natgillin/translations-raw huggingface dataset:
YERVOY is for intravenous use.
Zdravilo YERVOY je namenjeno za intravensko uporabo.
Cytotoxic T-lymphocyte antigen-4 (CTLA-4) is a key regulator of T-cell activity.
Citotoksični T limfocitni antigen 4 (CTLA-4; “Cytotoxic T-lymphocyte antigen-4”) je ključni regulator T-celične aktivnosti.
Median OS and estimated 1-year, 2-year, 3-year and 4-year survival rates are presented in Table 9.
Mediana OS in ocenjeni deleži preživetja po 1-letu, 2-letih, 3-letih in 4-letih so prikazani v preglednici 9.
Moderate diarrhoea or colitis that either is not controlled with medical management or that persists (5-7 days) or recurs
Prebavila: zmerna driska ali kolitis, ki kljub zdravljenju nista nadzorovana, vztrajata (5-7 dni) ali se ponavljata
Two patients treated with ipilimumab 10 mg/kg experienced a partial response, one of which was a durable response for more than 1 year.
Pri dveh bolnikih, ki sta prejemala ipilimumab v odmerku 10 mg/kg, je bil dosežen delni odziv, pri enem trajni odziv, ki je trajal več kot 1 leto.
Randomisation was stratified by PD-L1 expression (≥ 5% vs. < 5% tumour cell membrane expression), BRAF status, and M stage per the American Joint Committee on Cancer (AJCC) staging system.
Randomizacija je bila razslojena glede na ekspresijo PD-L1 (≥ 5 % v primerjavi z < 5 % ekspresije celične membrane tumorja), status BRAF in M stadij po kriterijih Ameriškega združenja za zdravljenje raka (AJCC - American Joint Committee on Cancer).
- inflammation of the skin that can lead to severe skin reaction (known as toxic epidermal necrolysis, Stevens-Johnson syndrome and Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)).
- vnetje kože, ki lahko napreduje do hude kožne reakcije (znana kot toksična epidermalna nekroliza, Stevens Johnsonov sindrom in reakcija na zdravilo z eozinofilijo in sistemskimi simptomi (DRESS-Drug Reaction with Eosinophilia and Systemic Symptoms)).
Immune-related adverse reactions, which can be severe or life-threatening, may involve the gastrointestinal, liver, skin, nervous, endocrine, or other organ systems.
Imunsko pogojeni neželeni učinki, ki so lahko resni ali življenjsko nevarni, lahko prizadenejo prebavila, jetra, kožo, živčevje, endokrine žleze ali druge organske sisteme.
You will be treated with YERVOY once every 3 weeks, for a total of 4 doses.
Zdravilo YERVOY boste prejeli enkrat na vsake 3 tedne, vsega skupaj 4 odmerke.
“+” denotes a censored observation.
“+” označuje krnjene podatke.
Patients with severe (Grade 3 or 4) endocrinopathy controlled with hormone replacement therapy may remain on therapy.
Pri bolnikih s hudo (stopnja 3 ali 4) endokrinopatijo, ki je nadzorovana s hormonskim nadomestnim zdravljenjem, se zdravljenje lahko nadaljuje.
Rare cases of toxic epidermal necrolysis (TEN) (including Steven Johnson Syndrome) have been observed, some with fatal outcome.
Poročali so o redkih primerih toksične epidermalne nekrolizie (TEN) (vključno s Stevens-Johnsonovim sindromom), v nekaterih primerih s smrtnimi izidom.
Solid organ transplant rejection
Zavrnitev presadka čvrstega organa
Preparing the infusion: Take care to ensure aseptic handling when you prepare the infusion.
Priprava raztopine za infundiranje: Pri pripravi raztopine za infundiranje morate zagotoviti aseptične pogoje.
The potential risk of treatment to the developing foetus is unknown.
Možno tveganje za razvijajoči se plod ni znano.
Use of ipilimumab in combination with nivolumab in melanoma patients with rapidly progressing disease.
Uporaba ipilimumaba v kombinaciji z nivolumabom pri bolnikih z melanomom s hitro napredujočo obliko bolezni
One female infant had unilateral renal agenesis of the left kidney and ureter, and one male infant had an imperforate urethra with associated urinary obstruction and subcutaneous scrotal edema.
Ena samička se je skotila z enostransko agenezijo leve ledvice in sečevoda, en samček pa z atrezijo sečnice s posledično obstrukcijo urinskih poti in podkožnim edemom modnika.
- inflammation of the nerves that can lead to paralysis.
- vnetje živcev, ki lahko napreduje do ohromelosti.
None had any infusion-related or peri-infusional hypersensitivity or anaphylactic reactions.
Pri nobenem bolniku ni prišlo do pojava z infuzijo povezane ali peri-infuzijske preobčutljivosti ali anafilaktične reakcije.
YERVOY can be used for intravenous administration either: without dilution, after transfer to an infusion container using an appropriate sterile syringe; or after diluting to up to 5 times the original volume of concentrate (up to 4 parts of diluent to 1 part of concentrate).
Zdravilo YERVOY se lahko aplicira intravensko: brez redčenja, po prenosu v infuzijski vsebnik z ustrezno sterilno injekcijsko brizgo, ali po redčenju do največ 5-kratnega začetnega volumna koncentrata (do 4 deli raztopine za redčenje na 1 del koncentrata).
Secondary efficacy endpoints of best overall response rate (BORR), stable disease (SD), disease control rate (DCR), and progression free survival (PFS) were based on mWHO criteria and determined by the investigator's assessment.
Sekundarni opazovani dogodki učinkovitosti: najboljši celokupni delež odziva (BORR-best overall response rate), stabilna bolezen (SD-stable disease), delež nadzorovane bolezni (DCR-disease control rate) in preživetje brez napredovanja bolezni (PFS-progression free survival) so temeljili na modificiranih kriterijih SZO in so jih ovrednotili raziskovalci.
YERVOY in combination with nivolumab may cause changes in the results of tests carried out by your doctor.
Zdravilo YERVOY v kombinaciji z nivolumabom lahko povzroči spremembe v rezultatih preiskav, ki jih bo opravil zdravnik.
Efficacy results for the intermediate/poor risk patients are shown in Table 12.
Rezultati učinkovitosti pri bolnikih s srednje ugodnim ali slabim prognostičnim obetom so prikazani v preglednici 12.
Reported in clinical studies and in the post-marketing setting.
Poročila iz kliničnih preskušanj in iz obdobja po prihodu zdravila na trg.
The majority were mild to moderate (Grade 1 or 2).
Večinoma so bili blagi do zmerni (stopnja 1 ali 2).
Pharmacotherapeutic group: Antineoplastic agents, monoclonal antibodies, ATC code: L01XC11.
Farmakoterapevtska skupina: Zdravila z delovanjem na novotvorbe (citostatiki), monoklonska protitelesa, oznaka ATC: L01XC11
Based on an exposure-response analysis in 497 patients with advanced melanoma, OS was independent of prior systemic anti-cancer therapy and increased with higher ipilimumab Cminss plasma concentrations.
Na osnovi analize izpostavljenosti-odziva pri 497 bolnikih z napredovalim melanomom, je bilo celokupno preživetje neodvisno od predhodnega sistemskega protitumorskega zdravljenja in večje pri višjih koncentracijah Cminss ipilimumaba v plazmi.
For additional information on warnings and precautions associated with nivolumab treatment, please refer to the nivolumab SmPC.
Za dodatne informacije glede opozoril in previdnostnih ukrepov povezanih z zdravljenjem z nivolumabom, upoštevajte SmPC za nivolumab.
Rate (95% CI) At 6 months At 12 months Progression-free survival Events
Delež (95 % IZ) v 6. mesecu v 12. mesecu Preživetje brez napredovanja bolezni Dogodki Razmerje ogroženostia
With protocol-specified management guidelines, time to resolution ranged from 0.7 to 2 weeks.
Po ukrepanju v skladu s smernicami, določenimi s protokolom, je čas do izboljšanja znašal od 0,7 do 2 tedna.
However, patients with brain metastases were included in this study, if they were free of neurologic symptoms related to metastatic brain lesions and if they did not require or receive systemic corticosteroid therapy in the 10 days prior to beginning ipilimumab therapy (see section 5.1).
Bolniki z zasevki v možganih pa so bili vključeni v to študijo, če niso imeli nevroloških simptomov, povezanih z metastatskimi spremembami v možganih in niso potrebovali ali prejemali sistemskega kortikosteroidnega zdravljenja v 10 dneh pred začetkom zdravljenja z ipilimumabom (glejte poglavje 5.1).
For patients with a history of autoimmune disease, see also section 4.4.
Za bolnike s predhodno avtoimunsko boleznijo glejte tudi poglavje 4.4.
Each ml of this medicinal product contains 0.1 mmol (or 2.30 mg) sodium.
En mililiter tega zdravila vsebuje 0,1 mmol (ali 2,30 mg) natrija.
Unexplained motor neuropathy, muscle weakness, or sensory neuropathy lasting > 4 days must be evaluated, and non-inflammatory causes such as disease progression, infections, metabolic syndromes and concomitant medication should be excluded.
Nepojasnjeno motorično nevropatijo, mišično oslabelost ali senzorično nevropatijo, ki trajajo več kot 4 dni, je treba ovrednotiti in izključiti nevnetne vzroke, kot so napredovanje bolezni, okužbe, metabolni sindrom in sočasno uporabljena zdravila.
Rare cases of SJS and TEN, some of them with fatal outcome, have been observed.
Poročali so o redkih primerih SJS in TEN, nekateri od njih so se končali s smrtnim izidom.
Tumour PD-L1 expression was determined using the PD-L1 IHC 288 pharmDx assay.
Ekspresija PD-L1 tumorja je bila določena s testom PD-L1 IHC 28-8 pharmDx.
By subgroup analysis, the observed OS benefit was consistent within most of the subgroups of patients (M [metastases]-stage, prior interleukin-2, baseline LDH, age, sex, and the type and number of prior therapy).
Pri analizi po podskupinah je bila opažena korist pri celokupnem preživetju konsistentna v večini podskupin bolnikov (M [metastaze]-stadij, predhodno zdravljenje z interlevkinom-2, izhodiščna vrednost LDH, starost, spol in vrsta ter število predhodnih zdravljenj).
CA184332 and CA184338
CA184332 in CA184338
It is not known whether ipilimumab gets into breast milk.
Ni znano, ali se ipilimumab izloča v materino mleko.
No differences in the spectrum of irARs reported in adults and the paediatric population were evident.
Razlike v spektru imunsko pogojenih neželenih učinkov pri odraslih in pediatrični populaciji niso bile očitne.
Stable disease was achieved in two patients at the ipilimumab 5mg/kg dose, one with a duration of > 22 months.
Stabilna bolezen je bila dosežena pri dveh bolnikih pri uporabi ipilimumaba v odmerku 5 mg/kg, pri enem s trajanjem > 22 mesecev.
Guidelines for permanent discontinuation or withholding of doses are described in Tables 3A and 3B for YERVOY as monotherapy, and in Table 3C for YERVOY in combination with nivolumab or administration of the second phase of treatment (nivolumab monotherapy) following combination treatment.
Smernice za trajno ukinitev zdravljenja ali zadržanje odmerka so prikazane v preglednicah 3A in 3B za zdravilo YERVOY v monoterapiji in v preglednici 3C za zdravilo YERVOY v kombinaciji z nivolumabom ali za drugo fazo zdravljenja (nivolumab v monoterapiji) po končanem kombiniranem zdravljenju.
Other organ systemsb: (e.g. nephritis, pneumonitis, pancreatitis, non-infectious myocarditis)
Drugi organski sistemib: (npr. nefritis, pljučnica, pankreatitis, ne-infektivni miokarditis)
While most immune-related adverse reactions occurred during the induction period, onset months after the last dose of ipilimumab has also been reported.
Večina imunsko pogojenih neželenih učinkov se je pojavila med indukcijskim obdobjem zdravljenja, vendar pa so poročali tudi o neželenih učinkih, ki so se pojavili več mesecev po uporabi zadnjega odmerka ipilimumaba.
Storage conditions and shelf life:
Shranjevanje in rok uporabnosti:
All Deaths, n (%)
Vsi smrtni izidi, n (%)
The use of systemic corticosteroids after starting ipilimumab treatment does not appear to impair the efficacy of ipilimumab.
Kaže, da uporaba sistemskih kortikosteroidov po začetku zdravljenja z ipilimumabom, ne vpliva na učinkovitost ipilimumaba.
The Kaplan-Meier OS curve revealed a plateau beginning around year 3 (OS rate = 21% [95% CI: 17-24]) that extended up to 10 years in some patients (see Figure 1).
Kaplan-Meierjeva krivulja celokupnega preživetja je pokazala začetni plato okoli leta 3 (delež celokupnega preživetja = 21 % [95 % IZ: 17-24]), ki je pri nekaterih bolnikih podaljšan do 10-ih let (glejte sliko 1).
There were no reports of severe or very severe (Grade 3 or 4) adrenal insufficiency, hyperthyroidism, or hypothyroidism.
O hudi ali zelo hudi (stopnja 3 ali 4) obliki insuficience nadledvične žleze, hipertiroidizma ali hipotiroidizma niso poročali.
An updated OS analysis was performed when all patients had a minimum follow-up of 24 months (see figure 7).
Ko so vse bolnike spremljali najmanj 24 mesecev, je bila izvedena dopolnjena analiza celokupnega preživetja (glejte sliko 7).
Pack size of 1.
Pakiranje po 1 vialo.
Ipilimumab is a fully human anti-CTLA-4 monoclonal antibody (IgG1κ) produced in Chinese hamster ovary cells by recombinant DNA technology.
Ipilimumab je popolnoma humano monoklonsko protitelo (IgG1κ) proti-CTLA-4, pridobljeno s tehnologijo rekombinantne DNA na ovarijskih celicah kitajskega hrčka.
In study CA184178, no new or unexpected irARs were observed, and the observed irARs were similar in frequency, intensity and organ site to what has been reported in adult studies.
V študiji CA184178 niso opazili novih ali nepričakovanih imunsko pogojenih neželenih učinkov, opaženi imunsko pogojeni neželeni učinki pa so bili po pogostnosti, intenzivnosti in organskih sistemih podobni kot pri študijah pri odraslih.
However, because of the potential for adverse reactions in nursing infants, a decision must be made whether to discontinue breast-feeding or to discontinue from YERVOY therapy taking into account the benefit of breast-feeding for the child and the benefit of YERVOY therapy for the woman.
Ker obstaja možnost za pojav neželenih učinkov pri dojenem otroku, se je treba odločiti med prenehanjem dojenja in prenehanjem zdravljenja z zdravilom YERVOY, pri čemer je treba pretehtati prednosti dojenja za otroka in prednosti zdravljenja za mater.
Rates of immune-related adverse reactions in HLA-A2*0201 positive patients who received ipilimumab in MDX010-20 were similar to those observed in the overall clinical program.
Delež imunsko pogojenih neželenih učinkov pri HLA-A2*0201 pozitivnih bolnikih, ki so v študiji MDX010-20 prejemali ipilimumab, je bil podoben deležu v celotnem kliničnem programu.
Progression Free Survival per Investigator (Months)
Preživetje brez napredovanja bolezni po oceni raziskovalca (meseci)
Rare myasthenia gravisd
Redki miastenija gravisd
Studies to evaluate the effect of ipilimumab on fertility have not been performed.
Študije, ki bi ovrednotile vpliv ipilimumaba na plodnost, niso bile izvedene.
Progressive signs of motor neuropathy must be considered immune-related and managed accordingly.
Znake napredovale motorične nevropatije je treba obravnavati kot imunsko pogojene in ustrezno zdraviti.
The YERVOY infusion should not be infused at the same time in the same intravenous line with other agents.
Zdravila YERVOY ne smete infundirati sočasno z drugimi zdravili preko iste intravenske linije.
The frequency of severe (Grade 3 or 4) diarrhoea and severe (Grade 3 or 4) colitis was 5% each.
Pogostnost hude driske (stopnja 3 ali 4) in hudega kolitisa (stopnja 3 ali 4) je bila pri obeh 5 %.
Adrenal insufficiency, hyperthyroidism, and hypothyroidism of any severity were each reported in 2% of patients.
O insuficienci nadledvične žleze, hipertiroidizmu in hipotiroidizmu vseh jakosti so poročali pri 2 % bolnikov.
Treatment with YERVOY in combination with nivolumab, should be continued for the four doses of combination therapy as long as clinical benefit is observed or until treatment is no longer tolerated by the patient.
Zdravljenje z zdravilom YERVOY v kombinaciji z nivolumabom mora trajati do prejema štirih odmerkov kombiniranega zdravljenja, če je prisotna klinična korist oziroma dokler bolnik zdravljenje prenaša.
Beginning in the third trimester, both ipilimumab groups experienced higher incidences of abortion, stillbirth, premature delivery (with corresponding lower birth weight), and infant mortality relative to control animals; these findings were dose-dependent.
V tretjem trimesečju brejosti pa so pri obeh skupinah, ki so prejemale ipilimumab, poročali o od odmerka odvisni večji pojavnosti splavov, mrtvorojenosti, prezgodnjih kotitev (z ustrezno nizko porodno telesno maso) in večjo umrljivostjo mladičev v primerjavi s kontrolnimi živalmi.
For additional information on clinical efficacy and safety associated with the dosing recommendations of nivolumab when administered as monotherapy following combination therapy with ipilimumab, please refer to the nivolumab SmPC.
Za dodatne informacije o klinični učinkovitosti in varnosti, ki sta povezani s priporočenim odmerjanjem nivolumaba v monoterapiji, po končani kombinirani terapiji z ipilimumabom, prosimo, glejte SmPC za nivolumab.
Patients with apparent tumour burden increase before completion of the induction period were continued on induction therapy as tolerated if they had adequate performance status.
Pri bolnikih, pri katerih se je tumorsko breme pred dokončanjem indukcijskega obdobja očitno povečalo, se je indukcijsko zdravljenje glede na prenašanje zdravila nadaljevalo, če je bila telesna zmogljivost bolnikov zadostna.
Ipilimumab as monotherapy or in combination with a PD-1 or PD-L1 inhibitor
Ipilimumab v monoterapiji ali v kombinaciji z zaviralcem PD-1 ali PD-L1
Clinical experience with ipilimumab-associated endocrinopathy is limited.
Kliničnih izkušenj z endokrinopatijami, povezanimi z ipilimumabom, je malo.
Patients with autoimmune disease
Bolniki z avtoimunsko boleznijo
Immune-mediated adverse reactions were observed infrequently (~3%) and included colitis (which resulted in a single fatality), dermatitis, and infusion reaction (possibly due to acute cytokine release resulting from a rapid injection rate).
Imunsko pogojeni neželeni učinki niso bili pogosti (približno 3 %) in so vključevali kolitis (ki se je v enem primeru končal s poginom), dermatitis in infuzijsko reakcijo (ki bi lahko bila povezana z akutnim sproščanjem citokinov zaradi hitrega injiciranja).
In intravenous repeat-dose toxicology studies in monkeys, ipilimumab was generally well tolerated.
Pri toksikoloških študijah pri ponavljajočih se intravenskih odmerkih so opice ipilimumab na splošno dobro prenašale.
Study CA184070 was a multi-center, Phase 1, open-label, dose-escalation study of ipilimumab in paediatric patients ≥1 year to ≤ 21 years of age with measurable/evaluable, untreatable, relapsed or refractory solid malignant tumors without a curative option with standard therapy.
Študija CA184070 je bila multicentrična, odprta študija 1. faze s povečevanjem odmerka ipilimumaba, izvedena pri pediatričnih bolnikih, starih ≥1 leto do ≤ 21 let z merljivimi/določljivimi, neozdravljivimi, ponovljenimi ali neodzivnimi solidnimi malignimi tumorji brez možnosti kurativnega zdravljenja s standardnimi oblikami zdravljenja.
A total of 945 patients were randomised to receive ipilimumab in combination with nivolumab (n = 314), nivolumab monotherapy (n = 316), or ipilimumab monotherapy (n = 315).
Skupno 945 bolnikov so randomizirali na zdravljenje z ipilimumabom v kombinaciji z nivolumabom (n = 314), nivolumabom v monoterapiji (n = 316) ali ipilimumabom v monoterapiji (n = 315).
Overall survival in MDX010-20 Ipilimumab 3 mg/kg n= 137
Celokupno preživetje v študiji MDX010-20 Ipilimumab 3 mg/kg n= 137
Patients should receive the entire induction regimen (4 doses) as tolerated, regardless of the appearance of new lesions or growth of existing lesions.
Med indukcijskim zdravljenjem morajo bolniki glede na prenašanje zdravila prejeti vse 4 odmerke, ne glede na pojav novih lezij ali razrast obstoječih.
There were no reports of severe (Grade 3 or 4) AST or ALT elevation.
O hudem zvišanju (stopnja 3 ali 4) vrednosti AST ali ALT niso poročali.
Symptoms of nerve problems may include muscle weakness, numbness or tingling in your hands or feet, loss of consciousness or difficulty waking up.
Simptomi okvare živcev lahko vključujejo mišično oslabelost, odrevenelost ali mravljinčenje v rokah ali nogah, izgubo zavesti ali težave pri prebujanju.
In clinical trials, a single dose of infliximab 5 mg/kg was added unless contraindicated.
V kliničnih preskušanjih so dodatno uporabili en sam odmerek infliksimaba (5 mg/kg), če njegova uporaba ni bila kontraindicirana.
50 mg/ml (5%) glucose solution for injection
50 mg/ml (5 %) raztopino glukoze za injiciranje.
The Kaplan-Meier curves for OS (with a minimum follow-up of 24 months) in intermediate/poor risk patients are shown in Figure 7.
Kaplan Meierjevi krivulji celokupnega preživetja (z najmanjšim obdobjem spremljanja 24 mesecev) pri bolnikih s srednje ugodnim ali slabim prognostičnim obetom sta prikazani na sliki 7.
Post authorisation efficacy study (PAES): In order to further elucidate the contribution of ipilimumab to the efficacy and toxicity of the combination regimen of nivolumab and ipilimumab, the MAH should conduct and submit the results of a randomised, clinical study comparing the efficacy and safety of the combination of nivolumab and ipilimumab to nivolumab monotherapy in previously untreated adult patients with intermediate/poorrisk advanced renal cell carcinoma and with an appropriate spectrum of PDL1 expression levels.
Študija učinkovitosti zdravila po pridobitvi dovoljenja za promet z zdravilom (PAES): Da bi podrobneje pojasnili prispevek ipilimumaba k učinkovitosti in toksičnosti kombiniranega režima zdravljenja z nivolumabom in ipilimumabom mora imetnik dovoljenja za promet z zdravilom izvesti in predložiti rezultate randomizirane klinične študije, ki učinkovitost in varnost kombiniranega zdravljenja z nivolumabom in ipilimumabom primerja z zdravljenjem z nivolumabom v monoterapiji pri predhodno nezdravljenih odraslih bolnikih z napredovalim karcinomom ledvičnih celic s srednje ugodnim ali slabim prognostičnim obetom in z ustreznim spektrom ravni ekspresije PD-L1.
Ipilimumab is most commonly associated with adverse reactions resulting from increased or excessive immune activity.
Uporaba ipilimumaba je bila najpogosteje povezana s pojavom neželenih učinkov zaradi povečane ali prekomerne imunske aktivnosti.
Among 131 patients who discontinued the combination due to adverse reaction after 28 months of follow-up, the ORR was 71% (93/131) with 20% (26/131) achieving a complete response and median OS was not reached.
Pri 131 bolnikih, pri katerih je bilo zdravljenje v kombinaciji zaradi neželenih učinkov prekinjeno, je po 28 mesecih spremljanja delež celokupnega odziva znašal 71 % (93/131), s popolnim odzivom pri 20 % (26/131) bolnikov, mediana OS pa ni bila dosežena.
YERVOY as monotherapy is indicated for the treatment of advanced (unresectable or metastatic) melanoma in adults, and adolescents 12 years of age and older (see section 4.4).
Zdravilo YERVOY je v monoterapiji indicirano za zdravljenje napredovalega (neoperabilnega ali metastatskega) melanoma pri odraslih bolnikih in mladostnikih, starih 12 let in starejših (glejte poglavje 4.4).
In case of overdose, patients must be closely monitored for signs or symptoms of adverse reactions, and appropriate symptomatic treatment instituted.
V primeru prevelikega odmerjanja je treba bolnika skrbno nadzirati glede pojava znakov ali simptomov neželenih učinkov in uvesti ustrezno simptomatsko zdravljenje.
Ipilimumab was administered every 3 weeks for 4 doses and then every 12 weeks thereafter in the absence of dose limiting toxicity (DLT) and disease progression.
Bolniki so ipilimumab prejemali vsake 3 tedne 4 odmerke, nato pa na vsakih 12 tednov v primeru odsotnosti toksičnosti, ki bi omejevala odmerek in napredovanja bolezni.
Grade 4 hypothyroidism Grade 4 hyperthyroidism Grade 4 hypophysitis Grade 3 or 4 adrenal insufficiency Grade 4 diabetes
Hipertiroidizem stopnje 4 Vnetje hipofize stopnje 4 Insuficienca nadledvičnih žlez stopnje 3 ali 4