qanastek/EMEA-V3 huggingface dataset:
Tablet coating:
Povidone, polysorbate 80, anhydrous lactose, lactose monohydrate, crospovidone, magnesium stearate Ir- Rita tal- Pillola:
Ink:
Titanium dioxide (E171), polysorbate 80, hypromellose, macrogol 400, carnauba wax Linka:
Shellac, propylene glycol, indigo carmine (E 132).
Shellac, propylene glycol, indigo carmine (E132).
What EVISTA looks like and contents of the pack EVISTA are white, oval, film coated tablets which are marked with the number 4165.
Id- Dehra ta ’ EVISTA u l- kontenuti tal- pakkett EVISTA huma pilloli bojod, ovali, miksija b’ rita u li għandhom in- numru 4165 stampat fuqhom.
They are packed in blisters or in plastic bottles.
Jiġu ġo folji jew fi fliexken tal- plastik.
The blister boxes contain 14, 28 or 84 tablets.
Il- kaxex tal- folji fihom 14, 28 jew 84 pilloli.
The bottles contain 100 tablets.
Il- fliexken huma ta ’ 100 pillola.
Not all pack sizes may be marketed.
Id- Detentur ta ’ l- Awtorizzazzjoni għat- tqegħid fis- Suq
Marketing Authorisation Holder Daiichi Sankyo Europe GmbH, Zielstattstrasse 48, D-81379 Munich, Germany.
Daiichi Sankyo Europe GmbH, Zielstattstrasse 48, D- 81379 Munich, Il- Ġermanja
- Lilly S. A., Avda. de la Industria 30, 28108 Alcobendas (Madrid), Spain.
Manifattur Lilly S. A., Avda. de la Industria 30, 28108 Alcobendas (Madrid), Spanja
26 For any information about this medicinal product, please contact the representative in your country:
26 Għal kull tagħrif dwar dan il- prodott mediċinali, jekk jogħġbok ikkuntattja lir- rapprezentant fil- pajjiż tiegħek:
Tel: +34 91 539 99 11 France Daiichi Sankyo France S. A. S.
Tel: +34 91 539 99 11
Tel: +351 21 4232010 România Medis, d. o. o., Slovenia Tel: +386 1 589 69 00 Slovenija Medis, d. o. o.
România Medis, d. o. o., Slovenia Tel: +386 1 589 69 00
This leaflet was last approved in:
Dan il- fuljett kien l- aħħar approvat f ’:
Detailed information on this medicine is available on the European Medicines Agency (EMEA) web site: http: / /www. emea. europa. eu
Informazzjoni dettaljata dwar din il- mediċina tinsab fuq il- website ta ’ l- Aġenzija Ewropeja dwar il - Mediċini (EMEA) http: // www. emea. europa. eu.
London, 24 April 2008 Doc.
Londra, 24 ta ’ April 2008 Dok.
QUESTIONS AND ANSWERS ON THE WITHDRAWAL OF A CHANGE TO THE MARKETING AUTHORISATION for EVOLTRA
MISTOQSIJA U TWEĠIBA DWAR L- IRTIRAR TA ’ MODIFIKA FL- AWTORIZZAZZJONI GĦAT- TQEGĦID FIS- SUQ għal EVOLTRA
International non-proprietary name (INN): clofarabine
Denominazzjoni Komuni Internazzjonali (DKI): klofarabina (clorafabine)
On 18 March 2008, Bioenvision Ltd, a wholly owned subsidiary of Genzyme Corporation, officially notified the Committee for Medicinal Products for Human Use (CHMP) that it wishes to withdraw its application for a change to the marketing authorisation for Evoltra.
Fit- 18 ta ’ Marzu 2008, Bioenvision Ltd, kumpanija totalment sussidjarja ta ’ Genzyme Corporation, b’ mod uffiċjali għarrfet lill- Kumitat għall- Prodotti Mediċinali għall- Użu mill- Bniedem (CHMP) li tixtieq tirtira l- applikazzjoni tagħha għal modifika fl- awtorizzazzjoni għat- tqegħid fis- suq ta ’ Evoltra.
The change concerned an extension of indication to add the treatment of acute myeloid leukaemia in elderly patients.
Din il- modifika kienet tirrigwarda estensjoni ta ’ indikazzjoni sabiex tkun tinkludi t- trattamenti ta ’ lewċemija mjelojde akuta f’ pazjenti anzjani.
Evoltra was designated as an orphan medicine for this condition on 8 May 2003.
Evoltra kien ikkwalifikat bħala mediċina orfni għal din il - kondizzjoni fit- 8 ta ’ Mejju 2003.
What is Evoltra?
X' inhu Evoltra?
Evoltra is a concentrate that is made up into a solution for infusion (drip into a vein).
Evoltra huwa konċentrat li jitħallat biex isir soluzzjoni għall- infużjoni (dripp fil- vina).
It contains the active substance clofarabine.
Fih is- sustanza attiva klofarabina.
Evoltra is already used to treat children with acute lymphoblastic leukaemia (ALL, cancer of the lymphocytes, a type of white blood cell).
Evoltra diġà jintuża fit- trattament ta ’ tfal li jkollhom lewċemija akuta linfoblastika (ALL, kanċer tal - linfoċiti, tip ta ’ ċellola bajda tad- demm).
It is used when the disease has not responded to, or has come back (relapsed), after at least two other treatments, and when no other treatment is expected to work.
Jintuża meta ma jintwera l- ebda effett fil- marda, jew meta l - pazjent jirkadi, wara tal- anqas żewġ trattamenti oħra, u meta l- ebda trattament ieħor huwa mistenni li jaħdem.
What was Evoltra expected to be used for?
Għal xiex kien mistenni li jintuża Evoltra?
In the new indication, Evoltra was also expected to be used to treat patients aged over 65 years who have acute myeloid leukaemia (AML, cancer of the myeloid cells, a type of immature white blood cell).
Fl- indikazzjoni l- ġdida, Evoltra kien mistenni wkoll li jintuża fit- trattament ta ’ pazjenti ta ’ ‘ l fuq minn 65 sena li jkollhom lewċemija mjelojde akuta (AML, kanċer fiċ- ċelloli mjelojdi, tip ta ’ ċellola bajda tad- demm li tkun immatura).
It was to be used in patients who are not suitable for intensive chemotherapy, because they have certain genetic abnormalities in their myeloid cells, ‘ secondary’ AML (AML following a previous blood disorder) or another disease in addition to AML, or because they are 70 years of age or older.
Kellu jintuża f’ pazjenti li mhumiex adatti għall- kimoterapija, minħabba li jkollhom ċerti anomaliji ġenetiċi fiċ- ċelloli mjelojdi tagħhom, AML ‘ sekondarja ’ (AML wara problemi preċedenti fid- demm) jew marda oħra minbarra AML, jew minħabba li l- età tal- pazjent tkun 70 sena jew aktar.
How is Evoltra expected to work?
Kif kien mistenni li jaħdem Evoltra?
The active substance in Evoltra, clofarabine, is a cytotoxic (a medicine that kills cells that are dividing, such as cancer cells).
Is- sustanza attiva f’ Evoltra, klofarabina, hija ċitotossika (mediċina li toqtol iċ- ċelloli li jkunu qed jimmultiplikaw, bħaċ- ċelloli tal- kanċer).
It belongs to the group of anti-cancer medicines called ‘ antimetabolites’.
Tappartjeni għall- grupp ta ’ mediċini ta ’ kontra l- kanċer magħrufa bħala ‘ antimetaboliti ’.
Clofarabine is an analogue of adenine, which is part of the DNA, the fundamental genetic material of cells.
Klorafabina hija analogu tal- adenina, li hija parti mid- DNA, il - materjal ġenetiku fundamentali taċ- ċelloli.
In the body, clofarabine takes the place of adenine, and interferes with the enzymes involved in making genetic material.
Fil- ġisem, klofarabina tissostitwixxi l- adenina, u jinterferixxi mal- enzimi involuti fil- produzzjoni tal- materjal ġenetiku.
This stops the cells making new DNA and slows down the growth of tumour cells.
Dan iwaqqaf iċ- ċelloli milli jipproduċu DNA ġdid u jnaqqas ir- ritmu tat- tkabbir taċ- ċelloli tat- tumuri.
The company presented results from one main study involving 66 patients aged 65 years or older with AML, who had not been treated before and were considered to be unsuitable for intensive chemotherapy.
Il- kumpanija ppreżentat riżultati minn studju ewlieni li kien jinvolvi 66 pazjent ta ’ età ta ’ 65 sena jew aktar li kellhom AML, li qatt ma rċevew trattament qabel u li ma kinux ikkunsidrati idonei għal kimoterapija intensiva.
The study did not compare Evoltra with any other treatment.
L- istudju ma qabbilx Evoltra ma ’ trattament ieħor.
The main measure of effectiveness was the number of patients who went into ‘ remission’ (clearance of leukaemia from the bone marrow and complete or partial recovery of blood cell counts to normal levels).
Il- kejl ewlieni tal- effikaċja kien in- numru ta ’ pazjenti li esperjenzaw ‘ remissjoni ’ (meta titneħħa l- lewċemija mill- mudullun tal - għadam u l- irkupru komplet jew parzjali tal- livelli normali tal- għadd ta ’ ċelloli tad- demm).
What was the recommendation of the CHMP at that time?
X' kienet ir- rakkomandazzjoni tas- CHMP dak iż- żmien?
Based on the review of the data and the company’ s response to the CHMP list of questions, at the time of the withdrawal, the CHMP had some concerns and was of the provisional opinion that Evoltra could not have been approved for the treatment of the treatment of AML in elderly patients.
Skont l- analiżi tad- dejta u t- tweġiba tal- kumpanija għal- lista ta ’ mistoqsijiet tas- CHMP, fi żmien l - irtirar, is- CHMP kellu xi tħassib u kien tal- opinjoni provviżorja li Evoltra ma setax jiġi approvat għat - trattament ta ’ AML f’ pazjenti anzjani.
What were the main concerns of the CHMP?
X' kien it- tħassib ewlieni tas- CHMP?
The CHMP was concerned that the main study was not sufficient to establish the benefit of Evoltra in the treatment of AML in elderly patients who were unsuitable for intensive chemotherapy, and that the results of a study comparing Evoltra with standard treatment would be necessary to determine the medicine’ s effectiveness.
Is- CHMP kellu tħassib dwar il- fatt li l- istudju ewlieni ma kienx suffiċjenti għall- istabbiliment tal - benefiċċju ta ’ Evoltra fit- trattament ta ’ AML f’ pazjenti anzjani li ma kinux idonei għall- kimoterapija intensiva, u li r- riżultati ta ’ studju li qabbel Evoltra ma ’ trattament standard kienu ikun meħtieġa biex tiġi determinata l- effikaċja tal- mediċina.
The Committee was concerned that the main study included a number of patients who could have been suitable for intensive chemotherapy and this could have made the effectiveness of Evoltra look more promising.
Il- Kumitat kellu tħassib li l- istudju ewlieni inkluda għadd ta ’ pazjenti li setgħu kienu idonei għall- kimoterapija intensiva u dan seta ’ jwassal biex l- effikaċja ta ’ Evoltra tidher iktar promettenti.
There were also some concerns over the medicine’ s side effects affecting the kidneys.
Kien hemm xi tħassib ukoll dwar l- effetti sekondarji tal- mediċina, li kienu jaffettwaw il- kliewi.
Therefore, at the time of the withdrawal, the CHMP’ s view was that a benefit of Evoltra had not been sufficiently demonstrated and any benefits did not outweigh the identified risks.
Għalhekk, fi żmien l- irtirar, l- opinjoni tas- CHMP kienet li l- benefiċċju ta 'Evoltra ma kienx intwera biżżejjed u li kwalunkwe benefiċċji li seta' kellu ma kinux jegħlbu r- riskji identifikati.
The letter from the company notifying the EMEA of the withdrawal of the application is available here.
L- ittra mill- kumpanija li tgħarraf lill- EMEA dwar l- irtirar tal- applikazzjoni tista ’ tiġi kkonsultata hawn.
What are the consequences of the withdrawal for patients in clinical trials or compassionate use programmes using Evoltra?
X’ inhuma l- konsegwenzi tal- irtirar għal dawk il- pazjenti li jkunu qegħdin jagħmlu provi kliniċi jew programmi ta ’ użu b’ kumpassjoni bl- użu ta ’ Evoltra?
The company informed the CHMP that this withdrawal has no consequences for patients enrolled in clinical trials or compassionate use programmes with Evoltra.
Il- kumpanija għarrfet lis- CHMP li dan l- irtirar ma kellux konsegwenzi għall- pazjenti li jkunu għaddejjin minn provi kliniċi jew programmi ta ’ użu b’ kumpassjoni b’ Evoltra.
If you are in a clinical trial or compassionate use programme and need more information about your treatment, contact the doctor who is giving it to you.
Jekk inti qed tieħu sehem fi prova klinika jew fi programm ta 'użu b’ kumpassjoni u tixtieq iżjed tagħrif dwar it- trattament tiegħek, ikkuntattja lit- tabib li jkun qed jagħtik dan it- trattament.
What is happening for Evoltra for treatment of ALL in children?
X’ qiegħed jiġri dwar l- użu ta ’ Evoltra fit- trattament ta ’ tfal bi ALL?
There are no consequences on the use of Evoltra in the authorised indication, for which the balance of benefits and risks remains unchanged.
Ma hemm l- ebda konsegwenza fuq l- użu ta ’ Evoltra fl- indikazzjoni awtorizzata, fejn il- bilanċ bejn il - benefiċċju u r- riskju jibqa ’ invarjat.
What is Evoltra?
X’ inhu Evoltra?
Evoltra is a concentrate that is made up into a solution for infusion (drip into a vein).
Evoltra huwa konċentrat li huwa magħmul f’ soluzzjoni għal infużjoni (dripp f’ vina).
It contains the active substance clofarabine.
Fih is- sustanza attiva clofarabine.
What is Evoltra used for?
Għalxiex jintuża Evoltra?
Evoltra is used to treat children with acute lymphoblastic leukaemia (ALL), which is a cancer of the lymphocytes (a type of white blood cell).
Evoltra jintuża biex jikkura tfal b’ lewkimja limfoblastika akuta (ALL), li hija kanċer tal- limfoċiti (tip ta ’ ċelloli bojod tad- demm).
It is used when the disease has not responded to or has come back (relapsed) after at least two other treatments, and when no other treatment is expected to work.
Jintuża meta l- marda ma tkunx wieġbet għal jew tkun reġgħet feġġet (rikaduta) wara mill- inqas żewġ trattamenti oħra, u meta ebda trattament ieħor ma jkun mistenni li jaħdem.
Evoltra has been studied in patients less than 21 years old when they first became ill with ALL.
Evoltra ġie studjat f’ pazjenti iżgħar minn 21 sena meta jomordu għall- ewwel darba b’ ALL.
Because the number of patients with ALL is low, the disease is considered ‘ rare’, and Evoltra was designated an ‘ orphan medicine ’ (a medicine used in rare diseases) on 5 February 2002.
Minħabba li n- numru ta ’ pazjenti b’ ALL huwa wieħed baxx, il- marda hija meqjusa bħala ‘ rari ’, u Evoltra ġie denominat bħala ‘ mediċina orfni ’ (mediċina wżata f’ mard rari) fil- 5 ta ’ Frar 2002.
How is Evoltra used?
Kif jintuża Evoltra?
Evoltra treatment should be started and supervised by a doctor who has experience in the management of patients with acute leukaemia.
Il- kura b’ Evoltra għandha tinbeda u tiġi mmonitorjata minn tabib li jkollu esperjenza fil- ġestjoni ta ’ pazjenti b’ lewkimja akuta.
The recommended dose is 52 mg per square metre body surface area (calculated using the child ’ s height and weight).
Id- doża rakkomandata hija 52 mg għal kull metru kwadru tal- erja tas - superfiċje tal- ġisem (ikkalkulata permezz tat- tul u l- piż tat- tifel/ tifla).
It is given by infusion lasting two hours every day for five days.
Tingħata permezz ta ’ infużjoni li ddum sagħtejn kuljum għal ħames t’ ijiem.
The treatment should be repeated every two to six weeks.
It- trattament għandu jiġi rripetut kull ġimagħtejn sa sitt ġimgħat.
Most patients who respond to treatment do so after one or two treatment cycles.
Ħafna mill- pazjenti li wieġbu għat- trattament jagħmlu dan wara ċiklu wieħed jew tnejn tat - trattament.
How does Evoltra work?
Kif jaħdem Evoltra?
The active substance in Evoltra, clofarabine, is a cytotoxic (a medicine that kills cells that are dividing, such as cancer cells).
Is- sustanza attiva f’ Evoltra, clofarabine, hija ċitotossika (mediċina li toqtol ċelloli li qegħdin jinqasmu, bħal ċelloli tal- kanċer).
It belongs to the group of anti-cancer medicines called ‘ antimetabolites’.
Tappartieni għall- grupp ta ’ mediċini kontra l- kanċers imsejjaħ 'antimetaboliti ’.
Clofarabine is an ‘ analogue ’ of adenine, which is part of the fundamental genetic material of cells (DNA and RNA).
Clofarabine huwa analogue ta ’ adenine, li huwa parti mill- materjal ġenetiku fundamentali taċ- ċelloli (DNA u RNA).
This means that clofarabine takes the place of adenine in the body, and interferes with the enzymes involved in making genetic material, called ‘ DNA polymerase’ and ‘ RNA reductase’.
Dan ifisser illi clofarabine jissostitwixxi adenine, u jinterferixxi mal- enzimi involuti fl- għemil tal- materjal ġenetiku, imsejjaħ 'polymerase tad- DNA' u 'reductase tal- RNA ’.
This stops the cells making new DNA and RNA, and slows down the growth of tumour cells.
Dan iwaqqaf liċ- ċelloli milli jagħmlu DNA u RNA ġodda, u jnaqqas il- veloċità li biha jikbru ċ- ċelloli tat- tumuri.
How has Evoltra been studied?
Kif ġie studjat Evoltra?
The effects of Evoltra were first tested in experimental models before being studied in humans.
L- effetti ta ’ Evoltra ġew ittestjati għall- ewwel darba f’ mudelli esperimentali qabel ma ġew studjati fuq il- bnedmin.
Evoltra has been examined in one study of 61 patients below 21 years of age with ALL.
Il -
Reproduction is authorised provided the source is acknowledged. patients had previously received at least two other types of treatment but were not eligible for any other treatment.
© European Medicines Agency, 2009, Reproduction is authorised provided the source is acknowledged. pazjenti kollha kienu rċevew għallinqas żewġ tipi ta ’ trattamenti oħrajn qabel iżda ma kinux eleġibbli għal xi trattament ieħor.
The average age of the treated patients was 12 years.
L- età medja tal- pazjenti ttrattati kienet ta ’ 12- il sena.
The main measure of effectiveness was the number of patients who went into ‘ remission’ (clearance of leukaemia from the bone marrow and complete or partial recovery of blood cell counts to normal levels).
Il- miżura ewlenija tal - effikaċja kienet in- numru ta ’ pazjenti li marru f ’ ‘ remissjoni ’ (ħelsien mil- lewkimja mill- mudullun tal - għadam u rkupru sħiħ jew parzjali tal- għadd taċ- ċelloli tad- demm għal livelli normali).
The study did not compare Evoltra with any other treatments.
L- istudju ma qabbilx Evoltra ma ’ xi trattamenti oħrajn.
What benefit has Evoltra shown during the studies?
Liema benefiċċju wera Evoltra waqt l- istudji mwettqa?
In the main study, 20% of the patients went into remission (12 out of 61).
Fl- istudju prinċipali, 20% tal- pazjenti marru f’ remissjoni (12 minn 61).
Overall, the patients in the study survived for an average of 66 weeks.
B’ mod ġenerali, il- pazjenti fl - istudju għexu għal medja ta ’ 66 ġimgħa.
After treatment with Evoltra, 10 patients were able to go on to have a stem cell transplant.
Wara trattament b’ Evoltra, 10 pazjenti setgħu jgħaddu għat- trapjant taċ- ċelloli staminali.
This is a complex procedure where the bone marrow of the patient, including the leukaemia cells, is destroyed and replaced by stem cells that ‘ recolonise’ the bone marrow.
Din hija proċedura kumplessa fejn il- mudullun tal- għadam tal- pazjent, inkluż iċ- ċelloli tal- lewkimja, jinqered u jiġi ssostitwit minn ċelloli staminali li ‘ jirrikolonizzaw ’ il- mudullun tal- għadam.
Stem cells are very young cells that are normally made in the bone marrow and can develop into all of the different types of blood cell.
Ċelloli staminali huma ċelloli żgħar ħafna li normalment isiru fil- mudullun tal- għadam u jistgħu jiżviluppaw fit- tipi differenti kollha taċ- ċelloli tad- demm.
What is the risk associated with Evoltra?
X’ inhu r- riskju assoċjat ma ’ Evoltra?
In studies, the most common side effects with Evoltra (seen in more than 1 patient in 10) were febrile neutropenia (low white blood cell counts with fever), anxiety, headache, flushing (reddening of the face), vomiting, diarrhoea, nausea (feeling sick), dermatitis (inflammation of the skin), pruritus (itching), pyrexia (fever), mucosal inflammation (inflammation of the moist body surfaces, such as the lining of the mouth) and fatigue (tiredness).
Fl- istudji, l- iktar effetti sekondarji komuni b’ Evoltra (li dehru f’ aktar minn pazjenti 1 minn kull 10) kienu newtropenja bid- deni (għadd baxx ta ’ ċelloli tad- demm bojod b’ deni), ansjetà, uġigħ ta ’ ras, fwawar (ħmura tal- wiċċ), rimettar, dijarrea, nawsea (dardir), dermatite (infjammazzjoni tal- ġilda), prurite (ħakk), pireksja (deni), infjammazzjoni mukożali (infjammazzjoni tal- uċuh tal- ġisem niedjin, bħall- inforra tal- ħalq) u għejja.
For the full list of all side effects reported with Evoltra, see the Package Leaflet.
Għal- lista sħiħa tal- effetti sekondarji kollha rrapportati b’ Evoltra, jekk jogħġbok ara l- Fuljett ta ’ Tagħrif.
Evoltra should not be used in people who may be hypersensitive (allergic) to clofarabine or any of the other ingredients.
Evoltra ma għandux jintuża f’ nies li jistgħu jkunu ipersensittivi (allerġiċi) għal clofarabine jew għal xi sustanza oħra tiegħu.
Evoltra must not be given to patients with severe kidney or liver disease.
Evoltra ma għandux jingħata lil pazjenti b’ mard serju tal- kliewi jew tal- fwied.
Because Evoltra is a cytotoxic medicine, it should not be used during pregnancy unless absolutely necessary and breast-feeding should be stopped before, during and after treatment.
Minħabba li Evoltra huwa mediċina ċitotossika, ma għandux jintuża matul tqala sakemm dan ma jkunx assolutament neċessarju u t- treddigħ għandu jitwaqqaf, qabel, matul u wara t- trattament.
Why has Evoltra been approved?
Għaliex ġie approvat Evoltra?
Patients with ALL who have not responded to or who have relapsed after receiving at least two treatments have a very poor chance of survival.
Pazjenti b’ ALL li ma jkunux wieġbu għal jew li jkunu rkadew wara li rċevew għallinqas żewġ trattamenti għandhom ċans dgħajjef ferm ta ’ sopravivenza.
The Committee for Medicinal Products for Human Use (CHMP) concluded that Evoltra treatment may provide a way of obtaining remission, and of facilitating a stem cell transplant.
Il- Kumitat għal Prodotti Mediċinali għal Użu mill- Bniedem (CHMP) ikkonkluda li t- trattament b' Evoltra jista 'jipprovdi mod kif tinkiseb remissjoni, u kif jiġi ffaċilitat it- trapjant ta' ċelloli staminali.
The Committee decided that Evoltra’ s benefits are greater than its risks for the treatment of ALL in paediatric patients who have relapsed or are refractory after receiving at least two prior regimens and where there is no other treatment option anticipated to result in a durable response.
Il- Kumitat iddeċieda li l- benefiċċji ta ’ Evoltra huma ikbar mir- riskji tiegħu għat- trattament ta 'ALL f' pazjenti pedjatriċi li jkunu rkadew jew li huma rifrattorji wara li jirċievu għallinqas żewġ reġimens preċedenti u fejn ma jkun hemm ebda għażla oħra għal trattament li tkun mistennija li tirriżulta f’ rispons li jdum.
The Committee recommended that Evoltra be given marketing authorisation.
Il- Kumitat irrakkomanda li Evoltra jingħata awtorizzazzjoni għat- tqegħid fis- suq.
Evoltra has been authorised under ‘ Exceptional Circumstances’.
Evoltra ġie awtorizzat taħt ‘ Ċirkostanzi Eċċezzjonali ’.
This means that, because the disease is rare, it has not been possible to obtain complete information about Evoltra.
Dan ifisser li minħabba li l- marda hija rari, ma kienx possibbli li jinġabar it- tagħrif kollu dwar Evoltra.
What information is still awaited for Evoltra?
Liema informazzjoni għadha mistennija għal Evoltra?
The company that makes Evoltra will carry out a study to look at the use of Evoltra in patients with kidney disease, and set up a registry to monitor the medicine ’ s side effects.
Il- kumpanija li tagħmel Evoltra sejra twettaq studju sabiex tħares lejn l- użu ta ’ Evoltra f’ pazjenti b’ mard tal- kliewi, u sejra tistabbilixxi reġistru sabiex timmonitorja l- effetti sekondarji tal- mediċina.
Which measures are being taken to ensure the safe use of Evoltra?
Liema miżuri qed jittieħdu sabiex jiġi assigurat użu sigur għal Evoltra?
The company that makes Evoltra will make sure that doctors know about the best way to use Evoltra, and encourage them to use the registry for monitoring side effects.
Il- kumpanija li tagħmel Evoltra sejra tagħmel żgur li t- tobba jkunu jafu l- aqwa mod kif għandu jintuża Evoltra u tħeġġiġhom jużaw ir- reġistru għall- monitoraġġ tal- effetti sekondarji.
Other information about Evoltra:
Informazzjoni oħra dwar Evoltra:
The European Commission granted a marketing authorisation valid throughout the European Union for Evoltra on 29 May 2006.
Il- Kummissjoni Ewropea tat awtorizzazzjoni għat- tqegħid fis- suq valida madwar l- Unjoni Ewropea kollha għal Evoltra fid- 29 ta ’ Mejju 2006.
The marketing authorisation holder is Genzyme Europe B. V.
Id- detentur tal- awtorizzazzjoni għat- tqegħid fis- suq huwa Genzyme Europe B. V.
The summary of opinion of the Committee for Orphan Medicinal Products for Evoltra is available here.
2/ 3 Is- sommarju tal- opinjoni tal- Kumitat għal Prodotti Mediċinali Orfni għal Evoltra huwa disponibbli minn hawnhekk.
The full EPAR for Evoltra is available here.
L- EPAR sħiħ għal Evoltra jista ’ jiġi kkonsultat hawnhekk
This summary was last updated in 01-2009.
Dan is- sommarju ġie aġġornat l- aħħar fi 01- 2009
Evoltra 1 mg/ ml concentrate for solution for infusion
Evoltra 1 mg/ ml konċentrat għal solużjoni għall- infużjoni
Each ml of concentrate contains 1 mg of clofarabine.
Kull ml ta ’ konċentrat fih 1 mg ta ’ clofarabine.
Each 20 ml vial contains 20 mg of clofarabine.
Kull kunjett ta ’ 20 ml fih 20 mg ta ’ clofarabine.
Each 20 ml vial contains 180 mg of sodium chloride.
Kull kunjett ta ’ 20 ml fih 180 mg ta ’ sodium chloride.
Concentrate for solution for infusion (sterile concentrate).
Konċentrat għal soluzzjoni għall- infużjoni (konċentrat sterili)
Clear, practically colourless solution with a pH of 4.5 to 7.5 and an osmolarity of 270 to 310 mOsm/ l.
Soluzzjoni ċara prattikament bla kulur b’ pH ta ’ minn 4. 5 sa 7. 5 u ożmolarità ta ’ min 270 sa 310 mOsm/ 1.
Treatment of acute lymphoblastic leukaemia (ALL) in paediatric patients who have relapsed or are refractory after receiving at least two prior regimens and where there is no other treatment option anticipated to result in a durable response.
It- trattament ta ’ lewkimja akuta limfoblastika (ALL) f' pazjenti pedjatriċi li rkadew jew huma refrattarji wara li ngħataw qabel ta 'l- anqas żewġ reġimeni u fejn ma hemm l- ebda għażla għal trattament ieħor li kien antiċipat li jwassal għal rispons dewwiem.
Safety and efficacy have been assessed in studies of patients ≤ 21 years old at initial diagnosis (see section 5.1).
Is- sigurtà u l- effikaċja kienu assessjati fi studji ta ’ pazjenti ta ’ ≤ 21 sena fid- dijanjosi inizjali (ara sezzjoni 5. 1).
Therapy must be initiated and supervised by a physician experienced in the management of patients with acute leukaemias.
It- terapija trid tibda u tkun issorveljata minn tabib li għandu esperjenza fil- immaniġġjar ta 'pazjenti li għandhom lewkimji akuti.
Adults (including the elderly):
Adulti (inklużi anzjani):
There are currently insufficient data to establish the safety and efficacy of clofarabine in adult patients (see section 5.2).
Bħalissa m' hemmx tagħrif suffiċjenti biex tistabbilixxi s- sigurtà u l- effikaċja ta ’ clofarabine f’ pazjenti adulti (ara sezzjoni 5. 2).
The recommended dose is 52 mg/ m2 of body surface area administered by intravenous infusion over 2 hours daily for 5 consecutive days.
Id- doża rrakkomandata hi 52 mg/ m2 ta ’ l- erja tas- superfiċje tal- ġisem mogħtija b’ infużjoni għal ġol- vini fuq perijodu ta ’ 2 sigħat kuljum matul 5 ġranet konsekuttivi.
Body surface area must be calculated using the actual height and weight of the patient before the start of each cycle.
L- erja tas - superfiċje tal- ġisem tal- ġisem trid ikun ikkalkulata permezz ta ’ l- użu tat- tul u piż attwali tal- pazjent qabel il- bidu ta ’ kull ċiklu.
Treatment cycles should be repeated every 2 to 6 weeks (from the starting day of the previous cycle) following recovery of normal haematopoiesis (i. e.
Iċ- ċikli tat- trattament għandhom ikunu ripetuti minn kull 2 sa 6 ġimgħat (mill- ġurnata tal- bidu taċ- ċiklu ta 'qabel) wara l- irkupru ta' l- ematopojesi normali (i. e.
ANC ≥ 0.75 × 109/ l) and return to baseline organ function.
ANC ≥ 0. 75 × 109/ 1) u għandna mmorru lura għall- funzjoni organika tal- linja bażi.
A 25% dose reduction may be warranted in patients experiencing significant toxicities (see below).
Jista ’ jkun hemm bżonn ta ’ tnaqqis ta ’ 25% fid- doża f’ pazjenti li qegħdin jesperjenzaw tossiċitajiet sinifikanti (ara hawn taħt).
There is currently limited experience of patients receiving more than 3 treatment cycles (see section 4.4).
Bħalissa l- esperjenza dwar l- użu f' pazjenti li qed jirċievu aktar minn 3 ċikli ta 'trattament hi limitata (ara sezzjoni 4. 4).
The majority of patients who respond to clofarabine achieve a response after 1 or 2 treatment cycles (see section 5.1).
Il- biċċa l- kbira tal- pazjenti li jirrispondu għal clofarabine jirnexxilhom jirrispondu wara ċiklu wieħed jew 2 ta 'trattament (ara sezzjoni 5. 1).
Therefore, the potential benefit and risks associated with continued therapy in patients who do not show haematological and/ or clinical improvement after 2 treatment cycles should be assessed by the treating physician (see section 4.4).
Għalhekk, il- benefiċċju u r- riskji potenzjali assoċjati mat - terapija kontinwa f' pazjenti li ma juru l- ebda titjib ematoloġikali u/ jew kliniku wara 2 ċikli ta 'trattament għandhom ikunu assessjati mit- tabib kuranti (ara sezzjoni 4. 4).
Children (weighing < 20 kg):
2 Tfal (jiżnu < 20 kg):
An infusion time of > 2 hours should be considered to help reduce symptoms of anxiety and irritability, and to avoid unduly high maximum concentrations of clofarabine (see section 5.2).
Ħin ta ’ infużjoni ta ’ > 2 sigħat għandu jkun meqjus biex jgħin fit- tnaqqis ta ’ sintomi ta ’ ansjetà u irritabilità, u biex jiġu evitati konċentrazzjonijiet għoljin massimi ta ’ clofarabine (ara sezzjoni 5. 2).
2 Children (< 1 year old):
Tfal (< 1 sena):
There are no data on the pharmacokinetics, safety or efficacy of clofarabine in infants.
M' hemm l- ebda tagħrif dwar il- farmakokinetiċi, sigurtà jew l- effikaċja ta ’ clofarabine fit- trabi.
Therefore, a safe and effective dosage recommendation for patients (< 1 year old) has yet to be established.
Għalhekk għad trid tiġi stabbilita rakkomandazzjoni ta ’ dożaġġ sigur u effettiv f 'pazjenti (< 1 sena).
Patients with renal insufficiency:
Pazjenti b’ insuffiċjenza renali:
There is no experience in patients with renal insufficiency (serum creatinine ≥ 2 x ULN for age) and clofarabine is predominately excreted via the kidneys.
M’ hemmx esperjenza dwar l- użu f’ pazjenti li jbatu minn insuffiċjenza renali (kreatinina tas- serum ≥ 2 x ULN għall- età) u clofarabine fil- biċċa l- kbira tal- każi jitneħħa mill - kliewi.
Therefore, clofarabine is contraindicated in patients with severe renal insufficiency (see section 4.3) and should be used with caution in patients with mild to moderate renal insufficiency (see section 4.4).
Għalhekk, clofarabine hu kontra- indikat f’ pazjenti li jbatu minn insuffiċjenza severa renali (ara sezzjoni 4. 3) u għandu jintuża bir- reqqa f ’ pazjenti li jbatu minn insuffiċjenza renali bejn mhux qawwija u moderata (ara sezzjoni 4. 4).
To date, there are insufficient data on the pharmacokinetics of clofarabine in patients with decreased creatinine clearance to advise a dose reduction in such patients.
S’ issa, m’ hemmx tagħrif suffiċjenti dwar il- farmakokinetiċi ta ’ clofarabine f’ pazjenti li jesperjenzaw tneħħija mnaqqsa ta ’ kreatinina biex jista ’ jingħata parir li għandha titnaqqas id- doża fil- każ ta ’ dawn il- pazjenti.
However, these limited data indicate that clofarabine may accumulate in patients with decreased creatinine clearance (see sections 4.4 and 5.2).
Imma, dan it- tagħrif limitat jindika li clofarabine għandu mnejn jakkumula f’ pazjenti b’ tneħħija mnaqqsa ta ’ kreatinina (ara sezzjonijiet 4. 4 u 5. 2).
Patients with hepatic impairment:
Pazjenti li jbatu minn indeboliment epatiku:
There is no experience in patients with hepatic impairment (serum bilirubin > 1.5 x ULN plus AST and ALT > 5 x ULN) and the liver is a potential target organ for toxicity.
M’ hemmx esperjenza dwar l- użu f’ pazjenti li jbatu minn indeboliment epatiku (serum bilirubin > 1. 5 x ULN (il- limitu ta ’ fuq tan- normal) kif ukoll AST u ALT > 5 x ULN) u l- fwied hu organu potenzjali bersall għat- tossiċità.
Therefore, clofarabine is contraindicated in patients with severe hepatic impairment (see section 4.3) and should be used with caution in patients with mild to moderate hepatic impairment (see section 4.4).
Għalhekk, clofarabine hu kontra - indikat f’ pazjenti li jbatu minn insuffiċjenza epatika severa (ara sezzjoni 4. 3) u għandu jintuża bir - reqqa f’ pazjenti li jbatu minn insuffiċjenza epatika bejn mhux qawwi u moderata (ara sezzjoni 4. 4).
Dose reduction for patients experiencing haematological toxicities:
Tnaqqis fid- doża fil- każ ta ’ pazjenti li qed jesperjenzaw tossiċitajiet ematoloġikali:
If the ANC does not recover by 6 weeks from the start of a treatment cycle, a bone marrow aspirate / biopsy should be performed to determine possible refractory disease.
Jekk l- ANC ma jirkuprax sa 6 ġimgħat mill- bidu taċ- ċiklu ta 'trattament, aspirat/ biopsija tal- mudullun ta' l- għadma għandha ssir biex jiġi determinat jekk hemmx xi marda refrattarja.
If persistent leukaemia is not evident, it is recommended that the dose for the next cycle be reduced by 25% of the previous dose following recovery of ANC to ≥ 0.75 × 109/ l.
Jekk il- lewkimja persistenti mhix evidenti, hu rrakkomandat lid- doża għaċ- ċiklu li jmiss għandha titnaqqas b’ 25% tad- doża preċedenti wara l- irkuprar ta ’ l- ANC għal ≥ 0. 75 × 109/ l.
Should patients experience an ANC < 0.5 × 109/ l for more than 4 weeks from the start of the last cycle, it is recommended that the dose for the next cycle be reduced by 25%.
Jekk il- pazjenti jesperjenzaw ANC < 0. 5 × 109/ l għal aktar minn 4 ġimgħat mill- bidu ta 'l- aħħar ċiklu, hu rrakkomandat lid- doża għaċ- ċiklu li jmiss titnaqqas b' 25%.
Dose reduction for patients experiencing non-haematological toxicities:
Tnaqqis fid- doża fil- każ ta ’ pazjenti li qed jesperjenzaw tossiċitajiet non- ematoloġikali:
Infectious events:
Każijiet infettivi:
If a patient develops a clinically significant infection, clofarabine treatment may be withheld until the infection is clinically controlled.
Jekk pazjent jiżviluppa infezzjoni klinikalment sinifikanti, it- trattament b’ clofarabine jista ’ jitwaqqaf sakemm l- infezzjoni tkun ikkontrollata klinikalment.
At this time, treatment may be reinitiated at the full dose.
F’ dan il- perijodu, it- trattament jista ’ jerġa ’ jinbeda u tingħata d- doża sħiħa.
In the event of a second clinically significant infection, clofarabine treatment should be withheld until the infection is clinically controlled and may be reinitiated at a 25% dose reduction.
Jekk ikun hemm infezzjoni oħra sinifikanti klinikalment, it- trattament bil- clofarabine għandu jitwaqqaf sakemm l- infezzjoni tkun klinikalment ikkontrollata u tista ’ terġa 'tingħata bi tnaqqis fid- doża ta ’ 25%.
Non-infectious events:
Każijiet li mhumiex infettivi:
If a patient experiences one or more severe toxicities (US National Cancer Institute (NCI) Common Toxicity Criteria (CTC) Grade 3 toxicities excluding nausea and vomiting), treatment should be delayed until the toxicities resolve to baseline parameters or to the point where they are no longer severe and the potential benefit of continued treatment with clofarabine outweighs the risk of such continuation.
Jekk il- pazjent jesperjenza wieħed jew aktar tossiċitajiet severi (tossiċitajiet Grad 3 tal- Kriterja tat- Tossiċità Komuni (CTC) ta ’ l- Istitut Nazzjonali tal- Kanċer (NCI) ta ’ l- US u liema tossiċitajiet jeskludu dardir u ramettar); it- trattament għandu jkun postpost sakemm it - tossiċitajiet jirrisolvu sal- parametri tal- linjabażi jew sal- punt fejn ma għadhomx severi aktar u l - benefiċċji potenzjali tat- trattament kontinwu b’ clofarabine ikun akbar mir- riskju tat- tali kontinwazzjoni.
It is then recommended that clofarabine be administered at a 25% dose reduction.
Imbagħad hu rrakkomandat li clofarabine jingħata f’ livell ta ’ doża mnaqqsa b’ 25%.
Should a patient experience the same severe toxicity on a second occasion, treatment should be delayed until the toxicity resolves to baseline parameters or to the point where it is no longer severe and the potential benefit of continued treatment with clofarabine outweighs the risk of such continuation.
Jekk pazjent jesperjenza l- istess tossiċità severa fit- tieni okkażjoni, it- trattament għandu jkun postpost sakemm it- tossiċità tirrisolvi sal- parametri tal- linjabażi jew sal- punt sakemm ma tkunx aktar severa u l- beneficcju potenzjali tat- trattament kontinwu b‘ clofarabine ikun akbar mir- riskju ta ’ tali kontinwazzjoni.
It is then recommended that clofarabine be administered at a further 25% dose reduction.
Imbagħad hu rrakkomandat li clofarabine jingħata f’ livell ta ’ doża mnaqqsa bi 25% oħra.
Any patient who experiences a severe toxicity on a third occasion, a severe toxicity that does not recover within 14 days (see above for exclusions), or a life-threatening or disabling toxicity (US NCI CTC Grade 4 toxicity) should be withdrawn from treatment with clofarabine (see section 4.4).
3 tossiċità diżabbilanti (tossiċità Grad 4 ta ’ CTC tal- NCI ta ’ l- US) m’ għandux jibqa ’ jingħata trattament b’ clofarabine (ara sezzjoni 4. 4).
Method of administration:
Kif għandha tingħata:
Evoltra 1 mg/ ml concentrate for solution for infusion must be diluted prior to administration (see section 6.6).
Evoltra 1 mg/ ml konċentrat għal soluzzjoni għall- infużjoni għandha tkun dilwita qabel ma tingħata (ara sezzjoni 6. 6).
The recommended dosage should be administered by intravenous infusion although it has been administered via a central venous catheter in ongoing clinical trials.
Id- dożaġġ rrakkomandat għandu jingħata permezz ta 'infużjoni għal ġol- vini għalkemm kien mogħti permezz ta ’ kateter minn ġol- vina ċentrali f’ provi kliniċi kontinwi.
Evoltra must not be mixed with or concomitantly administered using the same intravenous line as other medicinal products (see section 6.2).
Evoltra ma għandhiex titħallat ma ’ jew tingħata fl- istess ħin permezz ta 'l- użu ta' l- istess linja minn ġol- vina ma ’ prodotti mediċinali oħra (ara sezzjoni 6. 2).
3 4.3 Contraindications
4. 3 Kontra- indikazzjonijiet
Hypersensitivity to clofarabine or to any of the excipients (see section 6.1).
Sensittività eċċessiva għal clofarabine jew għal kwalunkwe sustanza oħra mhux attiva (ara sezzjoni 6. 1).
Use in patients with severe renal insufficiency or severe hepatic impairment.
L- użu f’ pazjenti li għandhom insuffiċjenza renali severa jew indeboliment epatiku sever.
Breastfeeding should be discontinued prior to, during and following treatment with Evoltra (see section 4.6).
It- treddiegħ għandu jitwaqqaf qabel, matul u wara t- trattament b’ Evoltra (ara sezzjoni 4. 6).
Evoltra is a potent antineoplastic agent with potentially significant haematological and non-haematological adverse reactions (see section 4.8).
Evoltra hi aġent antineplastiku qawwi u għandha reazzjonijiet avversi ematoloġikali u non - ematoloġikali li huma potenzjalment sinifikanti (ara sezzjoni 4. 8).
The following parameters should, therefore, be closely monitored in patients undergoing treatment with clofarabine: • Complete blood and platelet counts should be obtained at regular intervals, more frequently in patients who develop cytopenias. • Renal and hepatic function prior to, during active treatment and following therapy.
Il- parametri li ġejjin għandhom, għalhekk, ikunu monitorjati bir- reqqa f’ pazjenti li jingħataw trattament b’ clofarabine: • Kownts kompleti tad- demm u l- plejtlits għandhom jittieħdu f’ intervalli regolari, aktar ta ’ spiss f’ pazjenti li jiżviluppaw ċitopenjas. • Il- funzjoni renali u epatika qabel, matul it- trattament attiv u wara t- terapija.
Clofarabine should be discontinued immediately if substantial increases in creatinine or bilirubin are observed. • Respiratory status, blood pressure, fluid balance and weight throughout and immediately after the 5 day clofarabine administration period.
Clofarabine għandu jitwaqqaf minnufih jekk ikunu osservati żidiet sostanzjali fil- kreatinina jew bil- bilirubin. • L- istatus respiratorju, pressjoni tad- demm, bilanċ tal- fluwidu u piż matul u immedjatament wara l - perijodu ta ’ 5 ġranet ta ’ għoti ta ’ clofarabine.
Patients undergoing treatment with clofarabine should be evaluated and monitored for signs and symptoms of tumour lysis syndrome and cytokine release (e. g. tachypnoea, tachycardia, hypotension, pulmonary oedema) that could develop into Systemic Inflammatory Response Syndrome (SIRS) / capillary leak syndrome or organ dysfunction (see section 4.8).
Pazjenti li qed jirċievu trattament b’ clofarabine għandhom ikunu evalwati u monitorjati għal sinjali u sintomi tas- sindrom tal- lysis tat- tumur u ħruġ ta ’ ċitokini (p. e. takipneja, takikardja, ipotensjoni, odema pulmonari) li jistgħu jiżviluppaw f’ Sindrom ta ’ Rispons Infjammatorju Sistemiku (SIRS) / sindrom ta ’ nixxija kapillari jew disfunzjoni organika (ara sezzjoni 4. 8).
Clofarabine should be discontinued immediately if patients show early signs or symptoms of SIRS / capillary leak syndrome or substantial organ dysfunction and appropriate supportive measures instituted.
Clofarabine għandu jitwaqqaf minnufih jekk il- pazjenti juru sinjali bikrin jew sintomi ta ’ SIRS/ sindrom ta ’ nixxija kapillari jew anormalità sostanzjali organika u għandhom jittieħdu miżuri adattati ta ’ appoġġ.
Further treatment with clofarabine, generally at a lower dose, can be considered when patients are stabilised and organ function has returned to baseline.
Aktar trattament b’ clofarabine, ġeneralment b' doża aktar baxxa, jista 'jitqies meta l- pazjenti ikunu stabilizzati u l- funzjoni ta' l- organu tkun marret lura għal bażilinja.
Therefore, the potential benefit and risks associated with continued therapy in patients who do not show haematological and/ or clinical improvement after 2 treatment cycles should be assessed by the treating physician.
Għalhekk, il- benefiċċju u r- riskji potenzjali assoċjati mat - terapija kontinwa f' pazjenti li ma juru l- ebda titjib ematoloġikali u/ jew kliniku wara 2 ċikli ta 'trattament għandhom ikunu assessjati mit- tabib kuranti.
Patients with cardiac disease and those taking medicinal products known to affect blood pressure or cardiac function should be closely monitored during treatment with clofarabine (see sections 4.5 and 4.8).
Pazjenti li jbatu minn mard kardijaku u dawk li qed jieħdu prodotti mediċinali li hu magħruf li jaffettwaw l- pressjoni tad- demm jew funzjoni kardijaka għandhom ikunu monitorjati sewwa matul it - trattament b’ clofarabine (ara sezzjonijiet 4. 5 u 4. 8).
There is no experience in patients with renal insufficiency (serum creatinine ≥ 2 x ULN for age) and clofarabine is predominately excreted via the kidneys.
M’ hemmx esperjenza dwar l- użu f’ pazjenti li jbatu minn insuffiċjenza renali (kreatinina tas- serum ≥ 2 x ULN għall- età) u clofarabine fil- biċċa l- kbira tal- każi jitneħħa mill- kliewi.
Therefore, clofarabine should be used with caution in patients with mild to moderate renal insufficiency (see sections 4.2 and 4.3).
Għalhekk wieħed għandu joqgħod attent meta juża clofarabine fil- każ ta ’ pazjenti li jbatu minn insuffiċjenza renali li tvarja bejn mhux qawwija u moderata (ara sezzjonijiet 4. 2 u 4. 3).
To date, there are insufficient data on the pharmacokinetics of clofarabine in patients with decreased creatinine clearance to advise a dose reduction in such patients.
S’ issa, m’ hemmx tagħrif suffiċjenti dwar il - farmakokinetiċi ta ’ clofarabine f’ pazjenti li jesperjenzaw tneħħija mnaqqsa ta ’ kreatinina biex jista ’ jingħata parir li għandha titnaqqas id- doża fil- każ ta ’ dawn il- pazjenti.
However, these limited data indicate that clofarabine may accumulate in patients with decreased creatinine clearance (see sections 4.2 and 5.2).
Imma, dan it- tagħrif limitat jindika li clofarabine għandu mnejn jakkumula f’ pazjenti b’ tneħħija mnaqqsa ta ’ kreatinina (ara sezzjonijiet 4. 2 u 5. 2).
The concomitant use of medicinal products that have been associated with renal toxicity and those eliminated by tubular secretion should be avoided particularly during the 5 day clofarabine administration period (see sections 4.5 and 4.8).
(ara sezzjonijiet 4. 5 u 4. 8).
There is no experience in patients with hepatic impairment (serum bilirubin > 1.5 x ULN plus AST and ALT > 5 x ULN) and the liver is a potential target organ for toxicity.
Mhemmx esperjenza dwar l- użu f’ pazjenti li jbatu minn indeboliment epatiku (serum bilirubin > 1. 5 x ULN kif ukoll AST u ALT > 5 x ULN) u l- fwied hu organu potenzjali bersall għat- tossiċità.
Therefore, clofarabine should be used with caution in patients with mild to moderate hepatic impairment (see sections 4.2 and 4.3).
Għalhekk clofarabine għandu jintuża bir- reqqa f ’ pazjenti li jbatu minn insuffiċjenza epatika li hi bejn mhix qawwija u moderata (ara sezzjonijiet 4. 2 u 4. 3).
The concomitant use of medicinal products that have been associated with hepatic toxicity should be avoided wherever possible (see sections 4.5 and 4.8).
L- użu konkomitanti ta ’ prodotti mediċinali li kienu assoċjati mat- tossiċità epatika għandu jkun evitat kemm jista ’ jkun (ara sezzjonijiet 4. 5 u 4. 8).
4 Any patient who experiences a severe toxicity (US NCI CTC Grade 3 toxicity) on a third occasion, a severe toxicity that does not recover within 14 days (excluding nausea and vomiting), or a life-threatening or disabling toxicity (US NCI CTC Grade 4 toxicity) should be withdrawn from treatment with clofarabine (see section 4.2).
Kwalunkwe pazjent li jesperjenza tossiċità severa fit- tielet okkażjoni (tossiċità Grad 3 ta ’ CTC tal- NCI ta ’ l- US), tossiċità severa li ma tirkuprax fi żmien 14- il ġurnata (barra minn dardir u ramettar) jew tossiċità fatali jew diżabbilanti (tossiċità Grad 4 ta ’ CTC tal- NCI ta ’ l- US) m’ għandux jibqa ’ jingħata trattament b’ clofarabine (ara sezzjoni 4. 2).
There are currently limited data on the safety and efficacy of clofarabine when administered for more than 3 treatment cycles.
Bħalissa hemm tagħrif limitat dwar is- sigurtà u l- effikaċja ta ’ clofarabine meta jingħata għal aktar minn 3 ċikli ta ’ trattament.
Each vial of Evoltra contains 180 mg of sodium chloride.
Kull kunjett ta ’ Evoltra fih 180 mg ta ’ sodium chloride.
This is equivalent to 3.08 mmol (or 70.77 mg) of sodium and should be taken into consideration for patients on a controlled sodium diet.
Dan hu ekwivalenti għal 3. 08 mmol (jew 70. 77 mg) ta 'sodju u għandu jkun ikkonsidrat fil- każ ta ’ pazjenti li qegħdin fuq dieta kkontrollata tas - sodju.
4.5 Interaction with other medicinal products and other forms of interaction
Prodotti mediċinali oħra li ma jaqblux ma ’ dan il- prodott u affarijiet li jistgħu jibdlu l - 4. 5 effett farmaċewtiku tal- prodott
No formal interaction studies have been performed to date with clofarabine.
Ma sarux studji formali s' issa b’ clofarabine.
However, there are no known clinically significant interactions with other medicinal products or laboratory tests.
Imma, m’ hemmx interazzjonijiet klinikalment sinifikanti ma ’ prodotti mediċinali oħra jew testijiet tal- laboratorju.
Clofarabine is not detectably metabolised by the cytochrome P450 (CYP) enzyme system.
Clofarabine mhuwiex metabolizzat b’ mod li jingħaraf bis- sistema enżimatika cytochrome P450 (CYP).
Therefore, it is unlikely to interact with active substances which inhibit or induce cytochrome P450 enzymes.
Għalhekk, x' aktarx ma jkun hemm l- ebda interazzjoni ma 'sustanzi attivi li jinibixxu jew jikkaġunaw l- enżimi cytochrome P450.
In addition, clofarabine is unlikely to inhibit any of the major 5 human CYP isoforms (1A2, 2C9, 2C19, 2D6 and 3A4) or to induce 2 of these isoforms (1A2 and 3A4) at the plasma concentrations achieved following intravenous infusion of 52 mg/ m2/ day.
Barra minn dan, mhux probabbli li clofarabine jinibixxi kwalunkwe wieħed mill- 5 iżoformi umani maġġuri CYP (1A2, 2C9, 2C19, 2D6 u 3A4) jew iħaffef 2 minn dawn l- iżoformi (1A2 u 3A4) fil- konċentrazzjonijiet tal- plażma li jintlaħqu wara l- infużjoni għal ġol- vini ta ’ 52 mg/ m2/ kuljum.
As a result, it is not expected to affect the metabolism of active substances which are known substrates for these enzymes.
B’ hekk, mhux mistenni, li jaffettwa l- metaboliżmu ta ’ sustanzi attivi li huma substrati magħrufa għal dawn l- enżimi.
Clofarabine is predominately excreted via the kidneys and the liver is a potential target organ for toxicity.
Il- biċċa l- kbira ta ’ clofarabine hu mneħħi permezz tal- kliewi u l- fwied hu organu bersall potenzjali għat- tossiċità.
Hence, the concomitant use of medicinal products that have been associated with renal toxicity and those eliminated by tubular secretion should be avoided particularly during the 5 day clofarabine administration period (see sections 4.4, 4.8 and 5.2).
Għalhekk, l- użu konkomitanti ta ’ prodotti mediċinali li ġew assoċjati mat- tossiċità renali u dawk eliminati mit- tnixxija tubulari għandhom ikunu evitati partikularment matul il- perijodu ta ’ għoti ta ’ 5 ġranet ta ’ clofarabine (ara sezzjonijiet 4. 4, 4. 8 u 5. 2).
In addition, the concomitant use of medicinal products that have been associated with hepatic toxicity should be avoided wherever possible (see sections 4.4 and 4.8).
Barra minn dan, l- użu konkomitanti ta ’ prodotti mediċinali li kienu assoċjati mat- tossiċità epatika għandu jkun evitat kulmeta dan hu possibbli (ara sezzjonijiet 4. 4 u 4. 8).