FrancophonIA/ELRC3.0 huggingface dataset:
English: Thromboembolism (clots in the blood vessels) may occur very rarely, usually associated with severe OHSS.
Slovenian: Trombembolizem (strdki v krvnih žilah) se pojavi zelo redko, navadno pa je značilen za hudo obliko sindroma hiperstimulacije jajčnikov.
English: In the body, FSH stimulates the production of eggs, and LH stimulates their release.
Slovenian: Folikle stimulirajoči hormon v telesu spodbuja tvorbo jajčec, luteinizirajoči hormon pa spodbudi njihovo sprostitev.
English: How is Pergoveris used?
Slovenian: Kako se zdravilo Pergoveris uporablja?
English: Mild or moderate OHSS is common, while severe OHSS is uncommon.
Slovenian: Blag ali zmeren sindrom hiperstimulacije jajčnikov je pogost, huda oblika tega sindroma pa redka.
English: How does Pergoveris work?
Slovenian: Kako zdravilo Pergoveris deluje?
English: It is intended for short-term use.
Slovenian: Namenjeno je kratkotrajni uporabi.
English: Ref.: EMEA/644240/2009 EMEA/H/C/396
Slovenian: : EMEA/644240/2009 EMEA/H/C/396
English: After five years, the marketing authorisation was renewed for a further five years.
Slovenian: Po petih letih je bilo dovoljenje za promet z zdravilom podaljšano za nadaljnjih pet let.
English: Every year, the European Medicines Agency will review any new information that may become available and this summary will be updated as necessary.
Slovenian: Evropska agencija za zdravila bo vsako leto pregledala vse razpoložljive nove podatke in po potrebi posodobila ta povzetek.
English: All the studies looked at the number of patients who had died after 28 days.
Slovenian: V vseh študijah so beležili število bolnikov, ki so umrli po 28 dneh.
English: If you want more information on the basis for the CHMP recommendations, read the Scientific Discussion (also part of the EPAR).
Slovenian: Če želite več informacij, ki temeljijo na priporočilih CHMP, preberite znanstveno razpravo (ki je prav tako del EPAR).
English: Xigris has been authorised under ‘Exceptional Circumstances'.
Slovenian: Zdravilo Xigris je bilo odobreno v „izjemnih okoliščinah“.
English: The recommended dose of Xigris is 24 micrograms per kilogram body weight per hour, given as a continuous infusion for 96 hours.
Slovenian: Priporočeni odmerek zdravila Xigris je 24 mikrogramov na kilogram telesne mase na uro, ki se daje kot neprekinjena infuzija v skupnem trajanju 96 ur.
English: The European Commission granted a marketing authorisation valid throughout the European Union for Xigris to Eli Lilly Nederland B.V. on 22 August 2002.
Slovenian: Evropska komisija je dovoljenje za promet z zdravilom Xigris, veljavno po vsej Evropski uniji, odobrila družbi Eli Lilly Nederland B.V.
English: It must not be used in patients below 18 years of age, in patients who have long-term liver disease, a brain tumour or pressure on the brain, in patients also receiving high-dose heparin (another medicine used to prevent blood clots) or in patients who currently have internal bleeding or are at risk of bleeding.
Slovenian: Ne sme se uporabljati pri bolnikih, mlajših od 18 let, pri bolnikih, ki imajo dolgotrajno obolenje jeter, možganski tumor ali pritisk v možganih, pri bolnikih, ki prejemajo heparin v visokih odmerkih (drugo zdravilo za preprečevanje krvnih strdkov), ali pri bolnikih, ki imajo notranjo krvavitev ali so v nevarnosti, da bodo krvaveli.
English: The toxins cause the patient's organs to fail, such as the heart, lungs and kidneys.
Slovenian: Toksini povzročajo odpoved organov bolnika, kot so srce, pljuča, ledvice.
English: The Committee for Medicinal Products for Human Use (CHMP) decided that Xigris's benefits are greater than its risks and recommended that it be given marketing authorisation.
Slovenian: Odbor za zdravila za uporabo v humani medicini (CHMP) je zaključil, da so koristi zdravila Xigris večje od z njim povezanih tveganj, in priporočil, da se za zdravilo odobri dovoljenje za promet.
English: For the full list of restrictions, see the Package Leaflet.
Slovenian: Za celoten seznam omejitev glejte navodilo za uporabo.
English: This means that it has not been possible to obtain complete information about Xigris.
Slovenian: To pomeni, da o zdravilu ni bilo mogoče pridobiti vseh informacij.
English: Xigris is used when the patient has two or more organs failing, in addition to best standard care such as antibiotics, medicines to support the organs and treatment in a specialised unit.
Slovenian: Zdravilo Xigris se uporablja, ko bolniku odpovedujeta dva organa ali več, kot dodatek najboljšemu standardnemu zdravljenju, kot so antibiotiki, zdravila za podporo organom in zdravljenje na specializiranem oddelku.
English: Other information about Xigris:
Slovenian: Druge informacije o zdravilu Xigris:
English: Sepsis is a condition when bacteria get into the bloodstream and produce harmful substances (toxins).
Slovenian: Sepsa je stanje, ko bakterije vstopijo v krvni obtok in tvorijo škodljive snovi (toksine).
English: Excessive blood clotting is a problem during severe sepsis, because blood clots can block the blood supply to important parts of the body such as the kidneys and lungs.
Slovenian: Pri hudi sepsi je težava čezmerno strjevanje krvi, ker lahko krvni strdki ovirajo oskrbo pomembnih delov telesa s krvjo, kot so ledvice in pljuča.
English: The company that makes Xigris will conduct an additional study looking at the safety and effectiveness of Xigris in patients with severe sepsis.
Slovenian: Družba, ki izdeluje zdravilo Xigris, bo opravila dodatno študijo, v kateri bo proučila varnost in učinkovitost zdravila pri bolnikih s hudo sepso.
English: • in the ADDRESS study, Xigris was compared with placebo in almost 3,000 patients who were at a lower risk of death than in the first two studies.
Slovenian: • v študiji ADRESS so zdravilo Xigris primerjali s placebom pri skoraj 3 000 bolnikih, ki so bili manj življenjsko ogroženi kot v prvih dveh študijah.
English: In the body, drotrecogin alfa limits how much thrombin (one of the factors involved in blood clotting) is produced, and also reduces the inflammation caused by the infection.
Slovenian: V telesu drotrekogin alfa omeji nastajanje trombina (enega od dejavnikov pri strjevanju krvi) ter zmanjša vnetje, ki ga povzroča okužba.
English: • in the ENHANCE study, over 2,000 patients received Xigris;
Slovenian: • v študiji ENHANCE je zdravilo Xigris prejelo več kot 2 000 bolnikov;
English: The active substance in Xigris, drotrecogin alfa (activated), is very similar to a natural anticoagulant found in the body called activated protein C. Drotrecogin alfa is produced by a method known as ‘recombinant DNA technology': it is made by a cell that has received a gene (DNA), which makes it able to produce drotrecogin alfa.
Slovenian: Zdravilna učinkovina zdravila Xigris, drotrekogin alfa (aktiviran), je zelo podobna naravnemu antikoagulacijskemu sredstvu v telesu, ki se imenuje aktiviran protein C. Drotrekogin alfa je izdelan z metodo, znano kot „tehnologija rekombinantne DNK“.
English: It contains the active substance drotrecogin alfa (activated).
Slovenian: Vsebuje zdravilno učinkovino drotrekogin alfa (aktiviran).
English: Xigris should not be used in people who may be hypersensitive (allergic) to drotrecogin alfa (activated), any of the other ingredients or bovine thrombin (a cow protein).
Slovenian: Zdravila Xigris ne smejo uporabljati osebe, ki utegnejo biti preobčutljive za (alergične na) drotrekogin alfa (aktiviran), katero koli drugo sestavino zdravila ali na goveji trombin (kravjo beljakovino).
English: Xigris is an anticoagulant, which means that it stops the blood coagulating (clotting).
Slovenian: Zdravilo Xigris je antikoagulant, kar pomeni, da preprečuje koagulacijo (strjevanje) krvi.
English: Fewer patients treated with Xigris had died at 28 days than patients treated with placebo.
Slovenian: V 28 dneh je umrlo manj bolnikov, ki so prejemali zdravilo Xigris, kot bolnikov, ki so dobivali placebo.
English: What benefit has Xigris shown during the studies?
Slovenian: Kakšne koristi je zdravilo Xigris izkazalo med študijami?
English: As with other anticoagulants, the most common side effect with Xigris is bleeding.
Slovenian: Kot pri vseh antikoagulacijskih sredstvih je tudi pri zdravilu Xigris najpogostejši neželeni učinek krvavitev.
English: What is the risk associated with Xigris?
Slovenian: Kakšna tveganja so povezana z zdravilom Xigris?
English: Xigris should be used by experienced doctors in institutions skilled in the care of patients with severe sepsis.
Slovenian: Zdravilo Xigris morajo uporabljati izkušeni zdravniki v ustanovah z usposobljenim osebjem za zdravljenje bolnikov s hudo sepso.
English: The full EPAR for Xigris is available here.
Slovenian: Celotno evropsko javno poročilo o oceni zdravila (EPAR) za zdravilo Xigris je na voljo tukaj.
English: The effect of Xigris was more marked when it was given within 24 hours of the start of organ failure, and in patients who had more than one organ failing.
Slovenian: Učinek zdravila Xigris je bil izrazitejši, če je bilo vzeto v 24 urah od pojava odpovedovanja organov, in pri bolnikih, ki jim je odpovedovalo več organov.
English: For the full list of all side effects reported with Xigris, see the Package Leaflet.
Slovenian: Za celoten seznam neželenih učinkov, o katerih so poročali pri uporabi zdravila Xigris, glejte navodilo za uporabo.
English: • in the PROWESS study, Xigris was compared with placebo (dummy treatment) in 1,690 patients;
Slovenian: • v študiji PROWESS so zdravilo Xigris pri 1 690 bolnikih primerjali s placebom (zdravilom brez zdravilne učinkovine);
English: What information is still awaited for Xigris?
Slovenian: Katere informacije o zdravilu Xigris še pričakujemo?
English: By using Xigris during sepsis, the risk of blood clots forming and damaging the organs is reduced.
Slovenian: Uporaba zdravila Xigris med sepso zmanjša nevarnost nastajanja krvnih strdkov, ki lahko poškodujejo organe.
English: Xigris drotrecogin alfa (activated) EPAR summary for the public
Slovenian: drotrekogin alfa (aktiviran)
English: Why has Xigris been approved?
Slovenian: Zakaj je bilo zdravilo Xigris odobreno?
English: Xigris should be used mainly when it can be started within 24 hours of the organ failure.
Slovenian: Zdravilo Xigris je treba uporabiti zlasti, ko je mogoče zdravljenje začeti v 24 urah od pojava odpovedovanja organov.
English: Xigris has been studied in three studies in severe sepsis:
Slovenian: Zdravilo Xigris so proučevali v treh študijah hude sepse:
English: Xigris is a powder that is made up into a solution for infusion (drip into a vein).
Slovenian: Zdravilo Xigris je prašek za pripravo raztopine za infundiranje (kapalne infuzije v veno).
English: Xigris is used in adult patients with severe sepsis.
Slovenian: Zdravilo Xigris se uporablja za zdravljenje bolnikov s hudo sepso.
English: Xigris should be started within 48 hours, and preferably within 24 hours, after the start of organ failure.
Slovenian: Zdravljenje z zdravilom Xigris se mora začeti v 48 urah od pojava odpovedovanja organov, najbolje pa v 24 urah.
English: How does Xigris work?
Slovenian: Kako zdravilo Xigris deluje?
English: Giving Xigris using an infusion pump is the recommended way to ensure that infusion rates are well controlled.
Slovenian: Za natančen nadzor hitrosti infundiranja se za odmerjanje zdravila Xigris priporoča uporaba infuzijske črpalke.
English: How has Xigris been studied?
Slovenian: Kako je bilo zdravilo Xigris raziskano?
English: What is Xigris used for?
Slovenian: Za kaj se zdravilo Xigris uporablja?
English: What is Xigris?
Slovenian: Kaj je zdravilo Xigris?
English: How is Xigris used?
Slovenian: Kako se zdravilo Xigris uporablja?
English: Risk minimisation measures
Slovenian: Ukrepi za zmanjšanje tveganja
English: The European Commission requested the Agency to give its opinion on whether the marketing authorisation for these products should be maintained, varied, suspended or withdrawn.
Slovenian: Evropska komisija je agencijo zaprosila, naj poda svoje mnenje, ali naj se dovoljenje za promet s tema zdraviloma ohrani, spremeni, začasno umakne ali prekliče.
English: Treatment should be discontinued if the symptoms of angina do not improve within 3 months.
Slovenian: Zdravljenje je treba prekiniti, če se simptomi angine ne izboljšajo v 3 mesecih;
English: Applying such a cut-off based on data from the BEAUTIFUL study is a reasonable measure to exclude patients who are likely to be at higher risk.
Slovenian: Uporaba take omejitve, ki temelji na podatkih iz študije BEAUTIFUL, je razumen ukrep za izključitev bolnikov, ki bodo verjetno izpostavljeni večjemu tveganju.
English: As the absolute risk is based on 69 events, the possibilities for further analysis to identify the contributing risk factors are limited.
Slovenian: Ker absolutno tveganje temelji na 69 dogodkih, so možnosti za nadaljnjo analizo za ugotavljanje sočasnih dejavnikov tveganja omejene.
English: CHMP opinion
Slovenian: Mnenje odbora CHMP
English: The results of the SIGNIFY study were published4 while this review was ongoing and are discussed below.
Slovenian: Rezultati študije SIGNIFY so bili objavljeni4, medtem ko je potekal pregled, in so opisani spodaj.
English: This highlights the need to comply with the currently authorized posology.
Slovenian: To je poudarilo potrebo po upoštevanju trenutno odobrenega odmerjanja.
English: No significant differences were also observed in any of the secondary endpoints.
Slovenian: Tudi pri sekundarnih opazovanih dogodkih niso opazili nobenih pomembnih razlik.
English: The frequency of atrium fibrillation (AF) was higher than currently described in the product information.
Slovenian: Pogostnost atrijske fibrilacije (AF) je bila večja, kot je trenutno opisano v informacijah o zdravilu.
English: • The PRAC considered Procoralan and Corlentor (ivabradine) in the procedure under Article 20 of Regulation (EC) No 726/2004, initiated by the European Commission.
Slovenian: • odbor PRAC je proučil zdravili Procoralan in Corlentor (ivabradin) v okviru postopka v skladu s členom 20 Uredbe (ES) št. 726/2004, ki ga je sprožila Evropska komisija;
English: • Reinforcement of the recommendation not to exceed the authorised posology.
Slovenian: • okrepiti je treba priporočila, naj se ne preseže odobreno odmerjanje;
English: Ivabradine was also associated with a significantly higher risk of bradycardia.
Slovenian: Ivabradin je bil prav tako povezan s pomembno večjim tveganjem bradikardije.
English: After three to four weeks of treatment, the dose may be increased to 7.5 mg twice daily depending on the therapeutic response.
Slovenian: Po treh do štirih tednih zdravljenja je mogoče odmerek povečati na 7,5 mg dvakrat na dan, kar je odvisno od terapevtskega odziva.
English: 2 - Detailed explanation of the scientific differences from PRAC recommendation
Slovenian: - Podrobna obrazložitev znanstvenih odstopanj od priporočila PRAC
English: Nevertheless information monitoring of patients for AF needs to be reinforced.
Slovenian: Kljub temu pa je treba informacije o spremljanju bolnikov za atrijsko fibrilacijo okrepiti.
English: The Product Information for Corlentor and Procoralan was revised to include the following:
Slovenian: Informacije o zdravilih Corlentor in Procorlan so bile spremenjene, tako da vključujejo naslednje:
English: The individual components of the endpoint were not significantly increased.
Slovenian: Posamezni komponenti opazovanega dogodka nista bili pomembno povečani.
English: Having reviewed the PRAC recommendation, the CHMP agreed with the overall scientific conclusions and grounds for recommendation.
Slovenian: Po pregledu priporočila odbora PRAC se je odbor CHMP strinjal s splošnimi znanstvenimi zaključki in razlogi za priporočilo.
English: An additional risk minimisation activity was required by the PRAC.
Slovenian: Odbor PRAC je zahteval dodatno ukrepanje za zmanjševanje tveganja.
English: Overall conclusion
Slovenian: Splošni zaključek
English: Other factors could not be directly related to a higher CV risk.
Slovenian: Drugih dejavnikov ni mogoče neposredno povezati z večjim kardiovaskularnim tveganjem.
English: • Concomitant use of grapefruit juice is now not recommended due to the potential for a pharmacokinetic interaction resulting in increased exposure to ivabradine.
Slovenian: • sočasna uporaba soka grenivke zdaj ni priporočena zaradi morebitne farmakokinetične interakcije, ki povzroči povečano izpostavljenost ivabradinu.
English: None of the factors identified in the SIGNIFY study had an impact on the beneficial effect of ivabradine observed in the SHIFT study.
Slovenian: Noben od dejavnikov, ki so jih ugotovili v študiji SIGNIFY, ni vplival na koristen učinek ivabradina, ki so ga opazili v študiji SHIFT.
English: In addition, the higher dose of 10 mg could clarify the higher incidence of bradycardia during the SIGNIFY study in comparison to other large studies with ivabradine, BEAUTIFUL and SHIFT.
Slovenian: Poleg tega bi lahko z večjim 10-miligramskim odmerkom pojasnili večjo incidenco bradikardije med študijo SIGNIFY v primerjavi z drugima velikima študijama z ivabradinom, BEAUTIFUL in SHIFT.
English: Given that the subgroup of symptomatic angina patients may correspond to the population of patients for whom one of the therapeutic indications for ivabradine is currently approved, the European Commission initiated on 8 May 2014 a procedure under Article 20 of Regulation (EC) No 726/2004 and requested the Agency to assess the above concerns and their impact on the benefit
Slovenian: Ker bi lahko podskupina bolnikov s simptomatsko angino pektoris ustrezala populaciji bolnikov, za katero je trenutno odobrena ena od terapevtskih indikacij ivabradina, je Evropska komisija 8. maja 2014 sprožila postopek v skladu s členom 20 Uredbe (ES) št. 726/2004 in agencijo zaprosila, naj oceni zgoraj navedene pomisleke ter njihov vpliv na razmerje med tveganji in koristmi zdravil Procoralan in Corlentor, odobrenih po decentraliziranem postopku.
English: Also a lower dose and different titration method was used in the SHIFT study when compared to the SIGNIFY study.
Slovenian: Prav tako sta bila v študiji SHIFT uporabljena manjši odmerek in druga metoda titracije kot v študiji SIGNIFY.
English: The CHMP considered it necessary to introduce a statement in section 4.8 of the Summary of Product Characteristics reflecting the incidence of atrial fibrillation in the SIGNIFY study.
Slovenian: Odbor CHMP je menil, da je treba v poglavje 4.8 povzetka glavnih značilnosti zdravila vključiti izjavo, povezano z incidenco atrijske fibrilacije v študiji SIGNIFY.
English: If atrial fibrillation develops during treatment, the benefits and risks of continued treatment with ivabradine should be carefully reconsidered.
Slovenian: Če se med zdravljenjem razvije atrijska fibrilacija, je treba skrbno pretehtati koristi in tveganja nadaljevanja zdravljenja z ivabradinom;
English: In the whole population (n=19102), ivabradine did not significantly affect the primary composite endpoint (PCE) or its individual components (CV death and non-fatal myocardial infarction).
Slovenian: V celotni populaciji (n = 19102) ivabradin ni pomembno vplival na primarni sestavljeni opazovani dogodek (PCE) ali njegovi posamezni komponenti (kardiovaskularna smrt in nesmrtni miokardni infarkt).
English: • Warnings added on measurement of heart rate, lack of benefit on clinical outcomes, and atrial fibrillation.
Slovenian: • dodana so opozorila glede meritve srčnega utripa, pomanjkanja koristi pri kliničnih izidih in atrijske fibrilacije;
English: The MAH is requested to submit within the agreed timelines, the final study protocol of the drug utilisation study.
Slovenian: Imetnika dovoljenja za promet z zdravilom so prosili, naj končni protokol študije o uporabi zdravila predloži v dogovorjenem roku.
English: Given the importance of ensuring that patient are not exposed to higher than recommended dose of ivabradine, the currently existing warning on concomitant intake of grapefruit juice should be strengthened to avoid a potential pharmacokinetic interaction.
Slovenian: Glede na pomembnost zagotavljanja, da bolniki niso izpostavljeni odmerkom, večjim od priporočenega odmerka ivabradina, je treba trenutno opozorilo o sočasnem vnosu soka grenivke okrepiti, da se prepreči morebitna farmakokinetična interakcija.
English: • The PRAC reviewed all data presented by the MAH on the safety and efficacy of ivabradine, including the results of the SIGNIFY study, as well as the views expressed by the cardiovascular scientific advisory group.
Slovenian: • odbor PRAC je pregledal vse podatke o varnosti ter učinkovitosti ivabradina, vključno z rezultati študije SIGNIFY, ki jih je predstavil imetnik dovoljenja za promet z zdravilom, in mnenja kardiovaskularne znanstvene svetovalne skupine;
English: Therefore it is considered that overall, the results of the SIGNIFY study do not impact on the heart failure indication.
Slovenian: Zato menijo, da rezultati študije SIGNIFY na splošno niso vplivali na indikacijo srčnega popuščanja.
English: The PRAC is of the opinion that the higher than approved dose used in the SIGNIFY study does not fully explain these findings.
Slovenian: Odbor je menil, da z odmerkom, večjim od odobrenega, ki je bil uporabljen v študiji SIGNIFY, ni mogoče popolnoma razložiti teh ugotovitev;
English: Therefore it is justified that ivabradine is discontinued or down titrated if the heart rate falls under 50 bpm.
Slovenian: Zato je upravičeno, da se uporaba ivabradina prekine ali zmanjša njegov odmerek, če srčni utrip pade pod 50 udarcev/min.
English: On 30 April 2014, the EMA received from the MAH a communication on the preliminary results of the SIGNIFY3 study.
Slovenian: Agencija EMA je 30. aprila 2014 od imetnika dovoljenja za promet z zdravilom prejela dopis s prvotnimi rezultati študije SIGNIFY3.
English: Scientific discussion
Slovenian: Znanstvena razprava
English: In another clinical study evaluating the impact of grapefruit juice on ivabradine pharmacokinetics, an intake of 600 ml given as 200 ml three times a day for 3 days a moderate interaction level was observed with a 2.3-fold increase in ivabradine exposure.
Slovenian: V drugi klinični študiji, ki je ocenjevala vpliv soka grenivke na farmakokinetiko ivabradina (skupno 600 ml v odmerkih 200 ml trikrat na dan tri dni zapored), so opazili zmerno stopnjo interakcije z 2,3-kratnim povečanjem izpostavljenosti ivabradinu.
English: The safety profile was dominated by adverse reactions already described for the product, notably all forms of bradycardia (17.9% ivabradine vs 2.1% placebo) and phosphenes (5.3% ivabradine vs 0.5% placebo).
Slovenian: Varnostni profil je večinoma vključeval neželene učinke, ki so že opisani v informacijah o zdravilu, predvsem vse vrste bradikardije (17,9 % za ivabradin in 2,1 % za placebo) in fosfene (5,3 % za ivabradin in 0,5 % za placebo).
English: Atrial fibrillation (AF) occurred in 5.3% of patients on ivabradine vs. 3.8% of patients on placebo.
Slovenian: Atrijska fibrilacija (AF) se je pojavila pri 5,3 % bolnikov, zdravljenih z ivabradinom, in 3,8 % bolnikov s placebom.
English: This is further supported by some of the data indicating that a heart rate <50 bpm is associated with a trend toward a higher CV risk.
Slovenian: To dodatno podpirajo nekateri podatki, ki kažejo, da je srčni utrip < 50 udarcev/min, povezan s trendom večjega kardiovaskularnega tveganja.
English: Due to the fact that the higher than approved dose used in the SIGNIFY study did not fully explain the findings of the study, it was considered key to benefit-risk balance to assess the effectiveness of the new risk minimisation measures and therefore this drug utilisation study is imposed as a condition to the marketing authorisation.
Slovenian: Ker z večjim odmerkom od odobrenega, ki je bil uporabljen v študiji SIGNIFY, ni bilo mogoče popolnoma razložiti ugotovitev študije, so menili, da je za razmerje med tveganji in koristmi ključna ocena učinkovitosti novih ukrepov za zmanjševanje tveganja, zato je izvedba te študije o uporabi zdravila pogoj za izdajo dovoljenja za promet z zdravilom.
English: In angina, the usual recommended starting dose of ivabradine is 5 mg twice daily (b.i.d.).
Slovenian: Običajni priporočeni začetni odmerek ivabradina pri angini pektoris je 5 mg dvakrat na dan (b.i.d.).