natgillin/translations-raw huggingface dataset:
Nutrition: loss of appetite, decrease in magnesium, calcium, potassium, phosphate, albumine in blood, and increase in blood sugar.
Prehrana: gubitak apetita, smanjenje magnezija, kalcija, kalija, fosfata, albumina u krvi i povećanje šećera u krvi.
Fever was reported in 87% of patients and graded as mild/moderate in 84% and severe in 3%.
Vrućica je prijavljena u 87% bolesnika i ocijenjena blagom/umjerenom u 84% i teškom u 3%.
In addition, busulfan might induce pulmonary toxicity that may be additive to the effects produced by other cytotoxic agents.
Osim toga, busulfan može inducirati plućnu toksičnost koja može povećati učinke ostalih citotoksičnih sredstava.
• Quantity of diluent: (A ml Busilvex) x (10) = B ml of diluent
• Količina otapala: (A ml Busilvex) x (10) = B ml otapala
As documented in clinical studies, no treated patients experienced cardiac tamponade or other specific cardiac toxicities related to Busilvex.
Kao što je dokumentirano u kliničkim ispitivanjima, nije bilo liječenih bolesnika koji su doživjeli kardijalnu tamponadu ili ostale specifične kardijalne toksičnosti povezane s Busilvexom.
Busilvex should be administered by intravenous infusion via central venous catheter.
Busilvex treba primijeniti intravenskom infuzijom putem centralnog venskog katetera.
In one article it was studied the role of busulfan in juvenile rats resulting in abnormal root development; a review of two cases of immunodeficiency disorders treated with busulfan and cyclophosphamide in which dental orthodontic treatment was provided; additional 2 case report of hypoplasia of permanent tooth germ is presented; one review assessed the long term effects of cytotoxic therapy concluding that tooth agenesis was more prevalent in patients treated with busulfan and cyclophosphamide; a study of 81 patients concluded that busulfan is as toxic as total body irradiation in causing disturbances in dental development; finally, a study of risk factors of tooth formation anomalies in paediatric cancers concluded that the high risk group of tooth agenesis was the subject with high dose chemotherapy under 4 years old.
U jednom članku proučavana je uloga busulfana u mladih štakora koja je kod njih izazvala abnormalan razvoj korijena zubi; pregled dvaju slučajeva poremećaja imunodeficijencije liječenih busulfanom i ciklofosfamidom kod kojih je provedeno ortodontsko liječenje; podnesena su i dodatna izvješća o 2 slučaja koji govore o hipoplaziji zametka trajnog zuba; jednim pregledom ocjenjivali su se dugotrajni učinci terapije citotoksičnim lijekovima gdje je zaključeno da je ageneza zuba prisutnija u bolesnika liječenih busulfanom i ciklofosfamidom; studijom provedenom na 81 bolesniku zaključeno je da je, što se tiče poremećaja dentalnog razvoja, busulfan jednako toksičan kao i zračenje cijelog tijela; i na kraju, studijom faktora rizika od anomalija u formiranju zubi u slučaju raka kod pedijatrijskih bolesnika zaključeno je da visokorizičnu skupinu ageneze zubi predstavlja ispitanik koji je primao visoku dozu kemoterapije u dobi mlađoj od 4 godine.
It seems that the recommended intravenous busulfan dose administered either as an individual infusion (3.2 mg/kg) or into 4 divided infusions (0.8 mg/kg) provided equivalent daily plasma exposure with similar both inter-and intrapatient variability.
Čini se da je preporučena doza intravenskog busulfana primijenjena ili kao pojedinačna infuzija (3,2 mg/kg) ili kao 4 podijeljene infuzije (0,8 mg/kg) pružila ekvivalentnu dnevnu plazmatsku izloženost sa sličnom varijabilnošću i kod istog i između više bolesnika.
- If Busilvex or diluted Busilvex solution contacts the skin or mucosa, wash them thoroughly with water immediately.
- Ako Busilvex ili razrijeđeni Busilvex dođe u doticaj s kožom ili sluznicom, odmah ih temeljito operite vodom.
The recommended dose of Busilvex in combination with cyclophosphamide or melphalan is based on your body weight varying between 0.8 and 1.2 mg/kg.
Preporučena doza Busilvexa u kombinaciji s ciklofosfamidom ili melfalanom temelji se na Vašoj tjelesnoj težini i varira između 0,8 i 1,2 mg/kg.
The solvent dimethylacetamide (DMA) may also impair fertility.
Otapalo dimetilacetamid (DMA) također može smanjiti plodnost.
The terminal half life ranged from 2.26 to 2.52 h.
Konačni poluvijek bio je u rasponu od 2,26 do 2,52 sati.
A single s.c. dose of 2.2 g/kg administered on gestation day 4 terminated pregnancy in 100% of tested hamster.
Jedna doza 2,2 g/kg s.c. (supkutano) primijenjena 4. dana gestacije uzrokovala je prekid trudnoće u 100% testiranih hrčaka.
It has been suggested that conditioning regimens containing fludarabine were associated with higher incidence of opportunistic infections after transplantation because of the immunosuppressive effect of fludarabine.
Pretpostavlja se da su protokoli kondicioniranja koji sadrže fludarabin povezani s većim incidencijama oportunističkih infekcija nakon presađivanja zbog imunosupresivnog učinka fludarabina.
Busulfan induced chromosomal aberrations in vitro (rodent and human cell) and in vivo (rodents and humans).
Busulfan je inducirao kromosomske aberacije in vitro (stanica glodavaca i ljudi) i in vivo (glodavci i ljudi).
A few cases of congenital abnormalities have been reported with low-dose oral busulfan, not necessarily attributable to the active substance, and third trimester exposure may be associated with impaired intrauterine growth.
Prijavljeno je nekoliko slučaja prirođenih abnormalnosti uz primjenu niskih peroralnih doza busulfana, što nije nužno povezano s djelatnom tvari, a izloženost u trećem tromjesečju može biti povezana s oštećenjem intrauterinog rasta.
No specific clinical trial was carried out to assess drug-drug interaction between intravenous busulfan and itraconazole or metronidazole.
Nisu provedena specifična klinička ispitivanja za procjenu lijek-lijek interakcije između intravenskog busulfana i itrakonazola ili metronidazola
A final concentration of approximately 0.5 mg/ml busulfan should be achieved.
Mora se postići konačna koncentracija od otprilike 0,5 mg/ml busulfana.
In these studies, a total of 1574 patients received FB as a reduced intensity conditioning (RIC) regimen prior to haematopoietic progenitor cell transplantation.
U tim ispitivanjima ukupno je 1574 bolesnika primilo FB kao protokol kondicioniranja smanjenog intenziteta prije presađivanja hematopoetskih progenitorskih stanica.
Higher doses can produce hepatic necrosis and liver damage can be seen following single high exposures.
Veće doze mogu uzrokovati nekrozu jetre, a oštećenje jetre može biti vidljivo nakon jedne izloženosti visokim dozama.
It is recommended to administer anticonvulsants 12 h prior to Busilvex to 24 h after the last dose of Busilvex.
Preporučuje se primjena antikonvulzivnih lijekova 12 sati prije davanja Busilvexa do 24 sata nakon zadnje doze Busilvexa.
For a microbiological point of view, the diluted solution should be used immediately.
S mikrobiološkog stajališta, razrijeđenu otopinu treba primijeniti odmah.
Busilvex is a potent cytotoxic medicine that results in profound decrease of blood cells.
Busilvex je snažan, citotoksičan lijek koji dovodi do izrazitog smanjenja broja krvnih stanica.
The occurrence of TMA is multifactorial and busulfan IV by itself cannot be considered as a main factor in the development of this reaction.
Na pojavu TMA utječe više faktora i intravenski (i.v.) busulfan sam po sebi ne može se smatrati glavnim faktorom razvoja ove reakcije.
Veno occlusive disease (VOD) was reported in 15% (4/27) and 7% (2/28) of the autologous and allogenic transplant respectively.
VOD) prijavljena je u 15% (4/27) autolognih i 7% (2/28) alogenih presađivanja.
Gastro-intestinal: bleeding in the stomach and/or the gut.
Probavni sustav: krvarenje u želucu i/ili crijevu.
The quantity of the diluent must be 10 times the volume of Busilvex ensuring the final concentration of busulfan remains at approximately 0.5 mg/ml.
Količina otapala mora biti 10 puta veća od volumena Busilvexa što će osigurati konačnu koncentraciju busulfana od približno 0,5 mg/ml.
A phase II clinical trial was performed to evaluate the influence of seizure prophylaxis treatment on intravenous busulfan pharmacokinetics.
Faza II kliničkog ispitivanja provedena je radi procjene utjecaja profilaktičke terapije napadaja na farmakokinetiku intravenskog busulfana.
Busilvex contains the active substance busulfan, which belongs to a group of medicines called alkylating agents.
Busilvex sadrži djelatnu tvar busulfan koji pripada skupini lijekova nazvanih alkilirajuće tvari.
The incidence of a-GVHD grades I-II was 46.4% (13/28), while the incidence of grade III-IV was 3.6% (1/28).
Pojavnost a-GVHD I-II stupnja bila je 46,4% (13/28), dok je incidencija III-IV stupnja bila 3,6% (1/28).
The principal toxic effect is profound myeloablation and pancytopenia but the central nervous system, liver, lungs, and gastrointestinal tract may also be affected.
Glavni toksični učinak je teška mijeloablacija i pancitopenija, no mogu biti pogođeni i središnji živčani sustav, jetra, pluća i probavni sustav.
As with other cytotoxic compounds, caution should be exercised in handling and preparing the Busilvex solution: - The use of gloves and protective clothing is recommended.
U rukovanju otopinom Busilvexa i njenoj pripremi je potreban oprez kao i s drugim citotoksičnim spojevima: - Preporučuje se uporaba rukavica i zaštitne odjeće.
Do not use polycarbonate syringes with Busilvex.
Ne upotrebljavajte polikarbonatne štrcaljke uz Busilvex.
Caution is recommended, particularly in those patients with severe hepatic impairment (see section
Preporučuje se oprez, osobito u onih bolesnika s teškim oštećenjem funkcije jetre (vidjeti dio 4.4).
Also, there are published case reports of increased plasma levels of busulfan after administration of metronidazole.
Objavljene su i prijave slučajeva povišenih razina busulfana u plazmi nakon primjene metronidazola.
Since busulfan is mainly metabolized through the liver, caution should be observed when Busilvex is used in patients with pre-existing impairment of liver function, especially in those with severe hepatic impairment.
Budući da se busulfan većinom metabolizira putem jetre, potreban je oprez kada se Busilvex primjenjuje kod bolesnika koji već imaju oštećenje funkcije jetre, naročito u onih s teškim oštećenjem funkcije jetre.
47% of patients experienced chills which were mild/moderate in 46% and severe in 1%.
47% bolesnika doživjelo je zimicu koja je bila ocijenjena blagom/umjerenom u 46% i teškom u 1% slučajeva.
The most serious side effects of Busilvex therapy or the transplant procedure may include decrease in circulating blood cell counts (intended effect of the medicine to prepare you for your transplant infusion), infection, liver disorders including blocking of a liver vein, graft versus host disease (the graft attacks your body) and pulmonary complications.
Najozbiljnije nuspojave liječenja Busilvexom ili postupka presađivanja mogu uključivati smanjenje cirkulirajućeg broja krvnih stanica (namjerni učinak lijeka radi pripreme za transplantacijsku infuziju), infekciju, poremećaje jetre uključujući začepljenje jetrene vene, reakciju presatka protiv domaćina (presadak napada Vaše tijelo) i plućne komplikacije.
Patients who are concurrently treated with busulfan and itraconazole or metronidazole should be closely monitored for signs of busulfan toxicity.
Bolesnike kojima se istovremeno daje busulfan i itrakonazol ili metronidazol treba pobliže pratiti zbog moguće pojave znakova toksičnosti busulfanom.
The effect of those anticonvulsant agents on busulfan pharmacokinetics was investigated in a phase II study (see section 4.5).
Učinak tih antikonvulzivnih sredstava na farmakokinetiku busulfana ispitivan je u fazi II ispitivanja (vidjeti dio 4.5).
The recommended dose of Busilvex is as follows: Actual body weight (kg)
Preporučena doza lijeka Busilvex je sljedeća: Stvarna tjelesna težina (kg)
The incidence of a-GVHD grades I-II was 13% (8/61), while the incidence of grade III-IV was 5% (3/61).
Pojavnost I-II stupnja a-GVHD-a bila je 13% (8/61), dok je incidencija III-IV stupnja bila 5% (3/61).
- 8 hours (including infusion time) after dilution when stored at 20 °C  5 °C
- 8 sati (uključujući vrijeme infuzije) nakon razrjeđivanja ako se čuva na temperaturi od 20 °C 
There have been two reports that busulfan is dialyzable, thus dialysis should be considered in the case of an overdose.
U dva je izvješća navedeno da je busulfan dijalizibilan pa u slučaju predoziranja treba razmotriti dijalizu.
There is limited clinical experience of the use of busulfan as a component of a conditioning regimen prior to HSCT in children with Fanconi's anaemia.
Postoji ograničeno kliničko iskustvo u primjeni busulfana kao komponente protokola kondicioniranja prije HSCT-a u djece s Fanconijevom anemijom.
For storage conditions after dilution of the medicinal product see section 6.3.
Uvjete čuvanja nakon razrjeđivanja lijeka, vidjeti dio 6.3.
PARTICULARS TO APPEAR ON THE INTERMEDIATE PACKAGING WITHOUT BLUE BOX { box containing 4 vials of 10ml}
PODACI KOJI SE MORAJU NALAZITI NA UNUTARNJEM PAKIRANJU BEZ PLAVOG OKVIRA {kutija koja sadrži 4 bočice od 10 ml}
The World Health Organisation has concluded that there is a causal relationship between busulfan exposure and cancer.
Svjetska zdravstvena organizacija (WHO) zaključila je da postoji uzročno-posljedična veza između izloženosti busulfanu i raka.
Therefore it is advised not to father child during the treatment and up to 6 months after treatment and to seek advice on cryo-conservation of sperm prior to treatment because of the possibility of irreversible infertility (see section 4.4).
Stoga se preporučuje da tijekom liječenja i do 6 mjeseci nakon liječenja ne začinju dijete i da zatraže savjet o kriokonzervaciji sperme prije liječenja zbog mogućnosti ireverzibilne neplodnosti (vidjeti dio 4.4).
The dose proportional increase of busulfan exposure was demonstrated following intravenous busulfan up to 1 mg/kg.
Dokazano je povećanje izloženosti busulfanu proporcionalno dozi nakon intravenskog busulfana do 1 mg/kg.
Multipack containing 8 (2 packs of 4) vials.
Višestruko pakiranje sadrži 8 (2 pakiranja od 4) bočice.
The pharmacokinetics of Busilvex has been investigated.
Farmakokinetika Busilvexa je ispitivana.
Pharmacokinetic/pharmacodynamic relationships:
Farmakokinetički/farmakodinamički odnosi:
It is unknown whether busulfan and DMA are excreted in human milk.
Nije poznato izlučuje li se busulfan i DMA u majčino mlijeko u ljudi.
Documentation on the safety and efficacy of Busilvex in combination with fludarabine (FB) prior to allogeneic HPCT derives from the literature review of 7 published studies involving 731 patients with myeloid and lymphoid malignancies reporting the use of intravenous busulfan infused once daily instead of four doses per day.
Dokumentacija o sigurnosti i djelotvornosti Busilvexa u kombinaciji s fludarabinom (FB) prije alogenog HPCT-a potječe iz pregleda literature 7 objavljenih ispitivanja koja uključuju 731 bolesnika s mijeloidnim ili limfoidnim malignim bolestima koja bilježe primjenu intravenskog busulfana infundiranog jednom dnevno umjesto četiri doza dnevno.
Busilvex must not be infused concomitantly with another intravenous solution.
Busilvex se ne smije infundirati istodobno s drugom intravenskom otopinom.
In this study, 24 adult patients received clonazepam (0.025-0.03 mg/kg/day as IV continuous infusions) as anticonvulsant therapy and the PK data of these patients were compared to historical data collected in patients treated with phenytoin.
U tom su ispitivanju 24 odrasla bolesnika primila antikonvulzivnu terapiju klonazepamom (0,025-0,03 mg/kg/dan u obliku kontinuirane intravenske (i.v.) infuzije) i farmakokinetički podaci tih bolesnika uspoređeni su s povijesnim podacima prikupljenim od bolesnika liječenih fenitoinom.
The review of the literature allows a comparison of PK series performed either within the same study or between studies and demonstrated unchanged dose-independent PK parameters regardless the dosage or the schedule of administration.
Pregled literature omogućuje usporedbu farmakokinetičkih serija provedenu bilo unutar istog ispitivanja bilo između ispitivanja i pokazao je da su farmokinetički parametri neovisni o dozi nepromijenjeni bez obzira na doziranje ili raspored primjene.
In pregnant rats, busulfan produced sterility in both male and female offspring due to the absence of germinal cells in testes and ovaries.
Busulfan je u trudnih štakora uzrokovao sterilnost u muškim i ženskim potomcima zbog odsutnosti zametnih stanica u testisima i jajnicima.
SPECIAL STORAGE CONDITIONS Store in a refrigerator (2C - 8C)
POSEBNE MJERE ČUVANJA Čuvati u hladnjaku (2C - 8C).
The 2-year OS rate was 61.9% (95%CI, 51.1-72.7%)].
Dvogodišnja stopa ukupnog preživljavanja (OS) iznosila je 61,9% (95%-tni CI, 51,1 - 72,7%).
During clinical trials with intravenous busulfan administered as 0.80 mg/kg four-times daily, 90% of patients AUCs were below the upper AUC limit (1500 µmol/L.minute) and at least 80% were within the targeted therapeutic window (900-1500 µmol/L.minute).
Tijekom kliničkih ispitivanja s intravenskim busulfanom primijenjenim u dozi od 0,80 mg/kg četiri puta dnevno, 90% vrijednosti AUC svih bolesnika bilo je ispod gornje granice AUC (1500 µmol/l.minuta) i najmanje 80% bilo je unutar ciljanog terapijskog okvira (900-1500 µmol/l.minuta).
Nervous system: confusion, nervous system disorders.
Živčani sustav: smetenost, poremećaji živčanog sustava.
Brain abscess, Inflammation of the skin, generalised infection.
Apsces mozga, upala kože, opća infekcija.
Brain abscess Cellulitis Sepsis
Apsces mozga Celulitis Sepsa
No evidence of an induction effect of phenytoin has been seen on Busilvex data.
Nisu zabilježeni dokazi indukcijskog učinka fenitoina iz podataka o Busilvexu.
The consequence of treatment with Busilvex at the recommended dose and schedule is profound myelosuppression, occurring in all patients.
Posljedica liječenja Busilvexom u preporučenoj dozi i rasporedu je teška mijelosupresija koja se javlja u svih bolesnika.
Platelet engraftment occurred at a median of 9 (range, 1-16) days after allo-HCT.
Primanje presatka trombocita dogodilo se u medijanu od 9 (raspon 1 - 16) dana nakon alogenog HCT-a.
The recommended dose and schedule of administration is: - fludarabine administered as a single daily one-hour infusion at 30 mg/m² for 5 consecutive days or 40 mg/m² for 4 consecutive days.
Preporučena doza i raspored primjene je sljedeći: - fludarabin primijenjen kao jednosatna infuzija jednom dnevnom od 30 mg/m² 5 uzastopnih dana ili od 40 mg/m² 4 uzastopna dana.
Intravenous administration of busulfan to mice significantly increased the incidences of thymic and ovarian tumours.
Intravenska primjena busulfana na miševima značajno je povećala učestalost tumora timusa i jajnika.
On the basis of the scientific conclusions for busulfan the CHMP is of the opinion that the benefitrisk balance of the medicinal product(s) containing busulfan is unchanged subject to the proposed changes to the product information
Na temelju znanstvenih zaključaka za busulfan, CHMP smatra da je omjer koristi i rizika lijeka(ova) koji sadrži(e) busulfan nepromijenjen, uz predložene izmjene informacija o lijeku.
In view of the data presented in the reviewed PSUR, the PRAC considered that changes to the product information of medicinal products containing busulfan were warranted.
U pogledu podataka prikazanih u pregledanom PSUR-u, PRAC smatra da su izmjene informacija o lijeku za lijekove koji sadrže busulfan opravdane.
The amount of Busilvex and diluent to be administered would be calculated as follows: for a patient with a Y kg body weight:
Količina Busilvexa i otapala koji se moraju primijeniti izračunavaju se na sljedeći način: za bolesnika s tjelesnom težinom Y kg:
Busulfan was shown to cause sterility in rodents.
Pokazalo se da busulfan uzrokuje sterilnost u glodavaca.
This study demonstrated that bodyweight was the predominant covariate to explain the busulfan pharmacokinetic variability in children over body surface area or age.
To je ispitivanje pokazalo prevladavajući utjecaj tjelesne težine na varijabilnost farmakokinetike busulfana u djece u odnosu na površinu tijela ili dob.
Cases of formation of blood clots in the small blood vessels may appear after hematopoietic cell transplantation (HCT) with high-dose of your treatment in combination with other medicines.
Slučajevi formiranja krvnih ugrušaka u malim krvnim žilama mogu se pojaviti nakon transplantacije hematopoetskih matičnih stanica (HCT), s visokim dozama terapije koja se kombinira s drugim lijekovima.
Creatinine elevated
Povišeni kreatinin
In this study, all, but one, patients engrafted, at a median of 15 (range, 10-23) days after allo-HCT.
U tom ispitivanju kod svih osim jednog bolesnika došlo je do primanja presatka u medijanu od 15 (raspon 10 - 23) dana nakon alogenog HCT-a.
You will receive this preparative medicine before receiving a transplant of either bone marrow or haematopoietic progenitor cell.
Ovaj pripremni lijek primit ćete prije presađivanja koštane srži ili hematopoetskih progenitorskih stanica.
The analysis of data through a population pharmacokinetic method indicated no difference on intravenous busulfan clearance between phenytoin and clonazepam based therapy and therefore similar busulfan plasma exposures were achieved whatever the type of seizure prophylaxis.
Analiza podataka populacijskom farmakokinetičkom metodom pokazala je da ne postoje razlike u klirensu intravenskog busulfana između liječenja koje se temelji na fenitoinu i klonazepamu pa su stoga postignute slične izloženosti plazme busulfanu bez obzira na vrstu profilaktične terapije napadaja.
However cardiac function should be monitored regularly in patients receiving Busilvex (see section 4.8).
No kardijalna se funkcija mora redovito nadzirati u bolesnika koji primaju Busilvex (vidjeti dio 4.8).
From a microbiological point of view, the product should be used immediately after dilution.
S mikrobiološkog stajališta lijek treba primijeniti odmah nakon razrjeđivanja.
* reported in post marketing experience ** include haemorrhagic cystitis induced by viral infection
* prijavljeno nakon stavljanja lijeka u promet ** uključuje hemoragični cistitis induciran virusnom infekcijom
Busulfan was mutagenic in Salmonella typhimurium, Drosophila melanogaster and barley.
Busulfan je bio mutagen u bakteriji Salmonella typhimurium, vinskoj mušici Drosophila melanogaster i ječmu.
Busulfan is metabolised mainly through conjugation with glutathione (spontaneous and glutathione-Stransferase mediated).
Busulfan se većinom metabolizira konjugacijom s glutationom (spontano i sudjelovanjem glutation-S-transferaze).
Thrombocytopenia (< 25x109/l or requiring platelet transfusion) occurred at a median of 5-6 days in 98% of patients.
Trombocitopenija (< 25x109/l ili potreba za transfuzijom trombocita) se pojavila u medijanu od 5-6 dana u 98% bolesnika.
As a conclusion, busulfan could be one risk factor of development TMA and a warning is section 4.4 of the Busilvex SmPC is considered warranted.
Stoga je zaključeno da bi busulfan mogao biti jedan od faktora rizika za razvoj trombotičke mikroangiopatije (TMA) pa se upozorenje u dijelu 4.4 Sažetka opisa svojstava lijeka za lijek Busilvex smatra opravdanim.
No age effect on busulfan clearance was evidenced from available intravenous busulfan data in patients over 60 years.
Nije zabilježen učinak dobi na klirens busulfana na temelju dostupnih podataka o intravenskom busulfanu u bolesnika iznad 60 godina.
Muscle and bone: back, muscle and joint pain.
Mišići i kosti: bol u leđima, mišićima i zglobovima.
On the basis of human data, busulfan has been classified by the International Agency for Research on Cancer (IARC) as a human carcinogen.
Na temelju podataka dobivenih na ljudima, Međunarodna agencija za istraživanja raka (IARC) klasificirala je busulfan kao humani karcinogen.
Do not use this medicine after the expiry date which is stated on the vial label and the carton after EXP.
Ovaj lijek se ne smije upotrijebiti nakon isteka roka valjanosti navedenog na naljepnici bočice i kutiji iza oznake „EXP“/ „Rok valjanosti“.