvestiti o vsakem neželenem učinku.
31 Booklet for male partners of women with child-bearing potential
- Brošura za moške partnerje žensk v rodni dobi
The information for male partners of women with child-bearing potential should include the following information:
- Podatki za moške partnerje žensk v rodni dobi morajo vključevati naslednje podatke:
• That Volibris may cause serious birth defects in unborn babies conceived before, during, or within a month after stopping treatment. • The need to ensure that women of child-bearing potential are using reliable contraception. • That Volibris cannot be taken if a woman is or might become pregnant.
• -- da lahko zdravilo Volibris povzroči resne okvare ploda, če ženska zanosi pred, med ali v enem mesecu po prekinitvi zdravljenja. • --- da morajo ženske v rodni dobi uporabljati zanesljivo metodo kontracepcije. • -- da ženska, ki je ali bi lahko bila noseča, ne sme jemati zdravila Volibris.
Patient reminder card
- Opozorilni kartonček za bolnika
This should include key messages regarding the need for regular blood and pregnancy tests and provide spaces for the dates of appointments and the results of tests.
Opozorilni kartonček za bolnika mora vključevati bistvene podatke o potrebnosti rednega izvajanja krvnih preiskav in testov za ugotavljanje nosečnosti ter imeti predvidne prostore za vpisovanje terminov in rezultatov opravljenih preiskav.
The MAH must ensure that the system of pharmacovigilance, as described in version 6.2 presented in Module 1.8.1. of the Marketing Authorisation Application, is in place and functioning before and whilst the product is on the market.
Imetnik dovoljenja za promet z zdravilom mora pred začetkom trženja zdravila vzpostaviti sistem farmakovigilance, kot je opisan v različici 6. 2 v modulu 1. 8. 1. vloge za pridobitev dovoljenja za promet z zdravilom, in ga vzdrževati ves čas trženja zdravila.