natgillin/translations-raw huggingface dataset:
The patient ’ s electrolyte and glycaemia levels, as well as haematologic, hepatic, renal and coagulation parameter tests must be monitored at least twice weekly, and more frequently for clinically unstable patients during the induction phase and at least weekly during the consolidation phase.
Nadzor ravni elektrolitov in sladkorja v krvi ter preiskave hematoloških, jetrnih, ledvičnih in koagulacijskih parametrov morate opravljati vsaj dvakrat tedensko, pri klinično nestabilnih bolnikih med indukcijskim zdravljenjem tudi pogosteje in med konsolidacijskim zdravljenjem vsaj enkrat tedensko.
Hyperleukocytosis:
Hiperlevkocitoza:
Treatment with TRISENOX has been associated with the development of hyperleukocytosis (≥ 10 x 103/μ l) in some patients.
Zdravljenje z zdravilom TRISENOX je pri nekaterih bolnikih povezano z nastankom hiperlevkocitoze (≥ 10 x 103/ μl).
There did not appear to be a relationship between baseline white blood cell (WBC) counts and development of hyperleukocytosis nor did there appear to be a correlation between baseline WBC count and peak WBC counts.
Ni ugotovljene povezave med osnovno vrednostjo števila belih krvnih celic (WBC – » white blood cell) in razvojem hiperlevkocitoze ali med osnovno in najvišjo vrednostjo WBC.
WBC counts during consolidation were not as high as during induction treatment and were < 10 x 103/μ l, except in one patient who had a WBC count of 22 x 103/ μ l during consolidation.
Število WBC med konsolidacijo ni bilo tako visoko, kot med indukcijskim zdravljenjem in je bilo < 10 x 103/ μl, razen pri enem bolniku, pri katerem je bilo med konsolidacijskim zdravljenjem število WBC 22 x 103/ μl.
Twenty patients (50%) experienced leukocytosis; however, in all these patients, the WBC count was declining or had normalized by the time of bone marrow remission and cytotoxic chemotherapy or leukopheresis was not required.
Pri dvajsetih bolnikih (50%) se je pojavila levkocitoza; vendar je pri vseh teh bolnikih število WBC padalo ali se je normaliziralo do remisije kostnega mozga in citotoksična kemoterapija ali levkofereza nista bili potrebni.
No formal assessments of pharmacokinetic interactions between TRISENOX and other therapeutic medicinal products have been conducted.
Uradne ocene farmakokinetičnih interakcij med zdravilom TRISENOX in drugimi zdravili niso opravili.
QT/ QTc prolongation is expected during treatment with TRISENOX, and torsade de pointes and complete heart block have been reported.
Med zdravljenjem z zdravilom TRISENOX lahko pričakujete podaljšanje intervala Q- T/ Q - Tc, poročali pa so tudi o aritmiji torsade de pointes in popolnem srčnem bloku.
Caution is advised when TRISENOX is coadministered with other medicinal products known to cause QT/ QTc interval prolongation such as macrolide antibiotics, the antipsychotic thioridazine, or medicinal products known to cause hypokalemia or hypomagnesaemia.
Pri skupni uporabi zdravila TRISENOX in drugih zdravil, za katere je znano, da povzročajo podaljšanje intervala Q- T/ Q- Tc, kot so makrolidni antibiotiki, antipsihotik tioridazin ali zdravila, za katera je znano, da povzročajo hipokaliemijo ali hipomagneziemijo, svetujemo previdnost.
Additional information about QT prolonging medicinal agents, is provided in Section 4.4.
Dodatne informacije o učinkovinah, ki podaljšujejo interval Q- T, so v poglavju 4. 4.
The influence of TRISENOX on the efficacy of other antileukaemic medicinal products is unknown.
Vpliv zdravila TRISENOX na učinkovitost drugih zdravil za levkemijo ni znan.
Arsenic trioxide has been shown to be embryotoxic and teratogenic in animal studies (see 5.3).
V raziskavah na živalih je dokazano, da je arzenov trioksid embriotoksičen in teratogen (glejte 5. 3).
Men, and women of childbearing potential must use effective contraception during treatment with TRISENOX.
Moški in ženske v rodni dobi morajo med zdravljenjem z zdravilom TRISENOX uporabljati ustrezna kontracepcijska sredstva.
Related adverse reactions of CTC grade 3 and 4 occurred in 37% of patients in clinical trials.
Do povezanih neželenih reakcij CTC stopnje 3 in 4 je prišlo pri 37% bolnikov v kliničnih preskušanjih.
The most commonly reported reactions were hyperglycaemia, hypokalaemia, neutropenia, and increased alanine amino transferase (ALT).
Najpogostejše reakcije so bile hipoglikemija, hipokaliemija, nevtropenija in povečana raven alanin- aminotransferaze (ALT).
Leukocytosis occurred in 50% of patients with APL, as determined by haematology assessments, rather than adverse event reports.
To so ugotovili s hematološkimi raziskavami in ne s poročili o neželenih učinkih.
Serious adverse reactions were common (1-10%) and not unexpected in this population.
V tej skupini so bile resne neželene reakcije pogoste (1- 10%) in pričakovane.
Those serious adverse reactions attributed to TRISENOX included APL differentiation syndrome (3), leukocytosis (3), prolonged QT interval (4, 1 with torsade de pointes), atrial fibrillation/ atrial flutter (1), hyperglycaemia (2) and a variety of serious adverse reactions related to haemorrhage, infections, pain, diarrhoea, nausea.
Med resne neželene reakcije, ki so jih pripisali zdravilu TRISENOX, so spadali sindrom diferenciacije APL (3), levkocitoza (3), podaljšan interval Q- T (4, 1 z aritmijo torsade de pointes), atrijska fibrilacija/ atrijska undulacija (1), hiperglikemija (2) in razne resne neželene reakcije, povezane s hemoragijo, okužbami, bolečinami, drisko in navzeo.
The table below lists the related grade 3 and 4 adverse drug reactions for the 107 patients treated with TRISENOX in clinical trials (frequencies defined as: common ≥ 1/ 100 to < 1/ 10, uncommon ≥ 1/ 1,000 to < 1/ 100).
Spodnja tabela prikazuje z zdravilom povezane neželene učinke stopnje 3 in 4 pri 107 bolnikih, zdravljenih z zdravilom TRISENOX pri kliničnih preskušanjih.
System Organ Class
Pri vsaki od skupin pogostosti so navedeni učinki od najvišje do najnižje resnosti (pogostnosti so opredeljene kot: pogosti ≥ 1/ 100 do < 1/ 10, občasni ≥ 1/ 1. 000 do < 1/ 100).
Blood and lymphatic system Neutropenia disorders Thrombocytopenia
V razvrstitvah pogostosti so neželeni učinki navedeni po padajoči resnosti.
5
5 Organski sistem bolezni krvi in limfatičnega sistema
Hypermagnesaemia
hiperglikemija hipokaliemija
System Organ Class Common disorders Hypokalaemia Nervous system disorders Paraesthesia
bolezni živčevja srčne bolezni
Uncommon Hypernatraemia Ketoacidosis
perikardni izlivi tahikardija
Cardiac disorders
žilne bolezni
Pericardial effusion Tachycardia
vaskulitis
Vascular disorders Respiratory, thoracic and Pleuritic pain mediastinal disorders Dyspnoea
bolezni dihal, prsnega koša in mediastinalnega prostora
Vasculitis Pulmonary alveolar haemorrhage Pleural effusion Hypoxia
pljučna alveolarna hemoragija plevralni izliv hipoksija
Gastrointestinal disorders Skin and subcutaneous tissue disorders Musculoskeletal and Bone pain connective tissue disorders Arthralgia
bolezni prebavil bolezni kože in podkožja
Diarrhoea Pruritus Erythema Myalgia
diareja pruritus eritem
General disorders and Pyrexia administration site Fatigue conditions
bolezni mišično- skeletnega sistema in vezivnega tkiva
Chest pain Pain
mialgija
Investigations ECG QT prolonged ALT increased
splošne težave in spremembe na mestu aplikacije
Hyperbilirubinaemia Hypomagnesaemia
povišana telesna temperatura utrujenost
Aspartate amino transferase increased
bolečine v prsih bolečine
During TRISENOX treatment, 13 of the 52 patients in the APL studies had one or more symptoms of APL differentiation syndrome, characterised by fever, dyspnoea, weight gain, pulmonary infiltrates and pleural or pericardial effusions, with or without leukocytosis (see Section 4.4).
Med zdravljenjem z zdravilom TRISENOX je 13 od 52 bolnikov v študijah akutne promielocitne levkemije imelo enega ali več znakov sindroma diferenciacije APL, za katerega so značilni povišana telesna temperatura, dispneja, pridobivanje telesne mase, pljučni infiltrati in plevralni ali perikardialni izlivi, z levkocitozo ali brez nje (glejte poglavje 4. 4).
Twenty-seven patients had leukocytosis (WBC ≥ 10 x 103/μ l) during induction, 4 of whom had values above 100,000/μ l.
Pri štirih izmed njih so bile njene vrednosti nad 100. 000/ μl.
Mortality in the pivotal studies from disseminated intravascular coagulation (DIC) associated haemorrhage was very common (> 10%), which is consistent with the early mortality reported in the literature.
V ključnih študijah je bila umrljivost zaradi hemoragije, povezane z diseminirano intravaskularno koagulacijo (DIC – » disaminated intravascular coagulation «), zelo pogosta (> 10%), kar sovpada z zgodnjo umrljivostjo, o kateri poroča literatura.
Arsenic trioxide can cause QT interval prolongation (see Section 4.4).
Arzenov trioksid lahko povzroči podaljšanje intervala Q- T (glejte poglavje 4. 4).
The risk of torsade de pointes is related to the extent of QT prolongation, concomitant administration of QT prolonging medicinal products, a history of torsade de pointes, preexisting QT interval prolongation, congestive heart failure, administration of potassium-wasting diuretics, or other conditions that result in hypokalaemia or hypomagnesaemia.
Nevarnost aritmije torsade de pointes je povezana s stopnjo podaljšanja intervala Q- T, sočasne uporabe zdravil za podaljšanje intervala Q- T, pojavljanjem aritmije torsade de pointes v preteklosti, že obstoječim podaljšanjem intervala Q- T, kongestivno srčno odpovedjo, uporabo diuretikov, ki ne varčujejo s kalijem ali drugimi stanji, ki lahko povzročijo hipokaliemijo ali hipomagneziemijo.
She went onto consolidation without further evidence of QT prolongation.
Konsolidacijsko zdravljenje je začela brez nadaljnjih znakov podaljšanja intervala Q- T.
Peripheral neuropathy, characterised by paresthesia/ dysesthesia, is a common and well known effect of environmental arsenic.
6 Periferna nevropatija, za katero je značilna parestezija/ disestezija, je pogost in dobro znan učinek arzena v okolju.
Forty-four percent of patients experienced symptoms that could be associated with neuropathy; most were mild to moderate and were reversible upon cessation of treatment with TRISENOX.
44 odstotkov bolnikov je imelo simptome, ki jih lahko povežemo z nevropatijo.
6 The following adverse events have been identified during the post-approval use of TRISENOX and have been included following consideration of the observed frequency, seriousness and possible causal relationship to TRISENOX.
Med uporabo po odobritvi zdravila TRISENOX so bili ugotovljeni naslednji stranski učinki in vključeni ob upoštevanju pogostosti, resnosti in verjetnosti povezave z zdravilom TRISENOX..
They are listed below by system organ class and frequency (frequencies are defined as: uncommon (≥ 1/ 1,000 to < 1/ 100), not known (cannot be estimated from the available data).
Našteti so spodaj po organskih sistemih in po pogostnosti (pogostnosti so opredeljene kot: občasni (≥ 1/ 1. 000 do < 1/ 100), neznana (ni jih možno oceniti z razpoložljivimi podatki).
System Organ Class Infection and Infestations
Organski sistem infekcija in okužbe
Uncommon Sepsis Pneumonia Herpes zoster
Občasni sepsa pljučnica herpes zoster
Blood and Lymphatics System Disorders
bolezni krvi in limfatičnega sistema
Metabolism and Nutrition Disorders Psychiatric Disorders Nervous System Disorders
presnovne in prehranske motnje psihiatrične motnje bolezni živčevja
Dehydration Fluid retention Confusional state Convulsions Dizziness
dehidracija zastajanje tekočine stanje zmedenosti konvulzije vrtoglavica
Eye Disorders Cardiac Disorders
bolezni oči srčne bolezni
Vision blurred Cardiac failure Ventricular tachycardia Ventricular extrasystoles
zamegljen vid srčna odpoved ventrikularna tahikardija ventrikularne ekstrasistolije
Vascular Disorders
žilne bolezni
Hypotension
nizek krvni tlak
Respiratory, Thoracic and Mediastinal Disorders
bolezni dihal, prsnega koša in mediastinalnega prostora
Gastrointestinal Disorders
bolezni prebavil
Vomiting Abdominal pain
bruhanje trebušne bolečine
Skin and Subcutaneous Disorders
bolezni kože in podkožja
Face oedema Rash
edem obraza izpuščaji
Renal and Urinary Disorders General Disorders and Administration Site Conditions Investigations
bolezni ledvic in sečil splošne težave in spremembe na mestu aplikacije Preiskave
Renal failure Oedema Chills Blood creatinine increased Weight increased
ledvična odpoved edem mrzlica povečan kreatinin v krvi zvišana telesna masa
If symptoms suggestive of serious acute arsenic toxicity (e. g. convulsions, muscle weakness and confusion) appear, TRISENOX must be immediately discontinued and chelating therapy with penicilamine at a daily dose ≤ 1 gm per day may be considered.
Če se pojavijo simptomi, značilni za resno akutno zastrupitev z arzenom (npr. krči, mišična slabotnost in zmedenost), morate zdravljenje z zdravilom TRISENOX nemudoma prekiniti in pretehtati kelacijsko zdravljenje z dnevnim odmerkom penicilamina (≤1 gram na dan).
For patients who cannot take oral medication, dimercaprol administered at a dose of 3 mg/ kg intramuscularly every 4 hours until any immediately life-threatening toxicity has subsided may be considered.
Pri pacientih, ki zdravil ne morejo jemati peroralno, se lahko uporabi dimerkaprol v odmerku 3 mg/ kg intramuskularno vsake 4 ure do upada življenjsko nevarne toksičnosti.
Thereafter, penicillamine at a daily dose ≤ 1 gm per day may be given.
Nato lahko uporabite penicilamin v odmerkih po ≤1 gram na dan.
In the presence of coagulopathy, the oral administration of the chelating agent Dimercaptosuccinic Acid Succimer (DCI) 10 mg/ kg or 350 mg/ m2 every 8 hours during 5 days and then every 12 hours during 2 weeks is recommended.
Pri koagulopatiji priporočamo peroralno uporabo sredstva za kelacijo sukcimera dimerkaptosukcinske kisline (DCI - » dimercaptosuccinic acid succimer «) v odmerkih po 10 mg/ kg ali 350 mg/ m2 vsakih 8 ur prvih 5 dni in nato naslednja dva tedna vsakih 12 ur.
Other antineoplastic agents, ATC code:
Farmakoterapevtska skupina: druga zdravila z delovanjem na novotvorbe, Oznaka ATC:
L01XX27
L01XX27.
7 TRISENOX has been authorised under “ Exceptional Circumstances”.
Zdravilo TRISENOX je pridobilo dovoljenje za promet v » izjemnih okoliščinah «.
This means that due to the rarity of the disease, it has not been possible to obtain complete information on this medicinal product.
To pomeni, da zaradi redkosti bolezni ni bilo mogoče pridobiti popolnih informacij o zdravilu.
The European Medicines Agency (EMEA) will review any new information which may become available every year and this SPC will be updated as necessary.
Evropska agencija za vrednotenje zdravil (EMEA) bo vsako leto ponovno pregledala vse nove podatke, ki bodo na voljo in posodobila povzetek glavnih značilnost zdravila, če bo potrebno.
Arsenic trioxide also causes damage or degradation of the fusion protein Pro-Myelocytic Leukaemia/ Retinoic Acid Receptor-alpha (PML/ RAR alpha).
Arzenov trioksid povzroča tudi poškodbe in razgradnjo fuzijske beljakovine receptorja za promielocitno levkemijo/ retinojsko kislino alfa (PML/ RAR- alfa).
Patients in the first study received a median dose of 0.16 mg/ kg/ day of TRISENOX (range 0.06 to 0.20 mg/ kg/ day) and patients in the multicentre study received a fixed dose of 0.15 mg/ kg/ day.
Bolniki v prvi študiji so prejemali mediano odmerka 0, 16 mg/ kg zdravila TRISENOX na dan (v obsegu od 0, 06 do 0, 20 mg/ kg/ dan), bolniki v multicentrični študiji pa fiksni odmerek 0, 15 mg/ kg/ dan.
TRISENOX was administered intravenously over 1 to 2 hours until the bone marrow was free of leukaemic cells, up to a maximum of 60 days.
Zdravilo TRISENOX so dajali intravensko v trajanju 1– 2 uri, dokler kostni mozeg ni bil brez levkemičnih celic, vendar največ 60 dni.
Patients with complete remission received consolidation therapy with TRISENOX for 25 additional doses over a 5 week period.
Prejeli so 25 dodatnih odmerkov v času 5 tednov.
Consolidation therapy began 6 weeks (range, 3-8) after induction in the single institution study and 4 weeks (range, 3-6) in the multicentre study.
V študiji z enim zavodom se je konsolidacijsko zdravljenje začelo 6 tednov (v obsegu 3 – 8 tednov), v multicentrični študiji pa se je začelo 4 tedne (v obsegu 3– 6 tednov) po indukciji.
Complete remission (CR) was defined as the absence of visible leukaemic cells in the bone marrow and peripheral recovery of platelets and white blood cells.
Popolna remisija (CR – » complete remission «) je bila opredeljena kot odsotnost vidnih levkemičnih celic v kostnem mozgu ter periferalna obnovitev krvnih ploščic in belih krvnih celic.
Patients in the single centre study had relapsed following 1-6 prior therapy regimens and 2 patients had relapsed following stem cell transplantation.
Pri bolnikih v enocentrični študiji je prišlo do relapsa po 1– 6 predhodih krogih zdravljenja in pri dveh bolnikih je prišlo do relapsa po transplantaciji zarodnih celic.
Patients in the multicentre study had relapsed following 1-4 prior therapy regimens and 5 patients had relapsed following stem cell transplantation.
Pri bolnikih v multicentrični študiji je prišlo do relapsa po 1– 4 predhodih krogih zdravljenja in pri 5 bolnikih je prišlo do relapsa po transplantaciji zarodnih celic.
Centre Trial N=12
Enocentrična študija N=12
TRISENOX Dose, mg/ kg/ day (Median, Range)
odmerek zdravila TRISENOX, mg/ kg/ dan (mediana, obseg)
0.16 (0.06 – 0.20)
0, 16 (0. 06 – 0. 20)
Complete Remission Time to Bone Marrow Remission (Median)
popolna remisija čas do remisije kostnega mozga (mediana)
11 (92%) 32 days
11 (92%) 32 dni
34 (85%) 35 days
34 (85%) 35 dni
Time to CR (Median) 18-Month Survival
čas do CR
The single institution study included 2 paediatric patients (< 18 years old), both of whom achieved CR.
Pri obeh je prišlo do CR.
The multicentre trial included 5 paediatric patients (< 18 years old), 3 of whom achieved CR.
Multicentrična študija je vključevala 5 pediatričnih bolnikov (starih < 18 let).
The Kaplan-Meier median CR duration for the single institution study is 14 months and has not been reached for the multicentre study.
Mediana trajanja CR po metodi Kaplan- Meier v enocentrični študiji je 14 mesecev.
At last follow-up, 6 of 12 patients in the single institution study were alive with a median follow-up time of 28 months (range 25 to 29).
Mediana časa sledenja je 28 mesecev (v obsegu od 25 do 29 mesecev).
In the multicentre study 27 of 40 patients were alive with a median follow-up time of 16 months (range 9 to 25).
Mediana časa sledenja je 16 mesecev (v obsegu od 9 do 25 mesecev).
Kaplan-Meier estimates of 18-month survival for each study are shown below.
Ocena 18- mesečnega preživetja po metodi Kaplan - Meier za obe študiji je prikazana spodaj.
Single Center Multicenter Study
Večcentr. raz
12 40
40
Cytogenetic confirmation of conversion to a normal genotype and Reverse Transcriptase - Polymerase Chain Reaction (RT-PCR) detection of PML/ RARα conversion to normal are shown in the table below.
Citogenetska potrditev pretvorbe v normalen genotip in odkrivanje pretvorbe PML/ RARα v običajno obliko z metodo polimerazne verižne reakcije z reverzno transkriptazo (RT- PCR - » reverse transcriptase – polymerase chain reaction «) je prikazana v tabeli spodaj.
Conventional Cytogenetics [t(15; 17)]
Navadna citogenetika [t( 15; 17)] odsotna prisotna ni mogoče vrednotiti RT- PCR za PML / RARα
Single Centre Pilot Trial N with CR = 11
Enocentrična pilotna študija N s CR = 11 8 (73%) 1 (9%) 2 (18%)
Multicentre Trial N with CR = 34
Multicentrična študija N s CR = 34 31 (91%) 0% 3 (9%)
Absent Present Not evaluable
negativna
31 (91%) 0% 3 (9%)
27 (79%)
RT-PCR for PML/ RAR α
pozitivna
Negative Positive Not evaluable
3 (27%)
8 (73%) 3 (27%) 0
4 (12%)
27 (79%) 4 (12%) 3 (9%)
3 (9%)
There is no experience on the effect of TRISENOX on the variant APL containing the t(11; 17) and t(5; 17) chromosomal translocations.
Izkušenj z učinki zdravila TRISENOX na obliko APL s kromosomskima translokacijama t( 11; 17) in t( 5; 17) ni.
9 In the total single dose range of 7 to 32 mg (administered as 0.15 mg/ kg), systemic exposure (AUC) appears to be linear.
V skupnem enojnem razponu odmerka od 7 do 32 mg (aplicirano kot 0, 15 mg/ kg), kaže, da je sistemska izpostavljenost (AUC) linearna.
The decline from peak plasma concentration of AsIII occurs in a biphasic manner and is characterized by an initial rapid distribution phase followed by a slower terminal elimination phase.
Upad iz največjih koncentracij AsIII v plazmi se pojavi na bifazni način, zanj pa je značilna začetna hitra porazdelitvena faza, ki jih sledi počasnejša končna faza izločanja.
After administration at 0.15 mg/ kg on a daily (n=6) or twice-weekly (n=3) regimen, an approximate 2-fold accumulation of AsIII was observed as compared to a single infusion.
Po uporabi 0, 15 mg/ kg v dnevnem (n = 6) ali dvakrat- tedenskem (n = 3) režimu odmerjanja so opazili približno 2- kratno nalaganje AsIII v primerjavi z enkratnim infundiranjem.
This accumulation was slightly more than expected based on single-dose results.
To nalaganje je bilo nekoliko višje od pričakovanega na podlagi rezultatov enkratnega odmerka.
The volume of distribution (Vd) for AsIII is large (> 400 L) indicating significant distribution into the tissues with negligible protein binding.
Volumen porazdelitve (Vd) za AsIII je velik (> 400 L), kar kaže na značilno porazdelitev v tkivu z zanemarljivo vezavo na beljakovine.
The pentavalent metabolites, MMAV and DMAV, are slow to appear in plasma (approximately 10-24 hours after first administration of arsenic trioxide), but due to their longer half-life, accumulate more upon multiple dosing than does AsIII.
Pentavalentni presnovki, MMAV in DMAV, se v plazmi pokažejo počasi (približno 10- 24 ur po prvem dajanju arzenovega trioksida), vendar se zaradi daljšega razpolovnega časa bolj nalagajo po več odmerkih kot AsIII.
Approximate accumulation ranged from 1.4- to 8-fold following multiple as compared to single dose administration.
Približen razpon nalaganja je bil od 1, 4 - do 8- krat po dajanju večkratnega odmerka v primerjavi z enkratnim odmerkom.
In vitro enzymatic studies with human liver microsomes revealed that arsenic trioxide has no inhibitory activity on substrates of the major cytochrome P450 enzymes such as 1A2, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1, 3A4/ 5, 4A9/ 11.
In vitro encimske študije človeških jetrnih mikrosomov so razkrile, da arzenov trioksid ne vpliva zaviralno na substrate večjih encimov citokroma P450 kot so 1A2, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1, 3A4/ 5, 4A9/ 11.
Approximately 15% of the administered TRISENOX dose is excreted in the urine as unchanged AsIII.
Približno 15% apliciranega odmerka zdravila TRISENOX se izloči v seču kot nespremenjen AsIII.
The total clearance of AsIII over the single-dose range of 7-32 mg (administered as 0.15 mg/ kg) is 49 L/ h and the renal clearance is 9 L/ h.
Skupni očistek AsIII v razponu enkratnega odmerka 7- 32 mg (aplicirano kot 0, 15 mg/ kg) je 49 L/ h in ledvični očistek je 9 L/ h.
Renal Impairment:
Okvarjeno delovanje ledvic:
Plasma clearance of AsIII was not altered in patients with mild renal impairment (creatinine clearance of 50-80 mL/ min) or moderate renal impairment (creatinine clearance of 30-49 mL/ min).
Očistek AsIII v plazmi ni bil spremenjen pri bolnikih z blago okvaro delovanja ledvic (očistek kreatinina 50- 80 mL/ min) ali zmerno okvaro delovanja ledvic (očistek kreatinina 30- 49 mL/ min).
The plasma clearance of AsIII in patients with severe renal impairment (creatinine clearance less than 30 mL/ min) was 40% lower when compared with patients with normal renal function (see section 4.4).
Očistek AsIII v plazmi bolnikov s hudo okvaro delovanja ledvic (očistek kreatinina pod 30 mL/ min) je bil 40% nižji v primerjavi z bolniki z normalnim delovanjem ledvic (glejte poglavje 4. 4).
Hepatic Impairment:
Okvarjeno delovanje jeter:
Limited reproductive toxicity studies of arsenic trioxide in animals indicate embryotoxicity and teratogenicity (neural tube defects, anophthalmia and microphthalmia) at administration of 1-10 times the recommended clinical dose (mg/ m2).
Omejene študije reproduktivne toksičnosti arzenovega trioksida na živalih so pri dajanju odmerka, 1 - 10- krat večjega od priporočenega (mg/ m2), pokazale embriotoksičnost in teratogenost (okvare nevralne cevi, anoftalmijo in mikroftalmijo).