FrancophonIA/ELRC3.0 huggingface dataset:
English: NAME OF THE MARKETING AUTHORISATION HOLDER Merck Europe B.V.
Croatian: NAZIV NOSITELJA ODOBRENJA ZA STAVLJANJE LIJEKA U PROMET Merck Europe B.V.
English: In patients who have previously been treated with immunomodulatory or immunosuppressive medicinal products the mode of action and duration of effect of the other medicinal product should be considered prior to initiation of MAVENCLAD (see section 4.2).
Croatian: U bolesnika koji su prethodno bili liječeni imunomodulatornim ili imunosupresivnim lijekovima, potrebno je razmotriti način djelovanja i trajanje učinka tog drugog lijeka prije početka liječenja lijekom MAVENCLAD (vidjeti dio 4.2).
English: Particularly close monitoring of haematological parameters is recommended in patients who have been exposed to an overdose of cladribine.
Croatian: Preporučuje se osobito pažljivo praćenje hematoloških parametara u bolesnika koji su bili izloženi predoziranju kladribinom.
English: Blood tests
Croatian: Krvne pretrage
English: • at least 800 cells/mm³ before initiating MAVENCLAD in year 2.
Croatian: • najmanje 800 stanica/mm³ prije započinjanja liječenja lijekom MAVENCLAD u 2. godini.
English: Because of the rapid and extensive intracellular and tissue distribution, haemodialysis is unlikely to eliminate cladribine to a significant extent.
Croatian: Zbog brze i opsežne distribucije unutar stanica i tkiva, kladribin se hemodijalizom najvjerojatnije neće ukloniti u značajnoj mjeri.
English: Lymphocyte counts must be
Croatian: Broj limfocita mora biti
English: Treatment with MAVENCLAD should not be initiated within 4 to 6 weeks after vaccination with live or attenuated live vaccines because of a risk of active vaccine infection.
Croatian: Liječenje lijekom MAVENCLAD ne smije se započeti unutar 4 do 6 tjedana nakon cijepljenja živim ili živim atenuiranim cjepivima zbog rizika od infekcije izazvane aktivnim cjepivom.
English: The metabolite 2-chloroadenine was a minor metabolite both in plasma and in urine, e.g. accounting only for ≤3% of plasma parent drug exposure after oral administration.
Croatian: Metabolit 2-kloroadenin bio je metabolit s malim udjelom i u plazmi i u mokraći, npr. odgovoran za samo ≤ 3 % izloženosti ishodišnom lijeku u plazmi nakon peroralne primjene.
English: A missed dose must be taken as soon as remembered on the same day according to the treatment schedule.
Croatian: Bolesnik mora uzeti propuštenu dozu istog dana, čim se sjeti, prema rasporedu liječenja.
English: It is expected that most patients recover to either normal lymphocyte counts or grade 1 lymphopenia within 9 months.
Croatian: U većine se bolesnika očekuje oporavak do normalnog broja limfocita ili limfopenije 1. stupnja unutar 9 mjeseci.
English: Variations in the expression levels of DCK and 5'-NTases between immune cell subtypes may explain differences in immune cell sensitivity to cladribine.
Croatian: Razlike u razini ekspresije DCK i 5'-NTaza između podvrsta imunoloških stanica mogu objasniti razlike u osjetljivosti imunoloških stanica na kladribin.
English: 500 cells/mm³, it should be actively monitored until values increase again.
Croatian: Ako broj limfocita bude manji od 500 stanica/mm³, potrebno ga je aktivno pratiti sve dok se vrijednosti ponovno ne povise.
English: Switching to and from cladribine treatment
Croatian: Prebacivanje s liječenja i na liječenje kladribinom
English: Safety and efficacy in patients with moderate or severe renal impairment have not been established.
Croatian: Sigurnost i djelotvornost u bolesnika s umjerenim ili teškim oštećenjem funkcije bubrega nisu ustanovljene.
English: Number of tablets to take Year 1 treatment course
Croatian: Broj tableta koji se uzima Ciklus liječenja u 1. godini
English: Take the missed dose on the next day and extend the number of days in that treatment week.
Croatian: Uzmite propuštenu dozu sljedećeg dana i onda produžite broj dana u tom tjednu liječenja.
English: Cladribine has no clinically meaningful inductive effect on CYP1A2, CYP2B6 and CYP3A4 enzymes.
Croatian: Kladribin nema klinički značajan indukcijski učinak na enzime CYP1A2, CYP2B6 i CYP3A4 enzymes.
English: Based on human experience with other substances inhibiting DNA synthesis, cladribine could cause congenital malformations when administered during pregnancy.
Croatian: Iskustvo u ljudi s primjenom drugih tvari koje inhibiraju sintezu DNK ukazuje na to da bi kladribin mogao prouzročiti kongenitalne malformacije ako se primjenjuje tijekom trudnoće.
English: The effect on lymphocyte count is dose-dependent.
Croatian: Učinak na broj limfocita ovisi o dozi.
English: Read the package leaflet for further information.
Croatian: Pročitajte uputu o lijeku za dodatne informacije.
English: In a study of the intracellular pharmacokinetics of Cd-AMP and Cd-ATP in patients with chronic myelogenous leukaemia, the levels of Cd-ATP were approximately half of the Cd-AMP levels.
Croatian: U ispitivanju unutarstanične farmakokinetike Cd-AMP-a i Cd-ATP-a u bolesnika s kroničnom mijeloičnom leukemijom, razine Cd-ATP-a bile su približno upola niže od razina Cd-AMP-a.
English: MAVENCLAD has no or negligible influence on the ability to drive and use machines.
Croatian: MAVENCLAD ne utječe ili zanemarivo utječe na sposobnost upravljanja vozilima i rada sa strojevima.
English: The Patient Guide should include an introduction to Mavenclad treatment, its side effects, potential risks and information on pregnancy prevention.
Croatian: Vodič za bolesnike treba uključivati upoznavanje s liječenjem lijekom Mavenclad, njegovim nuspojavama i mogućim rizicima te informacije o sprječavanju trudnoće.
English: Cladribine is not a relevant substrate to cytochrome P450 enzymes and does not show significant potential to act as inhibitor of CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1 and CYP3A4.
Croatian: Kladribin nije važan supstrat enzima citokroma P450 i ne pokazuje značajan potencijal djelovanja kao inhibitor CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1 i CYP3A4.
English: 2 consecutive doses (for example both Day 3 and Day 4 doses), take the missed doses for the next 2 days, and then extend the treatment week by 2 days.
Croatian: Ako propustite 2 uzastopne doze (na primjer, i dozu za 3. i dozu za 4. dan), uzmite propuštene doze tijekom iduća 2 dana, a zatim produžite taj tjedan liječenja za 2 dana.
English: Initiation of treatment with MAVENCLAD must be postponed for 4 to 6 weeks to allow for the full effect of vaccination to occur.
Croatian: Početak liječenja lijekom MAVENCLAD mora se odgoditi za 4 do 6 tjedana kako bi se omogućilo cjepivu da postigne puni učinak.
English: Based on a population pharmacokinetic analysis including patients with normal renal function and with mild renal impairment, total clearance in patients with mild renal impairment (CLCR = 60 mL/min) is expected to decrease moderately, leading to an increase in exposure of 25%.
Croatian: Na temelju analize populacijske farmakokinetike koja je uključila bolesnike s normalnom funkcijom bubrega i blagim oštećenjem funkcije bubrega, očekuje se umjereno smanjenje ukupnog klirensa u bolesnika s blagim oštećenjem bubrega (CLCR = 60 ml/min), koje dovodi do povećanja izloženosti za 25 %.
English: If two consecutive doses are missed, the same rule applies, and the number of days in the treatment week is extended by two days.
Croatian: Ako se propuste dvije uzastopne doze, vrijedi isto pravilo, a taj tjedan liječenja produljuje se za dva dana.
English: Moderate or severe renal impairment (creatinine clearance <60 mL/min) (see section 5.2).
Croatian: Umjereno ili teško oštećenje funkcije bubrega (klirens kreatinina < 60 ml/min) (vidjeti dio 5.2).
English: If you change from other MS treatments to MAVENCLAD, your doctor will check that your blood cell counts (lymphocytes) are normal before you start treatment.
Croatian: Ako prelazite s drugih lijekova za MS na MAVENCLAD, liječnik će provjeriti imate li normalan broj krvnih stanica (limfocita) prije nego što započnete s liječenjem.
English: A small study in cancer patients has shown a cerebrospinal fluid/plasma concentration ratio of approximately 0.25.
Croatian: Malo ispitivanje u onkoloških bolesnika pokazalo je da je omjer koncentracije u cerebrospinalnom likvoru i plazmi približno 0,25.
English: Following both oral and intravenous administration, the parent compound cladribine was the main component present in plasma and urine.
Croatian: I nakon peroralne i nakon intravenske primjene, ishodišni spoj kladribina bio je glavna sastavnica prisutna u plazmi i mokraći.
English: Cd-AMP is further phosphorylated to cladribine diphosphate (Cd-ADP) and cladribine triphosphate (Cd-ATP).
Croatian: Cd-AMP se dalje fosforilira u kladribin-difosfat (Cd-ADP) i kladribin-trifosfat (Cd-ATP).
English: In dividing cells, Cd-ATP interferes with DNA synthesis via inhibition of ribonucleotide reductase and competes with deoxyadenosine triphosphate for incorporation into DNA by DNA polymerases.
Croatian: U stanicama koje se dijele, Cd-ATP ometa sintezu DNK putem inhibicije ribonukleotid reduktaze i natječe se s deoksiadenozin-trifosfatom za ugradnju u DNK pomoću DNK polimeraza.
English: The carcinogenic potential of cladribine was assessed in a long-term 22-month study with subcutaneous administration in mice and in a short-term 26-week study by oral route in transgenic mice.
Croatian: Kancerogeni potencijal kladribina bio je procijenjen u dugotrajnom 22-mjesečnom ispitivanju s potkožnom primjenom u miševa i kratkotrajnom 26-tjednom ispitivanju s primjenom peroralnim putem u transgeničnih miševa.
English: Before you start a treatment course, your doctor will do a blood test to check that the levels of lymphocytes (a type of white blood cells) are in an acceptable range.
Croatian: Prije nego što započnete ciklus liječenja, liječnik će Vam provesti krvnu pretragu da provjeri jesu li razine limfocita (jedne vrste bijelih krvnih stanica) u prihvatljivom rasponu.
English: Treatment with oral cladribine leads to rapid reductions in circulating CD4+ and CD8+ T cells.
Croatian: Liječenje peroralnim kladribinom dovodi do brzog smanjenja broja cirkulirajućih CD4+ i CD8+ T stanica.
English: When oral cladribine was given in fasted state, median Tmax was 0.5 h (range 0.5 to 1.5 h).
Croatian: Kad se peroralni kladribin davao natašte, medijan Tmax iznosio je 0,5 h (raspon od 0,5 do 1,5 sati).
English: Cladribine has been shown to exert long-lasting effects by preferentially targeting lymphocytes and the autoimmune processes involved in the pathophysiology of MS.
Croatian: Pokazalo se da kladribin ima dugotrajne učinke tako što ciljano djeluje prvenstveno na limfocite i autoimune procese uključene u patofiziologiju MS-a.
English: In patients with mild renal impairment (creatinine clearance 60 to 89 mL/min), no dosage adjustment is considered necessary (see section 5.2).
Croatian: U bolesnika s blagim oštećenjem funkcije bubrega (klirens kreatinina od 60 to 89 ml/min), prilagodba doze ne smatra se potrebnom (vidjeti dio 5.2).
English: Read the 'Step-by-Step Guide' at the end of this package leaflet on how to handle the childresistant package and how to take the tablets included in the pack.
Croatian: U „Vodiču kroz korake uzimanja” na kraju ove upute o lijeku pročitajte kako rukovati pakiranjem sigurnim za djecu i kako uzimati tablete uključene u pakiranje.
English: The following definitions apply to the frequency terminology used hereafter:
Croatian: U daljnjem tekstu primjenjuju se sljedeće definicije za opis učestalosti:
English: The recommended cumulative dose of MAVENCLAD is 3.5 mg/kg body weight over 2 years, administered as 1 treatment course of 1.75 mg/kg per year.
Croatian: Preporučena kumulativna doza lijeka MAVENCLAD je 3,5 mg/kg tjelesne težine tijekom 2 godine, primijenjena u obliku 1 ciklusa liječenja od 1,75 mg/kg godišnje.
English: It is not known whether cladribine is excreted in human milk.
Croatian: Nije poznato izlučuje li se kladribin u majčino mlijeko.
English: No increased incidence of lymphoproliferative disorders or other tumour types (apart from Harderian gland tumours, predominantly adenomas) was seen in mice.
Croatian: U miševa nije bila opažena povećana incidencija limfoproliferativnih poremećaja ili drugih vrsta tumora (osim tumora Harderove žlijezde, pretežno adenoma).
English: Cladribine is incorporated into DNA strands and inhibits DNA synthesis and repair.
Croatian: Kladribin se ugrađuje u lance DNK i inhibira sintezu i popravak DNK.
English: It is currently unknown whether Mavenclad may reduce the effectiveness of systemically acting hormonal contraceptives.
Croatian: Trenutačno nije poznato može li Mavenclad smaniti učinkovitost hormonskih kontraceptiva sa sistemskim djelovanjem.
English: Cladribine was also assessed in a 1-year monkey study by the subcutaneous route.
Croatian: Kladribin je također bio procijenjen u ispitivanju na majmunima u trajanju od 1 godine u kojem je bio primijenjen supkutanim putem.
English: • Important identified risks Severe (Grade ≥ 3) lymphopenia, to ensure compliance to haematological testing and treatment requirements; Herpes zoster infections, to ensure awareness of signs and symptoms suggestive for these infections; Tuberculosis, to raise awareness about this risk.
Croatian: • Važni utvrđeni rizici Teška (≥ 3. stupnja) limfopenija, kako bi se osigurala suradnja u pogledu hematoloških pretraga i zahtjeva liječenja; Infekcije herpes zosterom, kako bi se osiguralo poznavanje znakova i simptoma koji bi mogli ukazivati na te infekcije; Tuberkuloza, da se podigne svijest o tom riziku.
English: Blood and lymphatic system disorders Very common: Lymphopenia.
Croatian: Poremećaji krvi i limfnog sustava Vrlo često:
English: As shown in Table 3 above, higher cumulative doses did not add any clinically meaningful benefit, but were associated with a higher incidence in ≥grade 3 lymphopenia (44.9% in the 5.25 mg/kg group vs. 25.6 % in the 3.5 mg/kg group).
Croatian: Kako je prikazano u tablici 3 gore, više kumulativne doze nisu donijele nikakvu klinički značajnu korist, ali su bile povezane s većom incidencijom limfopenije ≥ 3. stupnja (44,9 % u skupini koja je primila 5,25 mg/kg naspram 25,6 % u skupini koja je primila 3,5 mg/kg).
English: (2) Push in the hooks on the sides of the carton simultaneously with your index finger and thumb, and keep hooks pushed.
Croatian: (2) Kažiprstom i palcem istovremeno pritisnite kvačice sa strane kutije prema unutra te ih držite pritisnute.
English: Single events of cancer have been observed in patients who had received cladribine in clinical studies.
Croatian: Opaženi su pojedinačni slučajevi raka u bolesnika koji su primali kladribin u kliničkim ispitivanjima.
English: The distribution of the total dose over the 2 years of treatment is provided in Table 1.
Croatian: Raspodjela ukupne doze tijekom 2 godine liječenja prikazana je u tablici 1.
English: CD8+ T cells have a less pronounced decrease and a faster recovery than CD4+ T cells, resulting in a temporarily decreased CD4 to CD8 ratio.
Croatian: CD8+ T stanice pokazuju manje izraženo smanjenje broja i brži oporavak nego CD4+ T stanice, što dovodi do privremeno smanjenog omjera CD4 i CD8 stanica.
English: The MAH shall ensure that in each MS where Mavenclad is marketed, all prescribers and patients who are expected to prescribe / use Mavenclad are provided with:
Croatian: Nositelj odobrenja za stavljanje lijeka u promet osigurat će da u svakoj državi članici u kojoj je Mavenclad stavljen na tržište, svi liječnici za koje se očekuje da će propisivati Mavenclad i bolesnici za koje se očekuje da će ga primjenjivati dobiju:
English: - The active substance is cladribine.
Croatian: - Djelatna tvar je kladribin.
English: Based on pooled population pharmacokinetic data from various studies, the median values for elimination were 22.2 L/h for renal clearance and 23.4 L/h for non-renal clearance.
Croatian: Na temelju objedinjenih podataka populacijske farmakokinetike iz različitih ispitivanja, medijan vrijednosti eliminacije iznosio je 22,2 l/h za bubrežni klirens i 23,4 l/h za nebubrežni klirens.
English: The metabolism of cladribine was studied in MS patients following the administration of a single 10-mg tablet and a single 3-mg intravenous dose.
Croatian: Metabolizam kladribina bio je ispitan u bolesnika s MS-om nakon primjene jedne tablete od 10 mg i jednokratne intravenske doze od 3 mg.
English: Initiation of cladribine treatment in immunocompromised patients, including patients currently receiving immunosuppressive or myelosuppressive therapy (see section 4.5).
Croatian: Započinjanje liječenja kladribinom u imunokompromitiranih bolesnika, uključujući i bolesnike koji primaju imunosupresivnu ili mijelosupresivnu terapiju (vidjeti dio 4.5).
English: MAVENCLAD contains the active substance cladribine, a cytotoxic (cell killing) substance that works mostly on lymphocytes, cells of the immune system that are involved in inflammation.
Croatian: MAVENCLAD sadrži djelatnu tvar kladribin, citotoksičnu tvar (ubija stanice) koja djeluje uglavnom na limfocite, stanice imunonosnog sustava uključene u upalu.
English: If lymphocyte counts drop below 200 cells/mm³, anti-herpes prophylaxis according to local standard practice should be considered during the time of grade 4 lymphopenia (see section 4.8).
Croatian: Ako broj limfocita padne ispod 200 stanica/mm³, potrebno je razmotriti profilaksu protiv herpesa sukladno lokalnoj standardnoj praksi za vrijeme limfopenije 4. stupnja (vidjeti dio 4.8).
English: Only traces of other metabolites could be found in plasma and in urine.
Croatian: Drugi su se metaboliti mogli pronaći u plazmi i mokraći samo u tragovima.
English: The use of MAVENCLAD with interferon beta results in an increased risk of lymphopenia.
Croatian: Primjena lijeka MAVENCLAD s interferonom beta povećava rizik od limfopenije.
English: A missed dose must not be taken together with the next scheduled dose on the following day.
Croatian: Propuštena doza ne smije se uzeti istovremeno s idućom planiranom dozom sljedećeg dana.
English: A treatment week consists of 4 or 5 days on which you receive 1 or 2 tablets daily (see Table 1).
Croatian: Tjedan liječenja traje 4 do 5 dana tijekom kojih uzimate 1 ili 2 tablete dnevno (pogledajte tablicu 1).
English: Patients received either placebo (n = 437), or a cumulative dose of cladribine of 3.5 mg/kg (n = 433) or 5.25 mg/kg body weight (n = 456) over the 96-week (2-year) study period in 2 treatment courses.
Croatian: Bolesnici su primili placebo (n = 437) ili kumulativnu dozu kladribina od 3,5 mg/kg (n = 433) ili 5,25 mg/kg tjelesne težine (n = 456) tijekom 96-tjednog (2 godine) trajanja ispitivanja u 2 ciklusa liječenja.
English: Because of these expression levels, cells of the innate immune system are less affected than cells of the adaptive immune system.
Croatian: Zbog tih razina ekspresije, imunološke stanice odgovorne za urođeni imunitet manje su zahvaćene nego imunološke stanice zadužene za stečen imunitet.
English: No studies have been conducted to evaluate the pharmacokinetics of cladribine in elderly or in paediatric MS patients, or in subjects with renal or hepatic impairment.
Croatian: Nisu provedena ispitivanja kojima bi se procijenila farmakokinetika kladribina u starijih osoba ili pedijatrijskih bolesnika s MS-om ili u ispitanika s oštećenjem funkcije bubrega ili jetre.
English: Year 1
Croatian: 1. godina
English: In these patients, treatment with cladribine 3.5 mg/kg resulted in a reduction of the annualised relapse rate compared to placebo (0.03 versus 0.30, risk ratio: 0.11, p <0.05).
Croatian: U ovih bolesnika, liječenje kladribinom u dozi od 3,5 mg/kg dovelo je do smanjenja anualizirane stope relapsa u usporedbi s placebom (0,03 naspram 0,30, omjer rizika: 0.11, p < 0.05).
English: Decreases in neutrophil count, red blood cell count, haematocrit, haemoglobin or platelet count compared to baseline values have also been observed in clinical studies, although these parameters usually remain within normal limits.
Croatian: U kliničkim su ispitivanjima također bila opažena smanjenja broja neutrofila, crvenih krvnih stanica, hematokrita, hemoglobina ili broja trombocita u odnosu na početne vrijednosti, iako su ti parametri obično ostajali unutar granica normalnih vrijednosti.
English: The effects of potent inducers of the efflux transporters BCRP and P-glycoprotein (P-gp) on the bioavailability and disposition of cladribine have not been formally studied.
Croatian: Učinci jakih induktora efluksnih prijenosnika BCRP i P-glikoproteina (P-gp) na bioraspoloživost i raspored kladribina nisu formalno ispitani.
English: Because of the cladribine-induced reduction in lymphocyte count, additive haematological adverse reactions may be expected if cladribine is administered prior to or concomitantly with other substances that affect the haematological profile (e.g. carbamazepine).
Croatian: Zbog smanjenja broja limfocita izazvanog kladribinom, mogu se očekivati dodatne hematološke nuspojave ako se kladribin primijeni prije ili istodobno s drugim tvarima koje utječu na hematološki profil (npr. karbamazepin).
English: In clinical studies, events of malignancies were observed more frequently in cladribine-treated patients compared to patients who received placebo (see section 4.8).
Croatian: U kliničkim ispitivanjima opaženo je da su se zloćudne bolesti javljale češće u bolesnika liječenih kladribinom nego u bolesnika koji su primali placebo (vidjeti dio 4.8).
English: The majority of patients in the placebo (87.0%) and the cladribine 3.5 mg/kg (91.9%) and 5.25 mg/kg (89.0%) treatment groups completed the full 96 weeks of the study.
Croatian: Većina bolesnika u skupini koja je primila placebo (87,0 %) i terapijskim skupinama koje su primile kladribin u dozi od 3,5 mg/kg (91,9 %) i dozi od 5,25 mg/kg (89,0 %) završili su punih 96 tjedana ispitivanja.
English: MAVENCLAD is for oral use.
Croatian: MAVENCLAD je namijenjen za peroralnu primjenu.
English: Initiation of cladribine treatment is contraindicated in immunocompromised patients, including patients currently receiving immunosuppressive or myelosuppressive therapy with, e.g., methotrexate, cyclophosphamide, cyclosporine or azathioprine, or chronic use of corticosteroids because of a risk of additive effects on the immune system (see section 4.3).
Croatian: Uvođenje liječenja kladribinom kontraindicirano je u imunokompromitiranih bolesnika, uključujući bolesnike koji trenutno primaju imunosupresivnu ili mijelosupresivnu terapiju, npr. metotreksatom, ciklofosfamidom, ciklosporinom ili azatioprinom, ili dugotrajno uzimaju kortikosteroide, zbog rizika od aditivnih učinaka na imunološki sustav (vidjeti dio 4.3).
English: Use effective contraception during the treatment and for at least 6 months after the last dose.
Croatian: koriste učinkovitu kontracepciju tijekom liječenja i najmanje 6 mjeseci nakon zadnje doze.
English: In a male mouse fertility study, malformed foetuses with agenesis of portions of appendage(s) distal the humerus and/or femur were seen.
Croatian: U ispitivanju plodnosti mužjaka miša bili su opaženi malformirani fetusi s agenezom udova distalno od humerusa i/ili femura.
English: Compared to the overall population, a greater effect was observed in time to 6-month sustained disability where cladribine reduced the risk of disability progression by 82% (hazard ratio = 0.18, 95% CI [0.07, 0.47]).
Croatian: U usporedbi s ukupnom populacijom, veći je učinak bio opažen u vremenu do 6-mjesečne postojane onesposobljenosti, u kojem je kladribin smanjio rizik od napredovanja onesposobljenosti za 82 % (omjer hazarda = 0,18; 95 % CI [0,07; 0,47]).
English: If this is not possible, selection of alternative concomitant medicinal products with no, or minimal ENT1, CNT3 or BCRP transporter inhibiting properties should be considered.
Croatian: Ako to nije moguće, potrebno je razmotriti odabir alternativnih lijekova za istodobnu primjenu koji ili nemaju, ili imaju minimalna svojstva inhibicije prijenosnika ENT1, CNT3 ili BCRP.