qanastek/EMEA-V3 huggingface dataset:
CNS medicines: caution is advised when YENTREVE is taken in combination with other centrally acting medicines or substances, including alcohol and sedative medicines (benzodiazepines, morphinomimetics, antipsychotics, phenobarbital, sedative antihistamines).
Mediċini li jaffettwaw is- CNS: hija rakkomandata l- attenzjoni meta YENTREVE jintuża flimkien ma ’ sustanzi jew mediċini oħra li jaġixxu fuq is- sistema nervuża ċentrali, li jinkludi l- alkoħol u l- mediċini sedattivi (benzodiazepines, morfinomimetiċi, anti- psikotiċi, phenobarbital u l- antistaminiċi sedattivi).
These medicines increase the risk of side effects; if you get any unusual symptom taking any of these medicines together with YENTREVE, you should see your doctor.
Dawn il- mediċini jżidu r- riskju ta ’ effetti sekondarji; jekk ikollok xi sintomu li mhux mistenni meta qiegħed/ qiegħda tieħu xi mediċini minn dawn flimkien ma ’ YENTREVE, għandek tmur għand it- tabib tiegħek.
Taking YENTREVE with food and drink YENTREVE may be taken with or without food.
Meta tieħu YENTREVE ma ’ l- ikel u max- xorb YENTREVE jista 'jittieħed ma' l- ikel jew fuq stonku vojt.
You should take extra care if you drink alcohol while taking YENTREVE.
Għandek toqgħod iżjed attent jekk tixrob l - alkoħol waqt li tkun qiegħed/ qiegħda tieħu YENTREVE.
You should use YENTREVE only after discussing the potential benefits and any potential risks to your unborn child with your doctor.
Tqala u Treddigħ Għid lit- tabib tiegħek jekk issir tqila jew qiegħda tipprova ssir tqila, waqt li qiegħda tieħu YENTREVE. Ghandek biss tuża YENTREVE wara li tkun iddiskutejt mat- tabib tiegħek il- benefiċċji possibbli u kull riskju possibbli għat- tarbija li għada ma twelditx.
The use of YENTREVE while breastfeeding is not recommended.
Mhuwiex rakkomandat l- użu ta ’ YENTREVE waqt it- treddigħ.
Do not drive or use any tools or machines until you know how YENTREVE affects you.
Sewqan u tħaddim ta ’ magni Issuqx u tagħmilx użu minn għodda jew tħaddem magni sakemm tkun taf b’ liema mod jaffettwak YENTREVE..
Important information about some of the ingredients of YENTREVE YENTREVE contains sucrose.
Tagħrif importanti dwar xi wħud mis- sustanzi ta ’ YENTREVE YENTREVE fih s- sucrose.
HOW TO TAKE YENTREVE
KIF GĦANDEK TIEĦU YENTREVE
Always take YENTREVE exactly as your doctor has told you.
Dejjem għandek tieħu YENTREVE skond kif qallek it- tabib.
The recommended dose of YENTREVE is one capsule of 40 mg twice a day (in the morning and late afternoon/ evening).
45 Id- doża rakkomandata ta ’ YENTREVE hija kapsula waħda ta ’ 40 mg darbtejn kuljum (filgħodu u tard wara nofsinhar/ filgħaxija).
YENTREVE is for oral use.
YENTREVE għandu jittieħed mill- ħalq.
To help you remember to take YENTREVE, you may find it easier to take it at the same times every day.
Biex tiftakar tieħu YENTREVE, tista ’ ssibha aktar faċli li teħodha kuljum fl- istess ħinijiet.
43 Do not stop taking YENTREVE without talking to your doctor.
Tieqafx tieħu YENTREVE mingħajr ma tkellem lit- tabib tiegħek.
If you take more YENTREVE than you should Call your doctor or pharmacist immediately if you take more than the amount of YENTREVE prescribed by your doctor.
Jekk tieħu YENTREVE aktar milli suppost Ċempel immedjatament lit- tabib jew lill- ispiżjar tiegħek jekk tieħu aktar ammont ta 'YENTREVE minn kemm ordnalek it- tabib.
If you forget to take YENTREVE Do not take a double dose to make up for forgotten doses.
Jekk tinsa tieħu YENTREVE M’ għandekx tieħu doża doppja biex tpatti għad dożi li tkun insejt tieħu.
Do not take more than the daily amount of YENTREVE that has been prescribed for you in one day.
Tieħux iżjed mill- ammont ta 'YENTREVE li ordnalek it- tabib għal ġurnata waħda.
If you stop taking YENTREVE Do not stop taking your capsules without the advice of your doctor even if you feel better.
Jekk tieqaf tieħu YENTREVE Tieqafx tieħu l- kapsuli tiegħek mingħajr ma tieħu l- parir tat- tabib anki jekk tħossok aħjar.
If your doctor thinks that you no longer need YENTREVE he will ask you to reduce your dose over 2 weeks.
Jekk it- tabib tiegħek jaħseb li m' għadx għandek bżonn tieħu YENTREVE huwa se jgħidlek biex tnaqqas id- doża fuq perijodu ta ’ ġimgħatejn.
Some patients, who suddenly stop taking YENTREVE after more than 1 week of therapy, have had symptoms such as dizziness, tingling feelings like pins and needles, sleep disturbances (vivid dreams, nightmares, inability to sleep), feeling restless or agitated, feeling anxious, feeling sick (nausea) or being sick (vomiting), tremor (shakiness), headaches, feeling irritable, diarrhoea, excessive sweating or vertigo..
Xi pazjenti li waqqfu jieħdu YENTREVE f' daqqa wara iżjed minn ġimgħa ta ’ kura kellhom sintomi bħal sturdament, sensazzjonijiet ta ’ tniggiż, problemi ta ’ irqad( ħolm stramb, ħmar il- lejl, ma tkunx tista ’ torqod), iħossuhom irrekweti u aġitati, iħossuhom ansjużi, iħossuhom ħażin (tqalligħ) jew jgħamillhom ħażin (rimettar), tregħid (ċaqliq ripetut) uġigħ ta 'ras, iħossuhom irritabbli, dijarea, għaraq esaġerat jew vertigo..
Like all medicines, YENTREVE can cause side effects, although not everybody gets them.
Bħal kull mediċina oħra, YENTREVE jista ’ jkollu effetti sekondarji, għalkemm ma jidhrux fuq kulħadd.
Very common side effects (these can affect more than 1 in 10 patients treated) Feeling sick (nausea), dry mouth, and tiredness.
Efetti sekondarji komuni ħafna (dawn jistgħu jaffettwaw iżjed minn pazjent 1 minn kull 10 pazjenti kkurati) Tħossok ma tiflaħx (tqalligħ), nixfa fil- ħalq u għeja,
Common side effects (these can affect from 1 to 10 users in 100 patients treated) • Anxiety, having abnormal dreams. • Dizziness, tremor or numbness, including numbness or tingling of the skin. • Being sick (vomiting), heartburn or breaking wind, lack of appetite. • Blurred eyesight. • Feeling the heart pumping in the chest or hot flushes. • Problems getting an erection, changes in orgasm or less sex drive. • (itchy) Rash. • Muscle pain, muscle tightness or muscle spasm.
Effetti sekondarji komuni (dawn jistgħu jaffettwaw minn 1 sa 10 pazjenti minn kull 100 pazjent ikkurat) • Ansjetà, ikollok ħolm mhux tas- soltu. • Sturdament, rogħda jew tirżiħ, inkluż it- tirżiħ jew tnemnin tal- ġilda • Tħossok ma tiflaħx (rimettar), ħruq ta ’ l- istonku jew tgħaddi l- arja, tnaqqis fil- piż jew nuqqas ta ’ aptit. • Vista mċajpra • Tħoss il- qalb tħabbat f’ sidrek jew fwawar. • Problemi biex ikollok erezzjoni, tibdil fl- orgażmu jew tnaqqis fil- ħajra għas- sess. • Raxx (bil- ħaqq) • Uġigħ fil- muskoli, riġidità fil- muskoli, spażmu fil- muskolu.
44 • Flushing, increase in blood pressure, feeling cold in your fingers and/ or toes, feeling dizzy (particularly when standing up too quickly), fast or irregular heart beat, night sweats, cold sweats, shivering or fainting. • Changes in ejaculation, abnormal periods, including heavy or prolonged periods • Allergic reactions, increased tendency to bruise, blisters or sensitivity to sunlight. • Muscle twitching. • Need to pass urine during the night or difficulty or inability to pass urine. • Grinding of teeth, dehydration, feeling hot/ cold, thirst, throat tightness or nose bleeds. • Increased level of cholesterol in the blood.
46 Effetti sekondarji mhux komuni( dawn jistgħu jaffettwaw minn 1 sa 10 pazjenti minn 1, 000 pazjent ikkurat) • Infjammazzjoni tal- gerżuma. • Tħossok aġitat, tħossok diżorjentat, tħossok bi ngħas, ma torqodx tajjeb, nuqqas ta ’ motivazzjoni jew tittewweb iżjed mis- soltu. • Ttiegħem l- affarijiet differenti mis- soltu, disturbi ta ’ attenzjoni jew spażmi u movimenti involontarji tal- muskoli. • Tnaqqiż fil- piż jew żieda fil- piż, tfewwiq, indiġestjoni jew gastroenterite. • Infjammazzjoni tal- fwied li tista ’ tkun il- kawża ta ’ uġigħ addominali, għeja jew il- ġilda tkun ta ’ kulur safrani. • Vertigo, tinnitus (is- sensazzjoni ta ’ ħsejjes fil- widnejn meta m’ hemm ebda ħoss madwarek), uġigħ fil- widnejn. • Il- ħabba ta ’ l- għajn tkun kbira (iċ- centru skur ta ’ l- għajnejn) jew disturbi fil- vista. • Ħmura fil- wiċċ, żieda fil- pressjoni tad- demm, tħoss is- swaba ’ ta ’ idejk jew/ u ta ’ saqajk kesħin, tħossok se tistordi (speċjalment meta tqum bil- wieqfa malajr wisq), tħabbit mgħaġġel jew irregolari tal- qalb, tegħreq matul il- lejl, tħoss l- għaraq ixoqq għalik, tregħid jew ħass ħażin. • Tibdil fl- eġakulazzjoni, pirjids mhux tas- soltu, li jinkludu pirjids b’ ħafna demm jew li jdumu • Reazzjonijiet allerġiċi, tendenza ogħla li titbenġel, infafet jew sensittività għad- dawl tax- xemx. • Ġbid involontarju tal- muskoli. • Il- bżonn li tgħaddi l- awrina matul il- lejl jew diffikultà jew inabbiltà biex tgħaddi l- awrina. • Tagħżiż tas- snien, diżidratazzjoni, tħossok sħun/ kiesaħ, għatxan, rassa fil- gerżuma jew tinfaraġ.
Rare side effects (these can affect from 1 to 10 users in 10,000 patients treated) • Mania (a disorder which symptoms are over activity, racing thoughts and decrease need for sleep), experiencing hallucinations • Increased level of sugar in the blood, low levels of sodium in the blood (the symptoms are feeling sick and unwell with weak muscles or confused), syndrome of inadequate secretion of anti-diuretic hormone (SIADH). • Bad breath. • Increased pressure in the eye. • Menopausal symptoms. • Sexual problems. • Abnormal manner of walking, contraction of the jaw muscle. • Decrease of activity of the thyroid gland, chest or stomach pain. • Need to pass more urine then usual or urine flow decreased.
Effetti sekondarji rari (dawn jistgħu jaffettwaw minn 1 sa 10 pazjenti minn kull 10, 000 pazjent ikkurat) • Manija (marda fejn is- sintomi huma li tkun attiv iżżejjed, ikollok ħsibijiet li jiġru bik u jonqos il- bżonn ta ’ l- irqad), ikollok l- alluċinazzjonijiet. • Żieda fil- livell taz- zokkor fid- demm, livelli baxxi ta ’ sodium fid- demm (is- sintomu huma tħossok ma tiflaħx u m’ intix f’ sikktek bil- muskoli dgħajfin jew konfuż), sindromu ta ’ sekrezzjoni insuffiċjenti ta ’ l- ormon kontra d- djuresi (SIADH). • Togħma ħażina fil- ħalq. • Żieda tal- pressjoni fl- għajnejn. • Sintomi tal- menopawża. • Problemi sesswali • Timxi b’ mod mhux normali, kontrazzjoni tal- muskolu tax- xedaq. • Tnaqqis fl- attività tal- glandola tat- tirojde, uġigħ fis- sider jew fl- istonku. • Il- bżonn li tgħaddi iżjed awrina mis- soltu jew ikun hemm tnaqqis fil- fluss ta ’ l- awrina.
Other possible side effects • Experiencing aggression and anger suicidal thoughts or behaviour. • A sensation of restlessness or an inability to sit or stand still, “ Serotonin syndrome” (a rare reaction which may cause feelings of great happiness, drowsiness, clumsiness, restlessness, feeling of being drunk, fever, sweating or rigid muscles), fits or stiffness. • Passing bright red blood in your stools vomiting blood, or black tarry stools (faeces). • Abnormal urine odour. • Yellow colouration of the skin (jaundice), hepatic failure, Stevens-Johnson syndrome, sudden swelling of skin of mucosa (angioedema).
Effett sekondarji oħra li jista ’ jkollok • Tħossok aggressiv u rrabjat., imġiba jew ħsibijiet ta ’ suwiċidju. • Sensazzjoni ta ’ irrekwitezza jew l- inkapaċità li wieħed joqgħod mingħajr ma jiċċaqlaq, “ Is - Sindromu ta ’ Serotonin ” (reazzjoni rari li tista ’ tikkawza sensazzjonijiet ta ’ kuntentezza kbira, ħedla, guffaġni, irrekwitezza, sensazzjoni bħallikieku fis- sakra, deni, muskoli riġidi jew għarqana), aċċessjonijiet jew ebusija. • Tgħaddi demm ta ’ kulur aħmar qawwi ma ’ l- ippurgar, tirremetti d- demm, jew l- ippurgar( il - feċi) ikun iswed bħall- qatran. • L- awrina jkollha riħa mhux tas- soltu. • Il- ġilda tisfar (suffejra), insuffiċjenza epatika, sindromu ta ’ Stevens- Johnson, nefħa f’ daqqa tal- ġilda jew tal- mukoża (anġjoedima).
HOW TO STORE YENTREVE
KIF TAĦŻEN YENTREVE
Do not use YENTREVE after the expiry date which is stated on the carton.
Tużax YENTREVE wara d- data ta ’ skadenza li tidher fuq il- kaxxa.
What YENTREVE contains The active substance is duloxetine.
Is- sustanza attiva hija duloxetine.
Each capsule contains 20 or 40 mg of duloxetine (as hydrochloride)
Kull kapsula fiha 20 mg jew 40 mg ta ’ duloxetine (bħala hydrochloride).
Black Iron Oxide-Synthetic (E172), Propylene glycol, Shellac.
Inkjostru iswed li jittiekel: iron oxide sintetiku iswed (E172), propylene glycol, shellac.
What YENTREVE looks like and contents of the pack YENTREVE is a hard gastro-resistant capsule.
YENTREVE issibu bħala kapsula gastro- reżistenti, iebsa.
Each capsule of YENTREVE contains pellets of the active substance with a covering to protect them from stomach acid.
Kull kapsula ta ’ YENTREVE fiha pellits tas- sustanza attiva b’ kisja sabiex tipproteġihom mill- aċidu ta ’ l- istonku.
YENTREVE is available in 2 strengths:
YENTREVE issibu f’ żewġ dożi:
The 40 mg capsule has an opaque orange body imprinted with ’ 40 mg’ and an opaque blue cap, imprinted with ‘ 9545’.
Il- kapsula ta ’ 40 mg għandha l- parti prinċipali oranġjo opak stampati b ’’ 40 mg ’ u għatu ċelesti opak, stampat b ’ '9545'.
The 20 mg capsule has an opaque blue body imprinted with ’ 20 mg’ and an opaque blue cap, imprinted with ‘ 9544’.
Il- kapsula ta ’ 20 mg għandha l- parti prinċipali ċelesti opak stampati b ’’ 20 mg ’ u għatu ċelesti opak, stampat b ’ '9544'.
YENTREVE 40 mg is available in blister packs of 28, 56, 98, 140 and 196 (2 x 98) capsules.
YENTREVE 40 mg issibu f’ pakketti b’ folji ta ’ 28, 56, 98, 140 u 196 (2 x 98) kapsula.
YENTREVE 20 mg is available in blister packs of 28, 56 and 98 capsules.
YENTREVE 20 mg issibu f’ pakketti b’ folji ta ’ 28, 56 u 98 kapsula.
For any information about this medicine, please contact the local representative of the Marketing Authorisation Holder:
Għal kull tagħrif dwar dan il- prodott mediċinali, jekk jogħġbok ikkuntattja lir- rappreżentant lokali tad - detentur ta ’ l- Awtorizzazzjoni għat- Tqegħid fis- Suq:
België/ Belgique/ Belgien S. A.
48 België/ Belgique/ Belgien S. A.
Tél/ Tel: + 32-(0)2 548 84 84 България ТП "Ели Лили Недерланд "Б .В. - България тел. + 359 2 491 41 40 Č eská republika Eli Lilly Č R, s. r. o.
Tél/ Tel: + 32 - (0) 2 548 84 84 Česká republika Eli Lilly ČR, s. r. o.
Tel: + 420 234 664 111 Danmark Eli Lilly Danmark A/ S Tlf.: +45 45 26 60 00 Deutschland Lilly Deutschland GmbH Tel. + 49-(0) 6172 273 2222
Τηλ: +30 210 629 4600
Tel: + 31(0)30 6025800 Norge Eli Lilly Norge A. S Tlf: +47 22 88 18 00
Tel: + 43 - (0) 1 711 780
Τηλ: +30 210 629 4600 España Spaly Bioquímica, S. A.
España Spaly Bioquímica, S. A.
Tel. +48 (0) 22 440 33 00 Portugal Lilly Portugal - Produtos Farmacêuticos, Lda Tel: + 351 21 412 66 00
Tel. +48 (0) 22 440 33 00
Tel: +33-(0) 1 55 49 34 34 Ireland Eli Lilly and Company (Ireland) Limited Tel: +353 (0) 1 661 4377
Tel: +33 - (0) 1 55 49 34 34
România Eli Lilly România S. R. L.
Ireland Eli Lilly and Company (Ireland) Limited Tel: +353 (0) 1 661 4377
Tel: + 40 21 4023000 Slovenija Tel: +386 (0)1 580 00 10
Slovenija Tel: +386 (0) 1 580 00 10
Tel: + 421 220 663 111 Suomi/ Finland Oy Eli Lilly Finland Ab Puh/ Tel: +358 (0)9 8545 250 Sverige Eli Lilly Sweden AB Tel: + 46-(0)8 7378800 United Kingdom Eli Lilly and Company Limited Tel: +44 (0) 1256 315999
Tel: + 421 (2) 59224 111 Suomi/ Finland Oy Eli Lilly Finland Ab Puh/ Tel: +358 (0) 9 8545 250 Sverige Eli Lilly Sweden AB Tel: + 46 - (0) 8 7378800 United Kingdom Eli Lilly and Company Limited Tel: +44 (0) 1256 315999
It explains how the Committee for Medicinal products for Human Use (CHMP) assessed the studies performed, to reach their recommendations on how to use the medicine.
Huwa jispjega kif il- Kumitat għal Prodotti Mediċinali għall- Użu mill- Bniedem (CHMP) ivvaluta l- istudji mwettqa, biex jagħti r- rakkomandazzjonijiet tiegħu dwar kif tintuża l- mediċina.
What is Yondelis?
X’ inhu Yondelis?
Yondelis is a powder that is made up into a solution for infusion (drip into a vein).
Yondelis hu trab li jinħall f’ soluzzjoni għall- infużjoni (dripp f’ vina).
It contains the active substance trabectedin.
Fih is- sustanza attiva trabectedin.
What is Yondelis used for?
Għalxiex jintuża Yondelis?
Yondelis is used to treat patients with advanced soft tissue sarcoma, a type of cancer that develops from the soft, supporting tissues of the body.
Yondelis jintuża fit- trattament ta ’ pazjenti b’ sarkoma avvanzata fit- tessut artab, tip ta ’ kanċer li jiżviluppa mit- tessuti rotob li jappoġġjaw il- ġisem.
It is used when treatment with anthracyclines and ifosfamide (other anticancer medicines) have stopped working, or in patients who cannot be given these medicines.
Jintuża meta l- kura bl- anthracyclines u b’ ifosfamide (mediċini oħra ta ’ kontra l- kanċer) ma jkunux għadhom jaħdmu, jew il- pazjenti ma jkunux jistgħu jieħdu dawn il- mediċini.
Because the number of patients with soft tissue sarcoma is low, the disease is considered ‘ rare’, and Yondelis was designated an ‘ orphan medicine ’ (a medicine used in rare diseases) on 30 May 2001.
Billi l- għadd ta ’ pazjenti b’ sarkoma fit- tessut artab huwa wieħed baxx, il- marda hija kkunsidrata ‘ rari ’, u Yondelis ġie kklassifikat bħala ‘ mediċina orfni ’ (mediċina użata fil- mardiet rari) fit- 30 ta ’ Mejju ta ’ l- 2001.
How is Yondelis used?
Kif jintuża Yondelis?
Yondelis must be given under the supervision of a doctor who is experienced in the use of chemotherapy.
Yondelis irid jingħata taħt is- superviżjoni ta ’ tabib speċjalizzat fl- użu tal- kemjoterapija.
It should only be used by qualified oncologists (cancer specialists) or other health professionals who are specialised in giving cytotoxic (cell-killing) medicines.
Għandu jintuża biss minn onkoloġisti kwalifikati (speċjalisti tal- kanċer) jew minn professjonisti tas- saħħa oħra li jkunu speċjalizzati fl- għoti ta ’ mediċini ċitotossiċi (li joqtlu ċ- ċelloli).
The recommended dose of Yondelis is 1.5 mg per square metre of body surface (calculated using the patient ’ s height and weight), given as a single intravenous infusion (drip into a vein) over 24 hours every three weeks.
Id- doża rrakkomandata ta ’ Yondelis hi 1. 5 mg kull metru kwadru ta ’ l- erja tas- superfiċje tal- ġisem (ikkalkulata mit- tul u mill- piż tal- pazjent), mogħtija bħala infużjoni waħdanija fil- vina (dripp fil- vina) li ddum tingħata 24 siegħa darba kull tliet ġimgħat.
Treatment carries on for as long as the patient shows a benefit.
It- trattament idum sakemm ikun jidher li l- pazjent qed jibbenefika.
It is recommended that Yondelis be given through a central venous line (a thin tube leading from the skin into the large veins just above the heart).
Hu rakkomandat li Yondelis jingħata permezz ta ’ katiter f’ vina ċentrali (tubu rqiq li jgħaddi mill- ġilda sal- vini kbar eżatt fuq il- qalb).
To prevent vomiting and to protect the liver, an infusion of dexamethasone (a corticosteroid) should be given before each Yondelis dose.
Biex jiġi evitat ir- rimettar u biex jiġi protett il- fwied, għandha tingħata infużjoni ta ’ dexamethasone (kortikosterojde) qabel kull doża ta ’ Yondelis.
Infusion with Yondelis should be delayed or the dose of Yondelis reduced if the patient ’ s blood counts are abnormal (such as low counts of white blood cells or platelets).
Jekk ir- riżultati tad- demm (bħall- ammont ta ’ ċelloli bojod tad- demm jew l- ammont ta ’ platelets) ikunu baxxi, l- infużjoni ta ’ Yondelis għandha tiġi posposta jew inkella għandha titnaqqas id- doża.
It should be used with caution in patients who have problems with their liver.
Għandu jintuża b’ kawtela f’ pazjenti li jkollhom problemi bil- fwied.
Yondelis must not be used in children until further information is available.
Yondelis m’ għandux jintuża fit- tfal sakemm jinkiseb iktar tagħrif.
It should not be used in those who have high bilirubin levels (a marker of certain liver problems) or who have severe problems with their kidneys.
Lanqas m’ għandu jintuża f’ dawk li jkollhom livelli għoljin ta ’ bilirubin (markatur ta ’ ċerti problemi fil- fwied jew li jkollhom problemi severi fil- kliewi.
For more information, see the Summary of Product Characteristics (also part of the EPAR).
Għal aktar tagħrif, ara s- Sommarju tal- Karatteristiċi tal- Prodott (li wkoll hu parti mill- EPAR).
How does Yondelis work?
Kif jaħdem Yondelis?
The active substance in Yondelis, trabectedin, is an anticancer medicine.
Is- sustanza attiva f’ Yondelis, trabectedin, hija mediċina ta ’ kontra l- kanċer.
It is a synthetic version of a chemical that was originally extracted from a species of tunicate or ‘ sea squirt’ (a marine animal).
Hija verżjoni sintetika ta ’ kimika li oriġinarjament kienet tiġi estratta mit- tunikat jew ‘ sea squirt ’ (animal marittimu).
7 Westferry Circus, Canary Wharf, London E14 4HB, UK Tel.
Il- kanċer 7 Westferry Circus, Canary Wharf, London E14 4HB, UK Tel.
(44-20) 74 18 84 00 Fax (44-20) 74 18 84 16 E-mail: mail@emea. europa. eu http: / /www. emea. europa. eu ©EMEA 2007 Reproduction and/ or distribution of this document is authorised for non commercial purposes only provided the EMEA is acknowledged preventing some genes in human cells from turning up their activity.
(44- 20) 74 18 84 00 Fax (44- 20) 74 18 84 16 E- mail: mail@ emea. europa. eu http: // www. emea. europa. eu ©EMEA 2007 Reproduction and/ or distribution of this document is authorised for non commercial purposes only provided the EMEA is acknowledged hu marda li fiha ċ- ċelloli jinqasmu malajr wisq, ġeneralment minħabba li l- mod ta ’ kif jaħdmu l- ġeni tagħhom ikun difettuż.
This can prevent the cells from dividing too quickly, slowing down the growth of various types of cancer, including sarcoma.
Dan jista ’ jipprevjeni ċ- ċelloli milli jinqasmu malajr wisq, u b’ hekk inaqqsu l- iżvilupp ta ’ diversi tipi ta ’ kanċer, inkluż is- sarkoma.
How has Yondelis been studied?
Kif ġie studjat YONDELIS?
The effects of Yondelis were first tested in experimental models before being studied in humans.
L- effetti ta ’ Yondelis għall- ewwel ġew ittestjati f’ mudelli esperimentali qabel ma ’ ġew studjati fil - bnedmin.
The effects of Yondelis were also studied in one main study involving 266 patients with liposarcoma (a sarcoma originating in fat cells) or leiomyosarcoma (a sarcoma originating in ‘ smooth’ or involuntary muscle cells) that was advanced or metastatic (had spread to other parts of the body).
L- effetti ta ’ Yondelis ġew studjati wkoll fi studju wieħed ewlieni li fih ħadu sehem 266 pazjent b’ liposarkoma (sarkoma li toriġina miċ- ċelloli tax- xaħam) jew leiomyosarcoma (sarkoma li torġina miċ- ċelloli tal- muskoli ‘ lixxi ’ jew involuntarji) avvanzata jew metastatika (mifruxa għal partijiet oħra tal- ġisem).
All of the patients had been treated previously with an anthracycline and ifosfamide but this treatment had stopped working.
Il- pazjenti kollha ikunu ġew trattati minn qabel b’ anthracycline u ifosfamide iżda dawn ikunu waqfu jaħdmu.
The study compared two different dosing schedules of Yondelis: three times per month, or once every three weeks.
L- istudju qabbel żewġ skedi ta ’ dożi differenti ta ’ Yondelis: tliet darbiet fix - xahar, jew darba kull tliet ġimgħat.
The main measure of effectiveness was the time until the disease got worse.
Il- mezz ewlieni tal- kejl ta ’ l- effettività kien iż- żmien sa ma ’ aggravat il- marda.
The study was still ongoing at the time of assessment.
L- istudju kien għadu għaddej fi żmien il- valutazzjoni.
What benefit has Yondelis shown during the studies?
X’ inhu l- benefiċċju ta ’ YONDELIS li ntwera f’ dawn l- istudji?
Yondelis was more effective when it was given once every three weeks than the alternative dosing schedule.
Yondelis kien iktar effettiv meta mogħti darba kull tliet ġimgħat mill- iskeda ta ’ dożi alternattiva.
In patients receiving it once every three weeks, it took an average of 3.8 months for their disease to get worse, compared with 2.1 months in those receiving Yondelis three times per month.
Fil - pazjenti li kienu qed jieħduh darba kull tliet ġimgħat, il- marda damet medja ta ’ 3. 8 xhur biex tiggrava, meta mqabbla ma ’ medja ta ’ 2. 1 xhur f’ dawk li kienu qed jieħdu Yondelis tliet darbiet kull xahar.
What is the risk associated with Yondelis?
X’ inhu r- riskju assoċjat ma ’ YONDELIS?
The most common side effects with Yondelis (seen in more than 1 patient in 10) are increased blood levels of creatine phosphokinase (marker of muscle breakdown) and of creatinine (a marker of kidney problems), decreased blood levels of albumin (a marker of liver problems), neutropenia (low levels of neutrophils, a type of white blood cell), thrombocytopenia (low levels of platelets in the blood), anaemia (low levels of red blood cells), leucopenia (low levels of leucocytes, a type of white blood cell), headache, vomiting, nausea (feeling sick), constipation, anorexia (loss of appetite), fatigue (tiredness), asthenia (weakness), hyperbilirubinaemia (high levels of bilirubin in the blood) and increased levels of liver enzymes in the blood (alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase and gamma-glutamyltransferase).
L- iktar effetti sekondarji komuni ma ’ Yondelis (li dehru f’ iktar minn pazjent wieħed minn kull 10) huma ż- żieda fil- livelli ta ’ creatine phosphokinase (markatur tat- tkissir tal- muskoli) u tal- kreatinina (markatur ta ’ problemi fil- kliewi), tnaqqis fil- livelli ta ’ l- albumina (markatur tal- problemi tal- fwied) fid- demm, newtropenja (livelli baxxi ta ’ neutrophils, tip ta ’ ċelloli tad- demm bojod), anemija (livelli baxxi ta ’ ċelloli tad- demm ħomor), leucopenia (livelli baxxi ta ’ leucocytes, tip ta ’ ċelloli tad- demm bojod), uġigħ ta ’ ras, remettar, dardir, kostipazzjoni, anoressija (nuqqas ta ’ aptit), għeja, astenja (dgħufija), livelli għoljin ta ’ bilirubin fid- demm, u żieda fil- livelli ta ’ enzimi tal- fwied fid- demm (alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase u gamma - glutamyltransferase).
For the full list of all side effects reported with Yondelis, see the Package Leaflet.
Għal- lista sħiħa ta ’ l- effetti sekondarji kollha rrappurtati b’ Yondelis, ara l - Fuljett ta ’ Tagħrif.
Yondelis should not be used in people who may be hypersensitive to trabectedin or any of the other ingredients.
Yondelis m’ għandux jintuża minn persuni allerġiċi għal trabectedin jew għal xi sustanzi oħrajn tiegħu.
It must not be used in patients who have any serious or uncontrolled infection, in combination with the vaccine for yellow fever, or in breast-feeding women.
Lanqas ma għandu jintuża minn pazjenti li jkollhom infezzjoni serja jew mhux ikkontrollata, flimkien ma ’ vaċċin tal- yellow fever, jew f’ nisa li jkunu qed ireddgħu.
Why has Yondelis been approved?
Għaliex ġie approvat YONDELIS?
The Committee for Medicinal Products for Human Use (CHMP) concluded that Yondelis’ s benefits are greater than its risks for the treatment of patients with advanced soft tissue sarcoma, after failure of anthracyclines and ifosfamide, or who are unsuited to receive these agents.
Il- Kumitat għall- Prodotti Mediċinali għall- Użu mill- Bniedem (CHMP) ikkonkluda li l- benefiċċji ta ’ Yondelis huma ikbar mir- riskji tiegħu fit- trattament ta ’ pazjenti b’ sarkoma fit- tessut artab, wara li l - anthracyclines u ifosfamide ma jkunux ħadmu, jew f’ pazjenti li ma jkunux jistgħu jieħdu dawn is - sustanzi.
The Committee noted that evidence of Yondelis’ s effects is mainly based on the treatment of liposarcoma and leiomyosarcoma.
Il- Kumitat innota li l- evidenza ta ’ Yondelis hija prinċipalment ibbażata fuq it- trattament tal - liposarcoma u tal- leiomyosarcoma.
The Committee recommended that Yondelis be given marketing authorisation.
Il- Kumitat irrakkomanda li Yondelis jingħata l- awtorizzazzjoni għat- tqegħid fis- suq.
Yondelis has been authorised under “ Exceptional Circumstances”.
Yondelis kien awtorizzat taħt “ Ċirkustanzi ta ’ Eċċezzjoni ”.
This means that because the disease is rare, it has not been possible to obtain complete information about Yondelis.
Dan ifisser li billi l- marda hi rari, ma kienx possibbli li jinkiseb tagħrif komplet dwar Yondelis.
Every year, the European Medicines Agency (EMEA) will review any new information that may become available and this summary will be updated as necessary.
Kull sena, l- Aġenzija Ewropea dwar il- Mediċini (EMEA) se tirrevedi kwalunkwe tagħrif ġdid li jista ’ jinkiseb u dan is- sommarju se jiġi aġġornat kif meħtieġ.
What information is still awaited for Yondelis?
X’ tagħrif għadu mistenni dwar YONDELIS?
The company that makes Yondelis will continue to assess which patients are more likely to respond to the medicine, and will carry out a study to investigate the effects of Yondelis in patients with a type of cancer called ‘ myxoid liposarcoma’.
Il- kumpanija li tagħmel Yondelis se tkompli tivvaluta liema pazjenti għandhom probabilità ikbar li jirrispondu għall- mediċina, u se tagħmel studju biex tistħarreġ l- effetti ta ’ Yondelis f’ pazjenti b’ tip ta ’ kanċer magħruf bħala ‘ myxoid liposarcoma ’.
Other information about Yondelis:
Tagħrif ieħor dwar Yondelis:
The European Commission granted a marketing authorisation valid throughout the European Union for Yondelis to Pharma Mar, S. A. on 17 September 2007.
Il- Kummissjoni Ewropea tat awtorizzazzjoni għat- tqegħid fis- suq valida madwar l- Unjoni Ewropea kollha għal Yondelis lil Pharma Mar, S. A. fil- 17 ta ’ Settembru 2007.
The record of Yondelis’ s designation as an orphan medicine is available here.
Ir- rekord tal- klassifikazzjoni ta ’ Yondelis bħala mediċina orfni huwa disponibbli minn hawnhekk.
The full EPAR for Yondelis can be found here.
L- EPAR sħiħ għal Yondelis huwa disponibbli minn hawnhekk.
EU Number EU/ 1/ 07/ 417/ 001
Numru ta ’ l- EU EU/ 1/ 07/ 417/ 001
Invented name Yondelis
Isem inventat Yondelis
Strength 0.25 mg
Qawwa 0. 25 mg
Pharmaceutical Form Powder for concentrate for solution for infusion
Għamla farmaċewtika trab għall- konċentrat għal soluzzjoni għall- infużjoni
Route of administration Intravenous use
Mnejn jingħata Użu għal ġol- vini
Packaging Vial (glass)
Il- pakkett Kunjett (tazza)
Package size 1 vial
Daqs tal- pakkett 1 kunjett
Powder for concentrate for solution for infusion
trab għall- konċentrat għal soluzzjoni għall- infużjoni
Yondelis 0.25 mg powder for concentrate for solution for infusion.
Yondelis 0. 25 mg trab għal konċentrat għal soluzzjoni għall- infużjoni.
Each vial contains 0.25 mg of trabectedin.
Kull kunjett fih 0. 25 mg ta ’ trabectedin.
1 ml of reconstituted solution contains 0.05 mg of trabectedin.
1 ml ta ’ soluzzjoni rikostitwita fih 0. 05 mg ta ’ trabectedin.
Each vial contains 2 mg of potassium and 0.1 g of sucrose.
Kull kunjett fih 2 mg ta ’ potassium u 0. 1 g ta ’ sucrose.
White to off-white powder.
Trab abjad għal abjad maħmuġ.
Yondelis is indicated for the treatment of patients with advanced soft tissue sarcoma, after failure of anthracyclines and ifosfamide, or who are unsuited to receive these agents.
Yondelis huwa indikat għall- kura ta ’ pazjenti b’ sarkoma avvanzata tat- tessuti morbidi, wara fallimenti ta ’ antraċiċlini u ifosfamide, jew għal dawk li mhumiex adattati biex jirċievu dawn il- mediċini.
Efficacy data are based mainly on liposarcoma and leiomyosarcoma patients.
Dejta dwar l- effikaċja hija ibbażata l- aktar fuq pazjenti b’ liposarkoma u lejomajosarkoma.
Yondelis must be administered under the supervision of a physician experienced in the use of chemotherapy.
Yondelis għandu jingħata minn tabib b’ esperjeza fl- użu tal- kimoterapija.
Its use should be confined to qualified oncologists or other health professionals specialised in the administration of cytotoxic agents.
L- użu tiegħu għandu jkun ristrett għal onkoloġisti kwalifikati jew professjonisti oħra tal- kura tas- saħħa speċjalizzati fl- għoti ta ’ mediċini ċitotossiċi.
The recommended dose is 1.5 mg/ m2 body surface area, administered as an intravenous infusion over 24 hours with a three-week interval between cycles.
Id- doża rakkomandata hi ta ’ 1. 5 mg/ m2 erja superfiċjali korporali, amministrata bħala infużjoni ġol- vina fuq medda ta ’ 24 siegħa b’ intervall ta ’ tliet ġimgħat bejn iċ- ċikli.
Administration through a central venous line is strongly recommended (see section 6.6).
Għoti minn ġo linja venuża ċentrali huwa rakkomandat bil- qawwa (ara sezzjoni 6. 6).
All patients must receive 20 mg of dexamethasone intravenously 30 minutes prior to Yondelis; not only as anti-emetic prophylaxis, but also because it appears to provide hepatoprotective effects.
Il- pazjenti kollha għandhom jirċievu 20 mg ta ’ dexamethasone ġol- vina 30 minuta qabel Yondelis; mhux biss bħala profilassi anti- emetika, iżda ukoll minħabba li tidher li tipprovdi effetti epatoprotettivi.
Additional anti-emetics may be administered as needed.
Anti- emetiċi addizjonali jistgħu jiġu mogħtija skond il- ħtieġa.
The following criteria are required to allow treatment with Yondelis:
Il- kriterji li ġejjin huma meħtieġa biex iħallu kura b’ Yondelis:
- Absolute neutrophil count (ANC) ≥ 1,500/ mm3
Għadd assolut ta ’ newtrofili (ANC) ≥ 1, 500/ mm3
- Platelet count ≥ 100,000/ mm3
Għadd tal- plejtlets ≥ 100, 000/ mm3
- Bilirubin ≤ upper limit of normal (ULN)
Bilirubin ≤ limitu ta ’ fuq tan- normal (ULN)
- Alkaline phosphatase ≤ 2.5 ULN (consider hepatic isoenzymes 5-nucleotidase or GGT, if the
Alkaline phosphatase ≤ 2. 5 ULN (ikkonsidra iżoenżimi epatiċi 5- nucleotidase jew GGT, jekk
elevation could be osseous in origin).
l- elevazzjoni tista ’ tkun ta ’ oriġini mill- għadam).
- Alanine aminotransferase (ALT) and Aspartate aminotransferase (AST) ≤ 2.5 x ULN
Alanine aminotransferase (ALT) u Aspartate aminotransferase (AST) ≤ 2. 5 x ULN
2
2 Rata ta ’ tneħħija ta ’ kreatinina ≥ 30 ml/ min
- Creatine phosphokinase (CPK) ≤ 2.5 ULN
Creatine phosphokinase (CPK) ≤ 2. 5 ULN
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 ittardjata sa 3 ġimgħat sakemm il- kriterji jintlaħqu.
Additional monitoring of haematological parameters bilirubin, alkaline phosphatase, aminotransferases and CPK should occur weekly during the first two cycles of therapy, and at least once between treatments in subsequent cycles.
Monitoraġġ addizjonali ta ’ parametriċi ematoloġiċi ta ’ bilirubin, alkaline phosphatase, aminotransferases u CPK għandu jseħħ kull ġimgħa waqt l- ewwel żewġ ċikli ta ’ terapija, u ta ’ l- anqas darba bejn trattamenti f’ ċikli sussegwenti.
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.
Dose adjustments during treatment
Aġġustamenti tad- doża waqt il- kura
Prior to re-treatment, patients must fulfil the baseline criteria defined above.
Qabel kura mill- ġdid, il- pazjenti jeħtieġu li jissodisfaw kriterji ta ’ riferiment bażi kif imfissra hawn fuq.
If any of the following events occur at any time between cycles, the dose must be reduced to 1.2 mg/ m2 for subsequent cycles:
Jekk xi wieħed mir- reazzjonijiet li ġejjin iseħħu waqt kwalunkwe żmien bejn iċ- ċikli, id- doża jeħtieġ li tkun imnaqqsa għal 1. 2mg/ m2 għal ċikli sussegwenti.
- Neutropenia < 500/ mm3 lasting for more than 5 days or associated with fever or infection
Newtropenja < 500/ mm3 li ddum għal aktar minn 5 ijiem jew li hi assoċjata ma ’ deni jew
- Thrombocytopenia < 25,000/ mm3
infezzjoni Tromboċitopenja < 25, 000/ mm3
- Increase of bilirubin > ULN and/ or alkaline phosphatase > 2.5 x ULN
- Żieda tal- bilirubin > ULN u/ jew alkaline phosphatase > 2. 5 x ULN
- Increase of aminotransferases (AST or ALT) > 2.5 x ULN which has not recovered by day 21
- Żieda fl- aminotransferases (AST or ALT) > 2. 5 x ULN li ma rkupratx sa jum 21
- Any other grade 3 or 4 adverse reactions (such as nausea, vomiting, fatigue)
- Reazzjonijiet avversi oħra grad 3 jew 4 (bħal ma ’ huma dardir, rimettar, għeja kbira)
Once a dose has been reduced because of toxicity, dose escalation in the subsequent cycles is not recommended.
Meta doża tkun ġiet imnaqqsa minħabba tossiċità, eskalazzjoni tad- doża f’ ċikli sussegwenti mhix irrakkomandata.
If any of these toxicities reappear in subsequent cycles in a patient exhibiting clinical benefit, the dose may be further reduced to 1 mg/ m2.
Jekk kwalunkwe minn dawn it- tossiċitajiet jerġgħu jitfaċċaw f’ ċikli sussegwenti f’ pazjent li qed jesibixxi benefiċċju kliniku, id- doża tista ’ tiġi mnaqqsa aktar għal 1 mg/ m2.
In the event that further dose reductions are necessary, treatment discontinuation should be considered.
Fil- każ li aktar tnaqqis fid- doża huwa meħtieġ, għandu jiġi kkonsidrat li titwaqqaf il- kura.
Duration of treatment
Dewmien tal- kura
In clinical trials, there were no pre-defined limits to the number of cycles administered.
Fi provi kliniċi, m’ hemm l- ebda limiti definiti minn qabel għan- numru ta ’ ċikli amministrati.
Treatment continued whilst clinical benefit was noted.
Il- kura tkompliet waqt li benefiċċju kliniku kien innotat.
Trabectedin has been administered for 6 or more cycles in 168 out of 569 (29.5%) patients treated with the proposed dose and schedule.
Trabectedin kien amministrat għal 6 ċikli jew aktar f’ 168 minn 569 (29. 5%) pazjent ittrattati bid- doża u skeda proposta.
This regime has been used for up to 38 cycles.
Dan ir- reġimen ġie użat għal sa 38 ċiklu.
No cumulative toxicities have been observed in patients treated with multiple cycles.
L- ebda tossiċitajiet kumulattivi ma ġew osservati f’ pazjenti ittrattati b’ ċikli multipli.
Special patient populations
Popolazzjonijiet ta ’ pazjenti speċjali
The safety and efficacy of trabectedin in paediatric patients have not yet been established.
Is- sigurtà u l- effikaċja ta ’ trabectedin f’ pazjenti pedjatriċi s’ issa għadhom ma ġewx stabbiliti.
Therefore, this medicinal product must not be used in children and adolescents until further data become available.
Għaldaqstant, dan il- prodott mediċinali m’ għandux jintuża fi tfal u adolexxenti sakemm aktar dejta tkun disponibbli.
No specific studies in elderly patients have been performed.
Ma ġew magħmula l- ebda studji speċifiċi f’ pazjenti anzjani.
Overall 20% of the 1164 patients in the integrated safety analysis were over 65 years.
Total globali ta ’ 20% ta ’ l- 1164 pazjent fl- analiżi ta ’ siġurta integrata kienu fuq il- 65 sena.
No relevant differences in the safety profile were seen in this patient population.
L- ebda differenzi relevanti fil- profili ta ’ sigurtà ma intwerew f’ din il- popolazzjoni ta ’ pazjenti.
It seems that plasma clearance and distribution volume of trabectedin are not influenced by age.
Jidher li r- rata ta ’ tneħħija mill- plażma u l- volum ta ’ distribuzzjoni ta ’ trabectedin mhumiex influwenzati mill- età.
Therefore, dose adjustments based uniquely on age criteria are not routinely recommended.
Għaldaqstant, aġġustamenti fid- doża ibbażati unikament biss fuq kriterji ta ’ età mhumiex rakkomandati skond ir- rutina.
3 No studies with the proposed regime have been conducted in patients with liver dysfunction.
3 Pazjenti b’ indeboliment fil- funzjoni epatika
Thus, data are not available to recommend a lower starting dose in patients with hepatic impairment.
Għalhekk, ma hemm l- ebda dejta li tirrakkomanda doża tal- bidu aktar baxxa f’ pazjenti b’ indeboliment epatiku.
However, special caution is advised and dose adjustments may be necessary in these patients since systemic exposure is probably increased and the risk of hepatotoxicity might be increased.
Madankollu, attenzjoni speċjali hija avżata u aġġustamenti fid- doża jistgħu jkunu meħtieġa f’ dawn il- pazjenti peress li esponiment sistemiku huwa probabilment miżjud u r- riskju ta ’ epatotossiċità jista ’ jiżdied.
Patients with elevated bilirubin must not be treated with Yondelis (see section 4.4).
Pazjenti b’ bilirubin għoli m’ għandhomx jiġu ttrattati b’ Yondelis (ara sezzjoni 4. 4).
Patients with impaired renal function
Pazjenti b’ indeboliment fil- funzjoni renali
Studies including patients with severe renal insufficiency (creatinine clearance < 30 ml/ min) have not been conducted and therefore Yondelis must not be used in this patient population (see section 4.4).
Studji li nkludew pazjenti b’ insuffiċjenza renali severa (rata ta ’ tneħħija ta ’ kreatinina < 30 ml/ min) ma sarux u għaldaqstant Yondelis m’ għandux jintuża f’ din il- popolazzjoni ta ’ pazjenti (ara sezzjoni 4. 4).
Considering the pharmacokinetic characteristics of trabectedin (see section 5.2), no dose adjustments are warranted in patients with mild or moderate renal impairment.
Meta tikkonsidera l- karatteristiċi farmakokinetiċi ta ’ trabectedin (ara sezzjoni 5. 2), l- ebda aġġustamenti fid- doża ma huma iġġustifikati f’ pazjenti b’ indeboliment renali ħafif għal moderat.
For instructions on reconstitution and dilution of the medicinal product before administration, see section 6.6.
Għal struzzjonijiet dwar ir- rikostituzzjoni u d- dilwazzjoni tal- prodott mediċinali qabel ma jingħata, ara sezzjoni 6. 6.
- Hypersensitivity to trabectedin or to any of the excipients
- Sensittività eċċessiva għal trabectedin jew għal xi sustanzi mhux attivi
- Concurrent serious or uncontrolled infection
Infezzjoni konkorrenti serja jew mhux ikkontrollata
- Breast-feeding (see section 4.6)
- Treddigħ (ara sezzjoni 4. 6)
- Combination with yellow fever vaccine (see section 4.4)
- Teħid flimkien ma ’ vaċċin tad- deni l- isfar (ara sezzjoni 4. 4)
Patients must meet specific criteria on hepatic function parameters to start treatment with Yondelis.
Il- pazjenti għandhom jissodisfaw kriterji speċifiċi fuq parametri ta ’ funzjoni epatika biex tinbeda kura b’ Yondelis.
Since systemic exposure to trabectedin is probably increased due to hepatic impairment and therefore the risk of hepatotoxicity might be increased, patients with clinically relevant liver diseases, such as active chronic hepatitis, must be closely monitored and the dose adjusted if needed.
Peress li esponiment sistemiku għal trabectedin huwa probabilment miżjud minħabba indeboliment epatiku u għaldaqstant ir- riskju ta ’ epatotossiċità tista ’ tiġi miżjuda, pazjenti b’ mard tal - fwied klinikament relevanti, bħal epatite kronika attiva, għandhom jiġu sorveljati mill- qrib u d- doża aġġustata jekk meħtieġ.
Patients with elevated bilirubin must not be treated with trabectedin (see section 4.2).
Pazjenti b’ bilirubin għoli m’ għandhomx jiġu trattati b’ trabectedin (ara sezzjoni 4. 2).
Creatinine clearance must be monitored prior to and during treatment.
Ir- rata ta ’ tneħħija ta ’ kreatinina għandha tiġi sorveljata qabel u wara l- kura.
Trabectedin must not be used in patients with creatinine clearance < 30 ml/ min (see section 4.2).
Trabectedin m’ għandux jintuża f’ pazjenti b’ rata ta ’ tneħħija ta ’ kreatinina < 30 ml/ min (ara sezzjoni 4. 2).
Neutropenia and thrombocytopenia
Newtropenja u tromboċitopenja
Grades 3 or 4 neutropenia and thrombocytopenia associated with trabectedin therapy have been very commonly reported.
Newtropenja u tromboċitopenja fi gradi 3 u 4 assoċjati ma ’ terapija bi trabectedin ġew irrapportati b’ mod komuni ħafna.
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).
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).
Patients who develop fever should promptly seek medical attention.
Pazjenti li jiżviluppaw deni għandhom iffitxu attenzjoni medika minnufih.
If this occurs, active supportive therapy should be started immediately.
Terapija attiva t’ appoġġ għandha tinbeda minnufih, jekk dan iseħħ.
Nausea and vomiting
Dardir u remettar
Anti-emetic prophylaxis with dexamethasone must be administered to all patients (see section 4.2).
Profilassi anti- emetika b’ dexamethasone għandha tiġi amministrata lill- pazenti kollha (ara sezzjoni 4. 2).
Rhabdomyolysis and severe CPK elevations (> 10 x ULN)
Rabdomajoliżi u elevazzjonijiet severa ta ’ CPK (> 10 x ULN)
Trabectedin must not be used in patients with CPK > 2.5 ULN (see section 4.2).
4 Trabectedin m’ għandux jintuża f’ pazjenti b’ CPK > 2. 5 ULN (ara sezzjoni 4. 2).
Rhabdomyolysis has been uncommonly reported, usually in association with myelotoxicity, severe liver function test abnormalities and/ or renal failure.
Rabdomajoliżi ġiet irrapportata mhux komunement, ġeneralment assoċjata ma ’ majelotossiċità, anormalitajiet severi tal- funżjoni tal- fwied u/ jew falliment renali.
If rhabdomyolysis occurs, supportive measures such as
Għaldaqstant, CPK għandha tkun sorveljata mill- qrib meta pazjent ikun qed jesperjenza xi wħud minn dawn it- tossiċitajiet.
4 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.
Treatment with Yondelis should be discontinued until the patient fully recovers.
Kura b’ Yondelis għandha tkun imwaqfa sakemm il - pazjent jirkupra bi sħiħ.
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.
Liver Function Test (LFT) abnormalities
Abnormalitajiet fit- Testijiet tal- Funzjoni tal- Fwied (LFT)
Reversible acute increases in aspartate aminotransferase (AST) and alanine aminotransferase (ALT) have been reported in most patients.
Żidiet akuti riversibbli f’ aspartate aminotransferase (AST) u alanine aminotrasferase (ALT) ġew irrapportati fil- maġġoranza tal- pazjenti.
Yondelis must not be used in patients with elevated bilirubin.
Yondelis m’ għandux jintuża f’ pazjenti b’ bilirubin għoli.
Patients with increases in AST, ALT and alkaline phosphatase between cycles may necessitate dose reduction (see section 4.2).
Pazjenti b’ żidiet f’ AST, ALT u alkaline phosphatase bejn iċ- ċikli jistgħu jkollhom bżonn tnaqqis fid- doża (ara sezzjoni 4. 2).
Injection site reactions
Reazzjonijiet fis- sit ta ’ l- injezzjoni
The use of central venous access is strongly recommended (see section 4.2).
L- użu ta ’ aċċess ċentrali venuż huwa rakkomandat b’ mod qawwi (ara sezzjoni 4. 2).
Patients may develop a potentially severe injection site reaction when trabectedin is administered through a peripheral venous line.
Pazjenti jistgħu jiżviluppaw reazzjoni potenzjalment severa fis- sit ta ’ l- injezzjoni meta trabectedin huwa amministrat minn ġo linja venuża periferali
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 potenti ta ’ l- enżima CYP3A4 għandu jiġi evitat (ara sezzjoni 4. 5).
If this is not possible, close monitoring of toxicities are required and dose reductions of trabectedin should be considered.
Jekk dan mhux possibbli, sorveljanza mill- qrib ta ’ tossiċitajiet hija meħtieġa u tnaqqis fid- doża ta ’ Yondelis għandha tiġi ikkunsidrata.
Caution should be taken if medicinal products associated with hepatotoxicity are administered concomitantly with trabectedin, since the risk of hepatotoxicity may be increased.
Għandha tittieħed il- kawtela jekk jingħataw prodotti mediċinali assoċjati ma ’ epatotossiċità flimkien ma ’ trabectedin, peress li r- riskju ta ’ epatotossiċità jista ’ jiżdied.
Concomitant use of trabectedin with phenytoin may reduce phenytoin absorption leading to an exacerbation of convulsions.
L- użu ta ’ trabectedin flimkien ma ’ phenytoin jista ’ jnaqqas l- assorbiment ta ’ phenytoin u jwassal għal taħrix tal- konvulżjonijiet.
Combination of trabectedin with phenytoin or live attenuated vaccines is not recommended and with yellow fever vaccine is specifically contraindicated (see sections 4.3 and 4.5).
L- għoti ta ’ trabectedin flimkien ma ’ phenytoin jew vaċċini ħajjin attenwati mhix rakkomandata u hija speċifikament kontra- indikata mal- vaċċin tad- deni l- isfar (ara sezzjoni 4. 3 u 4. 5).
The concomitant use of trabectedin with alcohol must be avoided (see section 4.5).
L- użu ta ’ trabectedin flimkien ma ’ l- alkoħol għandu jiġi evitat (ara sezzjoni 4. 5).