natgillin/translations-raw huggingface dataset:
Efficacy and safety of oral cladribine were evaluated in a randomised, double-blind, placebocontrolled clinical study (CLARITY) in 1,326 patients with relapsing-remitting MS. Study objectives were to evaluate the efficacy of cladribine versus placebo in reducing the annualised relapse rate (ARR) (primary endpoint), slowing disability progression and decreasing active lesions as measured by MRI.
Učinkovitost in varnost peroralnega kladribina so ocenili v randomizirani, dvojno slepi, s placebom kontrolirani klinični študiji (CLARITY) pri 1.326 bolnikih z recidivno remitentno MS. Cilji študije so bili ocena učinkovitosti kladribina v primerjavi s placebom, opredeljena kot zmanjšanje stopnje recidiva na letni stopnji (annualised relapse rate - ARR) (primarni opazovani dogodek), upočasnitev napredovanja prizadetosti in zmanjšanje aktivnih lezij, merjeno s slikanjem z MR.
- If you lose a tablet, contact your doctor for advice.
- Če tableto izgubite, se posvetujte z zdravnikom.
There was no difference in annualised relapse rate between patients with relapsing-remitting MS and patients with secondary progressive MS with relapses.
Razlike v stopnji recidivov na letni ravni med bolniki z recidivno remitentno MS in bolniki s sekundarno progresivno MS z recidivi ni bilo.
Do not take MAVENCLAD at the same time as any other medicine.
Ne jemljite zdravila MAVENCLAD sočasno z drugimi zdravili.
Read the package leaflet for further information.
Za več informacij preberite priloženo navodilo.
Do not take the missed dose along with the next scheduled dose.
Izpuščenega odmerka ne vzemite skupaj z naslednjim načrtovanim odmerkom.
Cladribine has no clinically meaningful inductive effect on CYP1A2, CYP2B6 and CYP3A4 enzymes.
Kladribin nima klinično pomembnega indukcijskega učinka na encime CYP1A2, CYP2B6 in CYP3A4.
Patients should be advised to undertake standard cancer screening after Mavenclad treatment;
je treba bolnikom svetovati, da opravijo po zdravljenju z zdravilom Mavenclad standardne presejalne preglede za raka;
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).
Pri bolnikih, ki so se predhodno zdravili z imunomodulatornimi ali imunosupresivnimi zdravili, je treba pred uvedbo zdravila MAVENCLAD upoštevati način delovanja in trajanje učinka drugega zdravila (glejte poglavje 4.2).
Other symptoms may be headache, burning, tingling, numbness or itchiness of the skin in the affected area, feeling generally unwell or feverish in the early stages of infection.
Drugi simptomi so lahko glavobol, pekoč občutek, mravljinčenje, odrevenelost ali srbenje kože prizadetega območja, splošno slabo počutje ali nekoliko zvišana telesna temperatura v zgodnjih fazah okužbe.
You will be tested to see if you have any infections before you start MAVENCLAD treatment.
Opravili bodo preiskave in ugotovili, ali imate kakršne koli okužbe, preden boste začeli zdravljenje z zdravilom MAVENCLAD.
A drug interaction study in MS patients showed that the bioavailability of 10 mg oral cladribine was not altered when co-administered with pantoprazole.
Študija medsebojnega delovanja pri bolnikih z MS je pokazala, da se biološka uporabnost 10 mg peroralnega kladribina ob sočasnem dajanju pantoprazola ni spremenila.
To decrease the risk for severe lymphopenia, lymphocyte counts must be determined before, during and after cladribine treatment (see section 4.4) and strict criteria for initiating and continuing cladribine treatment must be followed (see section 4.2).
Za zmanjšanje tveganja za hudo limfopenijo je treba pred in med zdravljenjem s kladribinom in po njem določiti število limfocitov (glejte poglavje 4.4) ter upoštevati stroge kriterije za uvedbo in nadaljevanje zdravljenja s kladribinom (glejte poglavje 4.2).
If you forget to take MAVENCLAD
Če ste pozabili vzeti zdravilo MAVENCLAD
No increased incidence in lymphoproliferative disorders and no tumours were seen in this study.
V tej študiji niso opazili povečane pogostnosti limfoproliferativnih bolezni, prav tako niso opazili nobenih tumorjev.
However, a baseline magnetic resonance imaging (MRI) should be performed before initiating MAVENCLAD (usually within 3 months).
Vendar pa je treba pred uvedbo zdravila MAVENCLAD opraviti izhodiščno slikanje z magnetno resonanco (MR) (običajno v 3 mesecih).
Although PML has not been observed with MAVENCLAD, as a precaution, you may have a head MRI (magnetic resonance imaging) before you start treatment.
Čeprav PML pri zdravilu MAVENCLAD niso opazili, vam lahko pred začetkom zdravljenja iz previdnosti naredijo slikanje glave z MR (slikanje z magnetno resonanco).
Lymphopenia may increase the risk of getting an infection.
Limfopenija zviša tveganje za okužbo.
Each treatment course consists of 2 treatment weeks, one at the beginning of the first month and one at the beginning of the second month of the respective treatment year.
Vsak ciklus zdravljenja je sestavljen iz 2 tednov zdravljenja, enega na začetku prvega meseca in enega na začetku drugega meseca posameznega leta zdravljenja.
Studies revealed a mean volume of distribution of cladribine in the range of 480 to 490 L. The plasma protein binding of cladribine is 20%, and independent of plasma concentration.
Študije so pokazale povprečni volumen porazdelitve kladribina v razponu od 480 do 490 l. Vezava kladribina na plazemske beljakovine je 20 % in ni odvisna od koncentracije v plazmi.
MAVENCLAD contains hydroxypropylbetadex that may interact with other medicines in your stomach.
Zdravilo MAVENCLAD vsebuje hidroksipropilbetadeks, ki lahko medsebojno deluje z drugimi zdravili v želodcu.
MAVENCLAD is for oral use.
Zdravilo MAVENCLAD je za peroralno uporabo.
Cd-AMP is further phosphorylated to cladribine diphosphate (Cd-ADP) and cladribine triphosphate (Cd-ATP).
Cd-AMP se naprej fosforilira v kladribin difosfat (cladribine diphosphate - Cd-ADP) in kladribin trifosfat (cladribine triphosphateCd-ATP).
Other common side effects - may affect up to 1 in 10 people - cold sore (oral herpes) - rash - hair loss - reduction in the number of certain white blood cells (neutrophils)
Drugi pogosti neželeni učinki - pojavijo se lahko pri največ 1 od 10 bolnikov - mehurčast izpuščaj na ustnicah (oralni herpes) - izpuščaj - izpadanje las - zmanjšanje števila nekaterih belih krvnih celic (nevtrofilcev)
Known BCRP inhibitors, which may alter the pharmacokinetics of BCRP substrates by 20% in vivo, include eltrombopag.
Med znane zaviralce BCRP, ki lahko spremenijo farmakokinetiko substratov BCRP za 20 % in vivo, sodi eltrombopag.
If necessary, you will be vaccinated against shingles before you start treatment.
Če bo potrebno, vas bodo pred začetkom zdravljenja cepili proti pasovcu.
It is currently unknown whether Mavenclad may reduce the effectiveness of systemically acting hormonal contraceptives.
Trenutno ni znano, ali lahko zdravilo Mavenclad zmanjša učinkovitost sistemsko delujočih hormonskih kontraceptivov.
Do not pop the tablets out of the blister.
Tablet ne vzemite ven iz pretisnega omota.
Table 2 shows how the total number of tablets per treatment week is distributed over the individual days.
Preglednica 2 prikazuje porazdelitev skupnega števila tablet na teden zdravljenja po posameznih dnevih.
You will need one or more packs to provide the correct number of tablets.
Za pravo število tablet boste potrebovali eno pakiranje ali več.
The magnitude of the effect in reducing the frequency of relapses and slowing disability progression in patients receiving the 3.5 mg/kg dose over 2 years was maintained in years 3 and 4 (see section 4.2).
Učinka zmanjšanje pogostnosti recidivov in upočasnitev napredovanja prizadetosti pri bolnikih, ki so 2 leti prejemali odmerek 3,5 mg/kg, sta v 3. in 4. letu ostala na enaki ravni (glejte poglavje 4.2).
There is no indication that cladribine pharmacokinetics might change in a time-dependent fashion after repeated administration.
Nič ne kaže, da bi se farmakokinetika kladribina po večkratnem dajanju lahko spremenila v odvisnosti od časa.
Make sure you have read all of the package leaflet including the step-by-step guide and keep it in a safe place.
Navodilo za uporabo in Navodilo po korakih v celoti preberite in ju shranite na varnem mestu.
MAVENCLAD has no or negligible influence on the ability to drive and use machines.
Zdravilo MAVENCLAD nima vpliva ali ima zanemarljiv vpliv na sposobnost vožnje in upravljanja strojev.
Table 1 Dose of MAVENCLAD per treatment week by patient weight in each treatment year
Preglednica 1 Odmerek zdravila MAVENCLAD na teden zdravljenja glede na telesno maso bolnika v vsakem letu zdravljenja
Renal clearance exceeded the glomerular filtration rate, indicating active renal tubular secretion of cladribine.
Ledvični očistek je presegel stopnjo glomerulne filtracije, kar kaže na aktivno ledvično tubularno izločanje kladribina.
The non-renal part of the elimination of cladribine (approximately 50%) consists of negligible hepatic metabolism and of extensive intracellular distribution and trapping of the active cladribine principle (Cd-ATP) within the targeted intracellular compartment (i.e. the lymphocytes) and subsequent elimination of intracellular Cd-ATP according to the life-cycle and elimination pathways of these cells.
Neledvični del izločanja kladribina (približno 50 %) sestavlja zanemarljiva jetrna presnova in obsežna intracelularna porazdelitev in ujetje aktivne oblike kladribina (Cd-ATP) znotraj ciljnega intracelularnega prostora (tj. limfocitov) in kasnejšim izločanjem intracelularnega Cd-ATP glede na življenjski cikel in poti izločanja teh celic.
MAVENCLAD contains hydroxypropylbetadex, which may be available for complex formation with other medicinal products, potentially leading to an increase in bioavailability of such a product (especially medicinal products with low solubility, see section 5.2).
Zdravilo MAVENCLAD vsebuje hidroksipropilbetadeks, ki lahko tvori komplekse z drugimi zdravili (zlasti s slabo topnimi zdravili), kar lahko povzroči zvišanje biološke uporabnosti takšnega zdravila (glejte poglavje 5.2).
The observed embryolethal and teratogenic effects are consistent with the pharmacologic mechanisms of cladribine.
Opažena smrtnost zarodkov in teratogeni učinki so v skladu s farmakološkim mehanizmom kladribina.
A high DCK to 5'-NTase ratio favours the accumulation of Cd-ATP, making lymphocytes particularly susceptible to cell death.
Visoko razmerje med dCK in 5'-NTazo podpira kopičenje Cd-ATP, kar naredi limfocite še posebej dovzetne za smrt celic.
While there were no effects on female fertility, reproductive function or general performance of offspring, cladribine was shown to be embryolethal when administered to pregnant mice, and the compound was teratogenic in mice (also following treatment of the males only) and rabbits.
Čeprav na plodnost pri ženskah, sposobnost razmnoževanja ali splošno uspevanje potomstva ni bilo učinkov, je imel kladribin embrioletalne učinke, če so ga dajali brejim mišim, ter teratogene učinke pri miših (tudi samo po dajanju zdravila samcem) in kuncih.
The lymphocyte counts of more than 75% of patients returned to the normal range by week 144 from the first dose of cladribine (approximately 90 weeks after the last dose of cladribine).
Pri več kot 75 % bolnikov se je število limfocitov do 144. tedna od prvega odmerka kladribina (približno 90 tednov po zadnjem odmerku kladribina) vrnilo v normalni razpon.
The potential consequences of P-gp induction on the bioavailability of cladribine have not been formally studied.
Možnih posledic indukcije P-gp na biološko uporabnost kladribina niso uradno raziskovali.
When administered with a high-fat meal, cladribine absorption was delayed (median Tmax 1.5 h, range 1 to 3 h) and Cmax was reduced by 29% (based on geometric mean), while AUC was unchanged.
Pri jemanju kladribina z obroki, ki vsebujejo veliko maščob, je bila njegova absorpcija zapoznela (mediana Tmax 1,5 h, razpon 1 do 3 h) in Cmax se je zmanjšala za 29 % (na podlagi geometrične sredine), medtem ko se AUC ni spremenila.
Cladribine cumulative dose 3.5 mg/kg (n = 433)
Skupni odmerek kladribina 3,5 mg/kg (n = 433)
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.
Kladribin za encime citokroma P450 ni pomemben substrat in ne kaže pomembnega potenciala, da bi deloval kot zaviralec encimov CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1 in CYP3A4.
INFORMATION IN BRAILLE mavenclad
PODATKI V BRAILLOVI PISAVI mavenclad
- dilazep, nifedipine, nimodipine, reserpine, cilostazol or sulindac (used to treat the heart, high blood pressure, vascular conditions or inflammation), or eltrombopag (used to treat conditions associated with bleeding).
- dilazepom, nifedipinom, nimodipinom, reserpinom, cilostazolom ali sulindakom (uporabljajo se za zdravljenje srca, visokega krvnega tlaka, žilnih bolezni ali vnetij), ali eltrombopagom (uporablja se za zdravljenje stanj, ki so povezana s krvavitvami).
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).
Pri teh bolnikih je zdravljenje s kladribinom 3,5 mg/kg povzročilo zmanjšanje stopnje recidivov na letni ravni v primerjavi s placebom (0,03 v primerjavi z 0,30, razmerje tveganja: 0,11, p < 0,05).
Renal clearance of cladribine was shown to be dependent on creatinine clearance.
Pokazalo se je, da je očistek kladribina odvisen od očistka kreatinina.
The dephosphorylation and deactivation of Cd-AMP is catalysed by cytoplasmic 5'-NTase.
Defosforilacijo in deaktivacijo Cd-AMP katalizira citoplazemska 5´-NTaza.
NAME OF THE MARKETING AUTHORISATION HOLDER Merck Europe B.V.
IME IMETNIKA DOVOLJENJA ZA PROMET Z ZDRAVILOM Merck Europe B.V.
As a result of a lower DCK/5'-NTase ratio other bone marrow derived cells are less affected than lymphocytes.
Kot rezultat nižjega razmerja med dCK in 5'-NTazo so druge celice, ki izvirajo iz kostnega mozga, manj prizadete kot limfociti.
3 Pull out tray until it stops
3 Izvlecite nosilec, dokler se ne zaustavi.
However, considering cladribine genotoxicity, male-mediated effects related to potential genetic alteration of differentiating sperm cells cannot be excluded.
Vendar pa glede na genotoksičnost kladribina ni možno izključiti učinkov, ki preko moškega vplivajo na morebitne genetske spremembe diferencirajočih se spermijev.
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.
Večina bolnikov iz skupine, ki je prejemala placebo (87,0 %), in skupin, ki sta prejemali kladribin 3,5 mg/kg (91,9 %) in 5,25 mg/kg (89,0 %), je zaključila polnih 96 tednov študije.
The distribution of the total dose over the 2 years of treatment is provided in Table 1.
Porazdelitev skupnega odmerka v 2 letih zdravljenja je razvidna iz preglednice 1.
When oral cladribine was given in fasted state, median Tmax was 0.5 h (range 0.5 to 1.5 h).
Po dajanju peroralnega kladribina na tešče je bila mediana Tmax 0,5 h (razpon 0,5 do 1,5 h).
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).
Če število limfocitov pade pod 200 celic/mm³, je treba v času limfopenije 4. stopnje razmisliti o profilaksi proti herpesu v skladu z lokalno standardno prakso (glejte poglavje 4.8).
Liver problems
Težave z jetri
What you need to know before you take MAVENCLAD
Kaj morate vedeti, preden boste vzeli zdravilo MAVENCLAD
A treatment week consists of 4 or 5 days on which you receive 1 or 2 tablets daily (see Table 1).
Teden zdravljenja vključuje 4 ali 5 dni, na katere prejmete 1 ali 2 tableti na dan (glejte preglednico 1).
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).
Uvedba zdravljenja s kladribinom je kontraindicirana pri bolnikih z oslabljenim imunskim sistemom, vključno z bolniki, ki trenutno prejemajo imunosupresivno ali mielosupresivno terapijo, npr. z metotreksatom, ciklofosfamidom, ciklosporinom ali azatioprinom, ali ki kronično uporabljajo kortikosteroide, zaradi tveganja za aditivne učinke na imunski sistem (glejte poglavje 4.3).
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.
Zdravilo MAVENCLAD vsebuje učinkovino kladribin, citotoksično snov (ki ubija celice), in deluje pretežno na limfocite, celice imunskega sistema, ki sodelujejo pri vnetju.
Acute short-term therapy with systemic corticosteroids can be administered during cladribine treatment.
Med zdravljenjem s kladribinom je možna akutna kratkoročna terapija s sistemskimi kortikosteroidi.
Patients randomised to the 5.25 mg/kg cumulative dose received additional treatment at weeks 9 and 13 of the first year.
Bolniki, randomizirani za prejemanje skupnega odmerka 5,25 mg/kg, so prejeli dodatno zdravljenje v 9. in 13. tednu prvega leta.
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).
Kot je prikazano v zgornji preglednici 3, večji skupni odmerki niso prinesli nobenih dodatnih klinično pomembnih prednosti, bili pa so povezani s povečano incidenco limfopenije ≥ 3. stopnje (44,9 % v skupini s 5,25 mg/kg v primerjavi s 25,6 % v skupini s 3,5 mg/kg).
You do not have to take the tablets at meal times.
Tablet vam ni treba jemati v času obrokov.
Cladribine has the potential to penetrate the blood brain barrier.
Kladribin lahko prehaja skozi krvno-možgansko bariero.
The role of hepatic function for the elimination of cladribine is considered negligible.
Ocenjuje se, da je vloga jeter pri izločanju kladribina zanemarljiva.
In addition, the cladribine 3.5 mg/kg treatment group was statistically significantly superior to placebo with regard to number and relative reduction of T1 Gd+ lesions, active T2 lesions and combined unique lesions as demonstrated in brain MRI over the entire 96 weeks of the study.
Poleg tega je bila skupina, zdravljena s kladribinom 3,5 mg/kg, statistično značilno boljša od placeba glede števila in relativnega zmanjšanja lezij T1 Gd+, aktivnih lezij T2 in skupnega števila posameznih lezij, kar so ugotavljali slikanjem možganov z MR ves čas 96-tedenske študije.
Inhibition of BCRP in the gastrointestinal tract may increase the oral bioavailability and systemic exposure of cladribine.
Zaviranje BCRP v prebavilih lahko zviša peroralno biološko uporabnost in sistemsko izpostavljenost kladribinu.
• Important potential risks Progressive multifocal leukoencephalopathy (PML), opportunistic infections (other than PML and tuberculosis) and severe infections, to ensure awareness of signs and symptoms suggestive of these risks; Malignancies, to raise awareness on this risk because: a.
Progresivna multifokalna levkoencefalopatija (PML), oportunistične okužbe (poleg PML in tuberkuloze) in hude okužbe, za zagotavljanje zavedanja znakov in simptomov, ki nakazujejo ta tveganja;
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.
V delečih se celicah Cd-ATP moti sintezo DNA z zaviranjem ribonukleotidne reduktaze in tekmuje z deoksiadenozin trifosfatom za vgrajevanje v DNA s polimerazami DNA.
The primary target organs identified in the repeat-dose toxicology studies by parenteral routes (intravenous or subcutaneous) up to 1-year duration in mice and monkeys were the lymphoid and haematopoietic system.
Primarni ciljni organi, opredeljeni v do eno leto trajajočih toksikoloških študijah s ponavljajočimi odmerki po parenteralnih potmeh (intravensko ali subkutano) pri miših in opicah sta bila limfni in krvotvorni sistem.
Cladribine was also assessed in a 1-year monkey study by the subcutaneous route.
Kladribin so ocenili tudi v enoletni študiji pri opicah s subkutano uporabo.
In vitro studies showed negligible transporter-mediated uptake of cladribine into human hepatocytes.
Študije in vitro so pokazale zanemarljiv privzem kladribina v humane hepatocite s pomočjo prenašalcev.
Initiation of cladribine treatment in immunocompromised patients, including patients currently receiving immunosuppressive or myelosuppressive therapy (see section 4.5).
Uvedba zdravljenja s kladribinom pri bolnikih z oslabljenim imunskim sistemom, vključno z bolniki, ki trenutno prejemajo imunosupresivno ali mielosupresivno zdravljenje (glejte poglavje 4.5).
• The treatment regimens;
• režime zdravljenja;
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.
Če pozabite vzeti 2 zaporedna odmerka (na primer odmerka za 3. in 4. dan), vzemite izpuščena odmerka v naslednjih 2 dnevih, nato pa teden zdravljenja podaljšajte za 2 dni.
Shingles will need to be treated, and MAVENCLAD treatment may need to be stopped until the infection is cleared.
Pasasti izpuščaj bo treba zdraviti in morda bo treba zdravljenje z zdravilom MAVENCLAD ustaviti, dokler okužba ne izzveni.
DCK is the rate limiting enzyme for conversion of the cladribine prodrug into its active triphosphate form, leading to selective depletion of dividing and non-dividing T and B cells.
Encim dCK omejuje hitrost pretvorbe predzdravila kladribina v njegovo aktivno trifosfatno obliko, kar povzroči selektivno zmanjševanje delečih in nedelečih se celic T in B.
However, testicular effects were observed in mice and monkeys (see section 5.3).
Vendar pa so pri miših in opicah opazili učinke na moda (glejte poglavje 5.3).
Very common (≥1/10)
Zelo pogosti (≥ 1/10)
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.
Učinkov močnih induktorjev izločevalnih prenašalcev BCRP in P-glikoproteina (P-gp) na biološko uporabnost in razporeditev kladribina niso uradno raziskovali.
Do not use this medicine after the expiry date which is stated on the label and the carton after EXP.
Tega zdravila ne smete uporabljati po datumu izteka roka uporabnosti, ki je naveden na nalepki in škatli poleg oznake EXP. Rok uporabnosti zdravila se izteče na zadnji dan navedenega meseca.
Treatment with MAVENCLAD must be initiated and supervised by a physician experienced in the treatment of MS.
Zdravljenje z zdravilom MAVENCLAD lahko uvede in nadzira le zdravnik, ki ima izkušnje z zdravljenjem MS.
The incidence of herpes zoster was higher during the period of grade 3 or 4 lymphopenia (<500 to 200 cells/mm³ or <200 cells/mm³) compared to the time when the patients were not experiencing grade 3 or 4 lymphopenia (see section 4.4).
Incidenca herpesa zostra je bila višja v obdobju limfopenije 3. ali 4. stopnje (< 500 do 200 celic/mm³ ali < 200 celic/mm³), v primerjavi z obdobjem, ko bolniki niso imeli limfopenije 3. ali 4. stopnje (glejte poglavje 4.4).
Patients randomised to the 3.5 mg/kg cumulative dose received a first treatment course at weeks 1 and 5 of the first year and a second treatment course at weeks 1 and 5 of the second year.
Bolniki, randomizirani na prejemanje skupnega odmerka 3,5 mg/kg, so prvi ciklusu zdravljenja prejeli v 1. in 5. tednu prvega leta ter drugi ciklus zdravljenja v 1. in 5. tednu drugega leta.