qanastek/EMEA-V3 huggingface dataset:
This medicine has been given “ conditional approval”.
Din il- mediċina ngħatat “ approvazzjoni b’ kondizzjoni ”.
The European Medicines Agency (EMEA) will review new information on the medicine every year and this leaflet will be updated as necessary. ---------------------------------------------------------------------------------------------------------------------------
L- Aġenzija Ewropeja dwar il- Mediċini ser tirrevedi l- informazzjoni l- ġdida dwar il - mediċini kull sena u dan il- fuljett ser jiġi aġġornat skond il- bżonn. --------------------------------------------------------------------------------------------------------------------- It- tagħrif li jmiss huwa maħsub għall- professjonisti fil- qasam mediku:
Doses higher than 1000 mg should be diluted in 150 ml 0.9% sodium chloride injection.
Dożi ogħla minn 1000 mg għandhom jiġu dilwiti f’ 150 ml ta ’ injezzjoni ta ’ 0. 9% sodium chloride.
The infusion line should be flushed with sodium chloride solution before and after Vectibix administration to avoid mixing with other medicinal products or IV solutions.
27 Il- pajp ta ’ l- infużjoni għandu jitlaħlaħ b’ soluzzjoni ta ’ sodium chloride qabel u wara l- għoti ta ’ Vectibix biex jiġi evitat taħlit ma ’ prodotti mediċinali oħra jew soluzzjonijiet IV.
27 Vectibix must be administered as an intravenous infusion via an infusion pump, using a low protein binding 0.2 or 0.22 micrometer in-line filter, through a peripheral line or indwelling catheter.
Vectibix għandu jingħata bħala infużjoni ġol- vini permezz ta ’ pompa ta ’ l- infużjoni, bl- użu ta ’ filtru tal- pajp tad- dripp ta ’ 0. 2 jew 0. 22 mikrometru, li jeħel b’ mod baxx mal- proteini, minn ġo pajp periferali jew kateter minn ġewwa.
Doses higher than 1000 mg should be infused over approximately 90 minutes.
Dożi akbar minn 1000 mg għandhom jiġu infużi fuq madwar 90 minuta.
What is Velcade?
X’ inhu Velcade?
Velcade is a powder that is made up into a solution for injection.
Velcade hu trab li huwa magħmul f’ soluzzjoni għall- injezzjoni.
It contains the active substance bortezomib.
Fih is- sustanza attiva bortezomib.
What is Velcade used for?
Għal xiex jintuża Velcade?
Velcade is an anticancer medicine.
Velcade hu mediċina kontra l- kanċer.
It is used to treat adults with multiple myeloma, a cancer of the plasma cells in the bone marrow.
Jintuża fit- trattament ta ’ adulti b’ mjeloma multipla, li huwa kanċer taċ- ċelloli tal- plażma fil- mudullun tal- għadma.
Velcade is used in the following groups:  patients who have not been treated before and who are not suitable for high-dose chemotherapy with bone marrow transplant.
Velcade jintuża fil- gruppi li jmiss:  f’ pazjenti li ma jkunux ġew itrattati qabel u li ma jkunux tajbin għal kemoterapija b’ dożi għolja bit- trapjant ta ’ l- għadma tal- mudullun.
In these patients, Velcade is used in combination with melphalan and prednisone (other medicines for multiple myeloma);  patients whose disease is progressive (getting worse) and who have failed to respond to at least one other treatment and have already had, or cannot undergo, a bone marrow transplant.
F’ dawn il- pazjenti Velcade jintuża flimkien ma ’ melphalan u prednisone (mediċini oħra għal mjeloma multipla)  pazjenti li l- marda tagħhom tkun waħda progressiva (dejjem tiggrava) u li ma rnexxielhomx jirrispondu lanqas għal trattament wieħed u li jkun diġà sarilhom jew ma jkunx jista ’ jsirilhom trapjant tal- mudullun.
Velcade is used on its own in these patients.
F’ dawn il- pazjenti Velcade jintuża waħdu.
How is Velcade used?
Kif jintuża Velcade?
Treatment with Velcade should only be started and given under the supervision of a doctor who has experience in the use of cancer chemotherapy.
It- trattament b’ Velcade għandu jinbeda u jiġi sorveljat minn tabib li jkollu esperjenza fl- użu tal - kemoterapija ta ’ kontra l- kanċer.
The recommended starting dose is 1.3 mg per square metre body surface area (calculated using the patient ’ s height and weight).
Id- doża inizjali rakkomandata hi ta ’ 1. 3mg għall- kull metru kwadru ta ’ l- erja tas- superfiċje tal- ġisem (li hija kkalkulata permezz tat- tkejjil tat- tul u l- piż tal- pazjent).
The solution is given as a three- to five-second injection through a catheter (a thin sterile tube) into a vein.
Is - soluzzjoni tingħata b’ injezzjoni intravenuża li ddum tingħata bejn tlieta u ħames sekondi, minn ġo katiter (tubu sterili rqiq).
When used in combination with melphalan and prednisone, Velcade is given twice a week on weeks 1, 2, 4 and 5 of a six-week treatment cycle.
Meta użat flimkien ma ’ melphalan u prednisone, Velcade jingħata darbtejn kuljum fl- ewwel, it- tieni, ir- raba ’ u l- ħames ġimgħa ta ’ trattament b’ ċiklu ta ’ sitt ġimgħat.
This cycle is repeated three more times, followed by five cycles of once-weekly injections.
Iċ- ċiklu jiġi ripetut għal tliet darbiet oħra u mbagħad jitkompla b’ ħames ċikli oħra b’ injezzjonijiet darba fil- ġimgħa.
When used on its own, Velcade is given twice a week on weeks 1 and 2 of a three-week treatment cycle.
Meta meħud waħdu, Velcade jingħata darbtejn fil- ġimgħa, fl- ewwel u fit- tieni ġimgħa ta ’ ċiklu ta ’ trattament ta ’ tliet ġimgħat.
Patients who respond fully to treatment should receive two more cycles, but patients who only partially respond to treatment should receive up to eight cycles.
Il- pazjenti li jirrispondu kompletament għat- trattament għandhom jingħataw żewġ ċikli oħra iżda dawk il- pazjenti li jirrispondu biss parzjalment għat- trattament għandhom jingħataw sa tmien ċikli ta ’ trattament.
If a patient develops severe side effects after a treatment cycle, the treatment must be suspended and the dose adjusted.
Jekk pazjent jiżviluppa effetti sekondarji severi wara ċiklu ta ’ trattament, it - trattament għandu jitwaqqaf u d- doża għandha tiġi aġġustata.
How does Velcade work?
Kif jaħdem Velcade?
The active substance in Velcade, bortezomib, is a proteasome inhibitor.
Is- sustanza attiva f’ Velcade, bortezomib, hija inibitur tal- proteasome.
It blocks the proteasome, which is a system within the cells that breaks down proteins when they are no longer needed.
Din timblokka l- proteasome, li hija s- sistema fiċ- ċelloli li tkisser il- proteini meta dawn ma jkunx għad hemm bżonnhom.
When
Meta l -
Reproduction is authorised provided the source is acknowledged. the proteins in the cancer cells, such as the proteins that control the growth of the cells, are not broken down, the cells are affected and they eventually die.
Reproduction is authorised provided the source is acknowledged. proteini fiċ- ċelloli tal- kanċer, bħall- proteini li jikkontrollaw kemm jikbru ċ- ċelloli, ma jitkissrux, dawn iċ- ċelloli jiġu affettwati u eventwalment imutu.
How has Velcade been studied?
Kif ġie studjat Velcade?
The effectiveness of Velcade has been studied in four main studies.
L- effikaċja ta ’ Velcade fil- mjeloma multipla ġiet studjata f’ erba ’ studji prinċipali.
The first study involved 682 patients who had not been treated before and were not suitable for high- dose chemotherapy with bone marrow transplant.
L- ewwel studju involva 682 pazjent li ma kienux ġew itrattati qabel u li ma kienux tajbin għal kemoterapija b’ doża għolja bi trapjant tal- mudullun.
The study compared the effects of adding Velcade to melphalan and prednisone with those of melphalan and prednisone alone.
L- istudju ipparaguna l- effetti ta ’ meta Velcade jingħata ma ’ melphalan u prednisone ma ’ dawk ta ’ melphalan u prednisone waħedhom.
The other three studies looked at patients who had received at least one previous treatment and whose disease was getting worse during their most recent treatment.
It- tliet studji l- oħra ħarsu lejn pazjenti li kienu diġà rċevew minn l- inqas trattament wieħed qabel u li l - marda tagħhom kienet sejra għall- agħar matul l- aħħar trattament li kellhom.
In one study, the effectiveness of Velcade was compared with that of high-dose dexamethasone (another medicine for multiple myeloma) in 669 patients.
F’ wieħed mill- istudji, l - effikaċja ta ’ Velcade tqabblet ma ’ dik ta ’ doża għolja ta ’ dexamethasone( mediċinia oħra għall - mjeloma multipla) f’ 669 pazjent.
In the other two studies, including a total of 256 patients, Velcade was not compared with any other treatments.
Fiż- żewġ studji l- oħra, li kienu jinkludu total ta ’ 256 pazjent, Velcade ma ġie mqabbel ma ’ ebda trattament ieħor.
The main measures of effectiveness were the number of patients who responded to treatment and the time taken for the disease to get worse.
Il- kejl ewlieli ta ’ l- effikaċja kien in- numru ta ’ pazjenti li rrispondew għat- trattament u kemm ikun għadda żmien qabel ma l- marda tkun qed tmur għall- agħar.
What benefit has Velcade shown during the studies?
X’ inhu l- benefiċċju ta ’ Velcade li ntwera f’ dawn l- istudji?
In patients who had not been treated before, adding Velcade to melphalan and prednisone increased the time until the disease got worse: it took an average of 20.7 months in patients receiving Velcade and 15.0 months in those receiving only melphalan and prednisone.
F’ pazjenti li ma kienux ġew itrattati qabel, iż- żieda ta ’ Velcade ma ’ melphalan u prednisone tawlet l - ammont ta ’ żmien sakemm ma l- marda bdiet tmur għall- agħar: damet medja ta ’ 20. 7 xhur f’ pazjenti li kienu qed jirċievu Velcade u 15. 0 – il xahar f’ dawk li kienu qed jieħdu mephalan u prednisone biss.
In patients who had been treated before, the time taken for the disease to get worse was, on average, 6.2 months with Velcade and 3.5 months with dexamethasone in the comparative study.
Fil- pazjenti li kienu ġew itrattati qabel, iż- żmien li damet il- marda sakemm ma iggravat kien medja ta ’ 6. 2 il- xahar b’ Velcade u 3. 5 xhur b’ dexamethasome fl- istudju kumparattiv.
In the other two studies, around 34% of the patients responded partially or completely to treatment with Velcade.
Fiż- żewġ studji l- oħra, madwar 34% tal- pazjenti irrispondew parzjalment jew kompletament għat- trattament b’ Velcade.
What is the risk associated with Velcade?
X’ inhu r- riskju assoċjat ma ’ Velcade?
The most common side effects with Velcade (seen in more than 1 patient in 10) are herpes zoster (shingles), thrombocytopenia (low blood platelet counts), anaemia (low red blood cell counts), neutropenia (too few of the white blood cells that fight infection), reduced appetite, peripheral neuropathy with paraesthesia (tingling or numbness and pins and needles), headache, dyspnoea (breathlessness), nausea (feeling sick), diarrhoea, vomiting, constipation, rash, myalgia (muscle pain), fatigue (tiredness) and pyrexia (fever).
L- iktar effetti sekondarji komuni b’ Vercade (li dehru f’ iktar minn pazjent wieħed minn kull 10) huma l- herpes zoster (il- ħruq ta ’ Sant Antnin), tromboċitopenja (livell baxx ta ’ platelets tad- demm), anemija (tnaqqis fil- għadd ta ’ ċelloli tad- demm ħomor), newtropenja (ammont żgħir wisq ta ’ ċelloli tad- demm bojod li jikkumbattu l- infezzjoni), tnaqqis fl- aptit, newropatija periferika bil- parestesija (tingiż jew tnemnim), uġigħ ta ’ ras, dispnea (qtugħ ta ’ nifs), nawżea (tħossok ma tiflaħx), dijarrea, remettar, stitikezza, raxx, mijalġija (uġigħ fil- muskoli), għejja u piressija (deni).
For the full list of all side effects reported with Velcade, see the Package Leaflet.
Għal- lista sħiħa ta ’ effetti sekondarji rappurtati ma ’ Velcade, ara l- Fuljett ta ’ Tagħrif.
It must not be given to patients with severe liver disease, ‘ acute diffuse infiltrative pulmonary disease’ (a severe lung problem) or pericardial disease (disease affecting the sac that surrounds the heart).
Velcade m’ għandux jingħata lil persuni allerġiċi għal bortezomib, boron jew għal kwalunkwe sustanza oħra, u m’ għandux jingħata lil pazjenti b’ mard tal- fwied sever ‘ marda infiltrattiva pulmonarja akuta ’ (problema gravi tal- pulmun jew marda perikardjatika (marda li taffettwa l- borża ta ’ madwar il- qalb).
Why has Velcade been approved?
Għaliex ġie approvat Velcade?
The Committee for Medicinal Products for Human Use (CHMP) decided that Velcade’ s benefits are greater than its risks for the treatment of multiple myeloma.
Il- Kumitat għall- Prodotti Mediċinali għall- Użu mill- Bniedem (CHMP) iddeċieda li l- benefiċċji ta ’ Velcade fit- trattament tal- mjeloma multipla huma ikbar mir- riskji tiegħu.
The Committee recommended that Velcade be given marketing authorisation.
Il- Kumitat irrakkomanda li Velcade jingħata l- awtorizzazzjoni għat- tqegħid fis- suq.
Velcade has been authorised under ‘ Exceptional Circumstances’, because, for scientific reasons, it has not been possible to obtain complete information on the medicine.
Velcade ġie awtorizzat skond ‘ Ċirkustanzi Eċċezzjonali ’, għax, għal raġunijiet xjentifiċi, ma kienx possibbli li jinkiseb tagħrif komplet dwar il- mediċina.
Every year, the European Medicines Agency (EMEA) will review any new information that may become available and this summary will be updated as necessary.
Kull sena, l- Aġenzija Ewropea għall- Mediċini (EMEA) se tirrevedi kwalunkwe tagħrif ġdid li jkun jista ’ jinkiseb dan is- sommarju jiġi aġġornat kif meħtieġ.
What information is still awaited for Velcade?
X’ tagħrif għad irid jinkiseb dwar Velcade?
The company that makes Velcade will carry out further studies looking in particular at the distribution of Velcade in the body (especially after repeated doses), and at the risk of patients developing amyloidosis (a build-up of a type of protein called amyloid in the body) or of amyloidosis getting worse.
Il- kumpanija li tagħmel Velcade se tagħmel iktar studji partikolarment dwar id- distribuzzjoni ta ’ Velcade fil- ġisem (speċjalment wara dożi ripetuti), u dwar ir- riskju għal pazjenti li jiżviluppaw amilojdożi (amyloidosis) (meta jkun hemm żieda fl- amilojdi, tip ta ’ proteina, fil- ġisem) jew ta ’ amilojdożi li tiggrava.
Other information about Velcade:
Tagħrif ieħor dwar Velcade:
The European Commission granted a marketing authorisation valid throughout the European Union for Velcade on 26 April 2004.
Il- Kummissjoni Ewropea tat awtorizzazzjoni għat- tqegħid fis- suq għal Velcade valida madwar l - Unjoni Ewropea kollha fis- 26 ta ’ April 2004.
The marketing authorisation holder is Janssen-Cilag International NV.
Id- Detentur ta ’ l- Awtorizzazzjoni għat- Tqegħid fis- Suq huwa Janssen- Cilag International NV.
The marketing authorisation was renewed on 26 April 2009.
L- Awtorizzazzjoni għat- Tqegħid fis- Suq ġiet imġedda fis- 26 ta ’ April 2009.
2/ 3 The full EPAR for Velcade is available here.
2/ 3 L- EPAR sħiħ għal Velcade huwa disponibbli minn hawn.
ANNEX A EU Number
Numru ta ’ l - EU/ EMEA
Invented name
< Isem Ivvintat > < Isem >
EU/ 1/ 04/ 274/ 001 EU/ 1/ 04/ 274/ 002
EU/ 1/ 04/ 274/ 001 VELCADE
VELCADE VELCADE
EU/ 1/ 04/ 274/ 002 VELCADE
3.5 mg 1 mg
1mg
Powder for solution for injection Powder for solution for injection
trab għal soluzzjoni għall - injezzjoni
vial (glass) vial (glass)
Fjala (ħġieġ)
1 vial 1 vial
Fjala waħda
VELCADE 1 mg powder for solution for injection
VELCADE 1 mg trab għal soluzzjoni għall- injezzjoni
QUALITATIVE AND QUANTITATIVE COMPOSITION
2. - GĦAMLA KWALITATTIVA U KWANTITATTIVA
Each vial contains 1 mg bortezomib (as a mannitol boronic ester).
Kull fjala fiha 1 mg bortezomib (bħala mannitol boronic ester).
After reconstitution, 1 ml of solution for injection contains 1 mg bortezomib.
Wara li jiġi rikostitwit, 1 ml tas- soluzzjoni għall- injezzjoni fiha 1 mg bortezomib.
White to off-white cake or powder.
Ċappa jew trab minn abjad sa offwajt.
VELCADE in combination with melphalan and prednisone is indicated for the treatment of patients with previously untreated multiple myeloma who are not eligible for high-dose chemotherapy with bone marrow transplant.
VELCADE flimkien ma ’ melphalan u prednisone huwa indikat għall- kura ta ’ pazjenti b’ majloma multipla li qatt ma kienet ikkurata qabel li m’ humiex eleġibbli għal doża għolja ta ’ kimoterapija bi trapjant tal- mudullun.
VELCADE is indicated as monotherapy for the treatment of progressive multiple myeloma in patients who have received at least 1 prior therapy and who have already undergone or are unsuitable for bone marrow transplantation.
VELCADE huwa indikat għall- kura waħedha ta 'pazjenti b' majloma multipla progressiva li ngħataw mill- inqas terapija waħda qabel u li diġà kollhom trapjant tal- mudullun jew ma jistgħux jagħmlu dan it- trapjant.
Treatment must be initiated and administered under the supervision of a physician qualified and experienced in the use of chemotherapeutic agents.
Il- kura għandha tinbeda u tingħata taħt is- superviżjoni ta 'tabib kwalifikat u bl- esperjenza fl- użu ta' sustanzi kemoterapewtiċi.
Posology for monotherapy The recommended starting dose of bortezomib is 1.3 mg/ m2 body surface area twice weekly for two weeks (days 1, 4, 8, and 11) followed by a 10-day rest period (days 12-21).
Pożoloġija għal monoterapija Id- doża tal- bidu rakkomandata ta 'bortezomib hija ta' 1. 3 mg/ m2 ta 'l- erja tas- superfiċje tal- ġisem darbtejn fil- ġimgħa għal ġimgħatejn (jiem 1, 4, 8, u 11), u wara jkun hemm perijodu ta' mistrieħ ta '10 ijiem (jiem 12- 21).
This 3-week period is considered a treatment cycle.
Dan il- perijodu ta '3 ġimgħat jitqies bħala ċiklu ta' kura.
At least 72 hours should elapse between consecutive doses of VELCADE.
Iridu jgħaddu mill- inqas 72 siegħa bejn żewġ dożi wara xulxin ta 'VELCADE.
It is recommended that patients with a confirmed complete response receive 2 additional cycles of VELCADE beyond a confirmation.
Huwa rakkomandat li pazjenti li jkollhom rispons sħiħ konfermat jirċievu żewġ ċikli oħra ta 'VELCADE wara l- konferma.
It is also recommended that responding patients who do not achieve a complete remission receive a total of 8 cycles of VELCADE therapy.
Huwa rakkomandat ukoll li pazjenti li jkollhom rispons imma li ma jkollhomx fejqan sħiħ mill- marda jirċievu 8 ċikli oħra ta 'kura b' VELCADE.
Currently there are limited data concerning re-treatment with VELCADE.
Bħalissa hemm tagħrif limitat dwar trattament mill- ġdid b' VELCADE.
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).
Bidliet fid- doża waqt il- kura u meta l- kura terġa 'tinbeda bħala monoterapija Il- kura b’ VELCADE trid tieqaf mill- bidu jekk ikun hemm xi tossiċitajiet mhux ematoloġiċi ta' Grad 3 jew ematoloġiċi ta 'Grad 4, ħlief għan- newropatija kif imfisser hawn taħt (ara wkoll sezzjoni 4. 4).
Once the symptoms of the toxicity have resolved, VELCADE treatment may be re-initiated at a 25% reduced dose (1.3 mg/ m2 reduced to 1.0 mg/ m2; 1.0 mg/ m2 reduced to 0.7 mg/ m2).
Meta s- sintomi tat- tossiċità jkunu marru, il- kura b' VELCADE tista terġa tibda tingħata b' doża mnaqqsa b' 25% (1. 3 mg/ m2 imnaqqsa għal 1. 0 mg/ m2; 1. 0 mg/ m2 imnaqqsa għal 0. 7 mg/ m2).
If the toxicity is not resolved or if it recurs at the lowest dose, discontinuation of VELCADE must be considered unless the benefit of treatment clearly outweighs the risk.
Jekk it - tossiċità ma tmurx jew jekk terġa 'tidher bl- iċken doża, għandu jitqies li ma titkompliex il- kura b' VELCADE sakemm il- benefiċċji tal- kura ma jkunux jegħlbu b' mod ċar ir- riskji.
2 Patients who experience bortezomib-related neuropathic pain and/ or peripheral neuropathy are to be managed as presented in Table 1 (see section 4.4).
2 Pazjenti li jkollhom uġigħ newropatiku u/ jew newropatija periferali relatati ma 'bortezomib għandhom ikunu trattati skond Tabella 1 (ara sezzjoni 4. 4).
Patients with pre-existing severe neuropathy may be treated with VELCADE only after careful risk/ benefit assessment.
Pazjenti li kellhom newropatija qawwija minn qabel jistgħu jiġu kkurati b' VELCADE wara li jitqiesu sew ir- riskji u l- benefiċċji.
Severity of neuropathy Grade 1 (paraesthesia, weakness and/ or loss of reflexes) with no pain or loss of function
Bidliet rakkomandati * fil- pożoloġija għal newropatija marbuta ma 'bortezomib Qawwa tan- newropatija Grad 1 (parestesija, dgħjufijau/ jew telfien tar - riflessi) bla uġigħ jew telfien ta ’ funzjoni Grad 1 bl- uġigħ jew Grad 2 (jinterferixxi fil - funzjoni imma mhux fl- attivitajiet tal- ħajja ta ’ kuljum)
Grade 1 with pain or Grade 2 (interfering with function but not with activities of daily living)
Bidla fil- pożoloġija Ma titteħidx azzjoni Naqqas għal 1. 0 mg/ m2
Grade 2 with pain or Grade 3 (interfering with activities of daily living)
Grad 2 bl- uġigħ jew Grad 3 (jinterferixxi fl - attivitajiet tal- ħajja ta ’ kuljum)
Withhold VELCADE treatment until symptoms of toxicity have resolved.
Waqqaf il- kura b’ VELCADE sakemm is- sintomi tat- tossiċità jgħaddu.
When toxicity resolves re-initiate VELCADE treatment and reduce dose to 0.7 mg/ m2 and change treatment schedule to once per week.
Meta t- tossiċità tgħaddi erġa 'ibda l- kura b’ VELCADE u naqqas id- doża għal 0. 7 mg/ m2 u biddel l- iskeda tal- kura darba fil- ġimgħa.
Grade 4 (sensory neuropathy which is disabling or motor neuropathy that is life threatening or leads to paralysis) and/ or severe autonomic neuropathy
Grad 4 (newropatija sensorjali inkapaċitanti jew Waqqaf VELCADE newropatija motorja li thedded il- ħajja jew twassal għal paraliżi) u/ jew newropatija awtonomika * Ibbażati fuq bidliet fil- pożoloġija fi studji ta ’ Fażi II u III ta 'majloma multipla u fl- esperjenza wara li l- prodott tħalla fis- suq.
Paediatric patients VELCADE is not intended for use in children below 18 due to lack of data on safety and efficacy (see sections 5.1 and 5.2).
Pazjenti tfal VELCADE mhux irrakkomandat għall- użu fit- tfal ta ’ taħt it- 18- il sena peress li m’ hemmx biżżejjed informazzjoni dwar is- sigurtà u l- effikaċja (ara sezzjonijiet 5. 1 u 5. 2).
Elderly patients There is no evidence to suggest that dose adjustments are necessary in the patients over 65 years of age (see section 4.8).
Pazjenti anzjani M' hemmx evidenza li tindika li hemm bżonn ta 'bidliet fid- doża għall- pazjenti li għandhom aktar minn 65 sena (ara sezzjoni 4. 8).
Renal impairment The pharmacokinetics of bortezomib are not influenced in patients with mild to moderate renal impairment (CrCL (Creatinine Clearance) > 20 ml/ min/ 1.73 m2); therefore, dose adjustments are not necessary for these patients.
Indeboliment tal- kliewi Il- farmakokinetika ta ’ bortezomib m’ hijiex influwenzata f’ pazjenti b’ indeboliment tal- kliewi ħafif sa moderat (CrCl (clearance tal- kreatinina) > 20 ml/ min/ 1. 73 m2); għalhekk aġġustamenti tad- doża m’ humiex meħtieġa għal dawn il- pazjenti.
It is unknown if the pharmacokinetics of bortezomib are influenced in patients with severe renal impairment not undergoing dialysis (CrCL < 20 ml/ min/ 1.73 m2).
M’ huwiex magħruf jekk il- farmakokinetika ta ’ bortezomib hijiex influwenzata f’ pazjenti b’ indeboliment qawwi tal- kliewi li mhumiex qegħdin fuq id- dijalisi (CrCl < 20 ml/ min/ 1. 73 m2).
Since dialysis may reduce bortezomib concentrations, VELCADE should be administered after the dialysis procedure (see section 5.2).
Minħabba li d- dijalisi tista ’ tnaqqas il- konċentrazzjonijiet ta ’ bortezomib, VELCADE għandu jingħata wara l- proċedura tad- dijalisi (ara sezzjoni 5. 2).
Hepatic impairment VELCADE has not been studied in patients with impaired hepatic function.
Indeboliment tal- fwied VELCADE ma ġiex studjat f' pazjenti b’ indeboliment tal- fwied.
Significant hepatic impairment may have an impact on the elimination of bortezomib and may increase the likelihood of interactions with other active substances.
Indeboliment sinifikanti fil- fwied jista 'jeffettwa t- tneħħija ta' bortezomib u jista 'jkabbar il- possibilità ta' interazzjonijiet ma sustanzi attivi oħra.
Patients with impaired liver function should be treated with extreme caution and a dose reduction should be considered (see sections 4.3 and 4.4).
Pazjenti bi ħsara fil- fwied għandha tingħatalhom kura b' kawtela kbira u għandu jitqies tnaqqis fid- doża (ara sezzjonijiet 4. 3 u 4. 4).
Posology for 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.
Pożoloġija għal terapija mħallta VELCADE (bortezomib) jingħata flimkien ma ’ melphalan mill- ħalq u prednisone mill- ħalq għal disa ’ ċikli ta ’ kura ta ’ 6 ġimgħat ’ il wieħed kif muri f’ Tabella 2.
In Cycles 1-4, VELCADE is administered twice weekly (days 1, 4, 8, 11, 22, 25, 29 and 32).
Fiċ- Ċikli 1- 4, VELCADE jingħata darbtejn fil- ġimgħa (jiem1, 4, 8, 11, 22, 25, 29 u 32).
In Cycles 5-9, VELCADE is administered once weekly (days 1, 8, 22 and 29).
Fiċ- Ċikli 5- 9, VELCADE jingħata darba fil- ġimgħa (jiem 1, 8, 22 u 29).
Melphalan and prednisone should both be given orally on days 1, 2, 3 and 4 of the first week of each cycle.
Kemm melphalan kif ukoll prednisone għandhom jingħataw mill- ħalq fil- ġranet 1, 2, 3 u 4 tal- ewwel ġimgħa ta ’ kull ċiklu.
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)
3 Tabella 2: Pożologija rrakkommandata għal VELCADE flimkien ma ’ melphalan u prednisone għall- pazjenti b’ majloma multipla li qatt ma kienet ikkurata qabel VELCADE Darbtejn fil- Ġimgħa (Ċikli 1- 4)
3
Vc (1. 3 mg/ m2)
Day
Jum 1
11 period
Jum Jum Jum Perjod 4 8 11
22
Jum Jum Jum Jum u ta ’ 22 25 29 32
period
Perjodu ta ’
M (9 mg/ m2)
mistrie ħ
Day
mistrieħ
Day Day Day
Jum Jum Jum Jum
rest -- -- --
Perjod -- -- --
rest
Perjodu
P (60 mg/ m2)
M (9 mg/ m
1 2 3 4 period
2)
2) 1 2
1 2
period
u ta ’
period
ta ’
Week
mistrieħ
1
5- 9)
2
Ġimgħa
Vc
Vc (1. 3 mg/ m2)
Day 22
Jum Perjo Jum Jum 8 du ta ’ 22 29 mistri eħ
Day 29
Perjodu ta ’ mistrieħ
rest
Jum Jum
1.3 mg/ m2)
Jum Jum
period
-- Perjo -- --
Day 1
1
Day Day Day 2 3 4
2 3
rest -- period
du ta ’ mistri eħ
rest period
mistrieħ
Vc = VELCADE; M = melphalan, P=prednisone
Vc = VELCADE; M = melphalan, P=prednisone
Dose adjustments for combination therapy
Aġġustamenti fid- doża għal terapija mħallta
Dose modification and re-initiation of therapy when VELCADE is administered in combination with melphalan and prednisone
Modifikazzjoni fid- doża u bidu mill- ġdid tat- terapija meta VELCADE jiġi amministrat flimkien ma ’ melphalan u prednisone
Prior to initiating a new cycle of therapy: • Platelet counts should be ≥ 70 x 109/ l and the absolute neutrophils count should be ≥ 1.0 x 109/ l • Non-haematological toxicities should have resolved to Grade 1 or baseline
Qabel ma jinbeda ċiklu ġdid ta ’ terapija: • L- għadd tal- plejtlits għandu jkun ta ’ ≥70 x 109/ l u l- għadd assolut ta ’ newtrofils għandu jkun ≥ 1. 0 x 109/ l • Tossiċitajiet mhux ematoloġiċi għandhom jkunu rrisolvew għal Grad 1 jew għall- linja bażi
Table 3: Posology modifications during subsequent cycles:
Tabella 3: Modifikazzjonijiet fil- pożoloġija waqt ċikli sussegwenti:
Toxicity Haematological toxicity during a cycle
Tossiċità Tossiċità ematoloġika waqt ċiklu
Posology modification or delay
Modifikazzjoni fil- pożoloġija jew dewmien
• If prolonged Grade 4 neutropenia or thrombocytopenia, or thrombocytopenia with bleeding is observed in the previous cycle
• Jekk tiġi osservata newtropenja jew tromboċitopenja tal- ġrad 4 li tieħu fit- tul, jew tiġi osservata tromboċitopenja bil - fsada fiċ- ċiklu ta ’ qabel Jekk l- għadd tal- plejtlits ikun ≤30 × 109/ l
Consider reduction of the melphalan dose by 25% in the next cycle.
Ikkunsidra tnaqqis ta ’ 25% mid- doża ta ’ melphalan fiċ- ċiklu li jmiss.
• If platelet counts ≤ 30 × 109/ l or ANC ≤ 0.75 x 109/ l on a VELCADE dosing day (other than Day 1)
• jew l- ANC ikun ≤0. 75 x 109/ l fil- jum meta jmiss doża ta ’ VELCADE (sakemm ma jkunx l- 1 Jum)
VELCADE therapy should be withheld
Il- kura b’ VELCADE m’ għandiex tingħata
• If several VELCADE doses in a cycle are withheld (≥ 3 doses during twice weekly administration or ≥ 2 doses during weekly administration)
• Jekk ħafna mid- dożi ta ’ VELCADE f’ ċiklu ma jingħatawx (≥ 3 dożi waqt l - għoti ta ’ darbtejn fil- ġimgħa jew ≥ 2 dożi waqt l- għoti ta ’ darba fil- ġimgħa)
VELCADE dose should be reduced by 1 dose level (from 1.3 mg/ m2 to 1 mg/ m2, or from 1 mg/ m2 to 0.7 mg/ m2) VELCADE therapy should be withheld until
Id- doża ta ’ VELCADE għandha titnaqqas b’ livell 1 ta ’ doża (minn 1. 3 mg/ m2 sa 1 mg/ m2, jew minn 1 mg/ m2 sa 0. 7 mg/ m2)
Grade ≥ 3 non-haematological toxicities
Tossiċitajiet mhux ematoloġiċi tal- grad ≥ 3
symptoms of the toxicity have resolved to Grade 1 or baseline.
Terapija b’ VELCADE għandha titwaqqaf sakemm is- sintomi tat- tossiċità jkunu rrisolvew għal Grad 1 jew għal- linja bażi.
Then, VELCADE may be reinitiated with one dose level reduction (from 1.3 mg/ m2 to 1 mg/ m2, or from 1 mg/ m2 to 0.7 mg/ m2).
Imbaghad VELCADE jista ’ jerġa ’ jinbeda bi tnaqqis ta ’ livell 1 tad- doża (minn 1. 3 mg/ m2 sa 1 mg/ m2, jew minn 1 mg/ m2 sa 0. 7 mg/ m2).
For VELCADE-related neuropathic pain and/ or peripheral neuropathy, hold and/ or modify VELCADE as outlined in Table 1.
Għal uġigħ newropatiku relatat ma ’ VELCADE u/ jew newropatija periferali, waqqaf u/ jew immodifika VELCADE kif deskritt f’ Tabella 1.
For additional information concerning melphalan and prednisone, see the corresponding Summary of Product Characteristics.
Għal aktar informazzjoni dwar melphalan u prednisone, ara s- Sommarju tal- Karatteristiċi tal- Prodott tagħhom.
Method of administration The reconstituted solution is administered as a 3-5 second bolus intravenous injection through a peripheral or central intravenous catheter followed by a flush with sodium chloride 9 mg/ ml (0.9%) solution for injection.
Metodu ta ’ kif jingħata Is- soluzzjoni rikostitwita tingħata bħala injezzjoni f’ daqqa ġol- vina fi 3- 5 sekondi minn kateter periferali jew ċentrali ġol- vina segwit minn tlaħliħa b’ soluzzjoni għall- injezzjoni ta ’ sodium chloride 9 mg/ ml (0. 9%).
4 4.3 Contraindications
4. 3 Kontra- indikazzjonijiet
Hypersensitivity to bortezomib, boron or to any of the excipients.
Sensittività eċċessiva għal bortezomib, boron jew għal xi wieħed mis- sustanzi mhux attivi.
Severe hepatic impairment (see section 4.4).
Indeboliment sever tal- fwied (ara sezzjoni 4. 4).
Acute diffuse infiltrative pulmonary and pericardial disease.
Mard akut difuż infiltrattiv pulmonari u perikardjali.
Gastrointestinal toxicity Gastrointestinal toxicity, including nausea, diarrhoea, vomiting and constipation are very common with VELCADE treatment.
Tossiċità gastro- intestinali Tossiċità gastro- intestinali, inkluż nawżeja, dijarrea, rimettar u stitikezza huma komuni ħafna waqt kura b' VELCADE.
Cases of ileus have been uncommonly reported (see section 4.8); therefore patients who experience constipation should be closely monitored.
Ġew rappurtati każijiet b’ mod mux komuni ta 'sadd fil- musrana (ara sezzjoni 4. 8) għalhekk pazjenti li jkollhom stitikezza għandhom jiġu mmonitorjati bir- reqqa.
Haematological toxicity VELCADE treatment is very commonly associated with haematological toxicities (thrombocytopenia, neutropenia and anaemia).
Tossiċità ematoloġika Il- kura b' VELCADE ħafna drabi tiġi assoċjata ma 'tossiċitajiet ematoloġiċi (tromboċitopenja, newtropenija, anemija).
The most common haematologic toxicity is transient thrombocytopenia.
L- aktar tossiċità komuni hija tromboċitopenja li tgħaddi.
Platelets were lowest at Day 11 of each cycle of VELCADE treatment.
L- għadd tal- plejtlets huwa l- iktar baxx f’ Jum 11 ta ’ kull ċiklu tal- kura b’ VELCADE.
There was no evidence of cumulative thrombocytopenia, including in the Phase II extension study.
M’ hemmx evidenza ta ’ tromboċitopenja kumulattiva, inkluż f’ Fażi II ta ’ l- istudju ta ’ estensjoni.
The mean platelet count nadir measured was approximately 40% of baseline.
Il- medja ta ’ l- għadd l- iktar baxx tal- plejtlets kien bejn wieħed u ieħor 40% tal- linja bażi.
In patients with advanced myeloma the severity of thrombocytopenia was related to pre-treatment platelet count: for baseline platelet counts < 75,000/μ l, 90% of 21 patients had a count ≤ 25,000/ μ l during the study, including 14 %< 10,000/μl; in contrast, with a baseline platelet count > 75,000/μl, only 14% of 309 patients had a count ≤25×109/l during the study.
F’ pazjenti b’ majloma avvanzata s - severità tat- tromboċitopenja kienet marbuta ma ’ l- għadd tal- plejtlets qabel il- kura: għal għadd mil - linja bażi tal- plejtlets < 75, 000/ μl, 90% ta ’ 21 pazjenti kellhom għadd ≤25, 000/ μl waqt l- istudju, inkluż 14% < 10, 000/ μl; b’ kuntrast, b’ għadd mil- linja bażi > 75, 000/ μl, 14% biss minn 309 pazjenti kellhom għadd ≤25×109/ l waqt l- istudju.
Platelet counts should be monitored prior to each dose of VELCADE.
L- għadd tal- plejtlets għandu jiġi monitorjat qabel kull doża ta ’ VELCADE.
Therapy should be held when the platelet count is < 25,000/μ l and re-initiated at a reduced dose after resolution (see section 4.2).
Għandha titwaqqaf it- terapija meta l- għadd ta ’ plejtlets ikun < 25, 000/ μl u jerġa ’ jinbeda b’ doża mnaqqsa wara r- riżoluzzjoni (ara sezzjoni 4. 2).
Potential benefit of the treatment should be carefully weighed against the risks, particularly in case of moderate to severe thrombocytopenia and risk factors for bleeding.
Il- benefiċċju potenzjali tal- kura għandu jitqies b' reqqa mar- riskju, speċjalment fil- każ ta ’ tromboċitopenja moderata jew severa u l- fatturi ta ’ riskju għal fsad.
Therefore, complete blood counts (CBC) including platelet counts should be frequently monitored throughout treatment with VELCADE.
Għalhekk, l- għadd sħih tad- demm (CBC) inkluż l- għadd tal- plejtlets għandu jiġi monitorjat b’ mod frekwenti matul il- kura b’ VELCADE.
Peripheral neuropathy Treatment with VELCADE is very commonly associated with peripheral neuropathy, which is predominantly sensory.
Newropatija periferali Il- kura b' VELCADE ħafna drabi tiġi assoċjata ma 'newropatija periferali, l- iktar dik sensorjali.
However, cases of severe motor neuropathy with or without sensory peripheral neuropathy have been reported.
Madankollu, ġew rappurati każijiet ta 'newropatija motorja severa b’ newropatija sensorjali periferali
The incidence of peripheral neuropathy increases early in the treatment and has been observed to peak during cycle 5.
L- inċidenza tan- newropatija periferali tikber fil- bidu tal- kura u ġiet osservata li tilħaq quċċata fil- 5 ċiklu.
It is recommended that patients be carefully monitored for symptoms of neuropathy such as a burning sensation, hyperesthesia, hypoesthesia, paraesthesia, discomfort, neuropathic pain or weakness.
Huwa rakkomandat li l- pazjenti jiġu mmonitorjati b' reqqa għal sintomi ta 'newropatija bħal sensazzjoni ta' ħruq, iperestesija, ipoestesija, parestesija, skumdità u uġigħ newropatiku jew dgħjufija.
Patients experiencing new or worsening peripheral neuropathy should undergo neurological evaluation and may require the dose and schedule of VELCADE to be modified (see section 4.2).
(ara sezzjoni 4. 2).
Neuropathy has been managed with supportive care and other therapies.
In - newropatija ġiet ikkontrollata b' kura ta ’ support u terapiji oħra.
Improvement in, or resolution of, peripheral neuropathy was reported in 51% of patients with ≥ Grade 2 peripheral neuropathy in the single-agent Phase III multiple myeloma study and 71% of patients with grade 3 or 4 peripheral neuropathy or peripheral neuropathy leading to discontinuation of treatment in Phase II studies, respectively.
It- titjib u r- riżoluzzjoni ta ’ newropatija periferali kien irrapurtat 51% tal- pazjenti b ’ newropatija periferali ta ’ Grad 2 jew inqas f’ Fażi III ta ’ l - istudju ta ’ majloma mutipla b’ sustanza waħda u 71% tal- pazjenti b’ newropatija periferali ta ’ grad 3 jew 4 li wassal għal twaqqif tal- kura fi studji ta ’ Fażi II, rispettivament.
In addition to peripheral neuropathy, there may be a contribution of autonomic neuropathy to some adverse reactions such as postural hypotension and severe constipation with ileus.
Apparti n- newropatija periferali, in- newropatija awtonomika tista 'tikkontribwixxi wkoll għal xi reazzjonijiet negattivi bħal m' hi ipotensjoni tal- qagħda u stitikezza qawwija b' sadda fil- musrana.
Information on autonomic neuropathy and its contribution to these undesirable effects is limited.
Informazzjoni dwar newropatija awtonomika u l- kontribut tagħha għal dawn l- effetti mhux mixtieqa hija limitata.
5 Seizures Seizures have been uncommonly reported in patients without previous history of seizures or epilepsy.
Attakki ta ’ puplesija Attakki ta 'puplesija ma tantx ġew rappurtati f' pazjenti li ma kellhomx diġa` storja ta' attakki ta 'puplesija jew epilessija.
Special care is required when treating patients with any risk factors for seizures.
Għandha tingħata attenzjoni speċjali waqt kura ta ’ pazjenti li għandhom fatturi ta 'riskju għal attakki ta ’ puplesija.
Hypotension VELCADE treatment is commonly associated with orthostatic/ postural hypotension.
Ipotensjoni Il- kura b' VELCADE ħafna drabi hija assocjata ma 'ipotensjoni ortostatika/ tal- qagħda.
Most undesirable effects are mild to moderate in nature and are observed throughout treatment.
Il- biċċa l- kbira ta 'l- effetti mhux mixtieqa huma minn ħfief għal moderati u jseħħu matul il- kura kollha.
Patients developing orthostatic hypotension on VELCADE did not have evidence of orthostatic hypotension prior to treatment with VELCADE.
Pazjenti li kellhom ipotensjoni ortostatika b 'VELCADE ma kellhomx ipotensjoni ortostatika qabel ma kienu bdew il- kura b' VELCADE.
Most patients required treatment for their orthostatic hypotension.
Il- biċċa l- kbira tal- pazjenti kellhom bżonn kura farmakoloġika minħabba ipotensjoni ortostatika.
A minority of patients with orthostatic hypotension experienced syncopal events.
Minoranza ta 'pazjenti b' ipotensjoni ortostatika kellhom episodji fejn intilfu minn sensihom.
Orthostatic/ postural hypotension was not acutely related to bolus infusion of VELCADE.
L- ipotensjoni ortostatika/ tal- qagħda ma kinitx relatata b' mod akut ma 'infużjoni f' daqqa ta' VELCADE.
The mechanism of this event is unknown although a component may be due to autonomic neuropathy.
Il- mekkaniżmu ta 'dan l- episodju mhux magħruf għalkemm parti minnu tista' tkun in- newropatija awtonomika.
Autonomic neuropathy may be related to bortezomib or bortezomib may aggravate an underlying condition such as diabetic or amyloidotic neuropathy.
In- newropatija awtonomika jista 'jkollha x' taqsam ma' bortezomib, jew bortezomib jista 'jħarrax kondizzjonijiet oħra li jkun hemm bħal newropatija dijabetika jew amilojdotika.
Caution is advised when treating patients with a history of syncope receiving medicinal products known to be associated with hypotension; or who are dehydrated due to recurrent diarrhoea or vomiting.
Pazjenti li fil- passat intilfu minn sensihom għandhom jiġu kkurati b' kawtela meta jkunu qed jingħataw prodotti mediċinali li huma magħrufin li huma assoċjati ma ’ l- ipotensjoni; dan jgħodd ukoll għal pazjenti li huwa disidratati minħabba dijarrea jew rimettar rikorrenti.
Management of orthostatic/ postural hypotension may include adjustment of antihypertensive medicinal products, rehydration or administration of mineralocorticosteroids and/ or sympathomimetics.
Il- kura ta ’ l - ipotensjoni ortostatika/ tal- qagħda tista 'tinkludi bdil fid- doża ta' prodotti mediċinali kontra l - ipertensjoni, reidratazzjoni jew l- amministrazzjoni ta 'mineralokortikosterojdi u/ jew simpatomimetiċi.
Patients should be instructed to seek medical advice if they experience symptoms of dizziness, light-headedness or fainting spells.
Il- pazjenti għandhom ikunu mgħarrfa li għandhom ifittxu parir mediku jekk ikollhom sturdament jew iħossu kollox idur bihom jew jintilfu minn sensihom.
Heart failure Acute development or exacerbation of congestive heart failure, and/ or new onset of decreased left ventricular ejection fraction has been reported during bortezomib treatment.
Insuffiċjenza tal- qalb Ġie rappurtat l- iżvilupp akut jew it- tħarrix ta 'insuffiċjenza tal- qalb konġestiva u/ jew insuffiċjenza tat - tfigħ ‘ il- barra ventrikolari tax- xellug waqt il- kura b' bortezomib.
In a single agent Phase III randomised, comparative study the incidence of heart failure in the VELCADE group was similar to that in the dexamethasone group.
Fi studju randomised komparattiv ta ’ Fażi III b’ sustanza waħda l- inċidenza ta ’ insuffiċjenza tal- qalb fil- grupp li kien qed jieħu VELCADE huwa simili għall- grupp li kien qed jieħu dexamethasone.
Fluid retention may be a predisposing factor for signs and symptoms of heart failure.
Iż- żamma tal- fluwidu jista 'jippredisponi għal sinjali u sintomi ta' attakk ta 'qalb.
Patients with risk factors for or existing heart disease should be closely monitored.
Għandha ssir attenzjoni partikolari lil pazjenti b’ fatturi ta ’ riskju ta ’ mard tal- qalb jew li diġà għandhom din il- marda
ECG investigations There have been isolated cases of QT-interval prolongation in clinical studies, causality has not been established.
Investigazzjonijiet ta ’ l- ECG Fi studji kliniċi kien hemm każijiet iżolati ta ’ prolungament ta ’ l- intervall QT, imma l- kawża ma ġietx stabbilita.
Pulmonary disorders There have been rare reports of acute diffuse infiltrative pulmonary disease of unknown aetiology such as pneumonitis, interstitial pneumonia, lung infiltration, and acute respiratory distress syndrome (ARDS) in patients receiving VELCADE (see section 4.8).
Distubi fil- pulmun Kien hemm rapporti rari ta ’ mard pulmonari akut infiltrat b’ mod diffuż b’ etjoloġija mhix magħrufa bħal pulmonite, pulmonija interstitjali, infiltrazzjoni tal- pulmun, sindromue ta ’ għeja respiratorja akuta (ARDS) f’ pazjenti li kienu qed jieħdu VELCADE (ara sezzjoni 4. 8).
Some of these events have been fatal.
Xi wħud minn dawn l- episodji kienu fatali.
A pre-treatment chest radiograph is recommended to determine if any additional diagnostic measures are necessary and to serve as a baseline for potential post-treatment pulmonary changes.
Huwa rrakkomandat illi qabel it- trattament isir radjograf tas- sider sabiex jiġi stabbilit jekk
In the event of new or worsening pulmonary symptoms (e. g. cough, dyspnoea), a prompt diagnostic evaluation should be performed and patients treated appropriately.
Jekk ikun hemm sintomi pulmonari ġodda jew li qed jiħraxu (ngħidu aħna tqaħqiħ, dispnea), għandha ssir mal- ewwel evalwazzjoni djanjostika u l- pazjenti jingħataw l- kura meħtieġa.
The benefit/ risk ratio should be considered prior to continuing VELCADE therapy.
Għandha tingħata kunsiderazzjoni tal- proporzjon tal- benefiċċju/ riskju qabel ma titkompla t- terapija b’ VELCADE.
In a clinical trial, two patients (out of 2) given high-dose cytarabine (2 g/ m2 per day) by continuous infusion over 24 hours with daunorubicin and VELCADE for relapsed acute myelogenous leukaemia died of ARDS early in the course of therapy, and the study was terminated.
Fi prova klinika, żewġ pazjenti (minn 2) li ngħataw doża qawwija ta ’ cytarabine (2 g/ m2 kuljum) b’ infużjoni kontinwa matul 24 siegħa b’ daunorubicin u VELCADE għal episodju ġdid ta ’ lewkemija akuta majloġenuża mietu minħabba ARDS fil- bidu tat- terapija, u l- istudju twaqqaf.
Therefore, this specific regimen with concomitant administration with high-dose cytarabine (2 g/ m2 per day) by continuous infusion over 24 hours is not recommended.
Għalhekk, din il - kura partikolari li tingħata flimkien ma ’ doża qawwija ta ’ cytarabine (2 g/ m2 kuljum) b’ infużjoni kontinwa matul 24 siegħa mhix rakkomandata.
Renal impairment Renal complications are frequent in patients with multiple myeloma.
Indeboliment tal- kliewi Komplikazzjonijiet tal- kliewi huma frekwenti f' pazjenti b' majloma multipla.
Such patients should be monitored closely (see sections 4.2 and 5.2).
Dawn il- pazjenti għandhom jiġu mmonitorjati bir- reqqa (ara sezzjonijiet 4. 2 u 5. 2).
Hepatic impairment Patients with hepatic impairment should be treated with extreme caution and a dose reduction should be considered (see sections 4.2, 4.3 and 5.2).
Indeboliment tal- fwied Pazjenti b’ indeboliment tal- fwied għandha tingħatalhom kura b' kawtela kbira u għandu jitqies tnaqqis fid- doża (ara taqsimiet 4. 2, 4. 3 u 5. 2).
6 Hepatic reactions Rare cases of acute liver failure have been reported in patients receiving multiple concomitant medications and with serious underlying medical conditions.
Reazzjonjiet epatiċi Ġew irrapurtati każijiet rari ta ’ insuffiċjenza akuta tal- fwied f’ pazjenti li kienu qed jieħdu medikazzjoni multipla fl- istess ħin u b’ kondizzjonijiet mediċi serji sottostanti.
Other reported hepatic reactions include increases in liver enzymes, hyperbilirubinaemia, and hepatitis.
Reazzjonijiet epatiċi oħra li ġew irrapurtati jinkludu żidiet fl- enżimi tal- fwied, iperbilirubinemija, u epatite.
Such changes may be reversible upon discontinuation of bortezomib (see section 4.8).
Dawn il- bidliet jistgħu jkunu reversibbli meta jitwaqqaf bortezomib (ara sezzjoni 4. 8).
Tumour lysis syndrome Because bortezomib is a cytotoxic agent and can rapidly kill malignant plasma cells, the complications of tumour lysis syndrome may occur.
Sindromu tal- lijasi tat- tumur Billi bortezomib huwa sustanza ċitotossika u jista 'joqtol malajr iċ- ċelloli malinji tal- plażma, jista' jkun hemm komplikazzjonijiet tas- sindromu tal- lysis tat- tumur.
The patients at risk of tumour lysis syndrome are those with high tumour burden prior to treatment.
Il- pazjenti li għandhom riskju tas- sindromu tal- lysis tat- tumur huma dawk li l- iktar ikollhom tumur qabel il- kura.
These patients should be monitored closely and appropriate precautions taken.
Dawn il- pazjenti jridu jkunu mmonitorjati sew u jkunu jridu jittieħdu l- prekawzjonijiet neċessarji.
Amyloidosis The impact of proteasome inhibition by bortezomib on disorders associated with protein accumulation such as amyloidosis is unknown.
Amilojdożi Mhux magħruf l- impatt ta 'l- inibizzjoni ta' proteasome minn bortezomib f' mard marbut ma 'l - akkumulu tal- proteina bħal m' hi amilojdożi.
Caution is advised in these patients.
Għandha ssir attenzjoni ma 'dawn il- pazjenti.
Concomitant medicinal products Patients should be closely monitored when given bortezomib in combination with potent CYP3A4-inhibitors.
Prodotti mediċinali li jittieħdu miegħu Il- pazjenti għandhom jiġu mmonitorjati b' attenzjoni meta bortezomib jingħata flimkien ma 'inibituri qawwija ta' CYP3A4.
Caution should be exercised when bortezomib is combined with CYP3A4- or CYP2C19 substrates (see section 4.5).
Għandha ssir attenzjoni meta bortezomib jintuża ma 'sostrati ta' CYP3A4 jew CYP2C19 (ara sezzjoni 4. 5).
Normal liver function should be confirmed and caution should be exercised in patients receiving oral hypoglycemics (see section 4.5).
Għandu jiġi kkonfermat li l- fwied qed jaħdem tajjeb u għandha ssir attenzjoni ma 'pazjenti li qed jingħataw ipogliċemiċi orali (ara sezzjoni 4. 5).
Potentially immunocomplex-mediated reactions Potentially immunocomplex-mediated reactions, such as serum-sickness-type reaction, polyarthritis with rash and proliferative glomerulonephritis have been reported uncommonly.
Reazzjonijiet potenzjali medjati mill- immunocomplex Ġew irrapurtati b’ mod mhux komuni reazzjonijiet li potenzjalment huma medjati mill - immunocomplex, bħalm’ huma reazzjoni tat- tip tal- mard tas- serum, poliartrite b’ raxx u glomerulonefrite proliferattiva.
Bortezomib should be discontinued if serious reactions occur.
Jekk ikun hemm reazzjonijiet serji l- kura b’ Bortezomib għandha titwaqqaf.
In vitro studies indicate that bortezomib is a weak inhibitor of the cytochrome P450 (CYP) isozymes 1A2, 2C9, 2C19, 2D6 and 3A4.
Studji in vitro jindikaw li bortezomib huwa inibitur dgħajjef għall- iżożimi 1A2, 2C9, 2C19, 2D6 U 3A4 taċ- ċitokromju P450 (CYP).
Based on the limited contribution (7%) of CYP2D6 to the metabolism of bortezomib, the CYP2D6 poor metabolizer phenotype is not expected to affect the overall disposition of bortezomib.
Billi CYP2D6 ftit (7%) jikkontribwixxi għall- metaboliżmu ta '
An interaction study based on data from 12 patients, assessing the effect of ketoconazole, a potent CYP3A4 inhibitor, showed a bortezomib AUC mean increase of 35% (CI90% [1.032 to 1.772]).
Studju dwar interazzjoni bbażat fuq data minn 12 il- pazjent fejn ġie investigat l- effett ta ’ ketoconazole, inibitur potenti ta ’ CYP3A4, wera ’ żieda medja ta ’ 35% fil- AUC (CI90% [1. 032 to 1. 772]).
Therefore patients should be closely monitored when given bortezomib in combination with potent CYP3A4 inhibitors (e. g. ketoconazole, ritonavir).
Ghalhekk il- pazjenti għandhom jiġu monitorjati bir- reqqa meta jingħataw bortezomib flimkien ma ’ inibituri potenti CYP3A4 (ngħidu aħna ketoconazole, ritonavir).