natgillin/translations-raw huggingface dataset:
Hepatitis or liver failure, which was fatal in some cases, has been reported with the use of stavudine and with other nucleoside analogues (see section 4.4).
Med uporabo stavudina in drugih nukleozidnih analogov so poročali o hepatitisu ali odpovedi jeter, ki je bila v nekaterih primerih usodna (glejte poglavje 4. 4).
6 Immune reactivation syndrome: in HIV-infected patients with severe immune deficiency at the time of initiation of combination antiretroviral therapy (CART), an inflammatory reaction to asymptomatic or residual opportunistic infections may arise (see section 4.4).
Pri s HIV okuženih bolnikih s hudo imunsko pomanjkljivostjo lahko ob uvedbi kombiniranega protiretrovirusnega zdravljenja (CART - "combination antiretroviral therapy") nastane vnetna reakcija na asimptomatične ali rezidualne oportunistične okužbe (glejte poglavje 4. 4).
Lipodystrophy and metabolic abnormalities: combination antiretroviral therapy has been associated with redistribution of body fat (lipodystrophy) in HIV patients including the loss of peripheral and facial subcutaneous fat, increased intra-abdominal and visceral fat, breast hypertrophy and dorsocervical fat accumulation (buffalo hump).
Pri bolnikih, okuženih s HIV, so kombinirano protiretrovirusno terapijo povezovali s prerazporeditvijo telesnega maščevja (lipodistrofijo), vključno z izgubo podkožnega maščevja periferno in na obrazu, zvečanjem znotrajtrebušnega in visceralnega maščevja, hipertrofijo prsi in dorzocervikalnim kopičenjem maščevja (bivolja grba).
The frequency of adverse reactions listed below is defined using the following convention: very common (≥ 1/ 10); common (≥ 1/ 100, < 1/ 10); uncommon (≥ 1/ 1,000, < 1/ 100); rare (≥ 1/ 10,000, < 1/ 1,000); very rare (< 1/ 10,000).
Pogostnost spodaj naštetih neželenih reakcij je opredeljena upoštevaje naslednjo konvencijo: zelo pogosti (≥ 1/ 10); pogosti (≥ 1/ 100, < 1/ 10); občasni (≥ 1/ 1. 000, < 1/ 100); redki (≥ 1/ 10. 000, < 1/ 1. 000); zelo redki (< 1/ 10. 000).
Undesirable effects (moderate to severe) were reported from 467 patients treated with Zerit in combination with lamivudine and efavirenz in two randomised clinical trials and an ongoing long-term follow-up study (total follow-up: median 56 weeks ranging up to 119 weeks).
O neželenih učinkih (zmernih do hudih) so poročali pri 467 bolnikih, zdravljenih z zdravilom Zerit v kombinaciji z lamivudinom in efavirenzom v dveh randomiziranih kliničnih preskušanjih in v potekajoči dolgoročni spremljevalni študiji (srednja vrednost skupnega časa spremljanja:
The following undesirable effects considered possibly related to study regimen based on investigators’ attribution, have been identified:
Ugotovljeni so bili naslednji neželeni učinki, ki so bili po presoji raziskovalcev morda povezani z raziskovano shemo:
Endocrine disorders:
7 Bolezni endokrinega sistema:
common: diarrhoea, abdominal pain, nausea, dyspepsia uncommon: pancreatitis, vomiting
pogosti: diareja, bolečine v trebuhu, navzea, dispepsija občasni: pankreatitis, bruhanje
uncommon: hepatitis or jaundice
občasni: hepatitis ali zlatenica
common: lipoatrophy, * lipodystrophy uncommon: lactic acidosis (in some cases involving motor weakness), anorexia
pogosti: lipoatrofija *, lipodistrofija občasni: laktacidoza (ki včasih vključuje motorično šibkost), anoreksija
common: peripheral neurologic symptoms including peripheral neuropathy, paresthesia, and peripheral neuritis; dizziness; abnormal dreams; headache, insomnia; abnormal thinking; somnolence
pogosti: periferni nevrološki simptomi, vključno s periferno nevropatijo, parestezijami in perifernim nevritisom; omotica; nenormalne sanje; glavobol, nespečnost; nenormalno mišljenje; zaspanost
7 *Lipoatrophy was observed in a long-term follow-up study of stavudine in combination with lamivudine and efavirenz (total follow-up: median 148 weeks ranging up to 207 weeks).
v kateri so dolgotrajno spremljali uporabo stavudina v kombinaciji z čas spremljanja: srednji čas 148 tednov; razpon do 207 tednov).
Discontinuation due to undesirable events was 7% for the patients treated with Zerit.
Zaradi neželenih učinkov je zdravljenje prekinilo 7% bolnikov, ki so jemali zdravilo Zerit.
Laboratory abnormalities reported in these two trials and an ongoing follow-up study included elevations of ALT (> 5 x ULN) in 3%, of AST (> 5 x ULN) in 3%, of lipase (≥ 2.1 ULN) in 3% of the patients in the Zerit group.
Med laboratorijskimi nenormalnostmi, opisanimi v teh dveh raziskavah in v potekajoči spremljevalni raziskavi, so bila zvišanja ALT (> 5 x ZNM) pri 3%, AST (> 5 x ZNM) pri 3% in lipaze (≥ 2, 1 ZNM) pri 3% bolnikov v skupini, ki je dobivala zdravilo Zerit.
Neutropenia (< 750 cells/ mm3) was reported in 5%, thrombocytopenia (platelets < 50,000/ mm3) in 2%, and low haemoglobin (< 8 g/ dl) in < 1% of patients receiving Zerit.
O nevtropeniji (< 750 celic/ mm3) so poročali pri 5%, trombocitopeniji (trombociti < 50. 000/ mm3) pri 2% in o nizkem hemoglobinu (< 8 g/ dl) pri < 1% bolnikov, ki so dobivali zdravilo Zerit.
Adolescents, children and infants: undesirable effects and serious laboratory abnormalities reported to occur in paediatric patients ranging in age from birth through adolescence who received stavudine in clinical studies were generally similar in type and frequency to those seen in adults.
Neželeni učinki in resne laboratorijske nenormalnosti, zabeleženi pri pediatričnih bolnikih v starosti od rojstva do konca adolescence, ki so v kliničnih raziskavah dobivali stavudin, so bili na splošno podobne vrste in podobno pogosti kot tisti pri odraslih.
These studies include ACTG 240, where 105 paediatric patients ages 3 months to 6 years received Zerit 2 mg/ kg/ day for a median of 6.4 months; a controlled clinical trial where 185 newborns received Zerit 2 mg/ kg/ day either alone or in combination with didanosine from birth through 6 weeks of age; and a clinical trial where 8 newborns received Zerit 2 mg/ kg/ day in combination with didanosine and nelfinavir from birth through 4 weeks of age.
Te raziskave vključujejo ACTG 240, v kateri je 105 pediatričnih bolnikov, starih od 3 mesece do 6 let, dobivalo zdravilo Zerit v odmerku 2 mg/ kg/ dan 6, 4 mesece (srednja vrednost trajanja terapije); kontrolirano klinično raziskavo, v kateri je 185 novorojenčkov dobivalo zdravilo Zerit v odmerku 2 mg/ kg/ dan bodisi samega ali v kombinaciji z didanozinom, in sicer od rojstva do 6 tednov starosti ter klinično raziskavo, v kateri je 8 novorojenčkov dobivalo zdravilo Zerit v odmerku 2 mg/ kg/ dan v kombinaciji z didanozinom in nelfinavirom od rojstva do 4 tedna starosti.
In study AI455-094 (see also section 4.6), the safety follow-up period was restricted to only six months, which may be insufficient to capture long-term data on neurological adverse events and mitochondrial toxicity.
V raziskavi AI455- 094 (glejte tudi poglavje 4. 6) so varnost spremljali le šest mesecev, kar je morda premalo, da bi zajeli dolgoročne podatke o nevroloških neželenih učinkih in toksičnosti za mitohondrije.
Relevant grade 3-4 laboratory abnormalities in the 91 stavudine treated infants were low neutrophils in 7%, low hemoglobin in 1%, ALT increase in 1% and no lipase abnormality.
8 stavudinom so bile: majhno število nevtrofilcev pri 7%, nizek hemoglobin pri 1% in zvišanje ALT pri 1%; nenormalnosti lipaze ni bilo.
There was, however, an increased infant mortality in the stavudine + didanosine (10%) treatment group compared to the stavudine (2%), didanosine (3%) or zidovudine (6%) groups, with a higher incidence of stillbirths in the stavudine + didanosine group.
V skupini, ki je dobivala stavudin in didanozin, je bila večja tudi incidenca mrtvorojenosti.
Postmarketing
Izkušnje po pridobitvi dovoljenja za promet
The following events have been reported spontaneously during postmarketing experience:
Po pridobitvi dovoljenja za promet so bili spontano prijavljeni naslednji neželeni dogodki:
Not known: thrombocytopenia
Ni znano: trombocitopenija
Metabolic and nutrition disorders:
Presnovne in prehranske motnje:
Common: asymptomatic hyperlactatemia, Not known: lactic acidosis
Pogosti: nesimptomatska hiperlaktatemija, Ni znano: laktacidoza
Not known: liver failure, hepatitis and hepatic steatosis
Ni znano: odpoved jeter, hepatitis in steatoza jeter
Not known: motor weakness (most often reported in the setting of symptomatic hyperlactatemia or lactic acidosis syndrome)
Ni znano: motorična šibkost (najpogosteje opisana v primeru simptomatske hiperlaktatemije ali sindroma laktacidoze)
Mitochondrial dysfunction: review of the postmarketing safety database shows that adverse events indicative of mitochondrial dysfunction have been reported in the neonate and infant population exposed to one or more nucleoside analogues (see also section 4.4).
Pregled zbirke podatkov o varnosti, zbranih v obdobju po pridobitvi dovoljenja za promet, kaže, da so se v populaciji novorojenčkov in dojenčkov, izpostavljenih enemu ali več nukleozidnim analogom, pojavili neželeni učinki, ki nakazujejo moteno delovanje mitohondrijev (glejte tudi poglavje 4. 4).
The HIV status for the newborns and infants ≤ 3 months of age was negative, for older infants it tended to be positive.
Novorojenčki in dojenčki stari ≤ 3 mesece so bili HIV - negativni, starejši dojenčki pa so bili praviloma pozitivni.
Experience in adults treated with up to 12 times the recommended daily dosage revealed no acute toxicity.
Izkušnje pri odraslih, ki so dobivali do 12- kratne priporočene dnevne odmerke, niso odkrile akutnih toksičnih učinkov.
The mean haemodialysis clearance of stavudine is 120 ml/ min.
Srednji hemodializni očistek stavudina je 120 ml/ min.
Nucleoside reverse transcriptase inhibitor, ATC code:
Farmakoterapevtska skupina: nukleozidni in nukleotidni zaviralci reverzne transkriptaze, Oznaka ATC:
Stavudine, a thymidine analogue, is an antiviral agent with in vitro activity against HIV in human cells.
Timidinski analog stavudin je protivirusno zdravilo, ki in vitro deluje proti HIV v človeških celicah.
It is phosphorylated by cellular kinases to stavudine triphosphate which inhibits HIV reverse transcriptase by competing with the natural substrate, thymidine triphosphate.
Celične kinaze ga fosforilirajo v stavudintrifosfat, ki zavira reverzno transkriptazo HIV, ker tekmuje z naravnim substratom, timidintrifosfatom.
It also inhibits viral DNA synthesis by causing DNA chain termination due to a lack of the 3’ -hydroxyl group necessary for DNA elongation.
Zavira tudi sintezo virusne DNA, ker povzroči zaključitev verige DNA zaradi pomanjkanja 3 '- hidroksilne skupine, potrebne za podaljševanje DNA.
Cellular DNA polymerase γ is also sensitive to inhibition by stavudine triphosphate, while cellular polymerases α and β are inhibited at concentrations 4,000-fold and 40-fold higher, respectively, than that needed to inhibit HIV reverse transcriptase.
Na zavrtje s stavudintrifosfatom je občutljiva tudi celična DNA- polimeraza γ, medtem ko je za zavrtje celične polimeraze α potrebna 4. 000- krat večja, za zavrtje celične polimeraze β pa 40- krat večja koncentracija kot za zavrtje reverzne transkriptaze HIV.
Stavudine treatment can select for and/ or maintain mutations associated with zidovudine resistance.
9 Zdravljenje s stavudinom lahko selekcionira in/ ali ohrani mutacije, povezane z odpornostjo proti zidovudinu.
Isolates containing these mutations remain sensitive to stavudine.
Izolati s temi mutacijami ostajajo občutljivi za stavudin.
The activity of stavudine is affected by multi-drug resistance associated mutations such as Q151 M.
Na delovanje stavudina vpliva odpornost proti več zdravilom, ki spremlja mutacije, kakršna je Q151 M.
A more than 10-fold reduced sensitivity to stavudine has been reported for some strains with reduced sensitivity to zidovudine and lamivudine.
Pri nekaterih sevih z manjšo občutljivostjo za zidovudin in lamivudin je bilo opisano več kot 10- kratno zmanjšanje občutljivosti za stavudin.
No mutations associated with high degree resistance specifically to stavudine have been revealed in vivo.
In vivo niso odkrili mutacij, ki bi jih spremljala visoka stopnja specifične odpornosti proti stavudinu.
Zerit has been studied in combination with other antiretroviral agents, e. g. didanosine, lamivudine, ritonavir, indinavir, saquinavir, efavirenz, and nelfinavir.
Zdravilo Zerit so raziskali v kombinaciji z drugimi protiretrovirusnimi zdravili, npr. z didanozinom, lamivudinom, ritonavirjem, indinavirjem, sakinavirjem, efavirenzom in nelfinavirjem.
Study AI455-099 was a 48-week, randomised, double-blind study with Zerit (40 mg twice daily), in combination with lamivudine (150 mg twice daily) plus efavirenz (600 mg once daily), in 391 treatment-naive patients, with a median CD4 cell count of 272 cells/ mm3 (range 61 to 1,215 cells/ mm3) and a median plasma HIV-1 RNA of 4.80 log10 copies/ ml (range 2.6 to 5.9 log 10 copies/ ml) at baseline.
Srednja vrednost števila celic CD4 v izhodišču je bila 272 celic/ mm3 (razpon od 61 do 1. 215 celic/ mm3), srednja vrednost HIV- 1 RNA v plazmi pa 4, 80 log10 kopij/ ml (razpon 2, 6 do 5, 9 log 10 kopij/ ml).
Study AI455-096 was a 48-week, randomised, double-blind study with Zerit (40 mg twice daily), in combination with lamivudine (150 mg twice daily) plus efavirenz (600 mg once daily), in 76 treatment-naive patients, with a median CD4 cell count of 261 cells/ mm3 (range 63 to 962 cells/ mm3) and a median plasma HIV-1 RNA of 4.63 log10 copies/ ml (range 3.0 to 5.9 log10 copies/ ml) at baseline.
Srednja vrednost števila celic CD4 v izhodišču je bila 261 celic/ mm3 (razpon od 63 do 962 celic/ mm3), srednja vrednost HIV- 1 RNA v plazmi pa 4, 63 log10 kopij/ ml (razpon 3, 0 do 5, 9 log10 kopij/ ml).
9 The results of AI455-099 and AI455-096 are presented in the table below:
Rezultati raziskav AI455- 099 in AI455- 096 so prikazani v spodnji tabeli:
Study
Raziskava
Percent of Percent of
Odstotek bolnikov s HIV RNA < 50 kopij/ ml
HIV RNA
Srednja sprememba HIV RNA od izhodišča
CD4 Mean
Srednja sprememba CD4 od izhodišča
AI455-099 (48 weeks) b
(log10 kopij/ ml) (celic/ mm3) AI455- 099 (48 tednov) b
patients with HIV patients with HIV Mean Change RNA < 400 RNA < 50 from Baseline copies/ ml copies/ ml (log10 Treatment Treatment copies/ ml) response (%)a response (%)a
a
change from Baseline (cells/ mm3)
odziv na zdravljenje (%)
Zerit + lamivudine + efavirenz (n = 391) AI455-096 (48 weeks) b
Zerit + lamivudin + efavirenz (n = 391) AI455- 096 (48 tednov) b
Zerit + lamivudine + efavirenz (n = 76) a
Zerit + lamivudin + efavirenz (n = 76) a
Percent of patients who have HIV RNA < 400 c/ ml or < 50 c/ ml and do not meet any criteria for treatment failure including the occurrence of a new AIDS-defining diagnosis. b These studies were designed to compare two formulations of Zerit.
Odstotek bolnikov, ki so imeli HIV RNA < 400 kopij/ ml ali < 50 kopij/ ml in pri katerih ni bil izpolnjen nobeden od kriterijev za neuspešno zdravljenje, vključno s kriteriji, ki definirajo AIDS. b Namen teh študij je bil primerjati dve farmacevtski obliki zdravila Zerit.
Only the data from the marketed formulation is presented.
Prikazani so le podatki o farmacevtski obliki, ki je na tržišču.
In adolescents, children and infants, use of stavudine is supported by evidence from adequate and well-controlled studies in adults with additional pharmacokinetic and safety data in paediatric patients (see also sections 4.8 and 5.2).
Pri mladostnikih, otrocih in dojenčkih uporabo stavudina podpirajo dokazi iz adekvatnih in dobro kontroliranih raziskav pri odraslih ter dodatni podatki o farmakokinetiki in varnosti pri pediatričnih bolnikih (glejte tudi poglavji 4. 8 in 5. 2).
Absorption: the absolute bioavailability is 86±18%.
Absolutna biološka uporabnost je 86 ± 18%.
After multiple oral administration of 0.5-0.67 mg/ kg doses, a Cmax value of 810±175 ng/ ml was obtained.
Po večkratnem zaužitju odmerkov 0, 5 – 0, 67 mg/ kg je bila dosežena vrednost Cmax 810 ± 175 ng/ ml.
Cmax and AUC increased proportionally with dose in the dose ranges, intravenous 0.0625-0.75 mg/ kg, and oral 0.033-4.0 mg/ kg.
Cmax in AUC sta se v območju intravenskih odmerkov od 0, 0625 do 0, 75 mg/ kg in peroralnih od 0, 033 do 4, 0 mg/ kg zvečevali sorazmerno.
In eight patients receiving 40 mg twice daily in the fasted state, steady-state AUC0-12h was 1284±227 ng⋅ h/ ml (18%) (mean ± SD [% CV]), Cmax was 536±146 ng/ ml (27%), and Cmin was 9±8 ng/ ml (89%).
10 Pri osmih bolnikih, ki so dobivali 40 mg dvakrat na dan na tešče, je bila AUC0- 12h v stanju dinamičnega ravnovesja 1284 ± 227 ng⋅ur/ ml (18%) (srednja vrednost ± SD [% IZ]), Cmax 536 ± 146 ng/ ml (27%) in Cmin 9 ± 8 ng/ ml (89%).
Distribution: the apparent volume of distribution at steady state is 46±21 l.
Navidezni volumen porazdelitve v stanju dinamičnega ravnovesja je 46 ± 21 l.
Four hours after administration, the CSF/ plasma ratio was 0.39±0.06.
Štiri ure po uporabi je razmerje med cerebrospinalno tekočino in plazmo 0, 39 ± 0, 06.
Binding of stavudine to serum proteins was negligible over the concentration range of 0.01 to 11.4 µg/ ml.
Vezava stavudina na beljakovine v serumu je bila v koncentracijskem območju od 0, 01 do 11, 4 µg/ ml zanemarljiva.
Metabolism: the metabolism of stavudine has not been elucidated in humans.
Presnova stavudina pri človeku ni pojasnjena.
Studies in monkeys indicate that approximately 50% is excreted unchanged in the urine, most of the remainder is hydrolysed to thymine and sugar.
Raziskave na opicah kažejo, da se približno 50% izloči nespremenjenega v urinu, večina preostalega pa hidrolizira v timin in sladkor.
Elimination: the terminal elimination half-life is 1.3±0.2 hours after a single dose, and 1.4±0.2 hours after multiple doses, and is independent of dose.
Končni razpolovni čas izločanja je 1, 3 ± 0, 2 ure po posamičnem odmerku in 1, 4 ± 0, 2 uri po več odmerkih ter ni odvisen od odmerka.
In vitro, stavudine triphosphate has an intracellular half-life of 3.5 hours in CEM T-cells (a human T-lymphoblastoid cell line) and peripheral blood mononuclear cells, supporting twice daily dosing.
In vitro ima stavudintrifosfat v T- celicah CEM (linija človeških T- limfoblastoidnih celic) in mononuklearnih celicah v periferni krvi znotrajcelični razpolovni čas 3, 5 ure, kar podpira odmerjanje dvakrat na dan.
Total clearance of stavudine is 594±164 ml/ min, and renal clearance is 237±98 ml/ min, indicating active tubular secretion in addition to glomerular filtration.
Skupni očistek stavudina je 594 ± 164 ml/ min, ledvični očistek pa 237 ± 98 ml/ min, kar nakazuje poleg glomerulne filtracije tudi aktivno tubularno sekrecijo.
After intravenous administration, 42±7% of dose is excreted unchanged in the urine.
Po intravenski uporabi se 42 ± 7% odmerka nespremenjenega izloči v urinu.
The corresponding values after oral single and multiple dose administration are 34±5% and 40±12%, respectively.
Ustrezna vrednost po posamičnem peroralnem odmerku je 34 ± 5% in po več peroralnih odmerkih 40 ± 12%.
The remaining 60% of the drug is presumably eliminated by endogenous pathways.
Preostalih 60% zdravila se verjetno izloči po endogenih poteh.
The half-life of stavudine is approximately 2 hours.
Razpolovni čas stavudina je približno 2 uri.
The pharmacokinetics of stavudine was independent of time, since the ratio between AUC(ss) at steady state and the AUC(0-t) after the first dose was approximately 1.
Farmakokinetika stavudina ni odvisna od časa, ker je razmerje med AUC( ss) v stanju dinamičnega ravnovesja in AUC( 0- t) po prvem odmerku približno 1.
10 pharmacokinetic characteristics of stavudine is low, approximately 15% and 25%, respectively, after oral administration.
Intra - in interindividualne razlike v farmakokinetičnih značilnostih stavudina po peroralni uporabi so majhne (približno 15% intra - in 25% interindividualno).
Adolescents, children and infants: total exposure to stavudine was comparable between adolescents, children and infants ≥ 14 days receiving the 2 mg/ kg/ day dose and adults receiving 1 mg/ kg/ day.
Celotna izpostavljenost stavudinu je bila primerljiva pri mladostnikih, otrocih in dojenčkih ≥ 14 dni, ki so dobivali odmerek 2 mg/ kg/ dan, in odraslimi, ki so dobivali 1 mg/ kg/ dan.
Apparent oral clearance was approximately 14 ml/ min/ kg for infants ages 5 weeks to 15 years, 12 ml/ min/ kg for infants ages 14 to 28 days, and 5 ml/ min/ kg for infants on the day of birth.
Navidezni peroralni očistek je bil približno 14 ml/ min/ kg pri otrocih, starih od 5 tednov do 15 let, 12 ml/ min/ kg pri dojenčkih, starih od 14 do 28 dni, in 5 ml/ min/ kg pri dojenčkih na dan rojstva.
Two to three hours post-dose, CSF/ plasma ratios of stavudine ranged from 16% to 125% (mean of 59%±35%).
59% ± 35%).
Renal impairment: the clearance of stavudine decreases as creatinine clearance decreases; therefore, it is recommended that the dosage of Zerit be adjusted in patients with reduced renal function (see section 4.2).
Očistek stavudina se zmanjšuje z zmanjševanjem očistka kreatinina, zato je pri bolnikih z zmanjšanim delovanjem ledvic odmerek zdravila Zerit priporočljivo prilagoditi (glejte poglavje 4. 2).
Hepatic impairment: stavudine pharmacokinetics in patients with hepatic impairment were similar to those in patients with normal hepatic function.
Farmakokinetika stavudina pri bolnikih z okvaro jeter je bila podobna kot pri bolnikih z normalnim delovanjem jeter.
Animal data showed embryo-foetal toxicity at very high exposure levels.
Pri živalih dobljeni podatki so pri zelo visoki ravni izpostavljenosti pokazali embrio- fetalne toksične učinke.
Stavudine was genotoxic in in vitro tests in human lymphocytes possessing triphosphorylating activity (in which no no-effect level was established), in mouse fibroblasts, and in an in vivo test for chromosomal aberrations.
Stavudin je bil genotoksičen v preizkusih in vitro v človeških limfocitih s trifosforilacijsko aktivnostjo (pri katerih niso ugotovili "ravni brez učinka" [no- effect level]), v mišjih fibroblastih ter v in vivo preizkusu za kromosomske aberacije.
Stavudine was carcinogenic in mice (liver tumours) and rats (liver tumours: cholangiocellular, hepatocellular, mixed hepatocholangiocellular, and/ or vascular; and urinary bladder carcinomas) at very high exposure levels.
11 Stavudin je bil pri zelo visoki ravni izpostavljenosti kancerogen pri miših (tumorji jeter) in podganah (tumorji jeter – holangiocelularni, hepatocelularni, mešani hepatoholangiocelularni – in/ ali žilni ter karcinomi sečnega mehurja).
No carcinogenicity was noted at doses of 400 mg/ kg/ day in mice and 600 mg/ kg/ day in rats, corresponding to exposures ~ 39 and 168 times the expected human exposure, respectively, suggesting an insignificant carcinogenic potential of stavudine in clinical therapy.
168- krat pričakovani izpostavljenosti pri človeku) niso zabeležili kancerogenosti, kar nakazuje, da je kancerogeni potencial stavudina med kliničnim zdravljenjem nepomemben.
Lactose Magnesium stearate Microcrystalline cellulose Sodium starch glycolate
Vsebina kapsule: laktoza magnezijev stearat mikrokristalna celuloza natrijev karboksimetilškrob
Gelatin Iron oxide colorant (E172) Silicon dioxide Sodium laurilsulphate Titanium dioxide (E171)
Ovojnica kapsule: želatina železov oksid kot barvilo (E172) koloidni silicijev dioksid natrijev lavrilsulfat titanov dioksid (E171)
Shellac Propylene Glycol Purified Water
Oznake na ovojnici kapsule so odtisnjene z užitnim črnim črnilom, ki vsebuje: šelak propilenglikol prečiščeno vodo kalijev hidroksid železov oksid (E172)
High-density polyethylene (HDPE) bottles with child resistant screw cap (60 hard capsules per bottle), or
Plastenke iz polietilena velike gostote (HDPE) z za otroke varno navojno zaporko (60 trdih kapsul v eni plastenki), ali
aclar/ aluminum blisters with 14 hard capsules per card and 4 cards (56 hard capsules) per carton.
pretisni omoti iz aclar/ aluminija s 14 trdimi kapsulami v pretisnem omotu in 4 pretisnimi omoti (56 trdih kapsul) v škatli.
08 May 1996 Date of last renewal:
8. maj 1996 Datum podaljšanja dovoljenja za promet:
08 June 2006
8. junij 2006
{month year}
{mesec leto}
Detailed information on this product is available on the website of the European Medicines Agency (EMEA) http: / /www. emea. europa. eu/.
Podrobne informacije o zdravilu so objavljene na spletni strani Evropske agencije za zdravila (EMEA) http: // www. emea. europa. eu /..