qanastek/EMEA-V3 huggingface dataset:
Other interactions that may affect serum concentrations The absorption of Tasigna is increased if it is taken with food, resulting in higher serum concentration (see sections 4.2, 4.4 and 5.2).
Interazzjonijiet oħra li jista ’ jkollhom effett fuq il- konċentrazzjoni fis- serum L- assorbiment ta ’ Tasigna jiżdied jekk tingħata ma ’ l- ikel, u dan iwassal għal konċentrazzjonijiet ogħla fis- serum (ara sezzjonijiet 4. 2, 4. 4 u 5. 2).
Grapefruit juice and other foods that are known to inhibit CYP3A4 should be avoided.
Il- meraq tal- grejpfrut u ikel ieħor li huma magħrufa li jinibixxu CYP3A4 għandhom jiġu evitati.
Pregnancy There are no data on the use of Tasigna in pregnant women.
Tqala M’ hemmx dejta dwar l- użu ta ’ Tasigna f’ nisa tqal.
The potential risk for humans is unknown.
Mhux mgħaruf ir- riskju potenzjali fuq in- nies.
Tasigna should not be used during pregnancy unless clearly necessary.
Tasigna m’ għandux jintuża waqt it- tqala jekk m’ hemmx bżonn ċar.
If it is used during pregnancy, the patient must be informed of the potential risk to the foetus.
Jekk jintuża waqt it- tqala, il- pazjent għandu jkun infurmat dwar ir- riskju potenzjali għall- fetu.
Women of childbearing potential must be advised to use effective contraception during treatment with Tasigna.
Nisa li jista ’ jkollhom it- tfal għandhom jingħataw parir sabiex jużaw mezz ta ’ kontraċezzjoni effettiv waqt il- kura b’ Tasigna.
Lactation It is not known whether nilotinib is excreted in human milk.
Treddigħ Mhux magħruf jekk nilotinib joħroġx fil- ħalib tal- mara.
Studies in animals demonstrate that it is excreted into milk.
Studji fl- annimali juru li joħroġ fil- ħalib.
Women should not breast-feed during treatment with Tasigna, as a risk to the infant cannot be excluded.
Nisa m’ għandhomx ireddgħu waqt li jkunu qed jieħdu l- kura b’ Tasigna, peress li r- riskju għat- tarbija ma jistax jiġi eskluż.
No studies on the effects of nilotinib on the ability to drive and use machines have been performed.
Ma sarux studji dwar l- effetti ta ’ nilotinib fuq il- ħila biex issuq jew tħaddem magni.
Patients experiencing dizziness, fatigue, visual impairment or other undesirable effects with a potential impact on the ability to drive or use machines safely should refrain from these activities as long as the undesirable effects persist (see section 4.8).
Pazjenti li jħossu sturdament, għeja, tnaqqis fil- vista jew effetti oħra mhux mixtieqa li jista ’ jkollhom impatt fuq il- ħila biex isuqu jew iħaddmu magni b’ mod sigur għandhom jevitaw li jgħamlu dawn l- attivitajiet sakemm l - effetti mhux mixtieqa jippersistu (ara sezzjoni 4. 8).
The data described below reflect exposure to Tasigna in 438 patients in an open-label multicentre study.
Id- dejta deskritta hawn taħt tirrifletti l- esponiment għal Tasigna f’ 438 pazjent fi studju open- label multriċentriku.
At cut-off, 46% of patients in chronic-phase CML (CML-CP) had a duration of exposure of 6 to 12 months and 18% of patients had a duration of exposure of more than 12 months.
Meta waqfu, 46% tal- pazjenti fil- fażi- kronika CML (CML- CP) kellhom esponiment li dam minn 6 sa 12- il xahar u 18% tal- pazjenti kellhom esponiment li dam aktar minn 12- il xahar.
62% of patients in accelerated-phase CML (CML-AP) had a duration of exposure of 3 to 12 months and 10% of patients had a duration of exposure of more than 12 months.
62% tal- pazjenti fil- fażi- aċċellerata CML (CML- AP) kellhom esponiment li dam minn 3 sa 12- il xahar u 10% tal- pazjenti kellhom esponiment li dam aktar minn 12- il xahar.
The dose was 400 mg twice daily.
Id- doża kienet ta ’ 400 mg darbtejn kuljum.
The median duration of exposure in days was 245 (1-502) for the CML-CP patients and 138 (2-503) for the CML- AP patients.
Il- medja tat- tul ta ’ l- esponiment f’ jiem kienet 245 (1- 502) għall- pazjenti b’ CML- CP u 138 (2- 503) għall- pazjenti b’ CML- AP.
The most frequent non-haematological drug-related adverse events were rash, pruritus, nausea, fatigue and headache.
Il- każijiet avversi l- aktar frekwenti mhux ematoloġiċi kienu raxx, ħakk, dardir, għeja u uġigħ ta ’ ras.
Most of these adverse events were mild to moderate in severity.
Ħafna minn dawn il- każijiet avversi kienu ħfief għal moderati fis- severità tagħhom.
Constipation, diarrhoea, bone pain, arthralgia, muscle spasms and peripheral oedema were observed less commonly and have been of mild to moderate severity.
Stitikezza, dijarea, uġigħ fl- għadam, artralġja, spażmi tal- muskoli u edema periferali dehru b’ mod anqas komuni u kienu ħfief jew moderati fis- severità tagħhom.
Discontinuation for adverse events regardless of causality was observed in 16% of CP and 14% of AP patients.
It- twaqqif minħabba każijiet avversi irrispettivament hux kawżati mill- mediċina dehru f’ 16% tal- pazjenti CP u 14% tal- pazjenti AP.
Treatment emergent haematological toxicities included thrombocytopenia (27%), neutropenia (15%) and anaemia (13%).
Tossiċitajiet ematoloġiċi li ħarġu mill- kura kienu jinkludu tromboċitopenja (27%), newtropenja (15%) u anemija (13%).
Pleural and pericardial effusions as well as complications of fluid retention occurred in < 1% of patients receiving Tasigna.
Effużjonijiet fil- plewra u perikardijaċi kif ukoll komplikazzjonijiet ta ’ ritenzjoni fluwida seħħew f ’ < 1% tal- pazjenti li kienu qed jirċievu Tasigna.
Congestive heart failure was observed in 1% of
Insuffiċjenza tal- qalb konġestiva dehret f’ 1% tal- pazjenti.
Gastrointestinal and CNS haemorrhage were reported in 3% and 1% of patients, respectively.
Emorraġġiji gastro- intestinali u tas- CNS kienu rrappurtati f’ 3% u 1% tal - pazjenti, rispettivament.
QTcF exceeding 500 msec was observed in < 1% of patients.
QTcF li qabżet il- 500 msek dehret f ’ < 1% tal- pazjenti.
No episodes of torsade de pointes (transient or sustained) were observed.
L- ebda episodju ta ’ torsade de pointes (mumentanju jew sostnut) ma kien osservat.
Non-haematological adverse reactions (excluding laboratory abnormalities) that are reported in at least 5% of the patients in Tasigna clinical studies are shown in Table 2.
Reazzjonijiet avversi mhux ematoloġiċi (esklużi anormalitajiet tal- laboratorju) li huma rrappurtati f’ mill- anqas 5% tal- pazjenti fi studji kliniċi b’ Tasigna qed jidhru f’ Tabella 2.
These are ranked under heading of frequency using the following convention: very common (≥ 1/ 10) or common (≥ 1/ 100 to < 1/ 10).
Dawn huma elenkati taħt it- titlu tal- frekwenza bil- konvenzjoni li ġejja: komuni ħafna (≥1/ 10) jew komuni (≥1/ 100 to < 1/ 10).
Adverse reactions (≥ 5% of all patients, n=438)
Reazzjonijiet avversi
System organ class
(≥5% tal- pazjenti kollha, n=438)
Frequency Adverse All reaction
Klassi tas - sistema ta ’ l - organu
grades
Frekwenza
Grade 3-4
Reazzjoni Gradi Grad avversa kollha 3- 4
Chronic phase Grade 3-4
Gradi tal- fażi kronika 3- 4
Accelerated phase Grade 3-4
Gradi tal - fażi aċċelerata 3- 4
%
2
Nervous system disorders
Disturbi gastro -
Very common Very common Very common Common Common
Komuni ħafna Komuni Common
Nausea Constipation Diarrhoea Vomiting Abdominal pain
Dijarea Rimettar Uġigħ fl- addome
Skin and
Disturbi fil -
subcutaneous tissue disorders
ġilda u fit -
Pruritus Alopecia
Ħakk
Musculoskeletal and connective tissue disorders
skeletrali u tal - connective tissue
Myalgia Arthralgia Muscle spasms Bone pain
Uġigħ fl- għadam
Metabolism and Common nutrition disorders
Komuni
General disorders and administration site conditions
Disturbi
Fatigue Asthenia Oedema peripheral
Għeja
Additional data from clinical trials The following adverse reactions were reported in patients in the Tasigna clinical studies at a frequency of less than 5% (common is ≥ 1/ 100 to< 1/10; uncommon is > 1/1,000 to< 1/100; single events are captured as frequency not known [cannot be estimated from the available data]).
Dejta oħra minn provi kliniċi Ir- reazzjonijiet avversi li ġejjin kienu rrappurtati f’ pazjenti fi studji kliniċi b’ Tasigna bi frekwenza ta ’ anqas minn 5% (komuni hija ≥1/ 100 sa < 1/ 10; mhux komuni hija > 1/ 1, 000 sa < 1/ 100; każijiet ta ’ darba qed jiġu meqjusa bħala frekwenza mhux magħrufa [ma tistax tittieħed stima mid- dejta disponibbli]).
For laboratory abnormalities, very common events (≥ 1/ 10) not included in Table 2 are also reported.
Għal anormalitajiet tal- laboratorju, każijiet komuni ħafna (≥1/ 10) mhux inklużi f’ Tabella 2 huma rrappurtati wkoll.
These adverse reactions are included based on clinical relevance and ranked in order of decreasing seriousness within each category.
Dawn ir- reazzjonijiet avversi huma inklużi bbażati fuq ir- rilevanza klinika tagħhom u huma elenkati skond is- serjetà tagħhom b’ dik l- aktar serja l- ewwel f’ kull kategorija.
7 Investigations:
Investigazzjonijiet:
Very common: lipase increased.
Komuni ħafna: żieda tal- lipase.
Common: blood amylase increased, alanine aminotransferase increased, aspartate aminotransferase increased, blood bilirubin increased, blood alkaline phosphatase increased, gamma- glutamyltransferase increased, blood creatinine phosphokinase increased, blood glucose increased, weight decreased, weight increased.
Komuni: żieda ta ’ l- amylase fid- demm, żieda ta ’ l- alanine aminotransferase, żieda ta ’ l- aspartate aminotransferase, żieda tal- bilirubin fid- demm, żieda ta ’ l- alkaline phosphatase fid- demm, żieda tal - gamma - glutamyltransferase, żieda tal- creatinine phosphokinase fid- demm, żieda tal- glucose fid - demm, tnaqqis fil- piż, żieda fil- piż.
Uncommon: blood lactate dehydrogenase increased, blood glucose decreased, blood creatinine increased, blood urea increased.
Mhux komuni: żieda tal- lactate dehydrogenase fid- demm, tnaqqis tal- glucose fid- demm, tnaqqis tal - krejatinina fid- demm, żieda ta ’ l- urea fid- demm.
Not known: troponin increased, blood potassium decreased, blood bilirubin unconjugated increased.
Mhux magħruf: żieda tat- troponin, tnaqqis tal- potassium fid- demm, żieda tal- bilirubin mhux konjugat fid- demm.
Cardiac disorders:
8 Disturbi fil- qalb:
Common: palpitations, electrocardiogram QT prolonged.
Komuni: palpitazzjonijiet, QT ta ’ l- elettrokardjogramma mtawwal.
Uncommon: cardiac failure, angina pectoris, atrial fibrillation, pericardial effusion, coronary artery disease, cardiomegaly, cardiac murmur, bradycardia.
Mhux komuni: insuffiċjenza kardijaka, angina pectoris, fibrillazzjoni ta ’ l- atrija, effużjoni fil - perikardju, mard ta ’ l- arterja koronarja, kardjomegalija, ħsejjes fil- qalb, bradikardija.
Not known: myocardial infarction, ventricular dysfunction, pericarditis, cardiac flutter, extrasystoles.
Mhux magħruf: infart mijokardijaku, funzjoni ħażina tal- ventrikoli, perikardite, tħabbit mgħaġġel tal - qalb, extrasystoles.
Common: febrile neutropenia, pancytopenia.
Komuni: newtropenja bid- deni, panċitopenja.
Uncommon: thrombocythaemia, leukocytosis.
Mhux komuni: tromboċitemja, lewkoċitożi.
Common: dizziness, paraesthesia.
Komuni: sturdament, parasteżija.
Uncommon: intracranial haemorrhage, migraine, tremor, hypoaesthesia, hyperaesthesia.
Mhux komuni: emorraġija ġol- kranju, emigranja, tregħid, ipoesteżija, iperesteżija.
Not known: brain oedema, loss of consciousness, optic neuritis, peripheral neuropathy.
Mhux magħruf: edema fil- moħħ, telf mis- sensi, nevrite ottika, newropatija periferali.
Uncommon: eye haemorrhage, visual acuity reduced, periorbital oedema, conjunctivitis, eye irritation, dry eye.
Mhux komuni: emorraġija fl- għajn, tnaqqis fl- akkutezza viżiva, edema mad- dawra ta ’ l- għajnejn, kunġunktivite, irritazzjoni ta ’ l- għajnejn, għajnejn xotti.
Not known: papilloedema, diplopia, vision blurred, photophobia, eye swelling, blepharitis, eye pain.
Mhux magħruf: papilloedema, diplopja, vista mċajpra, fotofobija, għajnejn minfuħin, blefarite, uġigħ fl- għajnejn.
Common: vertigo.
Komuni: vertigo.
Not known: hearing impaired, ear pain.
Mhux magħruf: jonqos is- smigħ, uġigh fil- widnejn.
Common: dyspnoea, dyspnoea exertional, cough, dysphonia.
Komuni: qtugħ ta ’ nifs, qtugħ ta ’ nifs waqt sforz, sogħla, disfonija.
Uncommon: pulmonary oedema, pleural effusion, interstitial lung disease, pleuric pain, pleurisy, epistaxis, pharyngolaryngeal pain, throat irritation.
Mhux komuni: edema fil- pulmun, effużjoni fil- plewra, mard fl- interstizzju tal- pulmun, uġigħ fil - plewra, plewriżi, epistassi, uġigħ fil- farinġi u fil- larinġi, irritazzjoni fil- grieżem.
Not known: pulmonary hypertension.
Mhux magħruf: pressjoni għolja fil- pulmun.
Common: abdominal discomfort, dyspepsia, flatulence.
Komuni: fastidju fl- addome, dispepsja, tifwiq.
Uncommon: pancreatitis, gastrointestinal haemorrhage, melaena, abdominal distension, mouth ulceration, gastroesophageal reflux, stomatitis, dry mouth.
Mhux komuni: pankrejatite, emorraġija gastro- intestinali, melenja, distensjoni ta ’ l- addome, ulċeri fil - ħalq, ittella ’ mill- istonku, stomatite, ħalq xott.
Not known: gastrointestinal ulcer perforation, retroperitoneal haemorrhage, haematemesis, gastric ulcer, oesophagitis ulcerative, subileus.
Mhux magħruf: ulċera fl- istonku tittaqqab, emorraġija retroperitonali, rimettar ta ’ demm, ulċera fl - istonku, infjammazzjoni ta ’ l- esofagu bl- ulċeri, imblukkar parzjali.
Uncommon: dysuria, micturition urgency, nocturia, pollakiuria.
Mhux komuni: disurja, urġenza biex tgħaddi l- awrina, nokturja, tgħaddi l- awrina ta ’ spiss ħafna.
Not known: renal failure, haematuria, urinary incontinence.
Mhux magħruf: insuffiċjenza renali, ematurja, inkontinenza ta ’ l- awrina.
Common: night sweats, eczema, urticaria, erythema, hyperhidrosis, dry skin.
Tgħereq ħafna matul il- lejl, ekżema, urtikarja, eritema, iperidrożi, ġilda xotta.
Uncommon: exfoliative rash, ecchymosis, swelling face.
Mhux komuni: raxx esfoljattiv, ekkimożi, nefħa tal- wiċċ.
Not known: erythema nodosum, skin ulcer, petechiae, photosensitivity.
Mhux magħruf: erythema nodosum, ulċera tal- ġilda, petekje, sensittività għad- dawl.
8 Musculoskeletal and connective tissue disorders:
Disturbi muskolu- skeletrali u tal- connective tissue:
Common: musculoskeletal chest pain, musculoskeletal pain.
Komuni: uġigħ muskolu- skeletrali fis- sider, uġigħ muskoluskeletrali.
Uncommon: muscular weakness.
Mhux komuni: dgħjufija muskolari.
Not known: arthritis, joint swelling.
Mhux magħruf: artrite, nefħa fil- ġogi.
Uncommon: hyperthyroidism.
Mhux komuni: ipertirojdiżmu.
Not known: hypothyroidism, thyroiditis.
Mhux magħruf: ipertirojdiżmu, tirojdite.
Metabolism and nutrition disorders:
9 Disturbi fil- metaboliżmu u n- nutrizzjoni:
Common: hypomagnesaemia, hyperkalaemia, hyperglycaemia.
Komuni: ipomagneżimja, iperkalimja, ipergliċemija.
Uncommon: hypokalaemia, hyponatraemia, hypocalcaemia, hypophosphataemia, dehydration, decreased appetite, increased appetite.
Mhux komuni: ipokalemja, iponatremja, ipokalċemija, ipofosfatimja, deidratazzjoni, tnaqqis fl- aptit, żieda fl- aptit.
Not known: diabetes mellitus, hypercalcaemia, hyperphosphataemia.
Mhux magħruf: dijabete mellitus, iperkalċimija, iperfosfetimja.
Uncommon: pneumonia, urinary tract infection, gastroenteritis, pharyngitis.
Mhux komuni: pulmonite, infezzjoni tal- passaġġ ta ’ l- awrina, gastro- enterite, farinġite.
Not known: sepsis, bronchitis, herpes simplex, candidiadis.
Mhux magħruf: sepsi, bronkite, herpes simplex, kandidijażi.
Common: hypertension, flushing.
Komuni: pressjoni għolja, fwawar.
Uncommon: hypertensive crisis, haematoma.
Kriżi ta ’ pressjoni għolja, ematoma.
Not known: shock haemorrhagic, hypotension, thrombosis.
Mhux magħruf: xokk emorraġiku, pressjoni baxxa, trombożi.
Common: pyrexia.
Komuni: deni.
Uncommon: chest pain, face oedema, gravitational oedema, influenza-like illness, chills, malaise.
Mhux komuni: uġigħ fis- sider, edema tal- wiċċ, edema gravitazzjonali, mard bħal ta ’ l- influwenza, dehxiet ta ’ bard, tħossok ma tiflaħx.
Uncommon: hepatitis.
Mhux komuni: epatite.
Not known: hepatotoxicity, hepatomegaly, jaundice.
Mhux magħruf: epatotossiċità, epatomegalija, suffejra.
Uncommon: breast pain, gynaecomastia, erectile dysfunction.
Mhux komuni: uġigħ tas- sider, ginekomastja, funzjoni ħażina ta ’ l- erezzjoni.
Common: insomnia.
Komuni: nuqqas ta ’ rqad.
Uncommon: depression, anxiety.
Mhux komuni: dipressjoni, ansjetà.
Not known: disorientation, confusional state.
Mhux magħruf: disorjentament, stat konfużjonali.
9 Clinically relevant or severe abnormalities of routine haematological or biochemistry laboratory values are presented in Table 3.
Anormalitajiet klinikament rilevanti jew severi tal- valuri ematoloġiċi jew biokimiċi f’ rutina tal - laboratorju qed jintwerew f’ Tabella 3.
Grade 3-4 laboratory abnormalities
Anormalitajiet tal- laboratorju ta ’ Grad
CML-CP n=318% Grade 3-4
3- 4
CML-AP n=120% Grade 3-4
CML- CP n=318% Gradi 3- 4
Haematological parameters
CML- AP n=120% Gradi 3- 4
- Neutropenia - Thrombocytopenia - Anaemia
Parametri ematoloġiċi - Newtropenja - Tromboċitopenja - Anemija Parametri biokimiċi
- Elevated creatinine - Elevated lipase - Elevated SGOT (AST) - Elevated SGPT (ALT) - Hypophosphataemia - Elevated bilirubin (total)
- Krejatinina għolja - Lipase għoli - SGOT (AST) għoli - SGPT (ALT) għoli - Ipofosfatemija - Bilirubin (totali) għoli
In the event of overdose, the patient should be observed and appropriate supportive treatment given.
F’ każ ta ’ doża eċċessiva, il- pazjent għandu jinżamm taħt osservazzjoni u kura ta ’ support xierqa għandha tingħata.
Protein-kinase inhibitors, ATC code:
ATC:
Tasigna is a potent inhibitor of the Abl tyrosine kinase activity of the Bcr-Abl oncoprotein both in cell lines and in primary Philadelphia-chromosome positive leukaemia cells.
Tasigna huwa inibitur potenti ta ’ l- attività Abl tyrosine kinase tal- Bcr- Abl onkoproteina sew fil- linji ta ’ ċelluli u fiċ- ċelluli tal- lewkemija pożittivi għall- kromosoma ta ’ Filadelfja primarja.
The substance binds with high affinity to the ATP-binding site in such a manner that it is a potent inhibitor of wild-type Bcr-Abl and maintains activity against 32/ 33 imatinib-resistant mutant forms of Bcr-Abl.
Is- sustanza teħel b’ affinità għolja mas- sit mnejn teħel l- ATP b’ tali mod li hija inibitur potenti tal- Bcr- Abl tat- tip aħrax u jibqa attiv kontra l- forom 32/ 33 mutanti reżistenti għal imatinib Bcr- Abl.
As a consequence of this biochemical activity, nilotinib selectively inhibits the proliferation and induces apoptosis in cell lines and in primary Philadelphia-chromosome positive leukaemia cells from CML patients.
Minħabba din l - attività biokimika, nilotinib jinibixxi b’ mod silettiv il- proliferazzjoni u jinduċi apoptożi f’ linji ta ’ ċelluli u f’ ċelluli ta ’ lewkemija pożittivi għall- kromosoma ta ’ Filadelfja primarja minn pazjenti b’ CML.
In murine models of CML, as a single agent nilotinib reduces tumour burden and prolongs survival following oral administration.
F’ mudelli ta ’ ġrieden b’ CML, nilotinib mogħti waħdu naqqas it- tagħbija tat- tumur u tawwal is- sopravivenza wara l- għotja mill- ħalq.
Tasigna has little or no effect against the majority of other protein kinases examined, including Src, except for the PDGF, Kit and Ephrin receptor kinases, which it inhibits at concentrations within the range achieved following oral administration at therapeutic doses recommended for the treatment of CML (see Table 4).
Tasigna għandu ftit li xejn jew l- ebda effett kontra l- maġġoranza tal- protein kinases oħra li ġew eżaminati, inkluż Src, minbarra l- PDGF, Kit u Ephrin receptor kinases, li tinibixxi b’ konċentrazzjonijiet fil- medda li tinkiseb wara l- għotja mill- ħalq b’ dożi terapewtiċi rakkomandati għall- kura ta ’ CML (ara Tabella 4).
Kinase profile of nilotinib (phosphorylation IC50 nM)
Profil kinase ta ’ nilotinib (fosforilazzjoni IC50 nM)
Clinical studies An open-label, uncontrolled, multicentre Phase II study was conducted to determine the efficacy of Tasigna in patients with imatinib resistant or intolerant CML with separate treatment arms for chronic
Studji kliniċi Sar studju tal- Fażi II multiċentriku, mhux bil- kontroll, open- label sabiex tinsab l- effikaċja ta ’ Tasigna f’ pazjenti reżistenti għal imatinib jew intolleranti għal CML b’ fergħat ta ’ kura separati għal marda fil - fażi kronika u aċċelerata.
10 and accelerated phase disease.
L- istudju għadu għaddej.
Efficacy was based on 320 CP patients and 119 AP patients enrolled.
L- effikaċja kienet ibbażata fuq it- 320 pazjent CP u l- 119 pazjent AP li ħadu sehem.
Median duration of treatment was 341 days for CP patients and 202 days for AP patients (see Table 5).
Il- medjan ta ’ kemm damet il- kura kienet 341 jum għall- pazjenti CP u 202 jiem għall- pazjenti AP (ara Tabella 5).
Tasigna was administered on a continuous basis (twice daily 2 hours after a meal and with no food for at least one hour after administration) unless there was evidence of inadequate response or disease progression.
Tasigna ingħata fuq bażi kontinwa (darbtejn kuljum sagħtejn wara ikla u ma ngħatax ikel mill- anqas siegħa wara li ngħatat d- doża) sakemm ma kienx hemm evidenza ta ’ rispons mhux adegwat jew avvanz tal- marda.
Dose escalation to 600 mg twice daily was allowed.
Kien permess li d- doża titella sa 600 mg darbtejn kuljum.
Duration of exposure with Tasigna
Tul ta ’ l- esponiment b’ Tasigna
Chronic phase n=320
Fażi kronika n=320
Accelerated phase n=119
Fażi aċċellerata n=119
Median duration of therapy in days
Medjan tat- tul tat- terapija f’ jiem
(25th-75th percentiles)
(il- 25- il- 75 perċentwali)
Resistance to imatinib included failure to achieve a complete haematological response (by 3 months), cytogenetic response (by 6 months) or major cytogenetic response (by 12 months) or progression of disease after a previous cytogenetic or haematological response.
Reżistenza għal imatinib kienet tinkludi nuqqas li jinkiseb rispons ematoloġiku komplet (fi żmien 3 xhur), rispons ċitoġenetiku (fi żmien 6 xhur) jew rispons ċitoġenetiku maġġuri (fi żmien 12- il xahar) jew avvanz tal- marda wara li jkun hemm rispons ċitoġenetiku jew ematoloġiku.
Imatinib intolerance included patients who discontinued imatinib because of toxicity and were not in major cytogenetic response at time of study entry.
Intolleranza għal imatinib kien jinkludi pazjenti li kellhom iwaqqfu imatinib minħabba tossiċità u li ma kellhomx rispons ċitoġenetiku maġġuri fi żmien meta daħlu fl- istudju.
Overall, 73% of patients were imatinib-resistant, while 27% were imatinib-intolerant.
11 B’ mod globali, 73% tal- pazjenti kienu reżistenti għal imatinib, filwaqt li 27% kienu intolleranti għal imatinib.
The majority of patients had a long history of CML that included extensive prior treatment with other antineoplastic agents, including imatinib, hydroxyurea, interferon, and some had even failed organ transplant (Table 6).
Il- maġġoranza tal- pazjenti kellhom passat twil ta ’ CML li kien jinkludi kura estensiva minn qabel b’ sustanzi antineoplastiċi oħrajn, inkluż imatinib, hydroxyurea, interferon, u xi wħud li kienu saħansitra tilfu trapjant ta ’ organu (Tabella 6).
The median highest prior imatinib dose had been 600 mg/ day for CP patients and 800 mg/ day for AP patients.
Il- medjan ta ’ l- ogħla doża ta ’ imatinib li ngħatat qabel kienet 600 mg/ jum għall- pazjenti CP u 800 mg/ jum għall- pazjenti AP.
The highest prior imatinib dose was ≥ 600 mg/ day in 75% of all patients, with 41% of patients receiving imatinib doses ≥ 800 mg/ day.
L- ogħla doża ta ’ imatinib li ngħatat qabel kienet ta ’ ≥600 mg/ jum f’ 75% tal- pazjenti kollha, b’ 41% tal- pazjenti li kienu qed jirċievu dożi b’ imatinib ta ’ ≥800 mg/ jum.
CML disease history characteristics
Karatteristiċi tal- passat tal- marda CML
Chronic phase (n=320)
Fażi kronika (n=320)
Accelerated phase (n=119)
Fażi aċċellerata (n=119)
Median time (range) Imatinib
Ħin medjan minn meta saret id- dijanjosi
since diagnosis in months
(medda) Imatinib
Median
96 (81%)
Resistant Intolerant without MCyR time of imatinib treatment in
Ħin medjan tal- kura b’ imatinib f’ jiem
226 (71%) 94 (29%) 973
(29%) 973
96 23
23
(81%) (19%) 976
(19%) 976
Prior hydroxyurea Prior interferon Prior bone marrow transplant
(il- 25- il- 75 perċentwali) Ingħataw hydroxyurea qabel Ingħataw interferon qabel Kellhom trapjant tal- mudullun qabel
83% 64% 8%
(515- 1, 485) 83% 64% 8%
92% 58% 8%
(488- 1, 543) 92% 58% 8%
The primary endpoint in the CP patients was major cytogenetic response (MCyR), defined as elimination (CCyR, complete cytogenetic response) or significant reduction to < 35% Ph+ metaphases (partial cytogenetic response) of Ph+ haematopoietic cells.
Ir- riżultat ewlieni f’ pazjenti CP kien rispons ċitoġenetiku maġġuri (McyR), definit bħala it- tneħħija (CcyR, rispons ċitoġenetiku komplet) jew tnaqqis sinifikanti għal < 35% Ph+ metafażi (rispons ċitoġenetiku parzjali) taċ- ċelluli impoietiċi Ph+.
Complete haematological response (CHR) in CP patients was evaluated as a secondary endpoint.
Rispons ematoloġiku komplet (CHR) f’ pazjenti CP kien evalwat bħala r- riżultat sekondarju.
The primary endpoint in the AP patients was overall confirmed haematological response (HR), defined as either a complete haematological response, no evidence of leukaemia or return to chronic phase.
Ir- riżultat ewlieni fil- pazjenti AP kien ir- rispons ematoloġiku (HR) ikkonfermat b’ mod globali, definit jew bħala rispons ematoloġiku komplet, bħala l- ebda evidenza ta ’ lewkemija jew bħala ritorn għall- fażi kronika.
The MCyR rate in 320 CP patients was 49%.
Ir- rata ta ’ MCyR f’ 320 pazjent CP kienet 49%.
Most responders achieved their MCyR rapidly within 3 months (median 2.8 months) of starting Tasigna treatment and these were sustained (median duration has not been reached).
Il- parti l- kbira ta ’ dawk li kellhom rispons kisbu l - MCyR tagħhom malajr fi żmien 3 xhur (medjan ta ’ 2. 8 xhur) minn meta bdew il- kura b’ Tasigna u dawn baqgħu sostenibbli (it- tul medjan ma ntlaħaqx).
Among 156 patients with MCyR 43 patients (27.6%) lost their MCyR.
Fost il- 156 pazjent b’ McyR 43 pazjent (27. 6%) tilfu l- McyR tagħhom.
2.8 months).
Pazjenti b’ CHR fil- linja bażi kisbu MCyR aktar malajr (1 kontra 2. 8 xhur).
Of CP patients without a baseline CHR, 70% achieved a CHR and median time to CHR was 1 month and median duration of CHR has not been reached.
Mill- pazjenti CP mingħajr CHR fil- linja bażi, 70% kisbu CHR u l- ħin medju għas- CHR kien xahar 1 u t- tul medjan tas- CHR ma ntlaħqitx.
11 The overall confirmed HR rate in 119 AP patients was 42%.
Ir- rata globali ta ’ HR konfermata f’ 119 tal- pazjenti AP kienet 42%.
Most responders achieved a HR early with Tasigna treatment (median 1.0 months) and these have been durable (median duration has not been reached).
Ħafna minn dawk li kellhom rispons kisbu HR minn kmieni bil- kura Tasigna (medjan xahar 1. 0) u dawn baqgħu fit- tul (it- tul medjan ma ntlaħaqx).
No patients have had a loss of CHR.
L- ebda pazjent ma kellu tnaqqis fis- CHR.
The MCyR rate was 27% with a median time to response of 2.0 months.
Ir- rata MCyR kienet 27% b’ ħin medjan għar- rispons ta ’ xahrejn.
The rates of response for the two treatment arms are reported in Table 7.
12 Ir- rati ta ’ rispons għaż- żewġ fergħat ta ’ kura huma rrappurtati f’ Tabella 7.
Response in CML
Rispons f’ CML
(Best Response Rate)
(L- aqwa Rata ta ’ Rispons)
Chronic Phase
Fażi kronika
Accelerated Phase
Fażi Aċċelerata
Haematological Response (%)
Rispons ematoloġiku (%)
Resistant (n=226)
Reżistenti (n=226)
Total (n=320)
Totali (n=320)
Total (n=119)
Totali (n=119)
Overall (95%CI)
(95% CI) Globali Komplet
-
- 86 (74- 94) -
Complete NEL Return to CP Cytogenetic Response (%)
NEL Marru lura għall- CP
86 (74-94) - -
-
701 (63-76) - -
701 (63- 76)
Major (95%CI) Complete Partial NEL = no evidence of leukaemia/ marrow 1
Maġġuri (95% CI) Komplet Parzjali
114 CP patients had a CHR at baseline and were therefore not assessable for complete haematological response
NEL = l- ebda evidenza ta ’ lewkemija/ rispons tal- mudullun 1 114 pazjent CP kellhom CHR fil- linja bażi u għalhekk ma setgħux jiġu stmati għal rispons ematoloġiku komplet.
Efficacy data in patients with CML-BC are not yet available.
Dejta dwar l- effikaċja f’ pazjenti b’ CML- BC għada mhux disponibbli.
Separate treatment arms were also included in the Phase II study to investigate Tasigna in a group of CP and AP patients who had been extensively pre-treated with multiple therapies including a tyrosine kinase inhibitor agent in addition to imatinib.
Fergħat ta ’ kura separati kienu wkoll inklużi fl- istudju ta ’ Fażi II sabiex jiġi investigat Tasigna fi grupp ta ’ pazjenti CP u pazjenti AP li qabel kienu ġew ikkurati b’ mod estensiv b’ ħafna terapiji inkluż l- inibitur ta ’ tyrosine kinase flimkien ma ’ imatinib.
The study is ongoing.
Dan l- istudju għadu għaddej.
Of these patients 30/ 36 (83%) were treatment resistant not intolerant.
Minn dawn il- pazjenti 30/ 36 (83%) kienu reżistenti għall - kura u mhux intolleranti.
In 22 CP patients evaluated for efficacy Tasigna induced a 32% MCyR rate and a 50% CHR rate.
F’ 22 pazjent CP evalwati għall- effikaċja Tasigna inudċit rata ta MCyR ta ’ 32% u rata ta ’ CHR ta ’ 50%.
In 11 AP patients, evaluated for efficacy, treatment induced a 36% overall HR rate.
Fi 11- il pazjent AP, evlawati għall- effikaċja, il- kura induċit rata ta ’ HR globali ta ’ 36%.
After imatinib failure, 24 different Bcr-Abl mutations were noted in 45% of chronic phase and 57% of accelerated phase CML patients who were evaluated for mutations.
Wara li imatinib falla, 24 Bcr- Abl mutazzjonijiet differenti kienu nnutati f’ 45% tal- fażi kronika u 57% tal- fażi aċċelerata tal- pazjenti b’ CML li kienu evalwati għall- mutazzjonijiet.
Tasigna demonstrated efficacy in patients harboring a variety of Bcr-Abl mutations associated with imatinib resistance, except T315I.
Tasigna wera effikaċja f’ pazjenti li kellhom vajetà ta ’ mutazzjonijiet Bcr- Abl assoċjati ma ’ reżistenza għal imatinib, ħlief T315I.
Absorption Peak concentrations of nilotinib are reached 3 hours after oral administration.
Assorbiment L- ogħla konċentrazzjonijiet ta ’ nilotinib jintlaħqu 3 sigħat wara li jingħata mill- ħalq.
Nilotinib absorption following oral administration was approximately 30%.
L- assorbiment ta ’ nilotinib wara li ngħata mill- ħalq kienet madwar 30%.
In healthy volunteers, Cmax and area under the serum concentration-time curve (AUC) of nilotinib are increased by 112% and 82%, respectively, compared to fasting conditions when Tasigna is given with food.
F’ voluntiera b’ saħħithom, is- Cmax u l- erja taħt il- kurva tal- konċentrazzjoni tas- serum- ħin (AUC) ta ’ nilotinib jiżdiedu b’ 112% u 82%, rispettivament, mqabbla ma ’ kundizzjonijiet ta ’ sawm meta Tasigna jingħata ma ’ l- ikel.
Administration of Tasigna 30 minutes or 2 hours after food increased bioavailability of nilotinib by 29% or 15%, respectively (see sections 4.2, 4.4 and 4.5).
L- għotja ta ’ Tasigna 30 minuta jew sagħtejn wara l- ikel iżid il- biodisponibilità ta ’ nilotinib b’ 29% jew 15%, rispettivament (ara sezzjonijiet 4. 2, 4. 4 u 4. 5).
Distribution The blood-to-plasma ratio of nilotinib is 0.71.
Distribuzzjoni Il- proporzjon tad- demm- għal- plażma ta ’ imatinib huwa 0. 71.
Plasma protein binding is approximately 98% on the basis of in vitro experiments.
It- twaħħil mal- proteina tal- plażma huwa madwar 98% fuq bażi ta ’ esperimenti in vitro.
Biotransformation Main metabolic pathways identified in healthy subjects are oxidation and hydroxylation.
13 Biotrasformazzjoni Il- mezzi metaboliċi maġġuri li kienu identifikati f’ individwi b’ saħħithom huma ossidazzjoni u idrosilazzjoni.
Nilotinib is the main circulating component in the serum.
Nilotinib huwa l- komponent ewlieni li jkun jiċċirkola fis- serum.
None of the metabolites contribute significantly to the pharmacological activity of nilotinib.
L- ebda wieħed mill - metaboli ma jikkontribwixxi b’ mod sinifikanti għall- attività farmakoloġika ta ’ nilotinib.
Nilotinib is primarily metabolised by CYP3A4, with possible minor contribution from CYP2C8.
Nilotinib huwa metabolizzat l- aktar permezz ta ’ CYP3A4, u jista ’ jkun hemm kontribuzzjoni minuri minn CYP2C8.
12 Elimination After a single dose of radiolabelled nilotinib in healthy subjects, more than 90% of the dose was eliminated within 7 days, mainly in faeces (94% of the dose).
Eliminazzjoni Wara doża waħda ta ’ nilotinib radjutikkettat f’ individwi b’ saħħithom, aktar minn 90% tad- doża tneħħiet fi żmien 7 ijiem, l- aktar fl- ippurgar (94% tad- doża).
Parent drug accounted for 69% of the dose.
Il- mediċina oriġinali kienet tgħodd 69% tad- doża.
Linearity / non-linearity Steady-state nilotinib exposure was dose-dependent, with less than dose-proportional increases in systemic exposure at dose levels higher than 400 mg given as once-daily dosing.
Linejarità/ nuqqas ta linejarità L- esponiment ta ’ nilotinib fi stat fiss kien jiddependi mid- doża, b’ żiediet li kienu anqas proporzjonali mid- doża f’ esponiment sistemiku b’ livelli ta ’ dożi ogħla minn 400 mg mogħtija darba kuljum.
Daily serum exposure to nilotinib with 400 mg twice-daily dosing at steady state was 35% higher than with 800 mg once-daily dosing.
Esponiment għal nilotinib fis- serum kuljum b’ 400 mg darbtejn kuljum fi stat fiss kien 35% ogħla milli b’ doża ta ’ 800 mg darba kuljum.
There was no relevant increase in exposure to nilotinib when the dose was increased from 400 mg twice daily to 600 mg twice daily.
Ma kienx hemm żieda rilevanti fl- esponiment għal nilotinib meta d - doża żdiedet minn 400 mg darbtejn kuljum għal 600 mg darbtejn kuljum.
Characteristics in patients Steady-state conditions were essentially achieved by day 8.
Karatteristiċi fil- pazjenti Kundizzjonijiet ta ’ stat fiss kienu miksuba ma ’ jum 8.
An increase in serum exposure to nilotinib between the first dose and steady state was approximately 2-fold for daily dosing and 3.8-fold for twice-daily dosing.
Żieda fl- esponiment ghal nilotinib fis- serum bejn l- ewwel doża u stat fiss kien madwar 2- darbiet għal dożi mogħtija darba kuljum u 3. 8- darbiet għal dożi mogħtija darbtejn kuljum.
The apparent elimination half-life estimated from the multiple-dose pharmacokinetics with daily dosing was approximately 17 hours.
Il- half- life ta ’ tneħħija apparenti stmata mill- farmakokinetika b’ ħafna dożi mogħtija darba kuljum kienet madwar 17- il siegħa.
Inter-patient variability in nilotinib pharmacokinetics was moderate to high.
Il- varjabilità bejn il- pazjenti fil - farmakokinetika ta ’ nilotinib kienet moderata għal għolja.
Nilotinib has been evaluated in safety pharmacology, repeated dose toxicity, genotoxicity, reproductive toxicity and phototoxicity studies.
Nilotinib ġie evalwat fi studji ta ’ sigurtà farmakoloġika, kif ukoll dwar tossiċità minn dożi ripetuti, ġenotossiċità, tossiċità fis- sistema riproduttiva u fototossiċità.
Nilotinib did not have effects on CNS or respiratory functions.
Nilotinib ma kellux effetti fuq is- CNS jew funzjonijiet respiratorji.
In vitro cardiac safety studies demonstrated a preclinical signal for QT prolongation, based upon block of hERG currents and prolongation of the action potential duration in isolated rabbit hearts by nilotinib.
Studji dwar is- sigurtà kardijaka in vitro wrew sinjal ta ’ qabel l- użu kliniku għal titwil tal- QT, bażat minn imblukkar tal- kurrenti hERG u titwil ta ’ kemm idum l- action potential fil- qlub ta ’ fniek iżolati minn nilotinib.
No effects were seen in ECG measurements in dogs or monkeys treated for up to 39 weeks or in a special telemetry study in dogs.
Ma dehrux effetti fuq il- miżuri ta ’ l- ECG fil- klieb u xadini ikkuurati sa ’ 39 ġimgħa jew fi studju speċjali b’ telemetrija fil - klieb.
Repeated-dose toxicity studies in dogs of up to 4 weeks’ duration and in cynomolgus monkeys of up to 9 months’ duration revealed the liver as the primary target organ of toxicity of nilotinib.
Studji dwar tossiċità minn dożi ripetuti fi klieb sa ’ 4 ġimgħat u f’ xadini cynomolgus sa ’ 9 xhur wrew li l- fwied huwa l- organu ewlieni li jintlaqat b’ tossiċità minn nilotinib.
Alterations included increased alanine aminotransferase and alkaline phosphatase activity and histopathology findings (mainly sinusoidal cell or Kupffer cell hyperplasia/ hypertrophy, bile duct hyperplasia and periportal fibrosis).
Tibdil kien jinkludi żiediet ta ’ l - alanine aminotransferase u l- attivita ta ’ l- alkaline phosphatase u sejbiet istopatoloġiċi (l- aktar taċ - ċelluli sinusojdali jew iperplażja/ ipertrofija taċ- ċelluli Kupffer, iperplażja tat- tubu tal- marrara u fibrożi periportali).
In general the changes in clinical chemistry were fully reversible after a four-week recovery period and the histological alterations showed partial reversibility.
B’ mod ġenerali, il- bidliet fil- kimika klinika kienu riversibbli għall- kollox wara perijodu ta ’ rkupru ta ’ erba ’ ġimgħat u l- bidliet istopatoloġiċi wrew riversibilità parzjali.
Exposures at the lowest dose levels at which the liver effects were seen were lower than the exposure in humans at a dose of 800 mg/ day.
L- esponimenti bl - aktar dożi baxxi li bihom dehru l- effetti fuq il- fwied kienu aktar baxxi mill- esponimenti fil- bniedem b’ doża ta ’ 800 mg/ jum.
Only minor liver alterations were seen in mice or rats treated for up to 26 weeks.
Bidliet fil- fwied minuri biss dehru fi ġrieden jew firien ikkurati għal 26 ġimgħa.
Mainly reversible increases in cholesterol levels were seen in rats, dogs and monkeys.
Żiediet fil- parti l- kbira riversibbli fil- livelli ta ’ kolesterol dehru fil- firien, klieb u xadini.
Genotoxicity studies in bacterial in vitro systems and in mammalian in vitro and in vivo systems with and without metabolic activation did not reveal any evidence for a mutagenic potential of nilotinib.
Studji dwar ġenotossiċità fuq sistemi bil- batteri in vitro u fuq sistemi mammali in vitro u in vivo b’ attivazzjoni metabolika jew mingħajrha ma wrew l- ebda evidenza li nilotinib jista ’ jkollu effett mutaġeniku.
Nilotinib did not induce teratogenicity, but did show embryo- and foetotoxicity at doses that also showed maternal toxicity.
Nilotinib ma ikkaġunax teratoġeniċità, iżda wera tossiċità fl- embriju u l- fetu b’ dożi li kienu wkoll tossiċi għall- omm.
Increased post-implantation loss was observed in both the fertility study, which involved treatment of both males and females, and the embryotoxicity study, which involved treatment of females.
Żieda fit- telf wara l- impjant dehret kemm fl- istudju dwar il- fertilità, li kien jinvolvi kura kemm ta ’ annimali maskili kif ukoll femminili, u fl- istudju dwar it- tossiċita għall- embriju, li kien jinvolvi kura ta ’ annimali femminili.
Embryo-lethality and foetal effects (mainly decreased foetal weights, premature fusion of the facial bones (fused maxilla/ zygomatic) visceral and skeletal variations) in rats and increased resorption of foetuses and skeletal variations in rabbits were present in the embryotoxicity studies.
Il- mewt ta ’ l- embriju u effetti fuq il- fetu (l- aktar tnaqqis fil- piż 14 tal- fetu, fużjoni prematura fl- għadam tal- wiċċ (xedaq/ żigomatiku fuzi) bidliet fl- intern u fl- għadam) fil- firien u żieda tar- risorbiment tal- feti u bidliet fl- għadam tal- fniek seħħew fl- istudji dwar tossiċita għall- embriju.
In a pre- and postnatal development study in rats, maternal exposure to nilotinib caused reduced pup body weight with associated changes in physical development parameters as well as reduced mating and fertility indices in the offspring.
Fi studju dwar l- iżvilupp ta ’ qabel u wara t- twelid fil- firien, l- esponiment għal nilotinib ikkawża tnaqqis fil- piż tal- wild assoċjat ma ’ tibdil fil- parametri ta ’ l- iżvilupp fiżiku kif ukoll fl- indiċi tat- tgħammir u fertilità tal- wild.
Exposure to nilotinib in females at No-Observed- Adverse-Effect-Levels was generally less or equal to that in humans at 800 mg/ day.
L- esponiment għal nilotinib fl- annimali femminili b’ Livelli- Fejn- Ma - Jidhirx- Effett- Avvers kien b’ mod ġenerali anqas jew daqs dak fil- bnedmin b’ 800 mg/ jum.
No effects on sperm count/ motility or on fertility were noted in male and female rats up to the highest tested dose, approximately 5 times the recommended dosage for humans.
Ma dehrux effetti fuq l- għadd/ motilità ta ’ l- isperma jew fuq il- fertilità fil- firien maskili u femminili sa l- ogħla doża li ġiet eżaminata, madwar 5 darbiet id- dożaġġ rakkomandat għall- bnedmin.
13 Nilotinib was shown to absorb light in the UV-B and UV-A range, is distributed into the skin and showed a phototoxic potential in vitro, but no effects have been observed in vivo.
Intwera li nilotinib jassorbi d- dawl fil- medda tal- UV- B u UV- A, jinfirex ġol- ġilda u wera li jista ’ jkun fototossiku in vitro, iżda ma dehrux effetti in vivo.
Therefore the risk that nilotinib causes photosensitisation in patients is considered very low.
Għaldaqstant ir- riskju li nilotinib jista ’ jikkawża fotosenitizzazzjoni fil- pazjenti huwa meqjus baxx ħafna.
Carcinogenicity studies with nilotinib have not been performed.
Ma sarux studji dwar l- effett kanċeroġenu b’ nilotinib.
Lactose monohydrate Crospovidone Poloxamer 188 Silica colloidal, anhydrous/ Colloidal silicon dioxide Magnesium stearate
Lactose monohydrate Crospovidone Poloxamer 188 Silica colloidal, anhydrous/ Colloidal silicon dioxide Magnesium stearate
Gelatin Titanium dioxide (E171) Yellow iron oxide (E172)
Gelatin Titanium dioxide (E171) Yellow iron oxide (E172)
Printing ink:
Inka tat- timbru:
Shellac Red iron oxide (E172) Soya lecithin (E322)
Shellac Red iron oxide (E172) Soya lecithin (E322)
Store in the original package in order to protect from moisture.
Aħzen fil- pakkett oriġinali sabiex tilqa ’ mill- umdità.
PVC/ PVDC/ Al and PA/ Al/ PVC/ Al blisters.
PVC/ PVDC/ Al u PA/ Al/ PVC/ Al folji.
Tasigna is available in weekly and monthly packs: • The weekly pack contains 28 capsules. • The monthly pack contains 112 capsules (4x28).
Tasigna jiġi f’ pakketti ta ’ ġimgħa jew ta ’ xahar: • Il- pakkett ta ’ gimgħa fih 28 kapsula. • Il- pakkett ta ’ xahar fih 112- il kapsula (4x28).
A monthly pack consists of 4 individual weekly wallets.
Pakkett ta ’ xahar fih 4 wollits ta ’ ġimgħa individwali.
15 ANNEX II
16 ANNESS II
• Brief background on Tasigna, its authorised indication and posology • Information on the cardiac risks associated with the use of Tasigna o That Tasigna can cause prolongation of the QT interval and that patients at risk of arrythmia, especially torsade de pointes, should not be prescribed Tasigna. o The need to avoid co-prescription with any other medicines that might prolong the QT interval o Caution in prescribing to patients with a history of or risk factors for coronary heart disease o That Tasigna may cause fluid retention, cardiac failure and pulmonary oedema
• Tagħrif fil- qosor fuq Tasigna, u l- indikazzjoni u l- pożoloġija awtorizzati għaliha. • Informazzjoni dwar ir- riskji kardijaċi assoċjati ma ’ Tasigna o Li Tasigna jista ’ jtawwal l- intervall QT u li pazjenti li għandhom riskju ta ’ arritmija, l- aktar torsade de pointes, m’ għandhomx jingħataw riċetti għal Tasigna. o Il- bżonn li jiġi evitat li jiġu ordnati flimkien kwalunkwe mediċini oħrajn li jistgħu jtawwlu l- intervall QT o Attenzjoni meta tiġi ordnata lill- pazjenti li fil- passat kellhom jew għandhom fatturi ta’ riskju għall- mard koronarju tal- qalb o Li Tasigna tista ’ tikkawża ritenzjoni ta ’ fluwidi, insuffiċjenza tal- qalb u edema pulmonari
17 • OTHER CONDITIONS
18 • KUNDIZZJONIJIET OĦRA
Pharmacovigilance system
Sistema ta ’ farmakoviġilianza
The MAH must ensure that the system of pharmacovigilance, as described in version 2, dated 23-Oct-06, presented in Module 1.8.1. of the Marketing Authorisation Application, is in place and functioning before and whilst the product is on the market.
L- MAH għandu jaċċerta ruħu li is- sistema ta ’ farmakoviġilanza, kif deskritta fil- verżjoni 2. 0 bid- data ta ’ t- 23- Ott- 06, preżentata f’ Modulu 1. 8. 1. ta ’ l- Applikazzjoni għall- Awtorizzazzjoni għat- Tqegħid fis- Suq, tkun f’ lokha u taħdem qabel u waqt li l- prodott ikun fis- suq.
Risk Management Plan
Pjan ta ’ l- Imaniġġar tar- Riskju
The MAH commits to performing the studies and additional pharmacovigilance activities detailed in the Pharmacovigilance Plan, as agreed in version 2, dated 19-Sep-07 of the Risk Management Plan (RMP) presented in Module 1.8.2. of the Marketing Authorisation Application and any subsequent updates of the RMP agreed by the CHMP.
L- MAH jintrabat li jwettaq l- istudji u l- attivitajiet l- oħra dwar il- farmakoviġilanza dettaljati fil- Pjan ta ’ Farmakoviġilanza, hekk kif miftihem fil- verżjoni 2, bid- data ta ’ d- 19- Sett- 07 tal- Pjan ta ’ l- Imaniġġar tar- Riskju (RMP) preżentat f’ modulu 1. 8. 2 ta ’ l- Applikazzjoni għall- Awtorizzazzjoni għat- Tqegħid fis- Suq u kwalunkwe aġġornamenti ta ’ l- RMP li jkun hemm wara kif miftihem mis- CHMP.
As per the CHMP Guideline on Risk Management Systems for medicinal products for human use, the updated RMP should be submitted at the same time as the next Periodic Safety Update Report (PSUR).
Skond il- Linja Gwida tas- CHMP dwar Is- Sistemi ta ’ l- Immaniġġar tar- Riskju għall- prodotti mediċinali għall- użu fil- bniedem, l- RMP imġedded għandu jiġi sottomess fl- istess ħin mar- Rapport ta ’ Aġġornament dwar is- Sigurtà Perjodiku (PSUR).
CARTON OF WEEKLY PACK
KARTUNA TAL- PAKKETT TA ’ ĠIMGĦA
Tasigna 200 mg hard capsules Nilotinib
Tasigna 200 mg kapsuli iebsin Nilotininb
Contains lactose – see the package leaflet for further information.
Fih lactose – ara l- fuljett ta ’ tagħrif għal aktar informazzjoni.
22 MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS
23 TAGĦRIF MINIMU LI GĦANDU JIDHER FUQ IL- FOLJI JEW FUQ L- ISTRIXXI
Tasigna 200 mg hard capsules Nilotinib
Tasigna 200 mg kapsuli iebsin Nilotinib
CARTON OF MONTHLY PACK
KARTUNA TAL- PAKKETT TA ’ XAHAR
Contains lactose – see the package leaflet for further information.
Fih lactose – ara l- fuljett ta’ tagħrif għal aktar informazzjoni.
112 hard capsules Monthly pack containing 4 wallets.
112- il kapsula iebsa Pakkett ta ’ xahar li fih erba ’ wolits.
INTERMEDIATE WALLET OF MONTHLY PACK
WOLIT TAN- NOFS TAL- PAKKETT TA ’ XAHAR
28 hard capsules Component of a monthly pack containing 4 wallets.
28 kapsula iebsa Jagħmel parti minn pakkett ta ’ xahar li fih erba ’ wolits.
What Tasigna is and what it is used for 2.
X’ inhu Tasigna u għalxiex jintuża 2.
Before you take Tasigna 3.
Qabel ma tieħu Tasigna 3.
How to take Tasigna 4.
Kif għandek tieħu Tasigna 4.
How to store Tasigna 6.
Kif taħżen Tasigna 6.
WHAT TASIGNA IS AND WHAT IT IS USED FOR
X’ INHU TASIGNA U GĦALXIEX JINTUŻA
What Tasigna is Tasigna is a medicine containing an active substance called nilotinib.
X’ inhu Tasigna Tasigna hija mediċina li fih sustanza attiva msejjħa nilotinib.
What Tasigna is used for Tasigna is used to treat a type of leukaemia called Philadelphia chromosome positive chronic myeloid leukaemia (Ph-positive CML).
Għalxiex jintuża Tasigna Tasigna jintuża biex jikkura tip ta ’ lewkemija imsejjħa lewkemija majelojde kronika pożittiva għall - komosoma ta ’ Filadelfja (CML Ph- pożittiva).
CML is a cancer of the blood which makes the body produce too many abnormal white blood cells.
CML huwa tumur tad- demm li jikkawża lill- ġisem biex jipproduċi wisq ċelluli bojod anormali.
Tasigna is used in patients with CML who are no longer benefiting from previous treatment including imatinib.
Tasigna jintuża f’ pazjenti b’ CML li m’ għadhomx jiksbu benefiċċju mill- kura li kienu jingħataw qabel inkluż imatinib.
It is also used in patients who experienced serious side effects with previous treatment and are not able to continue taking it.
Jintuża wkoll f’ pazjenti li kellhom effetti sekondarji serji bil- kura li ngħataw qabel u li ma jistgħux ikomplu jieħduha.
How Tasigna works In patients with CML, a change in DNA (genetic material) triggers a signal that tells the body to produce abnormal white blood cells.
Kif jaħdem Tasigna F’ pazjenti b’ CML, bidla fid- DNA (materjal ġenetiku) jibda sinjal li jgħid lill- ġisem biex jipproduċi ċelluli bojod tad- demm anormali.
Tasigna blocks this signal, and thus stops the production of these cells.
Tasigna jimblokka dan is- sinjal, u b’ hekk iwaqqaf il- produzzjoni ta ’ dawn iċ- ċelluli.
Monitoring your Tasigna treatment You will have regular tests, including blood tests, during treatment.
Kif tiġi monitorjata l- kura b’ Tasigna Ser isirulek testijiet regolari, inklużi testijiet tad- demm, waqt il- kura.
These will monitor the amount of blood cells (white blood cells, red blood cells and platelets) in your body to see how Tasigna is tolerated.
Dawn ser jimmonitorjawlek l - ammont ta ’ ċelluli tad- demm (ċelluli bojod tad- demm, ċelluli ħomor tad- demm u plejtlits) f’ ġismek sabiex ikun magħruf kemm tiflaħ għal Tasigna.