natgillin/translations-raw huggingface dataset:
Dosing regimens in Phase II and Phase III studies Phase
Shema odmerjanja v preskušanjih II. in III. faze
Treatment schedule
shema odmerjanja
Dose
II
Regimen
intravensko) 1, 3 mg/ m2 (bolus
Day 1,4,8,11, (rest Day 12-21) 1.3 mg/ m2 (intravenous bolus) Vc* 1.3 mg/ m2 a) Days 1,4,8,11, (Rest Day 12-21) (intravenous bolus) b) Days 1,8,15,22 Dex 40 mg (oral) a) Days 1– 4, 9 – 12, 17– 20Days 1– 4
a) dan 1, 4, 8, 11 (premor 12. - 21. dan) b) dan 1, 8, 15, 22
Q3 weeks x 8cycles (extension**) a) Q3weeks x 8, then b) Q5 weeks x 3 a) Q5 week x 4 b) Q4 week x 5
a) 3 tedne x 8, nato b) 5 tednov x 3
Add Dex*** 20 mg (oral) (Days 1,2,4,5,8,9, 11,12)
20 mg (peroralno) (dan 1, 2, 4, 5, 8, 9, 11, 15 12)
Q3 weeks
3 tedne
*a) is the initial treatment, a) and b) represent a full course of treatment **An extension study authorised patients benefiting from treatment to continue receiving VELCADE ***If after 2 or 4 cycles of VELCADE, the patients had progressive disease or stable disease, respectively, they could receive dexamethasone
* a) je začetno zdravljenje, a) in b) predstavljata celoten krog zdravljenja. ** Podaljšanje preskušanja, z namenom omogočiti bolnikom nadaljnjo korist od zdravljenja z zdravilom VELCADE. *** Če je bolezen po dveh ali štirih krogih zdravljenja z zdravilom VELCADE napredovala ali ni bilo odziva na zdravljenje, so bolniki lahko prejeli še deksametazon.
Patient characteristics in Phase II and Phase III studies
Značilnosti bolnikov v preskušanjih druge in tretje faze
Phase II Vc
Vc II. faza
Phase III Vc
Vc III. faza
Phase III Dex
Dex III. faza
Patient number, ITT analysis Male% Median age, yrs (range) Caucasian Karnofsky PS > 80% Platelets < 75,000/μ l Hemoglobin < 100g/ l Median Creatinine Clearance, ml/ min (range) 74
št. bolnikov, analiza skupine bolnikov, ki naj bi jih zdravili (intent to treat, ITT)
202 60 59 (34-84) 81% 80 21% 44% (14-221)
60 59 (34- 84) 81 80 21%
333 56 61 (33-84) 90% 87% 6% 32% 73.3 (15.6-170.7)
56 61 (33- 84) 90% 87% 6%
336 60 61 (27-86) 88% 84% 4% 28% 73.3 (15.3-261.1)
60 61 (27- 86) 88% 84% 4%
Myeloma IgG Myeloma IgA Myeloma light chain Median duration since diagnosis (yrs) Chromosome 13 abnormalities Median β 2-microglobulin (mg/ l) Median number prior treatment lines* (range)
hemoglobin < 100 g/ l mediana vrednost očistka kreatinina, ml/ min (območje) IgG plazmocitom IgA plazmocitom plazmocitom lahke verige mediana vrednost trajanja od diagnoze (leta) napake na kromosomu 13 mediana vrednost konc. β2 mikroglobulina (mg/ l)
60% 24% 14% 4.0 15% 3.5 6 (2-15)
44% 74 (14- 221) 60% 24% 14% 4, 0 15% 3, 5
1 prior line > 1 prior line
1 predhodnja vrsta terapije > 1 predhodnja vrsta terapije
n =132 (40%) n = 186 (60%) n =
n=132( 40%) n=186 (60%)
*Including steroids, alkylating agents, anthracyclines, thalidomide and stem cell transplants
* Vključno s steroidi, alkilirajočimi učinkovinami, antraciklini, talidomidom in transplantati matičnih celic
16 Table 11:
Preglednica 11:
Patient exposure to treatment with VELCADE during Phase II and III studies
Izpostavljenost bolnikov zdravljenju z zdravilom VELCADE v preskušanjih II. in III. faze
Received at least 1 dose Completed 4 cycles
prejeli najmanj 1 odmerek zaključili 4 kroge zdravljenja
n = 202 62%
n=202 27% (8 krogov)
n = 332
n=332
a) all initial cycles (number) b) full course (number) c) extension *
a) vsi začetni krogi (število) b) celotno zdravljenje
27% (8 cycles) NA N= 63 pts (median 7 cycles) or total median 14 cycles (range 7-32)
NA
29% (8 cycles) 9% (11 cycles) NA
29% (8 krogov) 9% (11 krogov)
36% (4 cycles) 5% (9 cycles) NA
36% (4 krogi) 5% (9 krogov)
*Patients could continue on treatment after completing 8 cycles, in case of benefit NA = not applicable
NA = ne velja za ta primer
In the Phase III study, treatment with VELCADE led to a significantly longer time to progression, a significantly prolonged survival and a significantly higher response rate, compared to treatment with dexamethasone (see Table 12), in all patients as well as in patients who have received 1 prior line of therapy.
Pri vseh bolnikih, kot tudi pri bolnikih, ki so pred tem že prejeli eno vrsto terapije, je preskušanje zdravljenja z zdravilom VELCADE vodilo do statistično značilno daljšega časa do napredovanja bolezni, statistično značilno podaljšanega preživetja in statistično značilno boljšega odziva na zdravljenje v primerjavi z zdravljenjem z deksametazonom (glejte preglednico 12).
As a result of a preplanned interim analysis, the Dexamethasone arm was halted at the recommendation of the data monitoring committee and all patients randomised to dexamethasone were then offered VELCADE, regardless of disease status.
Bolnikom, ki so
Due to this early crossover, the median duration of follow-up for surviving patients is 8.3 months.
16 bili randomizirani na deksametazon so ponudili zdravilo VELCADE, ne glede na status njihove bolezni.
Regardless of β 2- microglobulin levels at baseline, all efficacy parameters (time to progression and overall survival, as well as response rate) were significantly improved on the VELCADE arm.
Neglede na koncentracijo β2 - mikroglobulina ob začetku zdravljenja, so se tudi vsi parametri učinkovitosti (čas do napredovanja bolezni in celokupno preživetje, kot tudi odziv na zdravljenje) v delu preskušanja z zdravilom VELCADE statistično značilno izboljšali.
In the refractory population of the Phase II study, responses were determined by an independent review committee and the response criteria were those of the European Bone Marrow Transplant Group.
Odziv na zdravljenje v populaciji bolnikov II. faze preskušanja, ki so bili odporni na zdravljenje, je ugotavljala neodvisna komisija, ki je uporabila kriterije za odziv Evropske skupine za transplantacijo kostnega mozga (European Bone Marrow Transplant Group).
The median survival of all patients enrolled was 17 months (range < 1 to 36+ months).
Mediana preživetje vseh bolnikov, vključenih v raziskavo je bila 17 mesecev (območje < 1 do 36 mesecev).
This survival was greater than the six-to-nine month median survival anticipated by consultant clinical investigators for a similar patient population.
Ta stopnja preživetja je bila večja od 6 do 9- mesečnega medianega preživetja, ki ga pričakujejo konziliarni klinični raziskovalci za podobno skupino bolnikov.
Patients who had received 2 to 3 prior therapeutic regimens had a response rate of 32% (10/ 32) and patients who received greater than 7 prior therapeutic regimens had a response rate of 31% (21/ 67).
Tisti, ki so prejeli več kot 7 predhodnih vrst zdravljenj pa so imeli stopnjo odziva 31% (21/ 67).
Table 12:
Preglednica 12:
Summary of
III. faza III. faza
disease outcomes from the Phase III and Phase II Phase III Phase III All patients 1 Prior line of therapy
III. faza > 1 predhodna vrsta
studies Phase III > 1 Prior line of
1 predhodna vrsta zdravljenja
Phase II prior
zdravljenja
therapy
predhodni vrsti zdravljenja
Time related
pogojeni
events TTP, days
dogodki
n=336a 106b
n=336a n=132a
n=132a 212d
106b 212d
n=119a 169d
169d
n=200a 148b
148b
[95% CI]
(dnevi [95% IZ]) 1- letno
[188, 267]
267]
1 year survival,%
preživetje,%
[95% CI]
95% IZ]
Vc
Vc n=315c
n=312c 2 (< 1) b
2 (< 1)
n=128 8 (6)
n=128
n=110 2 (2)
n=110
n=187 12 (6)
n=187
n=202 0 (0)
n=202
n=193 (4)**
n=193
CR + nCR
CR
16 (13)
12 (6)
4 (4)
0 (0)
25 (13)
(4) **
1 (< 1)
41 (13) b
(10)**
5 (2) b
CR+ nCR + PR CR + nCR+
CR + nCR CR+ nCR + PR
56 (18) b
56 (18)
57 (45) d
16 (13) 57 (45) d
29 (26) d
4 (4) 29 (26)
64 (34) b
25 (13) 64 (34) b
27 (13) b
1 (< 1) 27 (13)
(27)**
CR + nCR+
PR+MR
PR+MR Mediana
Median duration
vrednost
189 (6.2)
(6, 2)
238 (7.8)
238
385*
(7, 8)
Days (months) Time to response
(4, 1)
17
385 *
CR + PR (days) a
CR + PR (dnevi) a
Intent to Treat (ITT) population b p-value from the stratified log-rank test; analysis by line of therapy excludes stratification for therapeutic history; p < 0.0001 c Response population includes patients who had measurable disease at baseline and received at least 1 dose of study drug. d p-value from the Cochran-Mantel-Haenszel chi-square test adjusted for the stratification factors; analysis by line of therapy excludes stratification for therapeutic history *CR+PR+MR **CR=CR, (IF-); nCR=CR (IF+) NA = not applicable, NE = not estimated
17 b p- vrednost iz stratificiranega testa log- ranga; v analizi po vrsti terapije ni bila vključena stratifikacija po terapevtski anamnezi, p < 0, 0001 c Populacija oz. skupina bolnikov, pri kateri so ovrednotili odziv na zdravljenje, vključuje bolnike, ki so imeli merljivo bolezen na začetku in so prejeli najmanj en odmerek raziskovalnega zdravila d p- vrednost iz Cochran- Mantel- Haenszelovega hi- kvadrat testa, korigiranega s faktorji stratifikacije; v analizi po vrsti terapije ni bila vključena stratifikacija po terapevtski anamnezi * CR+PR+MR; ** CR=CR, (IF -); nCR=CR (IF+) NA = ne velja za ta primer, NE = odziva ni bilo mogoče oceniti
In the Phase II study, patients who did not obtain an optimal response to therapy with VELCADE alone were able to receive high-dose dexamethasone in conjunction with VELCADE (see Table 9).
Bolniki v preskušanju II. faze, ki niso dosegli optimalnega odziva na zdravljenje z zdravilom VELCADE v monoterapiji, so poleg zdravila VELCADE lahko prejemali tudi deksametazon v velikih odmerkih (glejte preglednico 6).
Eighteen percent of patients achieved, or had an improved response (MR (11%) or PR (7%)) with combination treatment.
Pri 18% bolnikov so dosegli odziv ali izboljšan odziv (MR (11%) ali PR (7%)) pri kombiniranem zdravljenju.
Following intravenous bolus administration of a 1.0 mg/ m2 and 1.3 mg/ m2 dose to 11 patients with multiple myeloma and creatinine clearance values greater than 50 ml/ min, the mean first-dose maximum plasma concentrations of bortezomib were 57 and 112 ng/ ml, respectively.
Po intravenski aplikaciji bolusnega odmerka 1, 0 mg/ m2 in 1, 3 mg/ m2 11 bolnikom z diseminiranim plazmocitomom in očistkom kreatinina večjim kot 50 ml/ min, sta bili povprečni vrednosti najvišjih plazemskih koncentracij bortezomiba po prvem odmerku 57 in 112 ng/ ml.
In subsequent doses, mean maximum observed plasma concentrations ranged from 67 to 106 ng/ ml for the 1.0 mg/ m2 dose and 89 to 120 ng/ ml for the 1.3 mg/ m2 dose.
Pri ponovljenih odmerkih so bile povprečne vrednosti najvišjih plazemskih koncentracij v razponu 67 do 106 ng/ ml pri odmerku 1, 0 mg/ m2 in 89 do 102 ng/ ml pri odmerku 1, 3 mg/ m2.
Distribution The mean distribution volume (Vd) of bortezomib ranged from 1659 l to 3294 l following single- or repeated-dose administration of 1.0 mg/ m2 or 1.3 mg/ m2 to patients with multiple myeloma.
Porazdelitev Po enkratnem ali večkratnem dajanju odmerkov 1, 0 mg/ m2 ali 1, 3 mg/ m2 bolnikom z diseminiranim plazmocitomom je bil povprečni volumen porazdelitve (Vd) 1659 l do 3294 l.
Over a bortezomib concentration range of 0.01 to 1.0 μ g/ ml, the in vitro protein binding averaged 82.9% in human plasma.
V razponu koncentracij bortezomiba od 0, 01 do 1, 0 μg/ ml je bila in vitro vezava na beljakovine povprečno 82, 9% v človeški plazmi.
The fraction of bortezomib bound to plasma proteins was not concentration- dependent.
Delež bortezomiba, vezanega na plazemske beljakovine, ni bil odvisen od koncentracije zdravila.
Metabolism In vitro studies with human liver microsomes and human cDNA-expressed cytochrome P450 isozymes indicate that bortezomib is primarily oxidatively metabolized via cytochrome P450 enzymes, 3A4, 2C19, and 1A2.
Presnova In vitro študije na človeških jetrnih mikrosomih in izocimih citokroma P450 s izraženo človeško cDNA kažejo, da se bortezomib v prvi vrsti oksidativno presnovi z encimi citokroma P450, 3A4, 2C19 in 1A2.
Elimination The mean elimination half-life (t1/ 2) of bortezomib upon multiple dosing ranged from 40-193 hours.
Izločanje Po ponavljajočih odmerkih je bil razpon razpolovnih časov bortezomiba 40- 193 ur.
Mean total body clearances were 102 and 112 l/ h following the first dose for doses of 1.0 mg/ m2 and 1.3 mg/ m2, respectively, and ranged from 15 to 32 l/ h and 18 to 32 l/ h following subsequent doses for doses of 1.0 mg/ m2 and 1.3 mg/ m2, respectively.
Po ponovljenih odmerkih je bil razpon 15 do 32 l/ h za odmerek 1, 0 mg/ m2 in 18 do32 l/ h za odmerek 1, 3 mg/ m2.
Special populations Hepatic impairment Formal studies in patients with severely impaired hepatic function have not been conducted to date (see section 4.4).
Posebne populacije Jetrna okvara Formalnih študij pri bolnikih s hudo jetrno okvaro doslej še niso opravili (glejte poglavje 4. 4).
In the absence of data VELCADE is contraindicated in patients with severe liver impairment (see section 4.3).
Zaradi pomanjkanja podatkov je zdravilo VELCADE pri bolnikih s hudo okvaro jeter kontraindicirano (glejte poglavje 4. 3).
Renal impairment
Ledvična okvara Pri bolnikih z različnimi stopnjami okvare delovanja ledvic so izvedli študijo farmakokinetike.
18 A pharmacokinetic study was conducted in patients with various degrees of renal impairment who were classified according to their creatinine clearance values (CrCL) into the following groups:
Bolnike so glede na vrednost očistka kreatinina (CrCL) razdelili v naslednje skupine: normalno delovanje ledvic (CrCL ≥ 60 ml/ min/ 1, 73 m2, n=12), blaga okvara ledvic (CrCL=40- 59 ml/ min/ 1, 73 m2, n=10), zmerna okvara ledvic (CrCL=20- 39 ml/ min/ 1, 73 m2, n=9),
Normal (CrCL ≥ 60 ml/ min/ 1.73 m2, n=12), Mild (CrCL=40-59 ml/ min/ 1.73 m2, n=10), Moderate (CrCL=20-39 ml/ min/ 1.73 m2, n=9), and Severe (CrCL < 20 ml/ min/ 1.73 m2, n=3).
18 resna okvara ledvic (CrCL < 20 ml/ min/ 1, 73 m2, n=3).
Patients were administered intravenous doses of 0.7 to 1.3 mg/ m2 of VELCADE twice weekly.
Bolniki so dvakrat na teden prejemali intravenske odmerke zdravila VELCADE v odmerku od 0, 7 do 1, 3 mg/ m2.
Exposure of VELCADE (dose-normalized AUC and Cmax) was comparable among all the groups (see section 4.2).
Izpostavljenost zdravilu VELCADE (AUC in Cmax normalizirana glede na odmerek) je bila primerljiva med vsemi skupinami (glejte poglavje 4. 2).
Bortezomib was positive for clastogenic activity (structural chromosomal aberrations) in the in vitro chromosomal aberration assay using Chinese hamster ovary (CHO) cells at concentrations as low as 3.125 μ g/ ml, which was the lowest concentration evaluated.
V in vitro preskusu kromosomskih aberacij z uporabo ovarijskih celic kitajskega hrčka (CHO celic) je bil bortezomib v koncentraciji le 3, 125 μg/ ml, ki je bila najnižja ovrednotena koncentracija, pozitiven na klastogeno aktivnost (strukturne kromosomske aberacije).
Fertility studies were not performed but evaluation of reproductive tissues has been performed in the general toxicity studies.
Raziskave razvojne toksičnosti pri podganah in kuncih so pokazale embriofetalno smrtnost pri odmerkih, toksičnih za samice, vendar ni bilo neposredne embriofetalne toksičnosti pri odmerkih, manjših od tistih, ki so bili toksični za mater.
In the 6-month rat study, degenerative effects in both the testes and the ovary have been observed.
Raziskave plodnosti niso opravili, opravili pa so ovrednotenje reproduktivnih tkiv v raziskavah splošne toksičnosti.
It is, therefore, likely that bortezomib could have a potential effect on either male or female fertility.
V 6- mesečni raziskavi na podganah so opažali degenerativne učinke tako na testise kot na ovarije, zato je verjetno, da bi bortezomib lahko vplival na plodnost samic ali samcev.
Peri- and postnatal development studies were not conducted.
Raziskave peri - in postnatalnega obdobja niso opravili.
In multi-cycle general toxicity studies conducted in the rat and monkey, the principal target organs included the gastrointestinal tract, resulting in vomiting and/ or diarrhoea; haematopoietic and lymphatic tissues, resulting in peripheral blood cytopenias, lymphoid tissue atrophy and haematopoietic bone marrow hypocellularity; peripheral neuropathy (observed in monkeys, mice and dogs) involving sensory nerve axons; and mild changes in the kidneys.
V raziskavah splošne toksičnosti z več krogi zdravljenja na podganah in opicah so bili poglavitni tarčni organi prebavila s posledičnim bruhanjem in/ ali drisko, ter krvotvorni organi s posledičnim zmanjšanjem števila krvnih celic v periferni krvi, zmanjšanjem limfatičnega tkiva ter hipocelularnostjo kostnega mozga, periferno nevropatijo (ki so jo opažali pri opicah, miših in psih) s prizadetostjo senzoričnih živčnih končičev in blagimi spremembami ledvic.
Based on animal studies, the penetration of bortezomib through the blood-brain barrier appears to be limited, if any and the relevance to humans is unknown.
Pomen teh podatkov za ljudi ni znan.
Cardiovascular safety pharmacology studies in monkeys and dogs show that intravenous doses approximately two to three times the recommended clinical dose on a mg/ m2 basis are associated with increases in heart rate, decreases in contractility, hypotension and death.
Farmakološka preskušanja kardiovaskularne varnosti zdravila pri opicah in psih kažejo povezavo med intravenskimi odmerki, ki so bili dva - do trikrat višji od priporočenega kliničnega odmerka (v mg/ m2), in povišanjem srčne frekvence, zmanjšanjem kontraktilnosti srca, hipotenzijo in smrtjo.
Mannitol (E 421) Nitrogen.
manitol (E 421) dušik
This medicinal product must not be mixed with other medicinal products except those mentioned in section 6.6.
Zdravila ne smete mešati z drugimi zdravili, razen s tistimi, ki so omenjena v poglavju 6. 6.
19 The reconstituted solution should be used immediately after preparation.
Če se rekonstituirane raztopine ne porabi takoj, je za čas in pogoje shranjevanja zdravila po pripravi odgovoren uporabnik.
If the reconstituted solution is not used immediately, in-use storage times and conditions prior to use are the responsibility of the user.
Rekonstituirana raztopina je kemično in fizikalno stabilna 8 ur pri temperaturi do 25 °C, če jo pred uporabo
However, the chemical and physical in-use stability of the reconstituted solution has been demonstrated for 8 hours at 25 °C stored in the original vial and/ or a syringe prior to administration, with a maximum of 8 hours in the syringe.
19 shranjujemo v originalni viali in/ ali injekcijski brizgi. V injekcijski brizgi se lahko zdravilo shranjuje največ 8 ur.
Keep the vial in the outer carton in order to protect from light.
Vialo shranjujte v zunanji ovojnini, zaščiteno pred svetlobo.
For storage conditions of the reconstituted medicinal product, see section 6.3.
Za pogoje shranjevanja pripravljene raztopine, glejte poglavje 6. 3.
Type 1 glass 5 ml-vial with a grey bromobutyl stopper and an aluminium seal, with a green cap.
5 ml, steklena viala, steklo tipa I, s sivim zamaškom iz bromobutilne gume in aluminijasto zaporko z zelenim pokrovčkom.
Pack containing 1 single-use vial.
Škatla z eno vialo za enkratno uporabo.
Therefore, caution should be used during handling and preparation of VELCADE.
Spošni previdnostni ukrepi Bortezomib je citotoksičen, zato je potrebna previdnost med pripravo in ravnanjem z zdravilom VELCADE.
Aseptic technique must be strictly observed throughout handling of VELCADE, since it contains no preservative.
Pri delu z zdravilom VELCADE morate ves čas strogo upoštevati aseptično pripravo, ker zdravilo ne vsebuje konzervansov.
Instructions for reconstitution Each vial must be reconstituted with 1 ml of sodium chloride 9 mg/ ml (0.9%) for injection.
Navodila za pripravo raztopine Vsako vialo morate rekonstituirati z 1 ml 9 mg/ ml (0, 9%) raztopine natrijevega klorida za injiciranje.
The reconstituted solution must be inspected visually for particulate matter and discolouration prior to administration.
Rekonstituirano raztopino morate pred uporabo vizualno pregledati, da ugotovite morebitne delce.
Disposal For single use only.
Odlaganje Samo za enkratno uporabo.
JANSSEN-CILAG INTERNATIONAL NV Turnhoutseweg 30 B-2340 Beerse Belgium
JANSSEN- CILAG INTERNATIONAL NV Turnhoutseweg 30 B- 2340 Beerse Belgija
DATE OF FIRST AUTHORISATION/ RENEWAL OF THE AUTHORISATION
20 Datum prve pridobitve dovoljenja za promet:
26/ 04/ 2004 Date of latest renewal:
26/ 04/ 2004 Datum zadnjega podaljšanja dovoljenja za promet:
VELCADE 3.5 mg powder for solution for injection
VELCADE 3, 5 mg prašek za raztopino za injiciranje
Each vial contains 3.5 mg bortezomib (as a mannitol boronic ester).
Vsaka viala vsebuje 3, 5 mg bortezomiba (v obliki estra manitola in borove kisline).
22 Dose adjustments during treatment and re-initiation of treatment for monotherapy VELCADE treatment must be withheld at the onset of any Grade 3 non-haematological or any Grade 4 haematological toxicities, excluding neuropathy as discussed below (see also section 4.4).
Zdravljenje z zdravilom VELCADE morate prekiniti ob pojavu katerekoli nehematološke toksičnosti 3. stopnje ali katerekoli hematološke toksičnosti 4. stopnje, z izjemo nevropatije, kot je opisano v nadaljevanju (glejte tudi poglavje 4. 4).
Patients who experience bortezomib-related neuropathic pain and/ or peripheral neuropathy are to be managed as presented in Table 1 (see section 4.4).
Bolnike, ki imajo nevropatično bolečino in/ ali periferno nevropatijo v povezavi z jemanjem bortezomiba, zdravite v skladu s Preglednico 1( glejte poglavje 4. 4).
Grade 1 with pain or Grade 2 (interfering with function but not with activities of daily living)
Priporočena * prilagoditev odmerjanja v primeru nevropatije v povezavi z bortezomibom Stopnja nevropatije Stopnja 1 (parestezije, oslabljeni in/ ali odsotni refleksi) brez bolečine ali izguba funkcije Stopnja 1 z bolečino ali stopnja 2 (motnje funkcije, vendar ne vsakdanjih dejavnosti)
Reduce to 1.0 mg/ m2
Prilagoditev odmerjanja ukrepanje ni potrebno zmanjšajte odmerek na 1, 0 mg/ m2
Grade 4 (sensory neuropathy which is disabling or motor neuropathy that is life threatening or leads to paralysis) and/ or severe autonomic neuropathy
Stopnja 4 (senzorična nevropatija, ki onemogoča vsakdanje dejavnosti ali motorična nevropatija, ki ogroža življenje ali vodi v paralizo) In/ ali močna avtonomna nevropatija
Elderly patients There is no evidence to suggest that dose adjustments are necessary in patients over 65 years of age (see section 4.8).
Starejši bolniki Ni znakov ali dokazov, ki bi potrdili, da je pri bolnikih, starejših od 65 let, potrebna prilagoditev odmerka (glejte poglavje 4. 8).
Renal impairment The pharmacokinetics of bortezomib are not influenced in patients with mild to moderate renal impairment (CCl > 20 ml/ min/ 1.73 m2); therefore, dose adjustments are not necessary for these patients.
Okvarjeno delovanje ledvic Pri bolnikih z blago do zmerno okvaro ledvic (očistek kreatinina (CrCL) > 20 ml/ min/ 1, 73 m2) ni vpliva na farmakokinetiko bortezomiba, zato pri njih prilagoditev odmerka ni potrebna.
It is unknown if the pharmacokinetics of bortezomib are influenced in patients with severe renal impairment not undergoing dialysis (CCl < 20 ml/ min/ 1.73 m2).
Ni znano ali je farmakokinetika bortezomibaspremenjena pri bolnikih s hudo okvaro delovanja ledvic, ki se ne zdravijo z dializo (CrCL < 20 ml/ min/ 1, 73 m2).
Posology combination therapy VELCADE (bortezomib) is administered in combination with oral melphalan and oral prednisone for nine 6-week treatment cycles as shown in Table 2.
Priporočeno odmerjanje pri kombiniranem zdravljenju
In Cycles 1-4, VELCADE is administered twice weekly (days 1, 4, 8, 11, 22, 25, 29 and 32).
Zdravilo VELCADE (bortezomib) se daje v kombinaciji s peroralnim melfalanom in prednizolonom.
In Cycles 5-9, VELCADE is administered once weekly
Zdravljenje traja devet 6- tedenskih krogov, kot je prikazano v Preglednici 2.
23 (days 1, 8, 22 and 29).
V krogih 1- 4 se zdravilo VELCADE daje dvakrat na teden (dnevi 1, 4, 8, 11, 22, 25, 29 in 32), v krogih 5- 9 pa enkrat na teden (dnevi 1, 8, 22 in 29).
Table 2: Recommended Posology for VELCADE in combination with melphalan and prednisone for patients with previously untreated multiple myeloma Twice weekly VELCADE (cycles 1-4)
Priporočeno odmerjanje zdravila VELCADE v kombinaciji z melfalanom in prednizolonom pri bolnikih s predhodno nezdravljenim diseminiranim plazmocitomom Odmerjanje zdravilaVELCADE dvakrat na teden (krogi 1- 4)
Day Day 8 Day
dan dan dan
r
pre -
Day -- -- Day Day 8 Day rest Day
dan
Day Day Day
dan
rest
dan
(
dan
1.3 mg/ m2) 2
Vc (1, 3 mg/ m
period
mor
Day Day Day Day 1 2
dan dan dan dan 1 2 3
rest period
pre - -- -- -- -- mor
Day 3 4
4