qanastek/EMEA-V3 huggingface dataset:
Men in fertile age and women of childbearing potential must use effective contraception during treatment and 3 months thereafter for women and immediately inform the treating physician if a pregnancy occurs, and 5 months after treatment for men (see section 4.6).
Irġiel f’ età fertili u nisa bil- possibilità li jkollhom it- tfal għandhom jużaw kontraċezzjoni effettiva waqt il- perijodu ta ’ kura u sa 3 xhur wara għan- nisa u għandhom jinfurmaw lit- tabib kuranti immedjatament jekk ikun hemm tqala, u 5 xhur wara kura ta ’ l- irġiel (ara sezzjoni 4. 6).
This medicine contains potassium, less than 1 mmol (39 mg) per vial, i. e. essentially “ potassium-free”.
Din il- mediċina fiha l- potassium, anqas minn 1 mmol (39 mg) kull kunjett i. e. essenzjalment “ mingħajr potassium ”.
Effects of other substances on trabectedin
Effetti ta ’ sustanzi oħra fuq trabectedin
In vivo interaction studies have not been performed.
Ma ġew magħmula l- ebda studji in vivo.
Since trabectedin is metabolised mainly by CYP3A4, co-administration of substances that inhibit this isoenzyme e. g. ketoconazole, fluconazole ritonavir or clarithromycin could decrease metabolism and increase trabectedin concentrations.
Peress li trabectedin huwa metabolizzat prinċipalment minn CYP3A4, l- għoti flimkien ta ’ sustanzi li jimpedixxu din l- iżoenżima eż. ketoconazole, fluconazole, ritonavir jew clarithromycin jistgħu jnaqqsu l- metaboliżmu u jżidu l- konċentrazzjonijiet ta ’ trabectedin.
If such combinations are needed, close monitoring of toxicities is required (see section 4.4).
Jekk dawn il- kumbinazzjonijiet huma meħtieġa, sorveljanza mill- qrib ta ’ tossiċitajiet hija meħtieġa (ara sezzjoni 4. 4).
Likewise co-administration with potent inducers of this enzyme (e. g. rifampicin, phenorbarbital, Saint John’ s Wort) may decrease the systemic exposure to trabectedin.
5 rifampicin, phenorbarbital, Saint John’ s Wort), jistgħu jnaqqsu l- esponiment sistemiku għal trabectedin.
Alcohol consumption must be avoided during treatment with trabectedin due to the hepatotoxicity of the medicinal product (see section 4.4).
Konsum ta ’ alkoħol għandu jiġi evitat waqt kura bi trabectedin minħabba l- epatotossiċità ta ’ dan il - prodott mediċinali (ara sezzjoni 4. 4).
Preclinical data have demonstrated that trabectedin is a substrate to P-gp.
Dejta ta ’ qabel l- użu kliniku wera li trabectedin huwa sottostrat għal P- gp.
Concomitant administration of inhibitors of Pgp, e. g. cyclosporine and verapamil, may alter trabectedin distribution and/ or 5 elimination.
L- għoti flimkien ta ’ impedituri ta ’ Pgp, eż. cyclosporine u verapamil, jistgħu ibiddlu l- firxa u/ jew l- eliminazzjoni ta ’ trabectedin.
CNS toxicity has not been established.
Ir- rilevanza ta ’ din l- interazzjoni eż. tossiċità tas- SNĊ ma ġietx stabbilita.
Caution should be taken in such situations.
Kawtela hija meħtieġa f’ sitwazzjonijiet bħal dawn.
No sufficient clinical data on exposed pregnancies are available.
Ma jeżisti l- ebda tagħrif kliniku suffiċjenti dwar tqaliet esposti.
However, based on its known mechanism of action, trabectedin may cause serious birth defects when administered during pregnancy.
Madankollu, skond il- mekkaniżmu ta ’ azzjoni magħrufa, trabectedin jista ’ jikkaġuna difetti tat- twelid serji meta jingħata waqt it- tqala.
Trabectedin should not be used during pregnancy unless clearly necessary.
Trabectedin m’ għandux jintuża waqt it- tqala sakemm mhux meħtieġ b’ mod ċar.
If it is used during pregnancy, the patient must be informed of the potential risk to the foetus (see section 5.3) and be monitored carefully.
Jekk huwa użat waqt it- tqala, il- pazjent għandu jkun infurmat dwar ir- riskju potenzjali għal- fetu (ara sezzjoni 5. 3) u jiġi sorveljat bir- reqqa.
If trabectedin is used at the end of pregnancy, potential adverse reactions should be monitored carefully in the newborns.
Jekk trabectedin huwa użat fl- aħħar tat- tqala, reazzjonijiet avversi potenzjali għandhom jiġu sorveljati bir- reqqa fit- trabi għadhom jitwieldu
Men in fertile age and women of childbearing potential must use effective contraception during treatment and 3 months thereafter for women and immediately inform the treating physician if a pregnancy occurs (see section 5.3) and 5 months after treatment for men (see section 4.4).
Irġiel f’ età fertili u nisa bil- potenzjal li jkollhom it- tfal għandhom jużaw kontraċezzjoni effettiva waqt kura u sa 3 xhur wara għan- nisa u jinfurmaw lit- tabib kuranti immedjatament jekk isseħħ tqala, u 5 xhur wara kura ta ’ l- irġiel (ara sezzjoni 4. 4).
Trabectedin can have genotoxic effects.
Trabectedin jista ’ jkollu effetti ġenotossiċi.
Advice on conservation of sperm should be sought prior to treatment because of the possibility of irreversible infertility due to therapy with Yondelis.
Għandu jiġi mfittex parir fuq il- konservazzjoni ta ’ l - isperma qabel il- kura minħabba l- possibbilità ta ’ infertilità irreversibbli minħabba terapija b’ Yondelis.
If pregnancy occurs during treatment the possibility of genetic counselling should be considered.
Jekk ikun hemm tqala waqt il- kura il- possibilità ta ’ konsultazzjoni ġenetika għandha tiġi kkonsidrata.
Genetic counselling is also recommended for patients wishing to have children after therapy.
Konsultazzjoni ġenetika għandha tkun rakkomandata għal pazjenti li jixtiequ li jkollhom it- tfal wara t - terapija.
It is not known whether trabectedin is excreted in human milk.
Mhux magħruf jekk trabectedin huwiex eliminat fil- ħalib uman.
The excretion of trabectedin in milk has not been studied in animals.
L- eliminazzjoni ta ’ trabectedin fil - ħalib ma gietx studjata fl- annimali.
Breast-feeding is contraindicated during treatment and 3 months thereafter (see section 4.3).
It- treddigħ huwa kontrindikat waqt il- kura u sa 3 xhur wara (ara sezzjoni 4. 3).
No studies on the effects of the ability to drive and to use machines have been performed.
Ma sarux studji fuq l- effetti fuq il- ħila li ssuq u tuża magni.
However, fatigue and/ or asthenia have been reported in patients receiving trabectedin.
Madankollu, għeja kbira u/ jew astenija ġew irrapportati f’ pazjenti li qed jirċievu trabectedin.
Patients who experience any of these events during therapy must not drive or operate machines.
Pazjenti li jesperjenzaw kwalunkwe minn dawn ir- reazzjonijiet waqt it- terapija m’ għandhomx isuqu jew iħaddmu magni.
Unless otherwise specified, the following safety profile of Yondelis is based on the evaluation in clinical trials of 569 patients treated up to April 2007 with the recommended treatment regime in several cancer types including soft tissue sarcoma, breast cancer, osteosarcoma, ovarian cancer, GIST, melanoma and renal carcinoma.
Sakemm mhux speċifikat xort ’ oħra, il- profil ta’ sigurtà ta ’ Yondelis li ġej huwa bażat fuq evalwazzjoni minn provi kliniċi ta ’ 569 pazjent ikkurati sa April 2007 bir- reġimen ta ’ kura irrakkomandat f’ diversi tipi ta ’ kanċer li jinkludu sarcoma tat- tessuti morbidi, kanċer tas- sider, osteosarkoma, kanċer ta ’ l- ovarju, GIST, melanoma u karċinoma renali.
Approximately 91% of patients can be expected to have adverse reactions of any grade.
Madwar 91% tal- pazjenti jistgħu jkunu mistennija li jkollhom reazzjonijiet avversi ta ’ kwalunkwe grad.
Around 40% of patients are expected to have adverse reactions of grade 3 or 4 severity.
Madwar 40% tal- pazjenti huma mistennija li jkollhom reazzjonijiet avversi ta ’ grad 3 jew 4 fis - severità tagħhom.
The most common adverse reactions of any severity grade were nausea, fatigue, vomiting, anorexia, neutropenia, and increases in AST/ ALT.
L- aktar reazzjonijiet avversi komuni ta ’ kwalunkwe grad ta ’ severità kienu dardir, għeja kbira, remettar, anoressja, newtropenja, u żidiet fl- AST/ ALT.
Fatal adverse reactions have occurred in 1.9% of patients.
6 Reazzjonijiet avversi fatali seħħew f’ 1. 9% tal- pazjenti.
They were often the result of a combination of events including pancytopenia, febrile neutropenia, some of them with sepsis, hepatic involvement, renal failure and rhabdomyolysis.
Huma ta ’ spiss kienu r- riżultat ta ’ taħlita ta ’ reazzjonijiet inklużi panċitopenja, newtropenja bid- deni, xi uħud b ’ infezzjoni, involviment tal- fwied, falliment renali u rabdomajoliżi.
The frequencies of the adverse reactions reported below are classified as very common (≥ 1/ 10), common (≥ 1/ 100 to < 1/ 10) and uncommon (≥ 1/ 1000 to < 1/ 100).
Il- frekwenzi ta ’ reazzjonijiet avversi rapportati hawn isfel huma kklassifikati bħala komuni ħafna (≥ 1/ 10), komuni (≥ 1/ 100 sa < 1/ 10) u mhux komuni (≥ 1/ 1000 sa < 1/ 100).
6 The table below displays the adverse reactions reported in ≥ 1% of patients according to the standard MedDRA system organ class.
It- tabella t’ hawn taħt turi r- reazzjonijiet avversi rapportati f’ ≥ 1% tal- pazjenti skond l- istandard MedDRA dwar is- sistema tal- klassifika ta ’ l- organi.
Both adverse events and laboratory values have been used to provide frequencies.
Sew l- avvenimenti avversi kif ukoll il- valuri tal - laboratorju ġew użati biex jinkisbu l- frekwenzi.
7 System Organ Class Investigations
7 Sistema tal- Klassifika ta ’ l- Organi
Adverse reactions reported in ≥ 1% of patients in clinical trials at the recommended regime [1.5 mg/ m2, 24 hour infusion every 3 weeks (24-h q3wk)] Very Common Blood creatine phosphokinase increased, Blood creatinine increased, Blood albumin decreased Common Weight decreased
Reazzjonijiet avversi rapportati f’ ≥ 1% ta ’ pazjenti fi provi kliniċi fir- reġim rakkomandat [1. 5 mg/ m2, 24 siegħa infużjoni kull 3 ġimgħat (24- h q3wk)]
Blood and Lymphatic System Disorders
Disturbi tad- demm Komuni Ħafna u tas- sistema limfatika
Very Common Neutropenia, Thrombocytopenia, Anaemia, Leukopenia Common Febrile neutropenia
Newtropenja, Tromboċitopenija, Anemija, Lewkopenja Komuni Newtropenja bid- deni
Nervous System Disorders
Disturbi fis- sistema Komuni Ħafna nervuża
Very Common Headache Common Peripheral sensory neuropathy, Dysgeusia, Dizziness, Paraesthesia
Uġigħ ta ’ ras Komuni Newtropatija sensorjali periferali, Disgewsja, Sturdament, Paraesteżija
Common Dyspnoea, Cough
Komuni Dispnea, Sogħla
Very Common Vomiting, Nausea, Constipation Common Diarrhoea, Stomatitis, Abdominal pain, Dyspepsia, Upper abdominal pain
Komuni Ħafna Remettar, Dardir, Stitikezza Komuni Dijarea, Stomatite, Uġigħ addominali, Dispepsja, Uġigħ addominali fil- parti ta ’ fuq
Skin and Subcutaneous Tissue Disorders
Disturbi fil- ġilda u Komuni fit- tessuti ta ’ taħt il- ġilda
Common Alopecia
Alopeċja
Musculoskeletal and Connective Tissue Disorders
Disturbi
Common Myalgia, Arthralgia, Back pain
Komuni
Metabolism and
muskolo- skeletriku Uġigħ fil- muskoli, Artralġja, Uġigħ fid- dahar u tal- connective tissue Disturbi fil- metaboliżmu u n- nutrizzjoni
Very Common
Komuni Ħafna Anoreksja Komuni Diżidrazzjoni, Tnaqqis fl- aptit, Ipokalemija
Nutrition DisordersAnorexia Common Dehydration, Decreased appetite, Hypokalaemia Infections and Infestations Vascular Disorders
Infezzjonijiet u infestazzjonijiet Disturbi vaskulari
Common Infection Common Hypotension, Flushing
Komuni Infezzjoni Komuni Ipotensjoni, Fwawar
General Disorders Very Common and Administration Fatigue, Asthenia Site Conditions
Disturbi ġenerali u Komuni Ħafna kondizzjonijiet ta ’ Għeja, Astenja mnejn jingħata
Common Pyrexia, Oedema, Oedema peripheral, Injection site reaction
Komuni Deni, Edima, Edima periferali, Reazzjoni fis- sit ta ’ l- injezzjoni
Hepatobiliary Disorders
Disturbi fil- fwied u Komuni Ħafna fil- marrara
Very Common Hyperbilirubinemia, Alanine aminotransferase increased, Aspartate aminotransferase increased, Blood alkaline phosphatase increased, Gamma-glutamyltransferase increased
Iperbilirubinemija, Żieda f’ alanine aminotransferase, Żieda f’ aspartate aminotransferase, Żieda fil- livell ta ’ alkaline phosphatase fid- demm, Żieda fil- Gamma- glutamyltransferase
Psychiatric Disorders
Disturbi psikjatriċi Komuni Insomnija
8 Most frequent adverse reactions
8 Reazzjonijiet avversi l- aktar frekwenti
Blood and Lymphatic system disorders
Disturbi tad- demm u tas- sistema limfatika
Neutropenia occurred in 77% of patients.
In- newtropenja seħħet f’ 77% tal- pazjenti.
Grade 3 and 4 neutropenia occurred in 26% and 24% of patients respectively).
Newtropenja ta ’ grad 3 u 4 seħħet f’ 26% u 24% rispettivament.
The analysis per cycle showed that neutropenia of grade 3 and 4 occurred in approximately 19% and 8% of cycles respectively Febrile neutropenia occurred in 2% of patients and in < 1% of cycles.
Newtropenja bid- deni seħħet fi 2% tal- pazjenti u f ’ < 1% taċ- ċikli.
Neutropenia followed a predictable pattern of rapid onset and reversibility, and was rarely associated with fever or infection.
In- newtropenja segwiet skema prevedibbli ta ’ bidu rapidu u riversibbilità, u rari kienet assoċjata ma ’ deni jew infezzjoni.
Grade 3 and 4 thrombocytopenia occurred in 11% and 2% of patients respectively.
Tromboċitopenja grad 3 u 4 seħħet fi 11% u 2% tal- pazjenti rispettivament.
The analysis per cycle showed that thrombocytopenia of grade 3 and 4 occurred in approximately 3% and < 1% of cycles respectively.
L- analiżi ta ’ kull ċiklu wriet li tromboċitopenja ta ’ grad 3 jew 4 seħħew f’ madwar 3% u < 1% taċ- ċikli rispettivament.
Bleeding events associated to thrombocytopenia occurred in < 1% of patients.
Reazzjonijiet ta ’ fsada assoċjati ma ’ tromboċitopenja seħħew f ’ < 1% tal- pazjenti.
Anaemia occurred in 93% of patients although 46% of patients were anaemic at baseline.
L- anemija seħħet f ’ 93% tal- pazjenti għalkemm 46% tal- pazjenti kienu anemiċi fil- linja bażi ta ’ riferiment.
Grade 3 and 4 anaemia occurred in 10% and 3% of patients respectively.
Anemija ta ’ grad 3 u 4 seħħet f’ 10% u 3% tal- pazjenti rispettivament.
The analysis per cycle showed that anaemia of grade 3 and 4 occurred in approximately 3% and 1% of cycles respectively.
L- analiżi ta ’ kull ċiklu uriet li anemija ta ’ grad 3 jew 4 seħħet f’ madwar 3% u 1% taċ- ċikli rispettivament.
Hepatobiliary disorders
Disturbi epatobiljari
AST/ ALT increases:
Żidiet fl- AST/ ALT:
Transient grade 3 increases of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were observed in 38% and 44% of the patients and grade 4 elevations in 3% and 7% of the patients, respectively.
Żidiet għaddiena ta ’ aspartate aminotransferase (AST) u alanine aminotransferase (ALT) ta ’ grad 3 kienu osservati f’ 38% u 44% tal- pazjenti u elevazzjonijiet ta ’ grad 4 fi 3% u f’ 7% tal- pazjenti, rispettivament.
The median time to reach the peak values was 5 days for both AST and ALT.
Iż- żmien medjan biex jintlaħqu valuri massimi kien ta ’ 5 ijiem kemm għal AST kif ukoll għal ALT.
Most of the values had decreased to grade 1 or resolved by day 14-15 (see section 4.4).
Il- maġġoranza tal- valuri kienu naqsu għal grad 1 jew irrisolvew sal- 14- 15 - il jum (ara sezzjoni 4. 4).
Grade 3 elevations of AST and ALT occurred in 12% and 20% of cycles respectively.
Elevazzjonijiet ta ’ grad 3 ta ’ AST u ALT seħħew f ’’ 12% u 20% taċ- ċikli rispettivament.
Grade 4 elevations of AST and ALT occurred in 1% and 2% of cycles respectively.
Elevazzjonijiet ta ’ AST u ALT grad 4 seħħew f’ 1% u 2% taċ- ċikli rispettivament.
Most transaminase elevations improved to grade 1 or to pre-retreatment levels within 15 days, and less than 2% of cycles had recovering times longer than 25 days.
Il - maġġoranza taż- żidiet fit- transaminases tjiebu għal- livelli ta ’ grad 1 jew ta ’ qabel il- kura mill- ġdid fi żmien 15- il jum, u anqas minn 2% taċ- ċikli kelhom żminijiet ta ’ rkupru itwal minn 25 jum.
ALT and AST increases did not follow a cumulative pattern but showed a tendency towards less severe elevations over time.
Żidiet fl - ALT u AST ma segwewx skema kumulattiva imma wrew tendenza lejn elevazzjonijiet anqas severi matul iż- żmien.
Hyperbilirubinemia:
Iperbilirubinimja:
Grades 1 to 2 bilirubin increases were observed in 23% of the patients.
Żidiet ta ’ bilirubin grad 1 jew 2 kienu osservati fi 23% tal- pazjenti.
Grade 3 hyperbilirubinemia occurred in 1% of patients.
Iperbilirubinimja grad 3 seħħet f’ 1% tal- pazjenti.
Bilirubin peaks approximately a week after onset and resolves approximately two weeks after onset.
Bilirubin jilħaq il- massimu madwar ġimgħa wara l- bidu u jirrisolvi madwar ġimgħatejn wara l- bidu.
Clinical manifestations of severe hepatic injury were uncommon with a lower than 1% incidence of individual signs and symptoms including jaundice, hepatomegaly or liver pain.
Manifestazzjonijiet kliniċi ta ’ ħsara epatika severa ma kinux komuni b’ inċidenza aktar baxxa minn 1% ta ’ sinjali u sintomi individwali li jinkludu suffejra, epatomegalija jew uġigħ fil- fwied.
Mortality in the presence of hepatic injury occurred in less than 1% of patients.
Fil- preżenza ta ’ ħsara epatika il- mortalità seħħet f’ anqas minn 1% tal- pazjenti.
Other adverse reactions
Reazzjonijiet avversi oħra
Nausea, vomiting, diarrhoea and constipation:
Dardir, remettar, dijarea u stitikezza:
Nausea and vomiting were reported in 63 and 38.5% of patients respectively.
Dardir u remettar kienu irrapportati f ’ 63 u 38. 5% tal- pazjenti rispettivament.
Grade 3-4 nausea and vomiting were reported in 6% and 6.5% of patients, respectively.
Dardir u remettar ta ‘ Grad 3- 4 kienu irrapportati f’ 6% u 6. 5% tal- pazjenti, rispettivament.
Grade 3-4 diarrhoea and constipation were reported in less than 1% of patients.
Dijarea u stitikezza Grad 3- 4 kienu irrapportati f’ anqas minn 1% tal- pazjenti.
Grade 3-4 mucositis was reported in less than 1% of the patients.
Mukożite Grad 3- 4 kienet irrapportata f’ anqas minn 1% tal- pazjenti.
Fatigue/ Asthenia:
Għeja kbira/ Astenija:
Grade 3-4 fatigue/ asthenia occurred in 9 and 1% of patients respectively.
Għeja kbira/ astenija Grad 3- 4 seħħew f’ 9 u 1% tal- pazjenti rispettivament.
Anorexia:
Anoreksja:
Grade 3-4 anorexia occurred in less than 1% of the patients.
Anoreksja ta ’ Grad 3- 4 seħħet f’ anqas minn 1% tal- pazjenti.
CPK elevations and rhabdomyolysis:
Elevazzjonijiet ta ’ CPK u rabdomajoliżi:
CPK elevations of any grade were observed in 26% of patients.
Elevazzjonijiet ta ’ CPK ta ’ kwalunkwe grad kienu osservati f’ 26% tal- pazjenti.
Grade 3 or 4 increases of CPK were observed in 4% of patients.
Żidiet ta ’ CPK Grad 3 jew 4 kienu osservati f’ 4% tal- pazjenti.
CPK increases in association with rhabdomyolysis were reported in less than 1% of patients.
Żidiet fis- CPK f’ assoċjazzjoni ma ’ rabdomajoliżi kienu rrapportati f’ anqas minn 1% tal- pazjenti.
9 Dyspnoea:
9 Dispnea:
Grade 3-4 dyspnoea reported as trabectedin related occurred in 2% of the patients.
Dispnea ta ’ Grad 3- 4 irrapportata bħala relatata ma’ trabectedin seħħet fi 2% tal- pazjenti.
Alopecia:
Alopeċja:
Alopecia was reported in approximately 3% of all patients, of which the majority was grade 1 alopecia.
Alopixja kienet irrapportata f’ madwar 3% tal- pazjenti kollha, ta ’ liema l- maġġoranza kienet alopeċja Grad 1.
There is limited data on the effects of trabectedin overdose.
Hemm dejta ristretta dwar l- effetti ta ’ doża eċċessiva ta ’ trabectedin.
The major anticipated toxicities are gastrointestinal, bone marrow suppression and hepatic toxicity.
It- tossiċitajiet maġġuri antiċipati kienu gastrointestinali, soppressjoni tal- mudullun u tossiċità epatika.
There is no specific antidote for trabectedin currently available.
Attwalment, ma hemm l- ebda antidotu speċifiku għal trabectedin.
In the event of an overdose, patients should be closely monitored and symptomatic supportive care measures instituted as required.
Fil- każ ta ’ doża eċċessiva, pazjenti għandhom ikun sorveljati mill - qrib u kura ta ’ appoġġ sintomatiku tinbeda skond il- ħtieġa
Antineoplastic agent, ATC code:
Mediċina anti- neoplastika, Kodiċi ATC:
Mechanism of action
Mekkaniżmu t’ azzjoni
Trabectedin binds to the minor groove of DNA, bending the helix to the major groove.
Trabectedin jorbot max- xaqq minuri tad- DNA, u jgħawweġ l- elika għax- xaqq maġġur.
This binding to DNA triggers a cascade of events affecting several transcription factors, DNA binding proteins, and DNA repair pathways, resulting in perturbation of the cell cycle.
Dan l- irbit mad- DNA iqanqal kaskata ta ’ reazzjonijiet li jeffettwaw diversi fatturi ta ’ transkrizzjoni, proteini ta ’ l - irbit tad- DNA, u mogħdijiet ta ’ tiswija tad- DNA, li jirriżultaw f’ perturbazzjoni taċ- ċiklu taċ- ċellola.
Trabectedin has been shown to exert antiproliferative in vitro and in vivo activity against a range of human tumour cell lines and experimental tumours, including malignancies such as sarcoma, breast, non-small cell lung, ovarian and melanoma.
Trabectedin ġie muri li jeżerċità attività antiproliferattiva in vitro u in vivo kontra varjetà ta ’ razez ta ’ tumur tal- bniedem, li jinkludu malinnitajiet bħalma huma sarkoma, sider, ċellola mhux żgħira tal - pulmun, ta ’ l- ovarju u melanoma.
The efficacy and safety of trabectedin is based in a randomised trial in patients with locally advanced or metastatic liposarcoma or leiomyosarcoma, whose disease had progressed or relapsed after treatment with at least anthracyclines and ifosfamide.
L- effikaċja u s- sigurtà ta ’ trabectedin hija bbażata fi prova randomised f’ pazjenti b’ liposarkoma jew lejomajosarkoma lokalizzata jew metastatika avvanzata, li l- marda tagħhom kienet avvanzat jew irkadiet wara l- kura b ’ ta ’ lanqas anthracyclines u ifosfamide.
In this trial trabectedin was administered either at 1.5 mg/ m2 as a 24-hour intravenous infusion every 3 weeks or at 0.58 mg/ m2 weekly as a 3-hour intravenous infusion for 3-weeks of a 4-week cycle.
F’ din il- prova trabectedin kien amministrat jew f’ 1. 5 mg/ m2 bħala infużjoni intravenuża ta ’ 24 siegħa kull 3 ġimgħat jew f’ 0. 58 mg/ m2 kull ġimgħa bħala infużjoni intravenuża għal 3 ġimgħat fuq ċiklu ta ’ 4 ġimgħat.
The protocol specified final time to progression (TTP) analysis showed a 26.6% reduction in the relative risk of progression for patients treated in the 24-h q3wk group (Hazard Ratio = 0.734 CI 0.554-0.974).
L - analiżi taż- żmien finali għal progressjoni (TTP) speċifikat fil- protokol wera tnaqqis ta ’ 2. 6% fir- riskju relattiv ta ’ progressjoni għal pazjenti kkurati fil- grupp ta ’ 24 siegħa kull 3 ġimgħat (Proporzjon ta ’ Riskju= 0. 734 CI 0. 554- 0. 974).
Median TTP values were 3.7 months (CI:
Valuri TTP medjani kienu 3. 7 xhur (CI:
2.1-5.4 m) in the 24-h q3wk group and 2.3 months (CI:
2. 1- 5. 4 m) fil- grupp ta ’ 24 siegħa kull 3 ġimgħat u 2. 3 xhur (CI:
2.0-3.5 m) in the 3-h qwk group (p=0.0302).
2. 0- 3. 5 m) fil- grupp ta ’ 3 sigħat kull ġimgħa (p=0. 0302).
No significant differences were detected in overall survival (OS).
L- ebda differenzi sinifikattivi ma dehru fis- sopravivenza totali (OS).
Median OS with the 24-h q3wk regime was 13.9 months (CI:
OS medjana bir- reġim ta ’ 24 siegħa kull 3 ġimgħat kienet 13. 9 xhur (CI:
12.5-18.6) and 60.2% of patients were alive at 1 year (CI:
12. 5- 18. 6) u 60. 2% tal- pazjenti kienu ħajjin f’ sena 1 (CI:
52.0-68.5%).
52. 0- 68. 5%).
Additional efficacy data are available from 3 single-arm Phase II trials with similar populations treated with the same regime.
Hemm dejta tal- effikaċja addizzjonali minn 3 provi Fażi II driegħ wieħed b’ popolazzjonijiet simili bl- istess regime.
These trials evaluated a total of 100 patients with lipo and leiomyosarcoma and 83 patients with other types of sarcoma.
Dawn il- provi evalwaw total ta ’ 100 pazjent b’ lipo u lejomajosarkoma u 83 pazjent b’ tipi oħra ta ’ sarkoma.
This means that due to the rarity of the disease it has not been possible to obtain complete information on this medicinal product.
Dan ifisser li minħabba li l- marda hija rari ma kienx possibbli li tinkiseb informazzjoni kompleta dwar dan il- prodott mediċinali.
The European Medicines Agency (EMEA) will review any new information which may become available every year and this SPC will be updated as necessary.
L- Aġenzija Ewropeja dwar il- Mediċini (EMEA) ser tirrevedi kull tip ta ’ informazzjoni ġdida li tista ’ toħroġ kull sena u ser taġġorna dan is- Sommarju tal- Karatteristiċi tal- Prodott, skond il- bżonn.
10 Systemic exposure after administration as a 24 hour constant rate intravenous infusion is dose proportional at doses up to and including 1.8 mg/ m2.
10 Esponiment sistemiku wara l- għoti bħala infużjoni intravenuża b’ rata kostanti fuq 24 siegħa hija proporzjonali f’ dożi sa u li jinkludu 1. 8 mg/ m2.
Trabectedin pharmacokinetic profile is consistent with a multiple-compartment disposition model.
Il- profil farmakokinetiku ta ’ trabectedin huwa konsistenti ma ’ mudell ta ’ dispożizzjoni b’ kompartamenti- multipli.
Following intravenous administration, trabectedin demonstrates a high apparent volume of distribution, consistent with extensive tissue and plasma protein binding (94 to 98% of trabectedin in plasma is protein bound).
Wara amministrazzjoni intravenuża, trabectedin juri volum ta ’ distribuzzjoni apparenti għoli, konsistenti ma ’ irbit estensiv ta ’ proteini fit- tessuti u fil- plażma (94 sa 98% ta ’ trabectedin fil- plażma huwa marbut mal- proteini).
The distribution volume at steady state of trabectedin in human subjects exceeds 5000 l.
Il- volum ta ’ distribuzzjoni ta ’ trabectedin fi stat fiss f’ suġġetti umani jaqbeż 5000 l.
Cytochrome P450 3A4 is the major cytochrome P450 isozyme responsible for the oxidative metabolism of trabectedin at clinically relevant concentrations.
Ċitokroma P450 3A4 hija ċ- ċitokroma P450 iżoenżima maġġura risponsabbli għal metaboliżmu ossidattiv ta ’ trabectedin f’ konċentrazzjonijiet klinikament relevanti.
Other P450 enzymes may contribute to metabolism.
Enżimi oħra P450 jistgħu jikontribwixxu għal metaboliżmu.
Trabectedin does not induce or inhibit major cytochrome P450 enzymes.
Trabectedin ma jinduċix jew jinibixxix enżimi ċitokromi P450 maġġuri.
Renal elimination of unchanged trabectedin in humans is low (less than 1%).
L- eliminazzjoni renali ta ’ trabectedin mhux mibdul fil- bnedmin hija baxxa (anqas minn 1%).
The terminal half-life is long (population value of the terminal elimination phase:
Il- half- life terminali hija twila (valur tal- popolazzjoni tal- fażi ta ’ eliminazzjoni terminali:
180-hr).
180- siegħa).
After a dose of radiolabelled trabectedin administered to cancer patients, faecal mean (SD) recovery of total radioactivity is 58% (17%), and urinary mean (SD) recovery is 5.8% (1.73%).
Wara doża ta ’ trabectedin radjutikketat mogħti lil pazjenti bil- kanċer, l- irkupru medju (SD) fl- ippurgar tar- radjuattività totali kien ta ’ 58% (17%), u l- irkupru medju (SD) awrinarju kien ta ’ 5. 8% (1. 73%).
Based on the population estimate for plasma clearance of trabectedin (31.5 l/ h) and blood/ plasma ratio (0.89), the clearance of trabectedin in whole blood is approximately 35 l/ h.
Ibbażat fuq l- istima tal- popolazzjoni għar- rata ta ’ eliminazzjoni mill- plażma ta ’ trabectedin (31. 5 l/ siegħa) u proporzjon ta ’ demm/ plażma (0. 89), ir- rata ta ’ eliminazzjoni ta ’ trabectedin fid- demm sħiħ hija madwar 35 l/ siegħa.
This value is approximately one-half the rate of human hepatic blood flow.
Dan il- valur huwa madwar nofs ir- rata taċ- ċirkolazzjoni tad- demm epatika umana.
Thus the trabectedin extraction ratio can be considered moderate.
Għalhekk il- proporzjon ta ’ qligħ ta ’ trabectedin hija kunsidrata moderata.
The inter-patient variability of the population estimate for plasma clearance of trabectedin was 51% and intra-patient variability was 28%.
Il- varjabilità bejn il- pazjenti ta ’ l- istima tal- popolazzjoni għar- rata ta ’ tneħħija ta ’ trabectedin kienet ta ’ 51% u l- varjabilità ġol- pażjenti kienet 28%.
A population pharmacokinetic analysis indicated that the plasma clearance of trabectedin is not influenced by age (range 19-83 years), or gender.
Analiżi tal- farmakokinetika tal- popolazzjoni indikat li r- rata ta ’ tneħħija ta ’ trabectedin mhix influwenzata mill- età (medda 19- 83 sena), jew sess.
The effects of race and ethnicity on trabectedin pharmacokinetics have not been studied.
L- effetti ta ’ razza u etniċità ta ’ farmakokinetiċi ta ’ trabectedin ma ġewx studjati.
Impaired renal function
Funzjoni renali indebolita
There is no relevant influence of renal function measured by creatinine clearance on trabectedin pharmacokinetics within the range of values (≥ 34.4 ml/ min) present in the patients included in the clinical studies.
Ma hemm l- ebda influwenza rilevanti fuq funzjoni renali mkejjla bir- rata ta ’ tneħħija ta ’ kreatinina fuq il- farmakokinetiċi ta ’ trabectedin fi ħdan il- medda ta ’ valuri (≥ 34. 4 ml/ min) preżenti f’ pazjenti li kienu inklużi fl- istudji kliniċi.
No data are available in patients with a creatinine clearance of less than 34.4 ml/ min.
Ma hemm l- ebda dejta f’ pazjenti b’ rata ta ’ tneħħija ta ’ kreatinina ta ’ anqas minn 34. 4 ml/ min.
The low recovery (< 9% in all studied patients) of total radioactivity in the urine after a single dose of 14 C-labelled trabectedin indicates that renal impairment has little influence on the elimination of trabectedin or its metabolites.
L- irkupru baxx (< 9% ta ’ pazjenti studjati) tar- radjuattività totali fl- awrina wara doża waħda ta ’ trabectedin ittikketat b’ 14C indikat li indeboliment renali għandu ftit influwenza fuq l- eliminazzjoni ta ’ trabectedin jew il- metaboliti tiegħu.
Impaired hepatic function
Funzjoni epatika indebolita
Although the population analysis showed no relationship between the serum liver enzymes concentrations and the plasma clearance of trabectedin, systemic exposure to trabectedin may be increased in patients with hepatic impairment; therefore close monitoring of toxicity is warranted.
Għalkemm l- analiżi tal- popolazzjoni ma wriet l- ebda relazzjoni bejn konċentrazzjonijiet fis- serum ta ’ l- enżimi tal- fwied u r- rata ta ’ tneħħija fil- plażma ta ’ trabectedin, esponiment sistemiku ta ’ trabectedin f’ pazjenti b’ indeboliment epatiku; għaldaqstant sorveljanza mill- qrib ta ’ tossiċità hija neċessarja.
Preclinical data indicate that trabectedin has limited effect on the cardiovascular, respiratory and central nervous system at exposures below the therapeutic clinical range, in terms of AUC.
Dejta ta ’ qabel l- użu kliniku tindika li trabectedin għandu effett ristrett fuq sistemi kardjovaskulari, respiratorji u nervużi ċentrali f’ esponimenti taħt il- medda klinika terapewtika, f’ termini ta ’ AUC.
The effects of trabectedin on cardiovascular and respiratory function have been investigated in vivo (anesthetised Cynomolgus monkeys).
L- effetti ta ’ trabectedin fuq il- funzjoni kardjovaskulari u repiratorji ġew mistħarrġa in vivo (xadini Cynomolgus illoppjati).
A 1 hour infusion schedule was selected to attain maximum plasma levels (Cmax values) in the range of those observed in the clinic.
Skeda ta ’ infużjoni ta ’ siegħa kienet magħżula biex tilħaq livelli massimi fil - plażma (valuri Cmax) fil- medda ta ’ dawk osservati fil- klinika.
The plasma trabectedin levels attained were 10.6 ± 5.4 (Cmax), higher than those reached in patients after infusion of 1500 μ g/ m2 for 24 (Cmax of 1.8 ± 1.1 ng/ ml) and similar to those reached after administration of the same dose by 3 hour infusion (Cmax of 10.8 ± 3.7 ng/ ml).
11 għal 24 (Cmax ta ’ 1. 8 ± 1. 1 ng/ ml) u simili għal dawk milħuqa wara għoti ta ’ l- istess doża minn infużjoni ta ’ 3 sigħat (Cmax ta ’ 10. 8 ± 3. 7 ng/ ml).
11 Myelosupression and hepatoxicity were identified as the primary toxicity for trabectedin.
Majelosoppressjoni u epatossiċità kienu identifikati bħala tossiċità primarja għal trabectedin.
Findings observed included haematopoietic toxicity (severe leukopenia, anaemia, and lymphoid and bone marrow depletion) as well as increases in liver function tests, hepatocellular degeneration, intestinal epithelial necrosis, and severe local reactions at the injection site.
Riżultati osservati kienu jinkludu tossiċità ematopoetika (lewkopinja severa, anemija, u tnaqqis limfojde u tal - mudullun) kif ukoll żidiet fit- testijiet tal- funzjoni tal- fwied, deġenerazzjoni epatoċellulari, nekrożi epiteljali intestinali u reazzjonijiet severi fis- sit ta ’ l- injezzjoni.
Renal toxicological findings were detected in multi-cycle toxicity studies conducted in monkeys.
Riżultati tossikoloġiċi renali kienu osservati fi studji ta ’ tossiċità ta ’ diversi ċikli magħmula fix- xadini.
These findings were secondary to severe local reaction at the administration site, and therefore uncertainly attributable to trabectedin; however, caution must be guaranteed in the interpretation of these renal findings, and treatment-related toxicity cannot be excluded.
Dawn ir- riżultati kienu sekondarji għal reazzjoni lokali severa fis- sit ta ’ l- għoti, u għaldaqstant mhux ċertament attribwiti għal trabectedin; madankollu, għandha tkun garantita l- kawtela fl- interpretazzjoni ta ’ dawn ir- riżultati renali, u tossiċità relatata mal- kura ma tistax tiġi eskluża.
Trabectedin is genotoxic both in vitro and in vivo.
Trabectedin huwa ġenotossiku kemm in vitro u in vivo.
Long-term carcinogenicity studies have not been performed.
Ma sarux studji ta ’ karċinoġeneċità fuq tul ta ’ żmien.
Fertility studies with trabectedin were not performed but limited histopathological changes were observed in the gonads in the repeat dose toxicity studies.
Ma sarux studji fuq fertilità bi trabectedin iżda bidliet istopatoloġiċi ristretti kienu osservati fil- gonadi fl- istudji ta ’ tossiċità tad- dożi ripetuti.
Considering the nature of the compound (cytotoxic and mutagenic), it is likely to affect the reproductive capacity.
B’ konsiderazzjoni tan- natura tat- taħlita (ċitotossika u mutaġenika), x’ aktarx li teffettwa l- kapaċita riproduttiva.
Potassium dihydrogen phosphate.
Potassium dihydrogen phosphate.
Phosphoric acid (for pH-adjustment).
Phosphoric acid (għal aġġustament tal- pH).
Potassium hydroxide (for pH-adjustment).
Potassium hydroxide (għal aġġustament tal- pH).
Yondelis must not be mixed or diluted with other medicinal products except those mentioned in section 6.6.
Yondelis m’ għandux jitħallat jew jiġi dilwit ma ’ prodotti mediċinali oħra ħlief dawk imsemmija f’ sezzjoni 6. 6.
36 months.
36 xahar.
After reconstitution, chemical and physical stability has been demonstrated for 30 hours up to 25ºC.
Wara r- rikostitutzzjoni, stabbilità kimika u fiżika intweriet għal 30 siegħa f’ temperatura sa 25ºC.
From a microbiological point of view, the reconstituted solution should be diluted and used immediately.
Mil- lat mikrobijoloġiku, is- soluzzjoni rikostitwita għandha tkun dilwita u użata minnufih.
If not diluted and used immediately, in-use storage times and conditions prior to use of the reconstituted product are the responsibility of the user and would normally not be longer than 24 hours at 2ºC to 8ºC, unless reconstitution has taken place in controlled and validated aseptic conditions.
Jekk ma tkunx dilwita u użata minnufih, il- ħinijiet ta ’ ħażna waqt l- użu u l- kondizzjonijiet qabel l- użu tal - prodott rikostitwit huma r- risponsibbilità ta ’ l- utent u normalment ikunu mhux itwal minn 24 sigħat f’ temperatura ta ’ bejn 2ºC sa 8ºC, sakemm ir- rikostituzzjoni ma tkunx saret f’ kondizzjonijiet asettiċi ikkontrollati u ivvalidati.
After dilution, chemical and physical stability has been demonstrated for 30 hours up to 25ºC.
Wara d- dilwazzjoni, l- istabbilità kimika u fiżika intweriet għal 30 siegħa f’ temperatura sa 25ºC.
For storage conditions of the reconstituted and diluted medicinal product, see section 6.3.
Għal kundizzjonijiet ta ’ ħażna tal- prodott mediċinali rikostitwit u dilwit, ara sezzjoni 6. 3.
6.5 Nature and contents of container
12 6. 5 In- natura tal- kontenitur u ta ’ dak li hemm ġo fih
12 Yondelis is supplied in a Type I colourless glass vial with a bromobutyl rubber stopper covered with an aluminium flip-off seal.
Yondelis huwa ipprovdut f’ kunjett tal- ħġieġ bla kulur Tip I b’ tapp tal- lastku bromobutyl mgħotti b’ siġill ta ’ l- aluminju li jgħola u jinqala ’ permezz ta ’ saba ’.
Each outer carton contains one vial.
Kull kartuna ta ’ barra fiha kunjett wieħed.
Preparation for intravenous infusion
Preparazzjoni għall- infużjoni intravenuża
Appropriate aseptic techniques must be used.
Għandhom jintużaw tekniċi asettiċi adattati.
Yondelis must be reconstituted and further diluted prior to infusion.
Yondelis għandu jiġi rikostitwit u dilwit qabel l- infużjoni.
Each vial containing 0.25 mg of trabectedin is reconstituted with 5 ml of sterile water for injections.
Kull kunjett li fih 0. 25 mg ta ’ trabectedin huwa rikostitwit b’ 5 ml ilma għall- injezzjoni sterili.
The solution obtained has a concentration of 0.05 mg/ ml and is for single-use only.
Is - soluzzjoni miksuba għandha konċentrazzjoni ta ’ 0. 05 mg/ ml u għandha tintuża darba biss.
Instructions for reconstitution
Struzzjonijiet għal rikostituzzjoni
A syringe is used to inject 5 ml of sterile water for injections into the vial.
Siringa hija użata biex tinjetta 5 ml ta ’ ilma għall- injezzjoni sterili għal ġol- kunjett.
Shake the vial until complete dissolution.
Ċaqlaq il- kunjett sakemm ikun hemm jinħall kollox.
The reconstituted solution results in a clear, colourless or slightly yellowish solution, essentially free of visible particles.
Is- soluzzjoni rikostitwita tirriżulta f’ soluzzjoni ċara, bla kulur jew xi ftit safranija, essenzjalment ħielsa minn frak viżibbli.
This reconstituted solution contains 0.05 mg/ ml of trabectedin.
Din is- soluzzjoni rikostitwita fiha 0. 05 mg/ ml ta ’ trabectedin.
It requires further dilution and is for single-use only
Hija teħtieġ aktar dilwazzjoni u għandha tintuża darba biss.
Instructions for dilution
Struzzjonijiet għad- dilwazzjoni
The reconstituted solution should be diluted with sodium chloride 9 mg/ ml (0.9%) solution for infusion or glucose 50 mg/ ml (5%) solution for infusion.
Is- soluzzjoni rikostitwita għandha tiġi dilwita b’ soluzzjoni għal infużjoni ta ’ sodium chloride 9mg/ ml (0. 9%) jew soluzzjoni ta ’ glucose għal infużjoni 50 mg/ ml (5%).
The required volume should be calculated as follows:
Il- volum meħtieġ huwa ikkalkulat kif ġej:
Volume (ml) = BSA (m2) x individual dose (mg/ m2) 0.05 mg/ ml
Volum (ml) = BSA (m2) x dożaġġ individwali (mg/ m2) 0. 05 mg/ ml
BSA = Body Surface Area
BSA = Erja Superfiċjali tal- Ġisem
If administration is to be made through a central venous line, the appropriate amount of reconstituted solution should be withdrawn from the vial and added to an infusion bag containing ≥ 50 ml of diluent (sodium chloride 9 mg/ ml (0.9%) solution for infusion or glucose 50 mg/ ml (5%) solution for infusion), being the concentration of trabectedin in the infusion solution ≤ 0.030 mg/ ml.
Jekk se jingħata permezz ta ’ linja ċentrali fil- vina, l- ammont adegwat ta ’ soluzzjoni rrikostitwita għandu jittieħed mill- kunjett u miżjud fil- borża ta ’ l- infużjoni li jkun fiha ≥ 50 ml tad- dilwent (soluzzjoni għall- infużjoni ta ’ sodium chloride 9 mg/ ml (0. 9%) jew soluzzjoni għall- infużjoni ta ’ glucose 50 mg/ ml (5%)), biex b’ hekk il- konċentrazzjoni ta ’ trabectedin fis- soluzzjoni għall- infużjoni tkun ≤ 0. 030 mg/ ml.
If central venous access is not feasible and a peripheral venous line has to be used, the reconstituted solution should be added to an infusion bag containing ≥ 1,000 ml of diluent (sodium chloride 9 mg/ ml (0.9%) solution for infusion or glucose 50 mg/ ml (5%) solution for infusion).
Jekk aċċess venuż ċentrali mhux possibbli u trid tintuża linja venuża periferali, is- soluzzjoni rikostitwita għandha tiġi miżjuda ġo borża ta ’ l- infużjoni li fiha ≥ 1, 000 ml ta ’ dilwent (soluzzjoni għall- infużjoni ta ’ sodium chloride 9 mg/ ml (0. 9%) jew soluzzjoni għall- infużjoni ta ’ glucose 50 mg/ ml (5%).
Parenteral solutions should be inspected visually for particles prior to administration.
Soluzzjonijiet parenterali għandhom jiġu spezzjonati viżwalment għal frak qabel l - għoti.
Once the infusion is prepared, it should be administered immediately.
La darba l - infużjoni hija ippreparata, hija għandha tiġi amministrata minnufih.
Instructions for handling and disposal
Struzzjonijiet għal manipulazzjoni u rimi
Yondelis is a cytotoxic anticancer medicinal product and, as with other potentially toxic compounds, caution should be exercised during handling.
Yondelis huwa prodott mediċinali ċitotossiku kontra l- kanċer u, bħal taħlitiet potenzjalment tossiċi oħra, għandha tintuża l- kawtela waqt il- manipulazzjoni.
Procedures for proper handling and disposal of cytotoxic medicinal products must be followed.
Proċeduri għal manipulazzjoni u rimi xieraq ta ’ prodotti mediċinali ċitotossiċi għandhom jiġu segwiti.
Personnel should be trained in the correct techniques to reconstitute and dilute the medicinal product and should wear protective clothing including mask, goggles and gloves during the reconstitution and dilution.
Personal għandhom jiġu mħarrġa fit- tekniċi korretti biex jirrikostitwixxu u jidilwu l- prodott mediċinali u għandhom jilbsu ħwejjeġ protettivi 13 inklużi maskra, nuċċali u ingwanti waqt ir- rikostituzzjoni u d- dilwiment.
Pregnant staff must be excluded from working with this medicinal product.
Impjegati tqal għandhom jiġu esklużi milli jaħdmu b’ dan il- prodott mediċinali.
13 Accidental contact with the skin, eyes or mucous membranes must be treated immediately with copious amounts of water.
Kuntatt aċċidentali mal- ġilda, l- għajnejn jew ir- riti mukożia għandu jiġi ttrattat minnufih b’ ammonti abbundanti ta ’ ilma.
Any unused product or waste material should be disposed of in accordance with local requirements for cytotoxic medicinal products.
Kull fdal tal- prodott li ma jkunx intuża jew skart li jibqa wara l- użu tal- prodott għandu jintrema kif jitolbu l- liġijiet lokali.
No incompatibilities have been observed between Yondelis and type I glass bottles, polyvinylchloride (PVC) and polyethylene (PE) bags and tubing, polyisoprene reservoirs and titanium implantable vascular access systems.
L- ebda inkompatibbil ma ġiet osservata bejn Yondelis u fliexken ta ’ ħġieġ tip I, boroż u pajpijiet tal - polyvinylchloride (PVC) u polyethylene (PE), kontenituri għall- ħażna magħmula minn polyisoprene u sistemi t’ aċċess vaskulari impjantabbli tat- titanju.
Avda. de los Reyes 1, Polígono Industrial La Mina 28770 Colmenar Viejo (Madrid) Spain
Avda. de los Reyes 1, Polígono Industrial La Mina 28770 Colmenar Viejo (Madrid) Spanja
17 September 2007
17 ta ’ Settembru 2007
Yondelis 1 mg powder for concentrate for solution for infusion.
Yondelis 1 mg trab għal konċentrat għal soluzzjoni għall- infużjoni.
Each vial contains 1 mg of trabectedin.
Kull kunjett fih 1 mg ta ’ trabectedin.
Each vial contains 8 mg of potassium and 0.4 g of sucrose.
Kull kunjett fih 8 mg ta ’ potassium u 0. 4 g of sucrose.
15
15 Alanine aminotransferase (ALT) u Aspartate aminotransferase (AST) ≤ 2. 5 x ULN
- Creatinine clearance ≥ 30 ml/ min
Rata ta ’ tneħħija ta ’ kreatinina ≥ 30 ml/ min
The same criteria as above must be met prior to re-treatment.
L- istess kriterji bħal t’ hawn fuq iridu jintlaħqu qabel kura mill- ġdid.
Otherwise treatment must be delayed for up to 3 weeks until the criteria are met.
Altrimenti l- kura trid tkun ittardjat sa 3 ġimgħat sakemm il- kriterji jintlaħqu.
The same dose should be given for all cycles provided that no grade 3-4 toxicities are seen and that the patient fulfils the re-treatment criteria.
L- istess doża għandha tingħata għaċ- ċikli kollha kemm- il darba ma tintwera l- ebda tossiċità ta ’ grad 3 - 4 u li l- pazjent jissodifa l- kriterji ta ’ kura mill- ġdid..
Prior to re-treatment, patients must fulfil the baseline criteria defined above.
Aġġustamenti tad- doża waqt il- kura Qabel kura mill- ġdid, il- pazjenti jeħtieġu li jissodisfaw kriterji ta ’ riferiment bażi kif imfissra hawn fuq.
- Any other grade 3 or 4 adverse reactions (such as nausea, vomiting, fatigue)
- Reazzjonijiet avversi oħra grad 3 jew 4 (bħal ma ’ huma dardir, remettar, għeja kbira)
Treatment continued whilst clinical benefit was noted.
Il- kura kompliet waqt li benefiċċju kliniku kien innotat.
16 No studies with the proposed regime have been conducted in patients with liver dysfunction.
16 Pazjenti b’ indeboliment fil- funzjoni epatika
A full blood cell count including differential and platelet count must be performed at baseline, weekly for the first two cycles and then once between cycles (see section 4.2).
Newtropenja u tromboċitopenja fi gradi 3 u 4 assoċjati ma ’ terapija bi trabectedin ġew irrapportati b’ mod komuni ħafna. Għadd sħiħ taċ- ċelloli tad- demm li jinkludu l- għadd divrenzjali u l- għadd tal - plejtlets għandhom isiru fil- linja ta ’ riferiment bażi, kull ġimgħa għall- ewwel żewġ cikli u mbagħad darba bejn iċ- ċikli (ara sezzjoni 4. 2).
Trabectedin must not be used in patients with CPK > 2.5 ULN (see section 4.2).
17 Trabectedin m’ għandux jintuża f’ pazjenti b’ CPK > 2. 5 ULN (ara sezzjoni 4. 2).
17 parenteral hydration, urine alkalinisation and dialysis should be promptly established, as indicated.
Jekk ikun hemm rabdomajoliżi, miżuri ta ’ appoġġ bħal ma ’ huma idratazzjoni parenterali, alkalinizzazzjoni ta ’ l- awrina u dijaliżi għandhom fil- pront jiġu stabbiliti, kif indikati.
Caution should be taken if medicinal products associated with rhabdomyolysis (e. g. statins), are administered concomitantly with trabectedin, since the risk of rhabdomyolysis may be increased
Kawtela għandha tittieħed jekk prodottti mediċinali assoċjati ma ’ rabdomajoliżi (eż. statins), huma amministrati flimkien ma ’ trabectedin, peress li r- riskju ta ’ rabdomajoliżi jista ’ jiżdied
Co-administration of Yondelis with potent inhibitors of the enzyme CYP3A4 should be avoided (see section 4.5).
L- għoti ta ’ Yondelis flimkien ma ’ impedituri ta ’ l- enżima CYP3A4 għandu jiġi evitat (ara sezzjoni 4. 5).
Men in fertile age and women of childbearing potential must use effective contraception during treatment and 3 months thereafter for women and immediately inform the treating physician if a pregnancy occurs, and 5 months after treatment for men (see section 4.6).
Irġiel f’ età fertili u nisa bil- possibilità li jkollhom it- tfal għandhom jużaw kontraċezzjoni effettiva waqt il- perijodu ta ’ kura u sa 3 xhur wara għan- nisa u għandhom jinfurmaw lit- tabib kuranti immedjatament jekk ikun hemm tqala, u 5 xhur wara l- kura ta ’ l- irġiel (ara sezzjoni 4. 6).
This medicine contains potassium, less than 1 mmol (39 mg) per vial, i. e. essentially “ potassium-free”.
Din il- mediċina fiha l- potassium, anqas minn 1 mmol (39 mg) f’ kull kunjett i. e. essenzjalment “ mingħajr potassium ”.
Likewise co-administration with potent inducers of this enzyme (e. g. rifampicin, phenorbarbital, Saint John’ s Wort) may decrease the systemic exposure to trabectedin.
18 rifampicin, phenorbarbital, Saint John’ s Wort), jistgħu jnaqqsu l- esponiment sistemiku għal trabectedin.
Concomitant administration of inhibitors of Pgp, e. g. cyclosporine and verapamil, may alter trabectedin distribution and/ or 18 elimination.
L- għoti flimkien ta ’ impedituri ta ’ Pgp, eż. cyclosporine u verapamil, jistgħu ibiddlu l- firxa u/ jew l- eliminazzjoni ta ’ trabectedin.
Men in fertile age and women of childbearing potential must use effective contraception during treatment and 3 months thereafter for women and immediately inform the treating physician if a pregnancy occurs (see section 5.3) and 5 months after treatment for men (see section 4.4).
Irġiel f’ età fertili u nisa bil- potenzjal li jkollhom it- tfal għandhom jużaw kontraċezzjoni effettiva waqt il- kura u sa 3 xhur wara għan- nisa u jinfurmaw lit- tabib kuranti immedjatament jekk isseħħ tqala, u 5 xhur wara l- kura ta ’ l- irġiel (ara sezzjoni 4. 4).
Breast-feeding is contraindicated during treatment and 3 months thereafter (see section 4.3).
It- treddigħ huwa kontra- indikat waqt il- kura u sa 3 xhur wara (ara sezzjoni 4. 3).
Approximately 91% of patients can be expected to have adverse reactions of any grade.
19 Madwar 91% tal- pazjenti jistgħu jkunu mistennija li jkollhom reazzjonijiet avversi ta ’ kwalunkwe grad.
The most common adverse reactions of any severity grade were nausea, fatigue, vomiting, anorexia, neutropenia, and increases in AST/ ALT.
L- aktar reazzjonijiet avversi komuni ta ’ kwalunkwe qawwa kienu dardir, għeja kbira, rimettar, anoressja, newtropenja, u żidiet fl- AST/ ALT.
Fatal adverse reactions have occurred in 1.9% of patients.
Reazzjonijiet avversi fatali seħħew f ’ 1. 9% tal- pazjenti.
The frequencies of the adverse reactions reported below are classified as very common (≥ 1/ 10), common (≥ 1/ 100 to < 1/ 10) and uncommon (≥ 1/ 1000 to < 1/ 100).
Reazzjonijiet avversi Il- frekwenzi ta ’ reazzjonijiet avversi rapportati hawn isfel huma kklassifikati bħala komuni ħafna (≥ 1/ 10), komuni (≥ 1/ 100 sa < 1/ 10) u mhux komuni (≥ 1/ 1000 sa < 1/ 100).